Impact of family history of diabetes and ethnicity on -cell function in obese, glucose-tolerant individuals

J Clin Endocrinol Metab. 2007 Dec;92(12):4656-63. doi: 10.1210/jc.2007-0919. Epub 2007 Sep 18.


Context: 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.

Objectives: 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.

Design: 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.

Setting: This study was performed in an Ambulatory General Clinical Research Center.

Subjects: SUBJECTS were healthy, nondiabetic individuals with or without a family history of T2DM.

Interventions: There were no interventions.

Main outcome measures: Comparison of SI, AIRg, AIRmax, DI, and DImax between Caucasians and African-Americans with or without a strong family history of T2DM were made.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • African Americans / statistics & numerical data
  • Arginine
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • European Continental Ancestry Group / statistics & numerical data
  • Female
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin-Secreting Cells / physiology*
  • Male
  • Middle Aged
  • Obesity / genetics*
  • Obesity / physiopathology*


  • Blood Glucose
  • Insulin
  • Arginine
  • Glucose