Reduced endothelial activation after exercise is associated with improved HbA1c in patients with type 2 diabetes and coronary artery disease

Objective: We have previously reported insignificant changes in HbA1c after exercise in patients with both type 2 diabetes and coronary artery disease. In this study, we investigated the effect of exercise on endothelial function and possible associations between changes in endothelial function and HbA1c. Methods: Patients with type 2 diabetes and coronary artery disease (n = 137) were randomised to 12 months exercise or standard follow-up. Endothelial function was assessed by circulating biomarkers (E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, von Willebrand factor, tissue plasminogen activator antigen, asymmetric dimethylarginine and L-arginine/asymmetric dimethylarginine ratio). Differences between the randomised groups were analysed by analysis of covariance and correlations by Spearman’s rho or Pearson’s correlation. Results: No effect of exercise on endothelial function was demonstrated. The changes in HbA1c in the exercise group correlated with changes in E-selectin (r = 0.56, p < 0.001), intercellular adhesion molecule-1 (r = 0.27, p = 0.052), vascular cell adhesion molecule-1 (r = 0.32, p = 0.022) and tissue plasminogen activator antigen (r = 0.35, p = 0.011). HbA1c decreased significantly more in patients with versus without a concomitant reduction in E-selectin (p = 0.002), intercellular adhesion molecule-1 (p = 0.011), vascular cell adhesion molecule-1 (p = 0.028) and tissue plasminogen activator antigen (p = 0.009). Conclusion: Exercise did not affect biomarkers of endothelial function in patients with both type 2 diabetes and coronary artery disease. However, changes in biomarkers of endothelial activation correlated with changes in HbA1c, and reduced endothelial activation was associated with improved HbA1c after exercise

Elevated levels of circulating microvesicles in coronary artery disease patients with type 2 diabetes and albuminuria: Effects of exercise training

Circulating microvesicles, released from activated/apoptotic cells, are involved in vascular complications and may be looked upon as biomarkers. Albuminuria is characteristic of disease progression in type 2 diabetes mellitus. We aimed to investigate quantitative and qualitative differences of circulating microvesicles in type 2 diabetes mellitus with and without albuminuria and whether 12-month exercise training influenced expression of circulating microvesicles.Coronary artery disease patients with type 2 diabetes mellitus (n = 75), of which 25 had albuminuria, were included. Annexin V+) circulating microvesicles were analysed by flow cytometry in citrated plasma. The exercise volume was 150 min per week.In albuminuria patients, circulating microvesicles from endothelial-(CD146+) and endothelial-progenitor-(CD309+) cells were significantly higher compared to those without ( p ⩽ 0.01, both). Receiver operating characteristic curve analysis of the endothelial circulating microvesicles shows an area under the curve of 0.704 (95% confidence interval: 0.57–0.84; p = 0.004). Albuminuria patients had more circulating microvesicles derived from activated leukocytes and monocytes and monocytes carrying tissue factor (CD11b+, CD11b+, CD142+, respectively, p ⩽ 0.05, all) and higher number of circulating microvesicles from activated platelets (CD62P+). Within exercising patients, circulating microvesicles from progenitor cells increased ( p = 0.023), however, not significantly different from controls.Coronary artery disease patients with type 2 diabetes mellitus and albuminuria had elevated number of circulating microvesicles from activated blood and vascular cells, rendering them as potential predictors of disease severity. The circulating microvesicles were limitedly affected by long-term exercise training in our population

Procoagulant activity in patients with combined type 2 diabetes and coronary artery disease: No effects of long-term exercise training

We investigated the effects of 12-month exercise training on hypercoagulability in patients with combined type 2 diabetes mellitus and coronary artery disease. Associations with severity of disease were further explored. Patients (n = 131) were randomized to exercise training or a control group. Blood was collected at inclusion and after 12 months. Tissue factor, free and total tissue factor pathway inhibitor, prothrombin fragment 1 + 2 (F1 + 2) and D-dimer were determined by enzyme-linked immunosorbent assay and ex vivo thrombin generation by the calibrated automated thrombogram assay. Tissue factor and ex vivo thrombin generation increased from baseline to 12 months (p < 0.01, all), with no significant differences in changes between groups. At baseline, free and total tissue factor pathway inhibitor significantly correlated to fasting glucose (p < 0.01, both) and HbA1c (p < 0.05, both). In patients with albuminuria (n = 34), these correlations were strengthened, and elevated levels of D-dimer, free and total tissue factor pathway inhibitor (p < 0.01, all) and decreased ex vivo thrombin generation (p < 0.05, all) were observed. These results show no effects of exercise training on markers of hypercoagulability in our population with combined type 2 diabetes mellitus and coronary artery disease. The association between poor glycaemic control and tissue factor pathway inhibitor might indicate increased endothelial activation. More pronounced hypercoagulability and increased tissue factor pathway inhibitor were demonstrated in patients with albuminuria

