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| ID | Type | Description | Link |
|---|---|---|---|
| 16GRNT31090037 | Other Grant/Funding Number | American Heart Association |
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| Name | Class |
|---|---|
| University of Alabama at Birmingham | OTHER |
| Yale University | OTHER |
| Tufts University | OTHER |
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Given that glutamate carboxylation or decarboxylation is key to the metabolic role of osteocalcin (at least in mouse models) and that carboxylation is vitamin K dependent, it is critical to isolate the effect of vitamin K manipulation on carboxylation of osteocalcin and its subsequent effect on glucose metabolism in clinical trials. The purpose of this randomized, double-blind, placebo-controlled clinical trial in adults is to determine whether eight weeks of daily supplementation with vitamin K2 (menaquinone-7) can improve markers in blood associated with diabetes risk.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo-Control | Placebo Comparator | The placebo-control group will take two placebo softgel capsules every day for 8 weeks. |
|
| Low-Dose Vitamin K2 (90-mcg/d) | Active Comparator | The low-dose vitamin K group will take one 90-mcg vitamin K2 (menaquinone-7) softgel capsule and one placebo softgel capsule every day for 8 weeks. |
|
| High-Dose Vitamin K2 (180-mcg/d) | Active Comparator | The high-dose vitamin K group will take two 90-mcg vitamin K2 (menaquinone-7) softgel capsules every day for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Dietary Supplement | Two placebo softgel capsules (containing no vitamin K2) every day for 8 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in insulin sensitivity | Insulin sensitivity will be calculated from plasma insulin and glucose concentrations measured during a 2-hour oral glucose tolerance test by using the oral glucose minimal model. | Change from baseline in insulin sensitivity at 8 weeks |
| Change in beta-cell function | Beta-cell function, as assessed by dynamic beta-cell responsitivity, will be calculated from plasma glucose and C-peptide concentrations measured during a 2-hour oral glucose tolerance test by using the oral C-peptide minimal model. | Change from baseline in beta-cell function at 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in prothrombin time (PT) | Change from baseline in PT at 8 weeks | |
| Change in activated partial thromboplastin time (aPTT) | Change from baseline in aPTT at 8 weeks | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Norman K Pollock, Ph.D. | Department of Pediatrics, Medical College of Georgia, Augusta University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Georgia; Augusta University | Augusta | Georgia | 30912 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21508147 | Background | Pollock NK, Bernard PJ, Gower BA, Gundberg CM, Wenger K, Misra S, Bassali RW, Davis CL. Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with beta-cell function. J Clin Endocrinol Metab. 2011 Jul;96(7):E1092-9. doi: 10.1210/jc.2010-2731. Epub 2011 Apr 20. | |
| 23616149 | Background |
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| Low-Dose Vitamin K2 Supplement (menaquinone-7; 90-mcg/d) | Dietary Supplement | One 90-mcg vitamin K2 softgel capsules (containing no vitamin K2) and one placebo softgel capsule everyday for 8 weeks. |
|
| High-Dose Vitamin K2 Supplement (menaquinone-7; 180-mcg/d) | Dietary Supplement | Two 90-mcg vitamin K2 softgel capsules every day for 8 weeks. |
|
| Change in arterial stiffness (PWV) |
Arterial stiffness will be assessed using carotid-femoral pulse wave velocity (PWV) by applanation tonometry. |
| Change from baseline in arterial stiffness at 8 weeks |
| Change in endothelial function (FMD) | Endothelial function will be assessed using brachial artery flow-mediated dilation (FMD) by ultrasound. | Change from baseline in endothelial function at 8 weeks |
| Gower BA, Pollock NK, Casazza K, Clemens TL, Goree LL, Granger WM. Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and beta-cell function in overweight adults. J Clin Endocrinol Metab. 2013 Jul;98(7):E1173-80. doi: 10.1210/jc.2013-1203. Epub 2013 Apr 24. |
| 23147574 | Background | Booth SL, Centi A, Smith SR, Gundberg C. The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol. 2013 Jan;9(1):43-55. doi: 10.1038/nrendo.2012.201. Epub 2012 Nov 13. |
| 25817542 | Background | Pollock NK. Childhood obesity, bone development, and cardiometabolic risk factors. Mol Cell Endocrinol. 2015 Jul 15;410:52-63. doi: 10.1016/j.mce.2015.03.016. Epub 2015 Mar 27. |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C062629 | menaquinone 7 |
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