Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes

Abstract

Objective: In type 1 diabetes, cardiovascular autonomic neuropathy (CAN) is associated with cardiovascular risk factors related to insulin resistance, which in turn are associated with low-grade systemic inflammation. Reduced heart rate variability (HRV) is considered one of the first indicators of CAN. Since the autonomic nervous system interacts with systemic inflammation, we evaluated CAN to study its possible association with low-grade systemic inflammation. Design: Cross-sectional study of a group of 120 subjects diagnosed with type 1 diabetes mellitus 14 years before. Methods: Information recorded: 1) clinical characteristics: sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure (BP), smoking, alcohol intake, insulin dose, HbA1c, and lipid profile; 2) plasma levels of soluble fractions of tumour necrosis factor a receptors 1 and 2, IL-6, and C-reactive protein; 3) insulin resistance by estimation of the glucose disposal rate (eGDR); and 4) tests for CAN: HRV in response to deep breathing (E/I ratio), HRV in response to the Valsalva maneuver, and changes in systolic BP responding to standing. Results: A significant negative correlation was found between E/I ratio and plasma concentrations of IL-6 (rZK0.244, PZ0.032), which remained significant after adjusting for potential confounding factors (age, sex, HbA1c, WHR, diastolic BP, triglycerides, HDL-cholesterol, retinopathy, nephropathy, peripheral neuropathy, insulin dose, and smoking; rZK0.231, PZ0.039). No other significant associations were found between inflammation-related proteins, tests for CAN, and eGDR. Conclusions: These findings suggest a link between low-grade inflammation and early alterations of CAN in type 1 diabetes and may be of importance in the pathogenesis of CAN and/or its clinical implications.

Decreased heart rate variability in patients with cirrhosis relates to the presence and degree of hepatic encephalopathy

“…Decreased HRV has been reported in a variety of clinical settings associated with increased production of inflammatory cytokines (6,(22)(23)(24)31). Circulating levels of inflammatory cytokines are increased in patient with cirrhosis (19,55) and positively correlate with the severity of hepatic encephalopathy in this patient population (19,43,44).…”

“…Contrary to the predictions of the classical concept of homeostasis, the output of a wide variety of physiological systems, such as the normal heart beat, fluctuates in a complex manner, even under resting conditions (1,21). Deceased variability or increased regularity of the cardiac rhythm has been reported in different clinical settings associated with systemic inflammation and increased production of inflammatory cytokines, such as sepsis, diabetes mellitus, ischemic heart disease, congestive heart failure, and hepatic failure; in these contexts, it is a negative predictor of outcome (5,6,(22)(23)(24)31).…”

“…However, it appears that the inflammatory cytokine IL-6 might play a role, since circulating levels of IL-6 correlate significantly with indexes of depressed HRV in various clinical conditions (5,22,54).…”

Deep breathing improves blunted baroreflex sensitivity even after 30 years of type 1 diabetes

“…As such, it cannot be excluded as playing at least a part in our patients as well. Endothelial dysfunction and low-grade inflammation have also been related to autonomic imbalance [37][38][39] and could modify the resting level of autonomic function and BRS. Preliminary findings from our group suggest in addition a possible role of chronic tissue hypoxia.…”

From the authors:

“…If not hypoxaemia, what other factors could cause autonomic neuropathy? In patients with cardiac disease [7], type 1 diabetes mellitus [8] and cirrhosishepatic encephalopathy [9], a link between low-grade inflammation and autonomic neuropathy has been proposed. These observations raise the possibility that low-grade inflammation [10] could be linked to autonomic neuropathy in COPD.…”