Publication News 146 - 28 October 2024
Is triglyceride reduction more crucial for DPN prevention than reduction of other blood lipids?
Aims: To investigate the association between blood lipid components, including triglycerides, and the risk of diabetic polyneuropathy (DPN) in individuals with type 2 diabetes (T2D).
Methods: The study included 1) a longitudinal population-based cohort of individuals newly diagnosed with T2D, and 2) a cross-sectional study of clinically recruited T2D patients, incorporating assessments of potential confounders. Blood lipids (triglycerides, HDL, LDL, and non-HDL cholesterol) were measured as part of routine diabetes care, with lipid concentrations categorized according to clinical guidelines (e.g., triglycerides <150 mg/dL (1.7 mmol/L), 150–204 mg/dL (1.7–2.3 mmol/L), and >204 mg/dL (2.3 mmol/L)). DPN was identified based on validated hospital diagnosis codes in the population-based cohort and the Michigan Neuropathy Screening Instrument questionnaire in the clinical cohort. Associations between lipid levels and DPN were evaluated using hazard ratios (HRs) and prevalence ratios (PRs) from Cox and Poisson regression, adjusted for age, sex, HbA1c, metabolic syndrome components, and lifestyle behaviors.
Results: 61,853 individuals were included in the population-based cohort and 4,823 in the clinical cohort, with a median age of 63 (quartiles 54–72) and 65 (quartiles 57–72) years, respectively. In the population-based cohort, the incidence rate of DPN was 3.6 per 1,000 person-years, with a median follow-up of 7.3 years, and DPN risk was most strongly associated with elevated triglycerides (HR 1.28, CI 1.13–1.45 for >204 mg/dL). In the clinical cohort, the prevalence of DPN was 18%. Elevated triglycerides were similarly linked to an increased prevalence of DPN, with adjusted PRs of 1.28 (CI 1.09–1.50) for 150–204 mg/dL and 1.40 (CI 1.21–1.62) for >204 mg/dL. HDL demonstrated weaker associations, while LDL/non-HDL cholesterol had minimal correlation with DPN risk. Achieving target levels of HDL, LDL, and cholesterol did not significantly reduce DPN risk, and no substantial difference in DPN risk was observed among statin users.
Conclusions: Elevated triglyceride levels, rather than LDL and non-HDL cholesterol, are linked to increased DPN risk, independent of lifestyle, HbA1c, and metabolic syndrome components.
Comments. Metabolic syndrome is a major risk factor of DPN in T2D. Clinical guidelines recommend treating dyslipidemia, a metabolic syndrome component, as it may offer a protective effect against DPN. However, the literature presents conflicting data on whether statin use effectively reduces DPN risk, and the evidence connecting specific lipid parameters to DPN risk remains uncertain. While preclinical studies report a direct nerve-damaging effect of triglycerides, the association between elevated triglycerides and DPN is less evident in clinical studies. Notably, the present study demonstrates that triglycerides exert a stronger effect on DPN risk than other lipid parameters. The current study is robust, combining a longitudinal population-based cohort and a cross-sectional clinical study, each complementing the other, providing a large dataset and substantial statistical power to adjust for important confounders. A few larger studies, such as FIELD and FENO-PREVENT, indicate that long-term use of triglyceride-lowering drugs (e.g., fenofibrate) may reduce DPN progression and amputation risk in individuals with T2D. Nonetheless, clinical studies evaluating the effect of triglyceride-lowering therapy on DPN are limited, with none including DPN prevention as a primary outcome. Based on the evidence from the present study, future intervention studies should investigate whether triglyceride reduction plays a more crucial role in DPN prevention than reduction of other blood lipids.
Anders Stouge
Reference. Kristensen FPB, Christensen DH, Callaghan BC, Nielsen JS, Højlund K, Andersen H, Dekkers OM, Groenwold RHH, Sørensen HT, Thomsen RW. Lipid Levels and Risk of Diabetic Polyneuropathy in 2 Danish Type 2 Diabetes Cohorts. Neurology. 2024 Jul 9;103(1):e209538. doi: 10.1212/WNL.0000000000209538. Epub 2024 Jun 4. PMID: 38833657.