title: beta-cell function and glucose and lipid oxidation in Graves' disease.
abstract: OBJECTIVE
  Abnormal glucose metabolism with impaired glucose tolerance has been documented in patients with thyrotoxicosis but the pathogenesis is not fully understood. Therefore, the aim of the present study was to study the beta-cell function and the meal induced oxidative glucose and lipid metabolism in patients with thyrotoxicosis.
  
  
  METHODS
  After an overnight fast the impact of hyperthyroidism on standard mixed meal induced glucose oxidation, lipid oxidation and beta-cell function was studied.
  
  
  METHODS
  Nine untreated patients with Graves' disease were compared to 9 age and weight matched healthy controls.
  
  
  METHODS
  Glucose and lipid oxidation were studied by indirect calorimetry before and after the meal. The insulin secretion rate was calculated by the 'combined model' approach, after which the insulin secretion rates and the ambient glucose levels were cross-correlated. The slope of these regression lines was used as a measure of beta-cell sensitivity to glucose and denotes the insulin secretory capacity. beta-Cell function was further evaluated by measurement of proinsulin and its conversion intermediates. Glucoregulatory hormones were also measured. The findings were correlated to the thyroid hormone levels.
  
  
  RESULTS
  Fasting blood glucose and post-prandial glucose response were increased in patients (P < 0.01). The hyperthyroid patients displayed a 'dual' beta-cell defect: (a) inability to increase the insulin response appropriately to hyperglycaemia and (b) increased proinsulin levels both in the fasting state and in response to a meal. Indirect calorimetry showed increased lipid oxidation in the fasting state and at the end of the meal (P < 0.01). No difference in glucose oxidation was demonstrated in the fasting state but the post-prandial glucose oxidation was enhanced in the patients (P < 0.01). The adrenaline response was normal, whereas the noradrenaline response was impaired or absent in the patients. The thyroid hormone levels were significantly correlated to fasting levels of blood glucose, insulin, free fatty acids and lipid oxidation, but not to fasting C-peptide, glucose oxidation or catecholamines.
  
  
  CONCLUSIONS
  Untreated Graves' disease was associated with glucose intolerance due to quantitative as well as qualitative beta-cell defects. The lipid oxidation was increased in the fasting state and at the end of the meal; after the meal the increase in glucose oxidation was more pronounced in the patients. Thyroid hormones thus increased the oxidation but not by an increase in catecholamines. Indeed, the post-prandial sympathetic response was blunted.
authors.affiliation: Steno Diabetes Centre, Gentofte, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Bech
authors.forename: P
authors.initials: P
authors.lastname: Damsbo
authors.forename: E
authors.initials: E
authors.lastname: Eldrup
authors.forename: H
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: M E
authors.initials: ME
authors.lastname: Røder
authors.forename: S G
authors.initials: SG
authors.lastname: Hartling
authors.forename: A
authors.initials: A
authors.lastname: Vølund
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D005260:Female; D005934:Glucagon / Q000097:blood; D018149:Glucose Intolerance / Q000378:metabolism / Q000503:physiopathology*; D006111:Graves Disease / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011384:Proinsulin / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013963:Thyroid Hormones; D005934:Glucagon; D011384:Proinsulin; D009638:Norepinephrine