NLRP3 Inflammasome in Diabetic Cardiomyopathy and Exercise Intervention.

Diabetic cardiomyopathy (DCM), as a common complication of diabetes, is characterized by chronic low-grade inflammation. The NLRP3 inflammasome is a key sensor mediating innate immune and inflammatory responses. However, the mechanisms initiating and promoting NLRP3 inflammasome activation in DCM is largely unexplored. The aim of the present review is to describe the link between NLRP3 inflammasome and DCM, and to provide evidence highlighting the importance of exercise training in DCM intervention. Collectively, this evidence suggests that DCM is an inflammatory disease aggravated by NLRP3 inflammasome-mediated release of IL-1ß and IL-18. In addition, chronic exercise intervention is an effective preventive and therapeutic method to alleviate DCM via modulating the NLRP3 inflammasome.

Cardiac rehabilitation goal attainment after myocardial infarction with versus without diabetes: A nationwide registry study.

BACKGROUND: Patients with first-time myocardial infarction (MI) and diabetes mellitus (DM) constitute a vulnerable subgroup of cardiovascular (CV) patients for which secondary prevention is particularly important. We investigated if patients with versus without DM differ in attaining four main lifestyle-related cardiac rehabilitation (CR) targets, one-year post-MI. METHODS: This national cohort study (2006-2015) identified individuals with and without DM at hospital admission in the Swedish cardiac registry, SWEDEHEART. CR goal attainment was assessed one year later. The study population included 47,907 unique patients with first-time MI <75 years at baseline (61.8 mean age, 26.7% women, 14.6% with DM). After imputation, propensity score matching was performed. Analyses were conducted with logistic regression. RESULTS: In the matched population, having DM was associated (OR [95% CI]) with lower odds of attaining the one-year post-MI CR goal for both smoking cessation (0.90 [0.81, 0.99]) and attendance in exercise training (0.88 [0.83, 0.95]), yet with higher odds of the <1.8 mmol LDL-C target (1.28 [1.19, 1.36]), and similar odds for the <140 mm Hg systolic blood pressure target (0.97 [0.91, 1.04]). In addition, women with DM were particularly unlikely to attend exercise training. CONCLUSIONS: Patients with first-time MI and DM are less likely to attain two of four selected CR goals compared to those without DM. The particularly low exercise training attendance by women with DM is of concern. Possibilities for tailored interventions targeting behavioural change for this high-risk group, including focused efforts to increase exercise training attendance in women with DM, should be investigated.

Swimming training attenuates the morphological reorganization of the myocardium and local inflammation in the left ventricle of growing rats with untreated experimental diabetes.

Diabetic cardiomyopathy is associated with cardiac remodeling, myocardial dysfunction, low-grade inflammation, and reduced cardiac adiponectin in patients with type 1 diabetes mellitus (T1DM). Alternatively, physical exercise is an important strategy for the management of diabetes. This study aimed to investigate the influence of low-intensity swimming training in cardiac cytokines, structural remodeling, and cardiomyocyte contractile dysfunction in growing rats with untreated experimental DM. Thirty-day-old male Wistar rats were divided into four groups (n=14, per group): sedentary control (SC), exercised control (EC), sedentary diabetic (SD), and exercised diabetic (ED). Diabetes was induced by streptozotocin (60 mg kg(-1), i.p.). Animals from exercised groups swam (5 days/week, 90 min/day, loading up to 5% body weight around the animal's chest) for 8 weeks. The left ventricle (LV) was removed for molecular, morphological, and cardiomyocyte mechanical analysis. Diabetic animals presented cardiac remodeling with myocardial histoarchitectural disorganization, fibrosis, and necrosis. The capillary density was lower in diabetic animals. LV cardiomyocytes from diabetic animals exhibited more prolonged time to the peak of contraction and time to half relaxation than those from control animals. The cardiac levels of interleukin 10, nitric oxide, and total and high molecular weight (HMW) adiponectin were significantly decreased in diabetic animals. Exercise training reduced the level of TNF-α, increased capillary density, and attenuated the histopathological parameters assessed in diabetic rats. In conclusion, the cardiac structural remodeling coexists with reduced levels of total and HMW adiponectin, inflammation, and cardiomyocyte contractility dysfunction in experimental DM. More important, low-intensity swimming training attenuates part of these pathological changes, indicating the beneficial role for exercise in untreated T1DM.

Depressive symptoms predict non-completion of a structured exercise intervention for people with Type 2 diabetes.

AIM: To quantify the impact of depressive symptoms on completion of exercise-based rehabilitation for Type 2 diabetes management. METHODS: Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale in a prospective cohort of consecutive patients with Type 2 diabetes entering a 6-month hybrid (home- and clinic-based) exercise rehabilitation programme. Attendance at exercise sessions was monitored and programme completion/non-completion was ascertained. RESULTS: Of the programme participants (n=624, mean age 55.6±10.5 years, 47% male), 26.8% endorsed significant depressive symptoms (depression score ≥16) and 68.1% completed the intervention, attending 54.6±30.0% of supervised exercise sessions. Baseline depressive symptoms (depression scale score ≥16) increased the risk of non-completion [hazard ratio 1.49 (95% CI 1.10-2.03); P = 0.010], and predicted fewer sessions attended (ß=-2.1, P= 0.002) in adjusted models. A depression score threshold of ≥10 (48.4% of participants) predicted non-completion [hazard ratio 1.60 (95% CI 1.19-2.17); P= 0.002) with optimum accuracy. Non-completions resulting from lack of interest (18.9 vs. 11.0%; P= 0.026) and medical complications (14.6 vs. 6.6%; P= 0.006) were more common among participants with depression scores ≥10. Greater hazard ratios for depression scores ≥10 were observed in subgroups not currently using insulin [hazard ratio 1.70 (95% CI 1.24-2.33); P= 0.001), or an antidepressant [hazard ratio 1.83 (95% CI 1.32-2.54); P<0.001]. CONCLUSIONS: Depressive symptoms were highly prevalent among participants with Type 2 diabetes entering exercise-based rehabilitation, and even mild depressive symptoms posed a significant barrier to completion. Depression screening may help target additional supports to facilitate completion of exercise interventions for people with Type 2 diabetes.

