Despite the high prevalence and impact on quality of life, costs and survival, there are still unresolved issues regarding diabetic polyneuropathy (DPN): the lack of definite knowledge of its pathogenesis; the limited preventive action of glycaemic control in type 2 diabetes; and the unavailability of effective evidence-based disease-modifying treatment. How can genetics provide the tools to address these gaps? Ziegler et al for the GDS Group explore the novel hypothesis that genetic variability in transketolase (TKT) might contribute to susceptibility to DPN in patients with newly diagnosed type 1 and type 2 diabetes (well characterised for DPN). TKT diverges excess glycolytic metabolites from the hexosamine, PKC, and AGE pathways to the pentose phosphate pathway, with a protective effect against hyperglycaemia-induced damage. Moreover, thiamine and its derivative benfotiamine are among the few disease-modifying agents still under consideration as DPN treatment. The Authors find significant associations of single-nucleotide polymorphisms (SNPs) of the TKT gene with the Total Symptom Score and thermal thresholds, in particular in male subjects with type 2 diabetes. Moreover, they measure plasma methylglyoxal (a glycating agent, whose availability is hindered by TKT) without however finding a relation with TKT SNPs. The link found between TKT genetic variability and nerve function measures is considered here in the context of DPN genetic studies and of experimental and clinical findings regarding thiamine and benfotiamine. The conclusion is that available data legitimates the decision to maintain focus on both the search for DPN genetic biomarkers and the therapeutic attempt to target thiamine, TKT and methylglyoxal.

Spallone, V. (2017). Might genetics play a role in understanding and treating diabetic polyneuropathy?. DIABETES/METABOLISM RESEARCH AND REVIEWS, 33(4), 2882-2886 [10.1002/dmrr.2882].

Might genetics play a role in understanding and treating diabetic polyneuropathy?

SPALLONE, VINCENZA
2017

Abstract

Despite the high prevalence and impact on quality of life, costs and survival, there are still unresolved issues regarding diabetic polyneuropathy (DPN): the lack of definite knowledge of its pathogenesis; the limited preventive action of glycaemic control in type 2 diabetes; and the unavailability of effective evidence-based disease-modifying treatment. How can genetics provide the tools to address these gaps? Ziegler et al for the GDS Group explore the novel hypothesis that genetic variability in transketolase (TKT) might contribute to susceptibility to DPN in patients with newly diagnosed type 1 and type 2 diabetes (well characterised for DPN). TKT diverges excess glycolytic metabolites from the hexosamine, PKC, and AGE pathways to the pentose phosphate pathway, with a protective effect against hyperglycaemia-induced damage. Moreover, thiamine and its derivative benfotiamine are among the few disease-modifying agents still under consideration as DPN treatment. The Authors find significant associations of single-nucleotide polymorphisms (SNPs) of the TKT gene with the Total Symptom Score and thermal thresholds, in particular in male subjects with type 2 diabetes. Moreover, they measure plasma methylglyoxal (a glycating agent, whose availability is hindered by TKT) without however finding a relation with TKT SNPs. The link found between TKT genetic variability and nerve function measures is considered here in the context of DPN genetic studies and of experimental and clinical findings regarding thiamine and benfotiamine. The conclusion is that available data legitimates the decision to maintain focus on both the search for DPN genetic biomarkers and the therapeutic attempt to target thiamine, TKT and methylglyoxal.
Pubblicato
Rilevanza internazionale
Commento
Esperti anonimi
Settore MED/13 - Endocrinologia
Settore MED/03 - Genetica Medica
eng
Con Impact Factor ISI
benfotiamine, diabetic neuropathy, genetic susceptibility, SNP, thiamine, transketolase
Spallone, V. (2017). Might genetics play a role in understanding and treating diabetic polyneuropathy?. DIABETES/METABOLISM RESEARCH AND REVIEWS, 33(4), 2882-2886 [10.1002/dmrr.2882].
Spallone, V
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/170651
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