{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T17:39:26Z","timestamp":1770917966622,"version":"3.50.1"},"reference-count":28,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,7,1]]},"abstract":"<jats:p>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 &amp;lt; 0.0005), BMI (r = 0.09; P &amp;lt; 0.0001), and female sex (P &amp;lt; 0.0001). Gamma globulin concentrations were familial, being positively correlated among siblings (r = 0.23; P &amp;lt; 0.0001) and between parents and their children (mother\/child: r = 0.17, P &amp;lt; 0.0001; father\/child: r = 0.25, P &amp;lt; 0.0001). Gamma globulin concentrations were higher with greater degrees of American Indian heritage (P &amp;lt; 0.004, with adjustment for age, sex, and BMI) and in the presence of a family history of type 2 diabetes (P &amp;lt; 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\u20131.30]; P &amp;lt; 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\u20131.24]; 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\u20131.23]; P &amp;lt; 0.0001), but not with the transition from IGT to diabetes (hazard rate ratio 1.04 [0.90\u20131.20]; 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.<\/jats:p>","DOI":"10.2337\/diabetes.50.7.1598","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1598-1603","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":54,"title":["Gamma Globulin Levels Predict Type 2 Diabetes in the Pima Indian Population"],"prefix":"10.2337","volume":"50","author":[{"given":"Robert S.","family":"Lindsay","sequence":"first","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Krakoff","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L.","family":"Hanson","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter H.","family":"Bennett","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William C.","family":"Knowler","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031207420289100_R1","doi-asserted-by":"crossref","unstructured":"Pickup JC, Crook MA: Is type II diabetes mellitus a disease of the innate immune system? 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