Relationship of low molecular weight fluorophore levels with clinical factors and fenofibrate effects in adults with type 2 diabetes

• Main Authors: Januszewski, Andrzej S., Chen, David, Scott, Russell S., O'Connell, Rachel L., Aryal, Nanda R., Sullivan, David R., Watts, Gerald F., Taskinen, Marja-Riitta, Barter, Philip J., Best, James D., Simes, John R., Keech, Anthony C., Jenkins, Alicia J.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Medicine; Diabetes; Endocrinology
• Online Access: https://hdl.handle.net/10356/153807
• Institution: Nanyang Technological University

People with diabetes are at risk of chronic complications and novel biomarkers, such as Advanced glycation end-products (AGEs) may help stratify this risk. We assessed whether plasma low-molecular weight AGEs, also known as LMW-fluorophores (LMW-F), are associated with risk factors, predict complications, and are altered by fenofibrate in adults with type 2 diabetes. Plasma LMW-F were quantified at baseline, after six weeks fenofibrate, and one year post-randomisation to fenofibrate or placebo. LMW-F associations with existing and new composite vascular complications were determined, and effects of fenofibrate assessed. LMW-F correlated positively with age, glycated haemoglobin (HbA1c), pulse pressure, kidney dysfunction and inflammation; and negatively with urate, body mass index, oxidative stress and leptin, albeit weakly (r = 0.04-0.16, all p < 0.01). Independent determinants of LMW-F included smoking, diastolic blood pressure, prior cardiovascular disease or microvascular complications, Caucasian ethnicity, kidney function, HbA1c and diabetes duration (all p ≤ 0.01). Baseline LMW-F tertiles correlated with on-trial macrovascular and microvascular complications (trend p < 0.001) on univariate analyses only. Six weeks of fenofibrate increased LMW-F levels by 21% (p < 0.001). In conclusion, LMW-F levels correlate with many risk factors and chronic diabetes complications, and are increased with fenofibrate. LMW-F tertiles predict complications, but not independently of traditional risk factors.