RHIGF-I ADMINISTRATION REDUCES INSULIN REQUIREMENTS, DECREASES GROWTH-HORMONE SECRETION, AND IMPROVES THE LIPID PROFILE IN ADULTS WITH IDDM

IDDM is associated with elevated circulating levels of growth hormone (On) and reduced insulin-like growth factor I (IGF-I). GH antagonizes the action of insulin-increasing insulin requirements in IDDM. The eff ects of subcutaneously administered rhIGF-I on glycemic control, insul in requirements, and GH secretion were studied in eight adults with ID DM. Patients received either placebo or rhIGF-I (50 mu g/kg b.i.d.) fo r 19 days in a randomized, double-blind, parallel-design, placebo-cont rolled trial. Overnight GH, plasma glucose, free insulin, IGF-I, fruct osamine, and lipid profiles were assessed during this period. rhIGF-I therapy increased IGF-I concentration from 117.1 +/- 14.2 (mean +/- SE ) ng/ml (baseline) to 310.5 +/- 40.6 and 257.1 +/- 41.2 ng/ml on day 5 (P < 0.01 vs. baseline) and day 20 (P < 0.01 vs. baseline), respectiv ely. After 19 days of rhIGF-I treatment, fructosamine concentrations w ere unchanged compared with baseline (439 +/- 32 vs. 429 +/- 35 mu mol /l, day -1 vs. day 20, respectively), yet insulin requirements were de creased by similar to 45% (0.67 +/- 0.08 vs. 0.36 +/- 0.07 U.kg(-1).da y(-1), day-1 vs. day 19, respectively, P < 0.005). After 4 days of rhI GF-I therapy, there was a decrease in free insulin levels (8.38 +/- 1. 47 vs. 4.98 +/- 0.84 mU/l, P < 0.05), mean overnight GH concentration (12.6 +/- 3.3 vs. 3.8 +/- 2.1 mU/l, P = 0.05), and total cholesterol a nd triglycerides (4.68 +/-, 0.31 vs. 4.25 +/- 0.35 mmol/l, P < 0.05, 1 .27 +/- 0.19 vs. 0.95 +/- 0.21 mmol/l, P < 0.001, respectively). There was no change in any variable in the placebo-treated patients. This s tudy demonstrates that subcutaneous administration of rhIGF-I decrease s insulin requirements and improves the plasma lipid profile while mai ntaining glycemic control in adults with IDDM. The excess nocturnal re lease of GH, characteristic of IDDM, is also decreased by rhIGF-I ther apy. Exogenous rhIGF-I therapy may have a role in the treatment of adu lts with IDDM, particularly in the setting of abnormal lipids and a hi gh insulin requirement.