Interactions between TCF7L2 genotype and growth hormone-induced changes in glucose homeostasis in small for gestational age children

Context The Transcription factor 7-like 2 (TCF7L2) rs7903146 gene polymorphism has been associated with risk of developing type 2 diabetes mellitus (DM), possibly by decreasing insulin secretion. Small for gestational age (SGA) birth has been associated with type 2 DM in later life. Growth hormone (GH) treatment reduces insulin sensitivity and increases insulin secretion. Therefore, GH-treated SGA children are an ideal group to investigate whether the TCF7L2 rs7903146 genotype is associated with changes in glucose homeostasis. Objective To determine the impact of the TCF7L2 rs7903146 polymorphism on changes in insulin secretion and insulin sensitivity during 4 years of GH treatment in children born SGA. Subjects A total of 246 Caucasian short children born SGA, with a median age of 7·8 years. Outcome measures Insulin sensitivity and insulin secretion were measured by the frequently sampled intravenous glucose tolerance test (FSIGT) (n = 68) and homeostasis model assessment (HOMA) calculations (all). Results There was no association between rs7903146 genotype and insulin sensitivity or insulin secretion at baseline but after adjustment for possible confounders, insulin secretion was higher in the CT/TT group than in the CC group. During GH treatment, carriers of the rs7903146 T allele had an increase in insulin secretion similar to that of carriers of the CC genotype. The decrease in insulin sensitivity was only significant in the CT/TT group, but the difference in decrease between genotype groups did not reach significance (P = 0·06). The disposition index (insulin secretion × insulin sensitivity), which is an estimate of beta cell function, was not associated with genotype and did not change during GH treatment. Conclusion The TCF7L2 rs7903146 polymorphism is not associated with the change in insulin secretion during GH treatment in short SGA children.

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