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Neurodegenerative disorders associated with diabetes mellitus

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Abstract

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B1 deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.

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Acknowledgements

The author thanks J.-C. von Kleist-Retzow, S.A. Shoichet, M. Vorgerd, and anonymous reviewers for critical comments on the manuscript, A. Duverger for help with French references, and R. Heidmann and D. Kollhof for excellent librarian support. The remarkable resources of http://www.Whonamedit.com regarding the historical contextualization of several syndromes are gratefully acknowledged [315]. The author is currently supported by Deutsche Diabetes Gesellschaft, Deutsche Forschungsgemeinschaft, Fritz-Thyssen-Stiftung, Wilhelm-Sander-Stiftung, and Wissenschaftsgemeinschaft Gottfried Wilhelm Leibniz/Leibniz-Gemeinschaft.

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  1. Department of Clinical Nutrition, German Institute for Human Nutrition, Potsdam-Rehbrücke, 114 Arthur-Scheunert-Allee, 14558, Nuthetal-Berlin, Germany

    Michael Ristow

  2. Department of Endocrinology, Diabetes, and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany

    Michael Ristow

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Ristow, M. Neurodegenerative disorders associated with diabetes mellitus. J Mol Med 82, 510–529 (2004). https://doi.org/10.1007/s00109-004-0552-1

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