vitamin-k-semiquinone-radical and Diabetes-Mellitus--Type-2

Medical nutrition treatment can manage diabetes and slow or prevent its complications. The comparative effects of micronutrient supplements, however, have not yet been well established. We aimed at evaluating the comparative effects of vitamin and mineral supplements on managing glycemic control and lipid metabolism for type 2 diabetes mellitus (T2DM) to inform clinical practice. Electronic and hand searches for randomized controlled trials (RCTs) were performed until June 1, 2022. We selected RCTs enrolling patients with T2DM who were treated with vitamin supplements, mineral supplements, or placebo/no treatment. Data were pooled via frequentist random-effects network meta-analyses. A total of 170 eligible trials and 14223 participants were included. Low to very low certainty evidence established chromium supplements as the most effective in reducing fasting blood glucose levels and homeostasis model assessment of insulin resistance (SUCRAs: 90.4% and 78.3%, respectively). Vitamin K supplements ranked best in reducing glycated hemoglobin A1c and fasting insulin levels (SUCRAs: 97.0% and 82.3%, respectively), with moderate to very low certainty evidence. Vanadium supplements ranked best in lowering total cholesterol levels with very low evidence certainty (SUCRAs:100%). Niacin supplements ranked best in triglyceride reductions and increasing high-density lipoprotein cholesterol levels with low to very low evidence certainty (SUCRAs:93.7% and 94.6%, respectively). Vitamin E supplements ranked best in reducing low-density lipoprotein cholesterol levels with very low evidence certainty (SUCRAs:80.0%). Our analyses indicated that micronutrient supplements, especially chromium, vitamin E, vitamin K, vanadium, and niacin supplements, may be more efficacious in managing T2DM than other micronutrients. Considering the clinical importance of these findings, new research is needed to get better insight into this issue.

Topics: Cholesterol; Chromium; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Micronutrients; Minerals; Network Meta-Analysis; Niacin; Primary Health Care; Randomized Controlled Trials as Topic; Vanadium; Vitamin E; Vitamin K; Vitamins

Type 2 diabetes mellitus (T2DM) is one of the leading causes of death worldwide. Genetic factors, some underlying medical conditions, and obesity are risk factors of T2DM. Unlike other risk factors which are non-modifiable, obesity is preventable and usually treatable, and is largely contributed by lifestyle factors. Management of these lifestyle factors may curb the development of T2DM and reduces T2DM prevalence. Dietary vitamins have been recommended as a lifestyle modification intervention to support obesity treatment. Vitamins correlate negatively with body weight, body mass index and body composition. Some of the vitamins may also have anti-adipogenic, anti-inflammatory and antioxidant effects. However, results from pre-clinical and clinical studies of the effects of vitamins on obesity are inconsistent. A clear understanding of the effects of vitamins on obesity will help determine dietary intervention that is truly effective in preventing and treating obesity as well as obesity-related complications including T2DM. This article reviews existing evidences of the effects of vitamin supplementation on obesity and obesity-related metabolic status.

Topics: Diabetes Mellitus, Type 2; Diet; Humans; Obesity; Vitamin A; Vitamin K; Vitamins

Diabetic peripheral neuropathy (DPN) is a pervasive and incapacitating sequela of diabetes, affecting a significant proportion of those diagnosed with the disease, yet an effective treatment remains elusive. Vitamins have been extensively studied, emerging as a promising target for diagnosing and treating various systemic diseases, but their role in DPN is not known. This review collates and synthesizes knowledge regarding the interplay between vitamins and DPN, drawing on bibliographies from prior studies and relevant articles, and stratifying the therapeutic strategies from prophylactic to interventional. In addition, the clinical evidence supporting the use of vitamins to ameliorate DPN is also evaluated, underscoring the potential of vitamins as putative therapeutic agents. We anticipate that this review will offer novel insights for developing and applying vitamin-based therapies for DPN.

