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Decreased Insulin Sensitivity and Compensatory Hyperinsulinemia after Hormone Treatment in Children with Short Stature¹

Department of Pediatrics and the Children’s Clinical Research Center, Yale University School of Medicine, New Haven, Connecticut 06510

Address all correspondence and requests for reprints to: Rubina A. Heptulla, M.D., Department of Pediatrics, Division of Endocrinology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510.

To assess the effects of GH treatment on carbohydrate and protein metabolism, we studied eight patients with short stature before and after the commencement of GH treatment. The hyperglycemic clamp procedure was employed to produce a hyperglycemic stimulus of 50 mg/dL above fasting levels for 120 min. These patients were then treated with 0.3 mg/kg·week GH for 6 months, after which they were restudied. Patients were compared to eight healthy control children matched for age, sex, and Tanner stage. Fasting plasma glucose did not change significantly, but fasting plasma insulin levels were higher after GH therapy (P < 0.005). Despite identical glucose increments during the glucose clamp procedure, both first and second phase insulin responses were markedly greater after instituting GH treatment. Even in the face of higher mean plasma insulin levels after GH treatment, the rate of insulin-stimulated glucose metabolism did not differ during the last 60 min of both studies. Hence, the rate of insulin-stimulated glucose metabolism/mean plasma insulin ratio (an index of insulin sensitivity) was sharply reduced after GH treatment (P < 0.01). During the clamp, the fall in circulating branched chain amino acid levels was significantly greater after GH therapy (P < 0.02). We conclude that glucose-stimulated insulin responses are increased in short children treated with GH and that such hyperinsulinemic responses compensate for reductions in insulin sensitivity. The compensatory hyperinsulinemic responses induced by GH therapy may serve a beneficial role by augmenting insulin’s anabolic effects on protein metabolism.

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