The occurrence rate of 28.3% of MeS in our subjects is noteworthy as only women with WC above 88 cm, who were all overweight or obese, were examined for the criteria of MeS. Although women with MeS had higher BMI, WC and FM, this finding indicates that abdominal obesity as defined by NCEP/ATP III,1
despite its pivotal role, is not sufficient for development of MeS. Adipose tissue dysfunction may be more relevant to insulin resistance and other metabolic changes observed in MeS than the amount of fat mass itself.34
In support of this notion, it has been reported that in young South Asian men, insulin resistance could be present even in the absence of increased intraperitoneal fat and this might be due to the large size and dysfunction of subcutaneous abdominal adipocytes.35
More work is needed to elucidate the role of adipose tissue cellularity and function in MeS development.
High occurrence of vitamin D deficiency and insufficiency in both groups of women with and without MeS (86% and 89%, respectively) is quite noticeable. Poor vitamin D status in obesity has already been reported.36
It is believed that extra body fat, by sequestrating vitamin D, may reduce its bioavailability.7
The reasons for this high prevalence could be many: including blood sampling during the cold season; the high latitude of Tehran; air pollution; very inefficient direct sun exposure; and the fact that there is no vitamin D fortification program ongoing in Iran at this time. Moreover, according to the Islamic regulations, women must be veiled so that only face and hands (from wrist to the fingers) are allowed to be exposed. This may also contribute to the high occurrence of poor vitamin D status in our subjects.
The link between vitamin D status and metabolic syndrome has been, and still is, under debate.11
We found no difference in circulating 25(OH)D concentrations or vitamin D status between women with and without MeS. However, lower vitamin D status was accompanied by higher glucose concentrations and 25(OH)D was found to be the predictor of plasma glucose only in women with MeS. The relationship between vitamin D and glycemic status has been studied in both diabetic and nondiabetic subjects.38
In a recent clinical trial, vitamin D replenishment has led to the improvement of glycemic status in the subjects with T2D.40
Some evidence indicates that 1,25(OH)2D, the active form of vitamin D, can boost insulin secretion by enhancing calcium flux in pancreatic beta cells.41
An in vitro study showed that 1,25(OH)2D can induce the expression of insulin receptor and insulin responsiveness in U-937 human promonocytic cells.42
In the current study, serum 25(OH)D was not associated with lipid profile, WC, WHR, and BMI. Unlike this finding, the association of vitamin D status with some components of MeS such as serum HDL and triglycerides has been reported.43
Data from the Third National Health and Nutrition Examination Survey (NHANESIII) showed an inverse association between 25(OH)D and MeS.44
In a study performed on 1017 morbidly obese subjects (68% female), parathyroid hormone (PTH) was identified as the predictor of MeS, even though no relationship between serum 25(OH)D and MeS was observed.45
Circulating 25(OH)D has been inversely associated with MeS in 1654 American adults independent of calcium intake and PTH, which were positively associated with MeS in older men.46
Other studies, however, have failed to show any contribution of vitamin D status in MeS.47
In a cross-sectional study on 542 Arab Americans, only men showed an association between vitamin D deficiency and components of MeS50
and there was no such association in Asian Indians at all.49
In the latter study, the prevalence of MeS in 441 Asian Indians, comprising 237 men and 204 women, was 27.9% and the occurrence of vitamin D insufficiency, defined as 25(OH) D < 50 nmol/L, was 65.5% with no gender difference.49
The discrepancies seen in the results of studies may be due to the different study populations, the seasons of the studies and the methods used for determination of 25(OH)D. The very high occurrence of vitamin D deficiency in our subjects could be due to blood sampling during cold seasons, when dermal synthesis of vitamin D is negligible. Moreover, it has been demonstrated that both radioimmunoassay (RIA) and competitive protein-binding assay (CPBA) may overestimate circulating 25(OH)D, compared to the HPLC method,31
that was used in this study.
The significantly lower serum concentrations of osteocalcin in women with MeS compared to the control group was of great importance. Lower serum osteocalcin concentrations in MeS have also been reported in other studies.14
Increased risk of MeS, independent of serum glucose, has been observed in Korean men and women who were in the lower quartiles (Q1–Q3) of serum osteocalcin, compared to those in the highest quartile.14
An MeS-related pro-inflammatory state seems to have a determining role in the further morbidities ascribed to MeS, including diabetes53
and cardiovascular disease (CVD).54
Assuming truncal fat being the core feature of MeS,2
the other components, notably inflammation, may emanate from the abdominal excess fat.55
However, significantly higher serum hsCRP in our subjects with MeS compared to the control group even after controlling for WC and FM indicates that systemic inflammation often accompanied by obesity may not originate solely from the adipose tissue. Lower inflammatory status, as judged by serum concentrations of CRP, has been suggested to have a protective role in the so-called “metabolically healthy but obese” phenotype against such comorbidities as cardiovascular disease (CVD).56
It has been hypothesized that chronic inflammatory stimuli together with diminished anti-inflammatory mechanisms may have a role in metabolic derangements and endothelial dysfunction in MeS.57
Dietary pattern may also contribute to the inflammatory process. Higher intakes of fruits and vegetables, which are rich in anti-inflammatory antioxidants, were inversely associated with serum levels of CRP and development of MeS,59
while red meat,60
high fat dairy products61
and hydrogenated oil62
consumption was associated with higher circulating inflammatory biomarkers and greater risk of MeS.
An inverse association between serum 25(OH)D and hsCRP may support the suggestion of an anti-inflammatory function of vitamin D. Though we found no significant difference in vitamin D status between women with and without MeS, 25(OH)D was the only predictor of both hsCRP and plasma glucose in the subjects with MeS.
Considering the anti-inflammatory effects of cholecalciferol,63
poor vitamin D status may contribute to the systemic inflammation often seen in obesity, thus favoring other metabolic derangements like insulin resistance and raised blood glucose. The possible anti-inflammatory effects of vitamin D must be evaluated in the controlled clinical trials.64
This study had some limitations. Blood samples were drawn during the cold seasons, when dermal synthesis of vitamin D is minimal, so the vitamin D status of our subjects did not necessarily reflect their status for the whole year. Because of the high proportion of vitamin D deficiency in both groups, it was difficult to show the differences, if any. Moreover, only women were enrolled in the study. Therefore the relationship between vitamin D status and MeS in men remains to be studied.
In conclusion, various degrees of vitamin D deficiency had more than 85% prevalence among overweight/obese middle-aged women in Tehran who participated in this study. Although there was no significant difference in either serum 25(OH)D or vitamin D status between women with and without MeS, 25(OH)D was a predictor of hsCRP, the biomarker of systemic inflammation, in women with MeS but not in the controls. Thus, vitamin D status may, at least in part, be a determining factor of systemic inflammation and the related metabolic derangements of MeS.