Gamma globulin levels predict type 2 diabetes in the Pima Indian population.
It has been proposed that inflammation or infection may contribute to the development of type 2 diabetes. We examined whether serum gamma globulin, a nonspecific measure of the humoral immune system, predicted changes in glucose tolerance in 2,530 members of the Pima Indian population, a group with a marked predisposition to type 2 diabetes. Cross-sectionally, gamma globulin was positively related to age (r = 0.08, P < 0.0005), BMI (r = 0.09; P < 0.0001), and female sex (P < 0.0001). Gamma globulin concentrations were familial, being positively correlated among siblings (r = 0.23; P < 0.0001) and between parents and their children (mother/child: r = 0.17, P < 0.0001; father/child: r = 0.25, P < 0.0001). Gamma globulin concentrations were higher with greater degrees of American Indian heritage (P < 0.004, with adjustment for age, sex, and BMI) and in the presence of a family history of type 2 diabetes (P < 0.04). Higher gamma globulin levels predicted risk of diabetes. In univariate analysis, a 1 SD difference in gamma globulin was associated with a 20% higher incidence of diabetes in those who were normal glucose tolerant at baseline (hazard rate ratio 1.20 [CI 1.11-1.30]; P < 0.0001) and remained as a significant predictor of diabetes, even when controlled for effects of sex, BMI, and 2-h glucose as additional predictors (hazard rate ratio for 1 SD difference in gamma globulin, 1.14 [1.05-1.24]; P = 0.002). Gamma globulin was also associated in univariate analysis with later development of impaired glucose tolerance (IGT) (hazard rate ratio 1.15 [1.07-1.23]; P < 0.0001), but not with the transition from IGT to diabetes (hazard rate ratio 1.04 [0.90-1.20]; P = 0.6). Thus, gamma globulin levels predict increased risk of diabetes in the Pima population. We suggest that immune function or activation may play a role in the development of type 2 diabetes.
Lindsay
R S
RS
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 1550 East Indian School Rd., Phoenix, AZ 85014, USA. rlindsay@mail.nih.gov
Krakoff
J
J
Hanson
R L
RL
Bennett
P H
PH
Knowler
W C
WC
D000328:Adult; D001130:Arizona; D015415:Biomarkers / Q000032:analysis; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000235:genetics; D005190:Family; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007198:Indians, North American; D008297:Male; D011237:Predictive Value of Tests; D012217:Rheumatoid Factor / Q000032:analysis; D015430:Weight Gain; D005719:gamma-Globulins / Q000032:analysis*
D015415:Biomarkers; D005719:gamma-Globulins; D012217:Rheumatoid Factor