[Obesity as a risk factor for developing non-insulin dependent diabetes mellitus--obesity and insulin resistance]

Obesity is considered to be one of the major risk factors for developing non-insulin dependent diabetes mellitus (NIDDM). Our cohort study for NIDDM in Aito, Shiga 1980-1990 confirmed that aging, higher body mass index (obesity) and high blood pressure were independent risk factors for developing NIDDM in Japan. In Pima Indians, decreased glucose disposal rate (GDR) is significantly related to percentage of body fat (%fat). Insulin signaling for glycogen synthesis in the skeletal muscles is impaired in the early stages of obesity. Although the molecular mechanism for insulin resistance in obesity is still unknown, hyperinsulinemia induces insulin receptor loss by means of the down regulation mechanism, and prolonged hyperglycemia may induce the impairment of insulin receptor kinase in the skeletal muscles in obese subjects. These dysfunctions in insulin signaling may cause the deterioration of insulin sensitivity, resulting in worsening glycemic control. Thus dysfunction of insulin receptor signaling in skeletal muscles may be a target for preventing diabetes in obese subjects.