The incidence and prevalence of T2DM is rapidly increasing in our part of world. There are multifactorial etiologies for development of T2DM. Increased iron level or iron overload and high serum ferritin level is considered to be one of them [8]. Therefore, we conducted this comparative cross-sectional study to delineate the association of serum ferritin with T2DM and correlation between and HbA1c, FBS, PBS and HbA1c in T2DM as well as healthy controls.
Elimam et al. have reported positive correlation between serum ferritin, HbA1c and CRP levels and highlighting the direct association of inflammation and glycemic control ongoing in T2DM patients [9]. There has not been a very consistent finding between elevated body iron stores and serum insulin and blood glucose levels [10]. A study conducted on 9,486 participants out of total 16573 individuals in the United State by Ford et al in 1999 reported that serum ferritin levels were lowest in non-diabetic, higher in pre-diabetic and highest in diabetic patients [11]. Similarly, a study from China by Liu et al. found an increase in the HOMA-IR values in parallel to the increases in serum ferritin levels and the decrease in insulin secretion from the pancreas [12]. In accordance to the present study, Wolide et al. reported significantly higher ferritin, waist circumference, BMI, and blood pressure values in patients with type 2 DM compared to the healthy control (p < 0.0001) [13]. A study by Andrews et al. conducted on diabetic obese and non-obese patients and healthy controls depicted higher serum ferritin and inflammatory status in obese patients than the control group reflecting a significant positive association of serum ferritin levels with type 2 DM and obesity [14].
Increased ferritin levels have been recognized as the marker of inflammation in T2DM patients [15]. Raised serum ferritin and CRP levels are a primary risk factor for the development of chronic diseases [15]. Our study depicts increased ferritin level in T2DM patients compared to healthy control which is in accordance to the studies reported from China, Japan, Bangladesh, Egypt, Spain, and Korea [16, 17, 18, 19, 20, 21 & 22]. Our findings are in accordance with the study of Raj et al. from India where serum ferritin was found higher in T2DM compared to healthy controls [8]. This possibly reflects the subclinical hemochromatosis developing in a long-standing diabetic patient.
Epidemiological studies have reported a strong association between elevated serum ferritin concentration and increased risk for diabetes [11]. Raised serum ferritin may possibly be related to the occurrence of micro and macro-vascular complications of diabetes. Optimum amount of iron is essential for all cellular metabolism and growth [8]. Iron is toxic when it is released from ferritin. Few studies have shown that high iron leading to the oxidative stress can induce T2DM [8, 11]. It is mediated by three key mechanisms: insulin deficiency, insulin resistance and hepatic dysfunction. Ferritin has been referred as a surrogate marker for insulin resistance possibly due to iron deposition in the liver leading to hepatic insulin resistance and increased hepatic glucose production [23, 24]. Elevated serum ferritin levels results in raised level of intra-hepatic oxidative stress and hepatic fibrosis which may further impair insulin extraction and insulin ability to suppress glucose production [23, 24].
Our findings revealed that median ferritin levels in diabetic patients was significantly higher in males compared to females 238 (151.8, 323.4) versus 158 (109, 233.5); p value = 0.02. This is in accordance with the studies reported by Chen et al. [16] and Han et al. [25] which have showed statistically significant positive association of serum ferritin levels with diabetes, metabolic syndrome and obesity in male patients than in female patients. In contrast to the present study, Dekker et al. worked on different ethnic groups which included 508 patients from the Netherlands, 597 African Surinamese patients, and 339 South Asian Surinamese patients aged between 35 to 60 years have reported positive correlation between serum ferritin levels and FBG in patients with type 2 DM. whereas a stronger positive correlation between FBS and serum ferritin was found in females than males patients among all ethnic groups [26].
A cohort study by Chen et al. evaluated the relationship between serum ferritin levels and the risk of developing T2DM in the 2,225 Chinese population. The researchers compared the findings between diabetic and non-diabetic patients which revealed a higher baseline serum ferritin levels, BMI, HOMA, blood pressure, HbA1c, cholesterol, HDL-C, ALT, and TAG values in T2DM patients compared to the non-diabetic group. This study also reported a significantly higher incidence of T2DM corresponding to one standard deviation increase in serum ferritin levels in Chinese males and concluded that serum ferritin levels could potentially be used as a biomarker in risk prediction for development of type 2 DM in males [16].
The study by Zhan et al., on 8,235 participants out of which 644 (7.8%) diabetics and 7,591 (92.2%) non-diabetics have shared their findings of higher serum ferritin levels in T2DM patients and a significant relationship with the HbA1c and HOMA-IR values. The researchers postulated that an elevated serum ferritin levels could be a marker of risk of developing DM [27].
This is a hospital based cross-sectional study conducted in a small group of T2DM patients, thus the result could not be generalized. Further, additional biomarkers for inflammation like HS-CRP, IL-6, TNF-α could have been done for more precise conclusion. It could not be assayed due to resource constraints.