Jenkins A B, Samaras K, Carey D G, Kelly P, Campbell L V
Metabolic Research Centre and Department of Biomedical Science, University of Wollongong, Wollongong, NSW.
Twin Res. 2000 Sep;3(3):148-51. doi: 10.1375/136905200320565427.
Homeostasis model assessment (HOMA) provides indices of insulin secretion (beta) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2 = 0.75, P<0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA') indices were obtained from beta' = (Ln(FPI) - c)/FPG and R' = (Ln(FPI) - c)*FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R'), 0.45 (beta), 0.39 (beta'), all P< 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA-beta and R were strongly related (r = 0.78, P<0.0001 vs. 0.13) demonstrating substantial misclassification. The relationship between beta' and R' (r = 0.13) was not different from that between the two direct measures and significant heritability of beta' (h2 = 0.68, P<0.01) and R' (h2 = 0.59, P<0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG.
稳态模型评估（HOMA）可根据空腹血糖（FPG）和空腹血浆胰岛素（FPI）水平得出胰岛素分泌（β）和胰岛素抵抗（R）的指标。然而，在一组214名女性双胞胎中，这些指标无法解释空腹血糖（FPG）的显著遗传力（h2 = 0.75，P<0.01）。这一结果与HOMA指标中胰岛素分泌和抵抗所产生的效应之间的错误分类一致。我们在此报告HOMA指标中这种错误分类的证据，并描述对该模型的一个小修改以纠正它。在43名非糖尿病受试者中获得了胰岛素抵抗（正常血糖钳夹法）和分泌（静脉注射葡萄糖推注）的直接测量值。通过对214名非糖尿病女性受试者数据中的遗传和环境影响进行统计建模来估计遗传力。修正的HOMA（HOMA'）指标由β' = （Ln(FPI) - c）/FPG和R' = （Ln(FPI) - c）*FPG得出，其中c是通过对Ln(FPI)与FPG进行回归分析得出的常数。两个模型的指标与直接测量值的相关性相似（r = 0.63（R），0.49（R'），0.45（β），0.39（β'），所有P<0.01）。直接测量的胰岛素抵抗和分泌无显著相关性（r = 0.13，P = 0.21）。然而，未修正的HOMA-β和R密切相关（r = 0.78，P<0.0001对比0.13），表明存在大量错误分类。β'与R'之间的关系（r = 0.13）与两种直接测量值之间的关系无差异，并且在双胞胎数据中β'（h2 = 0.68，P<0.01）和R'（h2 = 0.59，P<0.05）的显著遗传力明显。对HOMA的提议修改显著减少了错误分类，并在FPG的遗传力中揭示了胰岛素抵抗和胰岛素分泌的单独成分。
