OBJECTIVE To study incident diabetic polyneuropathy (DPN) prospectively during the first 13 years after a screening-based diagnosis of type 2 diabetes and determine the associated risk factors for the development of DPN.

RESEARCH DESIGN AND METHODS We assessed DPN longitudinally in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION) using the Michigan Neuropathy Screening Instrument questionnaire (MNSIQ), defining DPN with scores ≥4. Risk factors present at the diabetes diagnosis associated with the risk of incident DPN were estimated using Cox proportional hazard models adjusted for trial randomization group, sex, and age.

RESULTS Of the total cohort of 1,533 people, 1,445 completed the MNSIQ at baseline and 189 (13.1%) had DPN at baseline. The remaining 1,256 without DPN entered this study (median age 60.8 years [interquartile range 55.6; 65.6], 59% of whom were men). The cumulative incidence of DPN was 10% during 13 years of diabetes. Age (hazard ratio [HR] 1.03 [95% CI 1.00; 1.07]) (unit = 1 year), weight (HR 1.09 [95% CI 1.03; 1.16]) (unit = 5 kg), waist circumference (HR 1.14 [95% CI 1.05; 1.24]) (unit = 5 cm), BMI (HR 1.14 [95% CI 1.06; 1.23]) (unit = 2 kg/m²), log₂ methylglyoxal (HR 1.45 [95% CI 1.12; 1.89]) (unit = doubling), HDL cholesterol (HR 0.82 [95% CI 0.69; 0.99]) (unit = 0.25 mmol/L), and LDL cholesterol (HR 0.92 [95% CI 0.86; 0.98]) (unit = 0.25 mmol/L) at baseline were significantly associated with the risk of incident DPN.

CONCLUSIONS This study provides further epidemiological evidence for obesity as a risk factor for DPN. Moreover, low HDL cholesterol levels and higher levels of methylglyoxal, a marker of dicarbonyl stress, are identified as risk factors for the development of DPN.

目的前瞻性研究基于筛查的2型糖尿病诊断后的13年内的糖尿病多发性神经病（DPN），并确定DPN发生的相关危险因素。

研究设计和方法我们使用密歇根州神经病筛查仪器调查表（MNSIQ）在盎格鲁-丹麦-荷兰人进行的初次医疗强化治疗糖尿病研究（ADDITION）的丹麦分支中纵向评估了DPN，定义了DPN得分≥4。使用针对试验随机分组，性别和年龄调整的Cox比例风险模型，评估糖尿病诊断中与DPN发生风险相关的风险因素。

结果在1,533人的总队列中，有1,445人在基线时完成了MNSIQ，在基线时有189人（占13.1％）完成了DPN。其余1,256个没有DPN的患者进入了这项研究（中位年龄为60.8岁（四分位间距为55.6； 65.6），其中59％是男性）。在糖尿病的13年中，DPN的累积发生率为10％。年龄（危险比[HR] 1.03 [95％CI 1.00; 1.07]）（单位= 1年），体重（HR 1.09 [95％CI 1.03; 1.16]）（单位= 5 kg），腰围（HR 1.14 [ 95％CI 1.05; 1.24]）（单位= 5厘米），BMI（HR 1.14 [95％CI 1.06; 1.23]）（单位= 2 kg / m ²），log ₂ 甲基乙二醛（HR 1.45 [95％CI 1.12; 1.89]）（单位=两倍），HDL胆固醇（HR 0.82 [95％CI 0.69; 0.99]）（单位= 0.25 mmol / L）和LDL胆固醇（HR 0.92 [95] ％CI 0.86; 0.98]）（单位= 0.25 mmol / L）与基线DPN发生风险显着相关。

结论本研究为肥胖作为DPN的危险因素提供了进一步的流行病学证据。此外，低HDL胆固醇水平和高水平的甲基乙二醛（二羰基应激的标志物）被确定为DPN发生的危险因素。