title: Vitamin K, circulating cytokines, and bone mineral density in older men and women. Toenail Selenium and Incidence of Type 2 Diabetes in U.S. Men and Women Effect of Vitamin K Supplementation on Insulin Resistance in Older Men and Women Consumption of sweet beverages and type 2 diabetes incidence in European adults: results from EPIC-InterAct Dietary Phylloquinone and Menaquinones Intakes and Risk of Type 2 Diabetes Phylloquinone supplementation improves glycemic status independent of the effects of adiponectin levels in premonopause women with prediabetes: a double-blind randomized controlled clinical trial Vitamin K2 Prevents Hyperglycemia and Cancellous Osteopenia in Rats with Streptozotocin-Induced Type 1 Diabetes
abstract: BACKGROUND Vitamin K modulates cytokines involved in bone turnover , including interleukin-6 ( IL-6 ) and osteoprotegerin in vitro . OBJECTIVE The objective of this study was to assess 1 ) associations between measures of vitamin K status [ plasma phylloquinone and serum percentage of undercarboxylated osteocalcin ( % ucOC ) ] and IL-6 , osteoprotegerin , and C-reactive protein ( CRP ) concentrations and 2 ) the effect of daily 500 mug phylloquinone supplementation for 3 y on cytokine concentrations . DESIGN Concentrations of IL-6 , osteoprotegerin , and CRP and bone mineral density ( BMD ) were measured at baseline and after 3 y of follow-up in 379 healthy men and women ( 60 - 81 y ; 58.5 % women ) participating in a r and omized trial that studied the effect of vitamin K supplementation on bone loss . RESULTS Cross-sectionally , plasma phylloquinone was inversely associated with IL-6 and CRP , whereas serum % ucOC was inversely associated with IL-6 . Osteoprotegerin was associated positively with plasma phylloquinone and inversely with % ucOC . No differences were observed in the 3-y change in IL-6 , osteoprotegerin , and CRP concentrations between participants who received phylloquinone supplementation and those who did not . Overall , no association was observed between the 3-y changes in circulating cytokines and BMD . CONCLUSIONS Poor vitamin K status was associated with high concentrations of cytokines involved in bone turnover , but vitamin K supplementation did not confer a decrease in cytokine concentrations . The healthy status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentrations . This trial was registered with www . clinical trials.gov as NCT00183001 OBJECTIVE Compelling biological pathways suggest that selenium ( Se ) may lower onset of type 2 diabetes mellitus ( T2DM )  , but very few studies have evaluated this relationship , with mixed results . We examined the association between toenail Se and incidence of T2DM . RESEARCH DESIGN AND METHODS We performed prospect i ve analyses in two separate U.S. cohorts , including 3,630 women and 3,535 men , who were free of prevalent T2DM and heart disease at baseline in 1982–1983 and 1986–1987 , respectively .  Toenail Se concentration was quantified using neutron activation analysis , and diabetes cases were identified by biennial question naires and confirmed by a detailed supplementary question naire . Hazard ratios of incident T2DM according to Se levels were calculated using Cox proportional hazards . RESULTS During 142,550 person-years of follow-up through 2008 , 780 cases of incident T2DM occurred . After multivariable adjustment , the risk of T2DM was lower across increasing quintiles of Se , with pooled relative risks across the two cohorts of 1.0 ( reference ) , 0.91 ( 95 % CI 0.73–1.14 ) , 0.78 ( 0.62–0.99 ) , 0.72 ( 0.57–0.91 ) , and 0.76 ( 0.60–0.97 ) , respectively ( P for trend = 0.01 ) . Results were similar excluding the few individuals ( 4 % ) who used Se supplements . In semiparametric analyses , the inverse relationship between Se levels and T2DM risk appeared to be linear . CONCLUSIONS At dietary levels of intake , individuals with higher toenail Se levels are at lower risk for T2DM . Further research is required to determine whether varying results in this study versus prior trials relate to differences in dose , source , statistical power , residual confounding factors , or underlying population risk OBJECTIVE —Vitamin K has a potentially beneficial role in insulin resistance , but evidence is limited in humans . We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women . RESEARCH DESIGN AND METHODS —This was an ancillary study of a 36-month , r and omized , double-blind , controlled trial design ed to assess the impact of supplementation with 500 μg/day phylloquinone on bone loss . Study participants were older nondiabetic men and women ( n = 355 ; aged 60–80 years ; 60 % women ) . The primary outcome of this study was insulin resistance as measured by homeostasis model assessment ( HOMA-IR ) at 36 months . Fasting plasma insulin and glucose were examined as the secondary outcomes . RESULTS —The effect of 36-month vitamin K supplementation  on HOMA-IR differed by sex ( sex × treatment interaction P = 0.02 ) . HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group versus the men in the control group ( P = 0.01 ) after adjustment for baseline HOMA-IR , BMI , and body weight change . There were no statistically significant differences in outcome measures between intervention groups in women . CONCLUSIONS —Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men Consumption of sugar-sweetened beverages has been shown , largely in American population s , to increase type 2 diabetes incidence . We aim ed to evaluate the association of consumption of sweet beverages ( juices and nectars , sugar-sweetened soft drinks and artificially sweetened soft drinks ) with  type 2 diabetes incidence in European adults . We established a case – cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . After exclusions , the final sample size included 11,684 incident cases and a subcohort of 15,374 participants . Cox proportional hazards regression models ( modified for the case – cohort design ) and r and om-effects meta-analyses were used to estimate the association between sweet beverage consumption ( obtained from vali date d dietary question naires ) and type 2 diabetes incidence . In adjusted models , one 336 g ( 12 oz ) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 ( 95 % CI 1.09 , 1.38 ) and 1.52 ( 95 % CI 1.26 , 1.83 ) , respectively . After further adjustment for energy intake and BMI , the association of sugar-sweetened soft drinks with type 2 diabetes persisted ( HR 1.18 , 95 % CI 1.06 , 1.32 ) , but the association of artificially sweetened soft drinks became statistically not significant ( HR 1.11 , 95 % CI 0.95 , 1.31 ) . Juice and nectar consumption was not associated with type 2 diabetes incidence . This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults OBJECTIVE To investigate whether dietary phylloquinone and menaquinones intakes are related to risk of type 2 diabetes .  RESEARCH DESIGN AND METHODS We used data from a prospect i ve cohort study in 38,094 Dutch men and women , aged 20–70 years .  Dietary phylloquinone and menaquinones intakes were assessed using a vali date d food frequency question naire . Diabetes case patients were ascertained mainly via self-report and verified against medical records . RESULTS During 10.3 years of follow-up , 918 incident cases of diabetes were documented . In a multivariate model adjusting for diabetes risk factors and dietary factors , phylloquinone intake tended to be associated ( P = 0.08 ) with a reduced risk of type 2 diabetes with a hazard ratio ( HR ) of 0.81 ( 95 % CI 0.66–0.99 ) for the highest versus the lowest quartile . For menaquinones intake , a linear , inverse association ( P = 0.038 ) with risk of type 2 diabetes was observed with an HR of 0.93 ( 0.87–1.00 ) for each 10-μg increment in the multivariate model . CONCLUSIONS This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes Background Vitamin K , as a cofactor in the gamma carboxylation of certain glutamic acid ( Gla ) residues , has been related to glucose metabolism and insulin sensitivity . Osteocalcin , also known as bone γ-carboxyglutamic acid , increases β-cell proliferation as well as insulin and adiponectin secretion , which improve glucose tolerance and insulin sensitivity . Thus , the purpose of the present study was to examine the possible role of adiponectin as a mediator of glucose homeostasis following phylloquinone supplementation in premonopause women with prediabetes . Methods Eighty two women were r and omized to consume vitamin k1 supplement ( n = 39 ) or placebo ( n = 43 ) for four weeks . Participants in vitamin K1 treatment group received one pearl softgel capsule containing 1000 micrograms phylloquinone while the placebo group received one placebo capsules daily for four weeks . The Blood sample s were collected at baseline and after a four-week intervention to quantify osteocalcin , adiponectin , leptin and relevant variables . Results Phylloquinone supplementation significantly increased serum adiponectin concentration ( 1.24 ± 1.90 compared with −0.27 ± 1.08 μg/ml ) , and did not alter total osteocalcin ( 0.50 ± 4.11 compared with 0.13 ± 1.85 ng/ml ) and leptin ( −0.29 ± 8.23 compared with −1.15 ± 5.25 ng/ml ) compared with placebo . Adjustments for total osteocalcin and adiponectin using analysis of covariance ( ANCOVA ) did not affect the association of glycemic status with related variables . Conclusions In conclusion our study demonstrated that phylloquinone supplementation  improved glycemic status in premonopausal prediabetic women independent of adiponectin . Trial registration This trial was registered in Iranian Registry of Clinical Trials with ID number of I RCT 2013120915724N1 The purpose of the present study was to examine the effect of vitamin K2 on cancellous and cortical bone mass in rats with streptozotocin (STZ)-induced type 1 diabetes . Twenty-seven male Sprague-Dawley rats aged 12 weeks were r and omized by the weight-stratified method into the following three groups : age-matched control group , STZ + vehicle group , and STZ + vitamin K2 group . STZ ( 40 + 50 mg/kg ) was administered intravenously twice during the initial 1-week period . Vitamin K2 ( menatetrenone , 30 mg/kg ) was administered orally 5 days a week . After 12 weeks of treatment , the serum glucose concentration and femoral length and weight were measured and histomorphometric analysis was performed on the cancellous and cortical bone of the distal femoral metaphysis and femoral diaphysis , respectively . STZ administration induced hyperglycemia and a decrease in femoral weight . The STZ + vehicle group also showed cancellous osteopenia due to a decrease in the number of osteoblasts/bone surface ( N.Ob/BS ) and the osteoblast surface (ObS)/BS without any significant changes in bone-resorption parameters , but it did not have a significant decrease in cortical bone mass . Administration of vitamin K2 to STZ-treated rats prevented the development of hyperglycemia and a decrease in femoral weight .  Vitamin K2 also prevented cancellous osteopenia by inhibiting the decrease in N.Ob/BS and ObS/BS without significantly affecting bone-resorption parameters , but it did not significantly increase cortical bone mass . These results suggest that vitamin K2 has beneficial effects on glucose concentration and cancellous bone mass in rats with STZ-induced type 1 diabetes
target: Sensitivity analysis showed that overall estimates were not affected by elimination of any study .
  We did not observe any evidence regarding publication bias .
  In conclusion , vitamin K supplementation had no signiﬁcant effect on glycemic control in healthy subjects .
background: Type 2 diabetes mellitus ( T2DM ) is one of the most important public health issues .
  Vitamin K supplementation might have favorable effect on risk factors of T2DM .
  The aim of this study was to perform a systematic review and meta- analysis of interventional studies to examine the effect of vitamin K supplementation on glycemic indices .