American Diabetes Association
supplementary_material_MNSI_rev.pdf (297.58 kB)

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

Download (297.58 kB)
posted on 2021-05-27, 07:08 authored by Lasse Bjerg, Sia K Nicolaisen, Diana H Christensen, Jens S Nielsen, Signe T Andersen, Marit E Jørgensen, Troels S Jensen, Annelli Sandbæk, Henning Andersen, Henning Beck-Nielsen, Henrik T Sørensen, Daniel R Witte, Reimar W Thomsen, Morten Charles
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.
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).
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.


Research reported in this paper is part of the International Diabetic Neuropathy Consortium research program, which is supported by a Novo Nordisk Foundation Challenge Programme (Grant number NNF14OC0011633). ADDITION-Denmark is funded by the National Health Services in Denmark, the Danish Council for Strategic Research, the Danish Research Foundation for General Practice, the Novo Nordisk Foundation, the Danish Center for Evaluation and Health Technology Assessment, the Danish National Board of Health, the Danish Medical Research Council, the Aarhus University Research Foundation, Novo Nordisk Scandinavia AB, Novo Nordisk UK, ASTRA Denmark, Pfizer Denmark, GlaxoSmithKline Pharma Denmark, Servier Denmark A/S, and HemoCue Denmark A/S. DD2 is funded by the Novo Nordisk Foundation (NNF17SA0030364), the Danish Agency for Science [grant number 09-067009, 09-075724], the Danish Health and Medicines Authority, and the Danish Diabetes Association. All project partners and fundings are listed on the website The funders of the current study had no role in the collection, analysis, or interpretation of the data. They had no role in study design or writing of the manuscript. The Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to and administered by Aarhus University. None of these studies are related to the current study.