Increased Peripheral Proinflammatory T Helper Subsets Contribute to Cardiovascular Complications in Diabetic Patients

Abstract

Background. Coronary atherosclerotic heart disease (CHD) is one of the major concerns in type 2 diabetes (T2D). The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. Methods. The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n = 42 and 67, resp.). Results. Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. Conclusions. Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.

The Role of Leukocytes in Diabetic Cardiomyopathy

“…Distinct T-lymphocytes subtypes, including T-helper subsets (Th) and T regulatory cells (Treg), regulate inflammation and insulin resistance. Increased frequency of Th1, Th17, and Th22 subsets were shown to contribute to coronary artery disease onset in diabetic patients after adjusting for age, sex, and duration of diabetes ( Zhao R.X. et al, 2014 ).…”

The complex immunological and inflammatory network of adipose tissue in obesity

“…In addition, in obese individuals, high levels of circulating Th22 cells and IL‐22 cytokine correlates with type 2 diabetes and coronary heart disease . CD4 T cells differentiate into Th22 cells in the presence of IL‐6 and TNF‐α, and are a novel subset that does not secrete IL‐17 (Th17 maker), IL‐4 (Th2 marker), or IFN‐γ (Th1 marker) .…”

Cardiomyopathy Associated with Diabetes: The Central Role of the Cardiomyocyte

“…Th and T regulatory (Treg) subsets significantly participate in inflammation, IR and vascular alteration in T2D. In particular, the contribution of Th1, Th17 and Th22 pro-inflammatory subtypes to coronary artery disease onset has been reported in DCM patients—after adjusting for age, sex and disease duration—along with a simultaneous decrease of the pro-regulatory anti-inflammatory Th2 subtype [77]; Treg cells with a suppressor function on Th1 are decreased as well. Consequently, the alteration of the Treg/Th17 and Treg/Th1 ratios in favor of pro-inflammatory subsets occurs in T2D patients [78].…”