A good management of diabetes requires at the same time self-regulation behaviour and a balanced involvement of family components. This study’s aims were: understanding fear of injections and perceptions of family conflicts in preadolescents and adolescents with type 1 diabetes mellitus and their mothers, comparing their perceptions, and identifying the risk factors impacting patients’ quality of life. Participants were one hundred and two patients (Mean age = 14.63, SD = 2.43; age range = 10-19 years; Females = 52) and their mothers (Mean age = 46.94, SD = 6.2, age range = 27-63 years), who filled in self and proxy-report questionnaires. Twenty % of patients and 14.7% of their mothers reported clinical score for fear of self-injection and blood testing. Mothers reported higher fear of injecting and family conflicts compared with the patients. Age, fear of injecting and family conflicts impacted significantly on patients’ quality of life perceptions. Clinical consideration and recommendations are given basing on the empirical results.

Abstract—Low-frequency Fahræus–Lindqvist-driven (not blood pressure-driven) oscillations in the small vessels are crucial because oscillations in small vessels support nutrient supply. Understanding of this is critical in type 2 diabetes mellitus (T2DM) to develop therapeutic measures to prevent Alzheimer's Disease Related Dementias: vascular factors contribute to cerebrovascular disease as well as mild cognitive impairment and dementia, which are predicted to affect 152 million people by 2050 (Alzheimer's Disease International London, UK, 2019). In this clinical study, we performed functional near-infrared spectroscopy (fNIRS) of the forehead to investigate the effect of the Mini-Cog with three-item recall test on the prefrontal cortex (PFC) activation and the relative oscillatory power in the 0.01–0.02-Hz (Fahræus–Lindqvist effect) and 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency bands in elderly (60 years and older) T2DM and age-matched controls. We found a significant (p<0.01) difference in the PFC activation between elderly subjects with T2DM and age-matched elderly controls. Moreover, power spectral density (PSD) analysis revealed a significantly lower relative power in 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency band in elderly subjects with T2DM during the Mini-Cog three-item recall test. Furthermore, a drop in the oscillatory power in the 0.01–0.02-Hz frequency band during Mini-Cog three-item recall test was found more pronounced in the elderly subjects with T2DM. Therefore, our study highlighted portable brain imaging to capture cerebrovascular reactivity to cognitive load that may provide a biomarker of cerebrovascular dysfunction in T2DM.Clinical Relevance— Our study establishes forehead portable brain imaging for monitoring cerebrovascular function in T2DM under cognitive load.

Diabetes is a group of diseases characterized by loss of β cell mass and/or -function, resulting in hyperglycemia. Approx. 537 million people worldwide suffer from diabetes – a number which is expected to increase. Diabetes is primarily treated by exogenous insulin, which comes with the challenges of maintaining glycemic control to prevent ketoacidosis and severe complications. The need for a curative treatment has initiated the research in β cell regeneration. Several studies in mice have identified essential genes for β cell fate, which can be manipulated in other cells to induce generation of new β cells. Zebrafish, a regeneration-positive animal model, has shown several different sources of new β cells, including regeneration by self-replication, neogenesis by duct-associated progenitor cells, and transdifferentiation of other endocrine islet cells. The animal models used in this research area are either limited by their low regenerative ability (mice), or their small size and remoteness from humans (zebrafish). There is a need for new animal models of diabetes, in which the molecular pathways of endogenous regeneration can be studied. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells. The axolotl has shown great regenerative capability, as they have proven capable of regenerating amputated limbs, and hearts with myocardial infarction, among other organs. This study aims to establish a diabetic axolotl model, investigate their regenerative ability in the pancreas, and examine the potential systemic effects of the induced disease. In a pilot study, five different protocols using STZ (streptozotocin) were tested, and the most optimal protocol was found. Furthermore, the glucose tolerance test was optimized to characterize the glycemic state of the animals. The effect of the treatment on blood glucose levels was measured to characterize the development and decline of the disease. The histological changes in the pancreas were examined. Moreover, the systemic effects of the STZ treatment were investigated in blood and urine. The study indicated that it is possible to induce diabetes in the axolotl, but variations between the animals should be minimized, or the sample size should be increased to conduct a satisfying experiment, as it was not possible to induce diabetes in all animals. Regeneration was not observed histologically, but a restoration of blood glucose levels was seen over the span of the experiment. Lastly, edema formation was observed in some of the STZ-treated animals, but the cause of edema remains undetermined.

Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.

Background and objectives: Induction of labor (IOL) is an event that occurs in up to one-quarter of pregnancies; less is known about the outcomes and safety of IOL in obese pregnant woman; no data is available on misoprostol vaginal insert (MVI) IOL in high-risk pregnancy obese women. Objectives: (1) to evaluate the rate of successful IOL with 200 μg MVI in obese (Body Mass Index - BMI over 30 kg/m2) high-risk pregnant women: late-term pregnancy, hypertension or diabetes, compared to obese non-high-risk ones; (2) to evaluate the safety profile of MVI in high-risk pregnancy obese patients. Study design: We conducted a cross-sectional study in "Filantropia" Clinical Hospital, Bucharest, Romania, from June 2017 to September 2019 (28 months). From a total of 11,096 registered live births, IOL was performed in 206 obese patients; 74 obese high-risk pregnant patients matched the inclusion criteria; of these, 33.8% pregnancies (n=25) were late-term (41 – 41+6 weeks), 43.2% (n=32) had associated pathologies (hypertension and diabetes); labor induction was guided using a standardized protocol. We evaluated the maternal and gestational age, parity, fetal tachysystole, hyper-stimulation, initial cervical status, time from induction to delivery, drug side effects, mode of delivery, and neonatal outcomes. Results: (a) The overall successful labor induction rate, evaluated by the vaginal delivery rate, was 71.6% (n=53), spontaneously or instrumentally assisted; 28.4% (n=21) births were unsuccessful MVI IOL, converted into caesareans. (b) No significant differences were found regarding the maternal outcomes; in terms of perinatal outcomes of safety, four cases of high-risk pregnancies vaginally delivered were associated with neonatal intensive care unit (NICU) admissions and a one-minute Apgar score under seven (5.4%). Most cases with adverse effects of misoprostol have been managed conservatively, except for three emergency C-section cases. Conclusions: Misoprostol vaginal insert is a safe choice in IOL in obese high-risk pregnancies with good maternal and perinatal outcomes.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10mg of delta-9-tetrahydrocannabinol (THC). 30-minutes following marijuana ingestion, participants imbibed a 75g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 minutes; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-to-30 minutes were detected (P=0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; P>0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

Structure-based design and synthesis of two biphenyl-N-acyl-β-D-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

The objective of this study was to identify circulating miRNAs affected by disease duration in newly diagnosed children with type 1 diabetes. Forty children and adolescents from The Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12 and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR and quantified for 179 human plasma miRNAs. The effect of disease duration was analyzed by mixed models for repeated measurements, adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p and hsa-miR-497-5p) were found to significantly change expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies ICA, IA-2A, GADA65 and 4 cytokines IL-4, IL-10, IL-21, IL-22 were associated with the miRNAs at different time points. Pathway analysis revealed association with various immune-mediated signaling pathways. Eight miRNAs, involved in immunological pathways changed expression levels during the first five years after diagnosis in children with type 1 diabetes, and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.

The switch from intermittently scanned continuous glucose monitoring (isCGM) to real-time (rt) CGM could improve glycemic management in suboptimal controlled type 1 diabetes patients, but long-term study is lacking. We evaluated retrospectively the ambulatory glucose profile (AGP) in such patients after switching from Free Style libre 1 (FSL1) to Dexcom G4 (DG4) over 1 year. Patients (n=21, 43±15 years, BMI 25±5, HbA1c 8.1±1.0%) had severe hypoglycemia and/or HbA1c≥8%. AGP metrics (time-in-range (TIR) 70-180 mg/dL, time-below-range (TBR)<70 mg/dL or <54 mg/dL, glucose coefficient of variation (%CV), time-above-range (TAR) >180 mg/dL or >250 mg/dL, glucose management indicator (GMI), average glucose) were collected the last 3 months of FSL1 use (M0) and of DG4 for 3, 6 (M6) and 12 (M12) months of use. Values were means ± standard deviation or medians [Q1;Q3]. At M12 versus M0, the higher TIR (50±17 vs. 45±16, P=0.036), and lower TBR<70 mg/dL (2.5 [1.6;5.5] vs. 7.0 [4.5;12.5], P=0.0007), TBR<54 mg/dL (0.7 [0.4;0.8] vs. 2.3 [0.8;7.0], P=0.007) and %CV (39±5 vs. 45±8, P=0.0009), evidenced a long-term effectiveness of the switch. Compared to M6, TBR<70mg/dL decreased, %CV remained stable, while the improvement on hyperglycemia exposure decreased (higher GMI, TAR and average glucose). This switch was a relevant therapeutic option, though a loss of benefit on hyperglycemia stressed the need for optimized management of threshold alarms. Nevertheless, few patients attained the recommended values for AGP metrics, and the reasons why some patients are “responders” vs “non-responders” warrant to be investigated.

Background: Level of perceived competence as a basic psychological need could trigger achievement of diabetes self-management goals. Due to lack of a specific data collection tool to measure level of self-competence among Persian speaking patients with diabetes this study was conducted for cross-cultural adaptation and psychometric assessment of the Persian version of Perceived Competence Scale for Diabetes (PCSD-P). Methods: Standard translation/back-translation procedure was carried out to prepare a preliminary draft of the PCSD-P. Content and face validity of the early draft were checked by an expert panel including 15 scholars in the field of health education and promotion as well as nursing education with experience of working and research on diabetes. The final drafted questionnaire was completed by 177 randomly selected patients with type 2 diabetes. Based on the collected data structural validity of the contrived version was appraised using exploratory and confirmatory factor analysis (EFA, CFA). Cronbach's alpha and Intraclass Correlation coefficients (ICC) were used to check the scale’s reliability and internal consistency. ; (3) Results: The estimated measures of Content Validity Index (CVI= 0.95) and Content Validity Ratio (CVR= 0.8) were in the range of acceptable recommended limits. The EFA analysis results demonstrated a single factor solution according to the items’ loadings for the component. The model fit indices i.e. RMSEA= 0.000, CFI=1, TLI=1, GFI= 0.998, NFI= 0.999 RFI= 0.995 confirmed consistency of the hypothesized one-factor solution. Values of the internal consistency and reliability coefficients were also in the vicinity of acceptable range (α= 0.892, ICC=0. 886, P= 0.001). Conclusions: The study findings revealed good internal validity and applicability of the PCSD-P to measure degree of self-competence among Persian speaking type 2 diabetes patients to manage the chronic disease. Due to unrepresentativeness of the study sample future cross-cultural test of PCSD-P on diverse and broader Persian speaking populations is recommended.

