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Randomized Controlled Trial
. 2025 Oct 1;48(10):1676-1684.
doi: 10.2337/dc25-0596.

Nonglycemic and Glycemic Risk Factors for Painful Neuropathic Symptoms and for Distal Symmetrical Polyneuropathy (DSPN) in the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study

William H Herman  1 , Adam Ciarleglio  2 , Brian C Callaghan  1 , Sharon L Edelstein  2 , Ronald Goldberg  3 , Neil H White  4 , James W Albers  1 ; Diabetes Prevention Program Research Group
Collaborators, Affiliations
Randomized Controlled Trial

Nonglycemic and Glycemic Risk Factors for Painful Neuropathic Symptoms and for Distal Symmetrical Polyneuropathy (DSPN) in the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study

William H Herman et al. Diabetes Care. .

Abstract

Objective: The clinical presentation, symptoms, and signs of neuropathy vary substantially. We determined whether painful neuropathic symptoms and distal symmetrical polyneuropathy (DSPN) were associated with different risk factors in a longitudinal study of Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPP/DPPOS) participants.

Research design and methods: We assessed neuropathy in 1,779 DPP/DPPOS participants ∼21 years after DPP randomization. Symptoms were assessed using the Michigan Neuropathy Screening Instrument (MNSI) questionnaire and signs using pinprick, vibration, and monofilament testing. We defined four mutually exclusive neuropathy phenotypes: 1) no symptoms or signs of DSPN, 2) neuropathic pain without signs, 3) other neurologic symptoms without pain or signs, and 4) DSPN (MNSI questionnaire score ≥4 or any signs). We used multinomial logistic regression models to compare nonglycemic and glycemic risk factors among participants to better understand risk factors associated with painful neuropathic symptoms and DSPN.

Results: Among the participants, 501 (28%) had no symptoms or signs, 144 (8%) had painful neuropathic symptoms without signs, and 473 (27%) had DSPN. Compared with participants with neither symptoms nor signs, those with painful neuropathic symptoms were more likely to be women, to have greater weight, and lower estimated glomerular filtration rate. Painful symptoms were not associated with glycemia. In contrast, DSPN, when compared with painful symptoms, was associated with older age, White race, and glycemic exposure.

Conclusions: In this cohort, risk factors for painful neuropathic symptoms and DSPN differed. Improved recognition of painful neuropathic symptoms and better consensus on diagnostic criteria may facilitate research into their causes, prevention, and treatment.

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Conflict of interest statement

Duality of Interest. B.C.C. receives research contracts from the American Academy of Neurology, is an associate editor of Neurology, consults for DynaMed, and performs medical legal consultations, including for the Vaccine Injury Compensation Program. No other potential conflicts of interest relevant to this article were reported.

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