Rasouli Neda, Spencer Horace J, Rashidi Amir Adel, Elbein Steven C
Research and Medical Services, Central Arkansas Veterans Healthcare System, 111J LR, 4300 West 7th Street, Little Rock, Arkansas 72205, USA.
J Clin Endocrinol Metab. 2007 Dec;92(12):4656-63. doi: 10.1210/jc.2007-0919. Epub 2007 Sep 18.
The increased insulin secretion in response to reduced insulin sensitivity (SI) is heritable, but whether the genetic predisposition is restricted to members of high-risk Caucasian families is unknown. Furthermore, the relative importance of insulin resistance and defective beta-cell compensation in the increased prevalence of type 2 diabetes (T2DM) in African-American compared with Caucasian individuals is uncertain.
We tested whether obese individuals with a family history of T2DM have decreased beta-cell compensation compared with obese controls without a family history of T2DM. In addition, we compared S(I) and insulin secretion measures in African-American and Caucasian individuals.
SI, acute insulin response to iv glucose (AIRg), maximally potentiated insulin response to arginine (AIRmax), and disposition indexes (DIs) (DI = SI * AIRg; DImax = SI * AIRmax) were compared among nondiabetic Caucasian and African-American individuals with and without a family history of diabetes.
This study was performed in an Ambulatory General Clinical Research Center.
SUBJECTS were healthy, nondiabetic individuals with or without a family history of T2DM.
There were no interventions.
Comparison of SI, AIRg, AIRmax, DI, and DImax between Caucasians and African-Americans with or without a strong family history of T2DM were made.
Obese subjects did not differ in SI, AIRg, or DI by family history of diabetes. African-Americans had 8% lower SI (P < 0.001), but 68% higher AIRg (P < 0.001) and 46% higher DI (P = 0.001) than age, gender, body mass index-matched Caucasian individuals. However, African-Americans had lower DImax compared with Caucasians.
We found no reduction in insulin secretion in obese subjects with a family history of T2DM compared with controls, but in general, African-Americans were more insulin resistant and had lower maximal beta-cell response (DImax). The paradoxical increased DI could be explained by the reduced hepatic insulin extraction.
胰岛素敏感性（SI）降低时胰岛素分泌增加具有遗传性，但这种遗传易感性是否仅限于高危白种人家庭的成员尚不清楚。此外，与白种人相比，非裔美国人2型糖尿病（T2DM）患病率增加中胰岛素抵抗和β细胞代偿缺陷的相对重要性尚不确定。
我们测试了有T2DM家族史的肥胖个体与无T2DM家族史的肥胖对照相比，β细胞代偿是否降低。此外，我们比较了非裔美国人和白种人的SI及胰岛素分泌指标。
在有和没有糖尿病家族史的非糖尿病白种人和非裔美国人个体中比较SI、静脉注射葡萄糖后的急性胰岛素反应（AIRg）、精氨酸最大增强胰岛素反应（AIRmax）和处置指数（DI）（DI = SI * AIRg；DImax = SI * AIRmax）。
本研究在门诊综合临床研究中心进行。
受试者为有或无T2DM家族史的健康非糖尿病个体。
无干预措施。
比较有或无T2DM家族史的白种人和非裔美国人之间的SI、AIRg、AIRmax、DI和DImax。
肥胖受试者的SI、AIRg或DI不因糖尿病家族史而异。与年龄、性别、体重指数相匹配的白种人个体相比，非裔美国人的SI低8%（P < 0.001），但AIRg高68%（P < 0.001），DI高46%（P = 0.001）。然而，与白种人相比，非裔美国人的DImax较低。
我们发现有T2DM家族史的肥胖受试者与对照组相比胰岛素分泌没有减少，但总体而言，非裔美国人胰岛素抵抗更强，最大β细胞反应（DImax）更低。DI的矛盾性增加可以用肝脏胰岛素摄取减少来解释。