Background: The course of obesity and type 2 diabetes (T2D) development is highly dependent on adipose tissue (AT) angiogenesis. Moreover, angiogenic microRNAs (miRNAs) play pivotal role in AT functionality. The aim of this study was to analyze the relationship of the human AT miR-221-3p/222-3p cluster and their regulatory network with obesity and T2D. Methods: miR-221-3p/222-3p and their target genes (TG) expression levels were measured in visceral and subcutaneous ATs from patients classified according to their BMI and to their glycemic status with a high degree of insulin resistance (IR) and T2D. In silico analyses of miR-221-3p/222-3p and their TGs were performed to identify relevant signaling pathways. Results: A multivariate analysis, including the simultaneous expression of miR-221-3p and miR-222-3p as dependent variables, showed significant differences considering the variables; tissue depot, obesity, IR and T2D altogether as independent variables. In addition, miRNAs and their TGs were differentially expressed according to obesity degree, glycemic status, and AT depot type. Our in silico analysis showed that miR-221-3p/222-3p cluster TGs are mostly involved in angiogenesis, WNT signaling pathway and apoptosis. Conclusion: These findings suggest that the miR-221-3p/222-3p cluster and their related regulatory networks could represent tangible targets for the management of obesity and associated metabolic disorders

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we explored whether PAK signaling should be targeted via chemoprevention to reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Systematic literature review provided the effect of anti-diabetic drugs on PAK signaling. Review of clinical studies revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-dependent diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM involves Wnt and G-protein signaling which is altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone is promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

The incidence of Type 1 Diabetes (T1D) in the Arab world, particularly, oil and gas rich Gulf Cooperative Council (GCC) countries has more than doubled in the last twenty years. Therefore, there is a dire need for careful systematic familial cohort studies, especially in high-risk populations. Several immunogenetic factors affect the pathogenesis of the disease. Genes in the human leukocyte antigen (HLA) account for the major genetic susceptibility to the disease. The triggering agents initiate disease onset by destruction of pancreatic β-cells. The autoantibodies against glutamic acid decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and zinc transporter-8 (ZnT-8A) comprise the most reliable biomarkers for T1D in both children and adults. Although three of the GCC countries, namely Kuwait, Saudi Arabia and Qatar are among the top 10 countries with high incidence rate of T1D, no proper diagnostic and prediction tools were applied in the region. Understanding the disease sequelae in a homogenous gene pool with high consanguinity in the GCC could help solve the challenges in understanding pathogenesis, as well as hasten the prevention of T1D. Arab states must incorporate T1D predictive and intervention policies on a war-footing basis to minimize the burden of this serious disease.

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. We aimed to assess whether a time trend in AAM with associated disease risk is also present in Mexico. For this, we used data of 30,826 women from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, whereas Welch-ANOVA was used to test for a time trend. AAM decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years). AAM (in years) was negatively associated with weight (β = -1.01 kg; 95 % CI -1.006, -1,004) and BMI (β = -1.01 kg/m2; -1.007, -1.006), and positively with height (β = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

Evolutionary psychology theories propose that contact with green, natural environments may benefit physical health, but little comparable evidence exists for brown, natural environments, such as the desert. In this study, we examined the association between “brownness” and “greenness” with fasting glucose among young residents of El Paso, Texas. We defined brownness as the surface not covered by vegetation or impervious land within Euclidian buffers around participants’ homes. Fasting glucose along with demographic and behavioral data was obtained from the Nurse Engagement and Wellness Study (N = 517). We found that residential proximity to brownness was not associated with fasting glucose when modeled independently. In contrast, we found that residential greenness was associated with decreased levels of fasting glucose, despite the relatively low levels of greenness within the predominantly desert environment of El Paso. A difference between the top and bottom greenness exposure quartiles within a 250 m buffer was associated with a 3.5 mg/dL decrease in fasting glucose levels (95% confidence interval: -6.2, -0.8). Our results suggest that within the understudied context of the desert, green vegetation may be health-promoting to a degree that is similar to other, non-desert locations in the world that have higher baselines levels of green.

Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis presents a critical synthesis of development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus, qualitatively synthesized. Out of these, 47 were included into quantitative synthesis. There was substantial heterogeneity in reporting of these outcomes (I²= 88.35%, Q= 317.64), with significant improvement (SMD=0.36, 95% CI: 0.23 to 0.49) noted in biomedical outcomes in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (P < 0.001). These interventions should be implemented in healthcare and community settings to improve health of patients suffering from DM and obesity.

Hypothesis: Anti-diabetic drugs modulate p-21 activated kinase (PAK) signaling Introduction: Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease associated with increased cancer risk. PAK signaling is implicated in cellular homeostasis when regulated, and cancer when unrestrained. Recent reports provided a role for PAK signaling in glucose homeostasis, but the role of PAKs in the pathogenesis of T2DM is unknown. Here we performed a mini-meta analysis to explore if anti-diabetic drugs modify PAK signaling pathways, and provide insight regarding modulation of these pathways to potentially reduce diabetes-associated cancer risk. Methods: PAK interacting partners in T2DM were identified using online STRING database. Correlation studies were performed via systematic literature review to understand the effect of anti-diabetic drugs on PAK signaling. Mini meta analysis correlated multiple clinical studies and revealed the overall clinical response rate and percentage of adverse events in piogliazone (n=53) and metformin (n=91) treated patients with PAK-associated diseases. Results: A total of 30 PAK interacting partners were identified (10: reduced beta-cell mass; 10: beta-cell dysfunction; 10: obesity-insulin resistance) which were highly associated with Wnt, and G-protein signaling. Anti-diabetic drug metformin activated signaling pathways upstream; whereas pioglitazone inhibited pathways downstream of PAK. Overall clinical response upon pioglitazone treatment was 53%. 79% of pioglitazone and 75% of metformin treated patients had adverse events. Pioglitazone reduced molecular-PAK biomarkers of proliferation (Ki67 and CyclinD1), and metformin had the opposite effect. Conclusions: PAK signaling in T2DM likely involves Wnt and G-protein signaling which may be altered by anti-diabetic drugs metformin and pioglitazone. Apart from the therapeutic limitations of adverse events, pioglitazone may be promising in chemoprevention, however long-term multi-centered studies, which initiate pioglitazone treatment early will be required to fully assess the full potential of these drugs.

The primary goal of this research is to examine the α-amylase inhibitory effect of phytoconstituents found in the roots of the Cyclea peltata plant. The extract will also be used to investigate the effect of root extract on α-amylase inhibition assay. The roots were gathered, processed, and extracted in petroleum ether before being kept at 4ºC. The extract was exposed to a preliminary phytochemical examination. The extract was employed in the α-amylase inhibition experiment at concentrations of 50, 100, 200, 400, 600, 800, and 1000 µg/ml with acarbose as a control. Molecular docking analysis was performed on the phytoconstituents cycleapeltine, cycleadrine, cycleacurine, cycleanorine, cycleahomine chloride, and acarbose on human pancreatic alpha-amylase 1B2Y. A preliminary phytochemical study revealed the presence of alkaloids, saponins, and terpenoids. The tests came back negative for flavonoids, steroids, and tannin. The root extract inhibited α-amylase at 69.42 ± 0.74 % at 1000 µg/ml and acarbose at 94.63 ± 0.57 %. The IC50 value was calculated and found to be 484.08 µg/ml for the extract and 42.47 µg/ml. The docking studies, revealed that cycleacurine (-4.751 Kcal/mol) has a comparable anti-diabetic effect to Acarbose (-6.713 Kcal/mol). Furthermore, the function groups –OH and –NH found in phytoconstituents interacted with the active site of 1B2Y similarly to acarbose. This provides evidence that the function groups –OH and –NH present in the phytoconstituents might inhibit alpha amylase.

Racial and ethnic disparities exist in diabetes prevalence, health services utilization, and out-comes including disabling and life-threatening complications. Home health care may especially benefit older adults with diabetes through individualized education, advocacy, care coordina-tion, and psychosocial support for patients and their caregivers. This study examined factors as-sociated with hospital discharge to home health care and subsequent utilization of home health care among a cohort of Medicare beneficiaries with diabetes, age 50 and older, living in the United States. The cohort (n=786,758) was followed for 14 days after a diabetes-related index hospitalization, using linked Medicare administrative, claims, and assessment data (2014-2016). Multivariate logistic regression models included patient demographics, comorbidities, hospital length of stay, geographic region, neighborhood area deprivation, and rural/urban setting. In ful-ly adjusted models, hospital discharge to home health care was significantly less likely among Hispanic (OR 0.8, 95% CI 0.8-0.8) and American Indian (OR 0.8, CI 0.8-0.8) compared to white patients. Among those discharged to home health care, all racial/ethnic minority patients were less likely to receive services within 14-days. Further work should focus on eliminating systemic racism in home health care referral and systemic barriers to receiving home health care services.

Permanent neonatal diabetes may occur either in isolation or associated with multi-organ syndromes. It is caused by mutations in the genes responsible for pancreatic β cell mass or function. We report new cases of consanguineous parents from Saudi Arabia with a homozygous deletion of exons 1and 2, and exon 5-9 of the GLIS3 gene, who presented with permanent neonatal diabetes associated with intrauterine growth retardation, severe congenital hypothyroidism without other manifestation in the liver, renal or eyes in the 1^st one and cystic renal changes in the 2^nd patient. Mutations in the GLI-similar 3 (GLIS3) gene encoding the transcription factor GLIS3 are a rare cause of neonatal diabetes and congenital hypothyroidism with only 15 reported patients worldwide to date.

Rising child obesity rate creates a need for tools quantifying metabolic changes in obese children and adolescents for purposes of comorbidities early detection or prevention. A candidate for such role seem to be miRNAs – in vivo serving as the suppressing factors of the gene expression. The aim of this study was to review the recent discoveries in this field and to conclude directions of research or application of studied molecules. Repeated browsing of databases, followed by screening for eligibility of results, led to final approval of 9 articles. Filtered studies examined the differences in miRNA (miR) expression levels of obese subjects and children suffering from obesity comorbidities. Studies concerning the endothelial dysfunction (ED) identified miR-630 as a possible treatment option. Search for the alternative markers in diagnosis of non-alcoholic fatty liver disease (NAFLD) suggested value of miR-199a-5p and miR-122. MiR-486, miR-146b and miR-15b may serve as a panel of markers grading the development of type 2 diabetes mellitus (T2DM) in children, although further research raised doubts in that matter. Another panel of miRNA molecules was indicated as useful in early detection of alterations leading to metabolic syndrome (MetS). No valid link between studied miRNAs and atherosclerosis (AS) was found. MiRNAs seem to be promising prognostic markers for the diagnosis of NAFLD, T2DM and MetS in children. Further studies are required to support these findings.

Type 1 diabetes (T1D) is an autoimmune condition where the body’s immune cells destroy their insulin-producing pancreatic beta-cells leading to dysregulated glycaemia. Individuals with T1D control their blood glucose through exogenous insulin replacement therapy, often using multiple daily injections or pumps. However, failure to accurately mimic intrinsic glucose regulation results in glucose fluctuations and long-term complications impacting key organs such as the heart, kidneys, and/or the eyes. It is well-established that genetic and environmental factors contribute to the initiation and progression of type 1 diabetes, but recent studies show that epigenetic modifications are also important. Here, we discuss key epigenetic modifications associated with type 1 diabetes pathogenesis and discuss how recent research is finding ways to harness epigenetic mechanisms to prevent, reverse, or manage type 1 diabetes.

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants (cat, sod, gpx, and gst) and the components of the insulin signaling pathway (insulin Rβ, irs-1, pi3k, akt, mtor) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes’ gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nfκb. Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components.

The prevalence of diabetes mellitus (DM), considered one of the most common metabolic disorders, has dramatically increased and resulted in higher rate of morbidity and mortality around the world, in the past decade. It is well known that insulin resistance in target tissues and a deficiency in insulin secretion from pancreatic β-cells are the main characteristic of type 2 diabetes. The aim of this study was the bio-evaluation of compounds isolated from three selected plant species; namely, Salvia africana-lutea, Leonotis ocymifolia and Plectranthus madagascariensis, for their glucose uptake ability. Methanolic extracts were produced from the arterial part of each plant. Compounds were identified using different spectroscopic techniques. The glucose uptake ability of each compound was then evaluated in mammalian cells using 2-deoxyglucose-6-phosphate. The cytotoxicity of each compound was established via the MTT assay. Chromatographic purification of the three plant species yielded fifteen pure terpenoids. Compounds 1 (p = 0.0031), 8 (p = 0.0053), and 6 (p = 0.0086), showed a marked increase in glucose uptake, with p values of p=0.0031, p=0.0053 and p=0.0086, respectively. Additionally, 1, 4 and 6 exhibited cytotoxicity toward mammalian tissue with a decrease in cell viability of ~70%, ~68% and ~67%, respectively. The results suggested that several compounds demonstrated a marked increase in glucose uptake while two of the compounds exhibited signs of cytotoxicity. It may, therefore, be suggested that these compounds be considered as potential candidates for novel plant-derived alternative therapies in the treatment of type 2 diabetes.

Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis in insulin-secreting beta-cells is essential. Several pathophysiological conditions and pharmacological agents disrupt the ER homeostasis, thereby causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways whenever the ER stress persists. ER stress has been linked to several diseases, such as cancers, obesity, and diabetes. Thus, the regulation of ER stress may provide possible therapeutic targets for many diseases. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, resulting in irreversible UPR activation and cells death. Despite much progress in understanding the pathophysiology of UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provided up-to-date information regarding the current status of UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

The prevalence of type-2 diabetes mellitus (T2D) is increasing worldwide and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be integrated daily in the diet are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially-available yogurt (control yogurt). Interestingly, we found that feeding of this synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the composition of gut microbiota compared to milk; conversely, the control yogurt negatively modulated the gut microbiota by significantly increasing the abundance of detrimental bacteria like Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected intact pancreatic islet morphology compared to the milk control, while the commercial yogurt demonstrated worse effects on pancreatic physiology. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a modality to prevent diabetes progression.

BACKGROUND AND PURPOSE—Atherosclerotic plaque instability and rupture in patients with asymptomatic carotid artery stenosis (ACAS) is a leading cause of major adverse cardiac events (MACE). This could be mainly evidenced in patients with pre-diabetes. Indeed, the altered glucose homeostasis and insulin resistance could cause over-inflammation of atherosclerotic plaque, favoring its conversion to unstable phenotype with rupture and MACE. Notably, the metformin therapy reducing the metabolic distress and the inflammatory burden, could lead to reduction of MACE in ACAS patients with pre-diabetes. In this setting, microRNAs (miRs) could be used as molecular biomarkers of atherosclerosis progression, plaque rupture and worse prognosis in normoglycemics (NG) vs. pre-diabetics metformin users (PDMU) vs. pre-diabetics non metformin users (PDNMU). However, the aim of our study was to investigate a wide miRNA panel in peripheral blood exosomes from patients with ACAS divided in NG vs. PDMU vs. PDNMU, and to associate the circulating miRNA expression profiles with MACE at 2 years of follow-up after endarterectomy. METHODS—The study included 234 patients with ACAS divided in NG (n 125), PDNMU (n 73) and PDMU (n 36). The miRs’ expression profiles of circulating exosomes were determined at baseline and at 2 years of follow-up by Affymetrix microarrays from plasma samples of the patients from any study cohort. Then we collected and analyzed MACE at 2 years of follow-up in NG vs. PDMU vs. PDNMU. RESULTS—prediabetics vs. NG had over-inflammation (p<0.05) and over expressed miR 24 and miR 27 at baseline. At 2 years of follow-up PDNMU vs. NG, PDMU vs. NG and PDNMU vs. PDMU over-expressed inflammatory markers and miR 24, miR 27, miR 100, miR 126 and miR 133 (p<0.05). Finally, at follow-up end we observed a significant difference about MACE comparing PDNMU vs. NG (n 27 (36.9%) vs. n 8 (6.4%); p<0.05), PDNMU vs. PDMU (n 27 (36.9%) vs. n 6 (16.6%); p <0.05), and PDMU vs. NG (n 6 (16.6%) vs. n 8 (6.4%); p<0.05). Admission glucose values (HR 1.020, CI 95% [1.001-1.038], p 0.029), atheromatous carotid plaque (HR 5.373, CI 95% [1.251-11.079], p 0.024), and miR 24 (HR 3.842, CI 95% [1.768-19.222], p 0.011) predicted MACE at 2 years of follow-up. CONCLUSIONS—Specific circulating miRs could be over-expressed in pre-diabetics and specifically in PDNMU vs. PDMU after endarterectomy. MiR24, hyperglycemia and atheromatous plaque could predict MACE at 2 years of follow-up.

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

Abstract Diabetes mellitus (DM) is an independent risk-factor for cardiovascular diseases. Plant-based dietary-patterns have been shown to positively impact the effects this cardiovascular risk-factor. The purpose of this study is to investigate the association of adherence to moringa, plantains, moringa-plantain combined, and other plant based dietary-patterns with glycemic-control among persons with type-2-diabetes Mellitus (T2DM). Facility-based cross-sectional-study was conducted among 530 T2DM patients in Ghana. Structured-questionnaires were used to collect demographic, anthropometric, and clinical variables. Adherence to plant-based dietary-patterns were assessed with 24-hour dietary-recall questionnaire. SPSS version-22 was used in data analysis. BMI, HbA1c%, HDL-cholesterol and LDL-cholesterol were significantly correlated with adherence to plant-based dietary-patterns (p-value < 0.05). After adjusting for confounders, adherence to: Plantain diets, standardized regression coefficient β (95%CI): -0.098 (-0.321, -0.022), Yam, β (95%CI): 0.148 (0.066, 0.496), Moringa diets β (95%CI): -0.095 (-0.325,-0.011) and Bean-diets β (95%CI): -0.112 (-0.577-.007) were significantly associated with glycemic control. Also adherence to: Plantain-moriga combined diets β (95%CI): -0.406 (-0.413, -0.049) and Plantain-beans combined diets β (95%CI): -0.128 (-0.188, -0.038) were significantly associated with glycemic control. Adherence to Plantain, Yam, Beans, Plantain-moriga combined diets, and Plantain-beans combined diets could be associated with glycemic control. Keywords: Diabetes mellitus, Adherence, Moringa, Plantain, Glycemic control, Ghana.

Short stature has been associated with increased various disease and all-cause death, but no reliable data exist the association between height and end-stage renal disease (ESRD) in diabetic patients. We investigated the relationship between short stature, development of ESRD, and mortality in type 2 diabetes. This study analyzed clinical data using the National Health Insurance Database in Korea. Height was stratified by five groups according to age and sex. Risk of ESRD and all-cause mortality was analyzed with Cox proportional hazards models. During a 6.9-year follow-up period, 220,457 subjects (8.4%) died and 28,704 subjects (1.1%) started dialysis. Short stature significantly increased the incidence of ESRD and all-cause mortality in the overall cohort analysis. In multivariable analysis, hazard ratios (HR) for development of ESRD comparing the highest versus lowest quartiles of adult height were 0.86 (95% confidence interval (CI), 0.83–0.89). All-cause mortality also decreased with highest height compared to patients with lowest height after fully adjusting for confounding variables (HR 0.79, 95% CI, 0.78–0.81). Adult height had an inverse relationship with newly diagnosed ESRD and all-cause in both males and females. Short stature is strongly associated with an increased risk of ESRD and all-cause mortality in type 2 diabetes.

Background/Aims: Screening for gestational diabetes mellitus (GDM) are currently done at 24 - 28 weeks of conception, missing out on the most vulnerable period of organogenesis and thus preventing clinicians from starting treatments until the late second or third trimester. MicroRNAs (miR) are small non-coding RNA molecules that could aid in detecting or predicting GDM through establishing a novel non-invasive prenatal testing (NIPT) tool. The objective of this study was to summarize the most recent updates on plasma microRNAs as GDM diagnostic biomarkers. Methods: Between April and June 2021, a PubMed literature search was undertaken to review recent articles on human plasma miR associated with GDM. Animal studies and papers that are written in languages other than English were excluded. Only plasma miRNAs were used to avoid coagulation biases. Results: A total of 31 miRNAs were found significantly upregulated in the plasma samples of patients with GDM. It was found mainly during the 2nd or 3rd trimester except for miR-223 and miR-23a that were upregulated at 9 – 11 weeks of gestation. Conclusion: Though extensive prospective cohort studies are required, miR-223 and miR-23a should be considered the most promising to develop a successful NIPT tool because they were found to be upregulated earliest, during the first trimester.

