Pain in diabetes-related polyneuropathy associated with adverse events, death

Patients with type 2 diabetes who had no diabetes-related polyneuropathy, diabetes-related polyneuropathy with pain, and diabetes-related polyneuropathy without pain were compared in an industry-funded retrospective study.


There was a significant association between pain in diabetes-related polyneuropathy (DPN) and an increased risk of vascular events and death in patients with type 2 diabetes, a study found.

Researchers performed a retrospective study at a large health system in Ohio to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, those who had DPN with pain (DPN+P), and those who had DPN without pain (DPN-P). Patients were first classified as no DPN, DPN+P, or DPN-P, and the researchers then looked at independent associations with DPN+P using models that accounted for demographics, socioeconomic characteristics, and comorbidities. Five of the authors received funding from Novartis to conduct the study, and two of the authors were Novartis employees and stockholders.

Primary study outcomes were defined as vascular events; a combination of myocardial infarction, ischemic stroke, or amputation; and time to death. Secondary outcomes included ED visits and hospitalizations. Results were published June 23 by the Journal of Clinical Endocrinology & Metabolism.

Of 43,945 patients (mean age, 64.6 years; 52.1% women), 13,910 (31.7%) had DPN. There were 9,104 (65.4%) classified as having DPN+P and 4,806 (34.6%) classified as having DPN-P. Vascular events occurred in 4,538 (15.1%) patients without DPN, 2,401 (26.4%) patients with DPN+P, and 1,006 (20.9%) patients with DPN-P. After adjustment, DPN+P remained a significant predictor of number of vascular events (incidence rate ratio [IRR], 1.55; 95% CI, 1.29 to 1.85) while no DPN was protective (IRR, 0.70; 95% CI, 0.60 to 0.82) when compared to DPN-P. Compared to DPN-P, DPN+P was also a significant predictor of death (hazard ratio [HR], 1.42; 95% CI, 1.25 to 1.61) and no association was seen between no DPN and mortality (HR, 1.12, 95% CI, 0.99 to 1.26).

The results of the study results warrant longitudinal study of the risk factors and natural history of pain in DPN, according to the authors. “Current options for neuropathic pain treatment are only modestly effective, have significant adverse effects, and may not sufficiently improve health-related quality of life,” they wrote. “It is reasonable to assume that effective treatment of pain, if available, may improve functional outcomes and health-related quality of life in DPN. If pain is truly a mediator of poorer medical outcomes in DPN, an even stronger case may be made for aggressively treating pain in DPN.”