Diabetic Polyneuropathy Early in Type 2 Diabetes Is Associated With Higher Incidence Rate of Cardiovascular Disease: Results From Two Danish Cohort Studies

Objective Symptoms indicative of diabetic polyneuropathy (DPN) early in type 2 diabetes may act as a marker for cardiovascular disease (CVD) and death. Research Design and Methods We linked data from two Danish type 2 diabetes cohorts, ADDITION-Denmark and DD2, to national healthcare registers. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was completed at diabetes diagnosis in ADDITION-Denmark and at a median of 4.6 years after diagnosis of diabetes in DD2. An MNSIq score ≥ 4 was considered as indicative of DPN. Using Poisson regressions, we computed incidence rate ratios of CVD and all-cause mortality comparing MNSIq scores ≥ 4 with scores < 4. Analyses were adjusted for a range of established CVD risk factors. Results In total, 1,445 (ADDITION-Denmark) and 5,028 (DD2) individuals were included in the study. Compared with MNSIq scores < 4, MNSIq scores ≥ 4 were associated with higher incidence rate of CVD, with incidence rate ratios (IRRs) of 1.79 [95% confidence interval (CI) 1.38-2.31] in ADDITION-Denmark, 1.57 (CI: 1.27-1.94) in the DD2, and a combined IRR of 1.65 (CI: 1.41-1.95) in a fixed-effect meta-analysis. MNSIq scores ≥ 4 did not associate with mortality; combined mortality rate ratio 1.11 (CI: 0.83-1.48). Conclusions The MNSIq may be a tool to identify a subgroup within individuals with newly diagnosed type 2 diabetes who has a high incidence rate of subsequent CVD. MNSIq scores ≥ 4, indicating DPN, were associated with a markedly higher incidence rate of CVD, beyond that conferred by established CVD risk factors.