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Review

Maturity-onset diabetes of the young (MODY): current perspectives on diagnosis and treatment

Pages 1047-1056 | Published online: 08 Jul 2019

References

  • Tattersall RB . Mild familial diabetes with dominant inheritance. Q J Med . 1974;43:339–357.4212169
  • McDonald TJ , Colclough K , Brown R , et al. Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes. Diabet Med . 2011;20:1028–1033. doi:10.1111/j.1464-5491.2011.03287.x
  • Owen KR , Roland J , Smith K , Hattersley AT . Adolescent onset type 2 diabetes in a non-obese Caucasian patient with an unbalanced translocation. Diabet Med . 2011;20:483–485. doi:10.1046/j.1464-5491.2003.00961.x
  • Ellard S , Ballanné-Chantelot C , Hattersley AT . Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia . 2008;51:546–553. doi:10.1007/s00125-008-0942-y 18297260
  • Froguel PM , Vallaire F , Sun G , et al. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin dependent diabetes mellitus. Nature . 1992;356:162–164. doi:10.1038/356162a0 1545870
  • Horikawa Y , Iwasaki N , Hara M , et al. Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) association with MODY. Nat Genet . 1997;17:384–385. doi:10.1038/ng1297-384 9398836
  • Soffers DA , Ferrer J , Clarke WL , Habener JF . Early-onset type-II diabetes mellitus (MODY 4) linked to IPF1. Nat Genet . 1997;17:138–139. doi:10.1038/ng1097-138 9326926
  • Vionnet N , Stoffel M , Takeda J , et al. Nonsense mutation in the glucokinase causes early-onset non-insulin-dependent diabetes mellitus. Nature . 1992;356:721–722. doi:10.1038/356721a0 1570017
  • Yamagata K , Furuta H , Oda N , et al. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature . 1996;384:458–460. doi:10.1038/384458a0 8945471
  • Yamagata K , Oda N , Kaisaki PJ , et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature . 1996;384:455–458. doi:10.1038/384455a0 8945470
  • Kavvoura FK , Owen KR . Maturity onset diabetes of the young: clinical characteristics, diagnosis and management. Pediatr Endocrinol Rev . 2013;10:234–242.
  • Kim SH . Maturity-onset diabetes of the young: what do clinicians need to know? Diabetes Metab J . 2015;39:468–477. doi:10.4093/dmj.2015.39.6.468 26706916
  • Thanabalansingham G , Pal A , Selwood MP , 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;35:1206–1212. doi:10.2337/dc11-1243 22432108
  • Hattersley AT , Greeley SA , Polak M , et al. ISPAD clinical practice consensus guidelines 2018: the diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes . 2018;19(Suppl.27):47–63. doi:10.1111/pedi.12772 30225972
  • Yorifuji T , Fujimaru R , Hosokawa Y , et al. Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY-type diabetes mellitus. Pediatr Diabetes . 2012;13:26–32. doi:10.1111/j.1399-5448.2011.00827.x 22060211
  • Hwang JS , Shin CH , Yang SW , Jung SY , Huh N . Genetic and clinical characteristics of Korean maturity-onset diabetes of the young (MODY) patients. Diabetes Res Clin Pract . 2006;74:75–81. doi:10.1016/j.diabres.2006.03.002 16632067
  • Shields BM , Hicks S , Shepherd MH , Colclough K , Hattersley AT , Ellard S . Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia . 2010;53:2504–2508. doi:10.1007/s00125-010-1799-4 20499044
  • Urakami T , Kuwabara R , Habu M , et al. Clinical characteristics of non-obese children with type 2 diabetes mellitus without involvement of β-cell autoimmunity. Diabetes Res Clin Pract . 2013;99:105–111. doi:10.1016/j.diabres.2012.11.021 23260852
  • Urakami T , Miyata M , Yoshida K , et al. Changes in annual incidence of school children with type 2 diabetes in the Tokyo metropolitan area during 1975–2015. Pediatr Diabetes . 2018;19:1385–1392. doi:10.1111/pedi.12750 30101568
  • Prudente S , Jungtrakoon P , Marucci A , et al. Loss-of-function mutations in APPL1 in familial diabetes mellitus. Am J Hum Genet . 2018;97:177–185. doi:10.1016/j.ajhg.2015.05.011
