Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and contaminated air. It has no nutritional or physiological value, but most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, Ca), which are required for cellular metabolism and functional integrity. The kidney is regarded as the principal site of Cd toxicity as it preferentially accumulates in the proximal tubular epithelium here. As these cells die due to toxic accumulation, Cd complexed with metallothionein are released into tubular lumen and excreted. Excretion of Cd, signifying current renal cell toxicity, is used as a measure of long-term Cd exposure. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and life-style factors that could induce excessive weight gain. Whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of obesity. Indeed, obesity may enhance diabetogenic effects of Cd. This review highlights Cd exposure sources and levels associated with diabetes type 2 along with the pathophysiologic mechanisms by which Cd disrupt glucose metabolism. Special emphasis is on roles of the liver and kidney in glucose homeostasis, heme-glucose cross-talk, and the involvement of heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide and a precursor substrate for producing a cytoprotective biochemical, bilirubin, whilst HO-2 appears to have also anti-diabetic and anti-obese actions.

Omentin is an adipokine mainly produced by visceral fat tissue, and it has two isoforms: omentin-1 and omentin-2. Omentin-1 is predominantly secreted by visceral adipose tissue, deriving specially from the stromal vascular fraction cells of white adipose tissue (WAT). Levels of omentin-1 are also expressed in other WAT depots, like epicardial adipose tissue. Omentin-1 exerts several beneficial effects in glucose homeostasis in obesity and diabetes. In addition, research has suggested that omentin may have atheroprotective (protective against the development of atherosclerosis) and anti-inflammatory effects, potentially contributing to cardiovascular health. This review highlights the potential therapeutic targets of omentin-1 in metabolic-related disorders.

Rabson-Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We are reporting the first case of Rabson-Mendenhall syndrome in a Paraguayan patient. The patient is a 5-year-old girl who presented with hypertrichosis, acanthosis nigricans, and nephrocalcinosis. Genetic testing by NGS revealed two pathogenic variants in exons 2 and 18 of the INSR gene; c.332G>T (p. Gly111Val) and c.3485C>T (p. Ala1162Val), in combined heterozygosis. The novel INSR c. 332G>T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software predicted it as pathogenic. The c. 3485C>T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and Rabson-Mendenhall syndrome. The management of Rabson-Mendenhall syndrome is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of Rabson-Mendenhall syndrome to the Paraguayan population and adds a novel pathogenic variant to the existing literature.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

The skeletal muscle plays a critical role in regulating systemic blood glucose homeostasis. Impaired skeletal muscle glucose homeostasis associated with type 2 diabetes mellitus (T2DM) has been observed to significantly affect the whole-body glucose homeostasis, thereby resulting in other diabetic complications. T2DM does not only affect skeletal muscle glucose homeostasis, but it also affects skeletal muscle structure and functional capacity. Given that T2DM is a global health burden, there is an urgent need to develop therapeutic medical therapies that will aid in the management of T2DM. Prediabetes is a prominent risk factor of T2DM that usually goes unnoticed in many individuals as it is an asymptomatic condition. Hence, research on prediabetes is essential because establishing diabetic biomarkers during the prediabetic state would aid in preventing the development of T2DM, as prediabetes is a reversible condition if it is detected in the early stages. Literature predominantly documents the changes in skeletal muscle during T2DM, but the changes in skeletal muscle during prediabetes remain unknown. In this review, we seek to review the existing literature on prediabetic and T2DM associated changes in skeletal muscle function.

Mucormycosis is an opportunistic fungal infection that is increasingly affecting patients with Coronavirus Disease (COVID-19). This connection is particularly pronounced in specific populations, including individuals with diabetes or those who have recently undergone corticosteroid therapy. Additionally, Cytomegalovirus (CMV) infection is a frequent complication among COVID-19 patients who have previously received corticosteroid or other immune-modulatory treatments. In this case report, we present the clinical details of a 56-year-old male who developed post-COVID pneumonia complicated by both cutaneous mucormycosis and CMV infection.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

Metabolic syndrome is a growing global health problem. Evidence suggests that diets rich in phytochemical-containing herbs and spices can contribute to reduced risk of chronic disease. This review assesses the scope of evidence supporting the use of herbs and spices in the diet for prevention or treatment of metabolic syndrome and associated health conditions. A search of PubMed and Scopus databases was carried out to assess the available clinical or cohort evidence for culinary doses of commonly used herbs and spices. Trials that were measuring health factors related to metabolic disorders or the health of individuals with metabolic syndrome or associated diseases were included. Out of a total of 1742 papers identified, there were 146 relevant studies on black pepper, chilli, cardamom, cinnamon, coriander, cumin, fennel, fenugreek, garlic, ginger, Nigella seed, rosemary, sage and turmeric. No relevant research was found for cloves, mint, oregano, parsley or thyme. Cinnamon, fenugreek and ginger were the herbs/spices with the most published trials on them and showed promise for glycaemic control. Cardamom appears to have potential to reduce inflammatory markers, and cinnamon, ginger and turmeric for blood lipids. Patients with type 2 diabetes were the population most likely to be included in studies, but the preventative benefits of herbs/spices in healthy populations were also investigated, particularly for chilli, ginger and cinnamon. There is evidence for the beneficial effect of culinary doses of many common herbs/spices in the prevention and treatment of metabolic syndrome and associated disorders.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes is attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of pro-inflammatory chemokines; CCL1, 2, 4 and 5 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a normal control group were enrolled. The demographic data, serum levels CCL-1, 2, 4 and 5 and the biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). n controls. We observed that male and female control patients had similar mean serum concentrations of pro-inflammatory chemokines CCL 1, 2, 4, and 5. Chemokines CCL1, CCL2, and CCL4 in the serum of Type 2 Diabetes Mellitus patients with normal or overweight body weights were significantly higher than the control group, regardless of gender. In T2DM individuals with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL1, 2, and 4 in T2DM) patients with increasing BMI. Serum CCL5 levels increased significantly in all T2DM patient groups. The increase in CCL5 was more predominant in normal-weight people as compared to overweight and obese T2DM patients. Conclusions. Male and female control patients had similar serum levels of pro-inflammatory chemokines CCL 1, 2, 4, and 5. The progressive rise in blood concentrations of three Pro-inflammatory chemokines; CCL1, 2, and 4 in T2DM patients with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM patient groups. The selective and more pronounced increase of CCL5 in the T2DM group with normal BMI as compared to patients with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 under-expression in overweight and obese T2DM patients is due to some unexplained counterbalancing processes.

African indigenous herbs and medicinal plants are extensively reported for their protective and therapeutic potential against Diabetes. However, most of the constituent phytochemicals that may account for the therapeutic activity are largely uninvestigated. Exploring novel phytochemical–target interactions in silico could help to provide useful insights into the mechanism underpinning the biological activities of these plants and their constituent phytochemicals. The aim of this study was to explore the interactions of terpene struc-tures previously reported from selected African antidiabetic with two emerging drug targets in diabetes. Structure-based virtual screening was used to screen 107 terpene structures against DPP-4 and PTP1B enzymes. The MD simulation, MM-GBSA free energy calculation and DFT were used to clarify the inter-actions of the in silico hits with the target enzymes. Molecular docking, post-docking Prime MM-GBSA analysis revealed the top terpenes with high binding affinity with the active site regions of DPP-4 and PTP1B. Ensemble docking revealed three triterpenes viz: cucurbitacin B (T1), 6-Oxoisoiguesterin (T4) and 20-Epi-isoiguesterinol (T2) as in silico hits which exhibit strong interaction potential with critical residues that define the catalytic triad (Ser630 and His740); oxyanion cavity (Ser631); hydrophobic S1 pocket (Tyr662) and the charged S2 pocket (Arg125) in the active site region of DPP-4. The interactions of these compounds with DPP-4 exhibited structural stability and conformational flexibility during 100 ns full atomistic MD simulation as indicated by the structure dynamics parameters including RMSD, RoG, SASA and hydrogen bond number. The post-MD MM/GBSA calculations further revealed the stability of the triterpene-DPP-4 complexes. Furthermore, Frontier molecular orbital calculations showed that, the triterpenes possess high interaction potential with the enzyme. The triterpenes showed desirable ADMET properties and drug-likeness. Therefore, cucurbitacin B, 6-Oxoisoiguesterin and 20-Epi-isoiguesterinol are recommended for experimental validation.

Utilization of medicine derived from plants has been documented in various traditional systems of medicines throughout the world for different diseases. Therefore, the current research work was carried out to evaluate the phytochemical and biological potential of Ficus carica L ethanolic leaf extract. For this purpose, physicochemical and phytochemical analysis, total phenolic and flavonoids contents was performed. Antioxidant potential was determined by FRAP, DPPH and H2O2 assay. Proteinase inhibition, heat induced hemolysis and BSA denaturation assay was carried out for inflammation. Antiglycation potential was assessed by fructosamine assay, Congo-red assay and estimation of free carbonyl groups. In-vivo antidiabetic, anti-obesity, effect on liver and kidney were investigated by high fat high sugar diet model. FTIR, HPLC and LCMS/MS analysis was performed to find out the compounds. Tablet based formulation was developed using wet granulation method and tested for physicochemical parameters. Results shows that total phenolic and flavonoids content was (333 mg GAE/g) and (123 mg RE/g) respectively, H2O2 assay shows 35.6% free radical inhibition potential, DPPH assay shows (IC50) inhibitory concentration at 0.58 mg/mL, and 88.769 µg/g Fe2SO4 solution FRAP values. Proteinase inhibition assay, Heat induced hemolysis and BSA-denaturation assay shows percentage inhibition of 28 ± 0.01, 55 ± 0.03 and 51.2 ± 0.05 respectively. In Antiglycation activity β-amyloid formation assay shows absorption of 0.017, Fructosamine assay shows inhibition of 19.4±0.06 and free carbonyl group estimation shows inhibition of 17.0±0.03. In in-vivo study FLE at (500 mg/kg) significantly decreased total bilirubin (p ≤ 0.001), decreased (p ≤ 0.05) alanine transferase, aspartate aminotransferase, alkaline phosphatase, decreased blood glucose, triglycerides and total cholesterol (p ≤ 0.01) while HDL (p ≤ 0.01) was significantly increased in comparison to obesity and diabetic-obesity groups. Different functional groups presence was confirmed by FTIR spectrum. HPLC analysis revealed the existence of ferulic acid, rutin, chlorogenic acid, coumarin and thymoquinone and these results are corelated by LC-MS/MS. Pre-compression characterization showed angle of repose (33.04°), bulk density (0.54 g/cm3), tapped density (0.73 g/cm3), compressibility index (35.179 %) and Hausner’s ratio (1.35), while the post-compression characterization showed weight variation 826±4.17 mg, thickness 10.50±0.25 kg/cm2, friability 0.57 %, and disintegration time 8.19 min. From the above results it is concluded that F. carica L. leaves extract has strong antioxidant, antidiabetic and hypolipidemic potential and can be used for an obesity and diabetes treatment.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes I attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of interleukins-10 , 19 and 22 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a control group were enrolled. The demographic data, serum levels of IL-10, IL-19, and IL-22, and biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). Both male and female T2DM subjects in Group A showed significant decreases in IL-10 levels as compared to controls; however, there were insignificant changes in IL-10 levels in Groups C and D. T2DM patients in groups C and D, in both males and females, depicted very significant (p 0.001) increases in IL-19 levels as compared to controls and group A. Patient groups A to D displayed a progressive elevation of Il-22 levels irrespective of gender, although significant alterations were seen only in groups B to D, with p 0.05 for group B and p 0.01 for groups C and D respectively, as compared to healthy controls. Conclusions. IL-10 showed a strong relationship with T2DM in males with varying degrees of obesity, but females depicted relatively higher IL-10 levels in obese and highly obese groups, pointing to a protective phenomenon. IL-19 levels showed significant increases in all four groups, irrespective of gender. IL-22 appears to be unrelated to T2DM per se but shows an association with varying degrees of obesity.

Diabetes mellitus is a chronic disease, commonly associated with unhealthy habits and obesity, and it is becoming a serious health issue worldwide. As a result, new approaches to treat diabetes are required, and a movement towards more natural ones is emerging. Consuming fruit and vegetables is advised to prevent diabetes since they contain several bioactive compounds. A simple and ef-fective strategy to include them in the diets of diabetic and obese people is through beverages. This review aimed to report the anti-diabetic potential of different vegetable and fruit beverages. These functional beverages demonstrated in vitro potential to inhibit α-glucosidase and α-amylase en-zymes, and to improve glucose uptake. In vivo, the beverage consumption showed a reduction of blood glucose, increase of insulin tolerance, improvement of lipid profile, control of obesity, and reduction of oxidative stress. This suggests the potential of vegetable and fruit-based functional beverages to be a natural innovative therapy for the management of diabetes.

