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
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.
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.