Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes.
Shunting of glycolytic intermediates into the pentose phosphate pathway has been suggested to protect from hyperglycaemia-induced microvascular damage. We hypothesized that genetic variability in the gene encoding transketolase, a key pentose phosphate pathway enzyme, contributes to early nerve dysfunction in recent-onset diabetes.



In this cross-sectional study, we assessed nine single nucleotide polymorphisms (SNPs) in the transketolase gene, plasma methylglyoxal concentrations, and clinical and quantitative measures of peripheral nerve function in 165 type 1 and 373 type 2 diabetic patients with a diabetes duration up to 1 year.



The Total Symptom Score was associated with transketolase SNPs rs7648309, rs62255988, and rs7633966, while peroneal motor nerve conduction velocity (MNCV) correlated only with rs7648309 (P < 0.01). Cold thermal detection threshold (TDT) (foot) was associated with transketolase SNPs rs11130362 and rs7648309, while warm TDT (hand) correlated with rs62255988 and rs7648309 (P < 0.01). After Bonferroni correction, the correlations of transketolase SNP rs7648309 with Total Symptom Score and rs62255988 with warm TDT (hand) remained statistically significant. Among subgroups, men with type 2 diabetes showed the strongest associations. No associations were observed between each of the nine tagged transketolase SNPs and plasma methylglyoxal concentrations.



The observed associations of genetic variation in transketolase enzyme with neuropathic symptoms and reduced thermal sensation in recent-onset diabetes suggest a role of pathways metabolizing glycolytic intermediates in early diabetic neuropathy. Copyright © 2016 John Wiley & Sons, Ltd.
Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Dan
D
Ziegler
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
Erwin
E
Schleicher
Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Alexander
A
Strom
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
Birgit
B
Knebel
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
Thomas
T
Fleming
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
Peter
P
Nawroth
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
Hans-Ulrich
HU
Häring
Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Nikolaos
N
Papanas
Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Julia
J
Szendrödi
Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Karsten
K
Müssig
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
Hadi
H
Al-Hasani
Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Michael
M
Roden
The GDS Group consists of M. Roden (speaker), H. Al-Hasani, A.E. Buyken, J. Eckel, G. Geerling C. Herder, A. Icks, J. Kotzka, O. Kuß, E. Lammert, J. Lundbom, D. Markgraf, K. Müssig, W. Rathmann, J. Szendrödi, D. Ziegler, and their co-workers who are responsible for the design and conduct of the GDS.
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D014174:Transketolase / Q000235:genetics*
D014174:Transketolase
diabetic polyneuropathy; nerve conduction velocity; neuropathic symptoms; single nucleotide polymorphisms; thermal detection thresholds; transketolase