Nonlinear Relationship Found Between Lipoprotein Cholesterol Ratio, Risk of Diabetic Kidney Disease
Non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol levels could potentially be a valuable biomarker for determining the risk of diabetic kidney disease.
Study results show a non-linear relationship between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) levels and the risk of diabetic kidney disease (DKD) for adults with type 2 diabetes. The investigators suggest that NHHR could be a valuable biomarker for determining who is at risk for DKD, facilitating early interventions.1
Diabetic kidney disease is a kidney disease that is caused by diabetes, which is the leading cause of kidney disease. Image Credit: Phushutter | stock.adobe.com
Diabetic kidney disease is a kidney disease that is caused by diabetes, which is the leading cause of kidney disease, according to the National Institute of Diabetes and Digestive and Kidney Diseases. When the kidneys are damaged, the organ cannot filter blood like usual; therefore, waste builds up in the body. Diabetic kidney disease occurs slowly, with damage occurring over many years.2
Treatment can include novel approaches, such as targeting inflammation and fibrosis with inhibitors of nuclear factor kappa-B, transforming growth factor-beta, and anti-inflammatory cytokines, according to a review published in Medicine. Other possible treatments could include stem cell therapy and gene therapy, and diagnostics could potentially be improved with artificial intelligence-based approaches. Although treatment and prevention have been advancing, many patients still progress to end-stage renal disease, signaling needs in earlier diagnostics.3
In the current study, patients with type 2 diabetes were included between 1999 and 2018, with 3242 being included after excluding patients with missing data and covariates. The average age was 58.8 years, and 48.5% were female. Additionally, the DKD composition ratio was approximately 38.79%. The mean NHHR for patients was 3.19, and the interquartile range from 1 to 4 was 0.31-2.08, 2.08-2.87, 2.87-3.89, and 3.89-26.67.1
When evaluated as a continuous variable, investigators found that NHHR did not have a linear relationship to the risk of DKD in both models 1 and 4. In model 1, investigators did not adjust for covariates, and the investigators found that Q2 was at the lowest risk of DKD when compared to the lowest NHHR quartile. After adjusting for demographics and lifestyle covariates, the risk of DKD in Q2 in both models 2 and 3 was still lower than the lowest NNHR quartile, according to the study investigators.1
In another analysis, the controlled for other covariates, including age, sex, race, smoking, alcohol use, hypertensions, cardiovascular disease, and more, the relationship was stable, indicating a 45% reduction in the risk of DKD for Q2 compared with Q. Investigators stated that the “trend showed a statistically significant interquartile regression trend in model 4 (p < 0.05), suggesting that changes in different NHHR quartiles were strongly associated with the risk of DKD.”1
Furthermore, the data showed that the risk of DKD for patients with diabetes was reduced by 37% for each unit increase of NHHR at 2.82 or less. There were not significant changes when NHHR was greater than 2.82, according to the study authors.1
“Early monitoring of NHHR in patients with T2DM may help assess risk and predict prognosis in this patient population,” the investigators concluded. “Keeping the NHHR in an appropriate range is beneficial in reducing the risk of DKD, and NHHR levels can be controlled in clinical practice by lipid-lowering medications, physical activity, weight management, and smoking cessation.”1
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REFERENCES
1. Cai DX, Huang YH, Lin NN, et al. The nonlinear relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol and the risk of diabetic kidney disease in patients with type 2 diabetes mellitus. Front Med (Lausanne). 2025;12:1492483. Published 2025 Feb 19. doi:10.3389/fmed.2025.1492483
2. National Institute of Diabetes and Digestive and Kidney Diseases. Diabetic Kidney Disease. February 2017. Accessed March 11, 2025. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/diabetic-kidney-disease
3. Elendu C, John Okah M, Fiemotongha KDJ, et al. Comprehensive advancements in the prevention and treatment of diabetic nephropathy: A narrative review. Medicine (Baltimore). 2023;102(40):e35397. doi:10.1097/MD.0000000000035397
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