We found that vitamin D deficiency was significantly associated with an increased risk of MetS based on the modified ATP III criteria and CDS criteria in elderly individuals. However, we did not find any statistical association between vitamin D deficiency and MetS based on the modified criteria (2012). We also found that vitamin D deficiency was inversely associated with the prevalence of elevated serum triglycerides and reduced HDL-C. No significant association was found between vitamin D deficiency and other components of MetS.
The majority of previous studies on the relationship of vitamin D with MetS among Chinese populations focused on middle-aged and elderly people, with an average age younger than 60 years[12, 22]. Some similar studies in other countries included those conducted in the United States[10] and the Netherlands[23], with average participant ages of 73.5 years and 71.2 years, respectively. The average age of our subjects was 85.2 years old.. MetS is associated with a variety of adverse health outcomes, including type 2 diabetes, cardiovascular disease, cancer and so on, which affect life expectancy in elderly individuals[24-26]. Among the elderly population, especially longaevous individuals, there are great differences in metabolic capacity, living habits, such as outdoor exercise time, and activity ability between elderly individuals and those younger than 60 years[10]. Moreover, with increasing age among the elderly, the ability to absorb and metabolize vitamin D decreases and body fat gradually accumulates, increasing the distributed volume and decreasing the biological activity of fat-soluble vitamin D in obese people[27]. Therefore, there are some characteristics of the relationship between vitamin D and MetS among the elderly and longevity groups that have been studied for the first time.
We also found that vitamin D deficiency and insufficiency were very common in the oldest-old adults; with increased age, serum vitamin D levels decrease. The level of vitamin D in elderly individuals over 100 years old was much lower than that reported among Chinese elderly individuals in Shanghai by Wei [12] in 2014, even though our sample collection occurred mainly concentrated in autumn when serum vitamin D levels are relatively high. This figure was slightly higher than 16.06 ng/ml in Chinese elderly individuals, as reported by Ling[9] and was similar to the level in those at an average age of 79 years in Taiwan[28]. The prevalence of vitamin D deficiency and insufficiency was 41.3% and 35.7%, respectively, which was lower than previously reported results[9, 10, 23] and was especially lower than the results of the study conducted in Lanzhou, China[6]. This deviation may be derived in part from the fact that some of the subjects came from southern provinces in China where serum vitamin D levels are higher than those in the north. In addition, some studies[29] have shown that serum vitamin D was associated with total mortality in the general population. There may be a survivor bias for people over 100 years old who were included in our study.
The most accepted criteria for defining MetS was first proposed by the WHO in 1999[30]. The major academic groups in the world, including the American Association of Clinical Endocrinologists (AACE) [31], ATP III[18], the Third Report of the National Cholesterol Education Program Expert Panel on Detection, the European Group for the Study of Insulin Resistance (EGIR) [32], and the International Diabetes Federation (IDF)[33], have proposed many different diagnostic definitions of MetS. Whether abdominal obesity should be used as a necessary diagnostic component has always been a topic of debate. The criteria change with varying study duration, demographic area, age and disease prediction ability[34, 35]. We studied the relationship of vitamin D with MetS based on different criteria simultaneously and further explored the causes of the differences.
We selected the latest three MetS criteria, among which WC or BMI criteria were modified in accordance with the WHO’s proposed cutoff points for Asians. The prevalence of MetS according to CDS , ATP III and 2012 were diffierent. We found similar statistical correlations between vitamin D levels and MetS based on the CDS and modified ATP III criteria[6, 8, 10, 11, 13, 14]. There were no significant correlations between vitamin D and MetS based on the modified criteria (2012) or the IDF (results not shown). The results remained the same whether various confounding factors were adjusted for or vitamin D levels were analyzed as continuous variables. A significant correlation between vitamin D and MetS was usually based on the ATP Ⅲ or modified ATP Ⅲ criteria in other similar studies[9, 10, 22]. Different diagnostic criteria may focus on different pathological mechanisms. The CDS and modified ATP III criteria include obesity as an equally important component as other components in the diagnosis, assuming that the pathological mechanism of MetS extends from insulin resistance to a syndrome consisting of obesity and adipose tissue metabolic disorders[36]. However, the modified criteria (2012) and the IDF regard WC as a necessary prerequisite, and the remaining components are equally important, which means that the criteria emphasize a pathological mechanism centered on central obesity and is applicable to obesity to groups with disorders of glucose and lipid metabolism. The ability to predict possible adverse outcomes in the future is an important factor that must be considered when proposing diagnostic criteria for MetS. Some previous studies have shown that the ability to predict the risk of cardiovascular disease and type 2 diabetes mellitus associated with MetS diagnosed by the modified ATP Ⅲ criteria is better than MetS diagnosed considering abdominal obesity a necessary diagnostic criterion. The ATP III criteria clearly identifies the burden of coronary heart disease associated with MetS[37].
