**Abstract**

Type 2 diabetes mellitus (DM2) results from the interaction between genetic and environmental factors which cause insulin resistance (IR) and deficit in insulin secretion. Genes encoding insulin-related enzymes or protein factors are candidates for the disease, most probably the insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI-3 K), calpain 10, and transcription factor 7-like 2 genes. Environmental factors that favor DM2 are android obesity, aging, glucotoxicity, and lipotoxicity. IR is the result of less insulin receptor binding, of less phosphorylation of the receptor, of IRS-1, of PI-3 K, and of glucose uptake by glucose transporters. At the hepatic level, glucose is produced by gluconeogenesis: in the muscle there is less glycogen deposition, and in adipocytes there is greater release of free fatty acids (FFA). Insulin secretion is the main pathogenic factor; relative insulin hyposecretion is not capable of compensating for the IR. Reduced incretin effect, hyperglucagonemia, and increased renal glucose reabsorption favor hyperglycemia. Disturbance of the microbiota releases proinflammatory adipocytokines which contribute to IR. Reactive oxygen species generation, caused by hyperglycemia and FFA, results in a decrease in insulin synthesis and action and also endoplasmic reticulum stress and mitochondrial dysfunction. Knowledge about the pathogenesis of DM2 has allowed the development of drugs for its treatment.

**Keywords:** type 2 diabetes, pathogenesis, environment, sleep disturbances, insulin resistance, glucotoxicity, lipotoxicity, microbiota
