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

Timothy ME Davis, Ashley E Makepeace, Sian Ellard, Kevin Colclough, Kirsten Peters, Andrew Hattersley and Wendy A Davis
Med J Aust 2017; 207 (8): 344-347. || doi: 10.5694/mja16.01201

Abstract

Objective: To determine the prevalence of monogenic diabetes in an Australian community.

Design: Longitudinal observational study of a cohort recruited between 2008 and 2011.

Setting: Urban population of 157 000 people (Fremantle, Western Australia).

Participants: 1668 (of 4639 people with diabetes) who consented to participation (36.0% participation).

Main outcome measures: Prevalence of maturity-onset diabetes of the young (MODY) and permanent neonatal diabetes in patients under 35 years of age, from European and non-European ethnic backgrounds, who were at risk of MODY according to United Kingdom risk prediction models, and who were then genotyped for relevant mutations.

Results: Twelve of 148 young participants with European ethnic backgrounds (8%) were identified by the risk prediction model as likely to have MODY; four had a glucokinase gene mutation. Thirteen of 45 with non-European ethnic backgrounds (28%) were identified as likely to have MODY, but none had a relevant mutation (DNA unavailable for one patient). Two patients with European ethnic backgrounds (one likely to have MODY) had neonatal diabetes. The estimated MODY prevalence among participants with diagnosed diabetes was 0.24% (95% confidence interval [CI], 0.08–0.66%), an overall population prevalence of 89 cases per million; the prevalence of permanent neonatal diabetes was 0.12% (95% CI, 0.02–0.48%) and the population prevalence 45 cases per million.

Conclusions: 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.

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  • Timothy ME Davis1
  • Ashley E Makepeace2
  • Sian Ellard3
  • Kevin Colclough4
  • Kirsten Peters1
  • Andrew Hattersley3
  • Wendy A Davis1

  • 1 University of Western Australia, Perth, WA
  • 2 Fiona Stanley Hospital, Perth, WA
  • 3 Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom
  • 4 Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom

Correspondence: tim.davis@uwa.edu.au

Acknowledgements: 

We are grateful to patients who participated in the Fremantle Diabetes Study Phase II (FDS2), and FDS2 staff for help with collecting and recording clinical information. We thank the biochemistry department at Fremantle Hospital and Health Service for performing laboratory tests. FDS2 has been supported by the National Health and Medical Research Council (NHMRC; project grants 513781 and 1042231). Timothy Davis is supported by an NHMRC Practitioner Fellowship (1058260). The funders had no role in the design and conduct of the study, or in the preparation of the manuscript and the decision to submit it for publication.

Competing interests:

No relevant disclosures.

  • 1. Murphy R, Ellard S, Hattersley AT. Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab 2008; 4: 200-213.
  • 2. Galler A, Stange T, Muller G, et al. Incidence of childhood diabetes in children aged less than 15 years and its clinical and metabolic characteristics at the time of diagnosis: data from the Childhood Diabetes Registry of Saxony, Germany. Horm Res Paediatr 2010; 74: 285-291.
  • 3. Ledermann HM. Maturity-onset diabetes of the young (MODY) at least ten times more common in Europe than previously assumed? Diabetologia 1995; 38: 1482.
  • 4. Shields BM, Hicks S, Shepherd MH, et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 2010; 53: 2504-2508.
  • 5. Karges B, Meissner T, Icks A, et al. Management of diabetes mellitus in infants. Nat Rev Endocrinol 2012; 8: 201-211.
  • 6. Ellard S, Bellanné-Chantelot C, Hattersley AT; European Molecular Genetics Quality Network MODY Group. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51: 546-553.
  • 7. Shields BM, McDonald TJ, Ellard S, et al. The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia 2012; 55: 1265-1272.
  • 8. Davis TM, Bruce DG, Davis WA. Cohort profile: the Fremantle Diabetes Study. Int J Epidemiol 2013; 42: 412-421.
  • 9. Australian Bureau of Statistics. Socio-economic indexes for areas. Updated Sept 2013. http://www.abs.gov.au/websitedbs/censushome.nsf/home/seifa (accessed Sept 2015).
  • 10. Ellard S, Lango Allen H, De Franco E, et al. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 2013; 56: 1958-1963.
  • 11. Shackleton S, Lloyd DJ, Jackson SN, et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat Genet 2000; 24: 153-156.
  • 12. Heidet L, Decramer S, Pawtowski A, et al. Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol 2010; 5: 1079-1090.
  • 13. Harvey JN, Craney L, Kelly D. Estimation of the prevalence of diagnosed diabetes from primary care and secondary care source data: comparison of record linkage with capture-recapture analysis. J Epidemiol Community Health 2002; 56: 18-23.
  • 14. Australian Bureau of Statistics. 4820.0.55.001. Diabetes in Australia: a snapshot, 2007–08. Sept 2011. http://www.abs.gov.au/ausstats/abs@.nsf/mf/4820.0.55.001 (accessed Jan 2017).
  • 15. Sewell MF, Presley LH, Holland SH, Catalano PM. Genetic causes of maturity onset diabetes of the young may be less prevalent in American pregnant women recently diagnosed with diabetes mellitus than in previously studied European populations. J Matern Fetal Neonatal Med 2015; 28: 1113-1115.
  • 16. Harron KL, Feltbower RG, McKinney PA, et al. Rising rates of all types of diabetes in south Asian and non-south Asian children and young people aged 0–29 years in West Yorkshire, UK, 1991–2006. Diabetes Care 2011; 34: 652-654.
  • 17. Al-Sheyab F, Khamaiseh E, Halaweh MA, Khaul RW. Characterization of glucokinase polymorphisms associated with maturity-onset diabetes of the young (MODY2) in Jordanian population. Tsitol Genet 2009; 43: 58-63.
  • 18. Ng MC, Cockburn BN, Lindner TH, et al. Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1α genes in patients with early-onset type 2 diabetes mellitus/MODY. Diabet Med 1999; 16: 956-963.
  • 19. Misra S, Shields B, Colclough K, et al. South Asian individuals with diabetes who are referred for MODY testing in the UK have a lower mutation pick-up rate than white European people. Diabetologia 2016; 59: 2262-2265.
  • 20. Søvik O, Irgens HU, Molnes J, et al. Monogenic diabetes mellitus in Norway. Norsk Epidemiologi 2013; 23: 55-60.
  • 21. Lindner TH, Cockburn BN, Bell GI. Molecular genetics of MODY in Germany. Diabetologia 1999; 42: 121-123.
  • 22. Moises RS, Reis AF, Morel V, et al. Prevalence of maturity-onset diabetes of the young mutations in Brazilian families with autosomal-dominant early-onset type 2 diabetes. Diabetes Care 2001; 24: 786-788.
  • 23. Chevre JC, Hani EH, Boutin P, et al. Mutation screening in 18 Caucasian families suggest the existence of other MODY genes. Diabetologia 1998; 41: 1017-1023.
  • 24. Giuffrida FM, Reis AF. Genetic and clinical characteristics of maturity-onset diabetes of the young. Diabetes Obes Metab 2005; 7: 318-326.
  • 25. Pearson ER, Starkey BJ, Powell RJ, et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 2003; 362: 1275-1281.
  • 26. Grulich-Henn J, Wagner V, Thon A, et al. Entities and frequency of neonatal diabetes: data from the diabetes documentation and quality management system (DPV). Diabet Med 2010; 27: 709-712.

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