Impact of overweight on glucose homeostasis in MODY2 and MODY3

Impact of overweight on glucose homeostasis in MODY2 and MODY3Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes, as it accounts for approximately 1%-2% of all cases of diabetes.1 MODY2 is caused by mutations in the gene encoding glucokinase (GCK), whereas MODY3 is due to mutations in the hepatocyte nuclear factor 1A (HNF1A) gene.Obesity has become prevalent and the aim of this study was to investigate to what extent BMI and age affected fasting serum glucose and glycosylated haemoglobin (HbA 1c ) in female and male MODY2 and MODY3 probands.We searched the Norwegian MODY Registry at the Department of Paediatrics and Adolescents, Haukeland University Hospital, for probands diagnosed with either MODY2 or MODY3.2,3 The study was approved by the regional ethics committee and carried out according with the Declaration of Helsinki.Informed consent was obtained from the patients or their parents.Since we included both children, adolescents and adults, a BMI z-score (BMIz) was calculated using the Norwegian BMI references. 4 Bivariate correlation between BMIz or age and fasting serum glucose or HbA 1c was determined by Spearman's rank analysis, whereas the rate of deterioration of fasting glucose or HbA 1c was determined using least linear square method.A significance level of 5% was used.Statistics were performed using IBM SPSS Statistics 24.We recruited 98 MODY2 and 103 MODY3 probands.Three pregnant MODY2 subjects were excluded from further analysis.In MODY2 patients, fasting glucose ranged from 5.6 to 8.6 mmol/L compared to 3.8 to 20 mmol/L in MODY3.Moreover, HbA 1c levels also showed less variation among MODY2 probands (range: 39-63 mmol/mol; 5.7%-7.9%)as compared to MODY3 participants (range: 31-103 mmol/ mol; 5%-11.6%).Then we investigated correlation between BMIz and fasting serum glucose or HbA 1c in female or male probands diagnosed with MODY2 or MODY3, respectively.In MODY2, we did not find any correlation between BMIz and fasting glucose in neither females (r = 0.066, p = 0.714) nor males (r = 0.133, p = 0.509).Lack of correlation between