Interleukin-6 and activin A are independently associated with cardiovascular events and mortality in type 2 diabetes: the prospective Asker and Bærum Cardiovascular Diabetes (ABCD) cohort study

Abstract

BackgroundNovel and robust cardiovascular (CV) markers are needed to improve CV morbidity and mortality risk prediction in type 2 diabetes (T2D). We assessed the long term predictive value of 4 novel CV risk markers for major CV events and mortality.MethodsWe included patients with T2D who had cytokines (interleukin [IL]-6 and activin A [actA]), a maximum stress ECG test (evaluated by the normalization pattern in early recovery phase) and echocardiography (evaluated by a measure of the left ventricular filling pressure - E/Em) assessed at baseline. The primary endpoint was time to first of any of the following events: myocardial infarction, stroke, hospitalization for unstable angina pectoris and death. All outcomes were adjudicated by independent experts. We used Cox proportional hazard modeling, Harrell C-statistic and the net reclassification improvement (NRI) to assess the additional value beyond conventional markers (age, gender, prior CV disease, HDL, creatinine, diastolic BP, microalbuminuria).ResultsAt baseline the study cohort (n = 135, mean age/diabetes duration/HbA1c: 59 yrs/7 yrs/7.6% [59 mmol/mol], 26% females) had moderate elevated CV risk (42% microalbuminuria, mean Framingham 10 year CV-risk 9.6%). During 8.6 yrs/1153.7 person years, 26 patients experienced 36 events. All 4 novel risk markers were significantly associated with increased risk of the primary endpoint, however, only IL-6 and actA improved C-statistic and NRI (+0.119/43.2%, +0.065/20.3% respectively) compared with the conventional CV risk factors.ConclusionsIL-6 and actA may provide prognostic information on CV events and mortality in T2D beyond conventional CV risk factors.Trial registrationClinicalTrials.gov: NCT00133718

Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus

“…Patients with DM are characterized by a state of chronic inflammation and abnormal activation of the innate immune system . Various inflammatory factors, such as monocyte chemoattractant protein‐1 (MCP‐1), tumor necrotic factor‐ α (TNF‐ α ), and C‐reactive protein (CRP) are upregulated in DM, and may play pivotal roles in the development of CVD in DM patients . Recently, gut microbiota were found to be related to obesity, metabolic endotoxemia, and low‐grade chronic inflammation .…”

“…[7][8][9][10][11][12] Various inflammatory factors, such as monocyte chemoattractant protein-1 (MCP-1), tumor necrotic factor-α (TNF-α), and C-reactive protein (CRP) are upregulated in DM, and may play pivotal roles in the development of CVD in DM patients. [13][14][15][16] Recently, gut microbiota were found to be related to obesity, metabolic endotoxemia, and low-grade chronic inflammation. [17][18][19][20] Gut microbiota participate in the energy homeostasis of the host by modulating its capacity to harvest energy from given nutrients and in subsequent fat storage, 17 and can be modulated by dietary fiber, polysaccharides, or high-fat diets.…”

Fibroblast growth factor 21 deletion aggravates diabetes-induced pathogenic changes in the aorta in type 1 diabetic mice

“…Diabetic vascular complications, including macroangiopathy, microangiopathy and peripheral vascular complications, are the most common diabetic complications in both type 1 [ 1 ] and type 2 [ 2 ] diabetes mellitus and make major contributions to diabetic mortality and morbidity [ 2 ]. Diabetic microvascular disease is a leading cause of blindness, renal failure and nerve damage.…”

Cardiovascular biomarkers in clinical studies of type 2 diabetes

“…In contrast to the findings of Herder et al, a recent case‐cohort study population comprising 3865 patients from the ADVANCE study affirmed that IL‐6 is a strong and independent predictor of major CV events and death in patients with T2D who have CHD or risk factors at baseline . Furthermore, in a population with T2D and moderately elevated CV risk, IL‐6 provided prognostic information on CV events and mortality beyond conventional CV risk factors . Interestingly, observing the progression of macrovascular complications among patients with T2D and healthy subjects during a 5‐year follow‐up, Wu et al found that IL‐6 has stronger predictive value in diabetic atherosclerosis development, as compared with non‐diabetic atherosclerosis.…”