Danadian K, Balasekaran G, Lewy V, Meza M P, Robertson R, Arslanian S A
Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, University of Pittsburgh, Pennsylvania, USA.
Diabetes Care. 1999 Aug;22(8):1325-9. doi: 10.2337/diacare.22.8.1325.
African-Americans are at increased risk for type 2 diabetes. We have previously demonstrated that African-American children are hyperinsulinemic and insulin resistant compared with their white American peers. The aim of the present investigation was to assess the impact of family history of type 2 diabetes on insulin sensitivity in African-American children.
A total of 13 prepubertal healthy children with negative family history (FH-) and 9 with positive family history (FH+) of type 2 diabetes underwent a 3-h hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp study to assess insulin sensitivity. The groups were comparable for age, pubertal status, total body adiposity determined by dual-energy X-ray absorptiometry, abdominal adiposity assessed by computed tomography scan at the level of L4-5 lumbar vertebra, and physical fitness measured by maximal oxygen consumption (VO2max).
The FH+, compared with the FH-, group had lower insulin-stimulated glucose disposal (10.9+/-1.2 vs. 14.2+/-0.9 mg x kg(-1) x min(-1), P = 0.035) and lower nonoxidative glucose disposal (5.7+/-0.8 vs. 8.3+/-0.6 mg x kg(-1) x min(-1), P = 0.015), with no differences in rates of glucose oxidation, fat oxidation, or insulin-mediated free fatty acid suppression. Fasting hepatic glucose production assessed with [6,6-2H2]glucose and basal rates of glucose and fat oxidation were not different between the two groups.
These data suggest that in African-American children, family history of type 2 diabetes is a risk factor for insulin resistance. These children manifest important metabolic alterations, including impaired insulin-stimulated total and nonoxidative glucose disposal early in the first decade of life. We propose that this familial tendency, combined with environmental influences, could lead to type 2 diabetes decades later.
非裔美国人患2型糖尿病的风险增加。我们之前已经证明，与美国白人同龄人相比，非裔美国儿童存在高胰岛素血症和胰岛素抵抗。本研究的目的是评估2型糖尿病家族史对非裔美国儿童胰岛素敏感性的影响。
对13名青春期前2型糖尿病家族史阴性（FH-）的健康儿童和9名家族史阳性（FH+）的儿童进行了一项为期3小时的高胰岛素血症（40 mU x m(-2) x min(-1)）-正常血糖钳夹研究，以评估胰岛素敏感性。两组在年龄、青春期状态、通过双能X线吸收法测定的全身脂肪量、通过L4-5腰椎水平的计算机断层扫描评估的腹部脂肪量以及通过最大耗氧量（VO2max）测量的身体素质方面具有可比性。
与FH-组相比，FH+组胰岛素刺激的葡萄糖处置较低（10.9±1.2 vs. 14.2±0.9 mg x kg(-1) x min(-1)，P = 0.035），非氧化葡萄糖处置较低（5.7±0.8 vs. 8.3±0.6 mg x kg(-1) x min(-1)，P = 0.015），而葡萄糖氧化、脂肪氧化或胰岛素介导的游离脂肪酸抑制率无差异。两组之间用[6,6-2H2]葡萄糖评估的空腹肝葡萄糖生成以及葡萄糖和脂肪氧化的基础速率无差异。
这些数据表明，在非裔美国儿童中，2型糖尿病家族史是胰岛素抵抗的一个危险因素。这些儿童表现出重要的代谢改变，包括在生命的第一个十年早期胰岛素刺激的总葡萄糖和非氧化葡萄糖处置受损。我们认为这种家族倾向与环境影响相结合，可能在几十年后导致2型糖尿病。
