Factors Showing the Growing Relation Between Vitamin D, Metabolic Syndrome, and Obesity in the Adult Population: A Systematic Review

Several theories suggest an inverse association between increasing adiposity, particularly abdominal fat, and low vitamin D levels. As a result, several routes are likely to impact how vitamin D, obesity, and metabolic syndrome (MetS) interact. This systematic study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. A comprehensive PubMed, PubMed Central, Google Scholar, and ScienceDirect database search was conducted for published papers over the previous five years. Studies were identified using the following criteria 1) participants, interventions, and outcomes (PIO) components, 2) free full text, 3) studies published in English, and 4) human studies, including systematic and narrative reviews and cross-sectional, observational studies, were among the inclusion and exclusion criteria. In total, 151 articles were returned, and 16 duplicates were rejected. After verifying the titles and abstracts of these records using the review's PIO components and eligibility criteria, 17 received a 70% or above score. On review of the literature, the release of adiponectin from fatty tissues was inversely correlated with body weight and BMI suggesting a link between vitamin D deficiency and insulin resistance.


Introduction And Background
Vitamin D deficiency is a global health problem affecting approximately one billion individuals worldwide [1]. Vitamin D is primarily required to absorb calcium, phosphate, and magnesium in the gut and prevent rickets. However, most of it is produced in the skin by UV irradiation of 7-dehydrocholesterol. The active form of vitamin D, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3), regulates transcriptional activity and is necessary for calcium homeostasis and metabolism. Vitamin D also has functions in adipogenesis, glucoseinsulin homeostasis, cell growth, non-alcoholic fatty liver disease, diabetes, insulin resistance, and metabolic syndrome [2,3]. Table 1 shows the vitamin D ranges [4].
increase the risk of diabetes and heart disease [5]. The number of persons affected with MetS has risen considerably in the previous two decades, now accounting for 20% to 25% of all adults in the United States and posing a significant public health threat [6]. MetS is defined by the presence of central (intraabdominal) obesity, hypertension (HT), hyperglycemia, raised triglyceride and cholesterol levels in the blood, along with low high-density lipoproteins (HDLs) and insulin resistance (IR). However, the classification and management of MetS is still up for debate. MetS is linked to an increased risk of cardiovascular disease and type 2 diabetes and is one of the most thoroughly studied factors [7].
Obesity has been more common worldwide in the previous 30 years, along with an increase in type 2 diabetes and vitamin D deficiency. According to the World Obesity Federation, if current trends continue, over one billion persons will be obese, and 2.7 billion will be overweight by 2025 [8]. Obesity is described as a build-up of abnormal or excessive fat and body weight of more than 20% of the ideal weight. Food addiction, genetic mutation, inadequate physical activity, endocrine disease, and poor dietary status contribute to the build-up of body fat [9]. Table 2 shows BMI ranges [10].

BMI ranges
Category of weight  In epidemiological studies, vitamin D levels in the blood have shown to be inversely related to MetS. Vitamin D is known to help the absorption of calcium and phosphorus in the gut. Vitamin D deficiency lowers intracellular calcium levels, which inhibits insulin release by cells, further worsening glucose tolerance. According to another study, vitamin D increases insulin receptors, which are necessary for glucose metabolism and insulin responsiveness [11].
According to increasing data, vitamin D insufficiency may be a risk factor for MetS. In some studies, increased vitamin D levels have been shown to lower the risk of MetS development. Supplementing with vitamin D, for example, has been shown to help obese and overweight patients lose abdominal visceral fat tissue. In addition, a three-month double-blind, randomized clinical trial of vitamin D treatment in women demonstrated that it reduced body fat mass regardless of BMI. These results support the theory that vitamin D levels are negatively related to MetS prevalence [11].
On the other hand, other research studies have been unable to replicate this association among these specific groups of people. As a result, investigations on the negative relationship between blood 25 hydroxyvitamin D (25(OH)D) and MetS were inconsistent. Furthermore, in the middle-aged and older population, there is a lack of sex-based data associating blood 25(OH)D levels with MetS. [11] In a crosssectional study of Australians aged 18-75 years, the prevalence of MetS was 65 percent lower in the upper quartile of serum vitamin D concentrations than in the lowest quartile [1].
There are various theories for the inverse link between increased adiposity, particularly abdominal obesity, and low plasma Vitamin D levels. Still, none of them has been able to explain the relationship altogether. As a result, many different potential mechanisms affect how vitamin D, obesity, and MetS interact. Consequently, additional study is required to uncover the causative relationship and to discover and establish vitamin D supplementation as a therapy for obesity and MetS [9].
However, investigations on the clinical implications of vitamin D have yielded mixed results, which raises the following question. Is vitamin D insufficiency in people with obesity just a coincidence, or does it significantly impact the development and progression of obesity and MetS [9]? For the reasons stated above, this study's primary goal (aim) is to perform a comprehensive literature evaluation to ascertain the function of vitamin D in developing metabolic syndrome and obesity and its influence on the adult population.

