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Insulin resistance indices are inversely associated with vitamin D binding protein concentrations.

ABSTRACT: We hypothesized that, similar to the coordinated homeostatic regulation of most hormones, the concentration of free and bioavailable 25-hydroxyvitamin D [25(OH)D] will be tightly controlled by total 25(OH)D and vitamin D binding protein (VDBP) and that the VDBP concentrations will be associated with insulin resistance status.Our primary objective was to investigate associations between total, free, and bioavailable 25(OH)D and VDBP. We also evaluated the relationships of VDBP with insulin resistance indices.The study design was cross-sectional in the setting of a university children's hospital. The relative concentration of bioavailable 25(OH)D to total 25(OH)D [bioavailable 25(OH)D/total 25(OH)D was expressed as a percentage [percentage bioavailable 25(OH)D].Subjects were 47, postmenarchal, female adolescents, with a mean age of 15.8±1.4 years, a mean body mass index of 23.1±4.0 kg/m2. The total 25(OH)D was strongly associated with VDBP (rho=0.57, P<.0001). At lower total 25(OH)D concentrations, the concentration of bioavailable 25(OH)D relative to total 25(OH)D was higher (23.8% vs 14.9%, P<.0001), whereas the relative concentration of free 25(OH)D was similar (P=.44). VDBP was inversely associated with fasting insulin (rho=-0.51, P=.0003) and homeostatic model assessment of basal insulin resistance (rho=-0.45, P=.002) and positively with whole-body insulin sensitivity (rho=0.33, P=.02); these relationships persisted after adjusting for percentage fat and attenuated after adjusting for race.Our data suggest that VDBP concentrations are regulated by total 25(OH)D levels to maintain adequate concentrations of bioavailable 25(OH)D. VDBP concentrations are inversely associated with hyperinsulinemia and insulin resistance.

SUBMITTER: Ashraf AP

PROVIDER: S-EPMC3879668 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Insulin resistance indices are inversely associated with vitamin D binding protein concentrations.

Ashraf Ambika P AP Huisingh Carrie C Alvarez Jessica A JA Wang Xudong X Gower Barbara A BA

The Journal of clinical endocrinology and metabolism 20131220 1

<h4>Context</h4>We hypothesized that, similar to the coordinated homeostatic regulation of most hormones, the concentration of free and bioavailable 25-hydroxyvitamin D [25(OH)D] will be tightly controlled by total 25(OH)D and vitamin D binding protein (VDBP) and that the VDBP concentrations will be associated with insulin resistance status.<h4>Objective</h4>Our primary objective was to investigate associations between total, free, and bioavailable 25(OH)D and VDBP. We also evaluated the relatio ...[more]

PMID: 24170105

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Project description:ContextDelta like noncanonical notch ligand 1 (DLK1) is a paternally expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation and has roles in development and metabolism.ObjectiveWe sought to investigate links between maternal pregnancy circulating DLK1 concentrations and: (1) maternal and fetal DLK1 genotypes, (2) maternal insulin resistance and secretion, and (3) offspring size at birth.Patients, design, and settingWe measured third-trimester maternal serum DLK1 concentrations and examined their associations with parentally transmitted fetal and maternal DLK1 genotypes, indices of maternal insulin resistance and secretion derived from 75-g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study.ResultsMaternal DLK1 concentrations were associated with the paternally transmitted fetal DLK1 rs12147008 allele (P = 7.8 × 10-3) but not with maternal rs12147008 genotype (P = 0.4). Maternal DLK1 concentrations were positively associated with maternal prepregnancy body mass index (P = 3.5 × 10-6), and (after adjustment for maternal body mass index) with both maternal fasting insulin resistance (Homeostatic Model Assessment of Insulin Resistance: P = 0.01) and measures of maternal insulin secretion in response to oral glucose (insulinogenic index: P = 1.2 × 10-3; insulin disposition index: P = 0.049). Further positive associations were found with offspring weight (P = 0.02) and head circumference at birth (P = 0.04).ConclusionThese results are consistent with a partial paternal or placental origin for the maternal circulating DLK1 which may lead to increased maternal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth.

Project description:BACKGROUND:Low tissue concentrations of carotenoids have been suggested to contribute to insulin resistance in obesity. OBJECTIVES:The objectives of the study were to 1) evaluate the relations of adipose tissue and serum carotenoids with body fat, abdominal fat distribution, muscle, adipose tissue and liver insulin resistance, and dietary intake; 2) evaluate the relations and distributions of carotenoids detected in adipose tissue and serum; and 3) compare serum carotenoids and retinol concentrations in subjects with and without obesity. METHODS:Post hoc analysis of serum and adipose tissue carotenoids in individuals [n = 80; 31 men, 49 women; age (mean ± SEM): 51.4 ± 1.1 y] who participated in 2 separate studies conducted at the Clinical Research Facility at the Garvan Institute of Medical Research (Sydney) between 2008 and 2013. Retinol, ?-carotene, ?-carotene, ?-carotene, lutein, lycopene, phytoene, and phytofluene were measured using HPLC. Body composition was measured by dual-energy X-ray absorptiometry. Insulin resistance was measured by 2-step hyperinsulinemic-euglycemic clamps with deuterated glucose (n = 64), and subcutaneous and visceral abdominal volume and liver and pancreatic fat by MRI (n = 60). Periumbilical subcutaneous fat biopsy was performed and carotenoids and retinol measured in the tissue (n = 16). RESULTS:We found that ?-carotene, phytoene, and phytofluene were stored in considerable amounts in adipose tissue (25% of adipose tissue carotenoids). Carotenoid concentrations in adipose tissue and serum correlated significantly, but they followed different distributions: ?-carotene was 3-fold higher in adipose tissue compared with serum, while lutein and lycopene made up 20% and 21% of serum carotenoids compared with 2% and 12% of adipose tissue carotenoids, respectively. Liver (P ? 0.028) and adipose tissue (P = 0.023), but not muscle (P ? 0.16), insulin resistance correlated inversely with many of the serum carotenoids. CONCLUSIONS:Multiple serum and adipose tissue carotenoids are associated with favorable metabolic traits, including insulin sensitivity in liver and adipose tissue in humans.