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Vitamin A; Vitamin K; Vitamins

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Insulin; Insulin Resistance; Vitamin K

Cardiovascular disease (CVD) remains the leading cause of mortality in patients with type 2 diabetes (T2D). The conventional therapies seem to offer minimal long-term cardioprotection against diabetes-related complications in patients living with T2D. There is a growing interest in understanding the therapeutic effects of food-derived bioactive compounds in protecting or managing these metabolic diseases. This includes uncovering the therapeutic potential of fat-soluble micronutrients such as vitamin K, which are abundantly found in green leafy vegetables. We searched the major electronic databases including PubMed, Web of Sciences, Scopus, Google Scholar and Science direct. The search retrieved randomized clinical trials and preclinical studies, reporting on the impact of vitamin K on CVD-related complications in T2D. The current review updates clinical evidence on the therapeutic benefits of vitamin K by attenuating CVD-risk factors such as blood lipid profiles, blood pressure, as well as markers of oxidative stress and inflammation in patients with T2D. Importantly, the summarized preclinical evidence provides a unique perspective into the pathophysiological mechanisms that could be targeted by vitamin K in the primary prevention of T2D-related complications. Lastly, this review further explores the controversies related to the cardioprotective effects of vitamin K, and also provides the basic information such as the source and bioavailability profile of this micronutrient is covered to highlight its therapeutic potential.

Topics: Cardiotonic Agents; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Micronutrients; Primary Prevention; Trace Elements; Vitamin K; Vitamins

In recent years, our knowledge regarding the physiological role of vitamin K has expanded beyond regulation of coagulation to include many other aspects of human health. In the present review, we aimed to evaluate the existing evidence for beneficial effects of vitamin K on type 2 diabetes and components of the metabolic syndrome as risk factors for cardiovascular disease. Increased dietary intake of vitamin K has been linked to lower incidence of type 2 diabetes mellitus (T2DM), possibly through its enhancement of insulin production and sensitivity. Additionally, higher plasma levels of vitamin K1 have been associated with lower T2DM risk and decreased insulin resistance, and supplementation trials also suggest a positive influence of vitamin K on glucose regulation. Vitamin K might also beneficially affect serum lipids and lipid metabolism. However, the available data remain controversial. Additionally, different studies use different approaches to assess vitamin K status owing to the absence of a generally accepted marker, which further complicates data evaluation. In conclusion, vitamin K possibly improves glucose and lipid metabolism and could be an emerging target in the context of prevention and control of T2DM, insulin resistance, and dyslipidemia.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Homeostasis; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Lipids; Vitamin K

Obesity and diabetes are important metabolic diseases and a major public health problem among the world, they have serious health and economic complications. Overweight and obesity are increased risk for deficiency of vitamin particularly shortage of fat soluble-vitamins. Studies reported that vitamin K supplementation reduces oxidative stress and metabolic risk biomarkers for diabetes, as well as reduces progression of insulin resistance. Vitamin K-dependent-protein osteocalcin (bone derived hormone) plays crucial roles in energy metabolism. There is a clear association between circulating vitamin k and dependent-osteocalcin concentrations with obesity and risk of Type 2 diabetes. Osteocalcin through molecular mechanisms improves insulin resistance, lipid and glucose profile, and mediate vitamin K positive effects. Insulin also signals osteocalcin to regulate bone mineralization. Normal carboxylation of vitamin K-dependent proteins/ hormones is a key step in preventing apoptosis and calcification of vascular endothelial cells. A missing relationship between bone, glucose and fat metabolism could clarify and manage many metabolic mechanisms. This review focuses on the physiological relationship between vitamin K-dependent-osteocalcin, metabolic and cardiovascular diseases through some molecular proteins and hormones including adipokines. A better understanding of the mechanism of action of osteocalcin modulated by vitamin K could help in implementing therapeutic drugs to cure metabolic diseases.

