vitamin-k-1 and Diabetes-Mellitus--Type-2

Vitamin K has been related to cardiovascular disease and cancer risk. However, data on total mortality are scarce. The aim of the present study was to assess the association between the dietary intake of different types of vitamin K and mortality in a Mediterranean population at high cardiovascular disease risk. A prospective cohort analysis was conducted in 7216 participants from the PREDIMED (Prevención con Dieta Mediterránea) study (median follow-up of 4.8 y). Energy and nutrient intakes were evaluated using a validated 137-item food frequency questionnaire. Dietary vitamin K intake was calculated annually using the USDA food composition database and other published sources. Deaths were ascertained by an end-point adjudication committee unaware of the dietary habits of participants after they had reviewed medical records and linked up to the National Death Index. Cox proportional hazard models were fitted to assess the RR of mortality. Energy-adjusted baseline dietary phylloquinone intake was inversely associated with a significantly reduced risk of cancer and all-cause mortality after controlling for potential confounders (HR: 0.54; 95% CI: 0.30, 0.96; and HR: 0.64; 95% CI: 0.45, 0.90, respectively). In longitudinal assessments, individuals who increased their intake of phylloquinone or menaquinone during follow-up had a lower risk of cancer (HR: 0.64; 95% CI: 0.43, 0.95; and HR: 0.41; 95% CI: 0.26, 0.64, respectively) and all-cause mortality (HR: 0.57; 95% CI: 0.44, 0.73; and HR: 0.55; 95% CI: 0.42, 0.73, respectively) than individuals who decreased or did not change their intake. Also, individuals who increased their intake of dietary phylloquinone had a lower risk of cardiovascular mortality risk (HR: 0.52; 95% CI: 0.31, 0.86). However, no association between changes in menaquinone intake and cardiovascular mortality was observed (HR: 0.76; 95% CI: 0.44, 1.29). An increase in dietary intake of vitamin K is associated with a reduced risk of cardiovascular, cancer, or all-cause mortality in a Mediterranean population at high cardiovascular disease risk. This trial was registered at http://www.controlled-trials.com as ISRCTN35739639.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Mediterranean; Female; Follow-Up Studies; Humans; Incidence; Male; Mediterranean Region; Middle Aged; Neoplasms; Plant Oils; Proportional Hazards Models; Prospective Studies; Risk Factors; Vegetables; Vitamin K; Vitamin K 1; Vitamin K 2

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

Limited evidence from human and animal studies has suggested that vitamin K has a potentially beneficial role in glucose metabolism and insulin resistance.. We analyzed the cross-sectional and longitudinal associations between dietary phylloquinone intake and type 2 diabetes in elderly subjects at high cardiovascular risk.. Cross-sectional associations were tested in 1925 men and women in the Prevention with the Mediterranean Diet trial. A longitudinal analysis was conducted on 1069 individuals free of diabetes at baseline (median follow-up: 5.5 y). Biochemical and anthropometric variables were obtained yearly. Dietary intake was collected during each annual visit by using a food-frequency questionnaire, and phylloquinone intake was estimated by using the USDA database. The occurrence of type 2 diabetes during follow-up was assessed by using American Diabetes Association criteria.. Dietary phylloquinone at baseline was significantly lower in subjects who developed type 2 diabetes during the study. After adjustment for potential confounders, risk of incident diabetes was 17% lower for each additional intake of 100 μg phylloquinone/d. Moreover, subjects who increased their dietary intake of vitamin K during the follow-up had a 51% reduced risk of incident diabetes compared with subjects who decreased or did not change the amount of phylloquinone intake.. We conclude that dietary phylloquinone intake is associated with reduced risk of type 2 diabetes. This trial was registered at http://www.controlled-trials.com as ISRCTN35739639.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Proportional Hazards Models; Regression Analysis; Socioeconomic Factors; Spain; Surveys and Questionnaires; Vitamin K 1

