Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 and -2 in Type 2 Diabetes

Effect of 1 year’s cardiovascular risk reduction therapy

  1. Muzahir H. Tayebjee, MRCP,
  2. H. Sern Lim, MRCP,
  3. Robert J. MacFadyen, MD and
  4. Gregory Y.H. Lip, MD
  1. From the Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, U.K
  1. Address correspondence and reprint requests to Professor Gregory Y.H. Lip, City Hospital, University Department of Medicine, Haemostasis Thrombosis and Vascular Biology Unit, Birmingham B18 7QH, U.K. E-mail: g.y.h.lip{at}bham.ac.uk

Cardiovascular risk reduction therapy in diabetic patients reduces vascular events (1) by retarding atherosclerosis and improving vascular reactivity. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are integral to the vascular changes of atheroma, and MMP-9 and TIMP-1 are raised in diabetes (2). We hypothesized that global risk reduction of intensified diabetes and cardiovascular risk management in type 2 diabetes would be associated with reductions in circulating markers of extracellular matrix turnover, namely MMP-9, TIMP-1, and TIMP-2.

RESEARCH DESIGN AND METHODS

Cross-sectional study

Eighty-six patients with type 2 diabetes (3) and treated hypertension with serum creatinine <120 mmol/l were recruited from local clinics (Table 1). Of these, 46% (n = 36) had a clinical history of cardiovascular disease. Data from these patients were compared with 49 healthy control subjects. Ethical approval and informed consent were obtained.

Interventional study

Sixty-five of the recruited diabetic patients (of whom 36 had cardiovascular disease) consented to intensified diabetes and cardiovascular risk management therapy. This consisted of 3 monthly consultations, lifestyle advice, and adjusting oral hypoglycemia therapy to achieve HbA1c <6.5%. Metformin (starting at 500 mg b.d.) was instigated in patients with a BMI >25 kg/m2 or added second-line in lean patients, who received initial treatment with gliclazide MR (30 mg o.d.) and vice versa. Insulin could be started if HbA1c remained >7.0% despite …

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