Association Between Serum Vitamin D and Metabolic Risk Factors in Korean Schoolgirls

Objectives

Vitamin D, a key regulator of bone metabolism, has been recently been linked with energy homeostasis and metabolic disorders in western countries. However, few studies have focused on the association of vitamin D with metabolic risk factors among Asian children. We studied the prevalence of vitamin D insufficiency and the association of 25-hydroxyvitamin D [25(OH)D] with metabolic risk factors in Korean schoolgirls.

Methods

The sample consisted of 320 13-year-old girls recruited from two middle schools in the city of Gwacheon, Korea (latitude 37°N), in July 2011. Anthropometric and blood biochemistry data were obtained for this cross-sectional observational study. We also obtained lifestyle data from questionnaires and dietary data from 3-day food diaries.

Results

Vitamin D deficiency [25(OH)D < 20 ng/mL] was noted in 63.8% of participants. The mean 25(OH)D level was not significantly lower in the overweight group. Level of physical activity and vitamin D intake did not significantly affect 25(OH)D. However, 25(OH)D levels were positively correlated with milk intake and negatively correlated with soft drink intake. Serum 25(OH)D had a negative relationship with fasting glucose and insulin resistance index (homeostasis model assessment-insulin resistance; HOMA-IR) after adjustment for physical activity and body mass index z score (r = −0.144, p = 0.015), and with metabolic risk score similarly (r = −0.141, p = 0.012). Levels of insulin, HOMA-IR, and systolic blood pressure were higher in girls with deficient 25(OH)D levels than in those with sufficient levels.

Conclusion

We found that low 25(OH)D levels were associated with higher blood glucose and insulin resistance. Korean girls with low 25(OH)D levels could be at increased risk for metabolic disorders.     

Serum and Dietary Vitamin D in Individuals with Class II and III Obesity: Prevalence and Association with Metabolic Syndrome

The association between vitamin D deficiency and metabolic syndrome (MS) in severe obesity is unclear and controversial. We analyzed serum and dietary vitamin D and their association with MS in 150 adults with class II and III obesity (BMI ≥ 35 kg/m²) from the DieTBra Trial ({"type":"clinical-trial","attrs":{"text":"NCT02463435","term_id":"NCT02463435"}}NCT02463435). MS parameters were high fasting blood glucose, low HDL cholesterol, high triglycerides, elevated waist circumference, and hypertension. Vitamin D deficiency was considered as a level < 20 ng/mL. We performed multivariate Poisson regression adjusted for sociodemographic and lifestyle variables. The prevalence of serum vitamin D deficiency was 13.3% (mean 29.9 ± 9.4 ng/mL) and dietary vitamin D median was 51.3 IU/day. There were no significant associations between vitamin D, serum, and diet and sociodemographic variables, lifestyle, and class of obesity. Serum vitamin D deficiency was associated with age ≥ 50 years (p = 0.034). After a fully adjusted multivariate Poisson regression, MS and its parameters were not associated with serum or dietary vitamin D, except for lower HDL, which was associated with serum vitamin D deficiency (PR = 0.71, 95% CI 0.52–0.97; p = 0.029). Severe obese individuals had a low prevalence of vitamin D deficiency, which was not associated with MS.     

Vitamin D status and the metabolic syndrome

The identification of vitamin D receptor expression in different tissues suggests a widespread role for vitamin D action beyond its classical function in bone and mineral metabolism. Recently, the importance of vitamin D status as a risk factor in the development of metabolic syndrome has been the focus of several studies.     

