Beneficial effects of rosiglitazone on novel cardiovascular risk factors in patients with Type 2 diabetes mellitus

• Published in: Diabetic medicine Vol. 25; no. 3; pp. 333 - 340
• Main Authors: Kadoglou, N. P. E., Iliadis, F., Angelopoulou, N., Perrea, D., Liapis, C. D., Alevizos, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2008; Blackwell
• Subjects: adiponectin; Adiponectin - metabolism; Aged; Biological and medical sciences; Blood Glucose - metabolism; diabetes mellitus; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - prevention & control; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise - physiology; exercise capacity; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Hypoglycemic Agents - therapeutic use; Male; matrix metalloproteinases; Medical sciences; Metalloproteases - metabolism; Middle Aged; Regression Analysis; rosiglitazone; Thiazolidinediones - therapeutic use; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Endocrinopathy; Type 2 diabetes; Physical exercise; Metalloendopeptidases; Cardiovascular disease; diabetes mellitus; Epidemiology; Adiponectin; Hypoglycemic agent; matrix metalloproteinases; Nutritional status; Human; Obesity; Nutrition; Enzyme; Nutrition disorder; Patient; Metabolic diseases; Thiazolidinedione derivatives; Peptidases; Risk factor; Cardiovascular risk; Rosiglitazone; exercise capacity; Hydrolases; Endocrinology
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2007.02375.x

Aim  Impaired exercise capacity, adiponectin, MMPs and TIMPs have all been implicated in the development of cardiovascular disease. The aim of our study was to determine the effects of rosiglitazone on these factors in diabetic patients. Methods  Seventy individuals with Type 2 diabetes were assigned randomly to either a rosiglitazone group (8 mg/day, RG) or a control group (CG) for 6 months. All participants took gliclazide 160 mg plus metformin 1700 mg in stable dose. None of the individuals had diabetic complications or had previously participated in an exercise programme. Anthropometric parameters, VO2 peak, oxygen pulse, glycaemic indices, lipid profile, adiponectin, insulin resistance, blood pressure and serum MMP‐9, TIMP‐1, TIMP‐2 levels were assessed at baseline and at the end of the study. After Bonferroni adjustment, a P‐value < 0.017 was assumed to be statistically significant. Results  Rosiglitazone treatment significantly increased VO2 peak (P < 0.0001), the duration of the exercise test (P < 0.0001), oxygen pulse (P = 0.010) and TIMP‐2 levels (P = 0.008) in comparison with CG. Insulin resistance, hyperglycaemia, diastolic blood pressure and MMP‐9 levels were also reduced (P < 0.017). Fat mass, lipid profile, TIMP‐1 levels and MMP9 : TIMP‐1 ratio were unaltered after rosiglitazone treatment. There were no significant changes in these parameters in control subjects. In univariate analysis, the rosiglitazone‐induced increment of VO2 peak was associated with alterations in plasma adiponectin (r = 0.691), HOMA‐IR (r = –0.782) and HbA1c (r = –0.676) (P < 0.017). These relationships retained significance after multiple regression analysis (P = 0.005). Conclusions  Rosiglitazone treatment increases cardiorespiratory fitness and modulates favourably serum adiponectin, MMP‐9 and TIMP‐2 levels. Whether these effects produce cardiovascular benefits in the long term requires further investigation.