Background: The research is conducted against the backdrop of the rising incidence of diabetes and the demand for novel approaches to improve patient outcomes. With the goal of revolutionizing conventional methods and addressing the changing healthcare landscape, the study concentrated on the application of AI technology in diabetes treatment. Objective: Examining the various ways AI can be used in diabetes care and assessing how it can enhance automated screenings, tailored treatment recommendations, predictive modeling, and patient self-management were the main goals of the study. Result: The findings demonstrated how well AI works to anticipate a patient's unique reaction to a therapy, assist medical personnel in making decisions, and give patients more control over their own care. Artificial intelligence (AI)-powered solutions showed promise in improving real-time monitoring and encouraging patient adherence, supporting a comprehensive strategy for managing diabetes. Conclusion: The research indicates that artificial intelligence (AI) has great potential to change the way diabetes is treated. However, it also highlights the need for more research, ethical issues, and validation of AI. The results advocate for joint efforts to ensure responsible and patient-centered technology innovation in diabetes care and encourage the integration of AI with new technologies.

Obesity, type 2 diabetes, and different forms of cancers are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches. Diabetes and cancer are among the most frequent and complex diseases and based on epidemiological evidence and study it can be concluded that the patients suffering from diabetes are considered to be significantly at higher risk for a number of cancer types. Both these diseases are among the highly complex and heterogeneous in nature. There are a number of evidences which support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of both these diseases type 2 diabetes and different types of cancers. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the common shared causes between type 2 diabetes and cancer which is difficult to unravel and understand. Furthermore, the real complexity arises during diagnosis from contended corroborations that specific drug(s) (individually or in combination) during diagnosis process of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidences from the studies where the origin, biological background, correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. we have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases diabetes and cancer.

Diabetes mellitus is a popular life-threatening disease and patients may gradually have started suffering from other diabetes-causing diseases such as heart attacks, stroke, hypertension, blurry vision, blindness, foot ulcer, amputation, kidney damage and other organ failures before diagnosis. Early detection can help reduce the fatality of this disease. Deep learning models have proven very useful in disease detection and computer-aided diagnosis. In this work, we proposed a deep unsupervised machine learning model for early detection of diabetes using voting ensemble feature selection and deep belief neural networks (DBN). Dataset was obtained from an online repository containing responses of prediagnosed patients to direct questionnaires administered in Sylhet Diabetes Hospital in Sylhet, Bangladesh. The dataset was preprocessed and preprocessed. Features were reduced using the ensemble feature selector. The DBN model was pretrained and tuned to obtain optimal performance. The model was also compared with other models with no multiple hidden layers. The DBN performed at its relative best with F1-measure, precision and recall of 1.00, 0.92 and 1.00 respectively. We conclude that DBN is a useful tool for an unsupervised early prediction of Type II diabetes mellitus.

Type 2 diabetes mellitus (T2DM) accounts for one-sixth of deaths, globally, whereas cancer is the second leading cause of death in the U.S. T2DM is a known risk factor for many cancers. This review examines the link of Reactive oxygen Species (ROS)-altered metabolic and signaling pathways in T2DM to cancer. These reprogrammed metabolic and signaling pathways are activated that contribute to diabetic complications, impact redox balance (Oxidative Stress), and have differential roles in early and late stages of cancer. If the respiratory chain is highly reduced (as under hyperglycemic conditions) or if reduced cofactors accumulate, ROS are greatly elevated. ROS may cause mutations in mitochondrial DNA (mtDNA) that result in further ROS elevation. Amplification of ROS results in activation of PKC, an overarching signaling pathway that activates MAPK with subsequent regulation of several factors that result in pathophysiological manifestations of T2DM and cancer. Upregulation of PKC leads to deregulation of NF-kß that regulates the PKB/P13/Akt pathway that orchestrates cell survival, growth, proliferation, and glucose metabolism manifested in cancer. It also affects Insulin Receptor Substrate (IRS-1), decreasing insulin stimulated glucose transport and glucose uptake, disrupting subsequent cell signaling pathways contributing to the development of T2DM. Dyslipidemia is a hallmark of T2DM and cancer. ROS-induced lipid peroxidation leads to systemic inflammation, producing inflammatory prostaglandins, cytokines and chemokines that result in tumor proliferation, rapid tumor growth, and modulation of immunity. The dual role of ROS in early and late stages of cancer make antioxidant therapy precarious and may be responsible for controversial results. A system that delivers an antioxidant directly to mitochondria may be useful in inhibiting formation of ROS early during the pre-diabetic stage whereas antioxidant therapy must be halted in later stages to retard metastasis.

Diabetes mellitus is a heterogeneous disease of complex etiology and pathogenesis. Hyperglycemia leads to many serious complications, but also directly initiates the process of β cell apoptosis. A potential strategy for the preservation of pancreatic β cells in diabetes may be to inhibit the implementation of pro-apoptotic pathways or to enhance the action of pancreatic protective factors. The HIPPO signaling pathway is proposed and selected as a target to manipulate the activity of its core proteins in therapy - basic research. MST1 and LATS2 as major upstream signaling kinases of the Hippo pathway are considered as target candidates for pharmacologically induced tissue regeneration and inhibition of apoptosis. Manipulating the activity of components of the HiPPO pathway offers a wide range of possibilities, and thus is a potential tool in the treatment of diabetes and the regeneration of β cells. Therefore, it is important to fully understand the processes involved in apoptosis in diabetic states and to fully characterize the role of this pathway in diabetes. Therapy consisting in slowing down or stopping the mechanisms of apoptosis may be an important direction of diabetes treatment shortly.

Type 2 diabetes mellitus (T2DM) is an endocrine illness associate with various changes in the immune system and adaptor protein levels. Cytokine dependent hematopoietic cell linker (CLNK) is an adapter protein that regulates immune receptor signaling and acts as a regulator of the receptor signaling of T-cells and natural killer T-cell. The role of CLNK in T2DM is not studied previously. In the present study, serum CLNK level was measured and correlated with some sociodemographic and insulin resistance (IR) parameters. This is achieved by performing measurement of CLNK and insulin parameters (glucose, insulin, and HbA1c in addition to the calculation of the functions of IR (HOMA2IR), insulin sensitivity (HOMA%S), and beta-cell function (HOMA%B)) in 60 T2DM patients and 30 controls. The results indicated a significant increase (p=0.025) in serum CLNK in patients group in comparison with the controls. Multivariate generalized linear model (GLM) analysis revealed no significant effect of age, BMI, and sex on the CLNK level. The results of tests for between-subjects showed that the CLNK affects diagnosis significantly (F=7.445, p=0.008, partial η² =0.081) and its effect is approximately the same as the effect of insulin (F=8.107, p=0.006, partial η² =0.087). The correlation study showed a highly significant positive correlation between CLNK and the duration of disease (rho=0.420, p<0.001). It can be concluded that the increase CLNK in T2DM revealing the role of the adaptor proteins level in the nature of disease. Elevation of CLNK level may be used as a predictor for diabetes complications, which needs more investigations.

Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, although coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly to multidrug-resistant Gram-negative bacteria, and lastly to a possibly fatal Candida glabrata. Development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

Background. Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods. A thorough manual examination of the relevant literature, covering over 35,000 papers. Results. Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion. Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

Gestational diabetes (GDM) is considered a significant and increasing problem worldwide. The growing body of evidence points out that a hostile intrauterine environment in mothers with GDM via epigenetic mechanisms induces "diabetogenic" and "obesogenic" changes in an offspring's DNA. This sets in motion a vicious intergenerational cycle of metabolic diseases gradually deteriorating the health of the human population. One of the most important players in this process seems to be altered microbiota/microbiome. There is a chance that the identification of specific epigenetic marks may provide a key for future diagnostic, prognostic and therapeutic solutions/measures in the field of person-alized medicine. Given the reversibility of most epigenetic changes, an opportunity arises to improve the long-term health of the human population/race. In this manuscript, we aim to summarize available data on epigenetic changes among women suffering from GDM and their progeny in association with changes in microbiome.

Type 2 diabetes has been linked to the expression of Human Leukocyte Antigens, principally to the major Histocompatibility Complex Class II and only scarce reports to Major Histocompatibility Complex class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC class I related to Type 2 diabetes in the Mexican population using the GWAS SIGMA database. This database contains information of 3,848 Mexican individuals with type 2 diabetes and 4,366 control individuals from the same population without clinical or hereditary history of the disease. The searching criteria considered a P value < 0.005 and odds ratio, OR > 1.0. Ten novel statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01), and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related with the development of Type 2 diabetes complications.

Pancreatic β-cell-specific clock knock-out mice develop β cell oxidative-stress and failure, as well as glucose-intolerance. How inflammatory stress affects the cellular clock is under-investigated. Real-time recording of Per2:luciferase reporter activity in murine and human pancreatic islets demonstrated that the proinflammatory cytokine Interleukin-1β (IL-1β) lengthened the circadian period. qPCR-profiling of core clock gene expression in insulin-producing cells suggested that the combination of the proinflammatory cytokines IL-1β and Interferon-γ (IFN-γ) caused pronounced but uncoordinated increases in mRNA levels of multiple core clock genes, in particular of Reverse-erythroblastosis virus α (Rev-erbα), in a dose- and time-dependent manner. The REV-ERBα/β agonist SR9009, used to mimic cytokine-mediated Rev-erbα induction, reduced constitutive and cytokine-induced Brain and muscle arnt-like 1 (Bmal1) mRNA levels in INS-1 cells as expected. SR9009 induced reactive oxygen species (ROS), reduced insulin-1/2 (Ins-1/2) mRNA and accumulated- and glucose-stimulated insulin secretion, reduced cell-viability, and increased apoptosis levels, reminiscent of cytokine toxicity. In contrast low (<5,0 μM) concentrations of SR9009 increased Ins-1 mRNA and accumulated insulin-secretion without affecting INS-1 cell viability, mirroring low-concentration IL-1β mediated β-cell stimulation. Inhibiting nitric oxide (NO) synthesis, the lysine deacetylase HDAC3 and the immunoproteasome reduced cytokine-mediated increases in clock gene expression. In conclusion, the cytokine-combination perturbed the intrinsic clocks operative in mouse and human pancreatic islets and induced uncoordinated clock gene expression in INS-1 cells, the latter effect associated with NO, HDAC3 and immunoproteasome activity.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D) yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycemic control, measures of insulin sensitivity and secretion), adverse events, and GRADE assessments. Quality was assessed using AMSTAR-2. Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C and omega-3 polyunsaturated fatty acids (-3 PUFAs) were superior to placebo for the primary outcome of HbA1c (MD -0.54%, -0.54% and ES -0.27 respectively). Probiotics were superior to placebo for HbA1c (WMD -0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD -0.17%). Magnesium, zinc, Vitamin C, probiotics and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

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.

