Inverse Correlation Between α-Klotho and Diabetic Biomarkers in Type 2 Diabetes: A Cross-Sectional Study

Abstract

Evidence suggests a link between diabetes and Klotho protein, demonstrated by reduced Klotho gene expression in individuals with diabetes, α- klotho the potential modulator of kidney health in DM. Klotho is primarily expressed in the kidneys and has an anti-inflammatory and antioxidant role, which may protect against the pathological processes that damage renal function in diabetes. Research conducted in Japan on postmenopausal women revealed a strong inverse relationship between Klotho levels and the insulin resistance marker HOMA-IR. Nevertheless, there have been no studies examining the connection between Klotho and diabetes related biochemical factors like uric acid, urea, and creatinine. This study aims to investigate the correlation between α-Klotho and biochemical markers in patients with diabetes mellitus. Analysis of biochemical parameters showed a significant increase in insulin, HbA1c, FBG, VLDL, cholesterol, and triglyceride levels in patients (both male and female) compared to the control group. Conversely, HDL levels decreased significantly, while LDL remained unchanged. Gene expression analysis indicated an increase in klotho protein expression in patient groups compared to the controls. Fold change analysis further confirmed significantly higher klotho expression in patients. The analysis of the fold change test showed a substantial increase in fold change level for both male and female patients compared to the control group, with a significant level. The statistical evaluation indicated a highly negative correlation between α-klotho expression and blood urea, as well as α-klotho expression and creatinine, at a significance level of P≤ 0.01. Nevertheless, there was a significant inverse relationship between α-klotho expression and HbA1c, as well as α-klotho expression and FBS at P≤ 0.05, while there was a significant positive relationship with LDL but no noticeable correlation between α-klotho expression and the other parameters studied. This study demonstrated an inverse correlation between α-klotho and diabetes- related biochemical markers. High HbA1c is associated with decreased klotho expression, suggesting glucose levels may suppress α-klotho gene transcription. Klotho levels were negatively correlated with urea and creatinine.