Utility of Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratio in Evaluating Incident Diabetes Risk

Abstract

Purpose

Diabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters.

Patients and Methods

This observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose–response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes.

Results

Of the 15,464 people aged 18–79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk.

Conclusion

In the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.

Keywords:

• non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol
• diabetes
• longitudinal cohort
• operator characteristic curve

Abbreviations

non-HDL-C/HDL-C, Non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio; RCS, restricted cubic spline; ROC, receiver operating characteristic curve; IDF, International Diabetes Federation; HDL-C, high-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol; TG, triglycerides; NAFLD, nonalcoholic fatty liver disease; WC, waist circumference; BMI, body mass index; AST, aspartate aminotransferase; FPG, fasting plasma glucose; TC, total cholesterol; GGT, gamma-glutamyl transferase; HbA1c, hemoglobin A1c; ALT, alanine aminotransferase; LDL-C, low-density lipid cholesterol; HR, hazard ratio; CI, confidence interval.

Data Sharing Statement

The datasets that support the conclusions of this article can be found in the Dryad repository (https://doi.org/10.5061/dryad.1n6c4).

Ethics Approval and Informed Consent

Informed consent for the use of study data has been authorized by the participants in previous studies, and the initial study protocol was approved by the Ethics Committee of Murakami Memorial Hospital.¹⁹ As a post-hoc analysis of the NAGALA cohort study, the institutional Ethics Committee of Jiangxi Provincial People’s Hospital reviewed the current research scheme and exempted the need for repeated ethical approval and informed consent (review No: 2021-066).

Ethics Statement

We confirm that the data accessed in this study complies with relevant data protection and privacy legislation.

Acknowledgments

We sincerely thank the teachers of the Jiangxi Cardiovascular Research Institute for their help with the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was funded by the Natural Science Foundation of Jiangxi Province [No. 20192BAB205007].