Macular Edema Reflects Generalized Vascular Hyperpermeability in Type 2 Diabetic Patients With Retinopathy

Abstract

OBJECTIVE—Diabetic maculopathy (DMa) is the most prevalent sight-threatening type of retinopathy in type 2 diabetes and a leading cause of visual loss in the western world. The disease is characterized by hyperpermeability of retinal blood vessels and subsequent formation of hard exudates and macular edema, the degree of which can be estimated by measurement of retinal thickness. We examined associations between retinal thickness as evaluated by optical coherence tomography scanning (OCT), glomerular leakage as evaluated by urinary albumin excretion rate (UAE), and general vascular leakage as evaluated by the transcapillary escape rate of albumin (TERalb) in type 2 diabetic patients with and without DMa. RESEARCH DESIGN AND METHODS—In 20 type 2 diabetic patients with DMa and 20 type 2 diabetic patients without retinopathy matched for age, sex, and duration of diabetes, we performed OCT, fundus photography, fluorescein angiography, and 24-h ambulatory blood pressure measurement. UAE was determined by radioimmunoassay. TERalb was determined as the initial disappearance of intravenously injected 125I-labeled human serum albumin. RESULTS—Patients with diabetic maculopathy had higher HbA1c (8.5 ± 1.5 vs. 7.4 ± 1.2%, P < 0.05) and higher total cholesterol (5.8 ± 0.7 vs. 5.2 ± 0.9 mmol/l, P < 0.05) than patients without retinopathy. UAE was higher in the DMa group than in the group with no retinopathy (9.3 ×/÷ 3.1 vs. 3.9 ×/÷ 1.9 μg/min, P < 0.01). There was no difference in TERalb between the two groups (6.0 ± 1.6 vs. 6.6 ± 1.5%, NS). In the group with DMa, OCT, TERalb, and UAE correlated significantly (OCT versus TERalb: r = 0.55, P < 0.05; OCT versus UAE: r = 0.58, P < 0.01; UAE versus TERalb: r = 0.81, P < 0.01). Conversely, there were no correlations between these three parameters in the group without retinopathy. CONCLUSIONS—Macular edema seems to reflect a generalized vascular leakage in type 2 diabetic patients.

Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden

“…In agreement, in our study, patients with maculopathy had the highest urinary levels of IgG2 and IgG2/IgG4 suggesting a widespread capillary damage with a general change in size selectivity of the basements membrane in the capillaries. We thus confirmed a previous study in type 2 diabetic patients with macular oedema who had a generalized vascular hyperpermeability with an increased transcapillary escape rate and urinary excretion rate of albumin (Knudsen et al 2002). In a previous study of patients with type 1 diabetes, both an increased excretion of IgG2 and IgG4 was found in normoalbuminuric patients (Torffvit and Rippe 1999).…”

“…A study of the transcapillary escape rate and the urinary excretion rate of albumin has suggested that macular edema reflects generalized vascular hyperpermeability at least in type 2 diabetic patients (Knudsen et al 2002). Measurements of urinary IgG2 together with IgG2/IgG4 ratios are used to assess glomerular size selectivity whereas urinary IgG4 evaluates charge selectivity (Tencer et al 1999).…”

Retinal Hemodynamics in Early Diabetic Macular Edema

“…The urinary albumin-to-creatinine ratio was higher in those with retinopathy and DME compared with those without retinopathy. Increased urinary albumin-to-creatinine ratio with increasing risk of DME reflects a decline in renal function and a shift in the osmotic balance of blood that might favor the development of DME (59,60).…”

Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients

“…An elevated pulse pressure (PP) is strongly associated with micro- [1][2][3][4][5] as well as macrovascular [1,[6][7][8] complications in type 2 diabetic patients. In a large observational study including 954 elderly type 2 diabetic patients [9], ambulatory PP was a strong and independent predictor of progression of nephropathy during a 2 year follow-up period.…”