INSULIN-LIKE GROWTH FACTOR-I IMPROVES GLUCOSE AND LIPID-METABOLISM IN TYPE-2 DIABETES-MELLITUS

Hyperglycemia, hyperinsulinemia, and insulin resistance cause vascular disease in type 2 diabetes mellitus. Dietary treatment alone often fails and oral drugs or insulin enhance hyperinsulinemia. In previous studies, an intravenous bolus of recombinant human insulin-like growth factor-I (rhIGF-I) caused normoglycemia in insulin-resistant diabetics whereas rhIGF-I infusions lowered insulin and lipid levels in healthy humans, suggesting that rhIGF-I is effective in insulin-resistant states. Thus, eight type 2 diabetics on a diet received on five treatment days subcutaneous rhIGF-I (2 x 120 mug/kg) after five control days. Fasting and postprandial glucose, insulin, C-peptide, proinsulin, glucagon, triglyceride, insulin-like growth factor-I and -II, and growth hormone levels were determined. RhIGF-I administration increased total IGF-I serum levels 5.3-fold above control. During the control period mean (+/-SD) fasting glucose, insulin, C-peptide, and total triglyceride levels were 11.0+/-4.3 mmol/liter, 108+/-50 pmol/liter, 793+/-250 pmol/liter, and 3.1+/-2.7 mmol/liter, respectively, and decreased during treatment to a nadir of 6.6+/-2.5 mmol/liter, 47+/-18 pmol/liter, 311+/-165 pmol/liter, and 1.6+/-0.8 mmol/liter (P < 0.01), respectively. Postprandial areas under the glucose, insulin, and C-peptide curve decreased to 77+/-13 (P < 0.02), 52+/-11, and 60+/-9% (P < 0.01) of control, respectively. RhIGF-I decreased the proinsulin/insulin ratio whereas glucagon levels remained unchanged. The magnitude of the effects of rhIGF-I correlated with the respective control levels. Since rhIGF-I appears to improve insulin sensitivity directly and/or indirectly, it may become an interesting tool in type 2 diabetes and other states associated with insulin resistance.