Article,
Plasma lipid metabolites associate with diabetic polyneuropathy in a cohort with type 2 diabetes
Affiliations
- [1] University of Michigan–Ann Arbor [NORA names: United States; America, North; OECD];
- [2] University of North Dakota [NORA names: United States; America, North; OECD];
- [3] Aarhus University [NORA names: AU Aarhus University; University; Denmark; Europe, EU; Nordic; OECD];
- [4] Steno Diabetes Center [NORA names: Steno Diabetes Centers; Hospital; Denmark; Europe, EU; Nordic; OECD];
- [5] University of Southern Denmark [NORA names: SDU University of Southern Denmark; University; Denmark; Europe, EU; Nordic; OECD];
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Abstract
OBJECTIVE: The global rise in type 2 diabetes is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy is the most frequent type 2 diabetes complication and is associated with poor outcomes. The metabolic syndrome has emerged as a major risk factor for diabetic polyneuropathy; however, the metabolites associated with the metabolic syndrome that correlate with diabetic polyneuropathy are unknown. METHODS: We conducted a global metabolomics analysis on plasma samples from a subcohort of participants from the Danish arm of Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION-Denmark) with and without diabetic polyneuropathy versus lean control participants. RESULTS: Compared to lean controls, type 2 diabetes participants had significantly higher HbA1c (p = 0.0028), BMI (p = 0.0004), and waist circumference (p = 0.0001), but lower total cholesterol (p = 0.0001). Out of 991 total metabolites, we identified 15 plasma metabolites that differed in type 2 diabetes participants by diabetic polyneuropathy status, including metabolites belonging to energy, lipid, and xenobiotic pathways, among others. Additionally, these metabolites correlated with alterations in plasma lipid metabolites in type 2 diabetes participants based on neuropathy status. Further evaluating all plasma lipid metabolites identified a shift in abundance, chain length, and saturation of free fatty acids in type 2 diabetes participants. Importantly, the presence of diabetic polyneuropathy impacted the abundance of plasma complex lipids, including acylcarnitines and sphingolipids. INTERPRETATION: Our explorative study suggests that diabetic polyneuropathy in type 2 diabetes is associated with novel alterations in plasma metabolites related to lipid metabolism.