Assessment of Liver Glucose Metabolism in Diabetic Subjects (CLAVA)

Type 2 diabetes is associated with hepatic insulin resistance. One consequence of insulin resistance of the liver is an altered hepatic glucose metabolism. This study investigates whether the whole body (M-value) and hepatic insulin sensitivity obtained by hyperinsulinemic euglycemic clamp is influenced by a preceding intravenous glucose tolerance test (Botnia Clamp) in subjects with type 2 diabetes.

The hyperinsulinemic euglycemic clamp represents the gold standard for measuring peripheral insulin sensitivity. The insulin sensitivity is described by the M-value,which is calculated from glucose infusion rates during the last 30min of the clamp. Glucose is metabolised in the periphery: 50% by neural tissues, 20% by splanchnic bed and liver, 15% by skeletal muscle, 5% by adipose tissue and 10% by blood cells and other tissues. Under hyperinsulinemic conditions there is a strong shift in glucose utilization: 85% skeletal muscle and 15% by neural tissues, splanchnic bed and liver, adipose tissue, blood cells and other tissues. The contribution of skeletal muscle varies with different insulin sensitivity. We now want to investigate whether there is a difference in tissue-specific insulin sensitivity measured from a Botnia clamp (intravenous glucose tolerance test (ivGTT) and following clamp) and a single hyperinsulinemic euglycemic clamp? After a 60min ivGTT blood glucose levels in type 2 diabetic subjects are still elevated compared to baseline. High blood glucose levels can influence several parameters and may also affect insulin sensitivity. Until now, it is not proven, that the clamp preceding ivGTT does not have a significant influence on the M-value.

Inclusion Criteria: newly diagnosed type 2 diabetes (during the last 12 months)or non-diabetic subjects Exclusion Criteria: severe chronic diseases hepatitis B, C oder HIV infection malignancies immune suppressive therapy psychiatric illnesses drug or alcohol abuse anemia renal dysfunction

Kahl S, Nowotny B, Piepel S, Nowotny PJ, Strassburger K, Herder C, Pacini G, Roden M. Estimates of insulin sensitivity from the intravenous-glucose-modified-clamp test depend on suppression of lipolysis in type 2 diabetes: a randomised controlled trial. Diabetologia. 2014 Oct;57(10):2094-102. doi: 10.1007/s00125-014-3328-3. Epub 2014 Jul 22.