GLUCOSE-INTOLERANCE IN 1ST-DEGREE RELATIVES OF PATIENTS WITH FRIEDREICHS ATAXIA IS ASSOCIATED WITH INSULIN RESISTANCE - EVIDENCE FOR A CLOSELY LINKED INHERITED TRAIT

Multiple and different genetic defects may be associated with the development of diabetes mellitus. Friedreich's ataxia (FA) is an autosomal recessively inherited neurologic disease associated with a high prevalence of diabetes. We previously demonstrated that patients with FA have insulin resistance prior to the development of overt diabetes mellitus. To determine if insulin resistance is an inherited characteristic in this group, we performed oral glucose tolerance tests (OGTT) on first-degree relatives, 21 parents and 17 siblings, of patients with FA. While fasting concentrations were normal, both glucose and insulin concentrations in response to oral glucose were significantly elevated compared with controls. Corrected insulin responses, CIR = 1 × 100/G (G-70) (I = insulin, G = glucose), were not different from controls, whereas peripheral insulin activities, A = 104/Ip Gp (p = values of I and G at peak glucose concentration), were significantly decreased (FA, 0.66 ± 0.11, P < .001; parents, 0.63 ± 0.06, P < .001; siblings, 0.72 ± 0.09, P < .01; v controls, 1.52 ± 0.19), indicating the presence of insulin resistance in patients and first-degree relatives. Multiple discriminant analysis was used to separate patients with FA from controls. The combination of GLUT (sum of glucose values 0 to 3 hours of the OGTT) and CIR achieved significant separation (P < .0004). Subsequent assignment of the relatives showed that 17 of 18 parents and 11 of 16 siblings (69%) fell in the range of FA, rather than with controls. These data suggest that insulin resistance is an inherited trait in this group. The pattern is consistent with insulin resistance being associated with the heterozygous state and thus closely linked to the genetic lesion of FA. © 1991.