Hepatic Insulin Resistance in Obese Non-Diabetic Subjects and in Type 2 Diabetic Patients
Article first published online: 6 SEP 2012
2002 North American Association for the Study of Obesity (NAASO)
Volume 10, Issue 3, pages 129–134, March 2002
How to Cite
Paquot, N., Scheen, A. J., Dirlewanger, M., Lefèbvre, P. J. and Tappy, L. (2002), Hepatic Insulin Resistance in Obese Non-Diabetic Subjects and in Type 2 Diabetic Patients. Obesity Research, 10: 129–134. doi: 10.1038/oby.2002.21
- Issue published online: 6 SEP 2012
- Article first published online: 6 SEP 2012
- Submitted for publication June 13, 2001. Accepted for publication in final form November 27, 2001
- glucose production;
- hepatic insulin sensitivity
Objective: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial.
Research Methods and Procedures: To estimate their hepatic insulin sensitivity, we measured the rate of exogenous insulin infusion required to maintain mildly elevated glycemia in obese patients with type 2 diabetes, obese non-diabetic patients, and lean control subjects during constant infusions of somatostatin and physiological low-glucagon replacement infusions. To account for differences in insulin concentrations among the three groups of subjects, an additional protocol was also performed in healthy lean subjects with higher insulin infusion rates and exogenous dextrose infusion.
Results: The insulin infusion rate required to maintain glycemia at 8.5 mM was increased 4-fold in obese patients with type 2 diabetes and 1.5-fold in obese non-diabetic patients. The net endogenous glucose production (measured with 6,6-2H2-glucose) and total glucose output (measured with 2-2H1-glucose) were ∼30% lower in the patients than in the lean subjects. Net endogenous glucose production and total glucose output were both markedly increased in both groups of obese patients compared with lean control subjects during hyperinsulinemia.
Discussion: Our data indicate that both obese non-diabetic and obese type 2 diabetic patients have a blunted suppressive action of insulin on glucose production, indicating hepatic and renal insulin resistance.