Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II diabetic patients

Abstract

A suppressed growth hormone (GH) response to GH-releasing hormone (GHRH) in both lean and overweight type II diabetics has been reported. Pyridostigmine (PD), an acetylcholinesterase inhibitor, elicits GH secretion when administered alone and enhances the GH response to GHRH in normal subjects. The aim of our study was to evaluate the effect of PD on GHRH-stimulated GH secretion in both lean and obese type II diabetic patients. We studied 16 patients with type II diabetes mellitus (seven lean and nine obese). Eleven nondiabetic subjects (six lean and five obese) served as controls. Each subject underwent treatment with (1) 120 mg PD orally or (2) 2 tablets of placebo orally, 60 minutes before intravenous (IV) injection of 100 μg GHRH-(1–29)NH 2. We have found no significant differences in GH responses to GHRH between obese diabetics and obese controls. On the other hand, the absolute GH levels were significantly suppressed in lean type II diabetics compared with lean controls at 15 and 30 minutes after GHRH injection. Obese diabetic subjects had slightly but not significantly decreased GH responses to GHRH + PD compared with obese nondiabetic subjects (8.36 ± 1.62 v 14.4 ± 7.62 μg/L). Lean type II diabetics showed a blunted GH release after GHRH + PD compared with normal-weight healthy subjects (GH peaks, 15.77 ± 2.17 v 40 88 ± 6.17 μg/L, P < .05). PD enhanced significantly the GH response to GHRH in obese diabetics, obese controls, and non-obese controls ( P < .05), but not in non-obese type II diabetics. On the basis of our data, it can be hypothesized that chronic, as well as acute, hyperglycemia in the presence of normal or elevated circulating insulin levels may cause a decrease in pituitary GH secretion through an enhancement in hypothalamic somatostatin tone. Moreover, that this altered cholinergic/somatostatin-mediated GH regulation is observed in both lean and obese diabetics suggests that the defects in GH secretion observed in type II diabetes cannot be simply ascribed to the increased body weight.