Background: Adipose tissue produces pro-inflammatory mediators involved in the atherosclerotic process. We investigated whether 12-month exercise training in patients with type 2 diabetes mellitus and coronary artery disease would reduce circulating levels and genetic expression of mediators in the interleukin-18, Caspase-1 and NLR pyrin domain containing 3 pathways. Correlations to glucometabolic variables; fasting glucose, HbA1c, duration of diabetes, insulin, C-peptide, insulin resistance (measured by homeostatic model assessment indexes -insulin resistance) and body mass index at baseline were further assessed. Methods: 137 patients (aged 41-81 years, 17.2% female participants) were included and randomized to a 12-month exercise programme or to a control group. Fasting blood and adipose tissue samples were taken at inclusion and after 12 months. Results: No statistically significant difference in changes of any variable between the intervention and the control group was found. At baseline, a positive correlation between insulin and homeostatic model assessment indexes -insulin resistance, interleukin-18 expression in adipose tissue and an inverse correlation between some glucometabolic variables and leukocyte expression of NLR pyrin domain containing 3 and Caspase-1 were observed. Conclusion: No significant effects of long-term exercise training were observed on the inflammasome-related mediators in our patients with combined coronary artery disease and type 2 diabetes mellitus. The observed correlations may indicate a pro-inflammatory state in adipose tissue by overweight and a compensatory downregulation of these mediators in circulating leucocytes.

IntroductionAdipokines are highly active biopeptides involved in glucose metabolism, insulin regulation and the development and progression of obesity and its associated diseases. It includes, among others, adiponectin, visfatin and tumor necrosis factor alpha (TNFα). The sources of adipokines and their associations with glucometabolic variables are not completely understood.AimIn this cross-sectional study, we aimed to investigate whether gene expression levels in subcutaneous adipose tissue (SAT) of selected adipokines and their corresponding circulating levels associate with the amount of AT in superficial (sSAT), deep (dSAT) and visceral AT (VAT), assessed by computed tomography (CT). Any association with glucometabolic variables were also explored.MethodsIn 103 healthy Caucasian men, aged 39.5 years, fasting venous blood and SAT samples from the gluteal region were collected. Ninety-four of the participants underwent CT assessment of the abdominal AT, which was divided into VAT, sSAT and dSAT. Circulating levels of adipokines were measured by ELISA and AT gene-expression by PCR. Insulin sensitivity was determined by glucose clamp, assessing glucose disposal rate (GDR).ResultsCirculating adiponectin and TNFα gene expression correlated inversely and positively to the amount of AT in all three compartments (r=-0.266 to -0.276, p<0.05 for all) and (r=0.323 - 0.368, p<0.05 for all), respectively, with strongest correlations to the amount in sSAT and dSAT. When dividing AT compartments into quartiles, a tendency was observed towards lower circulating adiponectin and higher TNFα gene expression levels, respectively, with increasing amount of sSAT and dSAT. Circulating adiponectin correlated inversely to insulin, C-peptide and waist circumference (r=-456 to -0.373, p<0.001) and positively to GDR (r=0.356, p<0.001). AT-expressed visfatin correlated inversely to insulin and C-peptide (r=-0.370 and r=-0.404, p<0.001).ConclusionIncreased amount of AT is associated with lower levels of adiponectin and increased levels of TNFα AT expression.

BackgroundInvestigate effects of long-term exercise on the remodeling markers MMP-9, TIMP-1, EMMPRIN and Galectin-3 in combined type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) patients. Any associations between these biomarkers and glucometabolic variables were further assessed at baseline.Methods137 patients (age 41–81 years, 17.2% females) were included and randomized to a 12-months exercise program or to a control group. Fasting blood samples and subcutaneous adipose tissue (AT) samples were taken at inclusion and after 12-months. The intervention was a combination of aerobic and strength training for a minimum of 150 min per week. Circulating protein levels were measured by ELISA methods and RNA was extracted from AT and circulating leukocytes. Expression levels were relatively quantified by PCR.ResultsAfter 12 months of intervention, both AT-expression and circulating levels of EMMPRIN were increased in the exercise group (p < 0.05, both) with significant difference in change between the two groups (p < 0.05 both). No significant effect was observed on MMP-9, TIMP-1 and Galectin-3. Levels of TIMP-1 (AT-expression and circulating) were significantly correlated to insulin, and HOMA2- after Bonferroni correction (p = 0.001, by 48 performed correlations).ConclusionThe increase in levels of EMMPRIN after long-term exercise training, might indicate some degree of AT remodeling in these patients after 12-months of exercise, whether beneficial or not. The remodeling markers were to some extent associated with glucometabolic variables in our population with the combined disease.Trial registration clinicaltrials.gov, NCT01232608. Registered 2 November 2010