Hepatic and peripheral insulin resistance: A common feature of Type 2 (non-insulin-dependent) and Type 1 (insulin-dependent) diabetes mellitus

R. A. DeFronzo, D. Simonson, E. Ferrannini

Research output: Contribution to journalArticlepeer-review

497 Scopus citations


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/1 in the latter group; the respective fasting plasma insulin levels were 19 ± 2 mU/l (p < 0.005 versus 13 ± 1 mU/l in 33 age-matched control subjects), and 9 ± 1 mU/l (p < 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 > p > 0.05) in the Type 2 diabetic patients and markedly elevated (65%, p < 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 < 0.01) and the Type 1 (4.77 ± 0.48 versus 7.03 ± 0.22 mg · min-1 · kg-1, p < 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-stimlated state. Both hepatic and peripheral resistance to the action of insulin contribute to diabetic hyperglycaemia.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
Issue number4
StatePublished - Oct 1982
Externally publishedYes


  • Type 1 and Type 2 diabetes
  • glucose clearance
  • hepatic glucose production
  • insulin resistance
  • insulin-mediated glucose metabolism

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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