The prevalence of monogenic diabetes in Australia: the Fremantle Diabetes Study Phase II

Abstract

One in 280 Australians diagnosed with diabetes have a monogenic form; most are of European ethnicity. Diagnosing MODY and neonatal diabetes is important because their management (including family screening) and prognosis can differ significantly from those for types 1 and 2 diabetes.

Prevalence of diabetes in Australia: insights from the Fremantle Diabetes Study Phase II

“…Genotyping for MODY 18 revealed one case of a novel GCK gene mutation (c.1253G>T; p. Ser418Ile) and a previously reported missense mutation known to be associated with familial partial lipodystrophy ( LMNA , c.1444C>T; p.Arg482Trp 22 ). Including this information refined the proportions with type 1 diabetes, type 2 diabetes, LADA, MODY and secondary diabetes to 7.9% (no change), 85.8%, 4.9%, 0.4% and 1.0% (no change), respectively.…”

“…Testing for GAD65 antibodies identified 158 (9.5%) positive results (72 in clinically defined type 2 diabetes, 1 confirming LADA in a participant requiring further information before categorisation, 8 in known LADA and 77 in type 1 diabetes). Genotyping for MODY 18 revealed one case of a novel GCK gene mutation (c.1253G > T; p. Ser418Ile) and a previously reported missense mutation known to be associated with familial partial lipodystrophy (LMNA, c.1444C > T; p.Arg482Trp 22 ). Including this information refined the proportions with type 1 diabetes, type 2 diabetes, LADA, MODY and secondary diabetes to 7.9% (no change), 85.8%, 4.9%, 0.4% and 1.0% (no change) respectively.…”

“…13 All participants aged <35 years at diagnosis were assessed using the UK MODY risk prediction models. 17,18 Those identified as probable MODY underwent subsequent genetic testing with analysis of all coding regions and exon/intron boundaries, as well as partial/whole gene deletions and duplications, of the known monogenic diabetes genes GCK, HNF1A, HNF4A, HNF1B, NEUROD1, INS, INSR, KCNJ11, ABCC8, PDX1, CEL, PAX6, GATA6, TRMT10A, WFS1, ZFP57, PCBD1, LMNA, PPARG, PLIN1 and POLD1, and the m.3243A > G maternally inherited diabetes and deafness (MIDD) mutation by targeted next generation sequencing (Agilent custom capture v5.1/Illumina HiSeq; Agilent Technologies LDA UK Ltd, Stockport, Cheshire, UK) 19 performed at the Molecular Genetics Laboratory, Royal Devon and Exeter National Health Service Foundation Trust, UK. Serum glutamic acid decarboxylase (GAD65) autoantibodies were determined using stored sera from the baseline assessment and a commercially available ELISA kit (RSR GAD65; RSR Limited, Cardiff, UK) run on an EVOLIS automated enzyme-linked immunosorbent assay (ELISA) workstation (Bio-Rad Laboratories, Sydney, NSW, Australia).…”

Alterations of Lipid Levels May Induce the Insulin Resistance in Type Two Diabetes Mellitus: A Systemic Review

“…Subtyping type one diabetes mellitus (T1DM) and type two diabetes mellitus (T2DM) in the populace concentrates achievable utilizing as often as possible accessible clinical data [4,5] A few investigations have revealed. The populace pervasiveness of different types of diabetes, for example, monogenic diabetes [6,7] and diabetes because of pancreatic infection [8]. Grouping of diabetes type is especially critical for frequency.…”

Explaining the high prevalence of young‐onset diabetes among Asians and Indigenous Australians

“…In this issue of the MJA , Davis and his co‐authors 4 report their attempt to ascertain the prevalence of MODY in a multi‐ethnic Australian population drawn from the Fremantle Diabetes Study. The authors applied the MODY risk equation developed in Europe 5 to patients diagnosed with diabetes before the age of 35.…”