Inflammation: A Key Factor in Diabetes Management Concealed by Lipids—Validation Across Multiple Populations

Abstract

Objectives: Diabetes diet management usually starts from blood lipids and blood sugar, whether inflammation is a new breakthrough in nutrient regulation. Lipid management such as low-density lipoproteincholesterol does not explain the high incidence of cardiovascular events in individuals with diabetes, and more comprehensive indicators for early risk stratification is needed.

Methods: 3241 patients with diabetes from Nanfang Hospital were included for cross-sectional analysis. 17144 participants with diabetes from UK Biobank were included for further prospective cohort study. Multivariable regression model, restricted cubic splines analysis, interaction test, Kaplan-Meier analysis, and mediation test were adopted. The ratio of high-sensitivity C-reactive protein (hs-CRP) and high-density lipoproteincholesterol (HDL-C) was our study variable.

Results: The cross-sectional analysis showed people with higher level of hs-CRP/HDL-C tended to develop dyslipidemia . In the prospective cohort, 1673 participants experienced cardiovascular events during 12.6 years of follow-up. Compared to the lowest quartile (Q1), hazard ratios and 95% confidence intervals of new-onset cardiovascular events in Q2-4 were 1.45(1.25-1.69), 1.72(1.48-2.00), and 2.02(1.75-2.34). A nonlinear positive correlation between hs-CRP/HDL-C and outcomes was observed and Kaplan-Meier analysis confirmed participants with higher hs-CRP/HDL-C levels were less likely to have disease-free survival in the next decade. Mediation test suggested lipid metabolism played a mediating role in outcomes. Similar results were observed in dyslipidemia and all-cause mortality.

Conclusions: These findings have implications for the choice of adjunctive treatments beyond statin and imply that aggressive inflammation-inhibiting therapies and dietary adjustment might be needed to further reduce cardiovascular risk.

ClinicalTrials: NCT06651983.