Matrix metalloproteinases in type 2 diabetes and non-diabetic controls: effects of short-term and chronic hyperglycaemia

Introduction: The role of matrix metalloproteinases (MMPs) in type 2 diabetes mellitus (DM) is not clear as increased activation of MMPs in the vasculature contrasts with decreased activity of MMPs in the kidneys, contributing to development of nephropathy. Material and methods: We measured serum MMP-2 and MMP-9 in 22 subjects with type 2 DM age (mean +/- SD) 56.7 +/- 16.8 years, BMI 31.8 +/- 4.6 kg/m(2), HbA(1c) 8.45 +/- 1.78% and in 32 controls, age 39.2 +/- 16.0 years, BMI 35.2 +/- 8.5 kg/m(2). In 15 subjects with 2 DM we also measured MMP-2 and MMP-9 at discharge from hospital and after 3 months (n = 8). In controls, MMP-2 and -9 were also measured during 75 g oral glucose tolerance test (OGTT). Results: Concentrations of MMP-2 and MMP-9 were lower in subjects with type 2 DM (219 +/- 62 ng/ml vs. 305 +/- 63 ng/ml and 716 +/- 469 ng/ml vs. 1285 +/- 470 ng/ml, for MMP-2 and MMP-9, respectively, p < 0.05). MMP-9 concentrations fell at 120 min of OGTT from 1675 372 ng/ml to 1276 422 ng/ml (p < 0.05). In diabetic subjects there was a correlation between MMP-9 and HbA(1c) (r = 0.51, p < 0.05). In subjects with diabetes there was a fall of HbA(1c), from 9.77 +/- 1.76% to 8.36 +/- 1.54% (p < 0.01), at three months post-discharge. There was no difference in MMP-2, but there was a fall in MMP-9 at three months post-discharge in comparison to concentrations observed at admission (854 +/- 560 ng/ml vs. 500 +/- 235 ng/ml, p = 0.02). Conclusions: Matrix metalloproteinases in type 2 and MMP-9 concentrations were lower in subjects with 2 DM than in non-diabetic controls. Regulation of MMPs appears to be complex as hyperglycaemia during OGTT results in a decrease in MMP-9, while chronic hyperglycaemia, reflected by HbA(1c), correlates with MMP-9 concentrations in subjects with 2 DM.