Abstrakt: |
OBJECTIVEInsulin-like growth factor-I (IGF-I) has both insulin-like and anabolic actions but unlike insulin, IGF-I circulates bound to a number of specific binding proteins that regulate its availability and activity. Patients with type 1 diabetes mellitus have low levels of circulating IGF-I despite increased growth hormone (GH) secretion, and are a group that may benefit from rhIGF-I therapy. Understanding the relationship between IGF-I and its binding proteins is necessary to appreciate the actions of exogenously administered rhIGF-I. Therefore, we examined the effects of 19 days' subcutaneous administration of rhIGF-I (50 μg/kg BID) on the levels of IGF-I, IGF-II and the IGF-binding proteins (IGFBPs), as well as the daily dose of insulin necessary to maintain glycaemic control in patients with type 1 diabetes mellitus. DESIGN AND PATIENTSThis was an open study, and the patients were studied initially while resident (days 1–5) in the hospital and thereafter (days 6–24) as outpatients. Serum was collected at baseline and at intervals throughout the study for the measurement of total IGF-I, IGF-II, IGFBP-1, -2, -3, free insulin and growth hormone (GH). Daily insulin doses and glucometer readings were recorded throughout the study. The changes in each of these variables were examined. The subjects were six adults (35.3 ± 4.0 years, mean ± SE), with type 1 diabetes, and all had reasonable glycaemic control (HbA1c 7.2 ± 0.5%). RESULTSrhIGF-I administration increased circulating total IGF-I over two-fold (15.3 ± 1.9 vs. 33.7 ± 5.4 nmol/l, mean ± SEM, P < 0.01, day 1 vs. day 20) and decreased plasma IGF-II concentration (85.0 ± 4.7 vs. 50.6 ± 4.7 nmol/l, P < 0.01, day 1 vs. day 20). The dose of insulin required for adequate glycaemic control decreased significantly during rhIGF-I therapy (46 ± 7 vs. 31 ± 8 U/day, P < 0.05, day -1 vs. day 19), as did the fasting free insulin concentration (8.4... [ABSTRACT FROM AUTHOR] |