Unraveling Epigenetic Signatures for Early Detection of Diabetes Nephropathy in Type 2 Diabetes: A Case–Control Investigation

Abstract

Background: Type 2 diabetes mellitus (T2DM) leads to a substantial elevation in the occurrence of various micro- and macrovascular complications. Approximately one-third of patients of both type 1 diabetes and T2DM develop diabetes nephropathy (DN). Emerging findings in epigenetic modifications indicate that differences in DNA methylation patterns could have a more substantial impact when assessing the susceptibility to type 2 diabetes mellitus (T2DM) in contrast to genetic variations. Methods: The study involved 298 participants, encompassing 75 individuals with type 2 diabetes mellitus (T2DM), 74 individuals with diabetes nephropathy (DN), and 149 healthy control subjects aged between 20 and 70 years. The concentrations of circulating adiponectin, insulin-like growth factor (IGF) 1, and IGF2 were quantified using enzyme-linked immunoassay. The amount of RNA in each sample (control, T2DM, and DN) was quantified, and its purity was checked using nanodrop. Real-time analysis of Adiponectin, IGF1, IGF2, and GAPDH genes was conducted using the SYBR Green polymerase chain reaction Master Mix assay. Results: Circulating levels of IGF1 level were significantly lower in both T2DM and DN, whereas it was slightly higher in T2DM than the DN. IGF2 circulating level was higher in both T2DM and DN as compared to control, whereas it was lower in T2DM when compared to DN. The gene expression level of adiponectin was reduced in both T2DM and DN when compared to the control group; however, it was higher in T2DM than in DN. The gene expression level of IGF1 was decreased in both T2DM and DN compared to the control group, with a more significant decrease in DN compared to T2DM. Conclusion: The measurement of circulatory levels of adiponectin, IGF1, and IGF2 in serum, along with gene expression analysis, provides valuable insights for predicting the progression from T2DM to DN. Consequently, these markers hold the potential to enhance early diagnosis, guide treatment strategies, and serve as innovative prognostic indicators for DN diagnosis.