Abstract

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

Highlights

  • Investigate effects of long-term exercise on the remodeling markers Matrix metalloproteinase (MMP)-9, tissue inhibitor of matrix metalloproteinase (TIMP-1), extracellular matrix metalloproteinase inducer (EMMPRIN) and Galectin-3 in combined type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) patients

  • Baseline correlations to glucometabolic variables (Table 3) We found some associations between the glucometabolic variables insulin, C-peptide, HOMA2-IR and body mass index (BMI) and the investigated markers EMMPRIN and TIMP-1

  • Circulating levels and Adipose tissue (AT) expression of EMMPRIN and TIMP-1 correlated to glucometabolic variables, and AT expression of the markers were not reflected in their circulating levels or leukocyte expression

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Summary

Introduction

Investigate 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. Depending on the stimuli it receives, the AT may undergo extensive remodeling, with extracellular matrix (ECM) degradation and infiltration of macrophages and other pro-inflammatory cells, creating both a local and a systemic inflammatory environment with subsequent production of pro-inflammatory mediators [2] This may precipitate decreased insulin-sensitivity and subsequently type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) [3]. There seems to be an association between body mass index (BMI) and plasma levels of MMP-9, suggesting AT as a potential source [8]

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