Background: Diabetes is a common non-communicable disease that is responsible for about 9% of all deaths and 25% reduction in life expectancy and nearly half of the diabetic patients are not aware of their disease. In this regard, diabetes screening to identify un-known diabetic patients is of great importance. Aims: The aims of this study were first to evaluate the performance of two commonly used diabetes screening tests that are currently recommended by the Iranian national screening program for diabetes (NSPD). Methods: The validities of the two diabetes screening tests were measured among 1057 participants older than 30 years. The studied screening tests included Capillary fasting blood glucose (CBG) and glycated hemoglobin (HbA1c). The golden standard for measuring the validity of the tests was venous fasting plasma glucose (VPG). Results: According to the results, the sensitivity of CBG and HbA1c tests were 69.01% and 84.5% and the specificity of the tests were 95.7% and 79.3% respectively. Positive and negative predictive values were 53.84% and 97.72% for CBG and 22.72% and 98.61% for HbA1c respectively. The recommended cut-points for CBG and HbA1c were 116.5 mg/dl and 7.15% respectively. Using these values as the new cut-points, sensitivity and specificity of CBG and HbA1c changed to 80.30% and 89.10%, and 77.50% and 94.20% respectively. Conclusions: Compared to several other countries, the performance of NSPD is relatively higher in Iran. ROC analysis suggested new cut-points for significantly better performance of NSPD.

Type 1 Diabetes mellitus (T1DM) occurs when insulin is not produced in the Pancreas due to the autoimmune destruction of the beta cells. The patients may be diagnosed after 80-90% of the beta cells are destroyed. Insulin remains the essential medicine in T1DM management, under continuous monitoring of glucose levels. T1DM management consists of a complex and precise set of self-care measures for the entire life; during this continuous process, the patients could become overwhelmed, angry, anxious, frustrated, and/or discouraged. Therefore, to be widely used and provide general benefits, new technologies for DM management must provide clinical advantages without compromising safety. The compliance of T1DM patients is also essential, thus improving their quality of life (QoL). Moreover, the accessibility of the new system for patients through healthcare coverage is critical; they must be able to buy the new devices and accessories and pay for their maintenance. In this context, our work aims to describe the most recent technologies regarding continuous glucose monitors (CGMs) and continuous subcutaneous insulin infusion (CSII) systems, correlated with psychosocial impact and capacity to improve T1DM patients' life quality.

Individuals with metabolic syndrome have increased risk for developing health conditions, in-cluding cardiovascular diseases and stroke. Modifiable risk factors, such as exercise and diet, are key components in the prevention and control of metabolic syndrome. Specifically, dietary pat-terns and habits are extremely successful in controlling more than one of the metabolic syn-drome risk factors. Meal timing and frequency have been associated with type 2 diabetes, cardi-ovascular diseases, and other chronic conditions. However, there is limited evidence linking metabolic syndrome to meal timing and meal frequency. This review summarizes and discusses how meal timing and frequency impact metabolic outcomes in adults.

Anti-diabetic effects of Glycine soja seed extract (GS) on Type 2 diabetes mellitus mouse model and human hepatocytes induced insulin resistance were investigated. 3 weeks old db/db mice were divided into 5 groups (n = 6) including two control groups and 3 GS treated groups with different doses. Oral administration of GS for 6 weeks to diabetic db/db mice reduced blood glucose level significantly in a dose dependent manner by 44.7% (300 mg/kg/day), 30.9% (150 mg/kg/day) and 21.1% (75 mg/kg/day). GS treatment also lowered significantly plasma level of HbA1c, insulin, IGF-1 and leptin, and increased that of adiponectin. GS treatment activated AMPK, and down-regulated GLUT2 in liver tissues of mice while up-regulated GLUT4 in muscle tissues of mice. In in vitro study with insulin resistance induced human hepatocyte, GS treatment increased glucose uptake and increased the activities of Akt and PPAR-γ in response to insulin. Treatment of GS appears to reduce blood glucose level by regulating energy metabolism positively through various metabolic pathways and reducing insulin resistance in Type 2 diabetes mellitus.

Increased chronic glucose is associated with pandemic diseases. To date, there is not a practical, as well as accurate sample for reflecting that level. We measured earwax glucose in 37 controls. They provided standard serum samples, Glycated Haemoglobin (HbA1c) and earwax samples on two time-points, one month a part. The specimens measured baseline fasting glucose, a follow-up postprandial glucose level and a between sample chronic glucose, calculated using the average level on the two occasions. The baseline earwax sample was obtained using a clinical method and the follow-up using a novel self-sampling earwax device. The earwax analytic time was significantly faster using the novel device in comparison to the clinical use of the syringe. Earwax accurately reflected glucose at both assessments with stronger correlations than HbA1c. Follow-up postprandial concentrations were more significant than their respective fasting baseline concentrations, reflecting differences in fasting and postprandial glycaemia and more efficient standardisation at follow up. Earwax demonstrated to be more predictable than HbA1c in reflecting systemic fasting, postprandial and long-term glucose levels and immune by confounders. Earwax glucose was approximately 60% more predictable than HbA1c in reflecting glycaemia over a month. The self-sampling device provided a sample that might accurately reflect chronic glycaemia.

Hospital readmission and length of stay prediction provide info to manage hospitals’ bed capacity and the number of required staff, especially during pandemics. We present a hybrid deep model called Genetic Algorithm-Optimized Convolutional Neural Network (GAOCNN) with a unique preprocessing method to predict hospital readmission and the length of stay in patients having various conditions. GAOCNN uses one-dimensional convolutional layers to predict hospital readmission and length of stay. The parameters of the layers are optimized using a genetic algorithm. To show the performance of the proposed model in patients with various conditions, we evaluate the model under three healthcare datasets; the Diabetes 130-US hospitals dataset, the COVID-19 dataset, and the MIMIC-III dataset. The diabetes 130-US hospitals dataset has information on both readmission and the length of stay, while COVID-19 and MIMIC-III datasets just include information on the length of stay. Experimental results show that the proposed model’s accuracy for hospital readmission is 97.2% for diabetic patients. Also, the accuracy of the length of stay prediction is 89%, 99.4%, and 94.1% for diabetic, COVID-19, and ICU patients, respectively. These results confirm the superiority of the proposed model compared to existing methods. Our findings offer a platform for managing healthcare funds and resources for patients with various diseases.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be routinely captured through standard surveillance activities. This study aimed to characterize the prevalence and demographic profile of dyslipidemia in T2D patients in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and blood tests. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (p = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (p = .013 and p = .036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (p = .029 and p = .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

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.

Since the discovery of mitochondrial-derived peptides (MDP), their participation in cellular metabolism is no longer considered as the sole function of the mitochondria, but importance was also attached to its role as a source of protective factors of metabolic stress. These peptides are encoded in the mitochondrial genome and translated into the mitochondria or cytoplasm, to signal within the cell or be released and bind to membrane receptors. The objective of this work was explored and compare the frequency of MT-RNR1 and MT-RNR2 variants in sequences obtained from T2D individuals and control population. 213 different mitochondrial polymorphisms previously reported in the literature associated with T2D and cardiovascular diseases were analyzed. We can found three variants in the MT-RNR1 not related with MOTS-c coding sequence: m.1189T>C (rs28358571), m.1420T>C (rs111033356), and m.1438A>G (rs2001030); and secondly, three polymorphisms associated to MT-RNR2 m.2667T>C (rs878870626) related to humanin, m.1811A>G (rs28358576) in SHPL3 and m.3027T>C (rs199838004) in SHPL6 associated with statistical differences between the T2D and control group. All these findings were previously related to cardiovascular complications in literature and, as far as we know, relating for the first time in diabetic patients.

Diabetes is a life-long illness, it requires life-long solution. Today’s treatment is trading one type of pain with another, never truly ride off the illness. When Artificial Pancreas (AP) offered a possibility of cure, it stirred up a great deal of interest in the diabetic community (1). The system was based on artificial intelligence. It can automate the dosing of insulin to reduce high blood sugar levels overnight. The most dangerous time for diabetes. Artificial Pancreas may be able to allow diabetic patients to sleep through the night without waking up to check and manage their blood glucose levels. It was a significant advancement. However, the achievement was limited: 76.4% in range with the system vs. 67.8% without the system. This accomplishment was creditable, but not optimal. If Artificial Pancreas was to be offered as a viable treatment for diabetes, it must be a life-long solution and must be a total solution. Artificial Pancreas has failed in this challenge. We decided to pursue an alternative approach, a self-regulated system: bioartificial pancreas. It has the potential became a complete cure.

Type 2 Diabetes Mellitus is being increasingly associated with dysfunction of cognition. Dementia, including vascular dementia and Alzheimer’s disease, is being recognized as comorbidities of this metabolic disorder. The progressive hallmarks of this cognitive dysfunction include mild impairment of cognition and cognitive decline. Dementia and mild impairment of cognition appear in older patients primarily. Studies on risk factors, neuropathology, and brain imaging have provided important suggestions for mechanisms that lie behind the development of dementia. It is a significant challenge to understand the disease processes related to diabetes which affect the brain and lead to dementia development. The connection between Diabetes Mellitus and dysfunction of cognition has been observed in many human and animal studies that have noted mechanisms related to Diabetes Mellitus are possibly responsible for aggravating cognitive dysfunction. This article attempts to narrate the possible association between type 2 diabetes and Dementia, reviewing studies that have noted this association in vascular dementia and Alzheimer’s disease and helping to explain the potential mechanisms behind the disease process. The Google search for ‘Diabetes Mellitus and Dementia’ was carried out. Also, the search was done using ‘Diabetes Mellitus,’ ‘Vascular Dementia,’ ‘Alzheimer’s Disease.’ The literature search was done from Google Scholar, Pubmed, Embase, ScienceDirect, and MEDLINE. Keeping in mind the increasing rate of Diabetes Mellitus, it is important to establish the type 2 diabetes effect on the brain and diseases of neurodegeneration. This narrative review aims to build awareness regarding different types of dementia and their relationship with diabetes.

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.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy that adversely affects maternal and offspring health. A variety of risk factors, such as BMI and age, have been associated with increased risks of gestational diabetes. However, in many cases gestational diabetes occurs in healthy nulliparous women with no obvious risk factors. Emerging data suggest that the tendency to develop gestational diabetes has genetic and environmental components. Here we develop a polygenic risk score for gestational diabetes. We further investigate relationships between the genetic architecture of GDM and genetically constructed risk factors and biomarkers. Our results show that genetics can be used as an early screening tool that identifies at-risk at higher risk of GDM before its onset to propose comprehensive monitoring and preventative programs to mitigate the risks.

