Effect of phylloquinone supplementation on glucose homeostasis in humans.
BACKGROUND
Under-γ-carboxylated osteocalcin (ucOC) increases insulin secretion and decreases glucose concentrations in mice.


OBJECTIVE
We determined whether changes in ucOC concentrations in humans were associated with changes in insulin and glucose concentrations.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Kumar
Rajiv
R
Nephrology Research Unit, Divisions of Nephrology and Hypertension and the Division of Endocrinology and Metabolism, Department of Medicine, Mayo Clinic, Rochester, MN, USA. rkumar@mayo.edu
Binkley
Neil
N
Vella
Adrian
A
D001786:Blood Glucose / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D017698:Postmenopause / Q000378:metabolism; D010837:Vitamin K 1 / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D014815:Vitamins; D015675:Osteocalcin; D010837:Vitamin K 1