Topics: Animals; Bone and Bones; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endocrine System; Female; Humans; Insulin Resistance; Male; Obesity; Osteocalcin; Vitamin K

Topics: Blood Glucose; China; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Insulin; Observational Studies as Topic; Vitamin K

Type 2 diabetes mellitus is a chronic disease that is characterized by hyperglycemia, insulin resistance, and dysfunctional insulin secretion. Glycemic control remains a crucial contributor to the progression of type 2 diabetes mellitus as well as the prevention or delay in the onset of diabetes-related complications. Vitamin K is a fat-soluble vitamin that plays an important role in the regulation of the glycemic status. Supplementation of vitamin K may reduce the risk of diabetes mellitus and improve insulin sensitivity. This mini-review summarizes the recent insights into the beneficial effects of vitamin K and its possible mechanism of action on insulin sensitivity and glycemic status, thereby suppressing the progression of diabetes mellitus.

Topics: Adult; Aged; Diabetes Complications; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Progression; Female; Glycemic Control; Humans; Insulin Resistance; Male; Middle Aged; Nutritional Status; Vitamin K; Young Adult

Type 2 diabetes is one of the most important public health diseases. Type 2 diabetes pathophysiology involves multiple pathways, in which micronutrients could play a role. Among them, interest has grown concerning vitamin K. The purpose of this review is to expose the latest studies on the role of vitamin K in glucose metabolism, a poorly known function of this vitamin.. Animal experimentations and human observational and interventional studies were analyzed to evaluate the role of this vitamin in glucose metabolism. Daily intake of vitamin K seems to improve glucose metabolism and low intakes could be involved in type 2 diabetes pathophysiology. Recent data show that vitamin K could act on glucose metabolism via downstream targets such as osteocalcin, growth arrest-specific 6 protein, and matrix Gla protein.. This review depicts new insights into the role of vitamin K in glucose metabolism regulation and depicts also the probable mechanisms underlying this association. Further studies will be needed to determine the dose and the duration of vitamin K treatment to achieve the strongest metabolic effect. Maybe the best strategy to improve glucose metabolism would be 'cocktails' of micronutrients associating vitamin K.

Topics: Diabetes Mellitus, Type 2; Glucose; Humans; Vitamin K; Vitamins

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. A systematic search was performed in electronic databases including PubMed, Science Direct, ProQuest, Institute of Scientific Information Web of Science, and Google scholar up to July 2017. We used a random effects model to estimate pooled effect size of fasting blood sugar (FBS), 2-h oral glucose tolerance test (2-h OGTT), fasting insulin (FINS), and homeostasis model assessment-estimated insulin resistance (HOMA-IR). Five clinical trials (533 participants) fulfilled the eligibility criteria of the present meta-analysis. Overall, meta-analysis could not show any beneficial effect of vitamin K supplementation on FBS (-0.91 mg/dl, 95% CI: -2.57, 0.76, p=0.28), FINS (-0.35 μIU/ml, 95% CI: -1.70, 1.00, p=0.61), HOMA-IR (-0.06, 95% CI: -0.32, -0.19, p=0.63), and 2-h OGTT (-4.00 mg/dl, 95% CI: -20.00, 11.99, p=0.62). 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. However, further studies should be performed on diabetic and pre-diabetic patients to determine the effect of vitamin K supplementation on impaired glycemic control.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Prediabetic State; Vitamin K

Adiponectin is an adipokine mainly secreted by adipocytes that presents antidiabetic, anti-inflammatory, and antiatherogenic functions. Therefore, modulation of adiponectin expression represents a promising target for prevention or treatment of several diseases including insulin resistance and type II diabetes. Pharmacological agents such as the nuclear hormone receptor synthetic agonists like peroxisome proliferator activated receptor γ agonists are of particular interest in therapeutic strategies due to their ability to increase the plasma adiponectin concentration. Nutritional approaches are also of particular interest, especially in primary prevention, since some active compounds of our diet (notably vitamins, carotenoids, or other essential nutrients) are direct or indirect lipid-activators of nuclear hormone receptors and are modifiers of adiponectin expression and secretion. The aim of the present review is to summarize current knowledge about the nutritional regulation of adiponectin by derivatives of active compounds naturally present in the diet acting as indirect or direct activators of nuclear hormone receptors.