Background: Fetal overgrowth is related to many perinatal complications including stillbirth, cesarean section, maternal and neonatal injuries, and shoulder dystocia. It is related to maternal diabetes, obesity, and gestational weight gain, but also happens in low-risk pregnancies. There is ongoing discussion regarding definitions, methods of detection, and classification. The method used for detection is of crucial importance as it draws a line between those at risk and low-risk populations. Methods: In this a narrative review of relevant evidence identified through PubMed search with one of the general terms (macrosomia, large-for-gestational-age) combined with the outcome of interest. Results: This revive summarizes evidence on the relation of fetal overgrowth with stillbirth, cesarean sections, shoulder dystocia, anal sphincter injury, and hemorrhage. Customized growth charts help to detect mothers and fetuses at risk of those complications. Relations between fetal overgrowth and diabetes, maternal weight, and gestational weight gain. Conclusions: a substantial proportion of complications are an effect of the fetus growing above its potential and should be recognized as a new dangerous condition of Fetal Growth Acceleration

Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of type 2 diabetic patients with MCI are linked to sarcopenia and/or its criterion remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, BMI, duration of diabetes, hypertension, dyslipidemia, smoking, drinking, eGFR, HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This is the first study to show that slow walking speed is a sole determinant for the presence of MCI in patients with type 2 diabetes. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

Bisphenols are widely used in the synthesis of polycarbonate plastics, epoxy resins and thermal paper, which are used in manufacturing items of daily use. Packaged foods and drinks are the main sources of exposure to bisphenols. These chemicals affect humans and animals by disrupting the estrogen, androgen, progesterone, thyroid, and aryl hydrocarbon receptor functions. Bisphenols exert numerous harmful effects because of their interaction with receptors, ROS formation, lipid peroxidation, mitochondrial dysfunction, and cell signal alterations. Both cohort and case-control studies have determined an association between bisphenol exposure and increased risk of cardiovascular diseases, neurological disorders, reproductive abnormalities, obesity, and diabetes. Prenatal exposure to bisphenol results in developmental disorders in animals. These chemicals also affect the immune cells and play a significant role in initiating the inflammatory response. Exposure to bisphenols exhibit age, gender, and dose-dependent effects. Even at low concentrations, bisphenols exert toxicity, and hence deserve a critical assessment for their uses. Since bisphenols have a global influence on human health, the need to discover the underlying pathways involved in all disease conditions is essential. Furthermore, it is important to promote the use of alternatives for bisphenols, thereby restricting their uses.

Older adults with diabetes are at elevated risk of complications following hospitalization. Home health care services mitigate the risk of adverse events and facilitate a safe transition home. In the United States, when home health care services are prescribed, federal guidelines require they begin within two days of hospital discharge. This study examined the association between timing of home health care initiation and 30-day rehospitalization outcomes in a cohort of 786,734 Medicare beneficiaries following a diabetes-related index hospitalization. Of these patients, 26.6% were discharged to home health care. To evaluate the association between timing of home health care initiation and 30-day rehospitalizations, multivariate logistic regression models including patient demographics, clinical, geographic variables, and neighborhood socio-economic variables were used. Inverse probability-weighted propensity scores were incorporated into the analysis to account for potential confounding between the timing of home health care initiation and the outcome in the cohort. Compared to patients who received home health care within the recommended first two days, patients who received delayed services (3-7 days after discharge) had higher odds of rehospitalization (OR 1.28, 95% CI 1.25-1.32). Among patients who received late services (8-14 days after discharge), the odds of rehospitalization were four times greater than for patients receiving services within 2 days (OR 4.12, 95% CI 3.97-4.28). Timely initiation of home health care following diabetes-related hospitalizations is one strategy to improve outcomes.

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

Type 2 diabetes (T2D) is characterized by hyperglycemia and insulin resistance. Cocoa may slow T2D development and progression. This study employed male and female BTBR.Cg-Lepob/ob/WiscJ and wild type (WT) controls to assess the potential for cocoa to ameliorate progressive T2D and compare responses between sexes. Mice received diet without (WT, ob/ob) or with cocoa extract (ob/ob + c) for 10 weeks. Glucose and insulin tolerance tests (GTT/ITT) were conducted at weeks 1, 5 and 2, 6, respectively. Cocoa provided mild non-significant protection against weight gain vs. ob/ob control in males but not females. Male ob/ob + c had increasing fasting glucose at weeks 1 and 5 GTTs, with significantly higher levels of fasting glucose than ob/ob control at week 5. This was not seen in females. Cocoa protected against elevated 4-hour fasting glucose in week 2, but not week 6, ITTs. Cocoa partly suppressed hyperinsulinemia in males but significantly amplified it in females and protected against loss of beta cell area in females only. The mechanisms of these sex-specific effects remain to be elucidated. This study informs additional experiments with larger sample sizes and demonstrates that sex differences must be considered when designing dietary interventions for T2D.

Abstract: Diabetes mellitus (DM) is associated with severe COVID-19 infection and complications. This study assessed COVID-19 vaccine acceptance and hesitancy in diabetes and explored reasons for nonvaccinating. This was a web-based cross-sectional survey using a mixed-method approach conducted between March-May 2021 corresponding to most SSA countries' early vaccine rollout period. Participants were those aged ≥18 years with self-reported DM in 11 Sub-Saharan African (SSA) countries. Responses to comments on reasons for vaccine hesitancy and facilitators for vaccine uptake were analyzed. Of the 73 participants with DM, 65.8% were males older than 35 years (86.3%), had post-secondary education (90%), and a significant proportion was from South Africa (39.7%), Nigeria (28.8%) and Ghana (13.7%). 64.4% had COVID-19 symptoms, 46.6% were tested for COVID-19, of which 19.2% tested positive. Few participants (6.8%) had taken the COVID-19 vaccination, 65.8% were willing to take the vaccine, while 26.0% either refused or hesitated to take the vaccine. The main reasons identified for not taking the vaccine were: advice from religious leaders, concerns about the vaccine safety, its effects, and efficacy, mistrust of the pharmaceutical companies, the conspiracy theories around the vaccines, the process of production, and the personal belief of the participants. However, participants stated they would take the vaccine if given more education about it, receive positive feedback from those vaccinated, are rewarded for taking the vaccine or if vaccination becomes a condition for travel and employment. The findings of this study showed that uptake of the COVID-19 vaccine was very low in this high-risk group. It is imperative that efforts to increase the uptake of vaccines, such as the provision of education and relevant information, are made.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

Background Polycystic ovary syndrome (PCOS) is a common hormonal disorder worldwide among women of reproductive age. It is characterized by endocrine, reproductive, and metabolic abnormalities. Insulin resistance (IR) is one of its most important clinical features, associated with metabolic disorders and increased risk of type 2 diabetes (T2D). This study aimed to explore the whole blood gene expression profiling related to IR in PCOS patients compared to controls. Methods Blood RNA was extracted from 5 PCOS and 5 non-PCOS women with matched age and BMI. Homeostasis model assessment (HOMA-IR) was used to estimate the IR. The expression of IR genes was analyzed by Profiler PCR array. Results Both groups have similar levels of HOMA-IR (p>0.05). However, differential expression levels were observed between them. Fourteen genes were upregulated and 26 genes were downregulated in PCOS samples. Among the upregulated genes (>2 fold-change, p-value<0.05) are ADIPOQ, ADIPOR1, OLR, IGF-1, and APOE. Downregulated genes (>-2 fold-change, p-value<0.05) include HK-2, IRS1, and SERPINE1. These genes are involved in insulin and adipokines signaling, commonly dysregulated in T2D. They are also involved in innate immunity and inflammatory processes and are essential for lipid and carbohydrate metabolism. Conclusion Our finding suggests that despite both groups having no difference in IR level, there are differentially expressed genes involved in the IR pathway.

The Seven Country study showed that traditional Japanese diet and Mediterranean diets are protective against cardiovascular diseases (CVDs). Japanese diet is considered the healthiest because it provides highest longevity and health to Japanese. DASH diet and Mediterranean style diets are also considered the healthy diets, although, it is possible that Indo-Mediterranean style diet may provide better protective effects among patients with CVDs, compared to other diets. The concept of Indo-Mediterranean type of diets was developed, after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France; The Lyon Heart Study. These workers found that eating alpha-linolenic acid rich Mediterranean style diet can cause significant decline in CVDs and all-cause mortality. Later on in 2018, PREDIMED Study from Spain also reported that a modified Mediterranean style diet can cause significant decline in CVDs, type 2 diabetes mellitus (T2DM) and cancer. The Indo-Mediterranean diet may be superior to DASH diet and Mediterranean diet because it contains millets, porridge, beans and spices; turmeric, cumin, fenugreek and coriander which may have better anti-inflammatory and cardio-protective effects. These foods are rich sources of nutrients; flavonoids, calcium and iron as well as proteins which are useful in the prevention of under as well as over-nutrition and related diseases. It is known that DASH diet and Mediterranean style diets have similar influence on CVDs. However, Indo-Mediterranean style diet, may be as good as Japanese diet, due to improved food diversity and high content of antioxidants in the diets.

In the text, the synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilide derivatives of amino acids are described. They have shown inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range, as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, also including glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.

The aim of this study was to analyze other possible new markers of severity that can be assessed in patients with type 2 diabetes and SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus and infected with the SARS-CoV-2 virus, and 45 healthy persons as control. The serum level of ceruloplasmin at hospital admission was statistically significant directly correlated with the severity of COVID-19 (Coronavirus disease) (p=0.037) and with the serum level of IL-6 (Interleukine 6) (p=0.000). Ceruloplasmin was statistically significant inversely correlated with serum iron level (p=0.000). However, we observed that ACE (Angiotensin converting enzyme) decreased in severe forms of the infection with SARS-CoV-2 virus in patients with type 2 diabetes (p=0.001). Moreover, the decrease in ACE level was correlated with an increase in IL-6 level in these patients (p=0.001). IL-6 increase was statistically significant inversely correlated with serum iron, transferrin and ACE levels. There was a noticed a decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p=0.000). In addition to the known severity factors in the context of infection with the new coronavirus, decreased concentrations of ceruloplasmin, ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters analyzed at the hospital admission could show the evolution towards the severe forms of infection with the SARS-CoV-2 virus.

C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.

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.

