Preprint Article Version 1 This version is not peer-reviewed

Four‑Stage Evolution of Diabetes or Whole Body Insulin Resistance (WBIR): Debunking of the Lipid‑Induced Insulin Resistance (LIIR) and Proposing of the Glycation‑Induced Insulin Resistance (GIIR)

Version 1 : Received: 20 September 2019 / Approved: 21 September 2019 / Online: 21 September 2019 (01:46:31 CEST)
Version 2 : Received: 8 October 2019 / Approved: 9 October 2019 / Online: 9 October 2019 (04:21:56 CEST)

How to cite: Lee, S.J.; Shin, S.W. Four‑Stage Evolution of Diabetes or Whole Body Insulin Resistance (WBIR): Debunking of the Lipid‑Induced Insulin Resistance (LIIR) and Proposing of the Glycation‑Induced Insulin Resistance (GIIR). Preprints 2019, 2019090247 (doi: 10.20944/preprints201909.0247.v1). Lee, S.J.; Shin, S.W. Four‑Stage Evolution of Diabetes or Whole Body Insulin Resistance (WBIR): Debunking of the Lipid‑Induced Insulin Resistance (LIIR) and Proposing of the Glycation‑Induced Insulin Resistance (GIIR). Preprints 2019, 2019090247 (doi: 10.20944/preprints201909.0247.v1).

Abstract

Even though it has long been known that diabetes develops in distinctive stages over a long span of time, no comprehensive diabetes development model has been developed yet. Insulin resistance (IR) plays a major role in development of diabetes. A widespread belief regarding IR is that it is a global parameter affecting the whole body simultaneously by merely impairing glucose uptake in tissues. However, investigation by a new methodology that we have named integrated approach suggests that IR not merely impairs glucose uptake in tissues but also produces tissue‑specific metabolic disruptions varying widely from tissue to tissue, and that IR would not necessarily develop simultaneously over the whole body but instead develop first preferentially in the muscle tissue with a relatively low cell turnover and then progresses in sequence to the subcutaneous adipose tissue to the visceral adipose tissue to the liver with higher cell turnovers. This is the most important rationale for subdividing IR into the four distinct tissue‑specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s‑AIR), visceral adipose insulin resistance (v‑AIR), and hepatic insulin resistance (HIR). Sequential development of tissue‑specific IRs, in the order of MIR, s‑AIR, v‑AIR, and HIR, producing tissue‑specific metabolic disruptions is nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin‑resistant stages. Four‑stage evolution from rapid weight gain to visceral obesity to rapid weight loss to full‑blown diabetic state not only complies well with the natural development history of diabetes, but also resolves most of controversies on diabetes or obesity. Development of the four‑stage WBIR evolution model, which also refutes the entrenched notion of the lipid‑induced insulin resistance (LIIR) but instead supports the glycation‑induced insulin resistance (GIIR) proposed in this study, may possibly be considered a breakthrough in study of diabetes or obesity.

Subject Areas

obesity; diabetes; insulin resistance (IR); whole body insulin resistance (WBIR); tissue specific insulin resistance; muscle insulin resistance (MIR); subcutaneous insulin resistance (s AIR); visceral adipose insulin resistance (v AIR); hepatic insulin resistance (HIR)

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