Topics: Adiponectin; Animals; Diabetes Mellitus, Type 2; Diet; Disease Models, Animal; Fatty Acids, Unsaturated; Fishes; Fruit; Humans; Insulin Resistance; PPAR gamma; Receptors, Cytoplasmic and Nuclear; Retinoid X Receptors; Seafood; Signal Transduction; Vegetables; Vitamin A; Vitamin D; Vitamin E; Vitamin K

Vitamins D and K are essential for maintaining bone and its deficiency has been associated with several chronic diseases.. To know the intake of vitamins D and K in female population and analyze their involvement on health.. Literature research regarding the topic.. Intake of vitamin D in the Spanish female population from 17 to 60 years is lower than the estimated average requirement in the 95.5% of the studied participants and 30.2% of the Spanish population does not meet the established adequate intake for vitamin K. Several studies have emphasized the importance of maintaining optimal nutrition status of vitamin D for its role in the maintenance of bone, but also for its involvement in body weight control and prevention of diseases (cardiovascular disease, type 2 diabetes, cancer). Vitamin K deficiency is also associated with decreased bone density and increased cardiovascular risk besides exerting a protective effect against type 2 diabetes.. In female population, the intake of vitamin K, but especially vitamin D, is often lower than recommended. Since a worse nutritional status in these vitamins is associated with damage in bone health, weight control, as well as an increased risk of several diseases, it seems appropriate to monitor and improve their intake.. Introducción: las vitaminas D y K juegan un papel esencial en el mantenimiento del hueso, y su deficiencia se ha asociado con diversas enfermedades crónicas. Objetivos: conocer la ingesta de vitaminas D y K en la población femenina y analizar la implicación de su deficiencia en la salud. Métodos: búsqueda bibliográfica en relación con el tema. Resultados: la ingesta de vitamina D en la población femenina española de 17 a 60 años es inferior al EAR en un 96,5% de las mujeres, y un 30,2% de la población española no cubre las IA de vitamina K. Diversos estudios han puesto de relieve la importancia de mantener una situación nutricional de vitamina D óptima, por su papel en el mantenimiento del hueso, pero también por su participación en el control de peso corporal y en la prevención de enfermedades (cardiovasculares, diabetes tipo 2, cáncer, etc.). El déficit de vitamina K también se asocia con una menor densidad ósea y un aumento del riesgo cardiovascular, además de ejercer un efecto protector frente a la diabetes tipo 2. Conclusiones: en el colectivo femenino, la ingesta de vitamina K, pero especialmente la de vitamina D es, con frecuencia, inferior a la recomendada. Dado que una peor situación nutricional en estas vitaminas se asocia con perjuicios en la salud ósea y en el control de peso, así como con un mayor riesgo de padecer diversas enfermedades, parece conveniente vigilar y mejorar el aporte dietético.

Topics: Bone Density; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Health Status; Humans; Nutritional Requirements; Nutritional Status; Spain; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency; Women's Health

The purpose of this study was to assess the possible clinical effects of vitamin K4 supplementation in individuals with type 2 diabetes namely insulin resistance, glycaemic control, and lipid profile.. This was a prospective randomised double-blind placebo-controlled clinical trial. A total of 106 patients were randomised to receive either 1 mg of vitamin K4 (menadiol diacetate) or placebo for 24 weeks.. Ninety patients (n = 45 in each study group) were included in the final analysis. After 24 weeks, homeostatic model assessment of insulin resistance (HOMA-IR) (16.54 ± 7.81 vs. 29.09 ± 36.56, P = 0.027) and fasting serum insulin (FSI) (6.86 ± 3.45 vs. 11.13 ± 12.66 µU/ml, P = 0.032) were significantly lower in the vitamin K group compared to placebo. Additionally, triglycerides (TG) (144.94 ± 50.7 vs. 172.8 ± 101.5 mg/dl, P = 0.031) and very low-density lipoproteins (VLDL) levels (28.9 ± 9.88 vs. 34.6 ± 20.30 mg/dl, P = 0.027) decreased significantly in the vitamin K group after 24 weeks compared to baseline. Moreover, more patients in the vitamin K group (35.6%) had their antidiabetic medication doses reduced after 24 weeks compared to placebo (13.3%, P = 0.029).. Vitamin K4 supplementation for 24 weeks is capable of improving insulin resistance and TG levels in individuals with type 2 diabetes. In addition, the improvement in insulin resistance was reflected in the decrease in antidiabetic medication doses. However, it did not affect fasting plasma glucose (FPG) or glycated haemoglobin (HbA. The study was registered on clinicaltrials.gov with ID: NCT04285450.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Prospective Studies; Vitamin K; Vitamins

