Glycaemic Variability and Glucose Excursions in GCK Diabetes Compared With Type 1 Diabetes and the Healthy Population

ABSTRACT Aim Monogenic diabetes due to abnormalities in the GCK gene causes lifelong hyperglycaemia without microvascular complications. We aimed to compare dysglycaemia in GCK diabetes to Type 1 diabetes. Methods We performed blinded Continuous Glucose Monitoring (CGM) in GCK diabetes ( n = 13, 6 male, median age 20 years, range 7–48 years). We assessed diabetes complications including retinal photography and first‐morning urine albumin: creatinine. We compared CGM results from GCK diabetes to 13 youth with Type 1 diabetes (median 16.8 years, range 11–18 years, case‐matched for sex, height, weight) and to published CGM results from healthy individuals. Results Participants with GCK diabetes had no detectable diabetes complications, despite higher percentage time > 10 mmol/L (median 5%, IQR 3%–11%, range 0%–50%) than healthy individuals (0%, IQR 0%–0.2%). Glycaemic variability (GV) by coefficient of variation in GCK diabetes was similar to healthy individuals, 17% ± 3% for both. Youth with Type 1 diabetes had higher GV (37% ± 5%, p < 0.001) and percentage CGM time 10–13.9 mmol/L (36%, IQR 26%–47%, p < 0.001) than those with GCK diabetes. Conclusions After life‐long diabetes duration of up to 48 years, GCK diabetes had no associated diabetes complications, despite individuals spending up to 50% time with elevated glucose 10–13.9 mmol/L. GCK diabetes had low GV, comparable to results from healthy individuals, but significantly lower than found in Type 1 diabetes. GCK diabetes may represent a model of dysglycaemia which can be tolerated over a lifetime without microvascular complications. Efforts to reduce GV may be of particular importance in minimising microvascular complications in Type 1 diabetes.