Abstract
Background: The impact of overweight and adipocyte size on the development of type 2 diabetes mellitus (T2DM) remains unclear. Aim: We studied (1) the relationship between the state of adipocytes and/or overweight/obesity, the development of T2DM and its clinical and laboratory features; and (2) weight loss effect on glycemic level, endogenous hyperinsulinism (HI), insulin resistance (IR), and T2DM. Methods: We designed a systematic review by searching Web of Science, EBSCO, Scopus/ Science-Direct, Google Scholar, PubMed, Cochrane, and Wolter Kluwer for articles published in 26 years (2000–2026). The study was based on a systematic review of 3853 articles published worldwide. Results: In total, 142 full-text articles were assessed for eligibility. As overweight increases, the size of adipose tissue, adipocytes, and cell radius increase. The increase in cell size overloads intracellular transport and internal organs. The development of IR is a conformational change in cellular receptors caused by an excessive increase in cell size. The increase in cell size with overweight gradually leads to hyperglycemia and HI with the development of IR and T2DM. Any targeted intentional weight loss in patients with T2DM improves metabolic and cardiovascular health, reduces blood pressure and blood sugar, and decreases HI, IR, and T2DM. Conclusions: IR is a protective response of cells that prevents oversaturation and overflow. Overweight is an independent risk factor for the development of HI, IR, and T2DM. Targeted weight loss leads to the cure of HI, IR and T2DM.