  • Osbak KK , Colclough K , Saint-Martin C , et al. Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat . 2009;30:1512–1526. doi:10.1002/humu.21110 19790256
  • 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;45:427–435. doi:10.1007/s00125-001-0770-9 11914749
  • Martin D , Bellarnne-Chantelot C , Deschamps I , Froguel P , Robert JJ , Velho G . Long-term follow-up of oral glucose tolerance test-derived glucose tolerance and insulin secretion and insulin sensitivity indexes in subjects with glucokinase mutations (MODY2). Diabetes Care . 2008;31:1321–1323. doi:10.2337/dc07-2017 18411240
  • 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;37:1230–1236. doi:10.2337/dc13-2248 24550216
  • Rudland VL , Hinchcliffe M , Pinner J , et al. Identifying glucokinase monogenic diabetes mellitus in a multiethnic gestational diabetes mellitus cohort: new pregnancy screening criteria and utility of HbA1c. Diabetes Care . 2016;39:50–52. doi:10.2337/dc15-1001 26109503
  • Steele AM , Shields BM , Shepherd M , Ellard S , Colclough K , Hattersley AT . Microvascular complication risk in patients with 50 years of moderate hyperglycemia: are target ranges for glycemia control appropriate? Abstract A77. Diabet Med . 2011;28(S1):2. doi:10.1111/j.1464-5491.2011.03281.x 21166840
  • Velho G , Blanche H , Vaxillaire M , et al. I dentification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia . 1997;40:217–224. doi:10.1007/s001250050666 9049484
  • Dukes ID , Sreenan S , Roe M , et al. Defective pancreatic beta-cell glycolytic signaling in hepatocyte nuclear factor 1alpha-deficit mouse. J Biol Chem . 1998;273:24457–24464. doi:10.1074/jbc.273.38.24457 9733737
  • Pontoglio M , Sreenan S , Roe M , et al. Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficit mouse. J Clin Invest . 1998;101:2215–2222. doi:10.1172/JCI2548 9593777
  • Colclough K , Bellanne-Chantelot C , Saint-Martin C , Flanagan SE , Ellard S . Mutations in the genes encoding the hepatocyte nuclear factor 1alpha and 4alpha in maturity-onset diabetes in the young and hyperinsulinemic hypoglycemia. Hum Mutat . 2013;34:669–685. doi:10.1002/humu.22279 23348805
  • Ellard S , Colclough K . Mutations in the genes encoding the transcription factors hepatocyte nuclear factor 1alpha (HNF1A) and 4alpha (HNF4A) in maturity-onset diabetes in the young. Hum Mutat . 2006;27:854–869. doi:10.1002/humu.20357 16917892
  • Frayling TM , Bulamn MP , Ellard S , et al. Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of maturity-onset diabetes of the young in the U.K. Diabetes . 1997;46:720–725. doi:10.2337/diab.46.4.720 9075818
  • 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;27:157–161. doi:10.1111/j.1464-5491.2009.02913.x 20546258
  • Pontoglio M , Prie D , Cheret C , et al. HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep . 2000;1:359–365. doi:10.1093/embo-reports/kvd071 11269503
  • Pearson ER , Boj SF , Steele AM , et al. Macrosomia and hyperinsulinaemic hypoglycemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med . 2007;4:e118. doi:10.1371/journal.pmed.0040118 17407387
  • Stoffel M , Duncan SA . The maturity-onset diabetes of the young (MODY) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci U S A . 1997;94:13209–13214. doi:10.1073/pnas.94.24.13209 9371825
  • Pearson ER , Pruhova S , Tack CJ , et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large Europea collection. Diabeteologia . 2005;48:878–885. doi:10.1007/s00125-005-1738-y
  • Lehto M , Bitzen PO , Isoma B , et al. Mutations in the HNF-4alpha gene affects insulin secretion and triglyceride metabolism. Diabetes . 1999;48:423–425. doi:10.2337/diabetes.48.2.423 10334325
  • Barbacci E , Reber M , Ott MO , Breilat C , Huetz F , Cereghini S . Variant hepatocyte nuclear factor 1 is required for visceral endoderm specification. Development . 1999;126:4795–4805.10518496
