Obesity, Diabetes and Peripheral Neuropathy in Patients With Class 3 Obesity

Overweight women being weighed by doctor
Peripheral neuropathy may be influenced by obesity and dyslipidemia. Researchers sought to examine this relationship.

In individuals with class 3 obesity, obesity itself may be as strong as prediabetes or type 2 diabetes (T2D) in driving the risk of peripheral neuropathy (PN), a study in the Journal of Clinical Endocrinology and Metabolism suggests.

The study analyzed plasma global metabolomics and targeted lipidomics in participants with obesity who either had PN (n=44) or didn’t have PN (n=44). These participants were matched for glycemic status and compared with a lean, non-neuropathic control participants (n=43).

The researchers sought to identify differential metabolites and lipids by PN and obesity status using data analyzed by Wilcoxon, logistic regression, partial least squares–discriminant analysis, and group-lasso. A sub-analysis was also performed by prediabetes and T2D status.

The mean body mass index (BMI) of participants with obesity with PN and without PN were 45.03±6.84 and 43.03±6.22, respectively, classifying both groups of participants with class 3 obesity.

In the metabolomics analysis as well as examination of triacylglycerols from lipidomics, lean vs obese comparisons found the most significant differences in gamma-glutamyl and branched-chain amino acid metabolism, regardless of PN status. When the investigators stratified participants by PN status within the obese population, they found differences in benzoate, polyamine, and purine biosynthesis metabolism.

According to lipidomics, diacylglycerols was the most significant subpathway that differentiated participants with obesity by PN status. Additional contributions were made from ceramides, dihydroceramides, phosphatidylcholines, and sphingomyelins. Discrimination by PN status was not affected by stratifying the obese group by glycemic status.

Researchers acknowledged many patients in the study were on statins for hyperlipidemia, which may have affected basic plasma lipid profiles. Additionally, the investigators noted that the study was limited by a lack of sensitive insulin resistance measures.

“We anticipate lipid signaling and complex lipids may be exciting avenues of investigation for PN associated with metabolic dysfunction, that is, obesity, prediabetes, and T2D,” the researchers said. “Inhibitors of complex lipid signaling, such as ceramides are an active area of research as antiobesity, anti-T2D, and anti-insulin resistance therapies, highlighting the potential significance of this research direction in PN.”

Disclosure: One study author declared affiliations with private medical industry interests.  Please see the original reference for a full list of authors’ disclosures.


Guo K, Savelieff MG, Rumora AE, et al. Plasma metabolomics and lipidomics differentiate obese individuals by peripheral neuropathy status. J Clin Endocrinol Metab. Published online November 20, 2021. doi:10.1210/clinem/dgab844