Dataset Information

Effect of phylloquinone supplementation on glucose homeostasis in humans.

ABSTRACT: Under-?-carboxylated osteocalcin (ucOC) increases insulin secretion and decreases glucose concentrations in mice.We determined whether changes in ucOC concentrations in humans were associated with changes in insulin and glucose concentrations.Twenty-one community-dwelling postmenopausal women received 1 mg phylloquinone daily for 12 mo (experimental group), and 21 subjects were treated with a placebo during the same period (control group). Total serum osteocalcin, ucOC, glucose, and insulin concentrations were measured before and 6 and 12 mo after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated and correlated with ucOC concentrations.Before administration of the placebo or phylloquinone, total osteocalcin, ucOC, glucose, and insulin concentrations and HOMA-IR (1.24 ± 0.15 for the control group compared with 1.93 ± 0.37 for the experimental group) did not differ. After treatment, total osteocalcin concentrations were similar at 6 and 12 mo. At 6 mo, serum ucOC concentrations in the experimental group were 0.96 ± 0.08 ng/mL compared with 2.94 ± 0.27 ng/mL in the control group (P < 0.001). At 12 mo, serum ucOC concentrations were 0.92 ± 0.09 ng/mL and 3.13 ± 0.26 ng/mL (P < 0.001) in experimental and control groups, respectively. Despite a decrease of ?200% in ucOC concentrations, HOMA-IR was similar in the 2 groups at 6 and 12 mo (at 6 mo, HOMA-IR was 2.24 ± 0.54 and 1.52 ± 0.23 in the experimental and control groups, respectively; at 12 mo, HOMA-IR was 2.13 ± 0.38 and 1.47 ± 0.22 in the experimental and control groups, respectively; P = NS).In postmenopausal women, phylloquinone administration is not associated with changes in insulin secretion and action despite reductions in ucOC concentrations. Changes in ucOC concentrations do not alter glucose metabolism in women. This trial was registered at clinicaltrials.gov as NCT00062595.

SUBMITTER: Kumar R

PROVIDER: S-EPMC2980972 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of phylloquinone supplementation on glucose homeostasis in humans.

Kumar Rajiv R Binkley Neil N Vella Adrian A

The American journal of clinical nutrition 20100929 6

<h4>Background</h4>Under-γ-carboxylated osteocalcin (ucOC) increases insulin secretion and decreases glucose concentrations in mice.<h4>Objective</h4>We determined whether changes in ucOC concentrations in humans were associated with changes in insulin and glucose concentrations.<h4>Design</h4>Twenty-one community-dwelling postmenopausal women received 1 mg phylloquinone daily for 12 mo (experimental group), and 21 subjects were treated with a placebo during the same period (control group). Tota ...[more]

PMID: 20881072

Similar Datasets

Project description:AimsThe burden and health costs of Type 2 Diabetes Mellitus continue to increase globally and prevention strategies in at-risk people need to be explored. Previous work, in both animal models and humans, supports the role of zinc in improving glucose homeostasis. We, therefore, aimed to test the effectiveness of zinc supplementation on glycaemic control in pre-diabetic adults.MethodsWe conducted a randomized, double-blind, placebo-controlled trial across 10 General Practitioner (GP) practices in NSW, Australia. The trial is known as Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD)Study. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4%, 39-46 mmol/mol) men and women (N = 98) were all assigned to a free state government telephone health coaching service (New South Wales Get Healthy Information and Coaching Service) and then randomised to either daily 30 mg zinc gluconate or placebo. Blood tests were collected at baseline, 1, 6 and 12 months for the primary outcomes (HbA1c, fasting blood glucose (FBG)); secondary outcomes included Homeostasis Model Assessment 2 (HOMA 2) parameters, lipids, body weight, height, waist circumference, blood pressure and pulse.ResultsThe baseline-adjusted mean group difference at 6 months, expressed as treatment-placebo, (95% CI) was -0.02 (-0.14, 0.11, p = 0.78) for HbA1c and 0.17 (-0.07, 0.42; p = 0.17) for FBG, neither of which were statistically significant. There were also no significant differences between groups in any of the secondary outcomes. Zinc was well tolerated, and compliance was high (88%).ConclusionWe believe our results are consistent with other Western clinical trial studies and do not support the use of supplemental zinc in populations with a Western diet. There may still be a role for supplemental zinc in the developing world where diets may be zinc deficient.Trial registrationAustralian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.

Project description:Chronic inflammation is a driving force for the development of metabolic disease including diabetes and obesity. However, the functional characteristics of T-cell senescence in the abnormal glucose homeostasis are not fully understood. We studied the patients visiting a hospital for routine health check-ups, who were divided into two groups: normal controls and people with prediabetes. Gene expression profiling of peripheral blood mononuclear cells from normal controls and patients with type 2 diabetes was undertaken using microarray analysis. We also investigated the immunometabolic characteristics of peripheral and hepatic senescent T cells in the normal subjects and patients with prediabetes. Moreover, murine senescent T cells were tested functionally in the liver of normal or mice with metabolic deterioration caused by diet-induced obesity. Human senescent (CD28-CD57+) CD8+ T cells are increased in the development of diabetes and proinflammatory cytokines and cytotoxic molecules are highly expressed in senescent T cells from patients with prediabetes. Moreover, we demonstrate that patients with prediabetes have higher concentrations of reactive oxygen species (ROS) in their senescent CD8+ T cells via enhancing capacity to use glycolysis. These functional properties of senescent CD8+ T cells contribute to the impairment of hepatic insulin sensitivity in humans. Furthermore, we found an increase of hepatic senescent T cells in mouse models of aging and diet-induced obesity. Adoptive transfer of senescent CD8+ T cells also led to a significant deterioration in systemic abnormal glucose homeostasis, which is improved by ROS scavengers in mice. This study defines a new clinically relevant concept of T-cell senescence-mediated inflammatory responses in the pathophysiology of abnormal glucose homeostasis. We also found that T-cell senescence is associated with systemic inflammation and alters hepatic glucose homeostasis. The rational modulation of T-cell senescence would be a promising avenue for the treatment or prevention of diabetes.

Project description:BACKGROUNDBeige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.METHODSBefore and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle.RESULTSThe clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and β cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in β cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSIONMirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal muscle do not express β3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves β cell function.TRIAL REGISTRATIONClinicaltrials.gov NCT02919176.FUNDINGNIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998.

Dataset Information

Effect of phylloquinone supplementation on glucose homeostasis in humans.

Publications

Effect of phylloquinone supplementation on glucose homeostasis in humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets