Wiener klinische Wochenschrift

, Volume 131, Issue 17–18, pp 435–441 | Cite as

How can maturity-onset diabetes of the young be identified among more common diabetes subtypes?

  • Jana Urbanova
  • Ludmila BrunerovaEmail author
  • Jan Broz
review article


Maturity onset diabetes of the young (MODY) represents a diabetes type which has an enormous clinical impact. It significantly alters treatment, refines a patient’s prognosis and enables early detection of diabetes in relatives. Nevertheless, when diabetes is manifested the vast majority of MODY patients are not correctly diagnosed, but mostly falsely included among patients with type 1 or type 2 diabetes, in many cases permanently. The aim of this article is to offer a simple and comprehensible guide for recognizing individuals with MODY hidden among adult patients with another type of long-term diabetes and in women with gestational diabetes.


MODY Type 1 diabetes mellitus Type 2 diabetes mellitus Gestational diabetes Differential diagnosis 



Special thanks to Michael Allen for language editing. The paper was supported by PROGRES Q36 and by MH CZ-DRO (“Kralovske Vinohrady University Hospital —FNKV, 00064173”).

Conflict of interest

J. Urbanova, L. Brunerova, and J. Broz declare that they have no competing interests.


  1. 1.
    Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care. 2011;34:1878–84.CrossRefGoogle Scholar
  2. 2.
    Online Mendelian Inheritance in Man, OMIM. Maturity-onset diabetes of the young; MODY. 2016. Accessed 15.2019.Google Scholar
  3. 3.
    Thanabalasingham G, Pal A, Selwood MP, Dudley C, Fisher K, Bingley PJ, et al. Systematic assessment of etiology in adults with a clinical diagnosis of young onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. Diabetes Care. 2012;35(6):1206–12.CrossRefGoogle Scholar
  4. 4.
    Brunerova L, Rahelic D, Ceriello A, Broz J. Use of oral antidiabetic drugs in the treatment of maturity-onset diabetes of the young (MODY): a minireview. Diabetes Metab Res Rev. 2018;34(1):e2940.CrossRefGoogle Scholar
  5. 5.
    Shepherd MH, Shields BM, Hudson M, Pearson ER, Hyde C, Ellard S, et al. A UK nationwide prospective study of treatment change in MODY: genetic subtype and clinical characteristics predict optimal glycaemic control after discontinuing insulin and metformin. Diabetologia. 2018;61(12):2520–7. Scholar
  6. 6.
    Gardner DS, Tai ES. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diab Meta Syndr Obes Targets Ther. 2012;5:101–8. Scholar
  7. 7.
    Tsai EB, Sherry NA, Palmer JP. Herold KC The rise and fall of insulin secretion in type 1 diabetes mellitus. Diabetologia. 2006;49(2):261–70.CrossRefGoogle Scholar
  8. 8.
    Slingerland A. Monogenic diabetes in children and young adults: challenges for researcher, clinician and patient. Rev Endocr Metab Disord. 2006;7:171–85.CrossRefGoogle Scholar
  9. 9.
    Průhová Š, Dušátková P, Neumann D, Hollay E, Cinek O, Lebl J, et al. Two cases of diabetic ketoacidosis in HNF1A-MODY linked to severe dehydration: is it time to change the diagnostic criteria for MODY? Diabetes Care. 2013;36(9):2573–4.CrossRefGoogle Scholar
  10. 10.
    Horikawa Y, Enya M, Mabe H, Fukushima K, Takubo N, Ohashi M, et al. NEUROD1-deficient diabetes (MODY6): Identification of the first cases in Japanese and the clinical features. Pediatr Diabetes. 2018;19(2):236–42. Scholar
  11. 11.
    Grzanka M, Matejko B, Szopa M, Kiec-Wilk B, Malecki MT, Klupa T. Assessment of newly proposed clinical criteria to identify HNF1A MODY in patients with an initial diagnosis of type 1 or type 2 diabetes mellitus. Adv Med. 2016; Scholar
  12. 12.
    Ellard S, Bellanné-Chantelot C, Hattersley AT. European Molecular Genetics Quality Network (EMQN) MODY group. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008;51(4):546–53.CrossRefGoogle Scholar
  13. 13.
    Shields BM, Shepherd M, Hudson M, McDonald TJ, Colclough K, Peters J, et al. Population-based assessment of a biomarker-based screening pathway to aid diagnosis of Monogenic diabetes in young-onset patients. Diabetes Care. 2017;40(8):1017–25.CrossRefGoogle Scholar
  14. 14.
