Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Sep;13(9):1465-1471.
doi: 10.1111/jdi.13860. Epub 2022 Jun 16.

Precision diabetes: Lessons learned from maturity-onset diabetes of the young (MODY)

Mustafa Tosur  1 , Louis H Philipson  2
Affiliations
Review

Precision diabetes: Lessons learned from maturity-onset diabetes of the young (MODY)

Mustafa Tosur et al. J Diabetes Investig. 2022 Sep.

Abstract

Maturity-onset of diabetes of the young (MODY) are monogenic forms of diabetes characterized by early onset diabetes with autosomal dominant inheritance. Since its first description about six decades ago, there have been significant advancements in our understanding of MODY from clinical presentations to molecular diagnostics and therapeutic responses. The prevalence of MODY is estimated as at least 1.1-6.5% of the pediatric diabetes population with a high degree of geographic variability that might arise from several factors in the criteria used to ascertain cases. GCK-MODY, HNF1A-MODY, and HNF4A-MODY account for >90% of MODY cases. While some MODY forms do not require treatment (i.e., GCK-MODY), some others are highly responsive to oral agents (i.e., HNF1A-MODY). The risk of micro- and macro-vascular complications of diabetes also differ significantly between MODY forms. Despite its high clinical impact, 50-90% of MODY cases are estimated to be misdiagnosed as type 1 or type 2 diabetes. Although there are many clinical features suggestive of MODY diagnosis, there is no single clinical criterion. An online MODY Risk Calculator can be a useful tool for clinicians in the decision-making process for MODY genetic testing in some situations. Molecular genetic tests with a commercial gene panel should be performed in cases with a suspicion of MODY. Unresolved atypical cases can be further studied by exome or genome sequencing in a clinical or research setting, as available.

Keywords: Maturity-onset diabetes of the young; Monogenic diabetes; Pediatric diabetes.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Maturity‐onset diabetes of the young in relation to different forms of diabetes mellitus. [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

References

    1. Fajans SS, Bell GI. MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011; 34: 1878–1884. - PMC - PubMed
    1. Hattersley AT, Greeley SAW, 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. - PubMed
    1. Tattersall RB, Fajans SS. A difference between the inheritance of classical juvenile‐onset and maturity‐onset type diabetes of young people. Diabetes 1975; 24: 44–53. - PubMed
    1. Velho G, Froguel P, Clement K, et al. Primary pancreatic beta‐cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young. Lancet 1992; 340: 444–448. - PubMed
    1. Vionnet N, Stoffel M, Takeda J, et al. Nonsense mutation in the glucokinase gene causes early‐onset non‐insulin‐dependent diabetes mellitus. Nature 1992; 356: 721–722. - PubMed

Supplementary concepts