Effects of 6-Month Vitamin D Supplementation on Insulin Sensitivity and Secretion: A Randomized, Placebo-Controlled Trial

Lemieux, Patricia; Weisnagel, S. John; Caron, Annabelle Z.; Julien, Anne–Sophie; Morisset, Anne‐Sophie; Poirier, Jonathan; Carreau, Anne‐Marie; Thewis, André; Robitaille, Julie; Bergeron, Jean; Vohl, Marie‐Claude; Gagnon, Claudia

doi:10.1016/j.jcjd.2018.08.040

Cited by 2 publications

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“…Prospective studies also revealed beneficial effects of vitamin D supplementation on insulin sensitivity [ 87 , 88 ], including a meta-analysis of prospective cohort studies [ 17 , 89 , 90 ]. Intriguingly, prospective studies comparing euglycemic-hyperinsulinemic clamps at baseline and after 12 and 24 weeks of vitamin D supplementation noted improved insulin sensitivity in obese insulin-resistant subjects [ 91 , 92 ] but not in T2D subjects [ 74 ], suggesting that the established metabolic defects of T2D are not easily reversed by vitamin D repletion.…”

Section: Discussionmentioning

confidence: 99%

Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice

Lontchi-Yimagou

Kang

Goyal

et al. 2020

Molecular Metabolism

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Objective Adipose tissue inflammation and fibrosis appear to contribute to insulin resistance in obesity. Vitamin D receptor ( Vdr ) genes are expressed by adipocytes, macrophages, and fibroblasts, all of which could potentially play a role in adipose tissue inflammation and fibrosis. As vitamin D has been shown to have direct anti-inflammatory effects on adipocytes, we determined whether specific vitamin D receptor-mediated effects on adipocytes could impact adipose tissue inflammation and fibrosis and ultimately insulin resistance. Methods We examined the effects of repleting vitamin D in 25(OH)D-deficient, insulin resistant, overweight-to-obese human subjects (n = 19). A comprehensive assessment of whole-body insulin action was undertaken with stepped euglycemic (∼90 mg/dL) hyperinsulinemic clamp studies both before and after the administration of vitamin D or placebo. Adipose tissue fibrosis and inflammation were quantified by real-time rt-PCR and immunofluorescence in subcutaneous abdominal adipose tissue. To determine whether vitamin D's effects are mediated through adipocytes, we conducted hyperinsulinemic clamp studies (4 mU/kg/min) and adipose tissue analysis using an adipocyte-specific vitamin D receptor knockout (VDR-KO) mouse model (adiponectin-Cre + VDR+/fl) following high-fat diet feeding for 12 weeks. Results 25(OH)D repletion was associated with reductions in adipose tissue expression of pro-inflammatory and pro-fibrotic genes, decreased collagen immunofluorescence, and improved hepatic insulin sensitivity in humans. Worsening trends after six months on placebo suggest progressive metabolic effects of 25(OH)D deficiency. Ad-VDR-KO mice mirrored the vitamin D-deficient humans, displaying increased adipose tissue fibrosis and inflammation and hepatic insulin resistance. Conclusions These complementary human and rodent studies support a beneficial role of vitamin D repletion for improving hepatic insulin resistance and reducing adipose tissue inflammation and fibrosis in targeted individuals, likely via direct effects on adipocytes. These studies have far-reaching implications for understanding the role of adipocytes in mediating adipose tissue inflammation and fibrosis and ultimately impacting insulin sensitivity.

