This study showed that 34.3% of MS patients were overweight and 21.3% were obese (55.6% of the patients had a BMI ≥ 25). This can be partly due to a national problem in Egypt; as in 2015, among the 20 most populous countries, the highest level of age-standardized adult obesity was observed in Egypt (35.3% of the population) [6]. This finding was previously corroborated in one Egyptian study among MS patients [7] which shall draw the attention of health care providers to the issue of obesity among the Egyptian MS patients and may suggest an increase in MS risk among people with elevated BMI.
Obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development [8]. Several observational studies have suggested that high BMI is associated with an increased risk of MS. For example, two studies stated that increased BMI at the age of 18 was associated with nearly two-fold increase in the risk of MS [9, 10]. Elevated BMI has shown to promote a pro-inflammatory state, due to the remarkable properties of the adipose tissue, which might be related to the pathogenesis of MS [2]. A potential mechanism for such association has been suggested is that obese people have lower serum levels of vitamin D metabolites than do normal-weight people [7], and vitamin D deficiency has been suggested lately as one of the environmental risk factors for MS. The association between obesity and MS suggests that prevention of adolescent obesity may contribute to reduced MS risk [10].
In this study, there was no significant correlation between BMI and the degree of disability as previously reported in one study [11]. The association between obesity and disability in MS in a prospective study is one of the ongoing researches in the unit.
Serum leptin levels were significantly higher among the MS patients compared to the controls (P < 0.0001). This can be related to the effect of the leptin, which is one of the pro-inflammatory cytokines that are produced by the adipose tissue and leads to an overall increased level of T cells (via a positive effect on thymocytes), proliferation of effector T cells, promotion of T helper 1 responses, reduction of regulatory T cells, and inhibition of transformation of naive T cells into the anti-inflammatory T helper 2 cells. Additionally, leptin increases macrophage and monocyte proliferation rates, thereby increasing the levels of inflammatory cytokines as tumor necrosis factor-alpha, interleukin-1, and interleukin-6 [4, 5]. Leptin results in a low-grade chronic inflammatory state with the activation of the innate immune system and may increase the options for activation of autoreactive T cells that are involved in the pathogenesis of MS [12].
Since leptin is excreted by the adipose tissue, it was expected to find a positive correlation between serum leptin and BMI. However, there was no correlation between serum leptin level and BMI in this study, suggesting a hypothesis that an external factor seems to affect the release of the leptin from the adipose tissue rather than the amount of the adipose tissue and may postulate that cytokines released by the adipose tissue such as the leptin can be considered as a risk factor for MS and can be high even in patients with normal BMI. Yet, in one study, serum leptin was correlated to BMI [13]. This study included naïve MS patients with EDSS ranging from 0 to 4. Also one study [14] reported that the correlation between serum leptin and BMI was maintained in MS patients with a low disability but lost in patients with high disability.
There was no significant correlation between serum leptin levels and degree of disability (assessed by EDSS) in this study. These conflicting results between the serum leptin and EDSS and type of MS between different studies may be partly due to different sample sizes and different inclusion and exclusion criteria, and in our study, one of the causes is most of the patients have lower disability 43.8% have EDSS less than 3 compared to 22.5% have a high disability with EDSS more than 6.
In the study done by Evangelopoulos et al. 2014, with 89 treatment-naïve relapsing-remitting multiple sclerosis (RRMS) and clinical isolated syndrome (CIS) patients, in which serum leptin levels positively correlated with disease duration in females with RRMS, but there was a lack of association with EDSS, something they argued might be because changes in leptin secretion are not directly related to accumulating central nervous system damage. On the contrary, another study by Rotondi et al. 2013, delivered on 84 patients, showed that severe disability in patients with relapsing-remitting multiple sclerosis is associated with profound changes in leptin secretion, while BMI, the major determinant of leptin level in physiological conditions, has a minor role in determining the serum levels of leptin in MS patients with a high EDSS score.
Also the absence of a significant association between serum leptin level and disease activity in this study may point to the point that leptin has a relationship to the pathogenesis of MS but seems not to be related to the activity or degree of disability of the disease. This also has to be validated in larger scale randomized trials.