Background: Transient Neonatal Diabetes Mellitus (TNDM) is a rare genetic beta cells dysfunction leading to hyperglycaemia that resolves in early childhood. About 80% of patients relapse during adolescence or adulthood. Glucose homeostasis had not been investigated in adulthood.
Objective and hypotheses: To investigate insulin secretion and insulin sensitivity in adults affected with TNDM or in their 1st degree mutated relatives.
Method: The patients originated from the French Neonatal Diabetes Study Group cohort. We selected those with TNDM and aged 18 years or more in September 2013, and their 1st degree adult mutated relatives. We measured insulin sensitivity using a two-step hyperinsulinemic euglycemic clamp and maximal insulin secretion in response to a graded intra-venous glucose infusion followed by a bolus of arginine. Body composition was assessed using dual energy X-ray absorptiometry.
Results: We included 15 individuals (6 males, 9 females). Median age was 36 (1855) years. Median BMI was 21 (17.530.9)kg/m2. We identified abnormalities in 6q24 (n=2, 13.3%), and mutations in ABCC8 (n=9, 60.1%) and KCNJ11 (n=2, 13.3%) genes. 2 (13.3%) patients had no identified molecular defect. 8 (53%) patients had a TNDM. Among them 6 (40%) had a recurrence of diabetes. 7 (47%) patients were 1st degree relatives. Among them, 4 (27%) had a diabetes. Mean insulin secretion rate in the last 40 minutes of the glucose ramp was as follow: 4.9 pmol/kg per min in 10 (67%) diabetic patients, and 12.5 pmol/kg per min in 5 (33%) non-diabetic patients, There was no significant disturbance in insulin sensitivity and the mean M-value was 12.8 mg/kg per min.
Conclusion: Our study suggests that monogenic diabetes in adulthood is due to a partial insulin secretion defect, not associated with insulin resistance. These results underscore the importance of genetic evaluation in order to personalize the treatment in adulthood.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology