To determine if patients with NIDDM (non-insulin dependent diabetes mellitus) and individuals at risk for developing the disease, share a common defect in hepatic glycogen storage (chief carbohydrate storage in animals) by infusion of fructose. Fasting hyperglycemia (increased blood sugar) is the result of increased hepatic glucose output (HGO) in patients with non-insulin dependent diabetes mellitus. Some have attributed the increase in HGO to increased gluconeogenesis (formation of glucose from molecules that are not carbohydrates.). However, recent studies suggest that the mechanisms responsible for increased HGO are more complex.
The aims of this study are: 1. To examine intrahepatic (within the liver) compensatory mechanisms in patients with NIDDM. Does increased gluconeogenesis fail to reduce glycogenolysis (breakdown of glycogen to glucose) in NIDDM. 2. To determine whether the punitive defect in hepatic glycogen storage is inherited or acquired. 3. To examine the mechanisms responsible for increased storage after a three-day fast in patients with NIDDM. 4. To examine G-6-Pase gene expression and enzyme activity in obese diabetic and non-diabetic patients for correlation with measures of insulin sensitivity. 5. To determine the effect of reduced insulin secretion on the regulation of G-6-Pase in vivo in man. The subjects will include 10-20 pairs of identical twins where only one twin exhibits NIDDM, recruited from the Virginia Twin Registry and 20 control subjects matched for age, sex, race, and body mass index. Each subject will undergo a standard 75 gm oral glucose tolerance test. Only patients with diet or hypoglycemic treatment will participate and medication will be discontinued for several days before the study. Body fat composition will be assessed by underwater weighing, and the distribution of body fat will be determined by using dual x-ray absorptiometry. A three day diet history will be taken. Subjects will then be admitted to the General Clinical Research Center for two sessions. The studies will be randomized, but not blinded. Following an evening meal, subjects will be at bedrest and fasting until the completion of the session. At a point during the first day, an infusion of glucose will be intravenously administered for the assessment of overall HGO. Another continuous infusion of glucose will be initiated. Baseline blood samples will be obtained. Several other types of blood tests will be done. Breath samples will be taken periodically and indirect calorimetry will be done. Urine will be collected for measurement of nitrogen. Subjects will return at a later date to the GCRC for repetition of tests.
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