The TRIB3 Q84R polymorphism and risk of early-onset type 2 diabetes

Sabrina Prudente, Daniela Scarpelli, Manisha Chandalia, Yuan Yuan Zhang, Eleonora Morini, Silvia Del Guerra, Francesco Perticone, Rong Li, Christine Powers, Francesco Andreozzi, Piero Marchetti, Bruno Dallapiccola, Nicola Abate, Alessandro Doria, Giorgio Sesti, Vincenzo Trischitta

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)190-196
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number1
DOIs
StatePublished - Jan 2009

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Prudente, S., Scarpelli, D., Chandalia, M., Zhang, Y. Y., Morini, E., Del Guerra, S., Perticone, F., Li, R., Powers, C., Andreozzi, F., Marchetti, P., Dallapiccola, B., Abate, N., Doria, A., Sesti, G., & Trischitta, V. (2009). The TRIB3 Q84R polymorphism and risk of early-onset type 2 diabetes. Journal of Clinical Endocrinology and Metabolism, 94(1), 190-196. https://doi.org/10.1210/jc.2008-1365