Background: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in an urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The purpose of this study was to assess the protective impact of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analogue) alone and in combination, on streptozotocin (STZ) diabetes-induced testicular dysfunction in rats. Material and methods: This study was carried on 50 male Sprague-Dawley rats; 10 normal rats were allocated as non-diabetic control group. 40 rats developed diabetes after receiving a single dose of STZ, then the diabetic rats were divided into four groups of equivalent number assigned as diabetic control, enalapril treated, paricalcitol treated, in addition to combined enalapril and paricalcitol treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress and inflammatory parameters as well as histopathological examination were assessed when compared to the normal and diabetic control rats. Results: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle stimulating hormone (FSH) as well as luteinizing hormone (LH) and the antioxidant enzyme activities were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6) as well as tumor necrosis factor-α (TNF-α) were significantly increased, along with sever distortion of testicular structure. Interestingly, treatment with paricalcitol and enalapril either alone or in combination significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH and LH, reduced insulin resistance, IL-6 and TNF-α levels and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs than monotherapy with enalapril alone. Conclusion: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving the diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory and anti-apoptotic properties), than monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

High hepcidin is linked to low-grade inflammation and lower iron levels. The consequence of testosterone replacement therapy (TRT) on inflammation and risk of cardiovascular disease (CVD) is undetermined. We investigate the effect of TRT on the inflammatory cardiovascular risk markers hepcidin-iron, fibroblast growth factor 23 (FGF23)-phosphate-klotho, and calprotectin pathways. Methods: A randomized, placebo-controlled, double-blinded study at an academic tertiary-care medical center. Interventions were testosterone gel (TRT, n=20) or placebo gel (n=19) for 24 weeks. We included 39 men (50─70 years) with type 2 diabetes (T2D) on metformin monotherapy with bioavailable testosterone levels <7.3 nmol/L. Body composition was assessed by DXA- and MRI-scans; main study outcomes were serum hepcidin-iron, FGF23, phosphate, klotho, and calprotectin. Results: Hepcidin levels decreased during TRT (β=-9.5 ng/mL, P<0.001), lean body mass (β=1.9 kg, P=0.001) increased, and total fat mass (β=-1.3 kg, P=0.009) decreased compared to placebo. Delta hepcidin was not associated with changes in lean body mass or fat mass. Iron and the pathways of FGF23-phosphate-klotho and calprotectin were unchanged during TRT. Conclusions: During TRT, the reduction in hepcidin was not associated with circulating iron levels, lean body mass, or fat mass; these findings suggested a direct anti-inflammatory effect of TRT and no indirect effect mediated through these factors.

Hospitalizations for patients with diabetes and dementia take a significant health and economic toll on older adults in the United States. The present study sought to examine the differences in hospitalization characteristics and outcomes associated with diabetes and dementia separately and together using discharge record data of Los Angeles County residents aged 50+ from the California Department of Health Care Access and Information for the period 2019-2021. Results from multiple linear regression analyses indicated that when compared to those with no diabetes or dementia, patients with diabetes alone exhibited the highest total charges, while those with comorbid diabetes and dementia exhibited lower charges (p≤.05). Results of a multinomial logistic regression found that patients with comorbid diabetes and dementia had the highest odds of having a length of stay of 7+ days (AOR=1.49; 95% CI=1.44-1.53). A matched-case control analysis found that comorbid diabetes and dementia was associated with significantly lower odds of hypertensive disease than diabetes alone (MOR=0.81; 95% CI=0.67-0.97). These results highlight the complexity of factors affecting variation in hospitalization outcomes across these distinct disease profiles. Findings suggest a need to carefully consider this complexity when developing health policies or strategies to improve hospitalization outcomes involving these disease conditions.

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.

Maternal hyperglycemia, induced by gestational diabetes mellitus (GDM), has detrimental effects on fetal vascular development, ultimately increasing the risk of cardiovascular diseases in offspring. The potential underlying mechanisms by which these complications occur are through functional impairment and epigenetic changes in fetal endothelial progenitor cells (EPCs), however, remain less defined. We confirm that intrauterine hyperglycemia leads to impaired angiogenic function of fetal EPCs, as observed through functional assays of outgrowth endothelial cells (OECs) derived from fetal EPCs of GDM pregnancies (GDM-EPCs). Notably, PCDH10 expression is increased in OECs derived from GDM-EPCs, which is associated with the inhibition of angiogenic function in fetal EPCs. Additionally, increased PCDH10 expression is correlated with hypomethylation of the PCDH10 promoter. Our findings demonstrate that in utero exposure to GDM can induce angiogenic dysfunction in fetal EPCs through altered gene expression and epigenetic changes, consequently increasing the susceptibility to cardiovascular diseases in offspring of GDM mothers.

β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation followed by deleterious effects at the cellular and systemic level is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders including metabolic syndrome, diabetes mellitus and cardiovascular diseases. In this review an interplay between pathways leading to MGO generation and scavenging is addressed, in regard to this system’s impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and elderly individuals. DM may accelerate the aging process, and the age-related declines in the estimated Glomerular Filtration Rate (eGFR), can pose a challenge to diagnose diabetic kidney disease (DKD) using standard diagnostic criteria especially with absence of severe albuminuria among the elderly. In the presence of CKD and DM, elderly patients may need multidisciplinary care due to susceptibility to various health issues e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to the elderly. We review the evidence that the benefits from these newer therapies apply equally to elderly and non-elderly patients and propose a framework for the management of DKD by discussing the nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), Sodium Glucose Co-Transporter two inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and Glucagon Like Peptide 1 Receptor Agonists (GLP1-RAs).

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with the pathogenesis of hypertension, but so far, the mechanism has not been well defined. We hypothesize that exposure to Cd causes a decline in the glomerular filtration rate (GFR), which in turn, causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73m2 (low eGFR). The mean blood Cd and mean urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. Prevalence odds ratio (POR) for hypertension rose twofold in those with a medium Cd burden and blood Cd levels of 0.61-1.69 µg/L. In the hypertensive group, the eGFR was inversely associated with age (β =−0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). Mean eGFR in those with hypertension was 7.5 mL/min/1.73m2 lower than those who were normotensive with the same Cd body burden. In addition, higher systolic blood pressure (SBP) values were associated with older age (β = 0.243), higher BMI (β = 0.113), lower eGFR (β = −0.106) and diabetes (β = 0.216). Mean SBP in those who had low eGFR and medium and heavy Cd body burden was 9.5 mmHg higher than those with the same Cd body burden and a normal eGFR. Thus, chronic environmental exposure to Cd that produces urinary and blood Cd levels of 0.57-0.61 µg/L, increases the risk of hypertension, and this could be mediated by a declining GFR.

Background: The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the Vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in Vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact molecular mechanism driving this down-regulation in T1DM is yet to be fully understood. This study aimed to decipher differences in the expression of genes associated with Vitamin D metabolism in T1DM patients and to ascertain if there is a correlation between serum 1,25(OH)2D3 levels and the expression of these genes. We also sought to understand the influence of specific microRNAs (miRNAs) on the expression of Vitamin D metabolism genes in peripheral blood mononuclear cells (PBMCs) of T1DM patients. Furthermore, the study delved into the potential implications of altered Vitamin D metabolism genes and miRNAs on autoimmune processes. Methods: Utilizing real-time PCR, we assessed the expression profiles of genes encoding for 1-hydroxylases (CYP27B1) and 24-hydroxylases (CYP24A1), as well as related miRNAs, in PBMCs from 30 T1DM patients and 23 healthy controls. ELISA tests facilitated the measurement of 1,25(OH)2D3, GAD65, and IA-2 levels. Results: Our findings showcased down-regulated CYP27B1 mRNA levels, while CYP24A1 expression remained stable compared to healthy subjects (CYP27B1, p = 0.0005; CYP24A1, p = 0.205, respectively). In T1DM patients, the levels of has-miR-216b-5p were found to be increased, while the levels of has-miR-21-5p were decreased in comparison to the control group. Notably, no correlation was identified between the expression of CYP27B1 in T1DM patients and the levels of has-miR-216b-5p, has-miR-21-5p, and 1,25(OH)2D3. A significant negative correlation was identified between CYP27B1 mRNA levels in PBMCs of T1DM and IA2, but not with GAD65. Conclusions: The study highlights there were reduced levels of both CYP27B1 mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of CYP27B1, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and CYP27B1 expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM.

Background: Very low-calorie ketogenic diet (VLCKD) is associated with improvement of metabolic and cardiovascular disorders. We aimed to evaluate the effects of VLCKD in patients with Cushing’s disease (CD) as adjunctive therapy to treatment for primary disease. Methods: We evaluated clinical, hormonal and metabolic parameters in 15 patients with CD and 15 controls at baseline and after 1 week and 3 weeks of VLCKD and further 2 weeks of low-carbohydrate ketogenic diet (LCKD). Results: After 5 weeks of diet a significant decrease in BMI (p=0.002), waist circumference (WC) (p=0.024), systolic (p=0.015) and diastolic blood pressure (p=0.005), ACTH (p=0.026), cortisone (p=0.025), total (p=0.006) and LDL cholesterol (p=0.017), triglycerides (p=0.016), alkaline phosphatase (p=0.008) and a significant increase in HDL cholesterol (p=0.017), vitamin D (p=0.015) and oral disposition index (Dio)(p=0.004) was observed in CD. A significant decrease in BMI (p=0.003), WC (p=0.002), systolic (p=0.025) and diastolic (p=0.007) blood pressure and total cholesterol (p=0.026) and increase in HDL cholesterol (p=0.001) and DIo (p&lt;0.001) was observed in controls. Conclusions: The current study confirms that ketogenic diet is effective in improving metabolic disorders and shows that a nutritional approach may be combined with conventional CD therapy in order to improve metabolic and cardiovascular comorbidities.

Background and Objectives: Cardiovascular disease is one of the leading causes of morbidity and mortality among the diabetic population. Given the high prevalence of diabetes mellitus (DM) in Saudi Arabia and the high prevalence of heart failure in the diabetic population, this study assesses the echocardiographic changes in Saudi patients with type 2 DM (T2DM) compared with healthy controls. Materials and Methods: In this retrospective case control study, 80 patients with diabetes (45 males, age: 58.78±10.2 years) were compared with 80 controls (45 males, age: 58.6±10 years) who underwent an echocardiographic study in the King Saud University Medical City, Riyadh, Saudi Arabia. Results: There were no significant differences between patients with diabetes and controls in terms of aortic root diameter, left atrium diameter, posterior wall, interventricular wall thickness, left ventricular diameters and ejection fraction. However, diastolic dysfunction was statistically significantly higher in the diabetic group compared with the control group (P &lt;0.05). Conclusions: This is the first case control study in Saudi Arabia that assesses echocardiographic parameters in T2DM patients. DM is an independent risk factor for diastolic dysfunction regardless of its association with hypertension and dyslipidemia.

Viscum album L., also known as “Mistletoe”, is a hemiparasitic plant native to the European continent that grows on various host trees. This plant contains a wide variety of active compounds that can be used for treat various diseases, such as diabetes, hypertension, as an anti- inflammatory and antioxidant. However, it is most indicated in human medicine for the adjuvant treatment of cancer patients. Both for its properties directed against neoplastic cells and for its antioxidant and anti-inflammatory properties. In Veterinary Medicine, I am very few studies are recorded for animals, although formulations are available for commercial use in oral and injectable form, mostly for homeopathic use. Many studies have been conducted on a large scale by groups of independent researchers and doctors in several countries, such as Switzerland, Germany and Brazil. Therefore, this review aimed to collect data on the use of Viscum album in Veterinary Medicine in order to encourage research in this sector not only in oncological diseases but in other directions in which Viscum can find use as an anti-pretensive and anti-diabetic agent. Introduction: Lectins, flavonoids, phenols such as phenylpropanoids, coumarins, sterols, lignans, terpenoids, phenylpropanoids, alkaloids, fatty acids and viscotoxins are among the main active ingredients present in the phytocomplexes of the Viscum album plant. In particular, Attention should be given to specific oligoproteins in consideration of their activity biological [1]. present in The foliage and fruits of V. album, as in other related species, contain low-weight proteins molecular type of thionin, called viscotoxins, as well as characteristic lectins, called viscolectins, both can contribute to its system defense and can be found in extracts and related products. These classes of Viscum microproteins have received considerable attention due to their contribution to effects cytotoxics and immunostimulants of mistletoe extracts used in medicine, as discussed later, including their mechanism of action [ 2–3] viscotoxins can increase the number of cells circulating naturalkillers and consequently improve the response host antitumor immunity [ 8]. Likewise, the a viscotoxin has an effective immunomodulatory impact on human and animal granulocytes [ 9, 10] and also acts on cellular apoptosis [11]. The cytotoxic action of viscotoxin is comparable to that of conventional chemotherapeutic agents [ 12].

In this study, we aimed to reveal the proinflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabe-tes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy partici-pants. Levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleu-kin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) were measured in the serum of the par-ticipants. The ANOVA Bonferonni and Kruskal Wallis Dunn tests were used for the comparison of the inflammation markers and vitamin D levels between the groups. Upon covariance analy-sis with age, gender and BMI; Vit D levels of T2DM group were found to be significantly lower (p<0.003). Proinflammatory markers and CRP were found to be significantly higher in predia-betic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the proinflammatory effects of Vit D on the initiation of inflammation in both prediabetes and diabetes mellitus.

