Background
Maturity Onset Diabetes of the Young is a group of monogenic disorders with autosomal mode of inheritance, estimated to affect 0.6-2% of people with diabetes.  To date, the prevalence of MODY in the Emirati population has not been established.  Of 107 patients screened as potential index cases  by our clinical service, 11 were found to have mutations in known MODY genes (10.3%).

Aims
To establish the utility of assessment of residual β-cell function through measurement of meal-stimulated ratio of urinary C-peptide to creatinine (UCPCR) to distinguish young Emirati patients with a possible diagnosis of MODY from those with type 1 diabetes.

Method
764 patients were recruited from clinical areas at Imperial College London Diabetes Centre (ICLDC), an outpatient diabetes and general endocrine clinic based in the United Arab Emirates.  UCPCR was measured two hours following a meal stimulus.  Patients were chosen for genetic screening based on the following criteria; age of onset <25, BMI < 30 kg/m2, negative IA2 antibodies and positive predictive value(PPV) of 0.55 as per values obtained from MODY probability calculator.

Results
64 individuals (mean age at diagnosis 14.8 years, range 1.62-27.9 years) with evidence of hyperglycaemia who were negative for anti-IA2 antibodies were genetically screened for MODY using targeted Next Generation Sequencing (NGS) techniques where 16 genes known to cause monogenic diabetes were analysed. In total, 12 individuals showed evidence of a mutation compatible with monogenic diabetes, 27 were clinically diagnosed as type 1 diabetes, 19 as type 2 diabetes, four as diabetes of unspecified type and two as impaired fasting glucose.
The participants with MODY were clinically distinguishable from those with type 2 diabetes on the basis of body habitus.  A body mass index cut-off of 25.6 kg/m2 gave a positive predictive value of 0.83 and negative predictive value of 0.69 (sensitivity 0.79, specificity 0.75, area under the receiver operator characteristic curve (AUC ROC) 0.829 (0.666-0.991); use of this cut-off would, however result in four individuals being falsely diagnosed with type 2 diabetes.
Emirati individuals with MODY were distinguishable from those with type 1 diabetes by excluding those without significant residual β-cell function, using UCPCR.  A UCPCR cut-off of 0.53 nmol/mmol gave negative predictive value of 1.0 and positive predictive value of 0.5 for the diagnosis of MODY  (sensitivity 1.0, specificity 0.52, AUC ROC 0.738 (0.576-0.900)).

Discussion
The choice of patients who should be genetically screened for MODY is increasingly complicated by the prevalence of type 2 diabetes in people aged under 30 years and of people with both type 1 diabetes and obesity.  Overweight and obesity do not rule out the possibility of monogenic diabetes in this group of IA-2 negative Emirati people and consequently screening should be considered even in people who do not meet the above mentioned criteria. Furthermore, UCPCR provides valuable discrimination between UAE Nationals with type 1 diabetes and those with monogenic diabetes.

The use of urinary C-peptide to creatinine ratio in screening for maturity onset diabetes of the young in Emirati people