Concentrations of matrix metalloproteinase 2 and 9 in patients with type 2 diabetes and in non-diabetic controls
KC Lewandowski1, E Banach2 & A Lewinski2
Background: Matrix metalloproteinases (MMPs) remodel extracellular matrix (ECM) in physiology as well as in cancer, inflammatory states and cardiovascular disease. In type 2 diabetes, there is evidence of activation of MMPs in vasculature, while decreased activity of MMPs and excessive accumulation of ECM is thought to contribute to the development of diabetic nephropathy.
Material and methods: We measured serum MMP-2, MMP-9 in 22 subjects with type 2 DM age (mean±S.D.) 56.7±16.8 years, BMI 31.8±4.6 kg/m2, HbA1c 8.45±1.78% and in 32 controls, age 39.2±16.0 years, BMI 35.9±9.25 kg/m2. In controls we also assessed parameters of insulin resistance (HOMA and insulin resistance index (IRI)), and in eight subjects MMP-2 and MMP-9 were also measured during 75 g oral glucose tolerance test (OGTT).
Results: Concentrations of both MMP-2 and MMP-9 were lower in subjects with type 2 DM (219±62 vs 305±63 ng/ml and 716±469 vs 1285±470 ng/ml, for MMP-2 and MMP-9, respectively, P<0.05). Control subjects were younger (P<0.05), but there was no significant difference in BMI. In diabetic subjects there was a significant correlation between MMP-9 and HbA1c (r=0.51, P<0.05), but neither group showed any correlation between MMPs and age or BMI. There was also no correlation between MMPs and HOMA or IRI. Interestingly, hyperglycaemia during OGTT did not change MMP-2 concentrations (367±36 vs 354±52 ng/ml, P=ns), but resulted in a significant fall in MMP-9 (from 1675±372 to 1276±422 ng/ml, P<0.05).
Conclusions: Concentrations of MMP-2 and MMP-9 were lower in subjects with type 2 diabetes than in non-diabetic controls. Regulation of concentrations of MMPs appears, however, to be complex, as short-lasting hyperglycaemia during OGTT results in a decrease in MMP-9 concentrations, while chronic hyperglycaemia, reflected by HbA1c, correlates with higher MMP-9 levels in subjects with type 2 diabetes. Further research is necessary to elucidate precise mechanisms responsible for diabetes-related alterations in concentrations of matrix metalloproteinases in humans.