Diabetic Retinopathy and Endothelial Dysfunction in Patients with Type 2 Diabetes Mellitus

BACKGROUND: We investigated the relationship between endothelial dysfunction and diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: We used a cross-sectional design to examine 167 patients with type 2 diabetes mellitus. All patients underwent biochemical and ophthalmological examination. We assessed endothelial dysfunction by a flow-mediated vasodilation method of the brachial artery. Changes in vasodilation (flow-mediated vasodilatation, %FMD) were expressed as percent change over baseline values. RESULTS: The mean+/-standard deviation of patient age was 54.1+/-8.6 years. The %FMD was significantly lower in patients with DR than without DR. The prevalence of retinopathy decreased across increasing tertiles of %FMD. After adjusting for patients' age, sex, diabetes duration, use of insulin, use of antihypertensive, antiplatelet, and lipid lowering medications, systolic blood pressure, fasting plasma glucose, 2-hour plasma glucose, glycated hemoglobin, and urinary albumin excretion, participants with a reduced %FMD were more likely to have DR (odds ratio, 11.819; 95% confidence interval, 2.201 to 63.461; P=0.004, comparing the lowest and highest tertiles of %FMD). CONCLUSION: Endothelial dysfunction was associated with DR, which was most apparent when the endothelial dysfunction was severe. Our study provides insights into the possible mechanism of the influence of endothelial dysfunction on the development of DR.

Inhibition of Neointima Formation and Migration of Vascular Smooth Muscle Cells by Anti-vascular Endothelial Growth Factor Receptor-1 (Flt-1) Peptide in Diabetic Rats / 대한흉부외과학회지

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCs' migration under high glucose conditions. MATERIAL AND METHOD: The balloon-injury method was employed to induce neointima formation by VEGF. For 14 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5 mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). RESULT: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, (0.15+/-0.04 mm2 and 36.03+/-3.78% compared to 0.24+/-0.03 mm2 and 61.85+/-5.11%, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from 52.82+/-4.20% to 38.11+/-6.89% by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCs. CONCLUSION: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition.

Glucose-Insulin-Potassium as an Adjunctive Therapy in Acute Myocardial Infarction

BACKGROUND AND OBJECTIVES: Glucose-insulin-potassium (GIK) fluid infusion may improve the myocardial energy metabolism in the ischemic condition. A prospective randomized clinical trial was designed to determine whether a GIK fluid infusion can reduce the ventricular remodeling in acute myocardial infarction. SUBJECTS AND METHODS: For the patients with acute myocardial infarction, during thrombolytic therapy with urokinase, GIK fluid (26% glucose 1000 mL, 50 IU insulin, and 80 mmol KCl) was administered for 24 hours. The ventricular volumes and function were evaluated by echocardiography during the admission period, at 6 months and at 12 months following discharge. RESULTS: This trial was done prospectively for 2 years in 73 patients; the GIK group included 41 patients and the control group included 32 patients. The median value of "the pain to door time" was 195 minutes in the GIK group and it was 120 minutes in the control group (p=NS). The wall motion score was 1.52+/-0.39 in the GIK group and it was 1.39+/-0.35 in the control group. The left ventricular volumes, ejection fractions, cardiac indices and the globular indices showed no significant difference between the two groups. The side effects of the GIK fluid were mild phlebitis in 6 patients (14.6%) and congestive heart failure in 5 patients (12.2%). CONCLUSION: This trial could not verify the beneficial effects of administering GIK fluid on the ventricular remodeling after acute myocardial infarction. The limitations of this trial were as follows: "the pain to door time" was too long and the severity of the myocardial infarction was mild. Low rates for the echocardiogrphy follow-up and the randomization failure in a few patients were also noted.