Methods
PRISMA 2020 standards were used to perform this systematic review [12].

Eligibility Criteria
Participants, interventions, and outcomes (PIO) components were used to select the studies. The studies selected included randomized controlled trials, observational studies, systematic reviews, and metaanalyses. In addition, the inclusion and exclusion criteria were added-papers from the last five years, free full text written in English, and papers with human subjects only.

Databases and Search Strategy
The PubMed, PubMed Central (PMC), Google Scholar, and Science Direct databases were used to perform a comprehensive search. All databases were searched from April 2, 2022, to April 20, 2022. The field search employed in the procedure was chosen based on keywords found in prior research and Medical Subject Headings (Mesh), as shown in Table 3, depending on the databases used.

Risk of Bias
The remaining full articles were assessed for quality and risk of bias using the following tools: Newcastle-Ottawa Scale (NOS), Assessment of Multiple Systematic Reviews 2 (AMSTAR 2), Scale for the Assessment of Narrative Review Articles 2 (SANRA 2), Appraisal tool for Cross-Sectional Studies (AXIS). Each tool has its own set of criteria and grading system. When a tool receives a "YES," "PARTIAL YES," or "1," it is awarded a point. When the number "2" appears, it is worth two points. Each evaluation instrument required a minimum score of 70%. Table 4 shows the quality appraisal tools of the articles.  give a list of papers that were eliminated and explain why? (8) Were the included studies adequately described by the review authors? (9) Was there a solid approach used by the review authors to assess the risk of bias (RoB) in the individual studies included in the review? (10) Are the funding sources for the research included in the review reported by the review authors? (11) If meta-analysis was justified, did the review authors apply adequate statistical procedures to combine the results?
(12) If a meta-analysis was conducted, did the authors consider the influence of RoB in individual studies on the meta-analysis or other evidence synthesis results? (13) When interpreting/discussing the review's findings, did the authors consider RoB in individual studies? (14) Is there an acceptable explanation and discussion of any heterogeneity in the review results provided by the review authors? (15) Did the review authors do an appropriate analysis of publication bias (small study bias) and address its anticipated influence on the review's outcomes if they used quantitative synthesis? (16) Did the authors disclose any possible conflicts of interest, such as any funds they received to perform the review? Scored as YES or NO. Partial Yes was considered as a point.

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Four: AlAnouti et al. [ (7) Crosssectional studies measured per the study's objectives? (9) Were the risk factor and outcome variables accurately quantified with instruments/measurements that have previously been trialed, piloted, or published? (10) Is it clear what was used to determine statistical significance and/or precision estimates? (11) Were the methods well-described such that they could be replicated? (12) Were the primary data adequately described? (13) Does the response rate concern non-response bias? (14) Was there any mention of non-responders if it was relevant? (15)  Weldegiorgis et al. [11] NOS (3) Casecontrol and cohort studies Eight items: (1) The exposed cohort's representativeness (2) Selection of the non-exposed cohort (3)

Data Collection, Items, and Analysis
Due to the apparent inter-variability of studies, such as the heterogeneity of participants, treatments, and clinical outcomes, this systematic review evaluates these experiments and reviews based on their results, applicability, and limitations. Narrative reviews, observational studies, cross-sectional studies, and systematic reviews were all read, evaluated, and tabulated. The first author's year, research type, illness, inclusion and exclusion criteria, significant findings, and funding sources were all collected from each study.

Outcome Assessment
Data collection, selection, appraisal, and analysis were all made by two independent investigators at each stage. If the group could not agree on whether or not an article was eligible, the complete text was evaluated.

