In a nutrition transition context, where excess adiposity but also inadequate iodine intake is of concern among children, our original study assessed the prevalence and the associated factors of the different forms of the within-subject double burden of excess of adiposity and inadequate iodine status among Tunisian 6–12 y. children. We showed that the most prevalent form of such a double burden was the co-occurrence of IAR (UIC ≥ 200) with overweight, which concerned one child out of ten. We also underlined that excess adiposity and the different types of inadequate iodine (ID, IAR and IE) status co-occurred independently.
As this study is to our knowledge the first to tackle that issue, comparisons are difficult. This prevalence is coherent with the observed significant prevalences of both iodine intake above requirements (one child out of two) and overweight (two children out of ten). Nevertheless, how the prevalence of the double burden derives from the prevalences of each single burden depends on whether their co-occurrence is synergistic (e.g. the probability of iodine intake above requirements increases if the child is overweight or vice versa), antagonistic (e.g. the probability of iodine intake above requirements decreases if the child is overweight and vice versa) or independent. In the present study, whatever the type of iodine inadequate status (i.e. deficiency or excess), our data were in accordance with the hypothesis of its independent co-existence with overweight. Beyond the observed prevalences, this also is consistent with the observed associations of the excess iodine and overweight double burden with the area of residence and socio-demographic characteristics: indeed in the case of probabilistic independence it can be shown that the measure of associations (RPR) of the double burden \({IAR}_{200}\& Ow\) with the co-factors should be identical (or at least close) to the product of the RPR for the single burden categories \({IAR}_{200} \& \stackrel{-}{Ow}\) and \(\stackrel{-}{{IAR}_{200} } \& Ow\) [15]. Nevertheless, there are several hypotheses that could be in favour of a non-independent co-occurrence of inadequate iodine status and overweight either at the physiological and environmental level.
As for the physiological level, several epidemiologic and clinical studies have examined links between thyroid function and obesity [11, 27–34]. A conceptual framework was elaborated in order to depict the different factors that could modulate the association between both tissues (in Additional file 1: Figure S1.) [11, 13, 16, 35–49]. Thyroid is deeply involved in the regulation of energy expenditure, basal metabolism, regulate food intake and thermogenesis. Theoretically, the slowdown of thyroid activity (hypothyroidism) is believed to cause low metabolic rate, reduced gluconeogenesis, reduced liposis and hence promoting weight gain [50, 51]. This hypothesis was consistent with the reported negative association between body mass index and thyroid hormones level [28, 30–32, 52].
More than adequate iodine intake may increase subclinical hypothyroidism [53]. In fact, a recent research conducted by Shan and al. [54] reported that subclinical hypothyroidism prevalence was significantly higher among population having more than adequate iodine (22.6% vs. 12.7% for adequate iodine intake, P < 0.01). A meta-analysis reported a significant risk of hypothyroidism pertaining to iodine excess [55]. In the other hand, it is thought that hypothyroidism could be a consequence of obesity [56, 57]. In fact, low chronic inflammation grade, typically observed in obese subjects, has been proposed to depress thyroid function [11, 32, 58]. The link seems to be ensured by the leptin and pro-inflammatory cytokines [59]. There are clear association between thyroid hypofunction and hyperleptinemia [33, 60]. This raise of hyperleptinemia is showing to increase the secretion of the pro-inflammatory cytokines. The different links between thyroid function, leptin and obesity have been extensively reviewed by Duntas and colleagues [33]. Iodine appeared to be an important link in a loop configuration characterizing the association between thyroid gland and fat tissue accumulation.
Beyond the physiological pathways discussed above, in the context of the nutrition transition that countries of the MENA region are experiencing, there are also external factors e.g. linked to the food environment that could increase the risk of both inadequate iodine status and excess adiposity at subject level. Generally, the nutrition transition is characterized by an increased intake of foods with a high sugar, fat and salt content, and Tunisia is no exception [10, 17, 61]. Indeed, several studies reported a very high salt consumption, from 11 to 14 g/day vs. the 5 g/day recommended. [62, 63]. Also, as part of a worldwide strategy to tackle iodine deficiency disorders [16], Tunisia has implemented a USI program since 1995 [18]. Failure in the program monitoring and control has resulted in inadequately iodized salt (as a quarter of the commercialized salt is excessively iodized) [22]. In a such a context subjects with diets with high sugar, fat and salt content which would make them more prone to excess adiposity, would also be more at risk of excess iodine (as a cumulative effect of high salt intake and inadequate salt iodization). So that would be in favour of a synergetic rather than independent co-occurrence. There could be also interactions with the metabolic pathways above, e.g. in relation with the interactions between thyroid function and adipose tissue.
Compared with all the elements in favour of a synergistic co-occurrence explained above, our observations (which are in accordance with the independence hypothesis) may be due to methodological limitations. As for measurements, urine spot measurements have known limitations for the assessment of iodine status at individual level and especially long-term high iodine intake [64]. Also, no data was available about thyroid function biomarkers (free thyroxin and thyroid stimulating hormone). We did not either estimate iodine intake e.g. by measuring dietary intake. More importantly, it could be that the metabolic pathways pertaining to the non-independent co-occurrence of iodine excess and excess adiposity (and/or their interactions with environmental factors) get fully activated only in the long term. So that they would not manifest themselves fully in this population of 6–12 y. children. Testing that hypothesis would require the same kind of data on the same subjects when they reach adulthood or at a least on a comparable sample of adults. So that the 6–12 y. age-class is a limitation of our study. Nevertheless, this is by recommendation of the WHO, as school age children are the target age class for assessment of iodine status [25].
Beyond assessing the nature of the co-occurrence of iodine status and excess adiposity (i.e. synergistic, antagonistic or independent), the study population of school-age children also has limitations regarding the assessment of the magnitude of the double burden in the whole population. Nevertheless, WHO also considers that iodine status of school-age children can be used as an approximative estimate of iodine status of the whole population [16]. Based on the assumption that iodine status and excess adiposity are co-occurring independently, one can then infer a rough estimate of the double burden by the product of our observed prevalence of iodine intake above requirements (about a half) and that of overweight among Tunisian adults (about two thirds) [61, 65]: so that about a third of Tunisian adults would be at risk of both iodine intake above requirements and overweight (and all the more for adult women which are much more prone to excess adiposity in this context). From the same reasoning one can infer that about one woman out of ten would also be affected by the co-occurrence of overweight and iodine deficiency. These estimates would be a lower bound if one takes into account that the co-occurrence of inadequate iodine status and excess adiposity is likely more synergistic than independent in older subjects (vs. our studied age-class for which our data was compatible with the independence hypothesis). But this estimated prevalence of subject-level co-occurrence of overweight and inadequate iodine intake are nevertheless significant from a public health point of view, especially with regards to intergenerational effects on risk of both chronic diseases and mental development [66] as we underlined they are higher among women which are much more prone to excess adiposity in the context.