ENERGY-METABOLISM AND SUBSTRATE OXIDATION IN ACROMEGALY

Short term GH administration increases Lipid breakdown and oxidation ( Lipid(ox)) and reduces glucose uptake and carbohydrate oxidation (CHOo x). It is not clear whether similar shifts in substrate oxidation occu r in acromegaly, and our aim was to investigate this. Using indirect c alorimetry, we compared energy expenditure, CHOox, and lipid(ox) in 20 acromegalic patients and 20 normal subjects pair-matched for sex, age , height, and weight. Investigations mere performed in the basal state (12-h fast) and during a 75-g oral glucose tolerance test (OGTT). Acr omegalic patients had significantly higher fasting glucose levels and greater glucose and insulin responses during an OGTT than normal subje cts. Fasting nonesterified free fatty acid and insulin-like growth fac tor (IGF)-binding protein-1 levels were similar in the two groups, and both were acutely suppressed by oral glucose to the same degree. Basa l energy expenditure was significantly greater in the acromegalic pati ents (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P < 0.05), who showed a tr end toward higher basal CHOox. Oral glucose resulted in a significantl y higher rise in energy expenditure in the normal compared to the acro megalic subjects. During the OGTT, CHOox significantly increased in bo th groups, but rose to a higher level in the acromegalic patients (177 +/- 10 vs. 138 +/- 9 mg/min; P = 0.004). Oral glucose significantly r educed lipid(ox) in both groups, but lipid(ox) was reduced to a signif icantly lower level in the acromegalic patients (32 +/- 4 vs. 46 +/- 3 mg/min; P = 0.004). In acromegaly, basal CHOox (r=0.56;P=0.01) and po stglucose CHOox (r=0.79; P=0.0001) were both positively correlated to IGF-I, but not to insulin and/or glucose. In normal subjects, postgluc ose CHOox was positively correlated to IGF-I. In summary, hyperinsulin emia in acromegaly was associated with higher glucose levels and a blu nted thermogenic response to glucose, and displayed no relationship to the pattern of substrate oxidation. CHOox was increased, and lipid(ox ) was reduced in acromegaly, and the extent of IGF-I elevation was rel ated to COOox in the basal and postglucose states. We conclude that 1) the chronic effects of GH excess on substrate oxidation differ from t he short term effects of GH administration; 2) impaired insulin action in acromegaly extends to effects on energy expenditure; and 3) IGF-I may he an important regulator of substrate oxidation in acromegaly.