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Ziegler, D.* ; Schleicher, E. ; Strom, A.* ; Knebel, B.* ; Fleming, T.* ; Nawroth, P.P.* ; Häring, H.-U. ; Papanas, N.* ; Szendrödi, J.* ; Müssig, K.* ; Al-Hasani, H.* ; Roden, M.*

Association of transketolase polymorphisms with measures of polyneuropathy in patients with recently diagnosed diabetes.

Diabetes Metab. Res. Rev. 33:e2811 (2017)

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BACKGROUND: Shunting of glycolytic intermediates into the pentose phosphate pathway (PPP) has been suggested to protect from hyperglycaemia-induced microvascular damage. We hypothesised that genetic variability in the gene encoding transketolase, a key PPP enzyme, contributes to early nerve dysfunction in recent-onset diabetes. METHODS: 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. RESULTS: The Total Symptom Score (TSS) 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 TSS 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. CONCLUSIONS: 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.

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