The tumour necrosis factor (TNF)-α system is activated in accordance with pulse pressure in normotensive subjects with type 1 diabetes mellitus

Abstract

Objective: Pulse pressure (PP) and inflammation are important predictors of cardiovascular disease (CVD), even in the normotensive. The age-related increase in PP can be diagnosed up to 20 years earlier in subjects with type 1 diabetes mellitus (T1DM) than in the general population. Some evidence suggests that PP can stimulate inflammation. Our aim was to study the relationship between PP and plasma inflammatory proteins in normotensive subjects with T1DM. Design: This was a cross-sectional study of a group of normotensive (<140/80 mmHg) subjects diagnosed with T1DM 14 years before. None of them had clinically proven CVD or inflammatory conditions or were on antiplatelet, antihypertensive, anti-inflammatory or lipid-lowering treatment. Methods: The following information was recorded: sex, age, body-mass index (BMI), waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), PP, mean blood pressure (MBP), smoking, alcohol intake, insulin dose, lipid profile, HbA1c, microvascular complications, and plasma concentrations of soluble receptor types 1 and 2 of tumour necrosis factor (TNF)-α (sTNFR1 and sTNFR2, respectively), interleukin-6, C-reactive protein, adiponectin and leptin. Results: A total of 112 subjects were evaluated (aged 27.4±6.6 years, 52.7% women, BMI: 20.4±2.7 kg/m2, WHR: 0.82±0.09, SBP: 112±12 mmHg, DBP: 68±9 mmHg, PP: 45±9 mmHg, MBP: 82±9 mmHg, HbA1c: 8.2% (7.3–9.0%), 41.1% microvascular complications). After adjusting for potential confounders, only inflammatory markers of the TNF-α system correlated significantly with PP (Pearson correlation coefficient between sTNFR1 and PP: r = 0.215, P = 0.030; and between PP and sTNFR2: r = 0.238, P = 0.020). Conclusion: In normotensive subjects with T1DM after 14 years of diagnosis, the activation of the TNF-α system is positively associated with PP levels. This finding might suggest a pathogenic role of the TNF-α system in the development of cardiovascular disease in T1DM.