Observational studies have reported lower risks of type 2 diabetes with higher vitamin K1 intake, but these studies overlook effect modification due to known diabetes risk factors.. To identify subgroups that might benefit from vitamin K1 intake, we examined associations between vitamin K1 intake and incident diabetes overall and in subpopulations at risk of diabetes.. Participants from the prospective cohort, the Danish Diet, Cancer, and Health Study, with no history of diabetes were followed up for diabetes incidence. The association between intake of vitamin K1, estimated from a food frequency questionnaire completed at baseline, and incident diabetes was determined using multivariable-adjusted Cox proportional-hazards models.. In 54 787 Danish residents with a median (interquartile range) age of 56 (52-60) years at baseline, 6700 individuals were diagnosed with diabetes during 20.8 (17.3-21.6) years of follow-up. Vitamin K1 intake was inversely and linearly associated with incident diabetes (P < .0001). Compared to participants with the lowest vitamin K1 intake (median:57 µg/d), participants with the highest intakes (median:191 µg/d) had a 31% lower risk of diabetes (HR; 95% CI, 0.69; 0.64-0.74) after multivariable adjustments. The inverse association between vitamin K1 intake and incident diabetes was present in all subgroups (namely, men and women, ever and never smokers, low and high physical activity groups, and in participants who were normal to overweight and obese), with differences in absolute risk between subgroups.. Higher intake of foods rich in vitamin K1 was associated with a lower risk of diabetes. If the associations observed are causal, our results indicate that more cases of diabetes would be prevented in subgroups at higher risk (men, smokers, participants with obesity, and those with low physical activity).

Topics: Denmark; Diabetes Mellitus, Type 2; Diet; Female; Humans; Male; Middle Aged; Neoplasms; Obesity; Prospective Studies; Risk Factors; Vitamin K 1; Vitamin K 2

Chronic kidney disease (CKD) is accompanied with extensive cardiovascular calcification, in part correlating with functional vitamin K deficiency. Here, we sought to determine causes for vitamin K deficiency beyond reduced dietary intake. Initially, vitamin K uptake and distribution into circulating lipoproteins after a single administration of vitamin K1 plus K2 (menaquinone 4 and menaquinone 7, respectively) was determined in patients on dialysis therapy and healthy individuals. The patients incorporated very little menaquinone 7 but more menaquinone 4 into high density lipoprotein (HDL) and low-density lipoprotein particles than did healthy individuals. In contrast to healthy persons, HDL particles from the patients could not be spiked with menaquinone 7 in vitro and HDL uptake was diminished in osteoblasts. A reduced carboxylation activity (low vitamin K activity) of uremic HDL particles spiked with menaquinone 7 vs. that of controls was confirmed in a bioassay using human primary vascular smooth muscle cells. Kidney menaquinone 4 tissue levels were reduced in 5/6-nephrectomized versus sham-operated C57BL/6 mice after four weeks of a vitamin K rich diet. From the analyzed enzymes involved in vitamin K metabolism, kidney HMG-CoA reductase protein was reduced in both rats and patients with CKD. In a trial on the efficacy and safety of atorvastatin in 1051 patients with type 2 diabetes receiving dialysis therapy, no pronounced vitamin K deficiency was noted. However, the highest levels of PIVKA-II (biomarker of subclinical vitamin K deficiency) were noted when a statin was combined with a proton pump inhibitor. Thus, profound disturbances in lipoprotein mediated vitamin K transport and metabolism in uremia suggest that menaquinone 7 supplementation to patients on dialysis therapy has reduced efficacy.

Topics: Animals; Diabetes Mellitus, Type 2; Humans; Mice; Mice, Inbred C57BL; Rats; Renal Insufficiency, Chronic; Tissue Distribution; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency

The fat-soluble K vitamins K1 and K2 play an essential role in the blood coagulation cascade and are made available predominantly through selective dietary intakes. They are less known for their nonessential roles in a family of vitamin K-dependent proteins that promote various functions of organs and systems in the body. A lack of vitamin K can characterize vitamin and nutritional element insufficiency, which is different from a clinically apparent vitamin deficiency.. This epidemiological study evaluated the nutritional status of vitamin K in a sample of the Indian population and vitamin K content in staple Indian foods.. Serum levels of vitamin K1 and vitamin K2 in the form of menaquinone-7 (MK-7) were assessed via high-performance liquid chromatography coupled with fluorescence detection in 209 patients with type 2 diabetes, 50 healthy volunteers, and common staple foods in India.. After comparing populations with high and low serum vitamin K levels from various geographical regions, our results indicated that the sample of healthy Indian individuals and the sample of Indian patients with type 2 diabetes had low (insufficient) levels of vitamin K2 (MK-7; range 0.3-0.4 ng/mL). No significant differences existed in vitamin K1-related and MK-7-related values between healthy male and female subjects, between male and female subjects with diabetes, and between the healthy sample and the sample of patients with diabetes. The staple, commonly consumed Indian foods that were tested in this study had undetectable levels of vitamin K2, while levels of vitamin K1 varied widely (range 0-37 µg/100 g).. Based on our sample's low serum levels of vitamin K2 (MK-7) as well as the low levels of vitamin K2 in their typical diet, we propose that the general Indian population could benefit from the consumption of vitamin K2 in the form of MK-7 supplements.. Clinical Trials Registry - India CTRI/2019/05/014246; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=21660&EncHid=&userName=014246; Clinical Trials Registry - India CTRI/2019/03/018278; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=32349&EncHid=&userName=018278.

Topics: Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Male; Vitamin K; Vitamin K 1; Vitamin K 2

Serum vitamin K was quantified in 3239 individuals with and 3808 without diabetes enrolled in Vejle Diabetes Biobank (2007-2010). Each individual was assessed for microangiography and macroangiopathy at enrollment based on registered diagnoses in the Danish National Patient Registry according to the International Classification of Disease 8 (1977-1993) and 10 (since 1994). Using multinomial logistic regression, relative risk ratios (RRRs) were calculated within each group of individuals with and without diabetes. RRRs were estimated for microangiopathic/macroangiopathic status compared with individuals without complications as a function of 1 nmol/L increments in K. Serum vitamin K

Topics: Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Vascular Diseases; Vitamin K 1; Vitamins

Topics: Cohort Studies; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Genotype; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors; Vitamin K 1

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

Vitamin K1 (phytomenadione or phytonadione) is a fat soluble vitamin used to treat certain coagulation disorders. Intra muscular injection of vitamin K1 can occasionally be complicated by different types of skin reactions: erythematous plaques, urticarial rashes or scleroderma-like lesions at the injection site. We report the case of a 52-year-old man presenting with 2 symmetrical erythematous-infiltrated scleroderma-like plaques localized on the right and left lower trunk. To correct the coagulation deficiency with hypoprothrombinemia developed as a consequence of HCV+ hepatitis, the patient was on vitamin K1 therapy, administered by i.m. injection (10 mg Vitamin K1/1 ml) once a day for 2 weeks. Three months after treatment interruption, ivory indurated morphoeiform plaques developed at the injection sites, assuming the typical appearance of a "cowboy's belt with revolver". The scleroderma-like lesions persisted 2 years after vitamin K1 withdrawal. We report this case to highlight the possibility that vitamin K1 injections can occasionally be complicated by different types of skin reactions such as sclerodermatous plaques. Due to the delay in the onset, to the variable clinical picture, to the persistence after therapy interruption, this kind of lesions can represent a tricky diagnostic challenge and in spite of different treatments can endure for years.

Topics: Diabetes Mellitus, Type 2; Erythema; Hepatitis C, Chronic; Humans; Hypoprothrombinemias; Injections, Intramuscular; Male; Middle Aged; Scleroderma, Localized; Vitamin K 1

To investigate whether dietary phylloquinone and menaquinones intakes are related to risk of type 2 diabetes.. We used data from a prospective cohort study in 38,094 Dutch men and women, aged 20-70 years. Dietary phylloquinone and menaquinones intakes were assessed using a validated food frequency questionnaire. Diabetes case patients were ascertained mainly via self-report and verified against medical records.. 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-microg increment in the multivariate model.. This study shows that both phylloquinone and menaquinones intakes may be associated with a reduced risk of type 2 diabetes.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Prospective Studies; Vitamin K 1; Vitamin K 2; Vitamins; Young Adult

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