The Global Burden of Disease Study (GBD) 2019 reveals an increasing prevalence of Type 2 Diabetes Mellitus (T2DM) from 1990 to 2019. This study delves into the role of dietary risk factors across different demographic and socioeconomic groups. Utilizing data from the GBD 2019, it analyzes age-adjusted T2DM metrics—death counts, Disability-Adjusted Life Years (DALYs), and Age-Standardized Rates (ASR)—stratified by age, sex, and region. The study employed Estimated Annual Percentage Changes (EAPCs) to track trends over time. Results show that in 2019, 26.07% of T2DM mortality and 27.08% of T2DM DALYs were attributable to poor diets, particularly those low in fruits and high in red and processed meats. Geographic variations in T2DM trends were significant, with regions like Southern Sub-Saharan Africa and Central Asia experiencing the most substantial increases in Age-Standardized Mortality Rate (ASMR) and Age-Standardized DALY Rate (ASDR). A positive correlation was noted between Socio-Demographic Index (SDI) and T2DM burden due to dietary risk factors. The study concludes that targeted public health initiatives promoting dietary changes could substantially reduce the global T2DM burden.

Diabetes is one of the fatal diseases that play a vital role in the growth of other diseases in the human body. Controlling and curing diabetes in its early stages is the most significant technique to avoid its effects of diabetes. However, lack of awareness and expensive clinical tests are the primary reasons to skip clinical diagnosis and take preventive methods in lower-income countries like Bangladesh, Pakistan, and India. From this perspective, the study aims to build an automated machine learning (ML) model, which will predict diabetes at an early stage using socio-demographic characteristics rather than clinical attributes. Because clinical features are not always known to all people from lower-income countries. To find the best fit supervised ML classifier of the model, we applied six classification algorithms and found that RF outperformed with an accuracy of 99.36%. In addition, the most significant risk factors were found based on the SHAP value by all the applied classifiers. The study reveals that polyuria, polydipsia, and delayed healing are the most significant risk factors for growing diabetes. The findings indicate that the proposed model is highly capable of predicting diabetes in the early stages.

Type 1 diabetes is a chronic condition that results from the destruction of insulin-producing β-cells in the pancreas. Current treatments for type 1 diabetes, such as insulin therapy and pancreatic islet transplantation, have several limitations and, hence not quite effective in the long run. As current therapy methods fail to slow disease development, novel strategies such as the development of a bioartificial pancreas are being seriously considered. Over the last decade, research has focused on tissue engineering, which aids in the design of biological alternatives for the repair and replacement of non-functional or damaged organs. Three dimensional (3D) bioprinting technology which employs 3D printing technology to generate 3D tissue-like structures from biomaterials and cells, offers a promising solution for the treatment of type 1 diabetes by providing the ability to generate functional endocrine pancreatic tissue. Bioprinted structures are therefore an important aspect of tissue engineering because they have been found to replicate the native extracellular matrix, promoting cell survival and proliferation. In this review, we extensively discussed about bioprinting endocrine pancreas for the treatment of type 1 diabetes particularly focussing on the choice of cells, biomaterials, growth factors, and essential considerations. Additionally, the key challenges and perspectives towards recapitulation of the pancreatic function of the pancreatic organ engineering technologies have also been discussed.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Abstract: Astrocytes (ACs) are the most abundant human cell in the brain and importantly, are the master connecting and communicating cells that provide structural and functional support of brain cells at all levels of organization. Further, they are recognized to be the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste and comprise the glymphatic system, which is critically dependent on the proper waste removal by the pvACef polarized aquaporin 4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role for synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI) and associate with white matter hyperintensities, lacunes, aging, accepted to be biomarkers for cerebral small vessel disease, increased in obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.

Coronavirus disease 2019 (COVID-19), an infectious disease pandemic, affected millions of people globally, resulting in high morbidity and mortality. Causing further concern, significant proportions of COVID-19 survivors suffer from the lingering health effects of severe acute respiratory syndrome virus 2 (SARS-CoV-2), the pathogen that causes COVID-19. One of the diseases manifesting as a post-acute sequela of COVID-19 is new-onset diabetes. This systematic review and meta-analysis will perform a comprehensive and systematic literature search to estimate the burden of new-onset diabetes after COVID-19. Specifically, this study will estimate the magnitude of the incidence, risk, and population-attributable fraction of new-onset diabetes. The study will also explore and summarize the data on the natural history or clinical course of the new-onset diabetes cases. Five bibliographic databases, including PubMed, MEDLINE, Embase, Scopus, and Web of Science, will be searched for eligible studies. The World Health Organization COVID-19 Research Database, preprint servers, and conference abstracts will also be searched. Cohort studies of COVID-19 patients of all ages providing data on new cases of diabetes in the post-acute phase of the illness will be included. The comparators to estimate the pooled risk ratio will be those with no diagnosis of COVID-19 or those infected with other respiratory tract infections. The findings of this study will likely inform clinical practice, public health guidelines, and policies for early detection and treatment of new-onset diabetes cases in the long-COVID phase. This protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: No.CRD42020200432).

The Mediterranean diet (MED) is highly recommended. Medical nutrition therapy is the cornerstone of diabetes treatment. We assessed adherence to the MED, and resultant micronutrient intake and glycemic control in youth with type 1 diabetes. Twenty adolescents, median age 18 years (interquartile range: 15.5-21), median diabetes duration 9 years (7-14), using continuous glucose monitoring devices, received personalized diet regimes based on MED. At 6 months post-intervention, the caloric intake remained unchanged; however, the carbohydrate proportion was lower (p=0.058) and the intakes of some monounsaturated fats increased (p=0.049). Sodium intake exceeded the recommended daily allowance by 250% (p=0.653), before and after the intervention. For blood glucose, the percent time-in-range 70-180 mg/dL improved from 52% (38-60) to 63% (47-71) (p=0.047). The total insulin dose decreased marginally, from 0.76 u/kg (0.64-0.97) to 0.72u/kg (0.61-0.89) (p=0.067). BMI z-score and waist circumference did not change (p=0.316 and p=0.161, respectively). Diastolic blood pressure percentile decreased from 73% (68-88) to 69% (50-79) (p=0.028), and LDL cholesterol from 114mg/ dl (105-134) to 104mg/dl (96-124) (p=0.059). The Israeli Mediterranean diet screener score increased, from 8 (7-11) to 13 points (12-14) (p=<0.001). The MED-based intervention demonstrated feasibility and improvements in glycemic outcomes and in certain nutritional parameters.

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones etc. and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases etc. and the list is increasing gradually. In this review, we summarize NETs mediated pathophysiology of different diseases, focus on some updated potential therapeutic approaches against NETs and share our future perspectives.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017/2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four parameter logistic) curves. The NHANES cohort (n=2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs 44 [25, 61] µmol/L, p&lt;0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs 53 [24, 104] mg/d, p=0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst the those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had lower a BMI than the NHANES cohort (26 [24, 28] kg/m2 vs 29 [25, 34] kg/m2, respectively). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes have 1.4- to 1.6-fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes.

Capsaicin, a lipophilic, volatile compound, is responsible for the pungent properties of chili peppers. In recent years, a significant increase in investigations into its properties has allowed the production of new formulations and the development of tools with biotechnological, diagnostic, and potential therapeutic applications. In this way, the possible clinical application of such compound is expanding every year. This opinion article aims to provide a synthesis of recent findings regarding the mechanisms by which capsaicin participates in the control of non-communicable diseases such as obesity, diabetes, and dyslipidemia. This opinion review also discusses the recent findings and clinical studies of the use of capsaicin in body weight control.

Aims: Multidisciplinary diabetic foot clinics have been shown to be an effective therapeutic model for reducing major amputations and mortality rates. The aim of this article is to assess the economic impact of the implementation of a multidisciplinary diabetic foot clinic in a hospital in Barcelona, Spain. Methods: Observational cost-benefit study of all subjects with diabetes admitted with the diagnosis of a major amputation due to diabetic foot from 2010 to 2020. Direct and indirect costs were compared before and after the introduction of the multidisciplinary diabetic foot clinic. Results: The individual cost per patient with diabetic foot was €14,768 before the implementation of the unit. After the implementation of the clinic, the expected cost was reduced to €5,985 due to a 40% reduction in the probability of hospitalization. Overall, the implementation of the clinic resulted in cost savings per patient valued at €8,783, of which, €7,165 are related to hospital benefits. Conclusion: The results of this analysis contributes to the evidence suggesting that multidisciplinary diabetic foot clinics are cost-effective, by demonstrating that they have a positive impact on patient health while also reducing the utilization of healthcare resources.

The clinical relationship between diabetes and inflammation is well-established. Various branches of science independently have confirmed that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with Type 2 diabetes mellitus (T2DM). Under diabetic condition, hyperglycemia, especially inflammation, and increased reactive oxygen species generation are bidirectionally associated. Inflammation, oxidative stress and tissue damage are believed to have a role in the development of diabetes. Although the exact mechanism underlying the oxidative stress and its impact on diabetes progression remains uncertain, the hyperglycemia-inflammation-oxidative stress interaction clearly plays a significant role in onset and progression of vascular disease, kidney disease, hepatic injury, pancreas damage and, therefore holds promise as a therapeutic target. Evidence strongly indicates that the use of multiple antidiabetic medications therapy fails to achieve the normal range for glycated hemoglobin target, signifying treatment resistant diabetes. Antioxidants with polyphenols are considered useful as adjuvant therapy for their potential anti-inflammatory effect and antioxidant activity. We aimed to analyze the current major points reported in preclinical in vivo and clinical studies of antioxidants in the prevention or treatment of inflammation in T2DM. Then, we will share our speculative vision of the future diabetes clinical trials.

Covid-19 pandemic has greatly affected the whole world since the beginning and it continues to affect it. The main aim of this study is to show how Covid-19 affect other mortal diseases; cancer, heart diseases, and diabetes in near future. With this purpose two mathematical models are proposed via Ordinary Differential Equations (ODEs); one for the relationship between Covid-19 and cancer and one for the relationship between Covid-19, diabetes and heart diseases. Afterwards, stability analyses of these models are demonstrated. In order to see the effect of parameters on the disease compartments, sensitivity analysis is applied. Results of sensitivity analysis revealed that huge percentage of people are still scared of visiting doctors and this may lead a massive increase in the diagnosis of other diseases for upcoming years. Moreover, figures displayed that there exists a relationship between diabetes and heart diseases. Especially, diabetes patients should be careful about their health situations and take care of their heart. In order to provide these, awareness of people should be developed.

Dear Ladies and Gentlemen, I thank you for suggesting to submit the manuscript with the title “Insulin resistance develops due to an imbalance in the synthesis of cyclic AMP and the natural cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP)” to the Editorial Board of the MDPI journal Stresses, and I ask for consideration to publish it in the journal Stresses. It was previously submitted to the MDPI journal Int. J. Mol. Sci. (IJMS-195 6513), but it was found that 1) it would not fit within the scope of this special edition and 2) it would primarily deal with cyclic PIP and would have not enough literature citation on the topic insulin resistance. The present version of the manuscript is improved, but the content is the same. The goal of this review is not to write again a summary on nearly all reports on insulin resistance as this was done by Dr. Petersen and Dr. Shulman, whose review has 961 literature citations. The present manuscript compiles what is known on cyclic PIP in relation to insulin resistance and the reason of writing this manuscript was that the discovered facts on cyclic PIP synthesis allow to suggest how insulin resistance most likely starts. Hitherto, reports on insulin resistance did not come close to this question. I am convinced that the manuscript makes an essential contribution to the question what causes the development of insulin resistance, and I have to say that stress overload is one of the reasons. Unfortunately, I have to mention a topic, about which I do not like to talk. Years ago, research groups postulated with rigor that the mediator of insulin action would be a peptide and then they suggested various, extracellularly synthesized glycans as mediators. They caused confusions and a high degree of disbelief in the matter of mediators of insulin action. In my review on cyclic PIP in IUBMB Life from 2020, I wrote in the introduction that cyclic PIP should not be confused with these mediators. But I cannot write this in the introduction of every report. I am keeping fingers crossed so that the editor in charge will find fair and openminded reviewers. Last not least I confirm that neither the manuscript nor any part of its content is currently under consideration or published in another journal. Kind regards, Henrich Wasner, PhD, BioReg Biopharm, TiLab; University of Illinois at Chicago; 2242 West Harrison St., Ste. 201, Chicago, Il 60612; USA

Pregestational and gestational diabetes mellitus are relevant complications of pregnancy and antidiabetic drugs are prescribed to obtain glycemic control and improve perinatal outcomes. The objective of this study was to highlight the prescription pattern of antidiabetics before, during and after pregnancy in Italy and to evaluate its appropriateness. A multi-database cross sectional population study using a Common Data Model was performed. In a cohort of about 450,000 women, the prescribing profile of antidiabetics seemed to be in line with the Italian standards for the treatment of GDM which currently do not recommend the use of oral antidiabetics and non-insulin injection, even if a small share of new users (up to 3.8% in the third trimester) used oral antidiabetics. A substantial variability in the prescription pattern was observed among the Italian regions considered: the highest increase was registered in Tuscany (4.2%), Umbria (3.5%) and Emilia-Romagna (2.6%) while the lowest in Lombardy (1.5%), Veneto (1.7%) and Apulia (1.7%). Analysing the prevalence of use of antidiabetics between foreign women we observed that the consumption during pregnancy was higher than Italians (second trimester: 1,8% vs 0,9%, third trimester: 3,6% vs 1,8%).

