Background: Distal symmetric polyneuropathy (DSPN) is a common microvascular complication of both type 1 and 2 diabetes with substantial morbidity burden and reduced quality of life. Its association with mortality is equivocal.
Purpose: To describe the association between DSPN and all-cause mortality in people with diabetes and further stratify by the type of diabetes based on a meta-analysis of published observational studies.
Data sources: We searched Medline from inception to May 2021.
Study selection: Original data were collected from case-control and cohort studies that reported on diabetes and DSPN status at baseline and all-cause mortality during follow-up.
Data extraction: was completed by diabetes specialists with clinical experience in neuropathy assessment.
Data synthesis: Data was synthesized using random-effects meta-analysis. The difference between type 1 and 2 diabetes was investigated using meta-regression.
Results: A total of 31 cohorts (n=155,934 participants, median 27.4% with DSPN at baseline, all-cause mortality 12.3%) were included. Diabetes patients with DSPN had an almost twofold mortality (HR: 1.96, 95%CI: 1.68-2.27, I2 = 91.7%), I2 = 91.7%) compared to those without DSPN that was partly explained by baseline risk factors (adjusted HR: 1.60, 95%CI: 1.37-1.87, I2 = 78.86%). The association was stronger in type 1 compared to type 2 diabetes (HR: 2.22, 95%CI: 1.43-3.45). Findings were robust in sensitivity analyses without significant publication bias.
Limitations: Not all papers reported multiple adjusted estimates. The definition of DSPN was heterogeneous.
Conclusions: DSPN is associated with an almost twofold risk of death. If this association is causal, targeted therapy for DSPN could improve life expectancy of diabetic patients.
Keywords: all-cause mortality; cohort studies; diabetes mellitus; distal symmetric polyneuropathy; meta-analysis; type 1 diabetes; type 2 diabetes.
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