Clinical and genetic characterization and long-term evaluation of individuals with maturity-onset diabetes of the young (MODY): The journey towards appropriate treatment

Author(s)

Franco, Pedro Campos ; Santana, Lucas Santos de ; Costa-Riquetto, Aline Dantas ; Santomauro, Augusto Cezar ; Jorge, Alexander A. L. ; Teles, Milena Gurgel

• Document type: Journal article
• Source: Diabetes Research and Clinical Practice; v. 187, p. 9-pg., 2022-05-01.

Abstract

Aims: To describe the clinical and genetic characteristics and long-term follow-up of a cohort with maturity-onset diabetes of the young (MODY), and to evaluate how molecular diagnosis impacted on treatment. Methods: A large observational, retrospective, cohort study included individuals referred to the University of Sa tilde o Paulo's Monogenic Diabetes Unit between 2011 and 2020. Comprehensive clinical and genetic evaluations were performed. Results: Overall, 228 individuals (190 GCK-MODY and 38 HNF1A-MODY) were enrolled. Sixty-two different GCK gene mutations (5 novel) and 17 HNF1A gene mutations (2 novel) were found. Data were available on treatment status for 76 index individuals with GCK-MODY. Before molecular diagnosis, nutritional intervention alone was used in 41 cases (53.9%). After molecular diagnosis, this number increased to 72 (94.8%). Glycated haemoglobin (HbA1c) remained stable over the 6-year follow-up period: 6.5% (47 mmol/mol) at the first and 6.3% (45 mmol/ mol) at the final visit (p = 0.056). Prior to molecular diagnosis, 7/21 (33.3%) HNF1A-MODY individuals were using sulfonylurea compared to 17/21 (81%) after testing. After a median of 5 years on sulfonylureas, HbA1c values improved from 7.5% (58 mmol/mol) to 6.5% (48 mmol/mol) (p = 0.006). Conclusions: Molecular diagnosis resulted in appropriate adjustment of treatment in approximately 80% of participants with GCK-MODY or HNF1A-MODY. (AU)

• FAPESP's process: 17/15365-5 - EXOME STUDY IN FAMILIES WITH CLINICAL DIAGNOSIS OF MODY (Maturity-Onset Diabetes of the Young) AND NEONATAL DIABETES
• Grantee: Milena Gurgel Teles Bezerra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/14703-4 - Exome study in families with clinical diagnosis of MODY (Maturity-Onset Diabetes of the Young) and Neonatal Diabetes
• Grantee: Lucas Santos de Santana
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/19920-2 - Next-generation sequencing analysis of patients with clinical diagnosis of MODY (maturity onset diabetes of the young)
• Grantee: Milena Gurgel Teles Bezerra
• Support Opportunities: Regular Research Grants