Obesity-independent hyperinsulinemia in nondiabetic first-degree relatives of individuals with type 2 diabetes.
A close association between obesity and hyperinsulinemia is well recognized, but it is not known whether this relationship is affected by the genetic susceptibility to type 2 diabetes. Insulin response to a 75-g oral glucose load was evaluated in healthy nondiabetic Caucasians with first-degree family history of diabetes (relatives, n = 55) and those without family history (nonrelatives, n = 33). A significant correlation between the BMI and insulin response (area under the curve [AUC] during the 2-h period) was seen in nonrelatives (r = 0.68, P < 0.0001) but not in the relatives (r = 0.12, P = 0.37). Multivariate analysis revealed that obesity (BMI) was the primary determinant of insulin response in nonrelatives (P < 0.001), whereas among the relatives, BMI had no significant impact (P = 0.28). Thus, these distinctions between the relatives and nonrelatives remained after adjusting for glucose level, age, and gender. Among first-degree relatives, the commonly observed association between BMI and insulin response is lost, and hyperinsulinemia is present even in the absence of obesity. First-degree family history of diabetes may confer insulin resistance that is independent of obesity. Alternatively, this could suggest a pathological regulation of an obesity-insulin feedback loop, e.g., a defective recognition of adiposity.
Ishikawa
M
M
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75235-8858, USA.
Pruneda
M L
ML
Adams-Huet
B
B
Raskin
P
P
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D012016:Reference Values; D044465:White People / Q000235:genetics*
D001786:Blood Glucose