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

During type 1 diabetes mellitus (T1DM) development, beta-cells undergo intense endoplasmic reticulum (ER) stress that could result in apoptosis through the failure of adaptation to the unfolded protein response (UPR). Islet transplantation is considered an attractive alternative among beta-cell replacement therapies for T1DM. To avoid the loss of beta-cells that will jeopardize the transplant´s outcome, several strategies are being studied. We have previously shown that prolactin induces protection against pro-inflammatory cytokines and redox imbalance-induced beta-cell death by increasing heat shock protein B1 (HSPB1) levels. Since the role of HSPB1 in beta cells has not been deeply studied, we investigated the mechanisms involved in unbalanced protein homeostasis caused by intense ER stress and overload of the proteasomal protein degradation pathway. We tested whether HSPB1-mediated cytoprotective effects involved UPR modulation and improvement of protein degradation via the ubiquitin-proteasome system. We demonstrated that increased levels of HSPB1: attenuated levels of pro-apoptotic proteins like CHOP and BIM, increased protein ubiquitination and the speed of proteasomal protein degradation. Our data showed that HSPB1 induced resistance to proteotoxic stress and thus enhanced cell survival via an increase in beta-cell proteolytic capacity. These results could contribute to generate strategies aiming at optimization of beta-cell replacement therapies.

The worldwide prevalence of type 2 diabetes (T2D) and prediabetes is rapidly increasing, particularly in children, adolescents, and young adults. Oxidative stress (OxS) has emerged as a likely initiating factor in T2D. The role of natural antioxidant products in combating T2D is best evaluated in the context of the complex physiological processes that modulate T2D-OxS such as glycemic control and exercise. The role of natural antioxidant compounds such as vitamin E in T2D must likewise be considered beyond their roles as inhibitors of OxS. In addition to antioxidant properties, vitamin E vitamers (tocopherols and tocotrienols) also exhibit distinct abilities to regulate cellular signal transduction pathways important to T2D progression. Most research on the role of vitamin E in T2D or prediabetes has been limited to tocopherols (Ts) but emerging trials with tocotrienols (T3s) show promise. Minimizing factors that induce chronic damaging OxS and maximizing natural antioxidant protective factors may provide a means of preventing or slowing T2D progression. This “optimal redox” (OptRedox) approach also provides a framework in which to discuss the potential benefits of natural antioxidant factors such as antioxidant products. Since early, effective intervention is critical, the OptRedox strategy would be optimally effective if implemented in the pediatric population.

Inflammation plays a key role in the development and progression of type-2 diabetes (T2D), a disease characterised by peripheral insulin resistance and systemic glucolipotoxicity. Visceral adipose tissue (AT) is the main source of inflammation early in disease course. Macrophages are innate immune cells that populate all peripheral tissues, including AT. Dysregulated AT macrophage (ATM) responses to microenvironmental changes are at the root of aberrant inflammation and development of insulin resistance, locally and systemically. The inflammatory activation of macrophages is regulated at multiple levels: cell surface receptor stimulation, intracellular signalling, transcriptionally and metabolically. This review will cover the main mechanisms involved in AT inflammation and insulin resistance in T2D. First, we will describe the physiological and pathological changes in AT that lead to inflammation and insu- lin resistance. We will next focus on the transcriptional and metabolic mechanisms described that lead to the activation of ATMs. We will discuss more novel metabolic mechanisms that influence macrophage polarisation in other disease or tissues contexts that may be relevant to future work in insulin resistance and T2D.

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain is associated with the progression of Alzheimer's Disease (AD).To address this burden of type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (https://www.clinicaltrials.gov/ct2/show/NCT04626453, https://www.clinicaltrials.gov/ct2/show/NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well-tolerated, even during the COVID pandemic. It was also safe, requiring minimal equipment and no supervision. The exercise instructions were easy to understand, making them suitable for older adults with cognitive decline.The near-infrared spectroscopy (NIRS) based brain and muscle oxygenation study provided evidence on brain overactivation among older adults with T2DM, supporting the compensatory theory. It also demonstrated that the 2-month combined exercise intervention effectively reduced brain overactivation and contributed to improved cognitive function. Operational modal analysis showed an exercise-related effect on the very low-frequency hemodynamic oscillations cluster, which may be associated with better vascular muscle and/or perivascular neurogenic regulation. Furthermore, we personalized the exercise duration and interval based on muscle oxygenation during physical tasks, leading to improvements in muscle oxidative capacity within just two months. This finding has practical implications for physical therapists, as they can target muscle oxygenation changes during physical tests to prescribe appropriate exercise doses for enhancing physical performance.

Type 2 diabetes (T2D) is associated with increased cardiovascular morbidity, mortality, and hospital admissions. There is variability in clinical practice. The objectives are to analyze the variability in the control of Blood Pressure (BP), HbA1c, and LDL-C in T2D patients and its influence on admissions due to cardiovascular events (CVE) Methods: We analyzed the electronic records in Primary Care Health centers in Navarra (Spain) and hospital admission for CVE. We follow 480637 people from 2012 to 2016. We calculated indicators of control of patients with T2D for each year, percentage with: HbA1c &lt; 7%; HbA1c &gt;= 9%; BP &lt;140/90 mmHg; LDL-C &lt;100 mg/dl. We used logistic and Cox regression. Results: Patients in the best control GP practices cluster are 2.5 times more likely to have HbA1c &lt;7% [OR: 2.46 (95% CI: 2.29-3.64)]. Poor HbA1c control ≥ 9% is more likely in the worst control cluster [OR: 1.73 (95% CI:1.63-1.83)]. The probability of admission for CVE increases with age, being male, low income, obesity, history of CVE, having HbA1c ≥ 9%, and belonging to a GP practice in the cluster of HbA1C ≥ 9% worst control. In contrast, it decreases in patients with HbA1c &lt;7%, BP&lt;140/90 mmHg and LDL &lt;100 mg/dl.

The Serra da Estrela Natural Park (NPSEs) in Portugal stands out as a well-preserved region abundant in medicinal plants, particularly known for their pharmaceutical applications in diabetes prevention and treatment. This comprehensive review explores these plants' botanical diversity, traditional uses, pharmacological applications, and chemical composition. The NPSEs boast a rich diversity with 138 medicinal plants across 55 families identified as traditionally and pharmacologically used against diabetes globally. Notably, the Asteraceae and Lamiaceae families are prevalent in anti-diabetic applications. In vitro studies reveal their significant inhibition of carbohydrate-metabolizing enzymes, and certain plant co-products regulate genes involved in carbohydrate metabolism and insulin secretion. In vivo trials demonstrate anti-diabetic effects, including glycaemia regulation, insulin secretion, antioxidant activity, and lipid profile modulation. Medicinal plants in NPSE exhibit various activities beyond anti-diabetic, such as antioxidant, anti-inflammatory, antibacterial, anticancer, and more. Chemical analysis identifies over fifty compounds like phenolic acids, flavonoids, terpenoids, and polysaccharides responsible for their efficacy against diabetes. The findings underscore the potential of NPSE medicinal plants as anti-diabetic candidates, urging further research to develop effective plant-based anti-diabetic drugs, beverages, and supplements.

The Bacillus Calmette-Guérin (BCG) vaccine has been used for over one hundred years to protect against the most lethal infectious agent in human history, tuberculosis. Over four billion BCG doses have been given and, worldwide, most newborns receive BCG. A few countries, including the United States, did not adopt the WHO recommendation for routine use of BCG. Moreover, within the past several decades, most of Western Europe and Australia, having originally employed routine BCG, have discontinued its use. This review article articulates the impacts of those decisions. The associated consequences include increased tuberculosis, increased infections caused by non-tuberculous mycobacteria (NTM), increased autoimmune disease (autoimmune diabetes and multiple sclerosis) and increased neurodegenerative disease (Parkinson’s disease and Alzheimer’s disease). This review also offers an emerged zoonotic pathogen, Mycobacterium avium ss. paratuberculosis (MAP) as a mostly unrecognized NTM that may have a causal role in some, if not all, of these diseases. Current clinical trials with BCG for varied infectious, autoimmune and neurodegenerative diseases have brought this century-old vaccine to the fore due to its presumed immuno-modulating capacity. With its historic success and strong safety profile, the new and novel applications for BCG may lead to its universal use –putting the Western World back onto the road not taken.

Growing evidence suggests that healthcare provider advice may increase tobacco cessation, reduce alcohol use, and improve the adoption of desirable lifestyle behaviors among patients. However, how brief interventions and other provider-patient interactions can shape cumulative adoption of multiple modifiable behaviors is less well studied for diabetes prevention and control. Using weighted internet panel survey data from a large socio-demographically diverse urban population in the United States (n=1,003), the present study describes differences in group characteristics among those who had been “ever diagnosed” with prediabetes/diabetes versus those who had not. It also examines the associations between the cumulative adoption of lifestyle behaviors and each of the following: a) lifetime prediabetes/diabetes diagnosis; b) brief lifestyle intervention exposure (i.e., received provider advice/encouragement); and c) recent provider-patient communication about diabetes. There were several group differences in “ever diagnosed” prediabetes/diabetes status by age, employment status, health status, nutrition knowledge, blood pressure/hypertension diagnosis, and diabetes-related health behaviors (p<0.05). Each of the three provider-patient interactions of interest were positively associated with a higher cumulative sum of adopted modifiable lifestyle behaviors for diabetes prevention and management. Results suggest that provider advice/provider-patient interactions of any type can have a salutary impact on whether individuals with prediabetes or type 2 diabetes will engage in recommended lifestyle behavior modifications.

The functioning of the parents’ emotional sphere is very important to a child’s mental and physical health. This study focused on investigating the association between mothers’ emotional intelligence (EI) and paediatric type I diabetes (T1DM) disease management in their children. We hypothesized that mothers’ EI is associated with T1DM outcomes. Mothers of children with T1DM aged 6-12 years were surveyed. One hundred and thirty-four mothers, the main caregivers of their diabetic children, provided measures of EI and completed a demographic questionnaire. The primary indicator of diabetes management was haemoglobin A1c (HbA1c; the main form of glycosylated haemoglobin). EI scales and subscales were associated with glycaemic management indices. Logistic regression analysis was applied for the assessment of the association between parents’ EI and their paediatric with T1DM disease management. The analysis demonstrated a statistically significant correlation between T1DM management and mothers’ ability to understand and control own emotions, to transform their own negative emotions into positive and to control own negative emotions. Mothers’ EI scales and subscales of understanding and regulating their own emotions, subscales of transforming their own negative emotions into positive ones and controlling their own negative emotions were statistically reliable predictors of glycaemic control in children with T1DM.

Over the last decade, Psidium guajava L. (guava) leaves have demonstrated their in vitro and in vivo effect against Diabetes mellitus (DM). However, there is a lack of literature concerning the effect of the individual phenolic compounds present in the leaves in DM disease. For this reason, the aim of the present work was the in silico evaluation of each phenolic compound. The identification of an 80% ethanol extract of guava leaves revealed the presence of 73 compounds. The in silico study carried out with the DIA-DB web server revealed that aldose reductase was the target protein with heterogeneous affinity. Naringenin exhibited the highest number of interactions with target proteins, and compounds like catechin, quercetin, naringenin and morin displayed similarities with known antidiabetic drugs. In conclusion, the computational workflow showed that guava leaves contain several compounds that can play a therapeutic role in the treatment of DM.

