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

Exp Clin Endocrinol Diabetes. 1999;107(5):318-22. doi: 10.1055/s-0029-1212119.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution
  • Arginine
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / genetics*
  • European Continental Ancestry Group / genetics
  • Family
  • Female
  • Genotype
  • Germany
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Glycine
  • Humans
  • Infusions, Intravenous
  • Insulin / administration & dosage
  • Insulin / pharmacology*
  • Insulin Receptor Substrate Proteins
  • Male
  • Metabolic Clearance Rate
  • Phosphoproteins / genetics*
  • Polymorphism, Genetic*


  • Blood Glucose
  • IRS1 protein, human
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Phosphoproteins
  • Arginine
  • Glycine