Authors
Year of publication

Conclusion/outcome
Lips et al. [25] October 2017 Fasting plasma glucose levels were shown to be somewhat lower, or insulin resistance improved in investigations. These effects are more seen in people who have vitamin D insufficiency and poor glucose tolerance.
Goncalves et al. [13] October 2017 Fat-soluble micronutrients such as vitamin D could contribute to preventing MetS due to their central role as hormone regulators.
Kheiri et al. [2] June 2018 Vitamin D deficiency is linked to hypertension and increased cardiovascular and all-cause mortality.
Rafiq et al. [8] August 2018 Low vitamin D levels are linked to increased BMI in both diabetic and non-diabetic patients in studies.
Vranić et al. [9] August 2018 The primary therapy option for both obesity-related dysmetabolic conditions and vitamin D insufficiency should be to change one's lifestyle through a balanced diet and exercise.
Hyppönen et al. [16] September 2018 Vitamin D has a variety of physiological and biochemical actions that may help to offset the negative effects of obesity on metabolism and minimize the risk of metabolic irregularities and tissue damage caused by obesity.
Park et al. [7] December 2018 Low blood vitamin D levels have been linked to obesity, diabetes, insulin resistance, and cardiovascular disorders, including hypertension.
Mutt et al. Weldegiorgis et al. [11] June 2019 A lower serum 25(OH)D level in middle-aged males is strongly linked to MetS.
Greco et al.
[ 26] June 2019 The close association between obesity, glucose homeostasis, and hypovitaminosis D is due to obesityrelated inadequate sun exposure and outdoor activities. Vitamin D storage in adipose tissue (lipophilic properties), insulin secretion, sensitivity, and the immune system also shows an association.
Miao et al. [27] February 2020 Vitamin D pills appear to be a viable strategy to lessen the impact of these disorders. Finally, vitamin D supplementation may provide a new foundation for medical treatment.
AlAnouti et al. [6] October 2020 Before reaching any firm conclusions on vitamin D level and its therapeutic relevance for dyslipidemia in MetS, more research is needed.
Melguizo-Rodríguez et al. [3] February 2021 Plasma vitamin D concentrations have been found to have an inverse connection with the characteristics of MetS, such as increased glucose, total cholesterol, low-density lipoprotein, lipids, glycated hemoglobin, and a high BMI.
Jha et al. [5] April 2021 Vitamin D plays a function in more than bone health and bone growth. Thus, an appropriate amount should be consumed.
Lee et al. [1] June 2021 In cohort and cross-sectional studies, a 25-nmol/L increase in blood vitamin D content was related to 15%, and 20% decreased risks of MetS, respectively, according to a dose-response meta-analysis.

Study Selection and Quality Assessment
There were 151 potentially relevant articles in the database search, out of which 16 duplicates were removed. After that, we had 135 articles left when the titles and abstracts of these records were screened based on the review's PIO elements and eligibility criteria. After the initial screening, 82 papers were excluded manually. Of the remaining 53 records, nine were not accessible. Finally, a quality assessment for 44 articles was done, and 17 studies with a score of 70% and above were accepted in the review. There were no new resources. The graphic below is a PRISMA flow diagram depicting the screening and study selection process ( Figure 1).

FIGURE 1: Flow chart of the study search selection
SANRA -Scale for the Assessment of Narrative Review Articles; AMSTAR 2 -Assessment of Multiple Systematic Reviews 2; NOS -Newcastle Ottawa Scale; AXIS -Appraisal Tool for Cross-sectional studies

Discussion
This section will discuss the pathophysiology of vitamin D and metabolic syndrome, how metabolic syndrome, vitamin D, and obesity are interlinked, and studies showing the relationship between MetS, vitamin D, and obesity.

Vitamin D Pathophysiology
Vitamin D is the most important fat-soluble vitamin that is involved in calcium and phosphorus metabolism as well as skeletal homeostasis. Cholecalciferol, or vitamin D3, is the most common form of vitamin D, which is made from 7-dehydrocholesterol, a precursor to cholesterol. Animal (cholecalciferol) and vegetable (ergocalciferol) diets also contain it. Vitamin D takes two hydroxylations in the body to become physiologically active, the first in the liver and the second in the kidney, resulting in the 1,25(OH)2 vitamin D or calcitriol form [3]. Figure 2 shows the pathophysiology of vitamin D.