In the case of type 2 diabetes, inhibitors of glycogen phosphorylase (GP) might prevent unwanted glycogenolysis under high glucose conditions and thus aim at the reduction of excessive glucose production by the liver. Anomeric spironucleosides, such as hydantocidin, present a rich synthetic chemistry and important biological function, e.g., inhibition of GP. Herein, the Suárez radical methodology is successfully applied to synthesize the first example of a 1,6-dioxa-4-azaspiro[4.5]decane system, not been previously constructed via a radical pathway, starting from 6-hydroxymethyl-b-D-glucopyranosyluracil. It is shown that in the rigid pyranosyl conformation the required [1,5]-radical translocation is a minor process. The stereochemistry of the spirocycles obtained was unequivocally determined based on the chemical shifts of key sugar protons in the ¹H NMR spectra. The two spirocycles were found to be modest inhibitors of RMGPb.

Chronic diseases such as childhood DM are a complex and continuous struggle as well as a great challenge both for the children who face the disease and for their parents. Type 1 DM is characterized by the complex management of the therapeutic treatment thus causing physical and psychological complications in family members. There are many families who, upon hearing the diagnosis of their child with DM, stand still in front of these new facts as their lives change. All these unprecedented conditions cause parents intense stress, discomfort and mental burden as the only thing that concerns them now is how the family will survive in the face of the current conditions they are experiencing as well as the future of the sick child. The purpose of this brief literature review is to present the research findings which are related to the quality of life among parents of children and adolescents with diabetes.

This review aimed at synthesizing the mechanisms and outcomes of metabolic surgery on hormones, adipokines, metabolomics, and at the molecular level. We reviewed the endocrine, microRNA, and metabolomics changes in human and animal models following metabolic surgery for the treatment of obesity and diabetes. PubMed, Science Direct, Scopus, and Google Scholar databases were searched up to February 2022. The most relevant studies in the area over the past 17 years have been considered for this review. In most cases, metabolic procedures especially those that include intestinal bypass components, showed remission of type 2 diabetes. This involves a variety of weight-independent mechanisms to improve glucose homeostasis, improving insulin sensitivity, and secretion. The miRNAs’ dysregulated expressions have essential roles in metabolic processes. Metabolic surgery is a potentially sustainable treatment that can modify a patient’s physiology and glucose regulation mechanism. The feasibility and role of miRNA are important for potential targeted genetic pathways in future obesity with type 2 diabetes management.

Objective: This study examined the impact of Japan’s state of emergency on trends in diabetes care during the coronavirus disease 2019 (COVID-19) pandemic. Design: A descriptive and retrospective study. Setting: Showa University Hospital, Japan. Participants: Patients with diabetes who received medical treatment from 2018 to 2020. Determinants of interest: Number of patients with diabetes visiting the hospital per week. To examine the impact of the Japan’s state of emergency, the number hospital visiting by patients with diabetes was summarized from 28 weeks of data, from calendar week 8 to week 35, for each year. Results: Compared with the mean of 2018 and 2019, no significant difference was found between the three periods (before, during, and after the state of emergency). However, the numbers of patients from both inside and outside Tokyo increased at 7 weeks after the state of emergency was lifted. Conclusions: A significant increase in the numbers of patients with diabetes was seen compared with the same period in 2018 and 2019, suggesting that the state of emergency may have hindered diabetes care. Therefore, patients with diabetes should be followed up continuous of diabetes care while keeping a close eye on measures.

Type 2 diabetes mellitus (T2DM) poses a significant public health challenge. Prioritising its prevention is essential. With the growing interest in wearable health technologies continuous glucose monitoring systems (CGMs) have expanded their scope, transitioning from exclusive use in diabetes management to lifestyle enhancement for individuals without diabetes. While CGMs primarily target glycaemic stabilization, their potential role in mitigating noncommunicable conditions, including T2DM, warrants exploration. This review examines the regulation of CGMs and critically assesses the purported benefits of CGMs for individuals without diabetes, as presented in the 'health and wellness' sector: (1) early dysglycaemia detection through glucose variability observation; (2) refining glycaemic control by tailoring nutrition according to postprandial glucose response; and (3) promoting and fine-tuning physical activity based on instantaneous data feedback. We find a lack of compelling evidence for the utility of CGMs in PNLD, including accuracy, data analysis and interpretation metrics, and user acceptability markedly under-researched. A paucity of research exists on the unanticipated negative consequences of CGM usage, such as obsessive symptom tracking and potential onset of disordered eating, like orthorexia. Given the increasing adoption of CGMs by individuals without diabetes, this review underscores the need of addressing these research gaps to ensure safety and reliability of CGMs in novel contexts. We emphasise the importance of refining CGM regulation in the UK, particularly when considering its ‘off-label’ use. Marrying robust scientific evidence with effective regulation is pivotal in fortifying the coherence, equity, and effectiveness of diabetes prevention initiatives, while protecting the wellbeing of CGM users.

Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly-progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. Combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate more accurate diagnosis and prediction of autoimmune disorders.

Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p&lt;0.001). CAR was significantly and positively correlated with age (r=0.15, p&lt;0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p&lt;0.001), triglyceride (r=0.17, p&lt;0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p&lt;0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p&lt;0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p&lt;0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.

Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultane-ously with Type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to pa-tients with both the conditions and may cause medication-related osteonecrosis of the jaws (MRONJ). It affects the differentiation and function of osteoclasts as well as thickness of cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and Stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. Histological examination was conducted, and expres-sion of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells were significantly less in the experi-mental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteo-clasts, and increased cortical bone formation in postmenopausal patients with MRONJ.

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.

Background. Cardiorespiratory fitness (CRF) is a predictor of chronic disease that is impractical to routinely measure in primary care settings. We used a new estimated cardiorespiratory fitness (eCRF) algorithm that uses information routinely documented in electronic health care records to predict abnormal blood glucose incidence. Methods: Participants were adults (17.8% female) 20-81 years old at baseline from the Aerobics Center Longitudinal Study between 1979 and 2006. eCRF was based on sex, age, body mass index, resting heart rate, resting blood pressure, and smoking status. CRF was measured by maximal treadmill testing. Cox proportional hazards regression models were established using eCRF and CRF as independent variables predicting the abnormal blood glucose incidence while adjusting for covariates. Results: Of 8,602 participants at risk at baseline, 3,580 (41.6%) developed abnormal blood glucose during an average of 4.9 years follow-up. The average eCRF of 12.03 ± 1.75 METs was equivalent to the CRF of 12.15 ± 2.40 METs within the 10% equivalence limit. In fully adjusted models, the estimated risks were the same (HRs = 0.96), eCRF (95% CIs = 0.93−0.99), and CRF (95% CI of 0.94−0.98). Each 1-MET increase was associated with a 4% reduced risk. Conclusion: Higher eCRF is associated with a lower risk of abnormal glucose. eCRF can be a vital sign used for research and prevention.

Objective: To visualize and analyze the published literature on diabetes and pyroptosis based on a bibliometric approach, so as to provide a comprehensive picture of the hot research directions and dynamic progress in this field. Methods: This study was based on the web of science core collection database to conduct a comprehensive search of the published literature in the field of diabetes and Pyroptosis from January 1985 to August 2022, including the published research literature in this field, as well as a visual analysis of the number of citations, year of publication, journal, author, research institution, country, and research topic. Results: A total of 139 literature on research related to diabetes and cellular scorch from 2011 to 2022 were retrieved, with a total of 3009 citations and a maximum of 255 citations for a single article, which had a first authorSchmid-Burgk, JL The first author of this article is from Germany; among 20 publishing countries, China leads with 100 articles; among 222 publishing institutions, Harbin Medical University leads with 18 articles and 184 citations; among 980 authors, Chen, X from China tops the list of high-impact authors with 5 articles and 29 citations; Among the 98 journals, "CELL DEATH DISEASE" ranked first in both volume and high impact journals with 4 articles and 29 citations; among 349 keywords, "pyroptosis" ranked first with a cumulative frequency of 65 times. The cluster analysis was divided into three categories, chronic complications of diabetes and pyroptosis (67 articles), diabetes and pyroptosis (60 articles), and diabetes combined with other diseases and pyroptosis (12 articles), and the number of articles related to diabetes and its chronic complications increased rapidly from 2019, among which, diabetic cardiomyopathy (27 articles) had the highest number of articles. Conclusions: Based on a comprehensive analysis of published literature in the field of diabetes and pyroptosis from 2011-2022, this study achieved a visual analysis of studies with significant and outstanding contributions to the field, thus framing a picture showing the development and changes in the field. At the same time, this study provides research information and direction for clinicians and investigators to conduct diabetes and pyroptosis related research in the future.

Background: The global prevalence of anxiety and depressive symptoms in adolescents has increased considerably during the COVID-19 pandemic. Mental health problems may compromise glycemic control in young people with type 1 diabetes; however, evidence of improved glycemic control in adolescents with T1D appeared early during the pandemic. This qualitative study aimed to provide a more in-depth understanding of how the COVID-19 pandemic affected adolescents with type 1 diabetes routines, experiences, T1D management, behaviors, and mental health. Methods: 24 adolescents, aged 15-18 years, with DM1, joined the discussion of focus groups in the context of the summer camp for diabetes. Word frequency and thematic analysis were conducted on adolescents’ narratives. Results: The word Frequency Analysis identified 'friends', 'family', and 'home' as the most frequent terms. Seven themes were identified: (1) COVID-19 and T1D; (2) emotional reactions to the COVID-19 pandemic; (3) changes in daily life; (4) feelings of loss; (5) coping with the COVID-19 pandemic; (6) the COVID-19 pandemic as an opportunity; (7) return to (new) normality. Conclusions The COVID-19 pandemic may have represented a more stressful condition for adolescents with DM1, facing additional challenges compared to their healthy peers. The results offer directions to the diabetes care team for a customized intervention while the consequences of the pandemic on adolescents’ health continue.

Vitamin D plays an essential role in embryogenesis and the course of intra- and postnatal periods and is crucially involved in the functioning of the mother-placenta-fetus system. Low quantity of Vitamin D during pregnancy can lead to the elevated risk for preeclampsia occurence. Despite the numerous studies on the association of Vitamin D deficiency and preeclampsia development, the current research on this theme is contradictory. In this review we summarize and analyze study data on the effects of vitamin D deficiency and supplementation on pregnancy, labor, fetal and neonatal outcomes.

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.