Vitamin K-dependent proteins are involved in (patho)physiological calcification of the vasculature and the bones. Type 2 diabetes mellitus (DM2) is associated with increased arterial calcification and increased fractures. This study investigates the effect of 6 months vitamin K2 supplementation on systemic arterial calcification and bone mineral density (BMD) in DM2 patients with a history of cardiovascular disease (CVD).. In this pre-specified, post hoc analysis of a double-blind, randomized, controlled clinical trial, patients with DM2 and CVD were randomized to a daily, oral dose of 360 µg vitamin K2 or placebo for 6 months. CT scans were made at baseline and follow-up. Arterial calcification mass was quantified in several large arterial beds and a total arterial calcification mass score was calculated. BMD was assessed in all non-fractured thoracic and lumbar vertebrae.. 68 participants were randomized, 35 to vitamin K2 (33 completed follow-up) and 33 to placebo (27 completed follow-up). The vitamin K group had higher arterial calcification mass at baseline [median (IQR): 1694 (812-3584) vs 1182 (235-2445)] for the total arterial calcification mass). Six months vitamin K supplementation did not reduce arterial calcification progression (β [95% CI]: - 0.02 [- 0.10; 0.06] for the total arterial calcification mass) or slow BMD decline (β [95% CI]: - 2.06 [- 11.26; 7.30] Hounsfield units for all vertebrae) when compared to placebo.. Six months vitamin K supplementation did not halt progression of arterial calcification or decline of BMD in patients with DM2 and CVD. Future clinical trials may want to pre-select patients with very low vitamin K status and longer follow-up time might be warranted. This trial was registered at clinicaltrials.gov as NCT02839044.

Topics: Bone Density; Calcification, Physiologic; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Humans; Vitamin K; Vitamin K 2

This study aimed to investigate the effects of vitamin K. In this double-blinded, placebo-controlled, randomized trial, 68 insulin-independent people with diabetes received either 180 µg MK-7 twice a day or placebo for 12 weeks. We assessed fasting plasma glucose (FPG) and insulin concentrations (primary outcomes), glycated hemoglobin (HbA1c), insulin sensitivity indices, and lipid profiles (secondary outcomes) at baseline and end of the trial.. At the end of the trial, FPG (effect size (ES) = - 0.68; p-adjusted = 0.031) and HbA1c (ES = - 0.36; p-adjusted = 0.004) were significantly lower in the vitamin K. Daily intake of 360 µg Vitamin K

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Glycated Hemoglobin; Glycemic Control; Humans; Insulin; Insulin Resistance; Vitamin K

We investigated the use of different antithrombotic therapies at baseline among patients with a history of atrial fibrillation (AF), type 2 diabetes, and established atherosclerotic cardiovascular disease (ASCVD) enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).. TECOS participants with a history of AF were stratified by CHA. Of the 14,671 TECOS participants, 1167 (8%) had a history of AF, of whom 51.6% were using vitamin K antagonists (VKA); 31.2% used VKA alone, 16.9% used aspirin plus VKA, 1.8% used clopidogrel plus VKA, and 1.7% used aspirin and clopidogrel plus VKA. Aspirin was used by 56.8%: 30.9% used aspirin alone and 7.3% aspirin plus clopidogrel. Clopidogrel alone was used by 2.9%, and 7.3% were not using any antithrombotic medication. Participants with a history of AF had a higher risk of cardiovascular events, including hospitalization for heart failure and all-cause mortality, than those without AF. White, older men with prior myocardial infarction, heart failure, peripheral artery disease, or prior stroke were more likely to develop new-onset AF than others without these characteristics.. Almost half of high-risk AF patients with diabetes and established ASCVD in TECOS were not treated with anticoagulation therapy despite clear guideline recommendations for such therapy, highlighting the challenge and potential for clinical improvements in managing these patients in clinical practice.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Topics: Aspirin; Atrial Fibrillation; Clopidogrel; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Male; Middle Aged; Platelet Aggregation Inhibitors; Sitagliptin Phosphate; Stroke; Time Factors; Treatment Outcome; Vitamin K