Metabolic Syndrome Pathophysiology
Genetics, a fatty diet, and a sedentary lifestyle are all variables that contribute to metabolic syndrome. As a result, increased insulin levels, visceral fatty tissue deposits, raised lipid levels, and HPO (hypothalamicpituitary axis) dysregulation occur. Finally, it plays a role in the development of diabetes and heart disease. Figure 3 shows the pathophysiology of metabolic syndrome.

Vitamin D Deficiency and Obesity
Obesity is a pathological condition defined by an abnormally high body weight due to the build-up of fat mass caused by gene mutations, a sedentary lifestyle, endocrine abnormalities, or poor nutritional status. Obesity is a significant global health issue linked to comorbidities such as metabolic syndrome, diabetes, hypertension, lung illnesses, non-alcoholic fatty liver disease, kidney problems, heart disease, skeletal abnormalities, and cancer. Furthermore, low blood vitamins such as vitamin B1 (thiamine), folate, and vitamin D are frequently associated with obesity [26].
Several epidemiological and experimental studies have demonstrated an inverse association between circulating vitamin D levels, central adiposity, and the development of obesity, as well as an association between low levels of serum 25-hydroxyvitamin D (25(OH)D), obesity, and metabolic syndrome, including both children and adults, and regardless of age. Furthermore, research has found that the link between obesity and the lack of vitamin D is not dependent on vitamin D supplementation and dietary changes. Excess adiposity, rather than insufficient intake, increases the risk of vitamin D deficiency in overweight and obese adults. However, the relationship between low vitamin D levels and various factors such as body fat, sun exposure, food intake, and exercise has yet to be discovered. Inadequate sun exposure and outdoor activities and changed expression of the vitamin D receptor (VDR) in adipose tissue are likely to be the main causes of the link between obesity and vitamin D insufficiency in obese people [26].
The genomic responses to vitamin D are caused by stereospecific interactions between the active metabolite (1,25(OH)2D) and its internal VDR, a steroid hormone receptor. After attaching to the hormone, VDR produces a heterodimer with the retinoid-X receptor (RXR) that binds to particular vitamin D response elements (VDREs) on DNA sequences, causing some gene products to be expressed or trans-repressed. Because it is produced by pancreatic β-cells, adipose tissue, and skeletal muscle, VDR regulates the expression of numerous genes that govern calcium/phosphate balance, cellular proliferation and differentiation, immunological response, glucose tolerance, and insulin sensitivity [26].
Adipogenesis is a series of processes that cause preadipocytes to develop into mature adipocytes, as well as adipocyte hypertrophy, which leads to obesity. In vitro research performed 30 years ago revealed that vitamin D might inhibit adipogenesis and that triglyceride accumulation in 3T3-L1 preadipocytes exposed to 1,25(OH)2D was decreased by 50% when compared to cells that were not treated. Following the findings, it was discovered that Cyp27b1, the gene encoding the enzyme that converts 25(OH)D to 1,25(OH)2D, is expressed in rodent and human fat tissue and that vitamin D inhibits adipogenesis via a competitive mechanism involving peroxisome proliferator-activated receptor-gamma (PPAR) and VDR. VDR and PPAR share a common heterodimeric binding partner, RXR, and higher VDR expression is linked to a decrease in PPAR-induced adipogenesis and a decrease in the mitotic clonal adipocyte population. Another study on murine mesenchymal cells treated with vitamin D confirmed reduced differentiation of adipocytes from bone marrow-derived cells [26].
VDR is also linked to thermogenesis regulation since it regulates uncoupling protein 1 (UCP1) and protein 2 (UCP2). The nuclear VDR activation of 1,25(OH)2D dramatically reduces the expression of UCP2 in human fat cells, which appears to play a role in the pathogenetic pathways of insulin resistance and diabetes development. Furthermore, in a clinical investigation, a low-energy diet and vitamin D treatment reduced fat mass and body weight. In contrast, vitamin D administration prevented diet-induced obesity in an in vivo mouse model [26].
Vitamin D is a fat-soluble vitamin, and body fat mass serves as a storehouse for vitamin D. Vitamin D may build up in the body and be extensively distributed. However, it is primarily stored in adipose tissue before being gradually released. The larger pool of the fat tissue in the visceral and subcutaneous areas impounds vitamin D and its compounds in obese people, lowering its bioavailability. An inverse relationship of 25(OH)D to body mass and adiposity was observed in obese persons following bariatric surgery [26].
Finally, obese people have decreased levels of solar exposure due to a lack of aerobic exercise, mobility, and psychological discomfort [26].

