Nagi D K, Knowler W C, Mohamed-Ali V, Bennett P H, Yudkin J S
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA.
Diabetes Care. 1998 Jan;21(1):127-33. doi: 10.2337/diacare.21.1.127.
To examine hyperinsulinemia, insulin secretion, and beta-cell function in Pima Indians, South Asians, and whites, populations at varying risk of diabetes.
We investigated 136 Pima Indian, 98 Asian, and 80 white nondiabetic and 172 Pima Indian, 40 Asian, and 49 white diabetic subjects. Highly specific assays for insulin, intact proinsulin, and des 31,32 proinsulin were used. Insulin secretion was assessed using ratio of increment (0 to 30 min) in insulin to glucose concentrations during an oral glucose tolerance test (OGTT).
Nondiabetic Pima Indians were significantly more obese than Asians and whites. Pima Indian subjects had significantly higher (P < 0.01) fasting insulin concentrations (median 109 pmol/l, range 40-250) than Asian (37 pmol/l, range 17-91) and white (30 pmol/l, range 10-82) subjects. These differences remained significant when controlled for obesity. Nondiabetic Pima Indians also had higher fasting C-peptide concentrations and higher early insulin secretion during an OGTT. Fasting concentrations of intact proinsulin and des 31,32 proinsulin were also significantly higher in Pima Indians (P < 0.01). However, the proportion of proinsulin-like molecules was significantly lower (P < 0.01) in Pima Indians (median 7.9% vs. 12.7% for South Asians and 12.2% for whites). Subjects with diabetes from the three ethnic groups showed significantly higher fasting insulin concentrations but lower 30-min insulin and lower ratios of increment (0-30 min) in insulin to glucose concentrations than did nondiabetic subjects. The proportion of proinsulin-like molecules was not significantly different in diabetic subjects from the three ethnic groups.
These specific assays for insulin indicate that after adjusting for obesity nondiabetic Pima Indians are truly hyperinsulinemic, which is consistent with their insulin resistance as measured by other methods. Hyperinsulinemia in this population with a high risk of diabetes is likely to be due to enhanced insulin secretion. Furthermore, in Pima Indians, the predominant beta-cell secretory product is insulin and not its precursors. We conclude that the differences in the risk of diabetes among these three groups are not due to differences in insulin secretion or insulin processing. Subjects with type 2 diabetes have defective early insulin secretion during OGTTs but show fasting hyperinsulinemia even when specific assays for insulin are used.
研究皮马印第安人、南亚人和白人这三个患糖尿病风险各异的人群中的高胰岛素血症、胰岛素分泌及β细胞功能。
我们调查了136名皮马印第安人、98名亚洲人和80名白人非糖尿病受试者，以及172名皮马印第安人、40名亚洲人和49名白人糖尿病受试者。采用了针对胰岛素、完整胰岛素原和去31,32胰岛素原的高特异性检测方法。在口服葡萄糖耐量试验（OGTT）期间，通过胰岛素增量（0至30分钟）与葡萄糖浓度的比值评估胰岛素分泌。
非糖尿病皮马印第安人的肥胖程度显著高于亚洲人和白人。皮马印第安受试者的空腹胰岛素浓度（中位数109 pmol/l，范围40 - 250）显著高于亚洲人（37 pmol/l，范围17 - 91）和白人（30 pmol/l，范围10 - 82）受试者（P < 0.01）。在控制肥胖因素后，这些差异仍然显著。非糖尿病皮马印第安人在OGTT期间还具有更高的空腹C肽浓度和更早的胰岛素分泌。皮马印第安人的完整胰岛素原和去31,32胰岛素原的空腹浓度也显著更高（P < 0.01）。然而，皮马印第安人中胰岛素原样分子的比例显著更低（P < 0.01）（中位数7.9%，南亚人为12.7%，白人为12.2%）。来自这三个种族的糖尿病受试者的空腹胰岛素浓度显著更高，但30分钟时的胰岛素水平更低，胰岛素与葡萄糖浓度的增量比值（0 - 30分钟）也低于非糖尿病受试者。来自这三个种族的糖尿病受试者中胰岛素原样分子的比例没有显著差异。
这些针对胰岛素的特异性检测表明，在调整肥胖因素后，非糖尿病皮马印第安人确实存在高胰岛素血症，这与通过其他方法测量的胰岛素抵抗一致。这个糖尿病高风险人群中的高胰岛素血症可能是由于胰岛素分泌增强所致。此外，在皮马印第安人中，主要的β细胞分泌产物是胰岛素而非其前体。我们得出结论，这三组人群患糖尿病风险的差异并非由于胰岛素分泌或胰岛素加工的差异。2型糖尿病患者在OGTT期间早期胰岛素分泌存在缺陷，但即使使用胰岛素特异性检测方法，也表现出空腹高胰岛素血症。
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