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

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.