Contribution of obesity to insulin resistance in noninsulin-dependent diabetes mellitus.
Inasmuch as previous studies have obtained conflicting results on the contribution of obesity to insulin resistance in noninsulin-dependent diabetes mellitus (NIDDM), we studied 10 nonobese and 10 obese NIDDM patients with the isoglycemic-(approximately 10 mmol/L)-hyperinsulinemic clamp (two insulin infusions of 4 and 40 mU/m-2 min-1), combined with [3-3H]glucose infusion and indirect calorimetry. As compared with nonobese patients, obese NIDDM patients had higher baseline peripheral and estimated portal plasma insulin concentrations (113 +/- 18 vs. 46 +/- 3 pmol/L and 288 +/- 53 vs. 98 +/- 6 pmol/L, respectively; P < 0.05) and less suppressed endogenous insulin production during clamp. Hepatic glucose production was greater in obese than in nonobese patients (basal, 16 +/- 1.1 vs. 12 +/- 0.5 mumol/kg-1 fat-free mass (FFM) min-1; clamp, 5.7 +/- 0.5 vs. 2.8 +/- 0.2 mumol/kg-1 FFM min-1, P < 0.05). Glucose utilization increased to a lesser extent in obese than in nonobese patients (49 +/- 5 vs. 73 +/- 7 mumol/kg-1 FFM min-1, P < 0.05) during clamp because of a lower increase in nonoxidative glucose metabolism (30 +/- 5 vs. 50 +/- 7 mumol/kg-1 FFM min-1, P < 0.05). Plasma free fatty acid concentrations and rates of lipid oxidation were greater in obese (P < 0.05) patients and correlated with hepatic glucose production (r = 0.79 and 0.50, P < 0.05). In conclusion, obesity exaggerates hepatic as well as extra-hepatic insulin resistance in NIDDM. The impaired inhibition of pancreatic beta-cell function by exogenous insulin contributes to exaggerated hyperinsulinemia in obese NIDDM.
Perriello
G
G
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, University of Perugia.
Misericordia
P
P
Volpi
E
E
Pampanelli
S
S
Santeusanio
F
F
Brunetti
P
P
Bolli
G B
GB
D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006019:Glycolysis; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity; D011168:Portal System; D012044:Regression Analysis
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin