The Impact of Diabetes and Metabolic Syndrome on Neuropathy

Diabetes is the most common form of peripheral neuropathy, accounting for nearly half of all cases.   On the flip side, diabetic peripheral neuropathy affects almost 50% of those with diabetes.  Diabetic peripheral neuropathy is the fifth most common cause of neurological disability worldwide and is associated with significant healthcare costs (nearly $1 trillion worldwide in 2021).

Metabolic syndrome is now recognized as a central contributor to the development of peripheral neuropathy, especially in those with type 2 diabetes.   Metabolic syndrome not only increases the likelihood of diabetes, independent of sugar levels, but also accelerates the progression of diabetic neuropathy in those with established diabetes.  A higher burden of metabolic syndrome also increases the likelihood of diabetic neuropathy, accelerates its progression, and shortens the time to symptom onset.

While this is all known, the relationship between both diabetes and metabolic syndrome burden with pain, neuropathy severity, and fiber type involvement in patients with established polyneuropathy is not clear.  So, a team of researchers from the University of Michigan, including Amro Stino, M.D, Clinical Associate Professor, and Brian Callaghan, M.D., M.S., the Eva L Feldman, M.D., Ph.D., Professor of Neurology, set out to investigate just that and published in the Annals of Clinical and Translational Neurology.

“We found that those with diabetic neuropathy were more likely to have pain, more severe nerve problems, and more mixed fiber involvement as compared to those without diabetes, explained Dr. Stino.  “Additionally, the more features of metabolic syndrome a person had, like high blood pressure, high blood sugar, or obesity, the more likely they were to have painful and possibly more serious nerve damage affecting multiple nerves.”

“Since we found that metabolic neuropathy and diabetic neuropathy were very similar in regard to pain, severity, and type of nerve involved (large, small, mixed),” explained Dr. Callaghan.  “This implies that these types of neuropathies may need similar treatments that address all the metabolic risk factors.”

Other authors: Long Davalos, M.D, and Masem Dimachkie, M.D., from Kansas University, Lavanya Muthukumar, M.S., from the University of Michigan, Simone Thomas, M.S., and Amet Hoke, M.D., Ph.D., from Johns Hopkins University, Evan Reynolds, Ph.D., from Michigan State University, A. Gordon Smith, M.D., from Virginia Commonwealth University, J. Robinson Singleton, M.D., from the University of Utah, Senda Ajroud-Driss, M.D., from Northwestern University, Stefanie Geisler, M.D., from Washington University, David Simpson, M.D., from Mount Sinai Medical Center, and the Peripheral Neuropathy Research Registry (PNRR) Study Group.

Paper cited: 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.