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Jeffrey D. McBride, Alicia Jenkins, Tim Lyons, Jian-Xing Ma; Serum Kallistatin is Increased in Type 2 Diabetic Patients with Microvascular Complications and Correlates with the Presence of Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1267.
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Human kallistatin is a secreted, glycoprotein and a serine proteinase inhibitor that specifically binds to tissue kallikrein, and it has multiple functions, e.g., anti-angiogenic, anti-fibrogenic, anti-inflammatory, and anti-oxidative activities independent of its direct tissue kallikrein inhibition. It is produced mostly by the liver, but is also secreted by the retina and blood vessels. Human kallistatin is decreased in the vitreous space of diabetics with retinopathy versus that in controls. Recently, our group reported that serum kallistatin is significantly elevated in type 1 diabetic patients with microvascular complications, compared to non-diabetic controls or diabetic patients without complications. Our hypothesis is that average serum kallistatin may be increased in the sera of type 2 diabetic patients compared to non-diabetic controls and type 2 patients without microvascular complications.
We collected serum samples from patients at the University of Oklahoma Health Sciences Center: 54 non-diabetic control subjects; 36 type 2 diabetic patients with no microvascular complications; and 44 type 2 diabetic patients with at least one microvascular complication (total n=134). We measured kallistatin concentration in the sera using a sandwich enzyme-linked immunosorbent assay (ELISA).
Serum kallistatin levels (µg/mL ± S.E.M.) were 26.5 ± 2.0 µg/mL in non-diabetic controls; 22.0 ± 1.9 µg/mL in type 2 patients without complications; and 32.8 ± 2.4 µg/mL in type 2 diabetic patients with microvascular complications (ANOVA, p= 0.0012). The trend was largely due to male patients: 23.3 ± 1.8 µg/mL in male controls; 24.4 ± 4.2 µg/mL in male type 2 patients without complications; and 35.2 ± 3.2 µg/mL in male type 2 diabetic patients with microvascular complications (ANOVA, p= 0.0026). Serum kallistatin levels were higher in type 2 diabetic patients with retinopathy (43.1 ± 6.5) versus type 2 diabetic patients with no retinopathy present (26.0 ± 1.5) (p= 0.00095). In type 2 diabetics, kallistatin levels correlated with hemoglobin A1c (p= 0.0094) and urine albumin/creatinine ratio (p= 0.0032).
Average serum kallistatin is elevated in the serum of type 2 diabetic patients with microvascular complications, suggesting potential value as a biomarker to predict retinopathy.
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