Exaggerated insulin secretion in Pima Indians and African-Americans but higher insulin resistance in Pima Indians compared to African-Americans and Caucasians.
OBJECTIVE
African-Americans have a higher prevalence of Type 2 diabetes than Caucasians, but a lower prevalence than Pima Indians. Studies suggest that both African-Americans and Pima Indians are more insulin resistant and have higher acute insulin secretory responses to glucose than Caucasians; however, a direct comparison between these three populations is lacking.


METHODS
We measured insulin secretory responses to intravenous glucose (acute insulin response, AIR, 25 g ivGTT); insulin action at physiological (M-low) and supra-physiological (M-high) levels of hyperinsulinaemia (2-step hyperinsulinaemic clamp); basal and insulin-suppressed endogenous glucose production in 30 African-Americans, 30 Pima Indians and 30 Caucasians with normal glucose tolerance who were carefully matched for age, sex, and body fat (hydrodensitometry or DEXA). A subgroup of 24 subjects from each group additionally underwent a standardized mixed meal test.


RESULTS
M-low was lower in Pima Indians (0.50 +/- 0.03) compared to Caucasians (0.59 +/- 0.02, P = 0.02) and African-Americans [0.58 +/- 0.03 mg/kgEMBS/min, log10 (means +/- SE), P = 0.03] but was not different between African-Americans and Caucasians. Basal endogenous glucose production was lower in Pima Indians (2.43 +/- 0.06) compared to African-Americans (2.70 +/- 0.06, P = 0.02) and was not different between Pima Indians and Caucasians (2.59 +/- 0.09 mg/kgEMBS/min) or African-Americans and Caucasians (all P > 0.18). Insulin-suppressed endogenous glucose production during the clamp was not different among the groups (all P > 0.40). AIR was higher in both African-Americans (13.51 +/- 0.26) and Pima Indians (13.72 +/- 0.27) compared to Caucasians (12.33 +/- 0.25 pM, log10, both P < 0.01). The areas under the curve for glucose in response to the oral glucose tolerance test and mixed meal test were higher in Pima Indians compared to African-Americans (P = 0.03 and P = 0.03, respectively) and Caucasians (P = 0.01, mixed meal test), but not different between African-Americans and Caucasians.


CONCLUSIONS
Exaggerated glucose-stimulated insulin secretion, manifested initially as an increased response to an intravenous glucose challenge, appears to be a characteristic in people with normal glucose tolerance at higher risk for diabetes. Lower whole-body insulin sensitivity in Pima Indians compared to African-Americans, however, may contribute to the higher risk for Type 2 diabetes in Pima Indians compared to African-Americans.
Stefan
N
N
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA. norbert.stefan@med.uni-tuebingen.de
Stumvoll
M
M
Weyer
C
C
Bogardus
C
C
Tataranni
P A
PA
Pratley
R E
RE
D000293:Adolescent; D000328:Adult; D001741:Black or African American; D019540:Area Under Curve; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000208:ethnology* / Q000378:metabolism; D007198:Indians, North American; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D044465:White People
D007328:Insulin; D005947:Glucose