Positive diagnosis of diabetes is currently easy, but typing diagnosis of diabetes still remains a challenge for every clinician. It is currently accepted that types of diabetes apart from T1D and T2D can expand and include several forms of diabetes mellitus; From gestational diabetes, to all forms of secondary diabetes mellitus due to medications, intercurrent disease but also infections, and finally monogenic diabetes, whose diagnosis is not always easy to establish. The aim is to reveal the difficulties that clinicians may face in the process of etiological diagnosis regarding the suspicion of this type of monogenic diabetes, through the study of 2 cases, in which MODY type diabetes was suspected. Today we recognize 17 different genetic mutations that can all lead to MODY diabetes, the most common mutation of which is GCK coding for the glucokinase, the real sensor of pancreatic Beta-cell. The truly stable glycemic profile, with an A1C ranging between 7% and 7.5%, confirmed with a TIR always above 70% and a good MAGE, but also the rarity of degenerative complications and pharmacological therapeutic abstention which can last for years, these would be the most striking clinical characteristics of a GCK MODY.
References
[1]
Yahaya, T.O. and Ufuoma, S.B. (2020) Genetics and Pathophysiology of Maturity-Onset Diabetes of the Young (MODY): A Review of Current Trends. Oman Medical Journal, 35, e126. https://doi.org/10.5001/omj.2020.44
[2]
Antal, Z. (2021) Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options. Endocrines, 2, 485-501. https://doi.org/10.3390/endocrines2040043
[3]
Skoczek, D., Dulak, J. and Kachamakova-Trojanowska, N. (2021) Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling. International Journal of Molecular Sciences, 22, Article No. 7553. https://doi.org/10.3390/ijms22147553
[4]
Fajans, S.S. and Bell, G.I. (2011) MODY: History, Genetics, Pathophysiology, and Clinical Decision Making. Diabetes Care, 34, 1878-1884. https://doi.org/10.2337/dc11-0035
[5]
Chakera, A.J., Steele, A.M., Gloyn, A.L., Shepherd, M.H., Shields, B., Ellard, S., et al. (2015) Recognition and Management of Individuals with Hyperglycemia Because of a Heterozygous Glucokinase Mutation. Diabetes Care, 38, 1383-1392. https://doi.org/10.2337/dc14-2769
[6]
Billings, L.K., Shi, Z., Resurreccion, W.K., Wang, C., Wei, J., Pollin, T.I., et al. (2022) Statistical Evidence for High-Penetrance MODY-Causing Genes in a Large Population-Based Cohort. Endocrinology, Diabetes & Metabolism, 5, e372. https://doi.org/10.1002/edm2.372
[7]
Sanyoura, M., Letourneau, L., et al. (2019) GCK-MODY in the US Monogenic Diabetes Registry: Description of 27 Unpublished Variants. Diabetes Research and Clinical Practice, 151, 231-236.
[8]
Froguel, P., Zouali, H., Vionnet, N., Velho, G., Vaxillaire, M., Sun, F., et al. (1993) Familial Hyperglycemia Due to Mutations in Glucokinase—Definition of a Subtype of Diabetes Mellitus. New England Journal of Medicine, 328, 697-702. https://doi.org/10.1056/nejm199303113281005
[9]
Barrio, R., Bellanné-Chantelot, C., Moreno, J.C., Morel, V., Calle, H., Alonso, M., et al. (2002) Nine Novel Mutations in Maturity-Onset Diabetes of the Young (MODY) Candidate Genes in 22 Spanish Families. The Journal of Clinical Endocrinology & Metabolism, 87, 2532-2539. https://doi.org/10.1210/jcem.87.6.8530
[10]
Rafique, I., Mir, A., et al. (2021) Causal Variants in Maturity Onset Diabetes of the Young (MODY)—A Systematic Review. BMC Endocrine Disorders, 21, Article No. 223.
Byrne, M.M., Sturis, J., Clément, K., Vionnet, N., Pueyo, M.E., Stoffel, M., et al. (1994) Insulin Secretory Abnormalities in Subjects with Hyperglycemia Due to Glucokinase Mutations. Journal of Clinical Investigation, 93, 1120-1130. https://doi.org/10.1172/jci117064
[13]
Ren, Q., Zhang, P., et al. (2023) A Comparison of Daily Glucose Fluctuation between GCK-MODY and Type 2 Diabetes Using Continuous Glucose Monitoring Technology. Diabetes, 72, 812-818. https://doi.org/10.2337/db22-0566
[14]
Naylor, R., Knight Johnson, A. and del Gaudio, D. (1993) Maturity-Onset Diabetes of the Young Overview. In: Adam, M.P., Ardinger, H.H., Pagon, R.A., et al., Eds., GeneReviews®, University of Washington, 1993-2024. http://www.ncbi.nlm.nih.gov/books/NBK500456/
[15]
Tuomi, T., Honkanen, E.H., Isomaa, B., Sarelin, L. and Groop, L.C. (2006) Improved Prandial Glucose Control with Lower Risk of Hypoglycemia with Nateglinide than with Glibenclamide in Patients with Maturity-Onset Diabetes of the Young Type 3. Diabetes Care, 29, 189-194. https://doi.org/10.2337/diacare.29.02.06.dc05-1314
[16]
Steele, A.M., Shields, B.M., Wensley, K.J., Colclough, K., Ellard, S. and Hattersley, A.T. (2014) Prevalence of Vascular Complications among Patients with Glucokinase Mutations and Prolonged, Mild Hyperglycemia. JAMA, 311, 279-286. https://doi.org/10.1001/jama.2013.283980
[17]
Hulín, J., Škopková, M., Valkoviˇcová, T., Mikulajová, S., Rosol’anková, M., Papcun, P., Gašperíková, D. and Staník, J. (2020) Clinical Implications of the Glucokinase Impaired Function—GCK MODY Today. Physiological Research, 69, 995-1011. https://doi.org/10.33549/physiolres.934487
[18]
Magdaleno, A., Venkataraman, S. and Perilli, G. (2017) Euglycemic DKA in MODY Patient: Empagliflozin to Blame. Endocrine Practice, 23, 41-42. https://www.proquest.com/openview/9a1494f6c14b4488c7e54b8465fe47dc/1?pq-origsite=gscholar&cbl=1896353
[19]
Ellard, S., Bellanné-Chantelot, C., Hattersley, A.T. and European Molecular Genetics Quality Network (EMQN) MODY Group (2008) Best Practice Guidelines for the Molecular Genetic Diagnosis of Maturity-Onset Diabetes of the Young. Diabetologia, 51, 546-553. https://doi.org/10.1007/s00125-008-0942-y
