Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus.

Hepatic glucose production (3H-glucose technique) and insulin-mediated glucose uptake (insulin clamp technique) were measured in 38 Type 2 (non-insulin-dependent) and 11 Type 1 (insulin-dependent) diabetic patients. Fasting plasma glucose concentration was 8.3 +/- 0.5 mmol/l in the former, and 9.6 +/- 1.3 mmol/l in the latter group; the respective fasting plasma insulin levels were 19 +/- 2 mU/l (p less than 0.005 versus 13 +/- 1 mU/l in 33 age-matched control subjects), and 9 +/- mU/l (p less than 0.01 versus 14 +/- 1 mU/l in 36 younger control subjects). In the fasting state, hepatic glucose production was slightly increased (15%, 0.1 greater than p greater than 0.05) in the Type 2 diabetic patients and markedly elevated (65%, p less than 0.001) in the Type 1 patients compared with their respective control groups. In both groups of diabetic subjects, the rates of hepatic glucose production were inappropriately high for the prevailing plasma glucose and insulin levels, indicating the presence of hepatic resistance to insulin. Basal plasma glucose clearance was also significantly reduced in both the Type 2 (34%) and the Type 1 (14%) diabetic subjects. The fasting plasma glucose concentration correlated directly with hepatic glucose production, and inversely with plasma glucose clearance. During the insulin clamp, plasma insulin was maintained at approximately 100 mU/l in all groups, while plasma glucose was maintained constant at the respective fasting levels. Total glucose uptake was reduced in both the Type 2 (4.57 +/- 0.31 versus 6.39 +/- 0.25 mg . min -1 . kg -1 in the control subjects, p less than 0.01) and the Type 1 (4.77 +/- 0.48 versus 7.03 +/- 0.22 mg . min -1 . kg -1, p less than 0.01)diabetic patients. Insulin-stimulated glucose clearance was reduced to a similar extent in Type 2 (54%) and Type 1 (61%) diabetic subjects, and correlated directly with fasting glucose clearance. These results show that insulin resistance is a common feature of both types of diabetes and can be demonstrated in the basal as well as the insulin-stimulated state. Both hepatic and peripheral resistance to the action of insulin contribute to diabetic hyperglycaemia.