Metabolomic Risk Predictors of Diabetic Foot Complications: a longitudinal observational study in Type 1 Diabetes

Abstract

Diabetic foot complications is a collective term used for the ailments of the foot that individuals with diabetes incur. The different entities of the term diabetic foot complications are closely linked to each other and several of the other complications of diabetes. Despite implementation of national and international preventive guidelines, diabetic foot complications are still a growing challenge to the individual and society in general. This highlights the need for new strategies in the treatment and prevention of diabetic foot complications. The aim of the study was to investigate associations between plasma metabolites and diabetic foot complications (diabetic foot ulcer (DFU), amputations and Charcot’s Arthropathy) in individuals with diabetes type 1. Non targeted plasma metabolites (n=75) were analyzed using mass spectrometry in a cohort comprising 637 individuals (55% male) with diabetes type 1. Cross sectional associations between metabolites and diabetic foot complications was analysed by linear regression at baseline and by Cox proportional hazards model at follow-up and adjusted for relevant confounders. The median follow up time was 10 years, age 55 (47, 64) years, diabetes duration 35 (25, 44) years and HbA1c 64 (56, 72) mmol/mol. In the adjusted model, four amino acids (proline, threonine, valine, and leucine) were associated with decreased incidence of Charcot’s arthropathy at baseline (padjusted< 0.5). In addition, the plasma levels of ribonic acid was associated with an increased risk of diabetic foot ulcers during follow-up (HR 1.38(1.06-1.8) p<0.05). This study identifies novel circulating metabolites, as potential biomarkers for risk of diabetic foot complications.One Sentence SummarySeveral plasma metabolites show promise as risk markers of diabetic foot complications.

Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

“…Through these studies, we have identified hydroxybutyrate isomers, ribose derivatives, and branched-chain amino acids that were associated with presence and development or progression of DR,8 kidney disease,5 and cardiovascular disease 10. Similar results were also identified in relation to cardiac autonomic neuropathy 4 11. Distal symmetric polyneuropathy (DSPN) remains to be investigated using similar methods.…”