Incidence Of Retinopathy In Type Research Articles

Impact of Age of Onset, Puberty, and Glycemic Control Followed From Diagnosis on Incidence of Retinopathy in Type 1 Diabetes: The VISS Study.

To evaluate sex, age at diabetes onset, puberty, and HbA1c, with subjects followed from diabetes diagnosis and during different time periods, as risk factors for developing diabetic simplex and proliferative retinopathy. In a population-based observational study, HbA1c for 451 patients diagnosed with diabetes before 35 years of age during 1983-1987 in southeast Sweden was followed for up to 18-24 years from diagnosis. Long-term mean weighted HbA1c (wHbA1c) was calculated. Retinopathy was evaluated by fundus photography and analyzed in relation to wHbA1c levels. Lower wHbA1c, diabetes onset ≤5 years of age, and diabetes onset before puberty, but not sex, were associated with longer time to appearance of simplex retinopathy. Proliferative retinopathy was associated only with wHbA1c. The time to first appearance of any retinopathy decreased with increasing wHbA1c. Lower wHbA1c after ≤5 years' diabetes duration was associated with later onset of simplex retinopathy but not proliferative retinopathy. With time, most patients developed simplex retinopathy, except for those of the category wHbA1c ≤50 mmol/mol (6.7%), for which 20 of 36 patients were without any retinopathy at the end of the follow-up in contrast to none of 49 with wHbA1c >80 mmol/mol (9.5%). Onset at ≤5 years of age and lower wHbA1c the first 5 years after diagnosis are associated with longer duration before development of simplex retinopathy. There is a strong positive association between long-term mean HbA1c measured from diagnosis and up to 20 years and appearance of both simplex and proliferative retinopathy.

Defective Myogenic Response of Retinal Vessels Is Associated With Accelerated Onset of Retinopathy in Type 1 Diabetic Individuals.

We seek to identify pathogenic mechanisms for diabetic retinopathy that can become therapeutic targets beyond hyperglycemia and hypertension. We investigated if a defective myogenic response of retinal arteries to increased perfusion pressure, which exposes capillaries to increased pressure and flow, is associated with the onset of clinical retinopathy. We examined prospectively the incidence of retinopathy in type 1 diabetic individuals tested 4 years earlier for the retinal arterial myogenic response, and in a cross-sectional study the prevalence of defective myogenic response in type 1 patients who had diabetic retinopathy. Among these, we contrasted early-onset (after 15 ± 2 years of diabetes, E-DR; n = 5) to late-onset (after 26 ± 3 years of diabetes, L-DR; n = 7) retinopathy. We measured the myogenic response using a laser Doppler blood flowmeter after a change in posture from sitting to reclining, which increases retinal perfusion pressure. Five of seven participants who 4 years prior had a defective myogenic response had now developed clinical retinopathy; as compared with only one of six participants who 4 years prior had a normal response (P = 0.10). In the cross-sectional study, all participants had normal retinal hemodynamics at steady state. In response to the postural change, only the E-DR group showed defective myogenic response (P = 0.005 versus controls, P = 0.02 versus L-DR) and abnormally high retinal blood flow (P = 0.016 versus controls). In type 1 diabetic patients, a defective myogenic response of retinal arteries to pressure is not required for the development of clinical retinopathy, but is prominently associated with an accelerated onset of retinopathy.

Prorenin and the (Pro)renin Receptor in Retinal Pathology

Blockade of angiotensin II (Ang II) has potential therapeutic benefit for ocular diseases including diabetic retinopathy and retinopathy of prematurity. Perhaps the most studied is diabetic retinopathy where angiotensin converting enzyme inhibition and angiotensin type 1 receptor blockade (AT1-RB) is beneficial. The importance of Ang II has recently been highlighted with DIRECT (DIabetic REtinopathy Candesartan Trial) reporting that the AT1-RB, candesartan, reduced the incidence of retinopathy in type 1 diabetic patients and enhanced regression in type 2 diabetic patients. Prorenin may also be a causative factor in diabetic retinopathy in humans, with early studies reporting that prorenin is elevated in both plasma and vitreous. Recently, interest in prorenin has re-emerged with the identification of a prorenin receptor [(P)RR] which binds both renin and prorenin and induces signal transduction pathways that are independent of Ang II. Studies by one group have reported that a particular (P)RR inhibitor provides protective effects in experimental retinopathy of prematurity and uveitis. However, controversy exists about the effectiveness of this (P)RR inhibitor with other groups failing to find organ protection. This review discusses these findings and evaluates whether prorenin and the (P)RR may be relevant for certain ocular diseases and a possible target for therapeutic intervention.

