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Targeted next-generation sequencing for maturity onset diabetes of the young (MODY) in a South Indian cohort of type 1 diabetes mellitus patients with preserved C-peptide

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International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Objective

MODY (maturity onset diabetes of the young) is a rare, monogenic, autosomal dominant form of diabetes occurring in young (< 25 years) individuals. It has a wide phenotypic variability and can be misdiagnosed as type 1 diabetes mellitus (T1DM). Appropriate detection of MODY has therapeutic and genetic implications. This study aimed to detect MODY among long standing, clinically diagnosed T1DM patients with preserved C-peptide levels.

Methods

This was a hospital-based cross-sectional study from central South India which included 100 clinically diagnosed T1DM patients (according to ADA criteria), with a duration of > 3 years. MODY probability score, urinary C-peptide to creatinine ratio (UCPCR), and relevant biochemical investigations were performed. Targeted next-generation sequencing (NGS) for MODY-related genes (13 genes) was done for individuals with UCPCR > 0.2.

Results

A UCPCR value of > 0.2 (suggestive of preserved endogenous insulin secretion) was observed in eight individuals. The mean HbA1c values were lower, and the MODY probability score was higher in individuals with preserved endogenous insulin (8.07% vs 9.53% and 2.8% vs 1.5%; p-value: 0.005 and 0.004 respectively). One of the eight individuals (12.5%) had a non-pathogenic gene variant in KLF11.

Conclusion

In a South Indian cohort of T1DM with preserved C-peptide, we could not find any case of MODY through targeted NGS. UCPCR can be used as a screening tool to identify cases needing genetic testing for MODY. Larger studies utilizing whole exome sequencing should be conducted to know the actual prevalence of MODY among T1DM.

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Data Availability

The data from the present study are not publicly available but can be made available from corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Endocrinology, Gandhi Medical College, 3rd Floor, Musheerabad, Secunderabad, Telangana, 500003, India

    Vijay Sheker Reddy Danda, Sandeep Reddy Devireddy, Srinivas Rao Paidipally, Piyush Lodha & Vivek Kyatham

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  1. Vijay Sheker Reddy Danda
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The present manuscript has been read and approved by all the authors. The requirements for authorship have been met, and each author believes that the manuscript represents honest work.

Concepts: Contributor 1, Contributor 2, Contributor 3, Contributor 4, Contributor 5

Design: Contributor 1, Contributor 2, Contributor 3, Contributor 4, Contributor 5

Definition of intellectual content: Contributor 1, Contributor 2, Contributor 3, Contributor 4, Contributor 5

Literature search: Contributor 1, Contributor 2, Contributor 3, Contributor 4, Contributor 5

Clinical studies: Contributor 1, Contributor 2, Contributor 3, Contributor 4, Contributor 5

Experimental studies, Data acquisition: Contributor 1, Contributor 2, Contributor 3, Contributor 4, Contributor 5

Data analysis: Contributor 1, Contributor 2, Contributor 4, Contributor 5

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Correspondence to Vijay Sheker Reddy Danda.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Approval for this study was obtained from the Institutional Ethical Committee (approval number: IEC/GMC/2019/04/8, dated 05/09/2019).

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Informed consent was obtained from all individual participants (or parents if minor) included in the study.

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Danda, V.S.R., Devireddy, S.R., Paidipally, S.R. et al. Targeted next-generation sequencing for maturity onset diabetes of the young (MODY) in a South Indian cohort of type 1 diabetes mellitus patients with preserved C-peptide. Int J Diabetes Dev Ctries (2023). https://doi.org/10.1007/s13410-023-01245-w

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