Association of Directly Measured Plasma Free 25(OH)D With Insulin Sensitivity and Secretion: The IRAS Family Study

Lee, C. Christine; Young, Kendra A.; Norris, Jill M.; Rotter, Jerome I.; Liu, Yeheng; Lorenzo, Carlos; Wagenknecht, Lynne E.; Cole, David E. C.; Haffner, Steven M.; Chen, Yii Der I.; Hanley, Anthony J.

doi:10.1210/jc.2017-00039

Cited by 11 publications

(5 citation statements)

References 35 publications

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“…Lee et al observed that free and total 25(OH)D were positively associated with tissue insulin sensitivity index and β-cell function among nondiabetic subjects. However, after adjustment for BMI, only free 25(OH)D was significantly associated with insulin secretion [55]. In our study, the associations between different forms of 25(OH)D (total, free and bioavailable) and T2D remained statistically significant after adjustment for BMI (0.95, CI 95% 0.93-0.97; 0.95, CI 95% 0.91-0.99; 0.88, CI 95% 0.78-0.99; respectively).…”

Section: Discussionmentioning

confidence: 89%

Total, Bioavailable, and Free 25-Hydroxyvitamin D Equally Associate with Adiposity Markers and Metabolic Traits in Mexican Adults

et al. 2021

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Epidemiological studies suggest a relationship between total 25-hydroxyvitamin D [25(OH)D], adiposity, and metabolic traits. The bioavailability of 25(OH)D is regulated by the albumin, vitamin D binding protein (VDBP), and variants of the GC gene. Therefore, it is not clear if bioavailable or free 25(OH)D offer additional benefits compared to total 25(OH)D when estimating the magnitude of these associations. Our aim was to evaluate the association between 25(OH)D (total, free and bioavailable) with adiposity and metabolic traits. This was a cross-sectional study of 1904 subjects from the Health Workers Cohort Study from Mexico. Free and bioavailable 25(OH)D were calculated based on VDBP and albumin determinations, using a formula adjusted for the GC gene diplotypes. Adiposity and metabolic traits were measured with standardized procedures. Free and bioavailable 25(OH)D levels correlated with total 25(OH)D, r = 0.71 and 0.70, respectively (p < 0.001). Total, bioavailable and free 25(OH)D levels were negatively associated with the adiposity marker (visceral adiposity index) and metabolic traits (metabolic syndrome, type 2 diabetes, triglycerides, triglycerides/HDL-c ratio, and triglycerides/glucose index) in multivariate regression models (ORs = 0.73 to 0.96). Our findings suggest that free and bioavailable 25(OH)D do not offer additional advantages over total 25(OH)D regarding its association with adiposity and several metabolic traits in Mexican adults.

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Section: Discussionmentioning

confidence: 89%

Total, Bioavailable, and Free 25-Hydroxyvitamin D Equally Associate with Adiposity Markers and Metabolic Traits in Mexican Adults

et al. 2021

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“…In non-bone health association studies, the results have been mixed. In some studies free serum 25(OH)D levels were inversely associated with coronary artery disease (125), pediatric inflammatory bowel disease (126) and ulcerative colitis (127), insulin sensitivity (128), reduction in lipid markers in statin patients (129), and acromegaly (130). However, in some other studies free 25(OH)D was inferior in asthma (131) and no better than total 25(OH)D for colorectal cancer in African-Americans (132).…”

