Type 2 diabetes mellitus is characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion. Its pathogenesis is poorly understood, but both genetic factors affecting insulin release and responsiveness and environmental factors such as obesity (see below) are important.
The importance of family history in predicting diabetes was emphasized in a Finnish study . Patients with type 2 diabetes who had no family history of type 1 or type 2 diabetes were older at onset and had preservation of endogenous insulin secretion as compared with patients who had a family history of diabetes. Those with a family history of only type 2 diabetes were more obese, had better endogenous insulin secretion, and were less likely to have islet-cell autoantibodies than patients with a family history of both type 1 and type 2 diabetes.
At all ages, the risk of impaired glucose tolerance (IGT) or type 2 diabetes rises with increasing body weight. Obesity acts at least in part by inducing resistance to insulin-mediated peripheral glucose uptake, which is an important component of type 2 diabetes. Reversal of obesity also decreases the risk of type 2 diabetes and, in patients with established disease, improved glycemic control. In addition to the degree of obesity, the distribution of excess adipose tissue is another important determinant of the risk of insulin resistance and type 2 diabetes. The degree of insulin resistance and the incidence of type 2 diabetes are highest in those subjects with upper body or abdominal obesity. Although insulin resistance and impaired insulin secretion in type 2 diabetes have a substantial genetic component, they can also be influenced, both positively and negatively, by behavioral factors, such as physical activity and smoking. The risk for type 2 diabetes is higher in women who have had gestational diabetes. These women have defects in both insulin secretion and insulin action, the severity of which correlate with the future risk of diabetes. Obesity is the most important risk factor for diabetes. In addition, genetic factors, ie, family history and ethnicity, physical inactivity and smoking are important contributors to the risk of developing diabetes. Identification of individuals at risk for diabetes is important as lifestyle modification (predominantly exercise and weight loss) successfully decreases the development of diabetes.
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