Familiality of quantitative metabolic traits in Finnish families with non-insulin-dependent diabetes mellitus. Finland-United States Investigation of NIDDM Genetics (FUSION) Study investigators

Hum Hered. 1999 Jun;49(3):159-68. doi: 10.1159/000022865.

Abstract

Type 2 diabetes mellitus (NIDDM) is a complex disorder encompassing multiple metabolic defects. There exists strong evidence for a genetic component to NIDDM; however, to date there have been few reports of linkage between genetic markers along the genome and NIDDM or NIDDM-related quantitative traits. We sought to determine whether individual quantitative traits which determine glucose tolerance exhibit familiality in Finnish families with at least one NIDDM-affected sibling pair. Tolbutamide-modified frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on unaffected offspring (n = 431) and spouses (n = 154) of affected sibling pairs sampled for the Finland-United States Investigation of NIDDM Genetics (FUSION) study. FSIGT data were analyzed using the Minimal Model to obtain quantitative measures of insulin sensitivity (SI), glucose effectiveness (SG), and insulin secretion assessed as the acute insulin response to glucose (AIR). The disposition index (DI), a measure of insulin resistance-corrected beta-cell function, was also derived as the product of SI and AIR. Variance components analysis was used to determine for each trait, the heritability (h2), the proportion of the total trait variance accounted for by additive genes. After adjustment for age, gender, and body mass index, h2 estimates were: SG: 18 +/- 9%, SI: 28 +/- 8%, AIR: 35 +/- 8%, and DI: 23 +/- 8%. We conclude that there is strong evidence for modest heritability of Minimal-Model-derived NIDDM-related quantitative traits in unaffected spouses and offspring of Finnish affected sibling pairs.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Family Health
  • Fasting
  • Female
  • Finland
  • Glucose / pharmacology
  • Glucose Tolerance Test / methods
  • Humans
  • Insulin / blood
  • Lipids / blood
  • Male
  • Middle Aged
  • Pedigree
  • Quantitative Trait, Heritable*
  • Tolbutamide / pharmacology

Substances

  • Blood Glucose
  • Insulin
  • Lipids
  • Tolbutamide
  • Glucose