Section: Human Studies Of Free 25(oh)dmentioning

confidence: 99%

Vitamin D Binding Protein and the Biological Activity of Vitamin D

et al. 2019

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Vitamin D has a long-established role in bone health. In the last two decades, there has been a dramatic resurgence in research interest in vitamin D due to studies that have shown its possible benefits for non-skeletal health. Underpinning the renewed interest in vitamin D was the identification of the vital role of intracrine or localized, tissue-specific, conversion of inactive pro-hormone 25-hydroxyvitamin D [25(OH)D] to active 1,25-dihydroxyvitamin D [1,25(OH)2D]. This intracrine mechanism is the likely driving force behind vitamin D action resulting in positive effects on human health. To fully capture the effect of this localized, tissue-specific conversion to 1,25(OH)2D, adequate 25(OH)D would be required. As such, low serum concentrations of 25(OH)D would compromise intracrine generation of 1,25(OH)2D within target tissues. Consistent with this is the observation that all adverse human health consequences of vitamin D deficiency are associated with a low serum 25(OH)D level and not with low 1,25(OH)2D concentrations. Thus, clinical investigators have sought to define what concentration of serum 25(OH)D constitutes adequate vitamin D status. However, since 25(OH)D is transported in serum bound primarily to vitamin D binding protein (DBP) and secondarily to albumin, is the total 25(OH)D (bound plus free) or the unbound free 25(OH)D the crucial determinant of the non-classical actions of vitamin D? While DBP-bound-25(OH)D is important for renal handling of 25(OH)D and endocrine synthesis of 1,25(OH)2D, how does DBP impact extra-renal synthesis of 1,25(OH)2D and subsequent 1,25(OH)2D actions? Are their pathophysiological contexts where total 25(OH)D and free 25(OH)D would diverge in value as a marker of vitamin D status? This review aims to introduce and discuss the concept of free 25(OH)D, the molecular biology and biochemistry of vitamin D and DBP that provides the context for free 25(OH)D, and surveys in vitro, animal, and human studies taking free 25(OH)D into consideration.

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“…However, both studies were underpowered for detection of minor effects. And finally, the effect of giving vitamin D to subjects with established T2DM do at best show a marginal effect on HbA 1c with a reduction of 0.32% in HbA 1c as compared with placebo according to a review by Lee et al that included nine trial with 3,324 participants (35).…”

Section: T2dmmentioning

confidence: 99%

The Role of Vitamin D Binding Protein, Total and Free 25-Hydroxyvitamin D in Diabetes

Jorde

2019

Front. Endocrinol.

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Vitamin D is important for bone health, but may also have extra-skeletal effects. Vitamin D and its binding protein DBP have immunological effects and may therefore be important in the development of type 1 diabetes (T1DM), and low serum levels of 25-hydroxyvitamin D (25(OH)D) are associated with later development of type 2 diabetes (T2DM). However, it has so far been difficult to convincingly show an effect of vitamin D supplementation on prevention or treatment of diabetes. The serum level of 25(OH)D has traditionally been used as a marker of a subject's vitamin D status. This measurement includes both 25(OH)D bound to DBP and albumin as well as the free from of 25(OH)D. However, according to the free hormone hypothesis, the free form is the biologically active. Previously the free form of 25(OH)D had to be calculated based on measurements of 25(OH)D, DBP, and albumin, but recently a method for direct measurement of free 25(OH)D has become commercially available. This is important in clinical conditions where the amount of DBP is affected, and has caused a renewed interest in which vitamin D metabolite to measure in clinical situations. In the present review the relations between DBP, total and free 25(OH)D in T1DM and T2DM are described.

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Association of Directly Measured Plasma Free 25(OH)D With Insulin Sensitivity and Secretion: The IRAS Family Study

Abstract: Our data showed that plasma free 25(OH)D had a slightly stronger association with SI compared with plasma total 25(OH)D, although the difference was modest and there were no marked differences in the associations between Hispanics and African Americans.

Cited by 11 publications

References 35 publications

Total, Bioavailable, and Free 25-Hydroxyvitamin D Equally Associate with Adiposity Markers and Metabolic Traits in Mexican Adults

Total, Bioavailable, and Free 25-Hydroxyvitamin D Equally Associate with Adiposity Markers and Metabolic Traits in Mexican Adults

Vitamin D Binding Protein and the Biological Activity of Vitamin D

The Role of Vitamin D Binding Protein, Total and Free 25-Hydroxyvitamin D in Diabetes

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