Background and Objectives: Similar to diabetes, the presence of left ventricular (LV) diastolic function (DD) has been reported in various studies which were conducted with people with a diagnosis of impaired fasting blood glucose (FBG). The study aimed to examine the effects of fasting blood glucose (FBG) levels on left atrial strain (LAS) estimated by two-dimensional echocardiography speckle tracking analyses in patients without known diabetes. Material and Methods: The study included 148 participants (74 female and 74 male) without a history of diabetes mellitus or chronic disease. The patients were divided into two groups as follows: individuals with FBG <100 mg/dl and those with FBG between 100-125 mg/dl after at least 8 hours of overnight fasting and according to these FBG levels STE measures were compared. Results: There was a significant decrease in the LA reservoir (52.3±15 vs. 44.5±10.7; p=0.001) and conduit strain (36.9±11.7 vs. 28.4±9.7; p=0.001) in the impaired FBG group. When the STE findings of both ventricles were compared, no significant difference was observed between the groups in right and LV strain imaging. Conclusion: In the earliest stage of LVDD, changes in atrial functional parameters become particularly evident. Echocardiographic analyses of these parameters can help to diagnose and determine the degree of LVDD while the morphological parameters are still normal. The addition of LAS imaging to the routine TTE study in patients with impaired FBG but without a DM diagnosis may be helpful in demonstrating subclinical LVDD or identifying patients at risk for LVDD in this patient group.

Background: Regardless of the indisputable benefits of insulin therapy, initiating insulin for diagnosed children with diabetes might be intimidating for parents. This study assesses the experience, fears, barriers and adherence to insulin use among the parents of diagnosed children with diabetes. Methods: A cross-sectional online survey was utilized for data collection from 218 participants between February and March 2023 in Jordan. The survey consisted of six sections to evaluate and assess: sociodemographic for both children with diabetes and their parents, the experience of using the insulin, the diabetes fear of self-injecting questionnaire (D-FISQ), the barriers for insulin administration including both sociocultural and other insulin-related factors, and insulin adherence. Results: More than 80% of the participants perceived a number of sociocultural barriers to insulin administration such as the tendency for addiction, lower efficiency of insulin than oral medication, and preference for complementary medicine over insulin. More than two-thirds of the participants complained of insulin-related barriers such as infections and sudden death in addition to learning the correct injection method. The general fear level was low, 8.56±7.87 (out of 45); however, more fear of insulin injection and self-testing was significantly associated with both sociocultural and insulin-related barriers, especially at the younger age. Conclusion: The results of this study indicated that parents have several barriers to insulin administration, mainly related to insulin injection. Therefore, more awareness about insulin therapy can help adjust the cooperation of patients, acceptance of treatment, ending with improving the quality of life and well-being.

Selenoproteins are a group of proteins containing selenium in the form of selenocysteine (Sec, U) as the 21st amino acid coded in the genetic code. Their synthesis is dependent on dietary selenium uptake and a common set of cofactors. Selenoproteins accomplish diverse roles in the body and cell processes by acting, for example, as antioxidants, modulators of the immune function, detoxification agents for heavy metals, and other xenobiotics, key compounds in thyroid hormone metabolism. Although the functions of all this protein family are still unknown, several disorders in their structure, activity or expression have been described by researchers. They concluded that selenium or cofactors deficiency, on one hand, or the polymorphism in selenoproteins genes and synthesis, on the other hand, are involved in a large variety of pathological conditions, including type 2 diabetes, cardiovascular, muscular, oncological, hepatic, endocrine, immuno-inflammatory, neurodegenerative diseases. This review is focused on specific roles in medicine only of selenoproteins that are each named after an alphabet letter, less known than the rest of them, regarding their implications in patho-logical processes of several prevalent diseases and also in disease prevention.

C-reactive protein to lymphocyte ratio (CLR) has been shown to be associated with diseases characterized by chronic, low-grade inflammation. Since type 2 diabetes (T2DM) is also associated with inflammation, we aimed to study the association between CLR and T2DM. Patients with T2DM who presented to internal medicine outpatient clinics of our institution were divided into 2 groups according to their glycosylated hemoglobin (HbA1c) levels as well-controlled (HbA1c&lt;7%) and poorly controlled (HbA1c≥7%) T2DM groups. Subjects assigned as healthy in routine check-up were included as control group. CLR values of the well and poorly controlled diabetics and control cases were compared. CLR of T2DM group (3.51 (0.03-21.78)) was significantly higher than that of the controls (0.65 (0.02-2.92)) (p&lt;0.001). CLR was found to have a sensitivity of 63.2% and a specificity of 97.3% in predicting T2DM. The CLR value of patients with poor diabetic control was 4.76 (0.06-21.78), while the CLR value of patients with well controlled disease was 2.53 (0.03-12.07) (p&lt;0.001). The sensitivity and specificity of the CLR in demonstrating poor diabetic control was 41.2% and the 86.1%, respectively. In conclusion, elevated CLR in T2DM patients and even more increased levels in poorly controlled diabetics suggest that CLR could be a useful additional diagnostic tool in treatment follow-up of the T2DM population.

The coronavirus disease 2019 (COVID-19) pandemic clearly has had a great influence on the lifestyle of the population, especially on patients with type 2 diabetes mellitus. During the COVID-19 outbreak, many countries/regions implemented social isolation measures, leading to an increase in negative behaviors and impairing the capability of diabetic patients to resist the COVID-19, ultimately causing a severe prognosis. Moreover, multiple studies have emphasized the significance of physical exercise in the management of type 2 diabetic patients infected with COVID-19 as the epidemic progressed. In our study, we selected research focusing on COVID-19-infected diabetic patients from Dec 1, 2019 to Aug 9, 2023 and sought to investigate the impact of type 2 diabetes on the immune function, inflammation factor levels, lung injury and mental disorders of patients, as well as to assess the risk of novel coronavirus pneumonia in these patients. And we also summarized the effects of high-intensity, moderate-intensity and low-intensity exercise on novel coronavirus pneumonia infection in type 2 diabetic patients and the mechanisms of their effects. Finally, diabetic patients with COVID-19 are suggested to perform low-intensity exercise to facilitate their recovery. Our study offers guidance for a proper understanding of the dangers of diabetes and the use of appropriate measures to reduce the risk of novel coronavirus pneumonia infections in type 2 diabetic patients.

Metabolic surgery can promote comprehensive physiological improvements to alleviate metabolic disorders, particularly for patients with type 2 diabetes. Nevertheless, the therapeutic scope has been limited owing to unexpectedly inconsistent surgical outcomes. Therefore, this study to overcome these obstacles by determining the fundamental mechanism underlying the conflicting outcomes. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified duodenal-jejunal bypass (DJB) procedures, were compared to understand the specific surgical patterns from different perspectives comprehensively. Patients in the nonobese group were exclusively included to prevent confounding effects from overweight patients with type 2 diabetes. Following intestinal anastomosis, the epithelial identity of the succeeding intestine was replaced by that of the proximal epithelium owing to altered crosstalk between the epithelium and opposing mesenchymal cells. Subsequent intestinal compensatory proliferation and rapid turnover rate accelerate the spread of the replaced epithelium. The main factors contributing to inconsistent outcomes of metabolic surgery are inadequate duodenal exclusion and inappropriate biliopancreatic limb length. Replacement of enteroendocrine cells during regeneration can lead to inconsistent outcomes in metabolic surgery. The type and density of enteroendocrine cells distributed at the terminal end of the proximal intestine play a significant role in diverse outcomes of metabolic surgery.

The number of people with gluten-related illnesses has been increasing and the available treatments include the introduction of a gluten-free diet. In the bakery industry, there are problems with gluten-free products, namely the important characteristics that this component gives to doughs and the low nutritional value they present. A disease that has also increased in recent years is diabetes mellitus, which is characterized by a lack of insulin and the effectiveness of its action (type 1 diabetes) or tissue insensitivity to the hormone (type 2 diabetes). In terms of treatments, there are several approaches: inhibition of digestive enzymes (α-amylase and α-glucosidase) or techniques based on mechanisms of action (stimulation of insulin production and release, insulin transport and decreased glucose absorption). Hyperglycemia is also associated with the production of reactive oxygen species, which leads to cell apoptosis. On the other hand, there was also an association with high levels of cholesterol in the body, which contributed to the development of other types of diseases. In this sense, macroalgae have been studied as a source of natural compounds and used as food supplements, due to their protein, amino acid and mineral content, and the anti-diabetic effect in controlling the glycemic index, oxidative stress and cholesterol have already been demonstrated. Seaweed emerges as a promising source of bioactive nutraceuticals for individuals with coeliac disease, diabetes, and hyperglycemia. The rising prevalence of gluten-related illnesses calls for effective treatments, and seaweed's potential in enhancing the nutritional value of gluten-free products is noteworthy. Additionally, its demonstrated anti-diabetic effects, including glycemic index control, oxidative stress reduction, and cholesterol management, make it a valuable dietary supplement. Further research is needed to explore the specific bioactivities of seaweed compounds and their mechanisms of action. Integrating seaweed-based nutraceuticals into diets could complement traditional treatments, offering potential health benefits to those with coeliac disease and diabetes.

Our findings indicate that all five phytocannabinoids reduce HG-HL-induced -cell loss likely through reducing apoptosis and pyroptosis. The protective effects of CBD, THCV, CBC, and CBN were seen in the GSIS impairment by HG-HL. Although all five phytocannabinoids tested in this research demonstrated the capability to inhibit β-cell dedifferentiation induced by HG-HL, CBD seems to be more effective compared to the other phytocannabinoids, as indicated by the specific biomarker responses of β-cells and progenitor cells to CBD.

(1) Background: Little research is done on the link of diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients, 27 of them had progressive DKD, defined as estimated glomerular filtration rate (eGFR) decline≥3 ml/min/year or increased albuminuria stage over the mean follow-up time of 5.89±1.73 years. Newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: Gastrointestinal symptom score demonstrated high reliability (Cronbach's α=0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p=0.019). The former group demonstrated more frequent bowel movement disorders (p=0.04). The scores correlated negatively with eGFR (r = -0.335; p = 0.001), positively with albuminuria (r=0.245; p=0.015), Hba1c (r=0.305, p=0.002), diabetes duration (r=0.251, p=0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, presence of lymphoid follicles and lymphoid aggregates. Conclusion: progression of DKD positively correlated with gastrointestinal symptoms, but more research is needed to clarify the causal relationships of the gut-kidney axis in T1D.

Background: Myocardial infarction (MI) is a major cause of mortality worldwide. Its presentation as ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) is influence by atherosclerosis risk factors. Aim: To assess the patterns of presentation and predicting risk factors of acute MI in Kosovo. Methods: This is a cross sectional study from the Clinic of Cardiology of the University Clinical Center of Kosovo, which included all patients hospitalized with acute MI over a period of 7 years (January 1st, 2014 to December 31st, 2020). Data was collected using a structured questionnaire and epidemiological patterns and risk factors were analyzed. Results: Among 7353 patients admitted with acute MI (age 63 ± 12 years, 29% female), 4366 (59.4%) patients had STEMI, and 2987 (40.6%) NSTEMI. Patients age was not different between the two groups (p=0.077). NSTEMI patients smoked less (48.3% vs. 54%, p<0.001), but were more diabetics (37.8% vs. 33.6%, p<0.001), more hypertensives (69.6% vs. 63%, p<0.001), frequently had family history for coronary artery disease (CAD) (40% vs 38%, p=0.009), and included more females compared to STEMI patients (32% vs 27%, p<0.001). The two groups of patients, did not differ in the prevalence of significant CAD on angiography (66.8% vs. 67.8%, p = 0.396), but NSTEMI patients underwent less primary percutaneous interventions compared with STEMI patients (43.6% vs. 55.2%, p < 0.001). Conclusion: In Kosovo, STEMI is commoner than NSTEMI, who were mostly males, more likely to have diabetes, hypertension and family history for CAD compared to those with NSTEMI. Smoking and arterial hypertension proved the strongest predictors of acute MI, in Kosovo, thus highlighting the urgent need for better atherosclerosis risk control and education strategy.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease characterised by insulin resistance and elevated blood glucose levels, affecting millions of people worldwide. T2DM patients with dyslipidaemia have an increased risk of cardiovascular disease (CVD). A complex interplay of risk factors such as hyperglycaemia, dyslipidaemia, hypertension, obesity, inflammation and oxidative stress favour the development of atherosclerosis, a central mechanism in the pathogenesis of cardiovascular disease. Dyslipidaemia, a hallmark of T2DM, is characterised by elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol and the presence of small, dense low-density lipoprotein (LDL) particles, all of which promote atherosclerosis. In this article, we have attempted to present various treatment strategies that include pharmacological interventions such as statins, ezetimibe, PCSK9 inhibitors, fibrates and omega-3 fatty acids. We have also tried to highlight the pivotal role of lifestyle modifications, including physical activity and dietary changes, in improving lipid profiles and overall cardiovascular health in T2DM patients. We have also tried to present the latest clinical guidelines for the management of dyslipidaemia in T2DM patients. In conclusion, the treatment of dyslipidaemia in T2DM patients is of great importance as it lowers lipid particle levels, slows the progression of atherosclerosis and ultimately reduces susceptibility to cardiovascular disease.

