Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 10, 2016; 7(1): 8-13
Published online Jan 10, 2016. doi: 10.4239/wjd.v7.i1.8
Tipping the balance: Haemoglobinopathies and the risk of diabetes
Henry J Baldwin, Aislinn E Green, Kayleigh M Spellar, Philip J Arthur, Hannah G Phillips, Jeetesh V Patel
Henry J Baldwin, Aislinn E Green, Kayleigh M Spellar, Philip J Arthur, Hannah G Phillips, Jeetesh V Patel, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom
Jeetesh V Patel, University of Birmingham Centre for Cardiovascular Sciences, Sandwell and West Birmingham Hospitals NHS Trust, West Midlands B18 7QH, United Kingdom
Jeetesh V Patel, Sandwell Medical Research Unit, Lyndon, Sandwell General Hospital, West Midlands B71 4HJ, United Kingdom
Author contributions: All authors contributed to the manuscript.
Conflict-of-interest statement: All authors declare that they have no competing interests.
Data sharing statement: This was a systematic review of the available literature and was not undertaken as a meta-analysis of data. As authors we did not undertake any statistical analyses nor did we generate any data. All the data and statistics reported in the review as those reported in the original articles (referenced to other authors). As such a datasharing statement would be inappropriate.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Jeetesh V Patel, Sandwell Medical Research Unit, Lyndon, Sandwell General Hospital, West Bromwich, West Midlands B71 4HJ, United Kingdom. jeeteshp@gmail.com
Telephone: +44-121-5073971 Fax: +44-121-5073216
Received: May 29, 2015
Peer-review started: June 3, 2015
First decision: September 17, 2015
Revised: October 28, 2015
Accepted: December 1, 2015
Article in press: December 2, 2015
Published online: January 10, 2016
Processing time: 226 Days and 13.6 Hours
Abstract

AIM: To establish a link between the risk of diabetes with haemoglobinopathies by examining available evidence of the effects of iron and blood glucose homeostasis from molecular to epidemiological perspectives.

METHODS: A systematic literature search was performed using electronic literature databases using various search terms. The International Diabetes Federation World Atlas was used to generate a list of populations with high rates of diabetes. PubMed, Scopus and Google Scholar were used to identify which of these populations also had a reported prevalence of haemoglobin abnormalities.

RESULTS: Abnormalities in iron homeostasis leads to increases in reactive oxygen species in the blood. This promotes oxidative stress which contributes to peripheral resistance to insulin in two ways: (1) reduced insulin/insulin receptor interaction; and (2) β-cell dysfunction. Hepcidin is crucial in terms of maintaining appropriate amounts of iron in the body and is in turn affected by haemoglobinopathies. Hepcidin also has other metabolic effects in places such as the liver but so far the extent of these is not well understood. It does however directly control the levels of serum ferritin. High serum ferritin is found in obese patients and those with diabetes and a meta-analysis of the various studies shows that high serum ferritin does indeed increase diabetes risk.

CONCLUSION: From an epidemiological standpoint, it is plausible that the well-documented protective effects of haemoglobinopathies with regard to malaria may have also offered other evolutionary advantages. By contributing to peripheral insulin resistance, haemoglobinopathies may have helped to sculpt the so-called “thrifty genotype”, which hypothetically is advantageous in times of famine. The prevalence data however is not extensive enough to provide concrete associations between diabetes and haemoglobinopathies - more precise studies are required.

Keywords: Diabetes; Ferritin; Haemoglobinopathy; Iron metabolism; Malaria

Core tip: Are diabetes and haemoglobinopathies linked? There is strong evidence to suggest that the processes involved in both iron and blood glucose homeostasis interact with one another. Metabolic disorders involving iron appear to contribute to the pathological process of diabetes at least on a cellular level. This article also examines prevalence data of diabetes and various haemoglobinopathies in certain populations to establish whether there is an association from an epidemiological perspective.