BETA-CELL FUNCTION AND GLUCOSE AND LIPID OXIDATION IN GRAVES-DISEASE

OBJECTIVE Abnormal glucose metabolism with impaired glucose tolerance has been documented in patients with thyrotoxicosis but the pathogenes is is not fully understood. Therefore, the aim of the present study wa s to study the beta-cell function and the meal induced oxidative gluco se and lipid metabolism in patients with thyrotoxicosis. DESIGN After an overnight fast the impact of hyperthyroidism on standard mixed meal induced glucose oxidation, lipid oxidation and beta-cell function was studied. PATIENTS Nine untreated patients with Graves' disease were c ompared to 9 age and weight matched healthy controls. MEASUREMENTS Glu cose and lipid oxidation were studied by indirect calorimetry before a nd after the meal. The insulin secretion rate was calculated by the 'c ombined model' approach, after which the insulin secretion rates and t he ambient glucose levels were cross-correlated. The slope of these re gression lines was used as a measure of beta-cell sensitivity to gluco se and denotes the insulin secretory capacity. beta-Cell function was further evaluated by measurement of proinsulin and its conversion inte rmediates. Glucoregulatory hormones were also measured, The findings w ere correlated to the thyroid hormone levels. RESULTS Fasting blood gl ucose and post-prandial glucose response were increased in patients (P < 0.01). The hyperthyroid patients displayed a 'dual' beta-cell defec t: (a) inability to increase the insulin response appropriately to hyp erglycaemia and (b) increased proinsulin levels both in the fasting st ate and in response to a meal. Indirect calorimetry showed increased l ipid oxidation in the fasting state and at the end of the meal (P < 0. 01). No difference in glucose oxidation was demonstrated in the fastin g state but the post-prandial glucose oxidation was enhanced in the pa tients (P < 0.01). The adrenaline response was normal, whereas the nor adrenaline response was impaired or absent in the patients, The thyroi d hormone levels were significantly correlated to fasting levels of bl ood glucose, insulin, free fatty acids and lipid oxidation, but not to fasting C-peptide, glucose oxidation or catecholamines. CONCLUSIONS U ntreated Graves' disease was associated with glucose intolerance due t o quantitative as well as qualitative beta-cell defects. The lipid oxi dation was increased in the fasting state and at the end of the meal; after the meal the increase in glucose oxidation was more pronounced i n the patients. Thyroid hormones thus increased the oxidation but not by an increase in catecholamines. indeed, the post-prandial sympatheti c response was blunted.