The Arg972 variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients.
The insulin receptor substrate-1 (IRS-1) gene has been considered a candidate for insulin resistance, type 2 diabetes, and coronary artery disease. To investigate the relationship between the common Gly(972)Arg IRS-1 variant and the presence of cardiovascular risk factors, 153 glucose-tolerant, unrelated offspring of type 2 diabetic patients were studied. There were no differences between Arg(972) IRS-1 carriers and noncarriers in age, gender, body mass index, waist/hip ratio, body composition, fasting glucose and insulin levels, and glucose or insulin levels during the oral glucose tolerance test. Insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, was significantly reduced in carriers of Arg(972) IRS-1 (P < 0.03). Carriers of Arg(972) IRS-1 displayed many features of the insulin resistance syndrome, including higher values for serum triglycerides (P < 0.01), total/high density lipoprotein cholesterol ratio (P < 0.01), free fatty acid levels (P < 0.04), systolic blood pressure (P < 0.04), microalbuminuria (P < 0.003), and intima-media thickness (P < 0.02). These results suggest that the Arg(972) IRS-1 variant could contribute to the risk for atherosclerotic cardiovascular diseases associated with type 2 diabetes by producing a cluster of insulin resistance-related metabolic abnormalities.
Marini
Maria Adelaide
MA
Laboratory of Molecular Medicine, Department of Internal Medicine, University of Rome-Tor Vergata, 00133 Rome, Italy.
Frontoni
Simona
S
Mineo
Davide
D
Bracaglia
Daniela
D
Cardellini
Marina
M
De Nicolais
Pierluigi
P
Baroni
Alessandra
A
D'Alfonso
Rossella
R
Perna
Michela
M
Lauro
Davide
D
Federici
Massimo
M
Gambardella
Sergio
S
Lauro
Renato
R
Sesti
Giorgio
G
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D008875:Middle Aged; D010290:Parents; D010750:Phosphoproteins / Q000235:genetics*; D017354:Point Mutation; D012307:Risk Factors
C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins