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 x 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.