Background: Novel technologies like continuous glucose monitor (CGM) systems are improving diabetes management by means of real-time sensor glucose levels, retrospective course of glucose and trend arrows. Continuous Glucose Monitoring (CGM) offers real-time alerts for (prognostic) hypo- and hyperglycemia, fast dropping or increasing glucose, and hence improving glycaemia under unstable conditions like during meals, physical activity and exercise management. Complex CGM systems challenge people with diabetes and health care professionals in interpreting rapid changes, sensor delay (~10-minute difference between interstitial and plasma glucose), and malfunctions. Enhanced prediction models are necessary for optimal insulin dosing, daily activities, and especially for future fully closed-loop systems. Methods: The aim of this study was to investigate the efficacy of three different predictive models for glucose responses: 1) an autoregressive integrated moving average model (ARIMA), 2) logistic regression, 3)and long short-term memory networks (LSTM), in predicting glucose levels after 15 minutes and one hour. We compared and evaluated the performance of these models in predicting hypoglycemia (<70 mg/dL), euglycemia (70-180 mg/dL), and hyperglycemia (>180 mg/dL). In more detail, by assessing metrics such as precision, recall, F1-score, and accuracy, we specifically assessed which model provided the most accurate and reliable predictions for glucose levels Results: As expected, ARIMA showed the worst accuracy especially predicting hypoglycaemia withing 1-hour (7.3%). The accuracy of the logistic regression model, predicting hypoglycemia during the first 15 min was higher (98%), comparing to LSTM (88%). However, the LSTM model (87%) exceeded the accuracy of hypoglycemia prediction of the logistic regression (83%) during an hour prognosis. The same pattern observed in hyperglycemia - ARIMA model (60%, 1 hour), logistic regression (96%, 15 minutes) and LSTM (85%, 1 hour) Conclusions: These findings suggest that different models may have varying strengths and weaknesses in predicting glucose levels, and the choice of model should be carefully considered based on the specific requirements and context of the clinical application. The logistic regression model was more accurate for the next 15 minutes, especially predicting hypoglycemia. However, the LSTM model exceeded logistic regression for the next one hour prediction. Future research could explore hybrid models or ensemble approaches that combine the strengths of multiple models to further improve the accuracy and reliability of glucose predictions.

Pregnant women with diabetes often present impaired fetal growth, which is less common if maternal diabetes is well-controlled. However, developing strategies to estimate fetal body composition beyond fetal growth that could better predict metabolic complications later in life is essential. This study aimed to evaluate subcutaneous fat tissue (femur and humerus) in fetuses with normal growth among pregnant women with well-controlled diabetes using a reproducible 3D-ultrasound tool and offline TUI (Tomographic Ultrasound Imaging) analysis. Additionally, three artificial intelligence classifier models were trained and validated to assess the clinical utility of the fetal subcutaneous fat measurement. A significantly larger subcutaneous fat area was found in three-femur and two-humerus selected segments of fetuses from women with diabetes compared to the healthy pregnant control group. The full classifier model that includes subcutaneous fat measure, gestational age, fetal weight, fetal abdominal circumference, maternal body mass index, and fetal weight percentile as variables, showed the best performance, with a detection rate of 70%, considering a false positive rate of 10%, and a positive predictive value of 82%. These findings provide valuable insights into the impact of maternal diabetes on fetal subcutaneous fat tissue as a variable independent of fetal growth.

Alexithymia as the inability to describe one's own feelings, is being increasingly researched. According to contemporary psychodynamic theories, negative emotions cannot be adequately named and externalized, but remain trapped in the body. Recent research shows the connection of alexithymia with numerous somatic diseases. Diabetes mellitus type 2 and obesity represent a great challenge in treatment, and the psychological profiles in these diseases are being studied more and more often. Therefore, alexithymia enters the focus of some research as one that could play a significant role namely in these diseases as the factor that makes a difference. The aim of this paper is a review of the literature with the purpose of understanding the current knowledge about the interconnection between alexithymia, obesity and type 2 diabetes mellitus.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and it has been implicated in the pathogenesis of inflammation, insulin resistance and obesity. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are the main form of vitamin D: the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity and cardiovascular disease. It's interesting to note that several long-term studies also revealed an inverse correlation between vitamin D level and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects, in fact while some studies demonstrated improvements in insulin sensitivity, glucose and lipid metabolism, others revealed no significant effect on glycemic control and inflammation. The aim of this review is to provide insight into the molecular basis of the relationship between vitamin D, insulin-resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

A preventive effect for tea and its bio active components in cardiovascular health has been suggested by the results of several epidemiological studies, treatments utilizing randomized controlled trials, and mechanistic investigations. Therefore, scientific interest in green tea's ability to prevent cardiovascular diseases (CVDs) is growing. Green tea benefits for the metabolic syndrome, which includes diabetes and hypertension but may also raise cholesterol levels. Additionally, green tea reduces the mortality from any cause, arrhythmia, stroke, coronary heart disease, heart failure, and other conditions.

Background: Gestational diabetes is a common complication during pregnancy that can lead to numerous adverse outcomes. Some studies suggest that probiotics may be used to treat gestational diabetes, however, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the effect of probiotics on blood glucose and pregnancy outcomes in women with gestational diabetes. Methods: A systematic search of PubMed, Embase, and Cochrane databases was performed (start date to August 22, 2023). Primary outcomes included fasting blood sugar (FBS), fasting serum insulin (FSI), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). Secondary outcomes included pregnancy and neonatal outcomes. Results: 15 articles (n = 1006 women) met the inclusion criteria and were included in the analysis. Compared to a placebo, probiotics can decrease FBS (MD -2.58, 95% CI -4.38 to -0.79, p &lt; 0.01), FSI (MD -2.29, 95% CI -3.40 to -1.18, p &lt; 0.01), HOMA-IR (MD -0.56, 95% CI -0.81 to -0.32, p &lt; 0.01), birthweight (MD -101.20, 95% CI -184.62 to -17.77, p = 0.02), neonatal intensive care unit (NICU) (RR 0.60, 95% CI 0.40 to 0.89, p = 0.01), and hyperbilirubinemia (RR 0.31, 95% CI 0.16 to 0.61, p &lt; 0.01), alongside higher QUICKI (MD 0.01, 95% CI 0.00 to 0.01, p &lt; 0.01). However, no other significant results were obtained. Conclusion: Probiotics may improve blood glucose indicators and reduce neonatal hyperbilirubinemia, NICU admissions, and birth weight in women with GDM.

The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades and the identification of differential glycemic responders can aid tailored treatment for prevention of pre-diabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among partic-ipants with elevated T2DM risk, to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary inter-vention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females, 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distin-guish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.

ObjectivesAbrus precatorius (AP) is a medicinal plant seldomly studied for its beneficial effects and as such significant gap exists in understanding the basis by which AP leaf bioactives (APLBs) elicit beneficial effects against diabetes mellitus (DM) type-1. MethodsWe estimated DM type-1 related parameters - total protein (TP), direct bilirubin (DB), urea, creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and serum glucose (SG) after treatment with methanol extracts of AP leaves (APMLE) for 21 days followed by histopathological analysis of kidney and liver sections. APLBs were collected from GCMS fractions, database and literature searches and common targets were cross-intersected with annotated DM type-1 genes from experimental GSE14503 microarray dataset and genecard database. Overlapping differentially expressed genes were collected, their protein-protein interaction network was constructed and analyzed using various bioinformatics tools: Enrichr, SRplot, GSEA, Cytoscape, PyRx, and Discovery Studio to provide insight into the potential molecular basis of APLBs in DM-type-1.Results 15 compounds were identified from GCMS analysis of APMLE. Antidiabetic potential of APMLE was observed with significant (p <0.05) normalization of SG, TP, DB, ALT, AST, ALP, urea & creatinine while hepatorenal photomicrographs indicated moderate safety of use. Erucic acid, oleic acid, phytol and stigmasterol interact with 25 type-1 DM biomarkers revealed to be enriched in lipid and prostaglandin metabolic processes, neuroactive ligand receptor interaction, PPAR signaling pathway, diabetic cardiomyopathy, and cAMP signaling pathway. Furthermore, PPARalpha (peroxisome proliferator-activated alpha) and SCD (stearoyl-coenzyme A desaturase) were revealed as core biotargets interacting with APLBs via hydrogen bond, hydrophobic interaction and van der Waals forces from docking study. ConclusionThis study demonstrated the potency of APLBs in vivo against type-1 DM. The potential basis of action has been studied from computational perspective. Future interests may provide additional experimental data into mechanisms by which APLBs elicit this remarkable ability.

Polymorphism of vitamin D3 receptor (VDR), has been associated with low bone mineral density and other immune and metabolic disorders; however, its impact on mortality of female dialysis patients is not well studied. This study aimed to identify bone mass-related factors, VDR gene polymorphism, and their interaction with morbid conditions that could influence all-cause mortality. In 246 female dialysis patients, age 43±11 years on continuous ambulatory dialysis peritoneal; 48%, haemodialysis; 23% and automated peritoneal dialysis; 29%. Tscore, Ca, PO4, albumin, hs-CRP, osteoprotegerin, fetuin, osteocalcin, iPTH, PINP and β-CTx were measured. PCR products were digested with Bsml to analyze VDR polymorphisms. Patients n=229; were followed for a median of 17 (15-31) months; 42 patients died. Bsml polymorphism, bb=64% and BB+Bb=36%. Hs-CRP was the risk of death in multivariate Cox Analysis. Patients with bb and inflammation had a higher risk of death (HR 2.48, 95% CI 1.08-5.68) persisted after adjustment for age, diabetes and iPTH (HR 2.33; 95% CI, 1.01-8.33) and after further adjustment for vintage, albumin, osteoprotegerin and vitamin D therapy (HR 3.49; 95% CI, 1.20-10.9). We may conclude that the presences of the bb genotype of VDR and inflammation have additive effects on all cause-mortality in females in CAPD, APD, and HD patients.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1,261 T2D patients and 1,105 control individuals. Our findings revealed significant associations between certain single nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p<0.001), m.14766C>T (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p<0.001), and m.16519T>C (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p=0.012) were significantly associated with diabetes probability. The variant m.16189T>C Previously reported in multiple studies in different populations, it was not found to be associated with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31,; p=0.83). These results provide evidence suggesting a link between some mtDNA polymorphisms and T2D, probably related to association rules and topological patterns and three-dimensional confirmation associated to regions where the changes are, rather than to point mutations in the sequence.

This scoping review comprehensively explores the existing literature on fenugreek (Trigonella foenum-graecum), a versatile herb known for its culinary and traditional medicinal uses. The review focuses on two key aspects: the hypoglycemic mechanism of fenugreek and its impact on milk production in breastfeeding women. By systematically analyzing and synthesizing the available evidence, this review aims to enhance our understanding of fenugreek's potential applications and identify research gaps for future systematic reviews. The search strategy targeted English-language animal studies published within the last five years that specifically investigated fenugreek's hypoglycemic mechanism and its effects on milk production. A total of 15,236 articles were initially identified from databases such as PubMed, Sci finder and ScienceDirect. After a rigorous selection process, including thorough evaluation of titles, abstracts, and full-texts, a subset of articles (including those titled "Impact of Fenugreek on Milk Production in Rodent Models of Lactation Challenge" and "Fenugreek Stimulates the Expression of Genes Involved in Milk Synthesis and Milk Flow through Modulation of Insulin/GH/IGF-1 Axis and Oxytocin Secretion") were included for detailed analysis. The findings 18 articles from the included studies demonstrate promising results regarding fenugreek's potential to stimulate milk production and regulate blood glucose levels. However, further research is necessary to unravel the underlying molecular pathways, establish optimal dosage guidelines, and assess long-term side effects. Overall, this scoping review offers valuable insights for lactating women seeking to enhance milk production and individuals managing blood sugar levels, providing potential alternative approaches for supporting lactation and glycemic control.

