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)

Abstract

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 HbA 1c levels. RESULTS Time spent in hypoglycemia (<3.9 mmol/L and <3.0 mmol/L) increased significantly with lower mean HbA 1c and mean glucose levels during both CGM and conventional therapy. During CGM, 24 (57.1%) individuals with HbA 1c <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 HbA 1c 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 HbA 1c 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 HbA 1c levels and is crucial for patients with MDI treatment if they are to have a chance to approach hypoglycemia targets.

Glycemic Metrics Derived From Intermittently Scanned Continuous Glucose Monitoring

“…This indicates that the wisdom of attempting TIR > 70% should always be evaluated on the background of achieved GMI or mean glucose and TBR. 20 We found a curvilinear relation between TIR and GMI and recognize a similar result from a pediatric population. 21…”

“…Even with a less ambitious TIR of 60%, a recent study noticed a corresponding mean TBR of 4.2% for patients with rtCGM and 7.7% for those with SMBG. 20 This underscores the importance of individualized and realistic treatment goals. We are not aware of similar presentations of data for comparison.…”

2021 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association

“…For adults who treated with MDIs of prandial and basal insulin or insulin pumps, training should be provided professionally and systematically (NRS, General). All adult T1DM patients should be encouraged to use real-time CGM devices to control blood glucose and lower the risk of hypoglycemia (RCT, General) [ 135 - 137 ]. Adults with T2DM who require MDIs may use realtime CGM devices for glycemic control (RCT, Limited) [ 138 ].…”

Hypoglycaemia: Still the main drawback of insulin 100 years on: “From man to mouse”

“…For these reasons, despite improvements in the diagnosis and treatment of diabetes, exposure to hypoglycaemia remains the most feared consequence of insulin treatment. The recent GOLD‐4 clinical trial reported that individuals with Type 1 diabetes and average blood glucose of 8 mmol/L spend 12% of their time below 3.9 mmol/L and 4.9% below 3 mmol/L 9 . Plasma blood glucose was measured using self‐monitoring blood glucose meters or continuous glucose monitors (CGM).…”

“…Plasma blood glucose was measured using self‐monitoring blood glucose meters or continuous glucose monitors (CGM). Time spent in the hypoglycaemic range was reduced in individuals with higher average blood glucose and those using CGM 9 . Non‐severe hypoglycaemia is estimated to occur twice weekly in people with Type 1 diabetes, whereas episodes of severe hypoglycaemia are predicted to occur between 1 and 3 annually in a large proportion of those with Type 1 diabetes 4,10 .…”