维生素D和钙对2型糖尿病的预防作用

越来越多的证据表明维生素D和钙在2型糖尿病的发病过程中发挥重要作用；联合补充维生素D和钙可预防2型糖尿病的发生，且对2型糖尿病高危人群如糖耐量异常者的作用尤为明显。本文综述了维生素D和钙的营养状况与2型糖尿病之间的关系、补充维生素D和钙对糖代谢的影响以及预防作用的可能机制。     

Vitamin D in Osteosarcopenic Obesity

Osteosarcopenic obesity is a unique clinical condition where low bone and muscle mass coexist in individuals with obesity. Alterations in adipose tissue, skeletal muscle and bone are strictly interconnected, and vitamin D plays key roles in several metabolic pathways that are involved in maintaining musculoskeletal health and glucose homeostasis. We reviewed the available literature on mechanisms underlying osteosarcopenic obesity, with a focus on the role of vitamin D in the pathogenesis and treatment of the condition. We found that, although evidence from large observational studies and pre-clinical experiments strongly supports a role of vitamin D deficiency in the pathogenesis of osteosarcopenic obesity, the common belief that vitamin D improves musculoskeletal health lacks solid clinical evidence, as trials specifically aimed at assessing the effects of vitamin D supplementation in patients with osteosarcopenic obesity are not available, and trials that investigated the role of vitamin D on muscle and bone health in other patient populations either showed no or even detrimental effects. We conclude that large observational and interventional studies including individuals with osteosarcopenic obesity representative of different sex, age and race are needed to better define the role of vitamin D in the pathogenesis and treatment of this condition.     

Metabolic Syndrome and Sarcopenia

Skeletal muscle is a major organ of insulin-induced glucose metabolism. In addition, loss of muscle mass is closely linked to insulin resistance (IR) and metabolic syndrome (Met-S). Skeletal muscle loss and accumulation of intramuscular fat are associated with a variety of pathologies through a combination of factors, including oxidative stress, inflammatory cytokines, mitochondrial dysfunction, IR, and inactivity. Sarcopenia, defined by a loss of muscle mass and a decline in muscle quality and muscle function, is common in the elderly and is also often seen in patients with acute or chronic muscle-wasting diseases. The relationship between Met-S and sarcopenia has been attracting a great deal of attention these days. Persistent inflammation, fat deposition, and IR are thought to play a complex role in the association between Met-S and sarcopenia. Met-S and sarcopenia adversely affect QOL and contribute to increased frailty, weakness, dependence, and morbidity and mortality. Patients with Met-S and sarcopenia at the same time have a higher risk of several adverse health events than those with either Met-S or sarcopenia. Met-S can also be associated with sarcopenic obesity. In this review, the relationship between Met-S and sarcopenia will be outlined from the viewpoints of molecular mechanism and clinical impact.     

Dietary Protein Restriction Improves Metabolic Dysfunction in Patients with Metabolic Syndrome in a Randomized,Controlled Trial

Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to determine whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. Twenty-one individuals diagnosed with metabolic syndrome were randomly assigned for caloric restriction (CR; n = 11, diet of 5941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, diet of 8409 ± 2360 KJ per day) and followed for 27 days. Like CR, PR promoted weight loss due to a reduction in adiposity, which was associated with reductions in blood glucose, lipid levels, and blood pressure. More strikingly, both CR and PR improved insulin sensitivity by 62.3% and 93.2%, respectively, after treatment. Fecal microbiome diversity was not affected by the interventions. Adipose tissue bulk RNA-Seq data revealed minor changes elicited by the interventions. After PR, terms related to leukocyte proliferation were enriched among the upregulated genes. Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has more significant potential to be used as adjuvant therapy for people with metabolic syndrome.     