Background. Human Milk (HM) is a dynamic nourishment: its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important evaluate the impact that gestational diseases have on HM components and if their presence, as source of oxidative stress in the mother, influence milk’s redox homeostasis. To assess Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) effect on milk’s total oxidative load, we chose to investigate both oxidative and antioxidant aspects, with respectively Lipid hydrop-eroxides (LOOHs) and Glutathione (GSH)). Methods. GSH and LOOHs were quantified using an ELISA test. To investigate the effect of pathology on redox homeostasis, mixed linear model with unistructural covariance structure was performed. Results. A total of 120 mothers were re-cruited. The GSH concentration results significant lower in GDM women than in healthy only in colostrum (p<0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. Discussion. Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the anti-oxidant composition of HM mainly in colostrum, but in case of PE, the composition of HM milk is preserved.

Background: The number of people with type 2 diabetes is increasing daily, and therefore effective therapy is needed to successfully regulate glycemia and reduce the risk of associated complications. Recently, an oral formulation of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide has become available. Therefore, the aim of our study was to compare the effectiveness of the new oral formulation and the existing injectable formulation of semaglutide in terms of glycemic and body weight control in a real-world setting. Patients and methods: This was a single-center retrospective observational study conducted at the Rijeka Clinical Hospital Centre. A total of 106 patients with inadequately controlled type 2 diabetes (HbA1 ≥ 7%) on different oral or basal insulin supported oral therapy were recruited from the diabetes outpatient clinic, and data from electronic medical records were retrospectively collected and analyzed from May 2021 to November 2022. All subjects were GLP-1 RA naive and consequently prescribed 0.5 or 1.0 mg once weekly injectable semaglutide (IS) or 7 mg or 14 mg once daily oral semaglutide (OS) for at least 6 months. Glycated hemoglo-bin (HbA1c), body weight, and body mass index (BMI) were assessed prior to semaglutide administration and after a 6-month follow-up period. The primary endpoint was the change from baseline in HbA1c, and sec-ondary endpoints were the change in body weight and the proportion of participants with a reduction in body weight of ≥ 5% and ≥ 10%, respectively, 6 months after the initiation of semaglutide treatment. Results: At 6-month follow-up, no significant difference was observed between the two formulations in terms of HbA1c reduction (IS -1.1% vs OS -1.4%, p=0.126) and weight loss (IS -6.50 kg vs OS -5.90 kg, p=0.714). Exactly the same proportion of participants in both groups achieved a weight loss of ≥ 5% (56.7%, n=30). A weight loss ≥ 10% was observed in 20.7% (n=11) of participants administered IS and 15.1% (n=8) of participants adminis-tered OS, respectively (p=0.454). Conclusion: In a real-world setting, oral semaglutide as add-on therapy to ongoing antihyperglycemic treatment in patients with inadequately controlled type 2 diabetes who had not previously received GLP-1 RA demonstrated the same effectiveness as injectable semaglutide in terms of gly-cemic control and weight loss after 6 months of treatment.

Culinary herbs and spices are widely used in daily diets. Pakistan flora is enriched with phytochemicals due to a diverse range of land. Phytochemicals, including volatile and non-volatile compounds, have captured much interest due to their numerous health advantages and significance in daily diet. The present study aimed to conduct in-depth metabolomic profiling of Pakistani-grown fenugreek leaves (Trigonella foenum-graecum), fennel seeds (Foeniculum vulgare), mint leaves (Mentha royleana), coriander seeds (Coriandrum sativum) and basil leaves (Ocimum basilicum) by using liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography–mass spectrometry (GC-MS). The first study was conducted to optimize extraction using different solvents (methanol, ethanol, chloroform, acetone, and water). Total phenolic content (TPC), total flavonoid content (TFC), and total condensed tannins (TCT) were quantified along with the antioxidant and anti-diabetic activities. The highest TPC (125.42 ± 10.89 mg GAE/g) and the highest antioxidant and anti-diabetic potential were quantified in mint. Seventy-one phytochemical metabolites were identified using LC-MS/MS, while forty-nine volatile constituents were identified using the GC-MS. A positive correlation was identified between phenolic contents and their biological activities. Furthermore, molecular docking helped to find drug molecules with more excellent anti-diabetic activity based on their binding affinities. This study suggests that selected medicinal herbs from Pakistan have significant nutraceutical and phytopharmaceutical potential. This study could further help in drug discovery.

Transferrin (TF) is a key iron carrier protein. Studies in human cohorts and in cultured adipocytes suggested that decreased transferrin expression and intracellular iron in adipocytes leads to impaired insulin responsiveness and causes differential expression of genes involved in metabolism, insulin action, and obesity. While suggestive, these studies did not definitively prove in an intact organism that altering TF expression in adipocytes is sufficient to affect glucose homeostasis and insulin resistance. In this study we created a mouse model of decreased transferrin expression only in adipocytes (Trf+/-Cre+/-) to test the hypothesis that iron trafficking in adipose tissue is sufficient to affect insulin sensitivity. Area under the glucose curve (AUCg) after intraperitoneal glucose administration was increased in the Trf+/-Cre+/- mice compared to wild type (WT) mice on a normal chow diet, and the mice were slightly heavier (p=0.02 for both). Homeostasis Model of Insulin Resistance (HOMA-IR) values were also significantly higher in the Trf+/- Cre+/- mice (p<0.05). Thus, supporting our hypothesis, analysis of mice with decreased expression of TF restricted to adipocytes showed that a decrease in adipocyte TF is sufficient to affect insulin resistance, weight, and glucose homeostasis.

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is impacted already during adolescence in a genetic rat model for obesity and type 2 diabetes. Cognitive functioning throughout adolescence and early adulthood was investigated in Zucker Diabetic Fatty (ZDF), ZDF lean and healthy outbred Long Evans rats using operant touchscreens. Blood glucose, insulin and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues and the prefrontal cortex. Adolescent ZDF obese rats outperformed lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in ZDF early adult obese rats. Histological analyses at early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent obese ZDF rats even display enhanced cognition despite their early diabetic profile.

Pancreatic ductal adenocarcinoma (PDAC) a highly malignant neoplasm, is classified as one of the most severe and devastating types of cancer. PDAC is a notable malignancy that exhibits a discouraging prognosis and a rising occurrence. The interplay between diabetes and pancreatic cancer exhibits a reciprocal causation. The identified metabolic disorder has been observed to possess noteworthy consequences on health outcomes, resulting in elevated rates of morbidity. The principal mechanisms involve the suppression of the immune system, the activation of pancreatic stellate cells (PSCs), and the onset of systemic metabolic disease caused by dysfunction of the islets. From this point forward, it is important to recognize that pancreatic cancer-related diabetes (PCRD) has the ability to increase the likelihood of developing pancreatic cancer. This highlights the complex relationship that exists between these two physiological states. Therefore, we investigate into the complex domain of PSCs, elucidating their intricate signaling pathways and the profound influence of chemokines on their behavior and final outcome. In order to surmount the obstacle of drug resistance and eliminate PDAC, researchers have undertaken extensive efforts to explore and cultivate novel natural compounds of the next generation. Additional investigation is necessary in order to comprehensively comprehend the effect of PCRD-mediated apoptosis on the progression and onset of PDAC through the utilization of natural compound. This study aims to examine the potential anticancer properties of natural compound in individuals with diabetes who are undergoing chemotherapy, targeted therapy, or immunotherapy. It is anticipated that these compounds will exhibit increased potency and possess enhanced pharmacological benefits. According to our research findings, it is indicated that naturally derived chemical compounds hold potential in the development of PDAC therapies that are both safe and efficacious.

In the aftermath of the COVID pandemic, post-COVID-19 syndrome (PCS) remains a challenge and may continue to represent a major health problem in the future. Moreover, the influence of type 2 diabetes and being overweight on PCS remains unclear. This study aimed to assess this influence. We performed an observational study from October 2020 to July 2022, which included 466 patients (269 males and 197 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms after 1 month of COVID-19 infection. The patients were divided into four groups according to the study objectives: patients with type 2 diabetes, overweight patients, overweight patients with type 2 diabetes, and normal-weight patients without type 2 diabetes. The clinical and demographic data collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. Our results showed that type 2 diabetes patients had a more difficult course of treatment and longer hospitalization. Moreover, more type 2 diabetes patients underwent rehabilitation than the other study groups. The prevailing symptoms in our patients with PCS were dyspnea and fatigue, mostly in female patients with type 2 diabetes. Our study also showed that more women with type 2 diabetes and more overweight women with type 2 diabetes suffered from secondary infections. Further, more overweight patients were treated in the intensive care unit compared to the other groups. However, our study showed an interesting result that patients with type 2 diabetes had the shortest PCS durations. Type 2 diabetes and being overweight are risk factors for PCS onset and prolonged duration. Therefore, our data that revealed a shorter duration of PCS in type 2 diabetes patients compared to the other investigated groups was unexpected. We believe that answering this question regarding the results will enable us to improve PCS treatment in general.

Diabetes mellitus is a widespread chronic metabolic disorder demanding regular blood glucose level surveillance (BGLs). Current invasive techniques, such as finger-prick tests, often result in discomfort for patients, leading to infrequent monitoring and potential health complications. The primary objective of this study was to design a novel, portable, non-invasive system for diabetes detection using breath samples, named as DiabeticSense, an affordable digital health device for early detection, encouraging immediate intervention. The device employed MOSFET-based electrochemical sensors to assess volatile organic compounds in breath samples, whose concentrations differ between diabetic and non-diabetic individuals. The system merged body vital signs with sensor voltages obtained by processing breath sample data to predict diabetic conditions. Our research used readings from 100 patients at a nationally recognised hospital to form the dataset. Data was then processed 10 using a Gradient Boosting Classifier model, and performance was cross-validated. The proposed system attained a promising accuracy of 86.6%, marking an improvement of 20.72% over an existing regression technique. The developed device introduces a non-invasive, cost-effective, and user-friendly solution for preliminary diabetes detection. It has the potential to increase patient adherence to regular monitoring.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

Mucinous breast carcinoma is a rare subtype of mammary neoplasm encountered in medical practice. It represents approximately 1-6% of all breast cancers and is more common in postmenopausal women. There are two subtypes of mucinous breast carcinoma: pure and mixed. We report the case of a 73-year-old Caucasian woman diagnosed with mucinous pancreatic cystadenoma in 2007. She underwent a surgical procedure involving pancreatectomy of the body and tail, along with multiple known cardiovascular and metabolic comorbidities. In November 2019, during a clinical-biological evaluation for associated diseases, a mucinous carcinoma of the right breast was accidentally detected and later confirmed through further investigations. For treatment, a surgical procedure was performed involving lower right quadrantectomy with right axillary lymph node dissection. The postoperative clinical course was favorable. In conclusion, we present the case of a patient diagnosed with mixed mucinous breast carcinoma, without axillary lymph node invasion. Postmenopausal women with diabetes, overweight, and obesity have an increased susceptibility to breast cancer, with our patient having all these risk factors. To date, no study has demonstrated the genetic or radiation implication in the occurrence of mucinous carcinomas, nor the possible development of mucinous carcinomas in series in the same patient. Current data are insufficient to provide recommendations for the screening of malignant mucinous tumors in subjects with significant cardiometabolic risk factors.

