Interactions of Aging and Insulin Therapy on Body Fat

Tobin, Brian

Abstract

The purpose of this study is to determine interactions of aging and insulin therapy upon the accumulation and distribution of body fat when treating the glucose intolerance of aging in an animal model of non-insulin-dependent diabetes mellitus (NIDDM). Obesity and glucose intolerance increase with age and are associated with the occurrence of NIDDM. By age 45, 13% of the population will develop diabetes; by age 65-74, this number increases to 25%. The social cost is great and includes hospitalization rates 70% greater than the general population. As a person ages, the percentage of body fat increases and the percentage of lean body mass decreases. These natural modifications may potentiate the progression of chronic diseases which manifest among older individuals. A loss of physical strength, functional status, and immune competence are related to a decreasing lean body mass. In addition, increased body fat is associated with obesity, glucose intolerance, diabetes, hyperlipidemia, and cardiovascular atherosclerotic disease. The role of aging specific clinical therapies in the management of glucose intolerance and diabetes of aged individuals is not clear, however. Intensive insulin therapy (IIT) benefits persons with insulin-dependent diabetes, yet IIT may not be appropriate for individuals with NIDDM. This is because IIT increases body fat and does not improve lean body mass. Newer oral agents such as Metformin improve insulin action, yet the effects of Metformin in aging and with IIT are unknown.
The specific aims of this study are to: 1) determine the independent and interactive effects of aging and NIDDM on changes in body composition of rats treated with IIT, and 2) delineate in aged animals the effect of improved delivery of insulin, achieved through Metformin administration. Using Zucker Diabetic Fatty (ZDF) rats studied at 6 and 15 mo of age, these experiments will determine if IIT alters the fat mass of NIDDM animals, and delineate the efficacy of Metformin alone and with IIT.