Summary
Friedreich's ataxia is known to be associated with diabetes mellitus in up to 20% of the patients. However, type, development and course of diabetes mellitus are not well characterised. We report on 3 patients (2 female and 1 male, age 13–20 years) with the combination of Friedreich's ataxia and diabetes mellitus. Diabetes mellitus was characterised as follows: (1) it was strictly insulin-dependent and ketosis-prone, (2) the average insulin requirement was 1 U/kg body weight, (3) the HLA haplotype was not typical of Type 1 (insulin-dependent) diabetes mellitus, (4) there were no positive immune parameters typical of Type 1 diabetes at the clinical onset of diabetes mellitus and (5) there was no remission. To evaluate a preclinical phase as in common autoimmune Type 1 diabetes, i.v. glucose tolerance tests (0.5 g glucose/kg body weight) were performed in 8 patients with Friedreich's ataxia without diabetes mellitus. Seven patients had normal early phase insulin response. In contrast, the glucose disappearance rate was slow in 4 and normal in 3 patients. One of the 8 patients showed a prediabetic metabolic state: the early-phase insulin response was abolished and the glucose disappearance rate was abnormal. The results suggest that diabetes in Friedreich's ataxia is caused by a loss of islet cells similar to common Type 1 diabetes but without HLA-association and without serologic evidence for autoimmune destruction of the islet cells.
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Harding AE (1981) Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain 104: 589–620
Andermann E, Remillard GM, Goyer C, Blitzer M, Andermann F, Barbeau A (1976) Genetic and family studies in Friedreich's ataxia. Can J Neurol Sci 3: 287–301
Harding AE, Zilkha KJ (1981) ‘Pseudo-dominant’ inheritance in Friedreich's ataxia. J Med Genetics 18: 285–287
Romeo G, Menozzi P, Ferlini A, Fadda S, Di Donato S, Uziel G, Lucci B, Capodaglio L, Filla A, Campagnella G (1983) Incidence of Friedreich's ataxia in Italy estimated from consanguineous marriages. Am J Human Genet 35: 523–529
Chamberlain S, Shaw J, Rowland A, Wallis J, South S, Nakamura Y, von Gabain A, Farrall M, Williamson R (1988) Mapping of mutation causing Friedreich's ataxia to human chromosome 9. Nature 334: 248–250
Thorén C (1962) Diabetes mellitus in Friedreich's ataxia. Acta Paediatr [Suppl.] 135: 239–247
Shapcott D, Melancon S, Butterworth RF, Khoury K, Collu R, Breton G, Geoffroy G, Lemieux B, Barbeau A (1976) Glucose and insulin metabolism in Friedreich's ataxia. Can J Neurol Sci 3: 361–364
Platz P, Jakobsen BK, Morling N, Ryder LP, Svejgaard A, Thomsen M, Christy M, Kromann H, Benn J, Nerup J, Green A, Hauge M (1981) HLA-D and -DR Antigens in genetic analysis of insulin-dependent diabetes mellitus. Diabetologia 21: 108–115
Drell DW, Notkins AL (1987) Multiple immunological abnormalities in patients with Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 132–143
Lernmark Å (1985) Molecular biology of Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 28: 195–203
Geoffroy G, Barbeau A, Breton G, Lemieux B, Aube M, Leger C, Bouchard JP (1976) Clinical description and roentgenologic evaluation of patients with Friedreich's ataxia. Can J Neurol Sci 3: 279–286
Hürter P, Barth N, Bierich JR (1969) Der i. v.-Glucosetoleranztest bei stoffwechselgesunden und diabetischen Kindern. Monatsschr Kinderheilkd 117: 518–522
Landin Olsson M, Sundkvist G, Lernmark Å (1987) Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titres of islet cell antibodies in Type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30: 327–332
Baekkeskov S, Landin M, Kristensen JK, Srikanta S, Bruining GJ, Mandrup-Poulsen T, de Beaufort C, Soeldner JS, Eisenbarth G, Lindgren F, Sundquist G, Lernmark Å (1987) Antibodies to a Mr 64000 human islet cell antigen precede the clinical onset of insulin-dependent diabetes. J Clin Invest 79: 926–934
Srikanta S, Ganda OP, Rabizadeh D, Soeldner JS, Eisenbarth GS (1985) First degree relatives of patients with Type 1 diabetes mellitus Islet-cell antibodies and abnormal insulin secretion. N Engl J Med 313: 461–464
Powers AC, Eisenbarth GS (1985) Autoimmunity to islet cells in diabetes mellitus. Ann Rev Med 36: 533–544
Spinas GA, Hansen BS, Linde S, Kastern W, Mø1vig J, Mandrup-Poulsen T, Dinarello CA, Nielsen JH, Nerup J (1987) Interleukin 1 dose-dependently affects the biosynthesis of (pro)insulin in isolated rat islets of Langerhans. Diabetologia 30: 474–480
Srikanta S, Ganda OP, Eisenbarth GS, Soeldner JS (1983) Isletcell antibodies in monozygotic triplets and twins initially discordant for Type 1 diabetes mellitus. N Engl J Med 308: 322–325
Srikanta S, Ricker AT, McGulloch DK, Soeldner JS, Eisenbarth GS, Palmer JP (1986) Autoimmunity to insulin, beta cell dysfunction and development of insulin-dependent diabetes mellitus. Diabetes 35: 139–142
Köhne G (1941) Über die Beziehungen der Friedreichschen Ataxie zum Diabetes mellitus. Deutsch Med Wochenschr 67: 177–179
James TN, Cobbs BW, Coghlan HC, McCoy WC, Fisch C (1987) Coronary disease, cardioneuropathy and conduction abnormalities in the cardiomyopathy of Friedreich's ataxia. Br Heart J 57: 446–457
Khan RI, Andermann E, Fantus GI (1986) Glucose intolerance in Friedreich's ataxia: Association with insulin resistance and decreased insulin binding. Metabolism 35: 1017–1023
Tolis G, Metha A, Andermann E, Harvey C, Barbeau A (1980) Friedreich's ataxia and oral glucose tolerance. Can J Neurol Sci 7: 397–400
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Schoenle, E.J., Boltshauser, E.J., Baekkeskov, S. et al. Preclinical and manifest diabetes mellitus in young patients with friedreich's ataxia: no evidence of immune process behind the islet cell destruction. Diabetologia 32, 378–381 (1989). https://doi.org/10.1007/BF00277262
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DOI: https://doi.org/10.1007/BF00277262