There is no previous study that has examined the relationship between circulating vitamin K1 (VK1) and vascular inflammation in type 2 diabetes (T2D). This study aims to examine the hypothesis that circulating VK1 deficiency may be associated with higher inflammation and insulin resistance in T2D patients and that VK1 supplementation regulates the NF-κB/Nrf2 pathway via activating VK-dependent Gla proteins and reduces vascular inflammation. The results showed that plasma VK1 levels were significantly lower and MCP-1, fasting glucose, HbA1c, and insulin resistance (HOMA-IR) were significantly higher in T2D patients compared to those in the controls. The lower levels of VK1 in T2D patients were significantly and inversely correlated with MCP-1 and HOMA-IR, which suggests that VK1 supplementation may reduce the vascular inflammation and insulin resistance in T2D. Using a high fat diet-fed T2D mice model this study further demonstrated that VK1 supplementation (1, 3, 5 μg per kg BW, 8 weeks) dose-dependently decreased the body weight gain, glucose intolerance, fasting glucose, glycated hemoglobin, HOMA-IR, and cytokine secretion (MCP-1 and IL-6) in T2D mice. Further cell culture studies showed that VK1 supplementation (1, 5, or 10 nM) decreased NF-κB phosphorylation and MCP-1 secretion and increased Nrf2 protein expression in high glucose (HG, 25 mM)-treated monocytes. Signal silencing studies with GGCX siRNA again depicted the role of VK-dependent Gla proteins in mediating the effect of VK1 on vascular inflammation in HG-treated cells. In conclusion, this study suggests that circulating VK1 has a positive effect in lowering vascular inflammation in T2D by regulating NF-κB/Nrf2 transcription factors via activating VK-dependent Gla proteins.

Topics: Animals; Calcium-Binding Proteins; Carbon-Carbon Ligases; Chemokine CCL2; Diabetes Mellitus, Type 2; Dietary Supplements; Extracellular Matrix Proteins; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Matrix Gla Protein; Mice; Middle Aged; Monocytes; NF-E2-Related Factor 2; NF-kappa B; Vitamin K

This study was conducted to examine the effects of vitamin D, K and Ca co-supplementation on carotid intima-media thickness (CIMT) and metabolic status in overweight diabetic patients with CHD. This randomised, double-blind, placebo-controlled trial was conducted among sixty-six diabetic patients with CHD. Participants were randomly allocated into two groups to take either 5µg vitamin D, 90 µg vitamin K plus 500 mg Ca supplements (n 33) or placebo (n 33) twice a day for 12 weeks. Fasting blood samples were obtained at the beginning of the study and after the 12-week intervention period to determine related markers. Vitamin D, K and Ca co-supplementation resulted in a significant reduction in maximum levels of left CIMT (-0·04 (sd 0·22) v. +0·04 (sd 0·09) mm, P=0·02). Changes in serum vitamin D (+6·5 (sd 7·8) v. +0·4 (sd 2·2) ng/ml, P<0·001), Ca (+0·6 (sd 0·3) v. +0·1 (sd 0·1) mg/dl, P<0·001) and insulin concentrations (-0·9 (sd 3·1) v. +2·6 (sd 7·2) µIU/ml, P=0·01), homoeostasis model for assessment of estimated insulin resistance (-0·4 (sd 1·2) v. +0·7 (sd 2·3), P=0·01), β-cell function (-2·1 (sd 9·0) v. +8·9 (sd 23·7), P=0·01) and quantitative insulin sensitivity check index (+0·007 (sd 0·01) v. -0·006 (sd 0·02), P=0·01) in supplemented patients were significantly different from those in patients in the placebo group. Supplementation resulted in significant changes in HDL-cholesterol (+2·7 (sd 7·0) v. -2·5 (sd 5·7) mg/dl, P=0·002), high-sensitivity C-reactive protein (-1320·1 (sd 3758·3) v. +464·0 (sd 3053·3) ng/ml, P=0·03) and plasma malondialdehyde concentrations (-0·4 (sd 0·5) v. -1·0 (sd 1·1) µmol/l, P=0·007) compared with placebo. Overall, vitamin D, K and Ca co-supplementation for 12 weeks among diabetic patients with CHD had beneficial effects on maximum levels of left CIMT and metabolic status. The effect of vitamin D, K and Ca co-supplementation on maximum levels of left CIMT could be a chance finding.