Diabetes mellitus, a metabolic disorder that is persistent in nature, is identified by an elevated concentration of glucose in the bloodstream. The disease has become a major public health problem, affecting millions of people globally, and is associated with significant morbidity and mortality. The increasing prevalence of diabetes and the lack of effective therapeutic interventions have led to the exploration of alternative and complementary forms of therapy, including ethnomedicine. Ethnomedicine is the study of traditional medical systems and the medicinal plants used by Indigenous communities. In other words, Ethnomedicine refers to the traditional medical practices and beliefs of a particular cultural or ethnic group. The most popular example of traditional medicine is the use of Aloe vera for the treatment of various diseases such as sunburn, cuts, burns, hypertension, diabetes, and jaundice for thousands of years [1]. In recent years, there has been increasing interest in the potential role of ethnomedicine in the management of diabetes, given its widespread use in many communities and its potential to offer cost-effective and culturally acceptable treatment options. It encompasses a range of traditional healing practices, including herbalism, acupuncture, and massage therapy. Despite the inconsistencies, there is growing evidence to suggest that certain ethnomedical practices may be effective in the management of diabetes [2,3]. For example, several studies have shown that certain herbal remedies, such as cinnamon, ginseng, and bitter melon, may have potential benefits in terms of improving glucose control and reducing the risk of complications associated with diabetes. Evidence-based ethnomedicine is an approach that applies scientific principles and methods to evaluate the efficacy and safety of traditional medical practices. This approach is crucial in the development of effective and safe ways to treat diabetes. To date, there have been numerous studies conducted to examine the efficacy and safety of various ethnomedical interventions for diabetes, including herbal remedies, dietary changes, and physical activity [4]. However, it is important to note that not all ethnomedical interventions for diabetes have been thoroughly evaluated, and many remain unproven. Furthermore, some interventions may be associated with significant risks, particularly in terms of drug interactions and adverse effects. As such, it is crucial that any ethnomedical interventions for diabetes be carefully evaluated using rigorous scientific methods and that patients be advised to consult with their healthcare provider before using any such interventions. It is important to note that the results of these studies have been mixed, with some showing promising results, while others have failed to demonstrate significant benefits. In this chapter, the evidence-based current state of ethnomedicine for diabetes was reviewed. We first provide an overview of diabetes and its pathophysiology, followed by a discussion of traditional medicinal practices used to treat the disease. We then present a systematic review of the scientific literature on the use of ethnomedicine for diabetes, focusing on herbal remedies and dietary interventions. Our review found that several medicinal plants offered promising results to treat all types of diabetes. For example, Gymnema sylvestre, a traditional Indian herb, has been shown to reduce blood glucose levels and improve insulin sensitivity [5]. Additionally, the use of bitter melon (Momordica charantia) has been shown to reduce fasting blood glucose levels and improve glucose tolerance in individuals with type 2 diabetes [6]. Another important aspect of ethnomedicine for diabetes is the use of dietary interventions [7]. Traditional diets, such as the Mediterranean diet, have been shown to have beneficial particularly in terms of improving glycaemic control, reducing the risk of cardiovascular disease, and insulin sensitivity [8]. Additionally, the use of low-carbohydrate diets, such as the ketogenic diet, has been shown to improve glycaemic control in individuals with type 2 diabetes [9]. Traditional medicine has a long history of treating the symptoms and managing the condition. However, the efficacy and safety of these traditional practices have not always been scientifically tested, and there is a lack of standardization and regulation in the production and use of traditional remedies for diabetes. This creates a challenge for healthcare providers and patients, who need to ensure that the treatments they use are safe and effective. Additionally, there is a need for further research to understand the mechanisms by which traditional remedies may be effective in managing diabetes and to determine the optimal dosage and administration methods [9]. Finally, it is also important to understand that the use of traditional remedies may interact with conventional medications, leading to adverse effects; for example, the use of Chinese traditional medicine, known as “herb ginseng,” for the treatment of various health conditions, including diabetes sometimes cause the side effect such as dizziness, confusion, and fainting while interacting with the anti-diabetic medications [10]. Therefore, it is important to approach the use of ethnomedicine for diabetes with caution and under the guidance of a qualified healthcare professional. In conclusion, evidence-based ethnomedicine offers a promising approach to the treatment of diabetes. While further research is needed to fully understand the mechanisms and safety of these interventions, the results to date suggest that traditional remedies and dietary interventions have the potential to be effective in the management of this disease. However, it is important to approach the use of ethnomedicine for diabetes with caution and under the guidance of a qualified healthcare professional and to continue to conduct rigorous scientific research to fully understand the benefits and risks associated with these interventions.

Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are two devastating diseases that may occur in non-diabetics or individuals with diabetes and when combined is referred to as cardiorenal disease. The impact of cardiorenal disease on society, the economy and the healthcare system is enormous. Although there are numerous therapies for cardiorenal disease, one therapy showing a great deal of promise is sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The SGLT family member, SGLT2, is often implicated in the pathogenesis of a range of diseases and dysregulation of the activity of SGLT2 markedly effects the transport of glucose and sodium across the luminal membrane of renal cells. Inhibitors of SGLT2 were developed based on the anti-diabetic action initiated by inhibiting renal glucose reabsorption, thereby increasing glucosuria. Of great medical significance, large-scale clinical trials utilising a range of SGLT2 inhibitors have demonstrated both metabolic and biochemical benefits via numerous novel mechanisms such as sympathoinhibition which will be discussed in this review. In summary, SGLT2 inhibitors clearly exert cardio-renal protection in diabetic and non-diabetic subjects in both pre-clinical and clinical settings by improving hyperglycemia, high blood pressure, hyperlipidemia and diabetic retinopathy. (188 Words)

Continuous glucose monitoring devices allow diabetes condition management. However, when limited data is available, one option is to increase their size by generating synthetic samples. From a homemade wearable prototype was created a real dataset with 18 instances and 53 attributes that capture characteristics of capillary and venous blood glucose, oxygen concentration, pulse rate, skin temperature, and 24 modules and 24 phases related to bio-impedance. The objective of this article is to generate synthetic datasets, and also it investigates the ideal features subset and optimal model for non-invasive diabetes prediction. Gaussian-Copulas (GC), conditional generative adversarial networks (CG), variational autoencoders, and Copula-GAN techniques' were used to generate five synthetic datasets. Experiments show that GC1 and GC2 datasets follow min/max boundaries and are not copies of the original data. Multilayer perceptron regressor outperformed (train and test) with 2.17, 2.51 in MAE; 9.29, 13.59 in MSE; 3.05, 3.69 in RMSE, and 0.95, 0.92 in R2 in GC1, and 2.64, 3.02 in MAE; 11.43, 15.11 in MSE; 3.38, 3.89 in RMSE, and 0.94, 0.92 in R2 in GC2 with eight features. Future work is necessary to explore autoencoder and generative architectures, datasets with diverse characteristics, and the effect of the number of features.

Erectile dysfunction (ED) is the inability to achieve or maintain an erection during sexual performance. ED is one of the most common and neglected complications of diabetes. Almost 35-75% of diabetic men around the world suffer from ED. Although the exact mechanism by which diabetes causes ED is not well understood. However, several studies suggested it may be related to damage to the nerve and vessels that supply the penis.

Type 1 diabetes (T1D) is one of the most prevalent endocrinological diseases among children and young adults, with a growing incidence rate reaching up to 2.9 new cases per year per 100 000 persons below 15 years of age. We report the rare case of a 20-year-old female patient with T1D, hemoglobin D (HbD) heterozygote variant and high myopia of -10,00 spheric diopters and describe the retinal microvascular alterations visible on OCT angiography (angio-OCT). The patient also presented severe stature deficit (less than 3 standard deviations) and delayed puberty, which could not be explained only by suboptimal glycemic control, indicated a possible hypopituitarism. The HbA1c level evaluated with high performance liquid chromatography (HPLC) method was 6.5%, a falsely low value due to the HbD hemoglobinopathy. On ophthalmic evaluation the angio-OCT scan showed the following retinal microvascular alterations for the RE: the FAZ area vas 0.39 mm2, the FAZ perimeter was 2.88 mm and the circularity index was 0.58; for the LE: the FAZ area vas 0.34 mm2, the FAZ perimeter was 3.21 mm and the circularity index was 0.41. Clinicians should consider high performance retinal screening methods such angio-OCT evaluation for young T1D patients, especially for those with associated pathologies like high myopia and hemoglobinopathies. Moreover, multiple evaluation methods of the HbA1c values are mandatory as hemoglobinopathies can interfere with HbA1c assay methods accuracy.

It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia means low bone regeneration and a chronic inflammatory response. The purpose of the study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on 5 groups of white female Wistar rats: group 1 - regeneration of a bone defect in healthy animals under a blood clot; group 2 - regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3 - bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4 - filling of a bone defect with a CH-SA-HA construct in healthy animals; Group 5 - filling of a bone defect CH-SA-HA in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.

Diabetes mellitus is a chronic disease that affects millions of people worldwide. Article focuses on detecting the presence of diabetes in patients using microarray gene data obtained from the pancreas. Handle the high-dimensional nature of the data, four different dimensionality reduction techniques, namely Bessel Function, Discrete Cosine Transform (DCT), Least Square Linear Regression (LSLR), and Artificial Algae Algorithm (AAA) are used. After reduced the data, Meta-heuristic algorithms are applied like Dragonfly Optimization Algorithm (DOA) and Elephant Herding Optimization Algorithm (EHO) for feature selection. Ten classification techniques are using to classify the data in both the format like without feature selection method and with feature selection method. The classification techniques are Non-Linear Regression (NLR), Linear Regression (LR), Gaussian Mixture Model (GMM), Expectation Maximum (EM), Bayesian Linear Discriminant Classifier (BLDC), Logistic Regression (LoR), Softmax Discriminant Classifier (SDC), Support Vector Machine (SVM) with linear kernel, Support Vector Machine (SVM) with polynomial kernel, and Support Vector Machine (SVM) with Radial Basis Function (RBF) kernel. Results showed that the AAA with SVM(RBF) achieved an accuracy of 90% without feature selection. However, when feature selection was applied, with EHO of AAA with SVM(RBF) exhibited the highest accuracy of 95.714%, followed closely by with DOA of AAA with SVM (RBF) at 94.28%.

Sphingolipids play an important role in the development of diabetes both type 1 and type 2 diabetes as well as in the development of both micro- and macro-vascular complications. Several reviews have been published concerning the role of sphingolipids in diabetes but most of the emphasis has been on the possible mechanisms by which sphingolipids, mainly ceramides, contribute to the development of diabetes. Research on circulating levels of the different classes of sphingolipids in serum and in lipoproteins and their importance as biomarkers to predict not only the development of diabetes but also of its complications has only recently emerged and it is still in its infancy. This review summarizes the previously published literature concerning sphingolipid-mediated mechanisms involved in the development of diabetes and its complications focusing on how circulating plasma sphingolipid levels and the relative content carried by the different lipoproteins may impact their role as possible biomarkers both in the development of diabetes and mainly in the development of diabetic complications. Further studies in this field may open new therapeutic avenues to prevent or arrest/reduce both the development of diabetes and progression of its complications.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications, as well as HbA1c. This cross-sectional observational study consisting of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values analyzing biochemical and body composition measurements. Shapiro-Wilk test with Lilliefors correction, non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-1 ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked with defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of altered mitochondrial dynamics in pancreatic β cells using ge-netic/pharmacologic approaches, and how these affect insulin secretion.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels. Despite the availability of pharmacological treatments, dietary plans, and exercise regimens, T2DM remains a significant global cause of mortality. Consequently, there is a growing interest in exploring lifestyle interventions, such as Intermittent Fasting (IF). This study aims to identify underlying patterns and principles for effectively improving T2DM risk parameters through IF. By analyzing data from multiple randomized clinical trials investigating various IF interventions in humans, a machine learning algorithm was employed to develop a personalized recommendation system. This system advises pre-diabetic and diabetic individuals on the most suitable IF interventions to improve T2DM risk parameters. With a success rate of 95%, this recommendation system offers highly tailored guidance, optimizing intermittent fasting's benefits for diverse population subgroups. The results of this study allow us to conclude that weight is the crucial feature for females, while age is the determining factor for males to reduce glucose levels in blood. By revealing patterns in diabetes risk parameters among individuals, this study not only provides practical guidance but also sheds light on the underlying mechanisms of T2DM, contributing to a deeper understanding of this complex metabolic disorder.

Type 1 diabetes (T1D) is associated with hyperglycaemia-induced hypoxia and inflammation. The study assessed the effects of a single high-intensity interval exercise (HIIE) on glycaemia (BG) and serum level of pro-inflammatory cytokines and an essential mediator of adaptive response to hypoxia in T1D patients. The macronutrients intake was also evaluated. Nine patients suffering from T1D for about 12 years and nine healthy individuals (CG) were enrolled and completed one session of HIIE at the intensity of 120% lactate threshold and duration of 4 x 5 min intermittent with 5 min rest after each bout of exercise. Capillary and venous blood was withdrawn at rest, immediately after and at the 24 h post-HIIE for analysis of BG, hypoxia-inducible factor alpha (HIF-1α), tumour necrosis factor alpha (TNF-α) and vascular-endothelial growth factor (VEGF). Pre-exercise BG was significantly higher in the T1D compared to the CG (p = 0.043). HIIE led to a significant decline in T1D patients’ BG (p = 0.027) and to a tendency for a lower BG at 24-h post-HIIE vs pre-HIIE. HIF-1α was significantly elevated in the T1D compared to CG and there was a trend for HIF-1α to decline, and VEGF, TNF-α to increase in response to HIIE in the T1D group. Both groups consumed higher and lower than recommended amounts of protein and fat, respectively. In T1D group, a tendency for a higher digestible carbohydrate intake and more frequent hyperglycaemic episodes on the day after HIIE were observed. HIIE was effective in reducing T1D patients’ glycaemia and improving the short-term glycaemic control. HIIE has the potential to improve adaptive response to hypoxia by elevating the serum level of VEGF. Patients’ diet and level of physical activity should be screened on a regular basis, and they should be educated on the glycaemic effects of digestible carbohydrates.

Background: Despite advances in diabetes-related treatments, the effects of the disease have not yet been adequately reversed or prevented in patients. Therefore, there is an urgent need to develop more effective medication-assisted treatments in this field. Methods: In this study, type 1 diabetes mice models was established using multiple low-dose alloxan, and the diabetic mice were treated with three doses of dimethyl fumarate (DMF) i.e low, medium, and high viz. 20, 40 and 80 mg/kg, respectively for a period of 21 days. Then, specific test were done to evaluate blood biochemical parameters, oxidative stress markers, inflammatory genes expression, and histopathological changes in the mice kidney and liver. Results: The obtained results showed remarkably improved anti-diabetic, hepato-renal-protective, and oxidative stress indexes of DMF in alloxan-induced diabetic mice (p< 0.001). Treated mice with DMF demonstrated a noteworthy decrease in blood glucose levels when compared with diabetic group (p< 0.001). Diabetic liver and kidney tissues showed marked dilation of bile ducts, tubules, infiltration, and inflammation. On the contrary, the histological features of the treated mice with DMF improve as shown by normal size of glomerular capillaries along with decrease in less dilatation of ducts in comparison with diabetic mice. The real-time quantitative PCR results indicated that DMF injection decreased the alloxan-induced increase of significant elevations in mRNA levels of pro-inflammatory cytokines and adhesion molecules such as TNF-α, IL-6, and NF-κB levels in both kidney and liver tissues. Meanwhile, mice treated with DMF showed an increase in Sirt1 and Nrf2 expression in comparison to diabetic group. Conclusion: In conclusion, it can be concluded that DMF treatment provides hepato-renal protective effects on alloxan-induced diabetic mice model by attenuating ROS inflammatory pathways. Keywords: Diabetes, Dimethyl fumarate, Alloxan, Anti-inflammatory responses, Hepato-renal-protective effects.