We found that the vitamin D level of people with MetS based on the modified ATP Ⅲ criteria but without MetS based on the modified criteria (2012) was 21.22 ng/ml, which was significantly lower than that of individuals with MetS based on the modified criteria (2012) but without MetS based on the modified ATP Ⅲ criteria (23.63 ng/ml), so the clustering characteristics of the MetS risk components related to vitamin D level changed in the elderly population. The component analysis revealed that rather than central obesity, vitamin D affected MetS mainly by affecting blood lipid metabolism. More mechanisms and prospective studies are needed to determine which diagnostic criteria are appropriate for different age groups when studying the relationship between vitamin D and MetS.
Some previous studies have shown that there are sex differences in the relationship between vitamin D and MetS[37, 38]. Subgroup analyses were carried out for gender, WC (increased or not) and BMI (increased or not) groups. The results showed that the ORs were similar between the different gender groups and BMI groups (results not shown). This finding may be related to the fact that all the women involved in our study were postmenopausal. A significant statistical correlation was found among elderly people with a normal WC, while no significant statistical correlation was found among elderly people with an increased WC. Vitamin D is a fat-soluble vitamin and is involved in fat metabolism. the lipid components played a very important role in the development of metabolic syndrome. This indicates that difference in fat distribution in the body may affect vitamin D metabolism and the relationship between metabolic syndrome and vitamin D. Some studies[39,40] have shown that vitamin D deficiency is closely related to body fat content and body fat distribution.
Many studies have found that vitamin D levels are significantly associated with blood lipid levels, and we found that vitamin D levels exhibited a significant correlation with triglycerides and HDL-C. Similarly, Sheena[9] and Vitezova[23] also found that vitamin D levels were negatively correlated with triacylglycerol and positively correlated with HDL-C. First, vitamin D plays a very important role in the formation of HDL-C molecules[41-43]. Second, active 25(OH)D metabolites can inhibit low-density lipoprotein cholesterol (LDL-C) deposition by promoting the differentiation of monocytes or macrophages and reducing the release of proinflammatory cytokines. Third, vitamin D can regulate the influx of calcium ions, which leads to a decrease in lipase activity and inhibits lipolysis. Fourth, vitamin D can directly act on the vitamin D receptor of pre-Q adipocytes, regulate the differentiation and metabolism of adipocytes, and stimulate the synthesis and secretion of lipoprotein lipase[44]. Finally, vitamin D can also reduce the synthesis and secretion of parathyroid hormone (PTH), enhance lipolysis activity and improve abnormal lipid metabolism[45-47].
Strengths
The study included the oldest population, including elderly people mostly over 80 years of age, to study the comprehensive relationships between vitamin D and MetS. We studied the relationship between vitamin D and MetS based on three MetS diagnostic criteria.
Limitations
There are several limitations to the study. First, the results are based data obtained with a cross-sectional study design. We revealed a link between only vitamin D and MetS but could not ascertain the causality of the result. Second, almost all of our biological samples were collected during the same season, so we could not assess the impact of seasonal factors on outcomes. Third, the relationship between vitamin D and metabolic function may be different in different age groups, so our findings are applicable to only the elderly population. In addition, a significant relationship between vitamin D and triglycerides as well as HDL-C was found, but no further measurement of PTH levels was performed. Finally, we adjusted for potential confounders, but we could not estimate the effects of other unmeasured potential confounding factors.