Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins

Abstract

There is plenty of evidence that Type II (non-insulindependent) diabetes mellitusis a disease with a strong genetic predisposition [1±3]. In Finland, the estimated lifetime relative risk (l) of developing diabetes for a sibling to a person with Type II diabetes is about three [4]. This value decreases with age suggesting that environmental factors become more important with increasing age. Obesity and physical inactivity are the most important triggers of the disease. Several twin studies have provided unequivocal support for the genetic nature of the adult-onset type of diabetes, i. Abstract Aims/hypothesis. To estimate the heritability of insulin sensitivity and insulin secretion, both of which are considered to contribute to the development of Type II (non-insulin-dependent) diabetes mellitus. Methods. Intraclass correlation coefficients and heritability estimates for insulin sensitivity (euglycaemic clamp) as well as first-phase and late-phase insulin secretion (intravenous glucose tolerance test) were calculated in 21 monozygotic and 20 dizygotic twin pairs of the same sex between 54 and 72 years of age. Results. Intrapair correlations for all traits were consistently higher in monozygotic than in dizygotic pairs. Insulin secretion correlated significantly only between monozygotic (first-phase r = 0.55; p = 0.003 and late-phase r = 0.66; p < 0.001) twins giving heritability estimates of 0.55 and 0.58, respectively. Insulinstimulated glucose uptake showed a more modest correlation between monozygotic twins (r = 0.46; p = 0.015). The heritability estimate was 0.37. The heritability estimate for waist-to-hip ratio was 0.76 in female and 0.70 in male twins. Conclusion/interpretation. Genetic variability seems to contribute to the variance of insulin sensitivity as well as of insulin secretion. In the current study, genetic variance accounted almost 60 % for the variance in glucose-stimulated insulin secretion and almost 40 % for the variance in insulin-stimulated glucose uptake. Our data is also compatible with findings in monogenic forms of diabetes in which genetic defects in insulin secretion play a predominant part in the pathogenesis of hyperglycaemia. [Diabetologia (2000) Corresponding author: M. Lehtovirta, Helsinki University Central Hospital, Department of Medicine, Division of Internal Medicine, PO Box 346, FIN-00 029 HYKS, Finland Abbreviations: MZ, Monozygotic; DZ, dizygotic; MODY, maturity-onset diabetes of the young; WHR, waist-to-hip ratio; FFM, fat-free mass; SBP, systolic blood pressure; DBP, diastolic blood pressure; FPI, first-phase insulin secretion in IVGTT; LPI, late-phase insulin secretion in IVGTT; Intraclass r, intraclass correlation coefficient; h 2 , heritability; A, additive component of variance; C, variance component due to shared environment; D, variance component due to dominance; E, variance component due to non-shared environmental influences.

Heritability of model-derived parameters of beta cell secretion during intravenous and oral glucose tolerance tests: a study of twins

“…A subset of twin pairs also underwent either a more detailed OGTT (plasma glucose and C-peptide measured at 0, 30, 60, 90 and 120 min; 33 MZ, 17 female/16 male; and 23 DZ, 11 female/12 male), or an IVGTT (21 MZ, six female/15 male; and 20 DZ, seven female/13 male), as described in detail in our previous work [17], or both (13 MZ, four female/nine male; and 14 DZ, five female/nine male). Data from the detailed OGTT were used for the calculation of OGTT beta index.…”

“…Study design Anthropometric measures and body composition were assessed as previously reported [17].…”

“…IVGTT and euglycaemic-hyperinsulinaemic clamp Details of the experimental procedures have been reported elsewhere [17]. Briefly, after an overnight fast, an IVGTT was performed, during which 0.3 g/kg body weight of glucose (maximum dose 35 g) was infused intravenously over 2 min, and blood samples for the analysis of plasma glucose and serum insulin were drawn at 0, 2, 4, 6, 8, 10, 20, 30, 40, 50 and 60 min.…”

“…Serum C-peptide concentrations were measured by RIA with an interassay CV of 9% (Linco, St. Charles, MO, USA). Lipids were measured as previously described [17].…”

“…For this paper we applied mathematical modelling to a database of results of IVGTTs performed in pairs of monozygotic (MZ) and dizygotic (DZ) twins [17], to assess the heritability (h 2 ) of early and late phases of glucosestimulated insulin secretion, as determined by a model of glucose-stimulated insulin secretion. We also estimated the h 2 for OGTT beta index, obtained using a database of results for OGTTs performed in MZ and DZ twins, which partially overlapped the IVGTT database.…”