Vitamin D Deficiency, Insulin Resistance, and Diabetes
Insulin resistance, the most prevalent cause of type 2 diabetes mellitus (T2DM), is caused by insulin signaling pathway dysregulation, which is caused by reduced insulin sensitivity. Obesity and hypovitaminosis D is associated in people and experimental animal models, according to emerging evidence. Although the underlying molecular pathways are unknown, vitamin D deficiency has been linked to insulin resistance and T2DM [26].
Vitamin D affects glycemic homeostasis through various processes, which include glucose-mediated insulin synthesis/secretion by -cells, regulation of hepatic and peripheral glucose uptake, and regulation of inflammation [26].
VDR and the 1-hydroxylase enzyme are present in pancreatic β-cells, and 1,25(OH)2D has been shown to act on pancreatic cells overwhelmed by inflammation and vitamin D deficiency. Furthermore, appropriate vitamin D levels are required to maintain extracellular calcium levels outside the cells and calcium inflow into -cells for insulin secretion. VDR signaling may play a key role in glucose-induced insulin secretion [26].
VDR signaling enhances insulin-induced glucose uptake in the liver, adipose, and muscle fiber tissues, and 1,25(OH)2D directly causes the insulin receptor activation and protein in both humans and experimental animal models, along with regulating insulin production and secretion. In addition, 1,25(OH)2D has been shown to increase GLUT-4 expression in muscle cells and promote its translocation in animal study adipocytes in vivo [26].
Low-grade chronic inflammation, which is present more in obese persons due to increased proinflammatory cytokine production by macrophages and adipocytes, is another important factor in obesity and insulin resistance affecting the immune system. Multiple studies have shown that in the presence of abdominal adiposity, vitamin D deficiency is linked to inflammation and decreased insulin sensitivity, whereas vitamin D treatment improves both outcomes. Vitamin D reduces adipocyte chemokine and cytokine release, as well as monocyte chemotaxis. Its effects on the systemic and tissue-specific inflammatory response have been attributed to a variety of factors, including suppression of the NF-κβ pathway, T-helper cell anti-inflammatory activation, reduction of toll-like receptor 4 (TLR-4) expression (which reduces the differentiation of dendritic cells) [26].
Adiponectin, which is secreted by fatty tissues in an opposite ratio to body weight and body mass index, could represent a potential link between vitamin D deficiency and insulin resistance. Adiponectin has been shown to have insulin-sensitizing capabilities in tissues as well as modulatory effects on gluconeogenesis, and its sensors are found in pancreatic β-cells. It is not clear how vitamin D interacts with adiponectin because adiponectin and glucose metabolism are mediated by osteocalcin, an osteoblast-derived protein that is impacted by vitamin D. 1,25(OH)2D influences adipogenesis through a VDR-dependent process that interacts with PPAR, they are most likely connected [26]. Figure 4 shows the interlinkage between metabolic syndrome, vitamin D, and obesity.

Vitamin D levels and Components of MetS
Of the 319 MetS participants, 26.3% were vitamin D deficient, whereas 55.2% were insufficient. Low vitamin D levels were powerfully linked to waist circumference, with 25.8% of the individuals deficient and 55.6% inadequate (p=0.001). The participants with low vitamin D levels had greater triglyceride (TG), high-density lipoprotein (HDL), and blood pressure (BP) than those with adequate vitamin D levels. However, the difference was not statistically significant ( Table 6). The fasting blood glucose (FBG) (110 mg/dl) (p=0.058), on the other hand, demonstrated a modest but negligible link with low vitamin D levels [21]. Table 6 shows vitamin D in relation to metabolic syndrome, waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting glucose [21].  The MetS and our individuals' vitamin D supplementation histories were compared. Of the 319 MetS patients, 57.4% did not use vitamin D supplements, whereas 42.6% did. Except for the TG (p = 0.07; Table 3), those who did not receive vitamin D had significant associations with one or more MetS components. As a result, vitamin D supplementation was linked to a reduced risk of MetS. We also looked at the possible causes of low vitamin D levels in the blood [21].