Effectiveness of tailored support for people with Type 2 diabetes after a first acute coronary event: a multicentre randomized controlled trial (the Diacourse-ACE study).

AIMS: To evaluate the effectiveness of a tailored, supportive intervention strategy in influencing diabetes-related distress, health status, well-being and clinical outcomes in people with Type 2 diabetes shortly after a first acute coronary event. METHODS: People with Type 2 diabetes and a recent first acute coronary event (n = 201) were randomized to the intervention group (three home visits by a diabetes nurse) or the attention control group (one telephone consultation). Outcomes were measured after discharge (baseline) and at 5 months (follow-up) using validated questionnaires for diabetes-related distress (Problem Areas in Diabetes), well-being (WHO Well-Being Index) and health status (Euroqol 5 Dimensions; Euroqol Visual Analogue Scale). ancova was used to analyse change-over-time differences between groups. RESULTS: Follow-up data were available for 81 participants in the intervention group (66.0 ± 9.3 years, 76% male) and 80 in the control group (65.6 ± 9.4 years, 75% male) participants. Mean diabetes-related distress was low after hospital discharge (intervention group: 8.2 ± 10.1; control group: 9.2 ± 12.4) and did not change after 5 months (intervention group: 9.2 ± 12.4; control group: 9.0 ± 11.2). Baseline well-being was less favourable but improved significantly in the intervention group (baseline: 58.5 ± 28.0; follow-up: 65.5 ± 23.7; P = 0.005), but not in the control group (baseline: 57.5 ± 25.2; follow-up: 59.6 ± 24.4; P = 0.481). Health status also improved in the intervention group (baseline: 69.9 ± 17.3; follow-up: 76.8 ± 15.6; P < 0.001) but not in the control group (baseline: 68.6 ± 15.9; follow-up: 69.9 ± 16.7; P = 0.470). A significant group effect was found for health status (F = 7.9; P = 0.006). CONCLUSIONS: Although the intervention had no effect on diabetes-related distress, this might be at least partially attributable to very low levels of diabetes-related distress at baseline. Interestingly, health status scores and well-being, which were less favourable at baseline, both improved after the tailored support intervention.

Nerve growth factor rescues diabetic mice heart after ischemia/reperfusion injury via up-regulation of the TRPV1 receptor.

AIMS: Nerve growth factor (NGF), a member of the neurotrophin family, plays an essential role in diabetic neuropathy and ischemic heart disease. In the present study, we explored the potential role of NGF and the involvement of TRPV1 receptor in isolated diabetic mouse hearts following ischemia/reperfusion (I/R) injury. METHODS: Adenovirus-mediated NGF gene delivery was performed on diabetic and sham hearts 8weeks after streptozotocin treatment. The sciatic nerve conduction velocity was recorded using a biological signal acquisition system. Forty-eight hours after heart surgery, mice were subjected to I/R injury using a Langendorff system. Several cardiac parameters and the expression of associated molecules were analyzed during the experiment. RESULTS: The sciatic nerve conduction velocity was reduced in diabetic mice compared with that in control mice. Decreased expression of NGF, TRPV1, and the downstream neurotransmitters CGRP and SP was observed in the diabetic hearts. Adenovirus-mediated NGF overexpression reversed the reduction in TRPV1 and downstream neuropeptides, resulting in improved cardiac recovery post-I/R injury in diabetic hearts. The protective effect of NGF was abolished by CGRP8-37 (a selective CGRP antagonist), while it was preserved by low-dose capsaicin. CONCLUSIONS: The NGF-induced up-regulation of TRPV1 via the increased synthesis and release of endogenous CGRP leads to improved cardiac performance in I/R-injured diabetic heart.

Cardiac rehabilitation in patients with type 2 diabetes mellitus and coronary disease: a comparative study.

INTRODUCTION AND AIMS: Diabetic patients have a 2-4 times higher risk of cardiovascular disease than non-diabetic individuals. The aims of this study are to evaluate the effects of a cardiac rehabilitation program (phase II) in patients with diabetes and coronary disease and to compare the results with regard to control of cardiovascular risk factors and improvement in functional capacity with coronary patients without diabetes. METHODS: This was a prospective study of patients diagnosed with ischemic heart disease referred for a cardiac rehabilitation program between January 2009 and June 2013. The population was divided into two groups: diabetic and non-diabetic. Patients were assessed at the beginning of phase II and three months later and the following parameters were recorded: body mass index, waist circumference, lipid profile, blood glucose and glycated hemoglobin in diabetic patients, blood pressure, smoking, physical activity level (using the International Physical Activity Questionnaire) and functional capacity (on treadmill stress testing). RESULTS: The study population consisted of 682 patients (253 diabetic and 429 non-diabetic). Diabetic patients were significantly older, had a worse cardiovascular risk profile (higher prevalence of overweight, dyslipidemia, hypertension and sedentary lifestyle) and lower functional capacity. At the end of phase II, there was a statistically significant improvement (p<0.05) in all risk factors and functional capacity, which was similar in both groups, except for body mass index, triglycerides and functional capacity. CONCLUSIONS: Diabetic patients may benefit from a cardiac rehabilitation program and achieve comparable results to non-diabetic patients.