Amino acid polymorphism Gly 972 Arg in IRS-1 is not associated to lower clamp-derived insulin sensitivity in young healthy first degree relatives of patients with type 2 diabetes.
The Gly 972 Arg variant in the insulin receptor substrate-1 (IRS-1) gene may interact with the pathogenesis of common insulin-resistance disorders raising the hypothesis that the mutation may predispose to type 2 diabetes. We examined the codon 972 variant in 144 non-diabetic first degree relatives of patients with type 2 diabetes (FDR), who underwent extensive phenotyping: Glucose tolerance was determined by an oral glucose load, insulin sensitivity by euglycaemic-hyperinsulinaemic glucose clamp (glucose metabolic clearance rate, MCR) and body composition by bioelectrical impedance. 20 (14%) of the FDR showed the Gly 972 Arg variant in heterozygous form, 2 (1.3%) probands were homozygous. Carriers of the polymorphism did not differ in MCR independent of body weight and total body fat. The polymorphism does not seem to determine clamp-derived insulin sensitivity. Despite identical fasting plasma glucose, carriers of the polymorphism showed a slightly lower fasting serum insulin and lower insulin response to an oral glucose load but higher glucose concentrations. In an obese subgroup (BMI > 25) the polymorphism did not show a higher frequency and was not associated with lower insulin sensitivity. In the investigated group of young, healthy relatives of type 2 diabetes patients, the frequency of the mutation corresponded to that of a diabetic population. In summary our data show that the polymorphism is not suitable to predict insulin resistance.
Koch
M
M
Medizinische Klinik der Universität Tübingen, Innere Medizin, Endokrinologie, Stoffwechselkrankheiten und Pathobiochemie, Germany. koch-rottenburg@t-online.de
Rett
K
K
Volk
A
A
Maerker
E
E
Haist
K
K
Deninger
M
M
Renn
W
W
Häring
H U
HU
D000328:Adult; D019943:Amino Acid Substitution; D001120:Arginine; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005190:Family; D005260:Female; D005838:Genotype; D005858:Germany; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D005998:Glycine; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D008657:Metabolic Clearance Rate; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
D001786:Blood Glucose; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D001120:Arginine; D005998:Glycine