    Steele AM, Wensley KJ, Ellard S, Murphy R, Shepherd M, Colclough K, et al. Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies. PLoS ONE. 2013;8:e65326.CrossRefGoogle Scholar
  15. 15.
    Stride A, Shields B, Gill-Carey O, Chakera AJ, Colclough K, Ellard S, et al. Cross sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia. Diabetologia. 2014;57(1):54–6.CrossRefGoogle Scholar
  16. 16.
    Pruhova S, Dusatkova P, Kraml PJ, Kulich M, Prochazkova Z, Broz J, et al. Chronic mild hyperglycemia in GCK-MODY patients does not increase carotid intima-media thickness. Int J Endocrinol. 2013; Scholar
  17. 17.
    Chakera AJ, Steele AM, Gloyn AL, Shepherd MH, Shields B, Ellard S, et al. Recognition and management of individuals with hyperglycaemia because of a heterozygous glucokinase mutation. Diabetes Care. 2015;38(7):1383–92.CrossRefGoogle Scholar
  18. 18.
    Stanik J, Dusatkova P, Cinek O, Valentinova L, Huckova M, Skopkova M, et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia. 2014;57(3):480–4.CrossRefGoogle Scholar
  19. 19.
    Steele AM, Shields BM, Shepherd M, Ellard S, Hattersley AT, Pearson ER. Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene. Diabet Med. 2010;27(2):157–61.CrossRefGoogle Scholar
  20. 20.
    Bowman P, Flanagan SE, Edghill EL, Damhuis A, Shepherd MH, Paisey R, et al. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia. 2012;55:123–7.CrossRefGoogle Scholar
  21. 21.
    Naylor R, Knight Johnson A, del Gaudio D. Maturity-onset diabetes of the young overview. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle: University of Washington; 2018. pp. 1993–2018. Available from: Scholar
  22. 22.
    Liu L, Nagashima K, Yasuda T, Liu Y, Hu HR, He G, et al. Mutations in KCNJ11 are associated with the development of autosomal dominant, early-onset type 2 diabetes. Diabetologia. 2013;56(12):2609–18.CrossRefGoogle Scholar
  23. 23.
    Sood S, Landreth H, Bustinza J, Chalmers L, Thukaram R. Neonatal diabetes: case report of a 9-week-old presenting diabetic Ketoacidosis Due to an activating ABCC8 gene mutation. Journal of Investigative Medicine High Impact Case Reports. 2017;5(1):2324709617698718.CrossRefGoogle Scholar
  24. 24.
    Pearson ER, Badman MK, Lockwood CR, Clark PM, Ellard S, Bingham C, et al. Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Diabetes Care. 2004;27(5):1102–7.CrossRefGoogle Scholar
  25. 25.
    Tonooka N, Tomura H, Takahashi Y, Onigata K, Kikuchi N, Horikawa Y, et al. High frequency of mutations in the HNF-1alpha gene in non-obese patients with diabetes of youth in Japanese and identification of a case of digenic inheritance. Diabetologia. 2002;45(12):1709–12. Dec.CrossRefGoogle Scholar
  26. 26.
    Clissold RL, Hamilton AJ, Hattersley AT, Ellard S, Bingham C. HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum. Nat Rev Nephrol. 2015;11(2):102–12. Scholar
  27. 27.
    Edghill EL, Bingham C, Slingerland AS, Minton JA, Noordam C, Ellard S, et al. Hepatocyte nuclear factor‑1 beta mutations cause neonatal diabetes and intrauterine growth retardation: support for a critical role of HNF-1beta in human pancreatic development. Diabet Med. 2006;23(12):1301–6.CrossRefGoogle Scholar
  28. 28.
    Weber P, Ambrosova P, Canov P, Weberova D, Kuklinek P, Meluzinova H, et al. GAD antibodies in T1D and LADA—relations to age, BMI, c‑peptide, IA‑2 and HLA-DRB1*03 and DRB1*04 alleles. Adv Gerontol. 2011;24(2):312–8.Google Scholar
  29. 29.
    Urbanová J, Rypáčková B, Procházková Z, Kučera P, Cerná M, Anděl M, et al. Positivity for islet cell autoantibodies in patients with monogenic diabetes is associated with later diabetes onset and higher HbA1c level. Diabet Med. 2014;31(4):466–71.CrossRefGoogle Scholar
  30. 30.
    Molven A, Ringdal M, Nordbø AM, Raeder H, Støy J, Lipkind GM, et al. Mutation in the insulin gene can cause MODY and antibody-negative type 1 DM. Diabetes. 2008;57:1034–42.CrossRefGoogle Scholar
  31. 31.
    Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present and future. Lancet. 2014;383(9922):1068–83. Scholar
  32. 32.
    Stride A, Vaxillaire M, Tuomi T, et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia. 2002;45:427–35. Scholar
  33. 33.
