The anti-inflammatory effects of aerobic exercise training in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a low-grade, chronic inflammatory disease, associated with increased cardiovascular risk. The purpose of this systematic review/ meta-analysis was to evaluate the effects of aerobic exercise training (AET) on inflammatory markers in T2DM patients. METHODS: The literature search was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library from their inception up to April 2022. We screened only for randomized controlled trials (RCTs) investigating the effects of AET on C-reactive protein (CRP) and adipokines: adiponectin, resistin, interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-a), along with changes in anthropometric indices and glycemic control in adult T2DM patients. Pooled post-exercise weighted mean differences (WMDs) with 95% Confidence Intervals (CIs) were calculated for all outcomes of interest between exercise-treated patients and controls. RESULTS: Twenty-six RCTs involving 1239 T2DM patients were retrieved from the databases for meta-analysis. The cumulative results showed that post-AET inflammatory markers were lower in exercise-treated patients compared to controls regarding CRP (mg/L): WMD: -0.91; 95%CIs: -1.43, -0.40; p < 0.001 resistin (mg/ml): (WMD: -2.08; 95%CIs: -3.32, -0.84; p < 0.001); TNF-a (pg/ml): (WMD: -2.70; 95%CIs: -4.26, -1.14; p < 0.001), and IL-6 (pg/ml): (WMD: -1.05; 95%CIs: -1.68, -0.43; p < 0.001). Those effects were accompanied by significant amelioration of fasting glucose (mg/dl) (WMD: -13.02; 95%CIs: -25.39, -0.66; p = 0.04), HbA1c (%) (WMD: -0.51; 95%CIs: -0.73, -0.28, p < 0.001), and fat mass (%) (WMD: -3.14; 95%CI: -4.71, -1.58; p < 0.001). Our meta-analysis demonstrated less-consistent results for adiponectin (µg/ml), (WMD: 1.00; 95%CI: -0.12, 2.12; p = 0.08) and body-mass index (kg/m2) (WMD: -1.34; 95%CI: -2.76, 0.08; p = 0.06) tending to differ between AET and control group. CONCLUSIONS: AET can significantly reduce the inflammatory burden in T2DM patients. by ameliorating the circulating levels of CRP, resistin, TNF-a and IL-6, even without accompanied significant weight-loss. The clinical impact of those anti-inflammatory effects of AET needs to be determined.

A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block.

Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases.