Serum Ferritin Level Linked to Male Type-2 Diabetes Mellitus Patients Amongst Residents of Hyderabad, Sindh

Introduction: Diabetes mellitus is a metabolic disorder which is caused by either deficiency of insulin or its disturbed action on peripheral receptors. Globally it is estimated that 451 million peoples were suffering from Diabetes mellitus type 2 in 2017 and this burden will rise to 693million in 2045.The relationship between diabetes mellitus and serum ferritin levels is intricately linked, sharing a common intersection in the liver where both glucose metabolism and iron metabolism converge. Aims and Objectives: To measure the serum ferritin levels among residents of Hyderabad with type 2 Diabetes Mellitus. Place and Duration of study: The study was conducted in the Outpatient Department (OPD) of Liaquat university Hospital from June 2022 to August 2022 (3 months). Material and Methods: The study consists of 100 subjects divided into two groups, a control group consists of 50 normal healthy people with normal fasting glucose below 100mg/dl and a Case group consists of 50 patients with fasting glucose level more than 125 mg/dl according to World Health Organization criteria. Their Serum ferritin levels were evaluated using the ELFA method, employing a commercially available kit supplied by Roche Cobas Integra. (cid:3) The results were analyzed on the software Graph Pad Prism 9, p-value (cid:148) 0.05 was taken as significant. Results: The frequency of Type 2 Diabetes mellitus was significantly higher in patients with increased serum ferritin levels (P=0.001) with an odds ratio of 1.838 , a sensitivity/specifity value of (0.50/0.56) and a robust likelihood ratio of 2.25. Conclusion: The study underscores a potential link between elevated serum ferritin and Diabetes Mellitus Type-2.


INTRODUCTION
Diabetes mellitus is a metabolic disorder characterized by dysregulation of insulin; a hormone responsible for regulating carbohydrate metabolism 1 .Diabetes mellitus comprises two primary types: Type-1, marked by inadequate insulin secretion from pancreatic beta cells; and Type-2, characterized by heightened peripheral resistance to insulin 2 .Iron stands as a vital micronutrient crucial for the human body, playing a pivotal role in various physiological processes.
The absorption of iron takes place within the small pivotal role in various physiological processes.The absorption of iron takes place within the small intestine, and subsequently, it traverses the bloodstream to reach the iron-utilizing units within the body.It is noteworthy that in the circulatory system, iron is transported by a glycoprotein known as transferrin 3 .The iron overload leads to inflammation in the liver and pancreas.It decreases the insulin release and insulin resistance at the tissue level leading to Diabetes or deteriorating already existing disease 4 .The iron circulates in the plasma by binding to protein called transferrin which is regulated by a specific hormone called Hepcidin (HAMP).It is found that in Diabetes these hormones decrease in the serum leading to hyperferritinemia.The pathophysiology of this association involves increased iron accumulation in the body, which causes oxidative stress and damages hepatocytes.This affects the secretion of insulin and disrupts the normal regulation of glucose metabolism 5 .Elevated ferritin levels not only contribute to insulin resistance but also disturb cholesterol levels, increasing the risk of cardiovascular events such as atherosclerosis,

Serum Ferritin Level Linked to Male Type-2 Diabetes Mellitus Patients Amongst Residents of Hyderabad, Sindh
arteriosclerosis, DVTs, metabolic syndromes, dyslipidemia, and even cancers 6 .Elevated serum ferritin levels in males are strongly associated with inflammation and oxidative stress, which play a critical role in the development of diabetes mellitus in the male population. 79] .Ferritin, as one of the acute phase reactants, increases during inflammatory processes such as diabetes, which results from hepatocyte injury 10 .The normal levels of ferritin in blood serum vary from male to female with average level in 24 to 336 ng/ml in adult men and from 25 to 200 ng/ml in adult women 11 .An insightful meta-analysis underscores a discernible association, revealing heightened prevalence in the development of diabetes mellitus amongst individuals exhibiting elevated serum ferritin levels and abnormal Hepcidin levels, in contrast to those maintaining normative serum ferritin and Hepcidin levels 12 .Although inherited hemochromatosis and thalassemia were the pathologic disorders that initially revealed the connection between iron and diabetes, excessive dietary iron levels also increase the risk of Diabetes.Iron is directly and causally involved in the etiology of Diabetes, through its mediation of both insulin resistance and -cell failure 13 .To mitigate the risk of diabetes mellitus, it is imperative to proactively manage lifestyle choices, maintain a well-balanced diet encompassing appropriate micro and macro nutrients, and utilize suitable therapeutic interventions.A pivotal aspect of this preventive approach involves vigilant monitoring and adjustment of ferritin levels to align with the established normal range 14 .Some other studies also shows that use of chelating agents also lowers chances of oxidative injury to insulin receptors and lowers the prevalence of Diabetes Mellitus Type-2 15 .The aim of this study is to investigate the serum ferritin levels amongst residents of Hyderabad with Type-2 Diabetes Mellitus.The rationale for the study is that, as this type of research has never been conducted in Hyderabad, Sindh, the findings will be included into guidelines for the management of diabetes mellitus in the local population.

MATERIAL AND METHODS
This comparative cross-sectional study was conducted from June 2022 to August 2022 after approval from Ethical Review Committee of Department of Physiology, Sindh University Jamshoro vide letter No Physiol/27, dated 10/03/2022.The venue was Outpatient Department of General Medicine in association with Research laboratory of Liaquat University Hospital Hyderabad.This study enrolled 100 male residents of District Hyderabad, Sindh.Male subjects were included due to differences in hematological parameters in males and females, and the hormonal influence of testosterone in males that affects the levels of serum ferritin compared to females.These confounding variables were considered for the accuracy of results, and only male subjects were included.The participants age ranged between 40 to 70 years.The control group consists of 50 normal healthy people with fasting glucose below 100mg/dl and Case group consisted of 50 patients with fasting glucose level more than 125 mg/dl.Only Diabetes Type 2 patients with a history of higher serum glycemic level (HbA1C level more than 6.5) for the last 2 years were selected.All those patients who were below 40 or more than 70 years, with history of blood transfusion, taking iron supplementation and having any chronic condition like hypertension were excluded from this study.The reluctant participants and those residing outside Hyderabad district are excluded.The consent of all the participants was taken in written and they were completely briefed about the aims, objective and procedure of the study.A thorough clinical examination including blood pressure and pulse was recorded by digital sphygmomanometer.The fasting blood sugar level was monitored by Care Sense glucometer made in Korea.The blood samples of all the patients were subjected to analysis in order to quantify plasma glucose through glucose oxidase-peroxidase method.Whole blood specimens were collected in vials of EDTA and were employed for the determination of HbA1c through the Immunoturbidimetric method.Serum ferritin levels were evaluated using the ELFA method, employing a commercially available kit supplied by Roche Cobas Integra.

Statistical Analysis:
The results were analyzed on the software Graph Pad Prism 9. Demographic data was analyzed by column option, while the Fischer's exact test was applied to deduce the P-value, which was considered significant at 0.05.

Age in DM2
Mean Stdv

LIMITATIONS
There were some limitations to our study.Firstly, this is a cross-sectional study with a small sample size.Secondly, it includes only male patients not females .Thirdly this study was conducted in one institution, and consequently, the findings cannot be generalized to all regions.

CONCLUSION
This study underscores the relation between high serum ferritin level and frequency of Type-2.diabetesmellitus

Table - 2: Association of serum ferritin level and Type- 2 Diabetes mellitus Fig-1: Association of serum ferritin level and Type-2 Diabetes mellitus (A Graphical Representation) DISCUSSION
Diabetes Mellitus21,22.Additionally, another study conducted byLi et al. and Shen et al. onMendelian randomization also failed to find any causal or significant relationship between patients with Type-2 Diabetes Mellitus and altered serum ferritin levels23.In conclusion, although there is compelling evidence linking blood ferritin levels to Type-2 Diabetes Mellitus, more investigation is required to clarify underlying mechanisms and