Free light chains are a biomarker for cardiovascular disease in patients with Type 1 diabetes

Aims: Light chains (kappa and lambda) are integral components of immunoglobulins that are synthesised in excess by plasma cells and filtered by the kidneys. Polyclonal free light chains (FLC) are frequently elevated in patients with renal disease or immunostimulatory disorders. Elevated (combined) polyclonal FLC have also been independently associated with morbidity and mortality in the general population, and more recently with cardiovascular disease (CVD) in patients with Type 2 diabetes. We aimed to investigate whether FLC are associated with CVD risk in patients with Type 1 diabetes. Methods: CVD risk was estimated in a cohort of 55 patients with Type 1 diabetes from the West Midlands chronic disease research database (CDRD) using the Procam and Q-risk CVD risk engines. FLC was determined using a monoclonal antibody based assay. Non-parametric statistical analyses were performed to determine whether FLC are associated with CVD risk. Results: Our cohort consisted of male and female, predominantly white British patients, mean age 48 years. The FLC kappa/lambda ratio was normal for our cohort. Q-risk 10 year score and Procam myocardial infarction risk scores were both significantly associated with FLC (p = 0.003 and p = 0.012 respectively), as well as duration of diabetes (p = 0.003), patient age (p = 0.006) and medical history of cardiac disease (p = 0.042). Summary: We show that CVD risk is significantly associated with FLC in patients with Type 1 diabetes. The mechanisms linking FLC with CVD risk remain unclear. Elevated polyclonal FLC are associated with inflammation, which in turn is associated with CVD risk. Alternatively FLC may be atherogenic and predispose to coronary artery disease.