digoxin and Diabetic-Retinopathy

To test the hypothesis that digoxin, an inhibitor of Na(+)-K(+)-ATPase activity, accelerates the progression of diabetic retinopathy.. We compared the incidence and risk of retinopathy in 120 digoxin-taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs. 1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading stereoscopic color photographs using the modified Airlie House classification scheme, and a two-step difference in baseline retinopathy grade was considered significant.. After controlling for other risk factors, we found no statistically significant association with either 4-year incidence of retinopathy (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients taking digoxin at baseline compared with those not taking digoxin.. These data suggest that digoxin therapy does not adversely affect the course of diabetic retinopathy.

Topics: Adult; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Digoxin; Female; Humans; Incidence; Longitudinal Studies; Male; Risk Factors; Wisconsin

In proliferative diabetic retinopathy (PDR), retinal ischemia promotes neovascularization (NV), which can lead to profound vision loss in diabetic patients. Treatment for PDR, panretinal photocoagulation, is inherently destructive and has significant visual consequences. Therapies targeting vascular endothelial growth factor (VEGF) have transformed the treatment of diabetic eye disease but have proven inadequate for treating NV, prompting exploration for additional therapeutic options for PDR patients. In this regard, extracellular proteolysis is an early and sustained activity strictly required for NV. Extracellular proteolysis in NV is facilitated by the dysregulated activity of matrix metalloproteinases (MMPs). Here, we set out to better understand the regulation of MMPs by ischemia in PDR. We demonstrate that accumulation of hypoxia-inducible factor-1α in Müller cells induces the expression of VEGF, which, in turn, promotes increased MMP-2 expression and activity in neighboring endothelial cells (ECs). MMP-2 expression was detected in ECs in retinal NV tissue from PDR patients, whereas MMP-2 protein levels were elevated in the aqueous of PDR patients compared with controls. Our findings demonstrate a complex interplay among hypoxic Müller cells, secreted angiogenic factors, and neighboring ECs in the regulation of MMP-2 in retinal NV and identify MMP-2 as a target for the treatment of PDR.

Topics: Animals; Diabetic Retinopathy; Digoxin; Enzyme Activation; Ependymoglial Cells; Female; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Retinal Neovascularization; Vascular Endothelial Growth Factor A

The aim of this study was to compare the intensity of typical late complications in diabetic patients (n = 65, 28 type I, 37 type II) who were not on glycoside drugs with low vs. high serum levels of digoxin-like immunoreactive factor (DLIF: group I, n = 42, DLIF < or = the detection limit of 0.2 ng ml-1; and group II, n = 23, mean +/- SEM: 1.17 +/- 0.31 [0.25-4.96] ng ml-1). For detection of nephropathy, urinary albumin excretion (24 h) and creatinine clearance tests were used. For coronary heart disease a questionnaire and standard ECG; for peripheral occlusive vascular disease a questionnaire; for eye disease a fundoscopy; for neuropathy a neurological score system; and for autonomic neuropathy a standardized test battery was employed. Patients with high DLIF levels showed better test results in vibratory perception (95.7 +/- 1.5 vs. 82.8 +/- 3.8%, normal finding = 100%, 2p = 0.016), had better percentile localizations concerning maximal pupillary area in darkness (28.4 +/- 6.6 vs. 8.1 +/- 1.8%, 2p = 0.0004), contraction velocity at 1 s (21.5 +/- 5.8 vs. 8.0 +/- 2.2%, 2p = 0.012), and dilation velocity at 6 s (23.0 +/- 6.8 vs. 10.5 +/- 2.5%, 2p = 0.041), had less retinopathy (with retinopathy: 26.1% vs. 64.3%, 2p = 0.0028), and better percentile localizations in the respiratory sinus arrhythmia test (68.4 +/- 7.3 vs. 44.1 +/- 4.9%, 2p = 0.0064). There was no difference concerning nephropathy, blood pressure, coronary heart disease and peripheral vascular disease. Separate analysis according to the type of diabetes confirmed the results in each group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Blood Proteins; Cardenolides; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Digoxin; Female; Humans; Male; Middle Aged; Saponins; Severity of Illness Index

Topics: Blood Proteins; Cardenolides; Catecholamines; Diabetes Mellitus; Diabetic Neuropathies; Diabetic Retinopathy; Digoxin; Erythrocyte Membrane; Humans; Hypertension; Insulin; Obesity; Saponins; Sodium-Potassium-Exchanging ATPase

In a population-based study in southern Wisconsin, 1370 diabetic persons diagnosed after 29 years of age were examined using standard protocols to determine the prevalence of proteinuria and associated risk variables. Proteinuria (greater than or equal to 0.30 g/L) was present in 18.0% of persons taking insulin and 12.2% of the persons not taking insulin. Proliferative retinopathy and proteinuria were associated with each other. Proteinuria was also associated with increasing duration of diabetes, high systolic blood pressure, use of digoxin, and being male, but not with a history of cigarette smoking or metabolic control as measured by glycosylated hemoglobin.

Topics: Adult; Age Factors; Aged; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Digoxin; Female; Humans; Hypertension; Male; Middle Aged; Proteinuria; Time Factors

Topics: Bilirubin; Blood Chemical Analysis; Creatine Kinase; Diabetic Retinopathy; Digoxin; False Positive Reactions; Fluorescein; Fluorescein Angiography; Fluoresceins; Humans; Hydrocortisone; Isoenzymes