Glycaemic Variability and Glucose Excursions in GCK Diabetes Compared with Type 1 Diabetes and the Healthy Population: Implications for Therapeutic Targets in Diabetes

Abstract

Lifelong hyperglycaemia is present in GCK diabetes without causing microvascular diabetes complications.<br><br>Methods: We performed blinded CGM in GCK diabetes (n=13, 6 male, 7 female, median age 20yrs, range 7-48yrs). We assessed for diabetes complications by retinal photography, first-pass urine albumin:creatinine, and fasting blood tests. We compared CGM results from GCK diabetes to CGM from 13 youth with type 1 diabetes (median 16·8yrs, 11-18yrs, case-matched for sex, height, weight) and to published CGM results from healthy individuals.<br><br>Findings: Participants with GCK diabetes had no detectable diabetes complications, despite higher percentage time 10-13·9 mmol/L (median 5%, IQR 3-11%, range 0-50%) than healthy individuals (0%, IQR 0-0·2%). Glycaemic variability in GCK diabetes was similar to healthy individuals (coefficient of variation, CV, 17±3% for both). Youth with type 1 diabetes had higher CV (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.<br><br>Interpretation: After life-long diabetes duration of up to 48 years, GCK diabetes was associated with no diabetes complications, despite individuals spending up to 50% CGM time 10-13·9 mmol/L. GCK diabetes was notable for low glycaemic variability, which was comparable to results from healthy individuals, and which was significantly lower than found in type 1 diabetes. GCK diabetes may be a model of dysglycaemia which can be tolerated over a lifetime without inducing microvascular complications. Thus, efforts to reduce glycaemic variability may be of particular importance in minimising microvascular complications in type 1 diabetes.