Prevalence, clinical features and complications of common forms of Maturity Onset Diabetes of the Young (MODY) seen at a tertiary diabetes centre in south India.
ABCC8-MODY
Asian Indians
Diabetes complications
HNF1A-MODY
HNF4A-MODY
India
MODY
MODY 1
MODY 12
MODY3
Maturity-onset diabetes of the young
Monogenic diabetes
South Asians
Journal
Primary care diabetes
ISSN: 1878-0210
Titre abrégé: Prim Care Diabetes
Pays: England
ID NLM: 101463825
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
30
09
2022
revised:
17
03
2023
accepted:
07
04
2023
medline:
1
8
2023
pubmed:
14
4
2023
entrez:
13
4
2023
Statut:
ppublish
Résumé
Maturity Onset Diabetes of the Young (MODY) is a form of monogenic diabetes caused by mutations in single genes, affecting adolescents or young adults. MODY is frequently misdiagnosed as type 1 diabetes (T1). Though several studies from India have reported on the genetic aspects of MODY, the clinical profile, complications and treatments given have not been reported so far, nor compared with T1D and type 2 diabetes (T2D). To determine the prevalence, clinical features, and complications of common forms of genetically proven MODY seen at a tertiary diabetes centre in South India and compare them with matched individuals with T1D and T2D. Five hundred and thirty individuals identified as 'possible MODY' based on clinical criteria, underwent genetic testing for MODY. Diagnosis of MODY was confirmed based on pathogenic or likely pathogenic variants found using Genome Aggregation Database (gnomAD) and American College of Medical Genetics (ACMG) criteria. The clinical profile of MODY was compared with individuals with type 1 (T1D) and type 2 (T2D) diabetes, matched for duration of diabetes. Retinopathy was diagnosed by retinal photography; nephropathy by urinary albumin excretion > 30 µg/mg of creatinine and neuropathy by vibration perception threshold > 20 v on biothesiometry. Fifty-eight patients were confirmed to have MODY (10.9%). HNF1A-MODY (n = 25) was the most common subtype followed by HNF4A-MODY (n = 11), ABCC8-MODY (n = 11), GCK-MODY (n = 6) and HNF1B-MODY (n = 5). For comparison of clinical profile, only the three 'actionable' subtypes - defined as those who may respond to sulphonylureas, namely, HNF1A, HNF4A and ABCC8-MODY, were included. Age at onset of diabetes was lower among HNF4A-MODY and HNF1A-MODY than ABCC8-MODY, T1D and T2D. Prevalence of retinopathy and nephropathy was higher among the three MODY subtypes taken together (n = 47) as compared to T1D (n = 86) and T2D (n = 86). This is one of the first reports of MODY subtypes from India based on ACMG and gnomAD criteria. The high prevalence of retinopathy and nephropathy in MODY points to the need for earlier diagnosis and better control of diabetes in individuals with MODY.
Sections du résumé
BACKGROUND
Maturity Onset Diabetes of the Young (MODY) is a form of monogenic diabetes caused by mutations in single genes, affecting adolescents or young adults. MODY is frequently misdiagnosed as type 1 diabetes (T1). Though several studies from India have reported on the genetic aspects of MODY, the clinical profile, complications and treatments given have not been reported so far, nor compared with T1D and type 2 diabetes (T2D).
AIM
To determine the prevalence, clinical features, and complications of common forms of genetically proven MODY seen at a tertiary diabetes centre in South India and compare them with matched individuals with T1D and T2D.
METHODS
Five hundred and thirty individuals identified as 'possible MODY' based on clinical criteria, underwent genetic testing for MODY. Diagnosis of MODY was confirmed based on pathogenic or likely pathogenic variants found using Genome Aggregation Database (gnomAD) and American College of Medical Genetics (ACMG) criteria. The clinical profile of MODY was compared with individuals with type 1 (T1D) and type 2 (T2D) diabetes, matched for duration of diabetes. Retinopathy was diagnosed by retinal photography; nephropathy by urinary albumin excretion > 30 µg/mg of creatinine and neuropathy by vibration perception threshold > 20 v on biothesiometry.
RESULTS
Fifty-eight patients were confirmed to have MODY (10.9%). HNF1A-MODY (n = 25) was the most common subtype followed by HNF4A-MODY (n = 11), ABCC8-MODY (n = 11), GCK-MODY (n = 6) and HNF1B-MODY (n = 5). For comparison of clinical profile, only the three 'actionable' subtypes - defined as those who may respond to sulphonylureas, namely, HNF1A, HNF4A and ABCC8-MODY, were included. Age at onset of diabetes was lower among HNF4A-MODY and HNF1A-MODY than ABCC8-MODY, T1D and T2D. Prevalence of retinopathy and nephropathy was higher among the three MODY subtypes taken together (n = 47) as compared to T1D (n = 86) and T2D (n = 86).
CONCLUSION
This is one of the first reports of MODY subtypes from India based on ACMG and gnomAD criteria. The high prevalence of retinopathy and nephropathy in MODY points to the need for earlier diagnosis and better control of diabetes in individuals with MODY.
Identifiants
pubmed: 37055265
pii: S1751-9918(23)00071-2
doi: 10.1016/j.pcd.2023.04.004
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
401-407Informations de copyright
Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest M/s Serdia Pharmaceuticals and M/s Servier are manufacturers of Gliclazide used in treatment of MODY.