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Metabolic syndrome represents a significant public health issue in the 21st century. Recent studies have established a correlation between elevated serum ferritin levels and various components of metabolic syndrome, as well as the overall risk of developing this condition. These findings suggest that ferritin may serve as a potential indicator of the risk associated with metabolic syndrome. Up to now, there is a lack of reports on the relationship between ferritin and metabolically healthy but obese individuals in West Bengal. Therefore, we sought to evaluate and establish a correlation between the low-grade inflammatory iron marker, ferritin, in individuals classified as Metabolically Healthy but Obese (MHO) as per Karelis criteria.
Obesity is a contributing factor to iron deficiency, which may occur with or without the presence of anemia. This relationship can be linked to specific mechanisms involved in the pathogenesis of obesity, including the presence of low-grade inflammation [1]. The diet in South Asia is composed of 90-95% non-heme iron, which contributes to the overall daily iron intake but is characterized by low absorption efficiency in the gastrointestinal tract [2]. Research indicates a negative correlation between body iron levels and body mass index (BMI) [3,4]. . Increased plasma volume, coupled with inflammation associated with higher levels of adiposity, is proposed as a potential connection between iron status and adiposity [1]. The association between iron status and inflammation is evidenced by the use of C-reactive protein (CRP) as a biomarker for inflammation. Serum concentrations of CRP are employed to substantiate and validate the correlation between elevated ferritin levels observed in obesity and the sustained presence of low iron levels [5]. However, to the best of our knowledge, no study evaluated serum ferritin in metabolically healthy but obese adults from this part of the country. We aimed to evaluate and establish a correlation between the low-grade inflammatory iron marker, ferritin, in individuals classified as Metabolically Healthy but Obese (MHO) as per Karelis criteria.
A single center prospective cross-sectional study was conducted. A total of 200 subjects between 18-60 years were included in the study. 100 Metabolically Healthy but Obese (MHO) as per Karelis criteria were included in the case group and 100 metabolically healthy normal-weight individuals (MHNW) were included in the control group. Patients with a history of conditions which influence the body iron stores such as pregnancy, alcoholism, hemochromatosis, hemoglobinopathies, diabetes mellitus, hepatitis, bleeding disorders, any acute illness during the last one month, as well as iron deficiency were excluded. Karelis criteria [6] required metabolically healthy subjects to have 4 of 5 of the following components: triglycerides ≤ 65.7 mg/dL or use of lipid-lowering drugs, HDL-c ≥ 50.3 mg/dL, LDL-c ≤ 100.5 mg/dL, HOMA ≤2.7, and CRP ≤3.0 mg/L.
All patients in both groups underwent detailed physical and clinical examinations. Serum ferritin level was performed by using an automated Chemiluminescence Immunoassay system. The normal range of serum ferritin defined at KPC Medical College & Hospital laboratory was 12–280 ng/mL (male) and 12–150 ng/mL (female).
Data was analysed using relevant automated softwares. The distributions of the participant characteristics were converted into percentages, and the successive data were presented as mean values with standard deviations. The mean value difference in serum ferritin levels for characteristics of the subjects and the metabolic components were calculated using an independent t-test and analysis of variance. Spearman Rho correlation was used considering p<0.05 significant
Ferritin showed a significant positive correlation with increasing BMI (p-value < 0.01). Serum ferritin levels were high in the case group subjects as compared to control groups (p < 0.001). The control group exhibited a lower average serum ferritin concentration compared to the study group. This disparity was consistent across both male and female patients in the two groups, with the mean serum ferritin levels for both genders in the control group being lower than those observed in the study group. Furthermore, all groups characterized by any three common components of metabolic syndrome demonstrated significantly higher average serum ferritin levels than the control group, with a high level of statistical significance (p<0.001).
Table 1 Characteristics of Age Distribution between Case and Control Group
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|
Case (MHO) |
Control (MHNW) |
p-value |
|
Age < 45 years |
39.6 % |
31.9% |
0.28 |
|
Age ≥ 45 years |
60.4 % |
68.1% |
Table 2 Characteristics of Gender Distribution between Case and Control Group
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|
Case (MHO) |
Control (MHNW) |
p-value |
|
Female |
46.3% |
50.1% |
0.43 |
|
Male |
53.7% |
49.9% |
Table 3 Comparison of Serum Ferritin Levels in the Case and Control Group
|
Ferritin Level |
Gender |
Case (MHO) |
Control (MHNW) |
p-value |
|
Normal |
Female |
43.3% |
86.4% |
<0.01 |
|
Male |
47.9% |
89.3% |
||
|
Increased |
Female |
56.7% |
13.6% |
<0.001 |
|
Male |
52.1% |
10.7% |
Ferritin expression is influenced by various factors, including cytokines released during inflammatory responses and liver disorders. Inflammation, in turn, triggers the liver to produce acute phase proteins. One of the most widespread conditions that fosters this chronic low-grade inflammatory state in the body is obesity [7]. The unexpected result of this research was the increased ferritin levels identified in the obese cohort, which exhibited a positive correlation with body mass index (BMI). Many investigations, comparing obese individuals with metabolic syndrome to those without, have indicated elevated ferritin levels and a positive association with BMI across these groups, similar to what we found in our study [1, 8, 9]. These findings challenge the notion of iron overload and suggest that a certain degree of inflammation may be responsible for the heightened ferritin levels observed. However, a study conducted on Iranian girls concluded a reduction in serum ferritin levels associated with obesity and such variations may be attributed to factors such as industrialization and a sedentary lifestyle, which are often coupled with the consumption of junk food that is low in iron density [10]. Over the recent years, research investigations have examined the relationship between serum ferritin levels and metabolic syndrome. Evidence suggests a positive correlation between increased serum ferritin and the presence of metabolic syndrome, as well as its individual components [11-13]. A Finland based study indicated that serum ferritin levels that rise over a period of 6.5 years are linked to the onset of metabolic syndrome in both genders [14]. In our analysis, the average serum ferritin concentration in the MHO group was found to be statistically significantly greater than the concentration observed in the MHNW group (p < 0.01). Furthermore, the mean ferritin levels for male and female patients within the MHO group were also elevated compared to their counterparts in the MHNW group.
Metabolically Healthy but Obese individuals show a unique picture of high ferritin levels. This may be an indication of fat cells playing a vital role in the production of acute phase reactants like ferritin which may not be the gold standard for the evaluation of iron status in obese individuals.
Declaration of interest: Authors declare that they have no conflict of interest.
Funding source: None.
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