    Pearson ER, Liddell WG, Shepherd M, Corrall RJ, Hattersley AT. Sensitivity to sulphonylureas in patients with hepatocyte nuclear factor-1alpha gene mutations: evidence for pharmacogenetics in diabetes. Diabet Med. 2000;17(7):543–5.CrossRefGoogle Scholar
  34. 34.
    McDonald TJ, Shields BM, Lawry J, Owen KR, Gloyn AL, Ellard S, et al. High sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care. 2011;34(8):1860–2.CrossRefGoogle Scholar
  35. 35.
    Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 2007;4(4):e118.CrossRefGoogle Scholar
  36. 36.
    Fajans SS, Bell GI, Paz VP, et al. Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60. Transl Res. 2010;156(1):7–14.CrossRefGoogle Scholar
  37. 37.
    Malecki MT, Jhala U, Antonellis A, Fields L, Doria A, Orban T, et al. Mutations in NEUROD1 are associated with the development of type two diabetes. Nat Genet. 1999;23:323–8. Scholar
  38. 38.
    Borowiec M, Liew CW, Thompson R, Boonyasrisawat W, Hu J, Mlynarski WM, et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci U S A. 2009;106:14460–5.CrossRefGoogle Scholar
  39. 39.
    Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, Dina C, Hamid YH, Joly E, et al. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci U S A. 2005;102:4807–12. Scholar
  40. 40.
    Plengvidhya N, Kooptiwut S, Songtawee N, Doi A, Furuta H, Nishi M, et al. PAX4 mutations in Thais with maturity onset diabetes of the young. J Clin Endocrinol Metab. 2007;92:2821–6.CrossRefGoogle Scholar
  41. 41.
    Prundate S, Jungtrakoon P, Marucci A, Ludovico O, Buranasupkajorn P, Mazza T, et al. Loss-of-function mutations in APPL1 in familial diabetes mellitus. Am J Hum Genet. 2015;97:177–85. Scholar
  42. 42.
    Raeder H, Johansson S, Holm PI, Haldorsen IS, Mas E, Sbarra V, et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat Genet. 2006;38:54–62.CrossRefGoogle Scholar
  43. 43.
    Gjesing AP, Rui G, Lauenborg J, et al. High prevalence of diabetes-predisposing variants in MODY genes among Danish women with gestational diabetes mellitus. J Endocr Soc. 2017;1(6):681–90. Scholar
  44. 44.
    American Diabetes Association. Classification and diagnosis of diabetes: standards of medical care in diabetesd 2018. Diabetes Care. 2018;41(Suppl. 1):S13–S27. Scholar
  45. 45.
    Chakera AJ, Steele AM, Gloyn A, et al. Recognition and management of individuals with hyperglycemia because of heterozygous glucokinase mutations. Diabetes Care. 2015;38:1383–92.CrossRefGoogle Scholar
  46. 46.
    Chakera AJ, Spyer G, Vincent N, Ellard S, Hattersley AT, Dunne FP. The 0.1% of the population with glucokinase monogenic diabetes can be recognized by clinical characteristics in pregnancy: the Atlantic Diabetes in Pregnancy cohort. Diabetes Care. 2014;37:1230–6.CrossRefGoogle Scholar
  47. 47.
    Rudland VL, Hinchcliffe M, Pinner J, Cole S, Mercorella B, et al. Identifying glucokinase monogenic diabetes in a multiethnic gestational diabetes mellitus cohort: new pregnancy screening criteria and utility of HbA1c. Diabetes Care. 2016;39(1):50–2. Scholar
  48. 48.
    Flack JR, Ross GP, Cheung NW. GCK monogenic diabetes and gestational diabetes: possible diagnosis on clinical grounds. Diabet Med. 2015;32(12):1596–601. Scholar
  49. 49.
    Lachance CH. Practical aspects of monogenic diabetes: a clinical point of view. Canadian Journal of Diabetes. 2016;40(5):368–75.CrossRefGoogle Scholar
  50. 50.
    Bellanné-Chantelot C, Lévy DJ, Carette C, Saint-Martin C, Riveline JP, Larger E, et al. Clinical characteristics and diagnostic criteria of maturity-onset diabetes of the young (MODY) due to molecular anomalies of the HNF1A gene. J Clin Endocrinol Metab. 2011;96:1346–51.CrossRefGoogle Scholar
  51. 51.
    Sung-Hoon K. Maturity-onset diabetes of the young: what do clinicians need to know? Diabetes Metab J. 2015;39(6):468–77.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Diabetologic centre II. , Department of Medicine, Third Faculty of Medicine and Faculty Hospital Kralovske VinohradyCharles UniversityPragueCzech Republic
  2. 2.Department of Medicine, Second Faculty of Medicine and Faculty Hospital MotolCharles UniveristyPragueCzech Republic

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