微量元素锌与代谢综合征相关疾病的研究进展

锌是人体必需的微量元素之一,是组成人体各种酶系统的必需成分,广泛参与体内各种代谢活动。代谢综合征(MS)是由肥胖、高血压、血脂紊乱和糖尿病等多种因素引起的心血管疾病综合征。微量元素锌与MS的发生有一定的相关性。本文对国内外的一些研究进行了整理和总结,分析了锌和MS相关疾病之间的关系,并对其机制进行探讨。     

Association of Serum 25(OH)D with Metabolic Syndrome in Chinese Women of Childbearing Age

Objective: To analyze the associations between serum 25(OH)D levels and the risk of metabolic syndrome (MetS) and its components, and the related genetic and non-genetic factors in non-diabetic women of childbearing age in China. Methods: Subjects were randomly selected from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. The data of sociodemographic characteristics and lifestyle factors were obtained through questionnaire survey. Anthropometry was measured by trained interviewers, and fasting blood was collected to test 25-hydroxyvitamin D [25(OH)D], total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and other related parameters. Generalized linear mode and multivariate logistic analysis were performed to analyze the associations between serum 25(OH)D and MetS and its components, adjusting for the possible confounders. Results: Body mass index (BMI), serum alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), 25(OH)D, phosphorus (P), and parathyroid hormone (PTH) levels were associated with the number of MetS’s components. G allele carriers of GC rs2282679 had higher diastolic blood pressure (DBP) and FBG levels compared with the TT genotypes, while higher genetic risk score (GRS) seemed to be associated with reduced HDL-C level. The odds ratio (OR) for MetS in lowest group of 25(OH)D was 1.533 (0.980–2.399) after adjusting for season, district, area type, latitude, age, BMI, PTH, P, ALT, CRE, interleukin-6 (IL-6), and hs-CRP, compared with the median group, but the association was not significant. An insufficient 25(OH)D concentration (<14.22 ng/mL) was significantly related to the risk of elevated waist circumference (WC) (OR = 1.612 (1.014–2.561)) and TG (OR = 2.210 (1.318–3.706)), and reduced HDL-C (OR = 1.639 (1.206–2.229)) after adjusting for the confounders among these women. Moreover, these relationships were not affected by vitamin D metabolism-related gene polymorphisms. Conclusion: After comprehensively considering various influencing factors, significant associations between insufficient serum 25(OH)D and MetS‘s components, including elevated WC, TG, and reduced HDL-C, were observed. However, MetS, hypertension, and hyperglycemia were not found independently associated with 25(OH)D levels.     

The Association of Gene Variants in the Vitamin D Metabolic Pathway and Its Interaction with Vitamin D on Gestational Diabetes Mellitus: A Prospective Cohort Study

The present prospective study included 2156 women and investigated the effect of gene variants in the vitamin D (VitD) metabolic and glucose pathways and their interaction with VitD levels during pregnancy on gestational diabetes mellitus (GDM). Plasma 25(OH)D concentrations were measured at the first and second trimesters. GDM subtype 1 was defined as those with isolated elevated fasting plasma glucose; GDM subtype 2 were those with isolated elevated postprandial glucose at 1 h and/or 2 h; and GDM subtype 3 were those with both elevated fasting plasma glucose and postprandial glucose. Six Gc isoforms were categorized based on two GC gene variants rs4588 and rs7041, including 1s/1s, 1s/2, 1s/1f, 2/2, 1f/2 and 1f/1f. VDR-rs10783219 and MTNR1B-rs10830962 were associated with increased risks of GDM and GDM subtype 2; interactions between each other as well as with CDKAL1-rs7754840 were observed (P_interaction < 0.05). Compared with the 1f/1f isoform, the risk of GDM subtype 2 among women with 1f/2, 2/2, 1s/1f, 1s/2 and 1s/1s isoforms and with prepregnancy body mass index ≥24 kg/m² increased by 5.11, 10.01, 10, 14.23, 19.45 times, respectively. Gene variants in VitD pathway interacts with VitD deficiency at the first trimester on the risk of GDM and GDM subtype 2.     

