EFFECTS OF A PHYSIOLOGICAL GROWTH-HORMONE PULSE ON SUBSTRATE METABOLISM IN INSULIN-DEPENDENT (TYPE-1) DIABETIC SUBJECTS

When present in inappropriate amounts GH induces substantial insulin resistance and it has furthermore been suggested that modest nocturnal surges of GH may precipitate the emergence of the dawn phenomenon. To characterize the metabolic effects of physiologically relevant, small-scale GH exposure, six type 1 diabetic subjects were studied for 5 h in the postabsorptive state after an iv pulse of either 210-mu-g GH or saline. Identical amounts of insulin were infused on both occasions to maintain a prevailing blood glucose concentration of 125 +/- 12 mg/100 ml. The GH bolus caused an increase in serum GH levels to a peak value of 22 +/- 2-mu-g/L after 10 min, a 70% increase in serum FFA (from 570 +/- 80 to 980 +/- 60-mu-mol/L) and a 400% increase in blood 3-hydroxybutyrate (3-OHB) (from 100 +/- 15 to 420 +/- 35-mu-mol/1) concentrations after 180 and 240 min respectively (P < 0.05). Blood glycerol and forearm uptake of 3-OHB rose in parallel (P < 0.01). Plasma glucose, isotopically measured glucose turnover and forearm glucose uptake was not affected by GH. Blood lactate concentrations increased (P < 0.05) and nonoxidative glucose use and lipid oxidation tended to increase with GH. Energy expenditure remained unaffected. These results suggest that under everyday conditions GH acts as an important regulator of fuel fluxes in type 1 diabetic subjects, the main effect being a transient stimulation of lipolysis. Since no significant effect on glucose metabolism was recorded, we do not presently find evidence to support a primary role for small surges of GH in the pathogenesis of the dawn phenomenon.