How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with Type 1 diabetes?

Diabet Med. 2020 Apr;37(4):513-521. doi: 10.1111/dme.13911. Epub 2019 Feb 11.


In 2011, the James Lind Alliance published a 'top 10' list of priorities for Type 1 diabetes research based on a structured consultation process. Whether reducing fluctuations in blood glucose can prevent long-term microvascular and macrovascular complications was one of these. In this narrative review, 8 years on, we have assessed the updated evidence for the assertion that increased glucose variability plays an independent and clinically important role in the complications of Type 1 diabetes, over and above mean blood glucose and the effects of hypoglycaemia: the 'glucose variability hypothesis'. Although studies in cultured cells and ex vivo vessels have been suggestive, most studies in Type 1 diabetes have been small and/or cross-sectional, and based on 'finger-prick' glucose measurements that capture glucose variability only in waking hours and are affected by missing data. A recent analysis of the Diabetes Control and Complications Trial that formally imputed missing data found no independent effect of short-term glucose variability on long-term complications. Few other high-quality longitudinal studies have directly addressed the glucose variability hypothesis in Type 1 diabetes. We conclude that there is little substantial evidence to date to support this hypothesis in Type 1 diabetes, although increasing use of continuous glucose monitoring provides an opportunity to test it more definitively. In the meantime, we recommend that control of glycaemia in Type 1 diabetes should continue to focus on the sustained achievement of target HbA1c and avoidance of hypoglycaemia.

Publication types

  • Review

MeSH terms

  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Blood Glucose Self-Monitoring
  • Diabetes Complications / blood
  • Diabetes Complications / etiology
  • Diabetes Complications / prevention & control*
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Glycemic Control* / methods
  • Glycemic Control* / standards
  • Humans
  • Hypoglycemic Agents / therapeutic use


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents