vitamin-k-1 and Insulin-Resistance

A relationship between osteocalcin (OC) levels and factors associated with energy metabolism and insulin resistance has been reported recently. The aim of this study was to investigate whether modulation of ostecalcin isoforms via vitamin K1 supplementation would affect glucose metabolism or insulin sensitivity in prediabetic and premenopause women.. Eighty-two prediabetic women were randomized to consume vitamin K1 supplement (n = 39) or placebo (n = 43) for 4 weeks. Participants in the vitamin K1 supplement group received one pearl softgel capsule containing 1000 μm of phylloquinone, and the placebo group received one placebo capsule daily for 4 weeks. Blood samples were collected at baseline and after the 4-week intervention period to quantify carboxylated OC (cOC), undercarboxylated OC (ucOC) and relevant variables.. Phylloquinone supplementation increased the serum levels of cOC and decreased ucOC, compared with placebo (12.53 ± 5.95 compared with 7.43 ± 4.85 ng/ml and 2.47 ± 1.91 compared with 4.79 ± 2.43 ng/ml, respectively; P < 0.001). Furthermore, intake of phylloquinone supplement led to significant decreases in %ucOC (17.97 ± 12.24 compared with 43.80 ± 19.86) and 2-h post-oral glucose tolerance test (OGTT) glucose (7.32 ± 1.50 compared with 8.62 ± 1.45 mmol/l), and 2-h post-OGTT insulin level (80.34 ± 42.24 compared with 112.43 ± 53.19 μIU/ml) and increased insulin sensitivity index (2.46 ± 0.71 compared with 1.75 ± 0.61) compared with placebo. Overall, a significant association was found between changes in %ucOC and changes in 2-h post-OGTT glucose (r = 0.308, P = 0.028).. The results of this study demonstrated that vitamin K1 supplementation for 4 weeks did not affect insulin resistance in premenopausal and prediabetic women but had beneficial effects on glycemic status and insulin sensitivity.

Topics: Adult; Blood Glucose; Dietary Supplements; Double-Blind Method; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Middle Aged; Osteocalcin; Prediabetic State; Premenopause; Vitamin K 1; Young Adult

Vitamin K has been related to glucose metabolism, insulin sensitivity and diabetes. Because inflammation underlies all these metabolic conditions, it is plausible that the potential role of vitamin K in glucose metabolism occurs through the modulation of cytokines and related molecules. The purpose of the study was to assess the associations between dietary intake of vitamin K and peripheral adipokines and other metabolic risk markers related to insulin resistance and type 2 diabetes mellitus.. Cross-sectional and longitudinal assessments of these associations in 510 elderly participants recruited in the PREDIMED centers of Reus and Barcelona (Spain). We determined 1-year changes in dietary phylloquinone intake estimated by food frequency questionnaires, serum inflammatory cytokines and other metabolic risk markers.. In the cross-sectional analysis at baseline no significant associations were found between dietary phylloquinone intake and the rest of metabolic risk markers evaluated, with exception of a negative association with plasminogen activator inhibitor-1. After 1-year of follow-up, subjects in the upper tertile of changes in dietary phylloquinone intake showed a greater reduction in ghrelin (-15.0%), glucose-dependent insulinotropic peptide (-12.9%), glucagon-like peptide-1 (-17.6%), IL-6 (-27.9%), leptin (-10.3%), TNF (-26.9%) and visfatin (-24.9%) plasma concentrations than those in the lowest tertile (all p<0.05).. These results show that dietary phylloquinone intake is associated with an improvement of cytokines and other markers related to insulin resistance and diabetes, thus extending the potential protection by dietary phylloquinone on chronic inflammatory diseases.. http://www.controlled-trials.com as ISRCTN35739639.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Cytokines; Diabetes Mellitus, Type 2; Diet, Mediterranean; Female; Follow-Up Studies; Humans; Insulin Resistance; Longitudinal Studies; Male; Middle Aged; Risk Factors; Vitamin K 1

Under-γ-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.

Topics: Blood Glucose; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Middle Aged; Osteocalcin; Postmenopause; Vitamin K 1; Vitamins

There is no previous study in the literature that has examined the relationship between circulating vitamin K1 (VK1) with glycemic status in type 2 diabetes (T2D). Moreover, scientific explanation for the beneficial role of VK1 supplementation in lowering glycemia in diabetes is yet to be determined. This study for the first time demonstrated that circulating VK1 was significantly lower in T2D patients compared to age-matched control subjects, and VK1 levels in T2D were significantly and inversely associated with fasting glucose and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], which suggest that boosting plasma VK1 may reduce the fasting glucose and insulin resistance in T2D patients. Using high-fat-diet-fed T2D animal model, this study further investigated the positive effect of VK1 supplementation on glucose metabolism and examined the underlying molecular mechanism. Results showed that VK1 supplementation [1, 3, 5 μg/kg body weight (BW), 8 weeks] dose dependently improved the glucose tolerance; decreased BW gain, fasting glucose and insulin, glycated hemoglobin, HOMA-IR and cytokine secretion (monocyte chemoattractant protein-1 and interleukin-6); and regulated the signaling pathway of hepatic glucose metabolism [sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK)/phosphoinositide 3-kinase/phosphatase and tensin homolog/glucose transporter 2/glucokinase/glucose 6 phosphatase], lipid oxidation (peroxisome proliferator-activated receptor alpha/carnitine palmitoyltransferase 1A) and inflammation (nuclear factor kappa B) in T2D mice. Comparative signal silencing studies also depicted the role of SIRT1/AMPK in mediating the effect of VK1 on glucose metabolism, lipid oxidation and inflammation in high-glucose-treated cultured hepatocytes. In conclusion, this study demonstrates that circulating VK1 has a positive effect on lowering fasting glucose and insulin resistance in T2D via regulating SIRT1/AMPK signaling pathway.

Topics: AMP-Activated Protein Kinases; Animals; Case-Control Studies; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Female; Glucose; Hepatocytes; Humans; Insulin Resistance; Lipid Metabolism; Male; Mice; Middle Aged; Sirtuin 1; Vitamin K 1

The skeletal protein osteocalcin is gamma-carboxylated by vitamin K. High serum uncarboxylated osteocalcin reflects low vitamin K status. In vitro and animal studies indicate that high uncarboxylated osteocalcin is associated with reduced insulin resistance. However, associations between osteocalcin and measures of insulin resistance in humans are less clear.. Our aim was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin (total, uncarboxylated, and carboxylated) and insulin resistance in older men and women.. Cross-sectional associations between serum measures of total osteocalcin, carboxylated osteocalcin, and uncarboxylated osteocalcin and insulin resistance were examined in 348 nondiabetic men and women (mean age: 68 y; 58% female) by using the homeostasis model assessment of insulin resistance (HOMA-IR). Associations between each form of osteocalcin at baseline and 3-y change in HOMA-IR were examined in 162 adults (mean age: 69 y; 63% female) who did not receive vitamin K supplementation.. Lower circulating uncarboxylated osteocalcin was not associated with higher HOMA-IR at baseline or at 3-y follow-up. Those in the lowest tertiles of total osteocalcin and carboxylated osteocalcin at baseline had higher baseline HOMA-IR (P = 0.006 and P = 0.02, respectively). The concentration of carboxylated osteocalcin at baseline was inversely associated with a 3-y change in HOMA-IR (P = 0.002).. In older adults, circulating uncarboxylated osteocalcin was not associated with insulin resistance. In contrast, elevated carboxylated osteocalcin and total osteocalcin were associated with lower insulin resistance, which supports a potential link between skeletal physiology and insulin resistance in humans. The role of vitamin K status in this association remains unclear and merits further investigation. This trial is registered at clinicaltrials.gov as NCT00183001.

Topics: Adiponectin; Aged; Blood Glucose; Body Mass Index; Calcium; Cholecalciferol; Cross-Sectional Studies; Exercise; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Models, Biological; Osteocalcin; Vitamin K 1; Vitamins

Limited evidence suggests that vitamin K may have a beneficial role in glucose homeostasis. No observational data exist on the associations between vitamin K intake and insulin sensitivity.. We aimed to examine associations between vitamin K intake and measures of insulin sensitivity and glycemic status in men and women aged 26-81 y.. We assessed the cross-sectional associations of self-reported phylloquinone (vitamin K(1)) intake with insulin sensitivity and glycemic status in the Framingham Offspring Cohort. Dietary and supplemental phylloquinone intakes were assessed by using a food-frequency questionnaire. Insulin sensitivity was measured by fasting and 2-h post-oral-glucose-tolerance test (OGTT) insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulin sensitivity index (ISI(0,120)). Glycemic status was assessed by fasting and 2-h post-OGTT glucose and glycated hemoglobin (HbA(1c)).. Higher phylloquinone intake was associated with greater insulin sensitivity and glycemic status, as measured by 2-h post-OGTT insulin and glucose and ISI(0,120), after adjustment for age, sex, waist circumference, lifestyle characteristics, and diet quality [2-h post-OGTT insulin: lowest and highest quintile, 81.0 and 72.7 microU/mL, respectively (P for trend = 0.003); 2-h post-OGTT glucose: 106.3 and 101.9 mg/dL, respectively (P for trend = 0.009); ISI(0,120): 26.3 and 27.3 mg L(2)/mmol mU min (P for trend = 0.009)]. Phylloquinone intake was not associated with fasting insulin and glucose concentrations, HOMA-IR, or HbA(1c).. Our findings support a potential beneficial role for phylloquinone in glucose homeostasis in men and women.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Blood Glucose; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Dietary Supplements; Fasting; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Longitudinal Studies; Male; Middle Aged; Nutritional Physiological Phenomena; Odds Ratio; Surveys and Questionnaires; Vitamin K 1