Increased DNA-glycation in type 2 diabetic patients: the effect of thiamine and pyridoxine therapy

Exp Clin Endocrinol Diabetes. 2012 Jun;120(6):329-34. doi: 10.1055/s-0031-1298016. Epub 2012 Jan 9.

Abstract

Background: It is well known that advanced glycation plays an important role in the progression of diabetic complications. Although several studies have been done on protein glycation, studies related to DNA glycation is limited. The aim of this study is primarily to investigate DNA glycation in diabetes mellitus and secondarily to observe the effects of vitamins B(1) and B(6).

Materials and methods: Patients with diabetes (n=31) were divided into 2 groups as patients with nephropathy (n=17) and without nephro-pathy (n=14). The control group was recruited from age and sex matched healthy individuals (n=30). In the experimental groups, DNA glycation was measured in DNA isolated from leukocytes. HbA(1c), thiamine pyrophosphate (TPP) and pyridoxal 5-phosphate (PLP) levels were determined in whole blood; glucose and insulin levels in plasma. Patients with nephropathy were further divided into 2 groups and were administered either vitamins B(1) + B(6) (n=6) or B(6) (n=11), for 5 months. All the measurements were performed both before and after the vitamin administration period.

Results: AGE-DNA levels were found significantly higher in diabetic patients (p<0.05) than the healthy controls. AGE-DNA and PLP levels were negatively correlated in control patients (r= - 0.361, p<0.05). The combined administration of B(1) and B(6) caused a significant decrease in AGE-DNA values (p<0.05).

Conclusion: This study shows that the combined administration of vitamins B(1) and B(6) to diabetic nephropathy patients causes a decrease in DNA glycation in leukocytes. Importantly the administration of vitamin B(6) alone did not have such an effect. To our knowledge, these are the first reported findings related to glycation of leukocyte nuclear DNA in diabetic nephropathy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • DNA / blood
  • DNA / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / metabolism
  • Female
  • Glycated Hemoglobin A / analysis
  • Glycation End Products, Advanced / blood
  • Glycation End Products, Advanced / metabolism*
  • Glycosylation / drug effects
  • Humans
  • Insulin / blood
  • Male
  • Middle Aged
  • Pyridoxine / pharmacology*
  • Pyridoxine / therapeutic use
  • Thiamine / pharmacology*
  • Thiamine / therapeutic use
  • Up-Regulation / drug effects

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Insulin
  • hemoglobin A1c protein, human
  • DNA
  • Pyridoxine
  • Thiamine