From the Department of Clinical Epidemiology (F.P.B.K., D.H.C., H.T.S., R.W.T.), Aarhus University Hospital and Aarhus University; Department of Endocrinology and Internal Medicine (D.H.C.), Aarhus University Hospital, Denmark; Department of Neurology (B.C.C.), University of Michigan, Ann Arbor; Steno Diabetes Center Odense (J.S.N., K.H.), Odense University Hospital; Department of Clinical Research (J.S.N., K.H.), University of Southern Denmark, Odense; Department of Neurology (H.A.), Aarhus University Hospital, Denmark; Department of Clinical Epidemiology (O.M.D., R.H.H.G.), Department of Endocrinology (O.M.D.), and Department of Biomedical Data Sciences (R.H.H.G.), Leiden University Medical Center, the Netherlands.
Neurology. 2024 Jul 9;103(1):e209538. doi: 10.1212/WNL.0000000000209538. Epub 2024 Jun 4.
Reduction of blood lipids may aid in preventing diabetic polyneuropathy (DPN), but evidence remains conflicting. We investigated the association between lipid parameters and DPN risk in individuals with type 2 diabetes mellitus (T2DM).
We conducted a population-based cohort study of individuals with newly diagnosed T2DM and a cross-sectional study using a clinically recruited T2DM cohort. Triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and non-HDL cholesterol were measured in routine diabetes care. Each lipid parameter was categorized according to the latest cutoffs in clinical guidelines on dyslipidemia. DPN was assessed with validated hospital diagnosis codes in the population-based cohort and with the Michigan Neuropathy Screening Instrument questionnaire in the clinical cohort. We calculated hazard ratios (HRs) using Cox regression and prevalence ratios (PRs) using Poisson regression.
We included 61,853 individuals in the population-based cohort (median age 63 [quartiles 54-72] years) and 4,823 in the clinical cohort (median age 65 [quartiles 57-72] years). The incidence rate of hospital-diagnosed DPN in the population-based cohort was 3.6 per 1000 person-years during a median follow-up of 7.3 years. Achieving guideline targets for HDL, LDL, and non-HDL cholesterol showed no association with DPN risk. By contrast, adjusted HRs (95% CI) for DPN were 1.02 (0.89-1.18) for triglyceride levels between 150 and 204 mg/dL (1.7-2.3 mmol/L) and 1.28 (1.13-1.45) for levels >204 mg/dL (2.3 mmol/L). In the clinical cohort with a DPN prevalence of 18%, DPN associated strongly with triglycerides >204 mg/dL (2.3 mmol/L) with an adjusted PR (95% CI) of 1.40 (1.21-1.62). The prevalence of DPN was modestly elevated for individuals with HDL cholesterol <39 mg/dL (1.0/1.3 mmol/L) in men and <50 mg/dL (1.3 mmol/L) in women (PR 1.13 [0.99-1.28]) and for individuals with non-HDL cholesterol >131 mg/dL (3.4 mmol/L) (PR 1.27 [1.05-1.52]). In both cohorts, spline models showed an increasing risk of DPN starting from triglyceride levels >124 mg/dL (1.4 mmol/L). All results were similar among statin users.
High triglyceride levels are a strong DPN risk factor. Future intervention studies shall determine whether triglyceride reduction is more important for DPN prevention than reduction of other lipids.
降低血脂可能有助于预防糖尿病性多发性神经病（DPN），但证据仍存在争议。我们研究了血脂参数与 2 型糖尿病（T2DM）患者 DPN 风险之间的关联。
我们进行了一项基于人群的新诊断为 T2DM 患者的队列研究和一项使用临床招募的 T2DM 队列的横断面研究。在常规糖尿病护理中测量甘油三酯、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和非 HDL 胆固醇。根据血脂异常临床指南的最新截止值对每个血脂参数进行分类。在基于人群的队列中使用经过验证的医院诊断代码评估 DPN，在临床队列中使用密歇根神经病筛查仪器问卷评估 DPN。我们使用 Cox 回归计算风险比（HR），使用泊松回归计算患病率比（PR）。
我们纳入了 61853 名基于人群的队列患者（中位年龄 63 [四分位数 54-72]岁）和 4823 名临床队列患者（中位年龄 65 [四分位数 57-72]岁）。在中位随访 7.3 年期间，基于人群的队列中医院诊断 DPN 的发病率为每 1000 人年 3.6 例。达到 HDL、LDL 和非 HDL 胆固醇的指南目标与 DPN 风险无关。相比之下，DPN 的调整后 HR（95%CI）在甘油三酯水平为 150-204mg/dL（1.7-2.3mmol/L）时为 1.02（0.89-1.18），在水平 >204mg/dL（2.3mmol/L）时为 1.28（1.13-1.45）。在 DPN 患病率为 18%的临床队列中，DPN 与甘油三酯 >204mg/dL（2.3mmol/L）强烈相关，调整后的 PR（95%CI）为 1.40（1.21-1.62）。男性 HDL 胆固醇 <39mg/dL（1.0/1.3mmol/L）和女性 <50mg/dL（1.3mmol/L）的个体 DPN 患病率适度升高（PR 1.13 [0.99-1.28]），非 HDL 胆固醇 >131mg/dL（3.4mmol/L）的个体（PR 1.27 [1.05-1.52]）。在两个队列中，样条模型显示 DPN 风险从甘油三酯水平 >124mg/dL（1.4mmol/L）开始呈上升趋势。所有结果在他汀类药物使用者中均相似。
高甘油三酯水平是 DPN 的一个强危险因素。未来的干预研究应确定降低甘油三酯是否比降低其他脂质对 DPN 预防更重要。