Associated Studies
A health survey of 1790 Japanese employees found a higher negative relationship between serum 25(OH)D level and MetS among those with morbidly obese than those with average weight. The model has been appropriately modified (for age, sex, smoking, alcohol consumption, physical activity, calcium intake, and BMI), and the chances of having any of the five MetS components were lower in the vitamin D sufficient group than in the vitamin D-deficient group (by 23% for high fasting plasma glucose, 13% for high triglycerides and low HDL-cholesterol, 48% for high blood pressure, and 8% for increased waist circumference); however, none of these associations were significant [13].
According to the Third National Health and Nutrition Examination Survey (NHANES III), among 6228 people, the highest quartile of 25(OH)D (81 nmol/l) protected against the development of T2DM. When this is compared to the lowest quartile (25(OH)D 43.9 nmol/l), the odds ratio for diabetes in the top quartile was 0.17 in Mexican Americans and 0.25 in non-Hispanic Whites [25].
A multivariate linear regression analysis discovered a substantial positive relationship between vitamin D insufficiency and waist circumference, HDL, and high triglyceride levels. A cross-sectional survey of 1205 Qatari people found that 28 % had MetS. 64% of this group was deficient in vitamin D, and those with MetS had a lower 25(OH)D level by 8%. Furthermore, high blood pressure was inversely related to 25(OH)D levels, especially in vitamin D deficient people [13].
A substantial negative connection between serum 25(OH)D and glycated hemoglobin (HbA1c) was discovered in the 1958 British Birth Cohort. HbA1c was lower in the group with serum 25(OH)D 25 nmol/l when compared to the group with serum 25(OH)D 75 nmol/l (5.37 percent against 5.12 percent), with an even higher difference among obese people [25].
One hundred twenty-six people with MetS and vitamin D insufficiency (serum level 20 ng/ml) were classified as obese or non-obese using a BMI threshold of 28 kg/m2. In a randomized control, the obese group had decreased blood vitamin D (p=0.05), and fasting plasma insulin, at the start. Despite a substantial rise in blood vitamin D levels in both the obese (from 11.4 to 26.8 ng/ml, p=0.05) and non-obese (from 17.4 to 38.7 ng/ml, p=0.05) groups after the one-year intervention (700 IU/day of vitamin D, or placebo), MetS risk variables did not change in treated patients [13].

Limitations
The included research was confined to the English language in only four databases from the last five years, which means that good publications from prior years may have been overlooked. Grey literature and other databases were not included. This article describes the fat-soluble vitamin D and its association with metabolic syndrome and obesity. Other fat-soluble vitamins A, E, and K are not mentioned, and their association needs to be studied in more detail. This study does not show the association of vitamin D with metabolic syndrome separately in males and females. This study is not precise about whether vitamin D supplementation helps prevents diabetes mellitus and how vitamin D affects hypertension, and if vitamin D supplementation will show changes in insulin resistance or a two-hour glucose plasma test.

Conclusions
This systematic review thoroughly examines the elements that show a growing relationship between vitamin D, metabolic syndrome, and obesity in adults. Vitamin D insufficiency is uncommon since it may be produced at sufficient levels in the body by simply exposing oneself to sunshine for 10 minutes every day. This review aimed to explore the effects of vitamin D on adipogenesis, with a focus on illnesses associated with adipose metabolic abnormalities. Adipogenesis is influenced by vitamin D in numerous ways. VDR is expressed in adipose tissue, which produces, stores, and degrades active vitamin D. Due to the close link between obesity, glucose homeostasis, and hypovitaminosis D, having a good vitamin D status may be desirable, and based on the known mechanisms involved in the action of vitamin D. Obese individuals may represent the primary recipients of vitamin D's effects on insulin sensitivity modulation and T2DM prevention. Vitamin D might help at least one of the five cardiovascular risk factors linked to MetS, with a more substantial benefit in healthy people. Supplementing with vitamin D may be more effective in the early stages of metabolic disease. However, the results of vitamin D supplementation intervention trials to improve insulin resistance and glucose tolerance are still debatable. Then there is the need for more longterm randomized controlled studies and meta-analyses focusing on obese patients with vitamin D deficiency and the careful selection of dosage, dosing schedule, and achievement of target 25(OH)D blood levels.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.