This study aimed to present a systematic meta-analysis examining the association between Helicobacter pylori (H. pylori) infection, hemoglobin A1c levels, and the development of type 1 diabetes mellitus. The initial search identified 451 articles related to the association between H. pylori infection and T1DM. Among them, 14 articles had 2,971 participants meeting the inclusion criteria for advanced meta-analysis. A significant association was observed between H. pylori infection and T1DM, with an odds ratio (OR) of 1.87 (95% confidence interval [CI]: 1.27–2.78, p = 0.002). A subgroup analysis on H. pylori status showed that a longer duration of diabetes diagnosis and higher hemoglobin A1c levels were significantly associated with H. pylori infection (p < 0.001 for both). However, there was no significant association between H. pylori infection and the diagnostic age of diabetes (p = 0.306). These findings contribute to the understanding of the association between H. pylori infection and T1DM, thereby highlighting the potential role of H. pylori in influencing the duration and glycemic control of diabetes.

With an increasing aging population worldwide, the concept of multimorbidity has attracted growing interest over recent years, especially in frailty, which leads to progressive multisystem decline and increased adverse clinical outcomes. The relative contribution of multiple disorders to overall frailty index in older populations has not been established so far. This study aimed to assess the association between the Vulnerable Elders Survey-13 (VES-13) score, which is acknowledged to be one of the most widely used measures of frailty, and the most common ac-companying diseases among hospitalized adults aged 60 years old and more. 2860 participants with an average age of 83 years were included in this study. Multiple logistic regression with adjustment for age and nutritional status was used to assess the independent impact of every particular disease on vulnerability. Diabetes mellitus type 2, coronary artery disease, atrial fibrillation, heart failure, chronic kidney disease, osteoarthritis, fractures, eyes disorders, depression, dementia, pres-sure ulcers, and urinary incontinence were associated with higher scores of VES-13. Hospital admission of older subjects with those conditions should primarily draw attention to the risk of functional decline and while qualifying older patients for further treatment, particularly in surgery and oncology. At the same time, lipid disorders, gastrointestinal diseases, higher body mass index and albumins level were related to lower risk of being vulnerable, what may be attributed to younger age and better nu-tritional status of those patients.

Type 1 diabetes imposes a complex and challenging routine on patients and caregivers. Therefore, considering individual experiences and personal facilitators to promote assertive interventions is crucial. However, no studies have addressed these perspectives in the Brazilian adult population. We aimed to identify psycho-behavioral characteristics perceived as facilitators for coping with the condition. We used a biographical method to conduct semi-structured, face-to-face, in-depth interviews for each participant. Transcripts were analyzed using inductive thematic analysis. Participants (n = 22) were aged 18–57 years (mean: 30.2, standard deviation (SD): 8.7), and the duration since diagnosis was approximately 20.6 years (SD: 4.6). Twelve (54.4%) were women, 13 (59.1%) used insulin pumps, 14 (63.6%) had at least a college degree, and 13 (59.1%) had HbA1C (glycated hemoglobin) levels above 58 mmol/mol (7.5%). Five major themes emerged: 1) peer learning, 2) ownership, 3) welcoming experiences, 4) equity, and 5) reframe the path (P.O.W.E.R.). All themes appeared in the lived experiences shared by participants with HbA1C levels below 58 mmol/mol (7.5%). Improved glycemic control can be achieved, and the challenges encountered in diabetes care within similar socioeconomic contexts can be addressed, by an interdisciplinary care team that takes P.O.W.E.R into consideration when providing person-centered care strategies.

Abstract: The surge of diabetes poses a significant global health challenge, particularly in Oman and the Middle East. Early detection of diabetes is crucial for proactive intervention and improved patient outcomes. This research leverages the power of machine learning, specifically, Convolutional Neural Networks (CNNs), to develop an innovative 4D CNN model dedicated to early diabetes prediction. A region-specific dataset from Oman is utilized to enhance health outcomes for individuals at risk of developing diabetes. The proposed model showcases remarkable accuracy, achieving an average accuracy of 98.49% to 99.17% across various epochs. Additionally, it demonstrates excellent F1 score, recall, and sensitivity, highlighting its ability to identify true positive cases. The findings contribute to the ongoing effort to combat diabetes and pave the way for future research in using deep learning for early disease detection and proactive healthcare.

In 2020, it is estimated that 7.8% of all live births in the United States were complicated with gestational diabetes, with around 10% of all pregnancies in North America involving gestational diabetes. GDM’s prevalence has been increasing over time, likely due to the population’s rising BMI and increasing maternal age. GDM has been long associated with increased complications in pregnancy, from preeclampsia and macrosomia in the short-term, to long term ramifications including the development of type 2 diabetes mellitus, cardiovascular disease, and potential effects on the offspring, including obesity, insulin resistance, hypertension, and increased risk of autism. Additionally, as the field of epigenetics continuously grows, we are able to further elucidate epigenetic mechanisms at play in the development of GDM and how these changes may affect the offspring. In this narrative review, we have compiled recent and relative clinical studies that highlight the role epigenetics may play in the development and perpetuation of GDM, as well as its possible effects on the offspring.

Vanadium is a well-known essential trace element, which usually exists in oxidation states in form of vanadate cation intracellularly. The pharmacological study of vanadium begins at the discovery of its unexpected inhibitory effect on ATPase. Thereafter, the protective effects on cells and the abilities in glucose metabolism regulation were observed from vanadium compound, leading to the application of vanadium compounds in clinical trials for curing diabetes. Alzheimer’s dis-ease (AD) is the most common dementia disease in elderly people. However, there is still no efficient agents for treating AD safely to date. This is mainly because of the complexity of the pathology, which are characterized by the senile plaques composed by amyloid-beta (Aβ) protein in the parenchyma of brain and the neurofibrillary tangles (NFTs) derived from hyperphosphorylated tau protein in neurocyte, along with mitochondrial damage, and eventually the central nervous system (CNS) atrophy. AD was also illustrated as type-3 diabetes, because of the observations of insulin deficiency and the high level of glucose in cerebrospinal fluid (CSF), as well as the im-paired insulin signaling in brain. In this review, we summarized the advance of applicating vanadium compound on AD treatment in experimental research and pointed out the limitation of the current study on using vanadium compounds in AD treatment. We hope it will help the future study in this field.

Diabetes and mental disorders have been recognized as two significant public health concerns globally. Recent research indicates that there is a bidirectional relationship between these two conditions, with each influencing the other's course and outcomes. Nutrition plays an essential role in the prevention and treatment of both mental disorders and diabetes. A comprehensive review of existing literature was conducted to examine the impact of anxiety and depression on the development of diabetes and the influence of diabetes on the occurrence of mental health disorders such as anxiety and depression. Additionally, the effects of nutrition on the prevention and management of mental disorders, diabetes, and related complications in at risk individuals were assessed. Our findings show that mental disorders, such as depression and anxiety increase the risk of developing type 2 diabetes and are associated with poorer glycemic control, increased diabetes-related complications, and higher mortality rates. Conversely, diabetes is also linked with an increased risk of developing mental health disorders, including depression, anxiety, and cognitive decline. The biological, psychological, and social factors that contribute to the comorbidity between these two conditions are complex and multifaceted. Therefore, an integrated approach to the management of both conditions is critical for improving patient outcomes and reducing the overall burden of disease. Nutritional interventions should be utilized to reduce the risk of diabetes in patients with anxiety and depression as well as enhance mental health in patients with diabetes.

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany and the retraction of phenformin (N-Phenethylbiguanide) because of the letal complication of acidosiss,metformin (1-1-dimethylbiguanide) was first released in France in 1959 and then in the USA in 1995 for oral treatment of diabetes type 2. Acute gastrointestinal side effects often lead to dose reduction and strongly limit adherence to therapy.Main long-term consequences are deficency of vitamin B12 and of iron and sometimes also acidosis development. Intravenously injected F18-labelled glucose in metformin-treated type 2 diabetics accumulates in the the small and even more in the large intestine.The densitometry picture observed in metformin-treated diabetics is similar to that observed in patients after bowel-cleansing or chronically taking different types of laxatives where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to „attraction“ of glucose from the hepatocyte to the intestine,possibly through its secretion into the bile.Metformin is not different from the other biguanides ,synthalin B and phenformin.The mechanism of action,and the side effects are comparable to those of laxatives.

Abstract: Background and Objectives: A growing number of epidemiologic studies have found that diabetes mellitus may increase cancer risk and is implicated in numerous other metabolic and inflammatory disorders. The increase in pro-inflammatory cytokines plays a major role in insulin resistance and leads to hypoalbuminemia, and micro- and macrovascular diabetes complications, including kidney disease and anemia. This study aimed to investigate the utility of CEA, CRP, serum albumin level, hemoglobin, and LDH as biomarkers for cancer risk and the biological implications of diabetes on the evolution and prognosis of oncological patients. Material and methods: We conducted a retrospective, longitudinal, observational study, on a total group of 434 patients, 217 diagnosed with a form of cancer and with type 2 diabetes as a comorbidity, and the other 217 – control group, without diabetes. These patients were admitted to the oncology clinic. In subgroups, the same number of patients was considered, depending on the location of the oncological pathology. Anemia, hypoalbuminemia, elevated lactate dehydrogenase, glycated hemoglobin, and C-reactive protein levels are more pronounced in subjects with type 2 diabetes and cancer. Conclusions: The presence of diabetes negatively affects the clinical and biological prognosis of cancer patients.

Nutrition, diabetes, and mental disorders are interconnected and significantly impact an individual's overall health and well-being. This comprehensive review aims to explore the complex interplay between nutrition, diabetes, and mental disorders, highlighting the latest research findings in this field. While the influence of nutrition on the development and management of both diabetes and mental disorders is widely recognized, there remains a gap in understanding the intricate interplay between nutrition, mental health, and diabetes. Diabetes is associated with an increased risk of mental disorders, including depression, anxiety, and cognitive decline. Mental disorders can also contribute to the development of diabetes through various mechanisms including increased stress, poor self-care behaviors, and adverse effects on glucose metabolism. Thus, the mechanisms linking nutrition, diabetes, and mental disorders are complex and multi-factorial. Inflammation, oxidative stress, gut microbiota alterations, and neuroendocrine dysregulation have emerged as potential pathways that may mediate the relationship between nutrition, diabetes, and mental disorders. Additionally, deficiencies in essential nutrients such as omega-3 fatty acids, vitamin D, B vitamins, zinc, chromium, magnesium, and selenium have been implicated in the pathogenesis of both diabetes and mental disorders. Our findings indicate that the use of personalized dietary interventions and targeted nutrient supplementation can improve metabolic and mental health outcomes in patients with type 2 diabetes.

Life is supported by metabolism, a vital physiological activity. It guarantees enough energy available to power every cellular activity. The primary cellular substrate, glucose, is where the majority of the energy needed by the cell to support all other life activities and the growth of living creatures is derived. The quality of life is greatly impacted by any disease or flaw that alters the metabolism of glucose. There is no known cure for the metabolic illness known as diabetes. As diabetes is so varied, the only effective treatments would be based on precision medicine and a molecular strategy. This review covers a wide range of topics, including the ability to recognize the various forms of diabetes, the anthropogenic and genetic influence of the cause of diabetes, the severity of the various forms of diabetes, its potential existential risk, the disease burden, and clinical methods for diagnosing them. The most recent research goes on to recommend ways to ameliorate the disease, including diet-based management, biotherapies, and other individual lifestyle choices. Futuristic therapy using molecular biology approach was suggested. Recent research found a direct correlation between an individual's lifestyle and the rate of gene mutation in diabetes. There is an existential risk associated with the sickness as the rate of the spread of the disease among population globally is faster than the world's population growth rate. It is possible to think of diabetes as a silent pandemic.

The study aimed to estimate the prevalence and association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with Type 2 Diabetes Mellitus (T2DM). According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged: 50–80 years) were divided into three groups: Non-sarcopenia (n = 38), Possible Sarcopenia (n = 31, 28.2%), and Sarcopenia (n = 41, 37.3%). Blood samples were collected and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D3 levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, there was a significant association between sarcopenia with BMI, body fat percentage (BF%), and dietary energy and protein intake. Low serum vitamin D3 is a significant risk factor for possible sarcopenia.