Abstract
INTRODUCTION: Monogenic diabetes accounts for 2-5% of diabetes. Although its identification has substantial therapeutic implications, more than 80% of affected individuals are undiagnosed or misdiagnosed as having type 1 or 2 diabetes. This consensus statement reviews genetic testing for monogenic diabetes in adults and provides evidence-based recommendations. With representation from the Australian Diabetes Society (ADS), Endocrine Society of Australia (ESA), Human Genetics Society of Australasia (HGSA), New Zealand Society for the Study of Diabetes (NZSSD) and Royal College of Pathologists of Australasia (RCPA), the writing group: (i) defined questions to be addressed, (ii) conducted critical literature reviews, (iii) graded the evidence, and (iv) generated recommendations that were refined until consensus was achieved. All contemporary literature was considered, with a focus on Australian and New Zealand data, where available. MAIN RECOMMENDATIONS: Indications for genetic testing for monogenic diabetes in adults include: (i) diabetes onset before 12 months of age, (ii) glucokinase (GCK)-hyperglycaemia phenotype, (iii) diabetes onset before 30 years of age without markers of type 1 or 2 diabetes, (iv) syndromic monogenic diabetes phenotype, or (v) high probability of monogenic diabetes using validated screening tools. Individuals undergoing genetic testing should be provided with comprehensive pre- and post-test counselling. Genetic testing typically involves next-generation sequencing, and should include classically syndromic genetic variants (eg, m.3243A>G, HNF1B variants) even in individuals with isolated diabetes. A molecular diagnosis facilitates gene-specific treatment, surveillance, reproductive planning and cascade testing of relatives. In pregnancies of individuals with GCK-hyperglycaemia, maternal treatment can be individualised to known or assumed fetal genotype. Individuals with monogenic diabetes variants of uncertain significance or negative results may be considered for further phenotype or genotype assessment and recruitment into research studies. CHANGES IN MANAGEMENT: This consensus statement aims to raise awareness of monogenic diabetes among clinicians involved in the care of patients with diabetes, and to improve genetic testing rates across Australia and New Zealand.