  • Edghill EL , Bingham C , Ellard S , Hattersley AT . Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet . 2006;43:84–90. doi:10.1136/jmg.2005.032854 15930087
  • Bingham C , Ellard S , Allen L , et al. Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1beta. Kidney Int . 2000;57:898–907. doi:10.1046/j.1523-1755.2000.057003898.x 10720943
  • Bingham C , Bulman MP , Ellard S , et al. Mutation in the transcription factor hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease. Am J Hum Genet . 2001;68:219–224. doi:10.1086/316945 11085914
  • Bellanne-Chantelot C , Chauveau D , Gautier JF , et al. Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med . 2004;140:510–517.15068978
  • Edghill EL , Bingham C , Singerland AS , et al. Hepatocyte nuclear factor-1beta mutations cause neonatal diabetes and intrauterine growth reduction: support for a critical role of HNF-1beta in human pancreatic development. Diabet Med . 2006;23:1301–1306. doi:10.1111/j.1464-5491.2006.01999.x 17116179
  • Stoffers DA , Thomas MK , Habener JF . Homeodomain protein IDX-1: a master regulator of pancreas development and insulin gene expression. Trends Endocrinol Metab . 1997;8:145–151. doi:10.1016/S1043-2760(97)00008-8 18406800
  • Schwitzgebel VM , Mamin A , Brun T , et al. Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. J Clin Endocrinol Metab . 2003;88:4398–4406. doi:10.1210/jc.2003-030046 12970316
  • Malecki MT , Jhala US , Antonellis A , et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat Genet . 1999;23:323–328. doi:10.1038/70539 10545951
  • Gonsorcikova L , Pruhova S , Cinek O , et al. Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1. Pediatr Diabetes . 2008;9(4 Pt 2):367–372. doi:10.1111/j.1399-5448.2008.00379.x 18331410
  • Rubio-Cabezas O , Minton JA , Kantor I , Williams D , Ellard S , Hattersley AT . Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities. Diabetes . 2010;59:2326–2331. doi:10.2337/db10-0011 20573748
  • Shields BM , McDonald TJ , Ellard S , Campbell MJ , Hyde C , Hattersley AT . 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. doi:10.1007/s00125-011-2418-8 22218698
  • DiabetesGenes. MODY Probability Calculator. Available from: http://www.diabetesgenes.org/content/mody-probability-calcualtor. Accessed June 27, 2019.
  • Owen KR , Thanabalasingham G , James TJ , et al. Assessment of high-sensitivity C-reactive protein levels as diagnostic discriminator of maturity-onset diabetes of the young due to HNF1A mutations. Diabetes Care . 2010;33:1919–1924. doi:10.2337/dc10-0288 20724646
  • McDonald TJ , Shields BM , Lawry J , et al. High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care . 2011;34:1860–1862. doi:10.2337/dc11-0323 21700917
  • Thanabalasingham G , Shah N , Vaxillaire M , et al. A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes. Diabetologia . 2011;54:2801–2810. doi:10.1007/s00125-010-2040-1 21814873
  • Bonner C , Nyhan KC , Bacon S , et al. Identification of circulating microRNAs in HNF1A-MODY carriers. Diabetologia . 2013;56:1743–1751. doi:10.1007/s00125-013-2939-4 23674172
  • Bakay M , Pandey R , Hakonarson H . Genes involved in type 1 daiabets: an update. Genes . 2013;4:499–521. doi:10.3390/genes4030499 24705215
  • Yang Y , Chan L . Monogenic diabetes: what it teaches us on the common forms of type 1 and type 2 diabetes. Endocr Rev . 2016;37:190–222. doi:10.1210/er.2015-1116 27035557
  • Flannick J , Ber NL , Bick AG , et al. Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes. Nat Genet . 2013;45:1380–1385. doi:10.1038/ng.2794 24097065
  • Thomsen SK , Gloyn AL . The pancreatic β cell: recent insights from human genetics. Trends Endocrinol Metab . 2014;25:425–434. doi:10.1016/j.tem.2014.05.001 24986330
  • Kawakita R , Hosokawa Y , Fujimaru R , et al. Molecular and clinical characterization of glucokinase maturity-onset diabetes of the young (GCK-MODY) in Japanese patients. Diabet Med . 2014;31:1357–1362. doi:10.1111/dme.12487 24804978
