Abstract
Maturity onset diabetes of the young (MODY) is a rare but increasingly recognized
cause of diabetes in young people. It is a monogenic disorder that typically presents
at <25 years of age, is non-insulin dependent and is familial, with an autosomal dominant
pattern of inheritance. The most common forms of MODY are caused by mutations in glucokinase
and hepatic nuclear factor 1 alpha or 4 alpha genes and account for almost 80% of
cases of MODY. MODY is commonly misdiagnosed as type 1 or type 2 diabetes and, as
a result, patients are often inappropriately managed with insulin when they can be
more effectively managed with oral sulfonylureas. Therefore, making the right diagnosis
is critical for effective treatment as well as for genetic counselling and, more important,
for patients' quality of life. In this review, we aim to raise awareness about MODY
among diabetes clinicians by describing key clinical and laboratory features of the
most common forms of MODY, outlining features that might help to differentiate MODY
from type 1 and type 2 diabetes and providing information about clinical tests and
tools that might assist in identifying patients who are most likely to benefit from
molecular genetic testing.
Résumé
Le diabète de la maturité apparaissant chez le jeune (MODY) est une cause rare, mais
de plus en plus reconnue, de diabète chez les jeunes. Cette maladie monogénique qui
se présente habituellement chez les jeunes de<25 ans est non insulinodépendante et
familiale, et se transmet selon un mode autosomique dominant. Les formes les plus
fréquentes de MODY sont causées par les mutations de la glucokinase et des gènes des
facteurs nucléaires hépatocytaires HNF-1alpha et HNF-4alpha, et représentent près
de 80 % des cas de MODY. On diagnostique souvent à tort le MODY comme étant un diabète
de type 1 ou de type 2 et, par conséquent, on prend souvent en charge les patients
de manière inappropriée par insuline alors qu'on peut les prendre en charge de manière
plus efficace par les sulfamides hypoglycémiants par voie orale. Par conséquent, l'établissement
d'un bon diagnostic est essentiel pour un traitement efficace ainsi que pour le conseil
génétique, et plus important pour la qualité de vie des patients. Dans cette revue,
nous avons pour objectif d'accroître la sensibilisation au MODY des cliniciens en
diabète en décrivant les principales caractéristiques cliniques et biologiques des
formes les plus fréquentes de MODY, en soulignant les caractéristiques qui aideraient
à différencier le MODY du diabète de type 1 et de type 2 et en donnant des renseignements
sur les examens et les outils cliniques qui aideraient à déterminer les patients qui
sont plus susceptibles de bénéficier des tests de génétique moléculaire.
Keywords
Mots clés
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of DiabetesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diabetes in the young: A global view and worldwide estimates of numbers of children with type 1 diabetes.Diabetes Res Clin Pract. 2014; 103: 161-175
- The diagnosis and management of monogenic diabetes in children and adolescents.Pediatr Diabetes. 2014; 15: 47-64
- Many faces of monogenic diabetes.J Diabetes Investig. 2014; 5: 121-133
- Maturity onset diabetes of the young: Identification and diagnosis.Ann Clin Biochem. 2013; 50: 403-415
- Maturity-onset diabetes of the young (MODY): How many cases are we missing?.Diabetologia. 2010; 53: 2504-2508
- Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: Results from the SEARCH for Diabetes in Youth.J Clin Endocrinol Metab. 2013; 98: 4055-4062
- Characteristics of maturity onset diabetes of the young in a large diabetes center.Pediatr Diabetes. 2015; (Epub ahead of print)
- Identifying monogenic diabetes in a pediatric cohort with presumed type 1 diabetes.Pediatr Diabetes. 2014; 16: 227-233
- Type 2 diabetes, medication-induced diabetes, and monogenic diabetes in Canadian children: A prospective national surveillance study.Diabetes Care. 2010; 33: 786-791
- Diabetes mellitus and heredity.BMJ. 1928; 2: 738-741
- Mild familial diabetes with dominant inheritance.Q J Med. 1974; 43: 339-357
- New insights from monogenic diabetes for “common” type 2 diabetes.Front Genet. 2015; 6: 251
- Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young.Diabetologia. 2008; 51: 546-553
- De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed.Diabetologia. 2014; 57: 480-484
- 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
- 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
- The genetic abnormality in the beta cell determines the response to an oral glucose load.Diabetologia. 2002; 45: 427-435
- Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia.JAMA. 2014; 311: 279-286
- Pregnancy outcome in patients with raised blood glucose due to a heterozygous glucokinase gene mutation.Diabet Med. 2009; 26: 14-18
- Mutations in the glucokinase gene of the fetus result in reduced birth weight.Nat Genet. 1998; 19: 268-270
- The long-term impact on offspring of exposure to hyperglycaemia in utero due to maternal glucokinase gene mutations.Diabetologia. 2007; 50: 620-624
- Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection.Diabetologia. 2005; 48: 878-885
- Clinical implications of a molecular genetic classification of monogenic β-cell diabetes.Nat Clin Pract Endocrinol Metab. 2008; 4: 200-213
- The type and the position of HNF1A mutation modulate age at diagnosis of diabetes in patients with maturity-onset diabetes of the young (MODY)-3.Diabetes. 2008; 57: 503-508
- HNF1alpha controls renal glucose reabsorption in mouse and man.EMBO Rep. 2000; 1: 359-365
- Lipoprotein composition in HNF1A-MODY: Differentiating between HNF1A-MODY and type 2 diabetes.Clin Chim Acta. 2012; 413: 927-932
- Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene.Diabet Med. 2010; 27: 157-161
- Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene.PLoS Med. 2007; 4: e118
- Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations.Eur J Endocrinol. 2010; 162: 987-992
- Persistent hyperinsulinemic hypoglycemia and maturity-onset diabetes of the young due to heterozygous HNF4A mutations.Diabetes. 2008; 57: 1659-1663
- Home urine C-peptide creatinine ratio testing can identify type 2 and MODY in pediatric diabetes.Pediatr Diabetes. 2013; 14: 181-188
- Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes.Diabet Med. 2011; 28: 1028-1033
- Diabetes susceptibility in the Canadian Oji-Cree population is moderated by abnormal mRNA processing of HNF1A G319S transcripts.Diabetes. 2008; 57: 1978-1982
- The prevalence of the HNF-1alpha G319S mutation in Canadian aboriginal youth with type 2 diabetes.Diabetes Care. 2002; 25: 2202-2206
- Clinical applications of diabetes antibody testing.J Clin Endocrinol Metab. 2010; 95: 25-33
- Urine C-peptide creatinine ratio is a noninvasive alternative to the mixed-meal tolerance test in children and adults with type 1 diabetes.Diabetes Care. 2011; 34: 607-609
- Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-{alpha}/hepatocyte nuclear factor 4-{alpha} maturity-onset diabetes of the young from long-duration type 1 diabetes.Diabetes Care. 2011; 34: 286-291
- 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
- The clinical utility of C-peptide measurement in the care of patients with diabetes.Diabet Med. 2013; 30: 803-817
- 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
- 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
- No deterioration in glycemic control in HNF-1alpha maturity-onset diabetes of the young following transfer from long-term insulin to sulphonylureas.Diabetes Care. 2003; 26: 3191-3192
- Treatment of young patients with HNF1A mutations (HNF1A-MODY).Diabet Med. 2015; 32: 526-530
Article info
Publication history
Published online: April 26, 2016
Accepted:
March 1,
2016
Received in revised form:
January 5,
2016
Received:
October 22,
2015
Identification
Copyright
© 2016 Canadian Diabetes Association.