Adiponectin in relation to exercise and physical performance in patients with type 2 diabetes and coronary artery disease

Introduction: Adipokines, expressed by adipose tissue (AT), have been associated with metabolic disturbances and coronary artery disease (CAD). The impact of exercise training on the AT in patients suffering from both diabetes and CAD is unknown. To gain knowledge on changes in ATs’ inflammatory profile in such a population, we investigated the effects of long-term exercise on selected adipokines and their associations with physical performance and glucometabolic variables. Adiponectin was selected based on its anti-atherogenic and anti-diabetic properties and visfatin and tumour necrosis factor (TNF) for their association with atherosclerosis and metabolic disorders. Not many studies have focused on the effects of long-term exercise training on adipokines in patients with concomitant T2DM and CAD. Methods: Patients with type 2 diabetes and CAD (n = 137), 41–81 years, 17.2% females, were randomized in a 1:1 manner to an exercise group, who underwent 1 year of 150 min weekly combined strength and endurance exercise, or a control group. AT from the gluteal region and blood samples were obtained at baseline and after 12 months, along with a physical performance test, assessed by the VO2 peak. Circulating protein levels were measured by ELISA. RNA was extracted from AT and expression levels were relatively quantified by PCR. Results: After 1 year, no significant difference in the change in the investigated markers between the intervention group and the control group was observed. Changes in circulating adiponectin and VO2 peak correlated in the total population (r = 0.256, p = 0.008). At baseline, circulating adiponectin and TNF correlated inversely with insulin and with C-peptide and VO2peak, respectively (p < 0.001, all). Conclusion: In this population with concomitant diabetes and CAD, ATs’ inflammatory profile remained unchanged apparently after 1 year of exercise intervention. Changes in the VO2peak were nevertheless, related to changes in circulating adiponectin levels. Trial registration: http://www.clinicaltrials.gov NCT01232608

Gut related inflammation and cardiorespiratory fitness in patients with CAD and type 2 diabetes: a sub-study of a randomized controlled trial on exercise training

Aim Gut leakage has been shown to associate with low-grade inflammation and lower cardiorespiratory fitness in diabetic subjects. We aimed to investigate whether gut leakage markers related to cardiorespiratory fitness in patients with both coronary artery disease and type 2 diabetes, and whether these were affected by long-term exercise training. Methods Patients with angiographically verified coronary artery disease and type 2 diabetes mellitus (n = 137) were randomized to either 12 months exercise intervention or conventional follow-up. A cardiopulmonary exercise test and fasting blood samples were obtained before and after intervention to assess VO2peak and the biomarkers soluble CD14, lipopolysaccharide-binding protein and intestinal fatty-acid binding protein as markers of gut leakage. Results 114 patients completed the intervention satisfactory. VO2peak correlated inversely to sCD14 (r = − 0.248, p = 0.004) at baseline. Dividing sCD14 into quartiles (Q), VO2peak was significantly higher in Q1 vs. Q2–4 (p = 0.001), and patients in Q2-4 (sCD14 > 1300 ng/mL) had an OR of 2.9 (95% CI 1.2–7.0) of having VO2peak below median ( 0.05) after 12 months. Conclusions Cardiorespiratory fitness related inversely to sCD14, suggesting physical capacity to be associated with gut leakage in patients with CAD and T2DM. Long-term exercise training did not affect circulating gut leakage markers in our population. Trial registration NCT01232608, Registered 02 November 2010—Retrospectively registered at https://clinicaltrials.gov/ct2/show/NCT01232608?term=NCT01232608&draw=2&rank=