Impact of waist-to-hip ratio on the genetic phenotype in probands of type 2 diabetes

Objective To explore the impact of waist-to-hip ratio (WHR) in type 2 diabetic probands on the phenotype of insulin resistance and β-cell function in normoglycemic first-degree relatives. Methods One hundred and eighty-six type 2 diabetic probands and 489 normoglycemic first-degree relatives were selected from 186 type 2 diabetes core families. 115 first-degree relatives (FDR1 group) of probands with low WHR (1st quartile: 0.92 for males and >0.89 for females) were identified to intensively study from 489 normoglycemic first-degree relatives. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin sensitivity, and β-cell function was quantified as the ratio of the incremental insulin to glucose responses over the first 30 min (△I30/△G30) during the oral glucose tolerance test. The latter measure was also adjusted for the assay of insulin sensitivity as it modulated β-cell function (△I,,30>·△G-1,30·HOMA-IR-1). Results The body mass index, the waist circumference and waist-to-height ratio in female first-degree relatives, systolic blood pressure, triglyceride and HOMA-1R were significantly higher in FDR2 group than those in FDR1 group andhigh density lipoprotein cholesterol,△I30/△G30, △I-130·HOMA-IR-1were significantly lower in FDR2 group than those in FDRI group (P < 0.05 or P < 0.O1). The waist circumference and waist-to-height ratio in relatives of probands with low and high WHR were positively correlated with the HOMA-IR. However, the least square regression analysis showed that the slope from regression in FDR2 group were significantly steeper than thatin FDR1 group(both P <0.01). Conclusion The normoglycemic first-degree relatives of the type 2 diabetic probands with high WHR had much more evident phenotype of insulin resistance and decreased β-cell function, and a slight increase in abdominal obesity had a greater impact on insulin resistance. Key words: Diabetes mellitus, type 2;  First-degree relatives;  Proband;  Insulin resistance;  β-cell function