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Section: Discussionmentioning

confidence: 99%

Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice

Lontchi-Yimagou

Kang

Goyal

et al. 2020

Molecular Metabolism

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“…A German population study of 7791 initially diabetes-free subjects aged 50-74 years reported a non-linear inverse relationship between 25(OH)D and risk of diabetes with a threshold of <40 nmol/L in women only after an 8-year follow-up, accounting for age, sex, season of blood draw, multi-vitamin supplement intake, frequent fish consumption, BMI, hemoglobin A1C, family history of diabetes, education, physical activity, smoking, hypertension, renal dysfunction, C-reactive protein, and fasting triglycerides [19]. A recent randomized clinical trial in Canada among 96 individuals with vitamin D insufficiency [mean 25(OH)D = 51.1 nmol/L at baseline] and at high risk of diabetes or with newly diagnosed type 2 diabetes found that vitamin D3 supplementation (5000 IU daily) for 6 months significantly increased peripheral insulin sensitivity and β-cell function [9]. Data on joint associations between vitamin D and PTH with diabetes and related risk factors are limited.…”

Section: Vitamin D and Pth With Incident Diabetesmentioning

confidence: 99%

“…The vitamin D and parathyroid hormone (PTH) endocrine system plays a role in modulating a myriad of cardiometabolic risk factors through binding to the nuclear vitamin D receptor in a variety of tissues; regulatory targets include insulin/glucose metabolism, the renin-angiotensin-aldosterone system (RAAS), endothelial function, immune response modulation, cell differentiation and growth, and vascular and cardiac cell function [4][5][6][7]. Despite inconclusive results from randomized clinical trials regarding the effect of vitamin D supplementation on risk of diabetes and its metabolic risk factors [8,9], data from observational studies have consistently shown associations between vitamin D deficiency and diabetes-related cardiometabolic disorders, such as obesity, hypertension, and chronic kidney disease (CKD) [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Combined associations of 25-hydroxivitamin D and parathyroid hormone with diabetes risk and associated comorbidities among U.S. white and black women

Jin

Manson

et al. 2021

Nutr. Diabetes

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Background/objectives There is evidence of black–white differences in vitamin D status and cardiometabolic health. This study aimed to further evaluate the joint associations of 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) with risks of diabetes and related cardiometabolic comorbidities among white and black women. Subjects/methods We cross-sectionally and prospectively analyzed data from 1850 black and 3000 white postmenopausal women without cardiovascular disease or dialysis at baseline from the Women’s Health Initiative—Observational Study. Weighted Cox proportional hazards analyses and weighted logistic regression models were used to examine the joint associations of 25(OH)D and PTH with incident diabetes and prevalence of other diabetes-related cardiometabolic comorbidities (including CKD, hypertension, or obesity). Results We identified 3322 cases of obesity (n = 1629), hypertension (n = 2759), or CKD (n = 318) at baseline and 453 incident cases of diabetes during 11 years of follow-up. Cross-sectionally, lower 25(OH)D and higher PTH were independently associated with higher prevalence of hypertension [odds ratio (OR) = 0.79; 95% confidence interval (CI): 0.72–0.87 and OR = 1.55; 95% CI: 1.39–1.73] among white women only. When stratified by diabetes status, compared to women with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L (65 pg/mL), women who did not have diabetes with vitamin D deficiency (<50 nmol/L) and PTH excess (>6.89 pmol/L) had higher prevalence of CKD, hypertension, or obesity (OR = 4.23; 95% CI: 2.90–6.18) than women who had diabetes (OR = 1.89; 95% CI: 0.96–3.71). Prospectively, lower 25(OH)D was associated with lower diabetes incidence [hazard ratio (HR) = 0.73; 95% CI: 0.62–0.86] in white women. Jointly, compared to the group with 25(OH)D ≥50 nmol/L and PTH ≤6.89 pmol/L, white women with 25(OH)D deficiency (<50 nmol/L) had elevated risk for diabetes, regardless of PTH levels. Conclusions Low 25(OH)D and high PTH were jointly associated with increased risk of diabetes among white women only. Their joint associations with high prevalence of CKD, hypertension, and obesity were more pronounced among women without diabetes.

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Effects of 6-Month Vitamin D Supplementation on Insulin Sensitivity and Secretion: A Randomized, Placebo-Controlled Trial

Cited by 2 publications

References 0 publications

Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice

Insulin-sensitizing effects of vitamin D repletion mediated by adipocyte vitamin D receptor: Studies in humans and mice

Combined associations of 25-hydroxivitamin D and parathyroid hormone with diabetes risk and associated comorbidities among U.S. white and black women

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