This Article Full Text Full Text (PDF) A correction has been published Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prudente, S. Articles by Trischitta, V. Search for Related Content PubMed PubMed Citation Articles by Prudente, S. Articles by Trischitta, V. Related Collections Diabetes and Insulin

The TRIB3 Q84R Polymorphism and Risk of Early-Onset Type 2 Diabetes

CSS-Mendel Institute (S.P., E.M., B.D., V.T.), 00198 Rome, Italy; Research Unit of Diabetes and Endocrine Diseases (S.P., V.T.) and Unit of Endocrinology (V.T.), CSS Scientific Institute, 71013 San Giovanni Rotondo, Italy; Department of Experimental and Clinical Medicine (D.S., F.P., F.A., G.S.), University Magna Græcia, 88100 Catanzaro, Italy; Department of Internal Medicine (M.C., R.L., N.A.) and The Center for Human Nutrition (M.C., R.L., N.A.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Research Division (Y.-Y.Z., C.P., A.D.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Medicine (Y.-Y.Z., A.D.), Harvard Medical School, Boston, Massachusetts 02114; Departments of Clinical Sciences (E.M., V.T.) and Experimental Medicine and Pathology (B.D.), "Sapienza" University, 00161 Rome, Italy; and Department of Endocrinology and Metabolism (S.D.G., P.M.), Metabolic Unit, Ospedale Cisanello, University of Pisa, 56127 Pisa, Italy

Address all correspondence and requests for reprints to: Vincenzo Trischitta, M.D., CSS-Mendel Institute, Viale Regina Margherita 261, 00198 Rome, Italy. E-mail: vincenzo.trischitta{at}uniroma1.it.

Context: The prevalence of type 2 diabetes (T2D), particularly among young adults, has been rising steadily during the past 2 decades. T2D, especially in its early-onset subtype, is under genetic control. TRIB3 inhibits insulin-stimulated Akt phosphorylation and subsequent insulin action. A TRIB3 gain-of-function polymorphism, Q84R (rs2295490), impairs insulin signaling.

Objective: The objective of the study was to verify the association of TRIB3 Q84R with: 1) T2D, either subtyped or not according to age at diagnosis (early-onset, <45 yr, or 45 yr); 2) insulin secretion and sensitivity in nondiabetic individuals; or 3) in vitro insulin secretion from isolated human islets.

Design: Four different case-control samples comprising a total of 5469 whites were examined. Insulinogenic and insulin sensitivity indexes and their interplay (disposition index) were assessed in 645 nondiabetic individuals at oral glucose tolerance test, glucose (16.7 mmol/liter)-induced in vitro insulin secretion was assessed in islets isolated from 54 nondiabetic donors.

Results: In the whole sample, the R84 variant was nominally associated with T2D (odds ratio 1.17, 95% confidence interval 1.00–1.36, P = 0.04). When stratifying according to age of diabetes onset, R84 carriers had an increased risk of early-onset T2D (odds ratio 1.32, 95% confidence interval 1.10–1.58, P = 0.002). Among 645 nondiabetic subjects, R84 carriers had higher glucose levels (P = 0.005) and lower insulinogenic (P = 0.03) and disposition index (P = 0.02) during the oral glucose tolerance test. R84 islets were more likely to display relatively low glucose-stimulated insulin release (P = 0.04).

Conclusions: The TRIB3 R84 variant is associated with early-onset T2D in whites. Alteration in the insulin secretion/insulin sensitivity interplay appears to underlie this association.

This article has been cited by other articles:

				H.-p. Gong, Z.-h. Wang, H. Jiang, N.-n. Fang, J.-s. Li, Y.-y. Shang, Y. Zhang, M. Zhong, and W. Zhang TRIB3 Functional Q84R Polymorphism Is a Risk Factor for Metabolic Syndrome and Carotid Atherosclerosis Diabetes Care, July 1, 2009; 32(7): 1311 - 1313. [Abstract] [Full Text] [PDF]