  • Yoon KH , Lee JH , Kim JW , et al. Epidemic obesity and type 2 diabetes in Asia. Lancet . 2006;368:1681–1688. doi:10.1016/S0140-6736(06)69703-1 17098087
  • Chan JCN , Malik V , Jin WP , et al. Diabetes in Asia. Epidemiology, risk factors and pathology. Jama . 2009;301:2129–2140. doi:10.1001/jama.2009.726 19470990
  • Tfayli H , Bacha F , Gungor N , Arslanian A . Phenotypic type 2 diabetes in obese youth; insulin sensitivity and secretion in islet-cell antibody negative vs. antibody positive patients. Diabetes . 2009;58:738–744. doi:10.2337/db08-1372 19073767
  • Pearson RB , Starkey BJ , Poweli RJ , Gribble FM , Clark PM , Hattersley AT . Genetic cause of hyperglycemia and response to treatment in diabetes. Lancet . 2003;362:1275–1281. doi:10.1016/S0140-6736(03)14571-0 14575972
  • Fajans SS , Brown MB . Administration of sulfonylureas can increase glucose-induced insulin secretion for decades in patients with maturity-onset diabetes of the young. Diabetes Care . 1993;16:1254–1261. doi:10.2337/diacare.16.9.1254 8404429
  • Shepherd M , Shields B , Ellard S , Rubio-Cabezas O , Hattersley AT . A genetic diagnosis of HNF-1A diabetes alters treatment and improves glycemic control in the majority of insulin-treated patients. Diabet Med . 2009;26:437–441. doi:10.1111/j.1464-5491.2009.02690.x 19388975
  • Raile K , Schober K , Konrad K , et al. Treatment of young patients with HNF1A mutations (HNF1A-MODY). Diabet Med . 2015;32:526–530. doi:10.1111/dme.12662 25483937
  • Campbell PK . Glimepiride: role of a new sulfonylurea in the treatment of type 2 diabetes mellitus. Ann Pharmacother . 1998;32:1044–1052. doi:10.1345/aph.17360 9793597
  • Urakami T . New insights into the pharmacological treatment of pediatric patients with type 2 diabetes. Clin Pediatr Endocrinol . 2018;27:1–8. doi:10.1297/cpe.27.1 29403151
  • Østoft SH , Babber JI , Hausen T , et al. Glucose-lowering effect and low risk of hypoglycemia in patients with maturity-onset diabetes of the young when treated with a GLP-1 receptor agonist: a double blind, randomized, crossover trial. Diabetes Care . 2014;37:1797–1805. doi:10.2337/dc13-3007 24929431
  • Urakami T , Habu M , Okuno M , Suzuki J , Takahashi S , Yorifuji T . Three years of liraglutide treatment offers continuously optimal glycemic control in a pediatric patient with maturity-onset diabetes of the young type 3. J Pediatr Endocrinol Metab . 2015;28:327–331. doi:10.1515/jpem-2014-0211 25332292
  • Tonouchi R , Mine Y , Aoki M , Okuno M , Suzuki J , Urakami T . Efficacy and safety of alogliptin in a pediatric patient with maturity-onset diabetes of the young type 1. Clin Pediatr Endocrinol . 2017;26:183–188. doi:10.1297/cpe.26.183 28804210
  • DeFronzo RA , Fleck PR , Wilson CA , Mekki Q . Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study. Diabetes Care . 2008;31(12):2315–2317. doi:10.2337/dc08-1035 18809631
  • Pratley RE , Kipnes MS , Fleck PR , Wilson C , Mekki Q . Efficacy and safety of the dipeptidyl peptidase-4inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide mono therapy. Diabetes Obes Metab . 2009;11(2):167–176. doi:10.1111/j.1463-1326.2008.01016.x 19125778
  • Nauck MA , Ellis GC , Fleck PR , Wilson CA , Mekki Q . Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicenter, randomized, double-blind, placebo-controlled study. Int J Clin Pract . 2009;63:46–55. doi:10.1111/j.1742-1241.2008.01933.x 19125992
  • Murphy R , Ellard S , Hattersley AT . Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab . 1974;4:200–213. doi:10.1038/ncpendmet0778
  • Zeitler P , Arslanian S , Fu J , et al. ISPAD clinical practice consensus guidelines 2018: type 2 diabetes mellitus in youth. Pediatr Diabetes . 2018;19(Suppl. 27):28–46. doi:10.1111/pedi.12719 29999228
  • Gat-Yablonski G , Shalitin S , Phillip M . Maturity onset diabetes of the young-review. Pediatr Endocrinol Rev . 2006;3(Suppl 3):514–520.17551475