Impact of family history of diabetes and ethnicity on β-cell function in obese, glucose-tolerant individuals
N Rasouli, HJ Spencer, AA Rashidi… - The Journal of Clinical …, 2007 - academic.oup.com
N Rasouli, HJ Spencer, AA Rashidi, SC Elbein
The Journal of Clinical Endocrinology & Metabolism, 2007•academic.oup.comContext: 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 β-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 β-cell …
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 β-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 β-cell …
Abstract
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 β-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 β-cell compensation compared with obese controls without a family history of T2DM. In addition, we compared SI 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 β-cell response (DImax). The paradoxical increased DI could be explained by the reduced hepatic insulin extraction.
Oxford University Press