Lehtovirta M, Kaprio J, Forsblom C, Eriksson J, Tuomilehto J, Groop L
Department of Medicine, University of Helsinki, Finland.
Diabetologia. 2000 Mar;43(3):285-93. doi: 10.1007/s001250050046.
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.
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.
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. Insulin-stimulated 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.
目的/假设:评估胰岛素敏感性和胰岛素分泌的遗传性,这两者均被认为与II型(非胰岛素依赖型)糖尿病的发生有关。
计算了21对同性别、年龄在54至72岁之间的单卵双胞胎和20对同性别双卵双胞胎的组内相关系数以及胰岛素敏感性(正常血糖钳夹法)、第一相和晚期胰岛素分泌(静脉葡萄糖耐量试验)的遗传度估计值。
单卵双胞胎中所有性状的配对内相关性始终高于双卵双胞胎。仅在单卵双胞胎之间胰岛素分泌存在显著相关性(第一相r = 0.55;p = 0.003,晚期r = 0.66;p < 0.001),遗传度估计值分别为0.55和0.58。胰岛素刺激的葡萄糖摄取在单卵双胞胎之间的相关性较低(r = 0.46;p = 0.015)。遗传度估计值为0.37。女性双胞胎腰臀比的遗传度估计值为0.76,男性双胞胎为0.70。
结论/解读:遗传变异似乎对胰岛素敏感性和胰岛素分泌的变异均有贡献。在本研究中,遗传变异几乎占葡萄糖刺激的胰岛素分泌变异的60%,占胰岛素刺激的葡萄糖摄取变异的近40%。我们的数据也与单基因糖尿病的研究结果一致,在单基因糖尿病中胰岛素分泌的遗传缺陷在高血糖发病机制中起主要作用。