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

Diabetes Obes Metab. 2019 Mar;21(3):454-466. doi: 10.1111/dom.13538. Epub 2018 Oct 15.


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.

Keywords: GLP-1 analogue; diabetic retinopathy; glycaemic control; insulin therapy; type 1 diabetes; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / pathology*
  • Disease Progression
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Insulin / therapeutic use*
  • Pregnancy


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin