Cluster ing of insul in resistance , total and central abdominal fat : same genes or same envi ronment ?
Obesi ty, insul in resistance and disturbed glucose metabol ism cluster wi thin the Insul in Resistance Syndrome (IRS). Whether this reflects shared genetic or envi ronmental factors detectable in ‘normal ’ populations (not selected for IRS features) is unknown. This study estimated (i ) genetic influences on IRS trai ts and (i i ) shared and specific genetic and envi ronmental factors on the relationships between these trai ts in heal thy female twins. Fasting insul in, glucose, total and central fat were measured in 59 monozygotic (MZ) and 51 dizygotic (DZ) female twin pai rs aged ( ± SD) 52 ± 13 years. Body fat was measured by dual -energy X-ray absorptiometry, insul in resistance and secretion by a modified homeostasis model assessment. Using intraclass correlation coefficients and univar iate model -fi tting analyses, genetic influences were found in total fat, central fat, insul in resistance, fasting glucose and insul in secretion, wi th genetic factors explaining 64, 57, 59, 75 and 68% of thei r var iance, respectively, using the latter technique. In matched analysis intra-pai r di fferences in total and central fat related to intra-pai r di fferences in insul in resistance (r 2 = 0.19, P < 0.001). Mul tivar iate model -fi tting showed a close genetic relationship between total and central fat (r = 0.88). The genetic correlation between IR and central fat (0.41) was significantly greater than that for total fat (0.24), suggesting that central fat is not only a predictor of, but shares considerable genetic influence wi th, insul in resistance. In Cholesky analysis, these genetic influences were separate from those shared between central and total fat. In conclusion, both shared and specific genetic factors regulate components of the IRS in heal thy females. However, there were discrete genetic influences on -cel l insul in secretion, not shared wi th other IRS components, suggesting that a separate genetic propensi ty exists for Type2 diabetes. These findings suggest we may understand the genetic and envi ronmental influences on IRS from the study of the normal population.