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Abnormalities in Insulin Sensitivity and Early-Phase Insulin Secretion

Neboja M. Lali, MD, PhD; Jelena Mari, MD; Marina Svetel, MD, PhD; Aleksandra Joti, MD, PhD; Elka Stefanova, MD, PhD; Katarina Lali, MD, PhD; Nataa Dragaevi, MD, PhD; Tanja Milii, MD; Ljiljana Luki, MD; Vladimir S. Kosti, MD, PhD

Arch Neurol. 2008;65(4):476-480.

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.

Design  Metabolic investigations.

Participants  Twenty-nine untreated, nondiabetic patients with HD and 22 control participants matched by age, sex, and socioeconomic background.

Main Outcome Measures  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.

Author Affiliations: Institutes of Endocrinology, Diabetes, and Metabolic Diseases (Drs N. M. Lali, Mari, Joti, K. Lali, Milii, and Luki) and Neurology (Drs Mari, Svetel, Stefanova, Dragaevi, and Kosti), Clinical Center of Serbia, Belgrade.