Abstract
Aim DNA methylation is thought to be involved in regulating the expression of key genes and inducing diabetic peripheral neuropathy (DPN). However, clinically, the level of whole-genome DNA methylation and its relationship with DPN remains unclear. Methods 186 patients with type 2 diabetes mellitus (T2DM) admitted to the Second Affiliated Hospital of Soochow University since Jul. 2016 to Oct. 2017 were enrolled in the study, including 100 patients in the DPN group and 86 patients in the non-DPN group, diagnosed with Toronto Clinical Scoring System (TCSS). Clinical and biochemical characteristics between the two groups were compared, and the correlations with TCSS scores were analyzed. Furthermore, the levels of genomic DNA methylation of leukocytes, measured with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), were also analyzed between the two groups. Results Age, duration, triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), creatinine, uric acid (UA), blood urea nitrogen (BUN), and C-reactive protein (CRP) were significantly higher in the DPN group. Estimated glomerular filtration rate (eGFR) and the level of genomic DNA methylation were much lower in the DPN group. Spearman correlation analysis showed that TCSS was positively correlated with age, duration, UA, and CRP and was negatively correlated with body mass index (BMI), eGFR, and the level of genomic DNA methylation. Interestingly, multiple stepwise regression analysis showed that only duration, genomic DNA methylation, and eGFR had impacts on TCSS. The results also showed that the levels of genomic DNA methylation did not change significantly whether or not there was renal injury. Another multiple stepwise regression analysis showed that TCSS and BMI were the influencing factors of genomic DNA methylation. Finally, we found that genomic DNA methylation levels were decreased significantly in the DPN group compared with the non-DPN group when the duration is ≥5 years or BMI ≥ 25 kg/m2. Conclusion Low level of genomic DNA methylation is a relative specific risk factor of diabetic peripheral neuropathy in patients with type 2 diabetes.
Highlights
IntroductionAccording to the report of the World Health Organization (WHO), there are about 422 million people with diabetes in the world (https://www.who.int/news-room/fact-sheets/ detail/diabetes), and the prevalence in adult is about 9.5% [1]
According to the report of the World Health Organization (WHO), there are about 422 million people with diabetes in the world, and the prevalence in adult is about 9.5% [1]
A total of 186 patients with type 2 diabetes mellitus were enrolled in the study, including 100 (53.8%) patients in the Diabetic peripheral neuropathy (DPN) group and 86 (46.2%) patients in the non-DPN group, divided by the Toronto Clinical Scoring System (TCSS) scores
Summary
According to the report of the World Health Organization (WHO), there are about 422 million people with diabetes in the world (https://www.who.int/news-room/fact-sheets/ detail/diabetes), and the prevalence in adult is about 9.5% [1]. In China, the latest prevalence of diabetes in adult is about 10.4% [2]. The complications of diabetes are the main cause of death and disabilities, which bring people huge spiritual and economic burden. Diabetic peripheral neuropathy (DPN) is one of the most common complications. The clinical manifestations of DPN are mainly distal limb paresthesia and movement disorders. Paresthesia is usually characterized by peripheral limbs’ numbness, burning and tingling pain, cold sensation, and formication, while movement disorders are characterized by moving weakly, inflexibly, and unsteadily. Severe DPN causes foot ulcer and amputation, seriously affecting life quality of the patients. It is important to study the risk factors of DPN and to find out the potential therapeutic targets
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