The Vitamin D Decrease in Children with Obesity Is Associated with the Development of Insulin Resistance during Puberty: The PUBMEP Study

Obesity and cardiometabolic risk have been associated with vitamin D levels even in children. The objective of the present study was to evaluate the association between insulin resistance (IR), cardiometabolic risk factors, and vitamin D in children from prepubertal to pubertal stages. A total of 76 children from the PUBMEP study, aged 4–12 years at baseline, were included. Children were evaluated in prepubertal and pubertal stages. Anthropometric measurements and selected cardiometabolic risk biomarkers, such as plasma glucose, blood lipids, insulin, adiponectin, leptin, and blood pressure, and serum 25-hydroxyvitamin D (25(OH)D) were determined. Children were categorized by obesity degree and IR status combined before and after puberty. Paired t-test and multivariate linear regression analyses were conducted. During puberty, the increase in triacylglycerols, insulin, and HOMA-IR and the decrease in QUICKI were significantly associated with the reduction in 25(OH)D (B = −0.274, p = 0.032; B = −0.219, p = 0.019; B = −0.250, p = 0.013; B = 1.574, p = 0.013, respectively) after adjustment by BMI-z, sex, and pubertal stage. Otherwise, prepubertal non-IR children with overweight/obesity that became IR during puberty showed a significant decrease in 25(OH)D and HDL-c, and an increase in waist circumference and triacylglycerol concentrations (p < 0.05 for all) over time. These results suggest that changes in IR seem to be associated with an effect on 25(OH)D levels during puberty, especially in children with overweight.     

Lower Levels of Vitamin D Are Associated with an Increase in Insulin Resistance in Obese Brazilian Women

Adult women are more likely to be obese than men. Moreover, there is evidence that obesity is a risk factor for increased insulin resistance (IR) and hypovitaminosis D (VITD), conditions related to metabolic and endocrinologic disturbance. We performed a cross-sectional study with 103 women diagnosed with obesity, recruited between 2009 and 2013, in an obesity referral outpatient clinic in Bahia, Brazil. Laboratory and clinical characteristics were compared between the groups according to the degree of obesity (I, II and III), and levels of 25-hydroxyvitamin D [25(OH)D] were used to define the VITD status (insufficiency and no insufficiency). We calculated the homeostatic model assessment-IR (HOMA-IR) index to assess insulin resistance in the groups. Our analyses revealed that HOMA-IR values and VITD levels were inversely correlated. Furthermore, we observed a distinct expression profile of values of laboratory markers according to 25(OH)D levels. Negative correlations were found between HOMA-IR and body mass index (BMI) in VITD insufficient participants but not in those with the sufficiency. Furthermore, multivariate regression demonstrated independent associations between lower levels of 25(OH)D and increased values of HOMA-IR. These findings suggests that lower levels of VITD are strongly associated with the increased IR in obese women.     

代谢综合征患者血浆内脂素水平的变化

目的探讨代谢综合征(MS)患者血浆内脂素(visfatin)水平及与胰岛素抵抗(IR)的关系。方法筛选MS患者45例、年龄、性别相匹配的健康成年人40例为对照组。ELISA法测定各组空腹血浆visfatin水平,同时检测空腹血糖(FPG)、胰岛素(FINS)、血脂、血压,测量身高、体重、腰围、臀围计算体重指数(BNI)、腰臀比(WHR),采用HOMA-IR模型公式计算胰岛素抵抗指数。结果MS组visfatin水平明显高于对照组,差异有统计学意义。在MS组,visfatin与BMI、WC、FPG、2hPG、FINS、TG、HOMA-IR呈正相关,r值分别为0.378,0.231,0.419,0.363,0.448,0.423,P均<0.05;与HDL-C无明显相关关系。多元逐步回归分析表明,BMI和visfatin是HOMA-IR的独立影响因素。结论MS患者血浆visfatin水平增高,visfatin与机体糖、脂代谢紊乱密切联系。     

