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?

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. What's new? Hyperglycaemia is the most important modifiable risk factor for both microvascular and macrovascular complications of Type 1 diabetes. Intensive control of blood glucose can substantially prevent and delay these complications. There is currently insufficient evidence to answer the James Lind research question ‘How tightly controlled do fluctuations in blood glucose need to be to reduce complications?’. Efforts to reduce complications by improving glycaemic control in Type 1 diabetes should continue to focus on sustained achievement of target HbA1c and avoidance of hypoglycaemia. More widespread use of continuous and flash glucose monitoring devices offers opportunities for more definitive research on this topic (both cohort and intervention studies).