A Systematic Review of Childhood Diabetes Research in the Middle East Region

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Abstract

Background: Diabetes mellitus (DM) is a common chronic disorder in children and is caused by absolute or relative insulin deficiency, with or without insulin resistance. There are several different forms of childhood DM. Children can suffer from neonatal diabetes mellitus (NDM), type 1 diabetes (T1DM), type 2 diabetes (T2DM), Maturity Onset Diabetes of the Young (MODY), autoimmune monogenic, mitochondrial, syndromic and as yet unclassified forms of DM. The Middle East has one of the highest incidences of several types of DM in children; however, it is unclear whether pediatric diabetes is an active area of research in the Middle East and if ongoing, which research areas are of priority for DM in children.

Objectives: To review the literature on childhood DM related to research in the Middle East, summarize results, identify opportunities for research and make observations and recommendations for collaborative studies in pediatric DM.

Methods: We conducted a thorough and systematic literature review by adhering to a list recommended by PRISMA. We retrieved original papers written in English that focus on childhood DM research, using electronic bibliographic databases containing publications from the year 2000 until October 2018. For our final assessment, we retrieved 429 full-text articles and selected 95 articles, based on our inclusion and exclusion criteria.

Results: Our literature review suggests that childhood DM research undertaken in the Middle East has focused mainly on reporting retrospective review of case notes, a few prospective case studies, systemic reviews, questionnaire-based studies, and case reports. These reported studies have focused mostly on the incidence/prevalence of different types of DM in childhood. No studies report on the establishment of National Childhood Diabetes Registries. There is a lack of consolidated studies focusing on national epidemiology data of different types of childhood DM (such as NDM, T1DM, T2DM, MODY, and syndromic forms) and no studies reporting on clinical trials in children with DM.

Conclusions: Investing in and funding basic and translational childhood diabetes research and encouraging collaborative studies, will bring enormous benefits financially, economically, and socially for the whole of the Middle East region.

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Most cited references 80

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Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.

Anna L. Gloyn, Ewan Pearson, Jennifer F Antcliff … (2004)

Patients with permanent neonatal diabetes usually present within the first three months of life and require insulin treatment. In most, the cause is unknown. Because ATP-sensitive potassium (K(ATP)) channels mediate glucose-stimulated insulin secretion from the pancreatic beta cells, we hypothesized that activating mutations in the gene encoding the Kir6.2 subunit of this channel (KCNJ11) cause neonatal diabetes. We sequenced the KCNJ11 gene in 29 patients with permanent neonatal diabetes. The insulin secretory response to intravenous glucagon, glucose, and the sulfonylurea tolbutamide was assessed in patients who had mutations in the gene. Six novel, heterozygous missense mutations were identified in 10 of the 29 patients. In two patients the diabetes was familial, and in eight it arose from a spontaneous mutation. Their neonatal diabetes was characterized by ketoacidosis or marked hyperglycemia and was treated with insulin. Patients did not secrete insulin in response to glucose or glucagon but did secrete insulin in response to tolbutamide. Four of the patients also had severe developmental delay and muscle weakness; three of them also had epilepsy and mild dysmorphic features. When the most common mutation in Kir6.2 was coexpressed with sulfonylurea receptor 1 in Xenopus laevis oocytes, the ability of ATP to block mutant K(ATP) channels was greatly reduced. Heterozygous activating mutations in the gene encoding Kir6.2 cause permanent neonatal diabetes and may also be associated with developmental delay, muscle weakness, and epilepsy. Identification of the genetic cause of permanent neonatal diabetes may facilitate the treatment of this disease with sulfonylureas. Copyright 2004 Massachusetts Medical Society

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Type I diabetes mellitus. A chronic autoimmune disease.

G S Eisenbarth (1986)

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Language bias in randomised controlled trials published in English and German.

M. Egger, T Zellweger-Zähner, M. Schneider … (1997)

Some randomised controlled trials (RCTs) done in German-speaking Europe are published in international English-language journals and others in national German-language journals. We assessed whether authors are more likely to report trials with statistically significant results in English than in German. We studied pairs of RCT reports, matched for first author and time of publication, with one report published in German and the other in English. Pairs were identified from reports round in a manual search of five leading German-language journals and from reports published by the same authors in English found on Medline. Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors' identities, affiliations, and other characteristics of trial reports. Main study endpoints were selected by two investigators who were unaware of trial results. Our main outcome was the number of pairs of studies in which the levels of significance (shown by p values) were discordant. 62 eligible pairs of reports were identified but 19 (31%) were excluded because they were duplicate publications. A further three pairs (5%) were excluded because no p values were given. The remaining 40 pairs were analysed. Design characteristics and quality features were similar for reports in both languages. Only 35% of German-language articles, compared with 62% of English-language articles, reported significant (p < 0.05) differences in the main endpoint between study and control groups (p = 0.002 by McNemar's test). Logistic regression showed that the only characteristic that predicted publication in an English-language journal was a significant result. The odds ratio for publication of trials with significant results in English was 3.75 (95% CI 1.25-11.3). Authors were more likely to publish RCTs in an English-language journal if the results were statistically significant. English language bias may, therefore, be introduced in reviews and meta-analyses if they include only trials reported in English. The effort of the Cochrane Collaboration to identify as many controlled trials as possible, through the manual search of many medical journals published in different languages will help to reduce such bias.

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Author and article information

Contributors

Saras Saraswathi: URI : http://loop.frontiersin.org/people/548626/overview

Sara Al-Khawaga: URI : http://loop.frontiersin.org/people/624578/overview

Naser Elkum: URI : http://loop.frontiersin.org/people/628141/overview

Khalid Hussain: URI : http://loop.frontiersin.org/people/155756/overview

Journal

Journal ID (nlm-ta): Front Endocrinol (Lausanne)

Journal ID (iso-abbrev): Front Endocrinol (Lausanne)

Journal ID (publisher-id): Front. Endocrinol.

Title: Frontiers in Endocrinology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-2392

Publication date (Electronic): 19 November 2019

Publication date Collection: 2019

Volume: 10

Electronic Location Identifier: 805

Affiliations

[1] ¹Division of Endocrinology, Department of Pediatrics, Sidra Medicine , Doha, Qatar

[2] ²College of Health & Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City , Doha, Qatar

[3] ³Biostatistics Section, Clinical Research Center, Research Services, Sidra Medicine , Doha, Qatar

Author notes

Edited by: Jehad Ahmed Abubaker, Dasman Diabetes Institute, Kuwait

Reviewed by: Stephanie Therese Chung, National Institutes of Health (NIH), United States; Mohammad G. Qaddoumi, Health Science Center, Kuwait

*Correspondence: Khalid Hussain khussain@ 123456sidra.org

This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Endocrinology

†These authors share first authorship

Article

DOI: 10.3389/fendo.2019.00805

PMC ID: 6882272

PubMed ID: 31824422

SO-VID: 11104cee-bd2f-41a6-87eb-9b177bb64a30

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 18 December 2018

Date accepted : 04 November 2019

Page count

Figures: 5, Tables: 7, Equations: 0, References: 102, Pages: 19, Words: 15280

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A Systematic Review of Childhood Diabetes Research in the Middle East Region

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Journal of the ASEAN Federation of Endocrine Societies

Most cited references 80

Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.

Type I diabetes mellitus. A chronic autoimmune disease.

Language bias in randomised controlled trials published in English and German.

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Cited by 9

Most referenced authors 2,419