维生素D与妊娠期糖尿病相关性及作用研究

目的研究维生素D和妊娠期糖尿病的相关性。方法对2016年8月-2017年9月收治的86例妊娠期糖尿病患者临床资料进行回顾性分析,将其设为观察组,选取同期接收的86例正常孕妇为对照组,所有孕妇均进行维生素D检测,分析妊娠期糖尿病与维生素D水平的相关性。结果两组孕妇孕周、糖尿病家族史各项基线资料相比,差异无统计学意义(P>0.05),观察组年龄相比对照组更大,观察组体质量(BMI)、空腹血糖(FBG)、餐后2 h血糖(2 hPBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)水平与对照组相比,相对更高;观察组维生素D、β细胞功能指数(HOMA-IS)水平与对照组相比,相对更低且差异具有统计学意义(P<0.05);将维生素D作为因变量,将年龄、BMI、FPG、2 hPBG、FINS、HOMA-IR、HOMA-IS作为自变量进行Pearson相关性分析,结果显示,FPG、2 hPBG、FINS、HOMA-IR、HOMA-IS均与维生素D有相关性,其中FPG、2 hPBG、FINS、HOMA-IR与维生素D呈负相关,HOMA-IS与维生素D呈正相关(P<0.05)。结论维生素D与妊娠期糖尿病具有相关性,妊娠期糖尿病孕妇血清内维生素D水平相比正常孕妇较低,维生素D缺乏可参与妊娠期糖尿病发生及发展中,分析其机制可能为增加胰岛素抵抗。     

Magnesium in Obesity,Metabolic Syndrome,and Type 2 Diabetes

Magnesium (Mg²⁺) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg²⁺ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg²⁺ deficiency, such as the lack of a clear definition of Mg²⁺ nutritional status, the use of different Mg²⁺ salts and dosage and the different duration of the Mg²⁺ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg²⁺, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.     

Obesity, Metabolic Syndrome, and Type 2 Diabetes: Inflammatory Basis of Glucose Metabolic Disorders

The latter half of the 20^th century has witnessed rapid advances in medicine. Concurrently, secular trends in lifestyle practices in our increasingly sedentary society have led to burgeoning rates of obesity, metabolic syndrome, and type 2 diabetes. The number of Americans with type 2 diabetes more than doubled between 1980 and 2004 and the prevalence increases with age. Potential causes of this growing epidemic include changes in dietary patterns, physical inactivity, and obesity but may also include as yet unidentified genetic and environmental determinants. In this regard, experimental data provide evidence for a direct link between obesity and subclinical inflammation and support the concept that the metabolic syndrome and type 2 diabetes are, at least in part, inflammatory conditions. Furthermore, elevated levels of inflammatory biomarkers are not only associated with the development of future diabetes but cardiovascular disease as well. These findings suggest that subclinical inflammation may be a contributing factor not only to the etiology of these metabolic disorders but also their cardiovascular complications.     

Association between the Mediterranean Diet and Metabolic Syndrome with Serum Levels of miRNA in Morbid Obesity

Background: The Mediterranean diet (MD) could be involved in the regulation of different miRNAs related to metabolic syndrome (MS). Methods: We analyzed the serum level of mir-let7a-5p, mir-21, mir-590, mir-107 and mir-192 in patients with morbid obesity and its association with the MD and MS. Results: There is an association between the adherence to MD and higher serum levels of mir-590. Mir-590 was lower in those patients who consumed >2 commercial pastries/week. Mir-let7a was lower in those who consumed ≥1 sweetened drinks, in those who consumed ≥3 pieces of fruit/day and in those who consumed less red than white meat. A lower mir-590 and mir-let7a, and a higher mir-192 level, were found in patients who met the high-density lipoprotein cholesterol (HDL) criterion of MS. A higher mir-192 was found in those patients who met the triglyceride criterion of MS and in those with type 2 diabetes (T2DM). Conclusions: There is an association between specific serum levels of miRNAs and the amount and kind of food intake related to MD. Mir-590 was positively associated with a healthy metabolic profile and type of diet, while mir-192 was positively associated with a worse metabolic profile. These associations could be suggestive of a possible modulation of these miRNAs by food.     

Monocyte-to-HDL Ratio (MHR) Predicts Vitamin D Deficiency in Healthy and Metabolic Women: A Cross-Sectional Study in 1048 Subjects

Vitamin D deficiency is often linked with Metabolic Syndrome, both being more frequent with ageing and associated with an increase inflammatory state. Recently, monocytes-to-high density lipoprotein (HDL) ratio (MHR) has emerged as a powerful index to predict systemic inflammation. In this cross-sectional study, we investigated the association between circulating vitamin D level (25-OH vitamin D) and inflammatory status in a population of 1048 adult individuals. Our study reveals an inverse association between 25-OH vitamin D levels and MHR in the overall population. When the population is stratified by gender, waist circumference, and body mass index (BMI), we observed that while in men this relation is strongly significative only in condition of central obesity, in women a lifelong negative correlation exists between circulating 25-OH vitamin D and MHR and it is independent of the metabolic status. These observations underscore the relevance of circulating biomarkers such as MHR in the prediction of systemic inflammatory conditions sustained by vitamin D deficiency also in healthy and young women.     

Association between Serum Vitamin D Metabolites and Metabolic Function in Healthy Asian Adults

The association between low vitamin D status and the development of type 2 diabetes mellitus is well established; however, intervention trials that increased serum vitamin D (through ultraviolet B exposure or dietary supplementation) provide mixed outcomes. Recent evidence suggests that metabolites directly related to vitamin D receptor activation—1α,25-dihydroxyvitamin D₃ and 24R,25-dihydroxyvitamin D₃—may be better markers of vitamin D repletion status. We tested the hypothesis that a vitamin D metabolite (VDM) index, calculated as the sum of normalized fasting serum concentrations of 1α,25-dihydroxyvitamin D₃ and 24R,25-dihydroxyvitamin D₃, is associated with metabolic function. We measured subcutaneous and visceral adipose tissue volume, intrahepatic triglyceride content, maximum oxygen uptake, insulin sensitivity (4 h hyperinsulinemic-euglycemic clamp), and insulin secretion (3 h meal tolerance test with mathematical modeling) and calculated the VDM index in 65 healthy Asian adults. Subjects with a low VDM index had lower peripheral insulin sensitivity and beta-cell function compared to subjects with a high VDM index (both p < 0.05), matched for age, sex, BMI, and serum 25-hydroxyvitamin D₃. Serum 25-hydroxyvitamin D₃ was not associated with peripheral insulin sensitivity or beta-cell function. Our results suggest that, rather than enhancing vitamin D substrate availability, upregulation of vitamin D action is more likely to lead to improvements in glucose homeostasis.     

Undercarboxylated Osteocalcin: A Promising Target for Early Diagnosis of Cardiovascular and Glycemic Disorders in Patients with Metabolic Syndrome: A Pilot Study

Lifestyle changes are causing an exponential increase in the prevalence of obesity and metabolic syndrome (MetS) worldwide. The most frequent complications of these are the development of diabetes (T2D) and cardiovascular disease (CVD). Accurate tools are needed to classify the cardiovascular risk (CVR) in the MetS population. In recent years, numerous biomarkers of bone metabolism have been associated with CVR. The aim of this study was to determine the levels of undercarboxylated osteocalcin (ucOC) in a cohort of patients with MetS and to analyse its association with MetS parameters and CVR as well as with T2D prevalence. A longitudinal study was conducted in which a MetS population was followed for one year. Weight change, adherence to the Mediterranean diet (MedDiet), ucOC levels, MetS parameters and CVR were analysed and CVR was calculated using different scores. Our results showed a decrease of CVR associated with a better adherence to the MetDiet resulting in higher HDL-C and ucOC levels though the improvement of MetS risk factors. This bone protein appeared as a potential biomarker to classify CVR in the MetS population, especially for MetS patients without prevalent T2D. Furthermore, ucOC serum levels could be good predictors of T2D prevalence.