Dietary Heme-Iron Intake Increases the Risk of T2D

Data from systematic analysis and dose-response meta-analysis suggests that people who take higher amounts of dietary heme-iron are at higher risk of developing type 2 diabetes.  

High iron intake has been associated with type 2 diabetes. However, no studies have been conducted to evaluate the impact of dietary iron intake on physiological glucose regulation in the body. Type 2 diabetes is a common metabolic disorder that results from too much glucose concentration in the blood due to either insulin failure or the inability of the body to utilize insulin well. Therefore, cells are deprived of glucose as much of it stays in the blood. Various studies have linked iron overload as a predisposing factor for type 2 diabetes. Initially, it was linked with thalassemia. However, iron plays a significant role in metabolism regulation through oxidant stress and intracellular signaling; additionally, it could directly cause type 2 diabetes through beta-cell failure or insulin resistance. A systematic review and dose-response meta-analysis of prospective cohort studies was then conducted to assess the long-term association between supplementary iron intake and the risk of type 2 diabetes. 

The study was conducted through a meta-analysis using preferred reporting items for systematic reviews and meta-analysis guidelines. A systematic literature review search was performed using PubMed and Scopus databases search terms. It involved screening research titles and abstracts using the inclusion and exclusion criteria to identify eligible studies. Data from the chosen studies were extracted in duplicate, and its certainty was rated using the grade approach. Random-effects models were also utilized. The systematic review considered published prospective cohort studies eligible if their participants were 18 years or older. The inclusion criteria also considered studies that reported dietary intake and iron supplementation exposure. 

Moreover, cohort studies provided estimates as relative risk and hazards ratio with a confidence interval of 95% for quantitative studies involving two or more categories of iron intake. Studies that reported dose-response to dietary iron supplementation were also eligible for the analysis. However, cohort studies that involved the assessment of gestational diabetes were excluded. 

Data were extracted by researchers adhering to the characteristics from the identified studies. The author’s name, publication date, age, and sex of the participants, follow-up duration, and assessment methods were extracted and recorded. Research variables used were also entered into a multivariable model. Non-randomized studies were evaluated for originality using the Robins-1 tool. Participants’ selection was also evaluated for each study to determine exposure and outcomes, thus minimizing biases. Statistical analysis was done using a random-effects model to estimate the relative ratio using a confidence interval of 95%. For instance, in some studies with sex-specific effect sizes, sex-specific estimates were combined. It utilized a fixed-estimate model and used combined effect in the analysis. Therefore, the relative risk was determined using the random-effects model. Subgroup analyses were also done to detect heterogeneity by age and geographical location of the participants. In addition, adjustments were made for confounding factors such as energy intake, saturated fats, smoking, physical exercises, and alcoholism. Sensitivity analysis was also conducted on the prospective studies. It was done through a visual examination of funnel plots. 

A random-effects meta-analysis was also conducted to estimate relative risks for contracting type 2 diabetes due to exposure to a specific amount of iron supplements for studies that showed sufficient dose-response information during the meta-analysis. A report was thus generated showing the distribution of cases and the reported effects of the iron intake. Eventually, a one-stage linear mixed-effects analysis was done to clarify the association between iron intake and body response. Through the meta-analysis, exposures were modeled based on Harrell’s percentiles of distribution and the correlation in each category of relative risk taken into account. Lastly, Stata version 15.0. A was utilized for statistical analysis whereby a p-value less than 0.05 was regarded as significant. After identifying 2943 articles, some studies were excluded from the analysis using the eligibility criteria described; therefore, thirty-two articles were used. Based on the study results, it is evident that high heme-iron intake contributed to type 2 diabetes. Higher heme intake was associated with a 20% higher risk of type 2 diabetes, a confidence interval of 95%, and a moderate grade, where n=11, CI 1.07,1.35, and I2 was 77%. Additionally, the dose-response analysis indicated a positive association between daily heme intake and an increase in the relative risk by 16% at a confidence level of 95%. (C I 1.03, 1.30). However, the analysis did not reveal any relevant association between dietary intakes of supplemental iron and the risk of developing type 2 diabetes. In light of these results, it is apparent that a higher intake of heme iron significantly contributes to the development of type 2 diabetes.  

Type 2 diabetes is a public health challenge. If not controlled, it impacts the health of the cardiovascular system, damaging the heart, blood vessels, and other significant organs such as the kidney and brain. Studies on the predisposing factors that contribute to the onset of type 2 diabetes are thus essential. In addition, they may yield valuable data that can be used to formulate evidence-based interventions to prevent type 2 diabetes. Therefore, this study was a utility as it led to revelations that could guide the utilization of dietary supplements.  

In conclusion, despite the study showing an association of high heme intake and a 20% increase in the risk of type 2 diabetes, the study had a weakness as the association between total heme iron intake and supplementary iron intake was not statistically significant. Therefore, it is recommendable for further studies to be conducted to uncover the relationship between iron status and genetic polymorphism with sufficient control for dietary supplementation of other components.  

Practice pearls: 

• Higher intake of heme-iron supplements increases the risk of developing type 2 diabetes 
• Results showed that the association between total non-heme-iron, supplementary iron intake, and type 2 diabetes was insignificant. 
• Higher heme-iron supplements should be avoided to reduce the risk of contracting type 2 diabetes.  

Shahinfar H, Jayedi A, Shab-Bidar S. Dietary iron intake and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective cohort studies [published online ahead of print, 2022 February 2]. Eur J Nutr. 2022;10.1007/s00394-022-02813-2. doi:10.1007/s00394-022-02813-2 

Njideka Aginam, PharmD Candidate, South College School of Pharmacy