Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review

Objectives. Diabetes mellitus (DM) is a major chronic metabolic disease in the world, and the prevalence has been increasing rapidly in recent years. The channel of KATP plays an important role in the regulation of insulin secretion. The variants in ABCC8 gene encoding the SUR1 subunit of KATP could...

Full description

Saved in:
Bibliographic Details
Main Authors: Meng Li, Xueyao Han, Linong Ji
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2021/9479268
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832561441991819264
author Meng Li
Xueyao Han
Linong Ji
author_facet Meng Li
Xueyao Han
Linong Ji
author_sort Meng Li
collection DOAJ
description Objectives. Diabetes mellitus (DM) is a major chronic metabolic disease in the world, and the prevalence has been increasing rapidly in recent years. The channel of KATP plays an important role in the regulation of insulin secretion. The variants in ABCC8 gene encoding the SUR1 subunit of KATP could cause a variety of phenotypes, including neonatal diabetes mellitus (ABCC8-NDM) and ABCC8-induced nonneonatal diabetes mellitus (ABCC8-NNDM). Since the features of ABCC8-NNDM have not been elucidated, this study is aimed at concluding the genetic features and clinical characteristics. Methods. We comprehensively reviewed the literature associated with ABCC8-NNDM in the following databases: MEDLINE, PubMed, and Web of Science to investigate the features of ABCC8-NNDM. Results. Based on a comprehensive literature search, we found that 87 probands with ABCC8-NNDM carried 71 ABCC8 genetic variant alleles, 24% of whom carried inactivating variants, 24% carried activating variants, and the remaining 52% carried activating or inactivating variants. Nine of these variants were confirmed to be activating or inactivating through functional studies, while four variants (p.R370S, p.E1506K, p.R1418H, and p.R1420H) were confirmed to be inactivating. The phenotypes of ABCC8-NNDM were variable and could also present with early hyperinsulinemia followed by reduced insulin secretion, progressing to diabetes later. They had a relatively high risk of microvascular complications and low prevalence of nervous disease, which is different from ABCC8-NDM. Conclusions. Genetic testing is essential for proper diagnosis and appropriate treatment for patients with ABCC8-NNDM. And further studies are required to determine the complex mechanism of the variants of ABCC8-NNDM.
format Article
id doaj-art-90668e728c7148caa7162701d070ecaf
institution Kabale University
issn 2314-6745
2314-6753
language English
publishDate 2021-01-01
publisher Wiley
record_format Article
series Journal of Diabetes Research
spelling doaj-art-90668e728c7148caa7162701d070ecaf2025-02-03T01:25:07ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/94792689479268Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic ReviewMeng Li0Xueyao Han1Linong Ji2Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, 100044, ChinaDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, 100044, ChinaDepartment of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing, 100044, ChinaObjectives. Diabetes mellitus (DM) is a major chronic metabolic disease in the world, and the prevalence has been increasing rapidly in recent years. The channel of KATP plays an important role in the regulation of insulin secretion. The variants in ABCC8 gene encoding the SUR1 subunit of KATP could cause a variety of phenotypes, including neonatal diabetes mellitus (ABCC8-NDM) and ABCC8-induced nonneonatal diabetes mellitus (ABCC8-NNDM). Since the features of ABCC8-NNDM have not been elucidated, this study is aimed at concluding the genetic features and clinical characteristics. Methods. We comprehensively reviewed the literature associated with ABCC8-NNDM in the following databases: MEDLINE, PubMed, and Web of Science to investigate the features of ABCC8-NNDM. Results. Based on a comprehensive literature search, we found that 87 probands with ABCC8-NNDM carried 71 ABCC8 genetic variant alleles, 24% of whom carried inactivating variants, 24% carried activating variants, and the remaining 52% carried activating or inactivating variants. Nine of these variants were confirmed to be activating or inactivating through functional studies, while four variants (p.R370S, p.E1506K, p.R1418H, and p.R1420H) were confirmed to be inactivating. The phenotypes of ABCC8-NNDM were variable and could also present with early hyperinsulinemia followed by reduced insulin secretion, progressing to diabetes later. They had a relatively high risk of microvascular complications and low prevalence of nervous disease, which is different from ABCC8-NDM. Conclusions. Genetic testing is essential for proper diagnosis and appropriate treatment for patients with ABCC8-NNDM. And further studies are required to determine the complex mechanism of the variants of ABCC8-NNDM.http://dx.doi.org/10.1155/2021/9479268
spellingShingle Meng Li
Xueyao Han
Linong Ji
Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review
Journal of Diabetes Research
title Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review
title_full Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review
title_fullStr Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review
title_full_unstemmed Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review
title_short Clinical and Genetic Characteristics of ABCC8 Nonneonatal Diabetes Mellitus: A Systematic Review
title_sort clinical and genetic characteristics of abcc8 nonneonatal diabetes mellitus a systematic review
url http://dx.doi.org/10.1155/2021/9479268
work_keys_str_mv AT mengli clinicalandgeneticcharacteristicsofabcc8nonneonataldiabetesmellitusasystematicreview
AT xueyaohan clinicalandgeneticcharacteristicsofabcc8nonneonataldiabetesmellitusasystematicreview
AT linongji clinicalandgeneticcharacteristicsofabcc8nonneonataldiabetesmellitusasystematicreview