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


OBJECTIVE
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.


METHODS
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.


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


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


METHODS
There were no interventions.


METHODS
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.
Rasouli
Neda
N
Research and Medical Services, Central Arkansas Veterans Healthcare System, 111J LR, 4300 West 7th Street, Little Rock, Arkansas 72205, USA. rasoulineda@uams.edu
Spencer
Horace J
HJ
Rashidi
Amir Adel
AA
Elbein
Steven C
SC
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D001120:Arginine; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D044465:White People / Q000706:statistics & numerical data
D001786:Blood Glucose; D007328:Insulin; D001120:Arginine; D005947:Glucose