Project description:Dyshomeostasis of vitamin D-binding protein (VDBP) has been implicated in the pathogenesis of various pregnancy complications, including preeclampsia, preterm birth, gestational diabetes, and adverse metabolic profiles in the offspring. VDBP polymorphisms have been consistently reported to contribute to this intriguing interplay. Until recently, the effects of VDBP polymorphism heterogeneity on maternal and neonatal adipomyokine profiles have not been investigated, specifically after incorporating the different maternal and neonatal 25-hydroxyvitamin D concentration cut-offs at birth. We aimed to investigate the potential effects of maternal and neonatal VDBP polymorphisms on adiponectin, irisin, and VDBP concentrations at birth, according to different cut-offs of vitamin D status, in maternal-neonatal dyads recruited from the sunny region of Northern Greece. We obtained blood samples from 66 mother-child pairs at birth. Results indicated that (i) Neonatal serum biomarkers were not affected by any included neonatal VDBP polymorphism according to different cut-offs of neonatal vitamin D status at birth, (ii) neonatal VDBP concentration was elevated in neonates with maternal rs7041 GG genotype, (iii) maternal 25(OH)D at ≤75 nmol/L resulted in increased concentrations of maternal VBDP and irisin concentrations in women with CC genotype for rs2298850 and rs4588,whereas this effect was also evident for this cut-off for neonatal VDBP concentrations at birth for GC genotype for rs 7041, and (iv) no significant effect of neonatal VDBP polymorphisms was observed on neonatal VDBP, adiponectin, or irisin levels when stratified according to maternal 25(OH)D cut-offs. In conclusion, these findings confirm that among women with the combination of CC genotype for rs2298850 and rs4588, a specific high cut-off of maternal 25(OH)D results in increasing maternal VBDP concentrations, hence providing a mechanistic rationale for aiming for specific cut-offs of vitamin D after supplementation during pregnancy, in daily clinical practice.

Project description:ObjectiveOsteoporosis (OP) can be considered a chronic complication of type 2 diabetes mellitus (T2DM). Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is associated with the pathogenesis of various inflammation-related diseases, e.g., T2DM and OP. Vitamin D affects the inflammatory pathway and inhibits an excessive inflammatory response. The current study investigated the inter-relationship between vitamin D and inflammasome activation in T2DM.MethodHepatocellular carcinoma (HepG2) cells and bone marrow stromal cells (BMSCs) were treated with Conditioned Medium of bone marrow mesenchymal stem cells after VitD treatment (CM-VitD), as well as phosphoinositide 3-kinase (PI3K) specific agonist, 740Y-P, or the PI3K specific inhibitor, LY294002, respectively, or both. 40 Eight-week-old female Sprague Dawley rats were selected and established as a DM model. The rats were injected with CM-VitD, as well as the 740Y-P specific agonist, or the LY294002 inhibitor, respectively, or both. A quantitative reverse transcription polymerase chain reaction and western blotting were conducted to evaluate the expression of messenger ribonucleic acid and protein in the RUX2 gene, alkaline phosphatase (ALP), OsteoPontiN (OPN), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid-binding protein 4 (FABP4), protein kinase B (AKT), PI3K, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, interleukin (IL)-1 beta (β), IL-18, and tumor necrosis factor alpha (TNF-α) in the BMSCs and liver tissue of rats. Enzyme-linked immunosorbent assay was used to detect the concentration of inflammatory factors in the cell supernatant and serum of rats.ResultsAn isolated co-culture of HepG2/insulin-resistance cells and BMSCs promoted the adipogenic transformation of the latter and inhibited the transformation of BMSCs into osteogenesis. The PI3K specific agonist, 740Y-P, significantly increased the expression of PI3K, AKT, NLRP3, ASC and Caspase-1 while the PI3K specific inhibitor, LY294002, does the opposite. Additionally, CM-VitD reduced the expression of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in BMSCs and rat liver via the PI3K/AKT pathway.ConclusionVitamin D can inhibit the inflammatory response induced by T2DM and promote the osteogenesis of BMSCs, which may play a key role in the treatment of type 2 diabetes patients with OP.

Project description:BackgroundThe mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.MethodsWe investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided.ResultsInsulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; P(trend) = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P(trend) = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (P(trend) = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile.ConclusionElevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.

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Insulin resistance indices are inversely associated with vitamin D binding protein concentrations.

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Insulin resistance indices are inversely associated with vitamin D binding protein concentrations.

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