Reversal of Lipid-Induced Insulin Resistance

The purpose of this study is to examine whether weight reduction decreases intramyocellular (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue in people who are insulin resistant and have a family history of type 2 diabetes. Hepatic mitochondrial oxidation will be assesses using a 3 hour triple tracer study (D7 glucose, 3-13C lactate and 13C4 beta-hydroxybutyrate).

Inclusion Criteria: * Healthy, sedentary, non-smoking and not taking any medications other than birth control pills. * Hematocrit \>35% * Subjects will have no systemic or organ disease including diabetes. * Subjects will have no history eating disorders. * Women must be using a form of birth control (sexual abstinence, birth control pills, Norplant, IUD or condoms) and will be studied between day 0 and 7 of their menstrual cycle. * Those who are taking birth control pills or have had a hysterectomy may be studied at any time. * Physical activity will be assessed using a standard questionnaire with an activity index cut off at 2.3. Exclusion Criteria: * Any subject, who does not fit the inclusion criteria. Including history of eating disorders, any systemic and organ disease including diabetes. Lactose intolerance Any blood count, clotting abnormalities HYpertriglyceridemeia (TG over 100 mg/dL) * Hematocrit \