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)

Diabetes Care. 2020 Sep;43(9):2017-2024. doi: 10.2337/dc19-2606. Epub 2020 Jul 8.

Abstract

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

Research design and methods: In the GOLD randomized crossover trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomized 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 hypoglycemia and various mean glucose and HbA1c levels.

Results: Time spent in hypoglycemia (<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 hypoglycemia <3.0 mmol/L and 23 (54.8%) had <4.0% time spent in hypoglycemia <3.9 mmol/L. During CGM, mean time spent in hypoglycemia 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% units more time with glucose levels <3.9 mmol/L and 2.8% units more time <3.0 mmol/L during SMBG compared with CGM.

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

Trial registration: ClinicalTrials.gov NCT02092051.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Blood Glucose Self-Monitoring
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Administration Schedule
  • Female
  • Glycated Hemoglobin / analysis*
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / blood*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / pathology
  • Injections, Subcutaneous
  • Insulin / administration & dosage*
  • Insulin / adverse effects
  • Male
  • Middle Aged
  • Sweden
  • Time Factors

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT02092051
  • figshare/10.2337/figshare.12357506