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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detailed in vivo and in vitro studies of glucose and insulin metabolism in Friedreich's ataxia patients and unaffected family members have further defined the extent of the abnormalities in carbohydrate metabolism. The high incidence of glucose intolerance and a hyperinsulinemic response to a glucose challenge in a high percentage of Friedreich's ataxia patients has been confirmed. An increased incidence of glucose intolerance among heterozygotes is suggested, while the siblings show a more normal distribution of diabetes and a nearly normal insulin response to the glucose tolerance test. Human growth hormone patterns are normal for all groups. Preliminary studies of insulin binding to erythrocytes suggest a difference in the binding characteristics among diabetic Friedreich's ataxia patients, while the binding in the non-diabetic Friedreich's ataxia group is similar to that of non-diabetic controls. Results from a small group of non-diabetic siblings suggest a normal insulin binding, while a tendency toward increased binding at low insulin concentrations among diabetic family members is noted.
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PMID:Glucose tolerance and erythrocyte insulin receptors in Friedreich's ataxia. 48 16

Our prospective survey of 50 ataxic patients confirms the previous finding of frequent clinical or chemical diabetes in Friedreich's ataxia. Eighteen percent of our typical cases have clinical diabetes and 40% at least an abnormal glucose tolerance curve. However, this finding does not appear to be specific to that form of ataxia. Furthermore, we have shown that most patients with ataxia have normal or low fasting insulin levels, but a hyperinsulinic response to a glucose load.
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PMID:Glucose and insulin metabolism in Friedreich's ataxia. 100 Apr 22

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 = I x 100/G (G-70) (I = insulin, G = glucose), were not different from controls, whereas peripheral insulin activities, A = 10(4)/Ip Gp (p = values of I and G at peak glucose concentration), were significantly decreased (FA, 0.66 +/- 0.11, P less than .001; parents, 0.63 +/- 0.06, P less than .001; siblings, 0.72 +/- 0.09, P less than .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 less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose intolerance in first-degree relatives of patients with Friedreich's ataxia is associated with insulin resistance: evidence for a closely linked inherited trait. 186 28

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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PMID:Preclinical and manifest diabetes mellitus in young patients with Friedreich's ataxia: no evidence of immune process behind the islet cell destruction. 266 85

We have characterized the abnormalities of glucose metabolism associated with Friedreich's ataxia (FA) by studying plasma glucose, insulin, growth hormone (GH), and glucagon before and after an oral glucose tolerance test (OGTT), an IV glucose load, and an IV arginine load, in 21 patients and in controls. Twelve patients were normotolerant (NT) to glucose, five glucose-intolerant (IT), and four diabetic (DM). Insulin secretion of IT patients was increased and delayed during OGTT. Interestingly, the insulin release during arginine load was significantly decreased in NT and IT as well as in DM patients. The GH response to OGTT was altered in IT patients. Plasma glucagon after an arginine load was significantly higher in patients than in controls. The results indicate that FA is associated with insulin resistance, beta-cell deficiency, and type I diabetes. These alterations might be genetically linked or metabolically related to the primary defect in FA. Their interplay or independent effects are responsible for abnormalities of glucose metabolism in FA.
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PMID:Glucose metabolism alterations in Friedreich's ataxia. 304 13

Friedreich's Ataxia (FA) is a neurologic disorder associated with a high prevalence of diabetes mellitus. To assess insulin secretion and insulin resistance, glucose and insulin responses to oral glucose and insulin binding to circulating monocytes and dextran gradient fractionated and unfractionated red blood cells (RBCs) were compared in 11 subjects with FA to 11 age-matched controls. Glucose and insulin responses were elevated from one to three hours after oral glucose in FA. The mean corrected insulin responses were not different while peripheral insulin activity (A) was significantly decreased (1.38 +/- 0.22 v 0.77 +/- 0.16, control v FA, P less than 0.025) indicating the presence of insulin resistance. A significant correlation between the degree of insulin resistance (A) and duration of neurologic symptoms was found (r = .65. P less than 0.025). Resistance to exogenous insulin was confirmed in ten subjects with FA by intravenous insulin tolerance tests (KITT, %/min, 6.25 +/- 0.90 v 3.93 +/- 0.61, P less than .05). Both FA and control groups showed highest insulin binding to fraction A (youngest) RBCs, but no difference was observed between the two groups. However, insulin binding to monocytes was significantly decreased in subjects with FA (% specific binding/10(7) cells/mL, 6.37 +/- 0.71 v 4.51 +/- 0.39, P less than 0.05, control v FA). This was associated with a decrease in apparent receptor affinity. We conclude that FA is associated with insulin resistance, which increases with the duration of neurologic impairment. The insulin binding to monocytes suggests that the insulin resistance may be partially explained by a receptor defect.
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PMID:Glucose intolerance in Friedreich's ataxia: association with insulin resistance and decreased insulin binding. 353 14

A 12 year old girl with Friedreich's ataxia, in whom progression from chemical to severe insulin-dependent diabetes mellitus occurred over a two year period, is presented. During the phase of subclinical diabetes her plasma immunoreactive insulin response to oral glucose was markedly increased, but when she became symptomatic gross insulin deficiency had supervened. This report draws attention to the unusual disorders of carbohydrate metabolism and insulin secretion that may occur in a variety of neurological conditions.
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PMID:Evolution of diabetes mellitus in a case of Friedreich's ataxia. 471 11

Treatment of rats with asparagine or glutamine caused substantial increases in glutamine concentrations in cerebellum and medulla oblongata. Insulin treatment caused a diminution of glutamate and GABA in these regions of brain. Since it is now well-established that glutamine is a very efficient precursor of the neurotransmitter pool of glutamate in mammalian brain, treatment with asparagine or glutamine could be of therapeutic (replacement) value in the treatment of neurological disorders such as Friedreich's ataxia, in which cerebral glutamate concentrations have been found to be diminished.
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PMID:Effect of asparagine, glutamine and insulin on cerebral amino acid neurotransmitters. 611 88

Glucose tolerance and insulin release were evaluated in 16 families with Friedrich's ataxia. Impaired glucose tolerance differed in incidence according to the method of evaluation, but was increased in number in parents and siblings of Friedreich's cases. Insulin output was not quantitatively different from normal, although the insulin peak was often delayed. This finding, in association with impaired glucose tolerance, suggest a defect in glucose entry into cells.
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PMID:Friedreich's ataxia and oral glucose tolerance: I. The effect of ingested glucose on serum glucose and insulin values in homozygotes, obligate heterozygotes and potential carriers of the Friedreich's ataxia gene. 701 24

In a study of glycosylated hemoglobins in Friedreich's Ataxia patients and in family members, the level was found to be higher in insulin dependent diabetics than in healthy non-diabetic control subjects (p < 0.01), but was similar to non-ataxic diabetic control subjects. Results for non-diabetic Friedreich's Ataxia patients and siblings were similar to those for non-diabetic control subjects while levels were slightly increased in the heterozygotes. It is concluded that in Friedreich's Ataxia patients and family members (apart from the insulin dependent diabetics), there was no hyperglycemia sufficient to be detected as an increase in glycosylated hemoglobins.
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PMID:Glycosylated hemoglobins in Friedreich's ataxia. 721 55


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