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Role of fructosamine-3-kinase in protecting against the onset of microvascular and macrovascular complications in patients with T2DM
  1. Giovanni Sartore1,
  2. Eugenio Ragazzi2,
  3. Silvia Burlina1,
  4. Renata Paleari3,4,
  5. Nino Cristiano Chilelli1,
  6. Andrea Mosca3,4,
  7. Francesca Avemaria3,
  8. Annunziata Lapolla1
  1. 1Department of Medicine (DIMED), University of Padova School of Medicine and Surgery, Padova, Italy
  2. 2Department of Pharmaceutical and Pharmacological Sciences, University of Padova School of Medicine and Surgery, Padova, Italy
  3. 3Department of Pathophysiology and Transplantation, University of Milan, Milano, Italy
  4. 4Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Ricerche (ITB-CNR), Milan, Italy
  1. Correspondence to Dr Eugenio Ragazzi; eugenio.ragazzi{at}


Introduction Microangiopathic and macroangiopathic complications are the main cause of morbidity and mortality in the diabetic population. Numerous publications have highlighted the role of glycation in the onset of complications of diabetes. In this context, the detection of fructosamine-3-kinase (FN3K)—an enzyme capable of counteracting the effect of hyperglycemia by intervening in protein glycation—has attracted great interest. Several studies have linked FN3K genetic variability to its enzymatic activity and glycated hemoglobin (HbA1c) levels. Here, we investigated the role of FN3K polymorphisms in the development of microvascular and macrovascular complications of diabetes.

Research design and methods The anthropometric and biochemical parameters, and any medical history of microangiopathic and macroangiopathic complications, were documented in a sample of 80 subjects with type 2 diabetes. All subjects were screened for FN3K gene and analyzed for the combination of three polymorphisms known to be associated with its enzymatic activity (rs3859206 and rs2256339 in the promoter region and rs1056534 in exon 6).

Results The combination of allelic variants of FN3K polymorphisms resulted in 13 distinct genotypic variants within the cohort. Comparison between genotypes showed no significant differences in terms of demographic, anthropometric and biochemical parameters, risk markers and long-term complications, except for a higher age and vitamin E levels associated with the genotype presenting GG at position −385, TT at position −232, and CC at c.900 A. Evaluating the microangiopathic and macroangiopathic complications as a whole, we found that they appeared significantly less present in this genotype compared with all other genotypes (p=0.0306).

Conclusions The group of patients carrying the favorable allele for the three polymorphisms of the FN3K gene revealed less severe microangiopathy and macroangiopathy, suggesting a protective role of this genotype against the onset of the complications of diabetes.

  • fructosamine-3-kinase
  • genetic polymorphisms
  • vasculopathy
  • diabetes mellitus, type 2

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  • Contributors GS designed the study, interpreted the data and revised the manuscript. AM, RP and FA carried analyses and contributed to interpretation of data. ER analyzed and interpreted the data, and wrote the manuscript. NCC and SB provided patient samples and contributed to the discussion. AL reviewed and critically edited the manuscript.

  • Funding This work was supported by Department of Medicine, University of Padua, and by Ministero dell’Istruzione, dell’Università e della Ricerca.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The study used information that is available in the database of the Department of Medicine (DIMED), University of Padua. The study was approved by ethical committee for clinical trials in Padua (approval no.149 DCCT/HBA1C) and was conducted in accordance with the Helsinki Declaration. Participants gave informed consent before taking part to the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.