Serum lipidomic determinants of human diabetic neuropathy in type 2 diabetes

Abstract

Objective The serum lipidomic profile associated with neuropathy in type 2 diabetes is not well understood. Obesity and dyslipidemia are known neuropathy risk factors, suggesting lipid profiles early during type 2 diabetes may identify individuals who develop neuropathy later in the disease course. This retrospective cohort study examined lipidomic profiles 10 years prior to type 2 diabetic neuropathy assessment. Methods Participants comprised members of the Gila River Indian community with type 2 diabetes ( n = 69) with available stored serum samples and neuropathy assessment 10 years later using the combined Michigan Neuropathy Screening Instrument (MNSI) examination and questionnaire scores. A combined MNSI index was calculated from examination and questionnaire scores. Serum lipids (435 species from 18 classes) were quantified by mass spectrometry. Results The cohort included 17 males and 52 females with a mean age of 45 years (SD = 9 years). Participants were stratified as with (high MNSI index score > 2.5407) versus without neuropathy (low MNSI index score ≤ 2.5407). Significantly decreased medium‐chain acylcarnitines and increased total free fatty acids, independent of chain length and saturation, in serum at baseline associated with incident peripheral neuropathy at follow‐up, that is, participants had high MNSI index scores, independent of covariates. Participants with neuropathy also had decreased phosphatidylcholines and increased lysophosphatidylcholines at baseline, independent of chain length and saturation. The abundance of other lipid classes did not differ significantly by neuropathy status. Interpretation Abundance differences in circulating acylcarnitines, free fatty acids, phosphatidylcholines, and lysophosphatidylcholines 10 years prior to neuropathy assessment are associated with neuropathy status in type 2 diabetes.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…Due to the elevated risk of mortality with these diseases, there is a need for strategies in its identification, prevention, and treatment within healthcare. In 2022, as evidenced in Figure 5, the bulk of research articles focussed on related diseases: CVD, 232–255 diabetes, 166,233,249,250,256–278 liver disease, 51,279–293 MetS 277,294,295 and obesity 277,295–305 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

Ultra‐high performance liquid chromatography coupled to tandem mass spectrometry‐based metabolomics study of diabetic distal symmetric polyneuropathy

“…Another study targeted the major risk factor for DSPN, lipids, and used lipidomics to assess the correlation between changes in the abundance of various lipid classes and neuropathy status 21 . In addition, some studies also found that the development of peripheral neuropathy might be associated with impaired tricarboxylic acid circulation and other glycolytic pathways by metabolomic methods.…”

Identification of blood metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with type 2 diabetes mellitus

“…17 A few molecules have also been investigated recently as plasma biomarkers of early stage T2DM and are associated with the later stages of DSPN, including medium-chain acylcarnitines, free fatty acids, phosphatidylcholines (PC), and lysophosphatidylcholines (lysoPC). 18 To address the unmet need for easily measurable biomarkers in the field of diabetic neuropathy, this study aimed to characterize the plasma metabolite profiles of participants with T2DM and identify potential biomarkers for DSPN.…”