Mechanisms for weight gain during blood glucose normalization

Secondary failure to dietary and maximal oral treatment leads to insulin therapy in type 2 diabetic patients. However, weight gain is a frequent side effect of insulin therapy in these patients. Mechanisms for this weight gain are complex. Insulin 1) reduces glycosuria and its caloric expenditure; 2) stimulates the stockage of fatty acids into triglycerides in adipose tissue, thus favoring an increase in adipose mass; 3) yields a positive nitrogen balance through an inhibition of muscle proteolysis, thus favoring an increase in lean mass. Most studies report an average 6 kg weight gain during the first year following the initiation of insulin therapy in type 2 diabetic patients. Analysing body composition variations shows that weight gain results both from an increase in fat mass (mean 63%) and an increase in lean mass (mean 37%). Preexisting obesity does not influence this weight gain. Finally, the 10 year-follow up of UKPDS showed a beneficial effect of insulin therapy on microangiopathy prevention, without increasing cardiovascular mortality as compared with type 2 diabetic patients on oral treatment. Thus, while weight gain seems mandatory, it should not refrain from initiating insulin therapy in poorly controlled type 2 diabetic patients, as its expected beneficial effects on the prevention of microangiopathy seem well established.