title: Glucose homeostasis in Huntington disease: abnormalities in insulin sensitivity and early-phase insulin secretion.
abstract: BACKGROUND
  Patients with Huntington disease (HD) develop diabetes mellitus more often than do matched healthy controls. Recent studies in neurodegenerative diseases suggested that insulin resistance constitutes a metabolic stressor that interacts with a preexisting neurobiological template to induce a given disorder.
  
  
  OBJECTIVE
  To investigate possible changes in insulin sensitivity and secretion, major determinants of glucose homeostasis, in a group of consecutive normoglycemic patients with HD.
  
  
  METHODS
  Metabolic investigations.
  
  
  METHODS
  Twenty-nine untreated, nondiabetic patients with HD and 22 control participants matched by age, sex, and socioeconomic background.
  
  
  METHODS
  Glucose tolerance, assessed by means of the glucose curve during oral glucose challenge; insulin sensitivity, assessed using homeostasis model assessment and minimal model analysis based on frequent sampling of plasma glucose and plasma insulin during the intravenous glucose tolerance test; and insulin secretion, determined by means of the acute insulin response and the insulinogenic index.
  
  
  RESULTS
  The evaluation of insulin sensitivity using homeostasis model assessment demonstrated higher homeostasis model assessment insulin resistance indices, and a lower sensitivity index when the minimal model approach was used, in patients with HD compared with controls (P = .03 and P = .003, respectively). In the assessment of early-phase insulin secretion, the acute insulin response and the insulinogenic index were lower in patients with HD compared with controls (P = .02). The number of CAG repeats correlated significantly only with acute insulin response (P = .003).
  
  
  CONCLUSIONS
  Besides impairment in insulin secretion capacity, a simultaneous decrease in insulin sensitivity, with an increase in the insulin resistance level, was found in normoglycemic patients with HD compared with controls. These data imply that progression of the insulin secretion defect in HD may lead to a failure to compensate for insulin resistance.
authors.affiliation: Institute of Endocrinology, Diabetes, and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Nebojsa M
authors.initials: NM
authors.lastname: Lalić
authors.forename: Jelena
authors.initials: J
authors.lastname: Marić
authors.forename: Marina
authors.initials: M
authors.lastname: Svetel
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jotić
authors.forename: Elka
authors.initials: E
authors.lastname: Stefanova
authors.forename: Katarina
authors.initials: K
authors.lastname: Lalić
authors.forename: Natasa
authors.initials: N
authors.lastname: Dragasević
authors.forename: Tanja
authors.initials: T
authors.lastname: Milicić
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Lukić
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostić
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin