Ocular hyperperfusion following onset of intensified insulin therapy is inversely correlated with plasma endothelin-1 in Type I diabetes

Abstract

Aims/hypothesis. It has been reported that improvement of metabolic control by intensified insulin therapy in patients with Type I (insulin-dependent) diabetes mellitus is associated with alterations in ocular blood flow. We hypothesized that these changes in ocular blood flow could be associated with alterations of plasma insulin, glucose or endothelin concentration. Methods. In 16 patients with Type I diabetes ocular haemodynamic parameters were assessed daily during the first 5 days of institution of intensified insulin therapy and plasma concentrations of glucose, insulin, and endothelin-1 plasma were measured. Retinal white blood cell flux was estimated with the blue field entoptic technique. Pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. Results. Retinal white blood cell flux (p=0.0015) and ocular fundus pulsation amplitude (p<0.001) increased during institution of strict metabolic control. Changes in ocular haemodynamic variables were inversely correlated with concentrations of plasma ET-1, but not with that of insulin or glucose. Conclusions/interpretation. These data indicate that institution of improved metabolic status is paralleled by rapid changes in the production of ET-1, which could in turn affect ocular perfusion. [Diabetologia (2002) aimed to achieve glycaemic control as close as possible to the non-diabetic range [1]. Moreover, the DCCT showed that total lifetime exposure to glycaemia is the principal determinant of the risk of retinopathy [2]. However, shortly after the institution of strict diabetic control some patients show progression of diabetic retinopathy [1,3]. Previous studies indicate that this progression of diabetic retinopathy is associated with changes in retinal blood flow [4,5,6].The reasons for these immediate changes in retinal blood flow and their role in the development of retinopathy are not clear. On the one hand alterations in concentrations of plasma insulin and plasma glucose could affect ocular vascular tone, because insulin and glucose induce vasodilation at the level of the ocular vasculature [7,8,9,10,11,12]. Alternatively the institution of strict metabolic control could exert effects The Diabetes Control and Complications Trial (DCCT) demonstrated a reduction in the development and progression of the long-term complications of Type I diabetes with intensive insulin therapy

Twelve‐hour reproducibility of retinal and optic nerve blood flow parameters in healthy individuals

“…When discussing the applicability of these devices for clinical studies and clinical routine, the intrinsic limitations of each method have to be considered in addition to the issues related to variability. The blue field entoptic technique assesses WBC flux only and experimental conditions that uncouple retinal RBC and WBC flux can be implemented easily (Fuchsjager‐Mayrl et al. 2002).…”

Response of retinal arteriole diameter to increased blood pressure during acute hyperglycaemia

“…Findings from animal and human studies suggest that such changes may include disturbances in the formation and release of vasoactive factors such as nitric oxide and endothelins (Lash et al. 1999; Nutt & O'Neil 2000; Bohlen & Nase 2001; Fuchsjager‐Mayrl et al. 2002; Taubert et al.…”

“…It is therefore conceivable that the reduced diameter response reported during oral administration of glucose may have been due to changes in the metabolism caused by factors other than glucose load. Findings from ani-mal and human studies suggest that such changes may include disturbances in the formation and release of vasoactive factors such as nitric oxide and endothelins (Lash et al 1999;Nutt & O'Neil 2000;Bohlen & Nase 2001;Fuchsjager-Mayrl et al 2002;Taubert et al 2004), and changes in plasma insulin (Su et al 1996). Therefore, further studies are needed to elucidate the role of each of these individual factors.…”

Risks and side effects of islet transplantation

“…This was thought to be similar to the changes in retinopathy that can occur with the sudden instigation of tight glycemic control with intensive insulin therapy [33,34] and may be correlated with changes in plasma endothelin-1 levels [35]. In these four cases, laser photocoagulation was required and stability was then achieved.…”