Twin study of genetic and environmental influences on glucose tolerance and indices of insulin sensitivity and secretion

Abstract

Aims/hypothesis. Family and twin studies have reported different estimates of the relative contribution of genetic and environmental factors to the quantitative traits glucose tolerance, insulin secretion, and insulin sensitivity. Our aims were to estimate these relative influences in a large sample of twins from the population and to assess the effect of age. Methods. In this population-based, cross-sectional study we gave an oral glucose tolerance test to 317 women and 290 men who were same-sex healthy twin pairs between 18 to 67 years of age. The genetic, common environmental and individual environmental variance components for fasting and 120-min glucose and for fasting and 30-min insulin as well as the linear effects of age on these components were estimated by multivariate analysis (using the software FISHER). Results. In women and men the heritability for fasting glucose was 12 and 38%, for 120-min glucose it was 38 and 43%, for fasting insulin it was 54 and 37%, and for 30-min insulin it was 57 and 47%, respectively. Under the assumption of no non-additive genetic effects (no intra-or inter-gene interaction) there was no strong evidence for common environmental effects, barring significant effects for fasting glucose in women. Heritability decreased with age for 120-min glucose in women and fasting insulin in men, whereas it increased for 120-min glucose in men. Conclusion/interpretation. This study indicates a limited additive genetic influence on the result of an OGTT, possibly with sex-specific age effects, and generally little or no influence of the common environment. Accordingly, there is a considerable individual environmental variation. [Diabetologia (2003[Diabetologia ( ) 46:1276[Diabetologia ( -1283

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

“…The data analysed in the present study were part of the GEMINAKAR study [14,23]. The study is a nationwide Danish project investigating the genetic epidemiology of a wide variety of phenotypes among Danish twins, including endophenotypes of the metabolic syndrome [14,23].…”

“…The study is a nationwide Danish project investigating the genetic epidemiology of a wide variety of phenotypes among Danish twins, including endophenotypes of the metabolic syndrome [14,23]. The twins were recruited from two cohorts of the nationwide, population-based Danish Twin Registry.…”

“…Blood was taken before oral glucose ingestion and 30 and 120 min later; it was then analysed using the glucose dehydrogenase oxidation method. Then, a two-site, two-step, time-resolved immunofluorometric assay was used to measure serum insulin concentration [14]. Cholesterol, HDL and TAG were measured on fasting blood samples by a colorimetric method (VITROS; Johnson & Johnson, New Brunswick, NJ, USA).…”

“…A wide range of heritabilities (mostly moderate to high) have been estimated for obesity traits (mean: 0.55; range: 0.37-0.80) [9][10][11][12][13][14]; insulin-related traits (mean: 0.38; range: 0.08-0.75) [9][10][11][13][14][15][16]; BP (mean: 0.41; range: 0.16-0.76) [9][10][11][12][13] and lipid traits (mean: 0.46; range: 0.20-0.70) [9][10][11][12][13]. However, the underlying mechanism of the clustering of these characteristics in an individual remains unclear [17].…”

“…Twins from the Danish Twin Registry have been used to estimate the heritability of each separate endophenotype associated with the metabolic syndrome in old twins born between 1921 and 1930 (40 for the county of Funen) and recently, based on 625 twin pairs from the study 'The importance of genes, familiar and common environment for the development of insulin resistance, abdominal adiposity and cardiovascular risk factors' (GEMINAKAR) [14,23]. The aim of the present study was to quantify genetic and environmental (co)variation between these endophenotypes in the GEMINAKAR cohort.…”