Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: A review

Abstract

Worsening of diabetic retinopathy (DR) is associated with the initiation of effective treatment of glycaemia in some patients with diabetes. It has been associated with risk factors such as poor blood-glucose control and hypertension, and it manifests prior to the long-term benefits of optimizing glycaemic control. The majority of evidence supports an association of large and rapid reductions in blood-glucose levels with early worsening of DR. Despite a general awareness of early worsening within the diabetes community, mechanisms to explain the phenomenon remain speculative. We provide an overview of early worsening of DR and its pathophysiology based on current data. We describe the phenomenon in various settings, including in patients receiving insulin- or non-insulin-based treatments, in those undergoing bariatric surgery, and in pregnant women. We discuss various mechanisms and theories that have been suggested to explain this paradoxical phenomenon, and we summarize the implications of these in clinical practice.

<p>Comparative Effectiveness of Long-Acting GLP-1 Receptor Agonists in Type 2 Diabetes: A Short Review on the Emerging Data</p>

“…Increased diabetic retinopathy (DR) events seen with semaglutide in SUSTAIN 6 are thought to be related to rapid reduction in glucose levels in subjects with poor glycaemic control and existing retinopathy. 11,23,24 It is of note that a non-significant increase in DR events was also seen in the CVOTs for both liraglutide and dulaglutide 10,14 consistent with an impact of potent glucose-lowering. Other aspects will also impact on clinical decisionmaking, for example, the injection preparation (problematic for exenatide ER and albiglutide) as well as the design of administration device, which may favour dulaglutide.…”

Pragmatic management of low‐energy diets in people with type 2 diabetes in primary care: a decision aid for clinicians

“…Patients commencing a low‐energy diet who have very poor glycaemic control will inevitably experience a significant reduction in carbohydrate intake and plasma glucose concentration. Very rapid improvement in diabetes control has been linked to microvascular complications particularly retinopathy, gastrointestinal disturbances and constitutional upset, especially in people taking insulin . Although there is no evidence per se that glycaemic improvement associated with short‐term use of‐low energy diets can precipitate or worsen pre‐existing microvascular disease, we pragmatically suggest that attempts are made to improve control as a precursor to joining a programme if the HbA 1c is > 10% or 86 mmol/mol.…”

Adjuvant Therapies in Diabetic Retinopathy as an Early Approach to Delay Its Progression: The Importance of Oxidative Stress and Inflammation

“…Reported cases have found this intervention beneficial in glycemic control, but there are no specific trials assessing VLCDs in DR [62,63]. Nevertheless, caution is needed since VLCDs lower than 600 kcal should only be employed under close clinical supervision [27], and rapid reduction of systemic glucose is associated with worsening of DR [64].…”