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Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study

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Abstract

The role of hyperhomocysteinemia as a risk factor for diabetic long-term complications has not been sufficiently evaluated in prospective studies, considering specific correlates of homocysteine (tHcy) concentration and traditional cardiovascular disease (CVD) risk factors. Fasting tHcy, vitamin B12 and folate plasma levels, the common methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, as well as clinical and lifestyle information were assessed in 216 type 2 diabetic patients attending two outpatient clinics, who had a follow-up evaluation at 65 ± 9 months for the incidence of macroangiopathy. At basal evaluation, mild hyperhomocysteinemia (tHcy ≥ 15 μmol/l) was diagnosed in 21.3% of participants. At follow-up, hyperhomocysteinemia and the distribution of MTHFR C677T genotype did not significantly differ according to the incidence of macroangiopathy. Multiple variables adjusted ORs (95% CI) for CVD associated with mild hyperhomocysteinemia were 1.01 (0.37–2.82); P > 0.05; those associated with MTHFR TT genotype were 0.46 (0.15–1.38); P > 0.05. Although the prevalence of hyperhomocysteinemia was higher in diabetic men (26.9%) than in women (16.1%; P > 0.05), similar results were also observed in a separate sex-analysis. At the multivariate analysis, including in the model other potential CVD risk factors, only creatinine clearance was a significant risk factor for the development of macroangiopathy. In this cohort of diabetic subjects, mild hyperhomocysteinemia and the MTHFR TT genotype are not significant risk factors for the development of macroangiopathy; impaired renal function was confirmed as a significant predictor of this complication.

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Conflict of interest statement

The authors state that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Policlinico Universitario “G. Martino” Via C. Valeria, University of Messina, 98124, Messina, Italy

    Giuseppina Tiziana Russo, Antonino Di Benedetto, Annalisa Giandalia, Marcello Previti, Enrico Di Cesare & Domenico Cucinotta

  2. Department of Health Sciences, Unit of Medical Statistics and Epidemiology, University of Pavia, Pavia, Italy

    Domenico Magazzù

  3. Metabolism and Diabetes Unit, ASL Turin 5, Chieri, Italy

    Carlo Bruno Giorda

  4. Department of Biochemical Sciences, University of Messina, Messina, Italy

    Riccardo Ientile

Authors
  1. Giuseppina Tiziana Russo
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  2. Antonino Di Benedetto
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  3. Domenico Magazzù
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  4. Annalisa Giandalia
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  5. Carlo Bruno Giorda
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  7. Marcello Previti
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  8. Enrico Di Cesare
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  9. Domenico Cucinotta
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Correspondence to Giuseppina Tiziana Russo.

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Russo, G.T., Di Benedetto, A., Magazzù, D. et al. Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study. Acta Diabetol 48, 95–101 (2011). https://doi.org/10.1007/s00592-009-0169-5

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  • DOI: https://doi.org/10.1007/s00592-009-0169-5

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