Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic patients.
OBJECTIVE
Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial.


METHODS
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-(2)H(2)-glucose) and total glucose output (measured with 2-(2)H(1)-glucose) were approximately 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.


CONCLUSIONS
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.
Paquot
Nicolas
N
Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart-Tilman, Liège, Belgium.
Scheen
André J
AJ
Dirlewanger
Mirjam
M
Lefèbvre
Pierre J
PJ
Tappy
Luc
L
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon