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Published on: May 2, 2025
Urinary matrix metalloproteinase-8 and -9 activities in type 2 diabetic subjects: A marker of incipient diabetic
Nynke J van der Zijl1, Roeland Hanemaaijer, Maarten E Tushuizen
1Department of Endocrinology/Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands. nj.vdzijl@vumc.nl
Abstract:
Matrix metalloproteinases (MMPs) may play a pathophysiological role in the development of diabetic nephropathy (DN). We hypothesized that urinary MMP activity in patients with type 2 diabetes mellitus (T2DM) is related to a decline in renal function. We determined MMP-2, -8 and -9 activity in 24-h urine collections in relation to risk factors for DN in T2DM patients with (UA, n=27) and without albuminuria (NA, n=48) and controls (CO, n=28). MMP-8 and -9 levels were highest in UA patients (P<0.01). Of UA patients, 93% had at least one MMP increased, compared to 78% of NA patients and 46% of CO (P=0.001). Age, diabetes duration, BMI, systolic blood pressure, fasting plasma glucose, HbA1c and renal function were determinants of MMP-8 and -9 (P<0.05). In summary, MMP-8 and -9 are highest in T2DM UA patients. MMP-9, showed the strongest associations with clinical parameters related to DN.
Insights
Urinary matrix metalloproteinases (MMPs), particularly MMP-8 and MMP-9, are elevated in patients with type 2 diabetes and albuminuria, indicating a link to kidney function decline.
Area of Science:
- Nephrology
- Endocrinology
- Biochemistry
Background:
- Diabetic nephropathy (DN) is a significant complication of type 2 diabetes mellitus (T2DM).
- Matrix metalloproteinases (MMPs) are implicated in the pathophysiological processes underlying DN.
- Urinary MMP activity may serve as a biomarker for renal function decline in T2DM.
Purpose of the Study:
- To investigate the relationship between urinary MMP activity and renal function in T2DM patients.
- To compare MMP levels in T2DM patients with and without albuminuria (UA) against healthy controls (CO).
- To identify clinical determinants associated with elevated MMP levels in T2DM.
Main Methods:
- Quantification of MMP-2, MMP-8, and MMP-9 activity in 24-hour urine collections.
- Study groups included T2DM patients with albuminuria (UA, n=27), T2DM patients without albuminuria (NA, n=48), and controls (CO, n=28).
- Analysis of risk factors for DN, including age, diabetes duration, BMI, blood pressure, glucose levels, HbA1c, and renal function.
Main Results:
- MMP-8 and MMP-9 levels were significantly higher in UA patients compared to NA and CO groups (P<0.01).
- Elevated MMP levels were observed in 93% of UA patients, 78% of NA patients, and 46% of CO.
- MMP-8 and MMP-9 levels were significantly associated with age, diabetes duration, BMI, systolic blood pressure, fasting plasma glucose, HbA1c, and renal function (P<0.05).
Conclusions:
- MMP-8 and MMP-9 are elevated in T2DM patients with albuminuria, suggesting a role in DN pathogenesis.
- MMP-9 demonstrated the strongest correlation with clinical parameters associated with diabetic nephropathy.
- Urinary MMP activity, particularly MMP-9, may serve as a valuable biomarker for assessing renal function and DN progression in T2DM.
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