Clinical Endocrine Section, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Institute of Neuroscience, National Research Council, Padova, Italy.
J Clin Endocrinol Metab. 2020 Apr 1;105(4):e1835-46. doi: 10.1210/clinem/dgaa070.
African Americans (AAs) are at a higher risk for developing type 2 diabetes compared with non-Hispanic whites (NHWs). The causal role of β-cell glucose sensitivity (β-GS) and insulin clearance in hyperinsulinemia in AA adults is unclear.
Using a cross-sectional study design, we compared β-cell function and insulin clearance in nondiabetic AAs (n = 36) and NHWs (n = 47) after a mixed meal test (MMT).
Insulin secretion rate, glucose sensitivity, rate sensitivity, and insulin sensitivity during MMT were derived from a mathematical model. Levels of insulin-degrading enzyme (IDE) and carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1), key players in insulin clearance, were measured (by enzyme-linked immunosorbent assay) in hepatic cytosolic fractions from age-, sex-, and body mass index-matched AA and NHW cadaveric donors (n = 10).
Fasting and mean postprandial plasma glucose levels were similar in both ethnic groups. AAs had significantly higher fasting and mean postprandial plasma insulin levels. However, fasting ISR, total insulin output, and insulin sensitivity during MMT were not different between the groups. β-GS and rate sensitivity were higher in AAs. Fasting and meal plasma insulin clearance were lower in AAs. Hepatic levels of IDE and CEACAM-1 were similar in AAs and NHWs. Hepatic IDE activity was significantly lower in AAs.
In this study, lower insulin clearance contributes to higher plasma insulin levels in AAs. Reduced insulin clearance may be explained by lower IDE activity levels in AAs. Further confirmatory studies are needed to investigate diminished insulin clearance in AAs as a result of lower IDE activity levels.
与非西班牙裔白人（NHW）相比，非裔美国人（AA）患 2 型糖尿病的风险更高。β 细胞葡萄糖敏感性（β-GS）和胰岛素清除率在 AA 成人高胰岛素血症中的因果作用尚不清楚。
本研究采用横断面研究设计，比较了非糖尿病 AA（n=36）和 NHW（n=47）在混合餐试验（MMT）后的β细胞功能和胰岛素清除率。
从数学模型中得出 MMT 期间胰岛素分泌率、葡萄糖敏感性、速率敏感性和胰岛素敏感性。测量了来自年龄、性别和体重指数匹配的 AA 和 NHW 尸检供体（n=10）肝胞质部分的胰岛素降解酶（IDE）和癌胚抗原相关细胞粘附分子-1（CEACAM1）水平（酶联免疫吸附试验），这两种物质是胰岛素清除的关键因素。
两组空腹和餐后平均血糖水平相似。AA 组空腹和餐后平均胰岛素水平明显较高。然而，两组间 MMT 期间的空腹胰岛素刺激率（ISR）、总胰岛素输出和胰岛素敏感性并无差异。AA 组的β-GS 和速率敏感性更高。AA 组空腹和餐时血浆胰岛素清除率较低。AA 和 NHW 之间的肝 IDE 和 CEACAM-1 水平相似。AA 组的肝 IDE 活性明显较低。
在这项研究中，较低的胰岛素清除导致 AA 患者的血浆胰岛素水平升高。AA 中较低的胰岛素清除可能归因于 IDE 活性水平较低。需要进一步的确认性研究来研究 AA 中由于 IDE 活性水平降低导致的胰岛素清除减少。
