Impaired insulin sensitivity and secretion in normoglycemic patients with spinocerebellar ataxia type 1.

We have recently shown an impairment in insulin sensitivity and insulin secretion in normoglycemic patients with Huntington disease (HD). To investigate whether such observations are HD-specific or may be common to other polyglutamine diseases, glucose homeostasis was studied in 12 unrelated, untreated normoglycemic patients with spinocerebellar ataxia type 1 (SCA1), another entity from the family of polyglutamine diseases, and 24 healthy, matched controls. Metabolic investigations included (a) glucose tolerance assessment on the basis of glucose curve during oral glucose challenge; (b) insulin sensitivity assessment by the homeostasis model assessment (HOMA) and the euglycemic insulin clamp (M value); and (c) insulin secretion by acute insulin response (AIR) and insulinogenic index. The evaluation of insulin sensitivity demonstrated higher HOMA-insulin resistance indices, and lower M values (P < 0.001 and P < 0.05, respectively), while both the AIR and the insulinogenic index were lower in patients with SCA1 compared to controls (P < 0.001 and P < 0.05, respectively). Our data suggested an impairment in insulin secretion capacity, as well as simultaneous decrease in insulin sensitivity, with an increase in insulin resistance level in patients with SCA1.