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

Abstract

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.

A case report of Maturity-onset diabetes of the young 12: large fragment deletion in ABCC8 gene with literature review

“…Sulphonylureas shut down the K ATP channel via SUR1 receptor in pancreatic β cells, reverse the opening of the K ATP channel that causes ABCC8 mutation, and normalize the secretion of insulin. However, sulphonylureas do not work for all types of ABCC8-mutation related diabetes, a previous study found that 73.3% of the patients owing to ABCC8 variants with SUs got successful glucose control (15). The efficacy also depends on the structural and functional disorder caused by different mutations (18).…”

“…The incidence of diabetic renal disease is low and is only seen in patients with three ABCC8 mutations. It should be noted that 34% of ABCC8neonatal diabetes mellitus (ABCC8-NDM) patients were associated with neurological disease, due to high expression of K ATP channel in both pancreas and nervous system, but the incidence of neurological complications was less than 1% in ABCC8-NNDM patients (15).…”

Single-Cell Gene Expression Analysis in Patients with Medullary Sponge Kidney and a Retrospective Study

“…ACAN variants have been reported to be associated with short stature in recent researches [26,27]. Additionally, ABCC8 was thought to be involved in the development of diabetes [28,29]. However, there was no direct evidence that ACAN and ABCC8 mutations were associated with the incidence of MSK.…”

Genetic Heterogeneity Correlated with Phenotypic Variability in Congenital Hyperinsulinism Caused by Mutation in ABCC8 Gene Associated with Early‐Onset Persistent Neonatal Hypoglycemia

“…In addition, heterozygous carriers of a mutation in the ABCC8 gene require long-term monitoring, as they present an increased risk for diabetes mellitus [39,40].…”