The Association Between HbA1c and Time in Hypoglycemia During CGM and Self-Monitoring of Blood Glucose in People With Type 1 Diabetes and Multiple Daily Insulin Injections: A Randomized Clinical Trial (GOLD-4)

Objective: According to recent guidelines, individuals with type 1 diabetes should spend less than 4.0% per day with glucose levels <3.9 mmol/L (<70 mg/dL) and less than 1.0% per day <3.0 mmol/L (<54 mg/dL).

Research methods: In the GOLD randomised cross-over trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomised to Continuous Glucose Monitoring (CGM) or conventional therapy with self-monitoring of blood glucose (SMBG) and evaluated over 16 months. We estimated the association between time spent in hypoglycaemia and various mean glucose and HbA1c levels.

Results: Time spent in hypoglycaemia (<3.9 mmol/L and <3.0 mmol/L) increased significantly with lower mean HbA1c and mean glucose levels during both CGM and conventional therapy. During CGM, 24 (57.1%) individuals with HbA1c <7.5 % (<58 mmol/mol) had <1.0% time spent in hypoglycaemia <3.0 mmol/L and 23 (54.8%) had <4.0% time spent in hypoglycaemia <3.9 mmol/L. During CGM, mean time spent in hypoglycaemia for individuals with mean HbA1c 7.0% (52 mmol/mol) was estimated to be 5.4% for <3.9 mmol/L and 1.5% for <3.0 mmol/L. The corresponding values during SMBG were 9.2% and 3.5%, respectively. Individuals with mean glucose levels of 8 mmol/L spent 4.9% more time with glucose levels <3.9 mmol/L and 2.8% more time <3.0 mmol/L during SMBG compared with CGM.

Conclusions: Reaching current targets for time in hypoglycaemia and at the same time HbA1c targets is challenging for type 1 diabetes patients treated with MDI both with CGM and SMBG monitoring. However, CGM is associated with considerably less time in hypoglycaemia than SMBG at a broad range of HbA1c levels and is crucial for patients with MDI treatment to have a chance to approach hypoglycaemia targets.