Metabolic syndrome burden is associated with pain in people with peripheral neuropathy

Aims: To determine the association between the number of prevalent metabolic syndrome components and diabetes with measures of peripheral neuropathy in people with polyneuropathy with and without diabetes.

Methods: Data from 1,112 individuals with polyneuropathy were analyzed for glycemic status, the number of metabolic syndrome components (hyperglycemia, hypertension, overweight, hypertriglyceridemia, low HDL cholesterol), neuropathy severity (Total Neuropathy Score-reduced), small and large fiber impairment (pinprick, vibration, proprioception examination), and pain.

Results: 265 individuals were labeled with diabetic peripheral neuropathy and 847 with non-diabetic peripheral neuropathy. Diabetes was associated with pain, a higher neuropathy severity, and a higher proportion of mixed fiber involvement. In unadjusted models, a higher number of prevalent metabolic syndrome components was associated with neuropathy severity and pain in the overall cohort and in the subgroup with normal glucose tolerance, but not in those subgroups with prediabetes or diabetes. Adjusted for age, sex, and height, the association between metabolic syndrome components and pain, but not neuropathy severity remained significant, whereas higher BMI was associated with more severe neuropathy.

Conclusions: An increasing metabolic syndrome burden may lead to a higher proportion of pain in people with peripheral neuropathy. Peripheral neuropathy of diabetic etiology may be characterized by a higher severity, a higher likelihood of pain, and a higher proportion of mixed fiber involvement compared to other etiologies.

Comments: This cross-sectional study contributes to the appreciation of overweight and metabolic syndrome as contributors to the development of peripheral neuropathy and pain in people with and without diabetes. However, several aspects need to be considered when interpreting the reported findings. Firstly, neuropathy severity was assessed using a composite score including both symptoms and signs, which can result in painless neuropathies being labeled as less severe despite significant nerve fiber loss and dysfunction. Secondly, the definition of pain used in the study does not appear to be limited to neuropathic pain; pain in general may be influenced by factors, primarily musculoskeletal conditions. Thirdly, the study did not examine whether metabolic syndrome itself may be associated with peripheral neuropathy, as only diabetes and higher BMI, but not abnormalities in HDL cholesterol, triglycerides, or blood pressure were associated with lower peripheral nerve function. Therefore, the question of whether a pure metabolic syndrome associated neuropathy exists remains elusive.

Gidon J Bönhof

Reference: Davalos L, Callaghan BC, Muthukumar L, Thomas S, Reynolds EL, Smith AG, Singleton JR, Höke A, Ajroud-Driss S, Dimachkie MM, Geisler S, Simpson DM; PNRR Study Group; Stino AM. The Impact of Diabetes and Metabolic Syndrome Burden on Pain, Neuropathy Severity and Fiber Type. Ann Clin Transl Neurol. 2025 May 19. doi: 10.1002/acn3.70072. Epub ahead of print. PMID: 40386990.

🔗 https://onlinelibrary.wiley.com/doi/10.1002/acn3.70072