Gamma globulin levels predict type 2 diabetes in the Pima Indians population

It has been proposed that inflammation or infection may contribute to the d evelopment of type 2 diabetes. We examined whether serum gamma globulin, a nonspecific measure of the humoral immune system, predicted changes in gluc ose tolerance in 2,530 members of the Pima Indian population, a group with a marked predisposition to type 2 diabetes. Cross-sectionally, gamma globul in,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 f amilial, 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 hi gher with greater degrees of American Indian heritage (P < 0.004, with adju stment for age, sex, and BMI) and in the presence of a family history of ty pe 2 diabetes (P < 0.04). Higher gamma globulin levels predicted risk of di abetes. In univariate analysis, a 1 SD difference in gamma globulin was ass ociated with a 20%, higher incidence of diabetes in those who were normal g lucose tolerant at baseline (hazard rate ratio 1.20 [CI 1.11-1.30]; P < 0.0 001) and remained as a significant predictor of diabetes, even when control led for effects of sex, BMI,and 2-h glucose as additional predictors (hazar d 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 (h azard rate ratio 1.04 [0.90-1.20]; P = 0.6). Thus, gamma globulin levels pr edict increased risk of diabetes in the Pima population. We suggest that im mune function or activation may play a role in the development of type 2 di abetes.