(Pro)renin Receptor: A Treatment Target for Diabetic Retinopathy?

Many lines of evidence implicate the renin-angiotensin system in the pathogenesis of diabetic retinopathy. A recent multicenter trial showed that angiotensin II type 1 (AT1) receptor blockade (ARB) reduced the incidence of retinopathy in type 1 diabetic patients and improved the regression of retinal disease in type 2 diabetic patients (1,2). However, the failure of ARB to prevent progression of diabetic retinopathy indicates a role for mechanisms additional to angiotensin II in its pathogenesis. In this issue of Diabetes , Satofuka et al. (3) provide evidence that prorenin and the (pro)renin receptor, acting in part through mechanisms unrelated to angiotensin II, may contribute to the pathogenesis of diabetic retinopathy. This evidence holds promise for new therapies for diabetic retinopathy and other complications of diabetes. Prorenin is a high–molecular weight biosynthetic precursor of renin. It has a low intrinsic activity of <2% of the activity of renin (4) because it has an amino-terminal 43–amino acid prosegment that masks the active site, thereby preventing access by the renin substrate—angiotensinogen. Renal juxtaglomerular cells are the only known site of renin production, whereas the kidney and a number of extrarenal tissues including adrenal, ovary, testis, placenta, and retina produce prorenin (5–7). Plasma prorenin concentrations are ∼10- to 20-fold higher than those of renin (4). Prorenin concentrations in plasma and vitreous fluid are increased in diabetic subjects (6,8), and plasma prorenin is a powerful marker for both prevalent and incident microvascular complications of diabetes, including nephropathy, retinopathy, and …

A 5‐year follow‐up study on the incidence of retinopathy in type 1 diabetes mellitus in relation to medical risk indicators

The aim of the present study was to describe the 5-year incidence of retinopathy in type 1 diabetes mellitus and to characterize risk indicators for the development and progression of retinopathy. A cross-sectional study of type 1 diabetic patients taken care of at a medical department. All type 1 diabetic patients attending the Department of Internal Medicine, University Hospital, Lund, during a 2-year period were offered ophthalmological examination. A total of 396 out of 461 (85.9%) initially examined type 1 diabetic patients formed the basis for this 5-year follow-up study. The degree of retinopathy was based on fundus photography or biomicroscopy. Degree of metabolic control was assessed by HbA1c levels, signs of nephropathy by albumin creatinine clearance ratio and urinary albumin levels. Blood pressure was measured in the supine position. Duration of diabetes, age, and insulin dosage were registered. The incidence of retinopathy was 47.2% and progression from background to severe retinopathy occurred in 41%. Risk indicators for the development of retinopathy were duration of diabetes (P < 0.001), degree of metabolic control (P < 0.001), insulin dosage (P < 0.05) and signs of nephropathy based on measurements of albumin creatinine clearance ratio (P < 0.01) and urinary albumin concentration (P < 0.05). Two risk indicators could be identified for progression of retinopathy, i.e. the degree of metabolic control (P < 0.01) and diastolic blood pressure (P < 0.05). The results suggest that apart from poor metabolic control, development of retinopathy in type 1 diabetes is associated with long diabetes duration and clinical signs of diabetic nephropathy. Progression of retinopathy is associated with poor metabolic control and elevated diastolic blood pressure levels.

Incidence of retinopathy in type I [insulin-dependent] diabetes: Association with clinical nephropathy

The association between the incidence of diabetic retinopathy and the development of diabetic nephropathy was studied in 110 Type I (insulin-dependent) diabetic patients during a period from 10 years before to 5 years after the onset of persistent proteinuria. This group of patients was compared with 110 diabetic patients, who were matched according to sex, age, and diabetes duration, but who were without proteinuria during the observation period. The cumulative incidence of proliferative retinopathy was 74% in patients with clinical nephropathy and 14% in patients free of proteinuria. The incidence of background retinopathy was 93% and 37%, respectively, and the incidence of retinopathy increased dramatically 5 years before the onset of proteinuria. Neither gender, age at onset of diabetes, nor blood pressure seemed to have much influence on the incidence of severe retinopathy. It is concluded that development of clinical diabetic nephropathy implies an extremely high risk of developing severe retinopathy. A common pathogenetic link may be suspected.