Topics: Aged; Blood Glucose; C-Reactive Protein; Calcium; Carotid Intima-Media Thickness; Cholesterol, HDL; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Insulin; Insulin Resistance; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress; Vitamin D; Vitamin K; Vitamins

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

B vitamins in the human distal gut are primarily derived from the gut microbiota because daily dietary vitamins are fully absorbed in the small intestine under normal dietary and physiological conditions. Quantitative determination of B vitamins in the distal gut and faecal samples is crucial for understanding the intricate relationship between gut B vitamins, gut microbiota, and host health. In this study, we developed a rapid, robust, and reliable method with a simple extraction procedure for the simultaneous analysis of seven B vitamins in human faeces using high-performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (HPLC-ESI-MS/MS) with stable isotope-labelled internal standards. A protein precipitation approach using methanol as the precipitant was employed to extract vitamin B from human faecal samples. Seven B vitamins were adequately separated and quantified within 9 min by HPLC-ESI-MS/MS with a Pursuit PFP column (2.0 ×150 mm, 3.0 µm), including vitamins B1, B2, B3, B5, pyridoxic acid, pyridoxine, and B7. The lower limits of quantification were within the range of 0.1-25 ng mL

Topics: Chromatography, High Pressure Liquid; Chromatography, Liquid; Diabetes Mellitus, Type 2; Feces; Humans; Obesity; Pyridoxic Acid; Tandem Mass Spectrometry; Vitamin A; Vitamin B Complex; Vitamin K

Topics: Diabetes Mellitus, Type 2; Diet; Humans; Iron, Dietary; Nutrition Surveys; Vitamin A; Vitamin K; Vitamins

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

The role of gamma-glutamyl-carboxylated growth arrest-specific 6 (cGas6) in mediating the beneficial effect of vitamin K (VK) on regulating glucose metabolism remains elusive. We took a three-pronged approach-evaluating human type 2 diabetes (T2D), high-fat diet (HFD)-fed mice, and in vitro cultured myotubes-to address this. Blood samples were collected from both T2D patients and control subjects; skeletal muscle and blood samples were collected from HFD-fed mice with or without VK supplementation (1, 3, and 5 µg/kg BW, 8 weeks); and the molecular mechanism of cGas6 was dissected using GGCX, Gas6, AXL, or IR siRNA-transfected cultured myotubes. Plasma cGas6 and VK were significantly lower in T2D patients compared with control; and cGas6 and the cGas6/Gas6 ratio were positively correlated with VK and inversely correlated with fasting glucose in T2D patients, suggesting an important role for plasma VK and cGas6 in maintaining glucose homeostasis in T2D. Animal studies revealed that VK supplementation dose-dependently upregulated plasma cGas6; stimulated the protein expression of cGas6, PI3K, pAKT, and GLUT4 in skeletal muscle; and reduced hyperglycemia in HFD-fed T2D mice. And in vitro mRNA knockdown studies demonstrated the requirement of cGas6 in mediating the positive effect of VK on glucose metabolism via stimulating the PI3K/pAKT/GLUT4 signaling pathway in high glucose-treated myotubes. These results demonstrate a significant involvement of cGas6 in mediating the beneficial effect of VK on regulating glucose homeostasis in T2D.

Topics: Adult; Animals; Biomarkers; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Intercellular Signaling Peptides and Proteins; Male; Mice; Middle Aged; Vitamin K

Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP.. 198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ≥6. Plasma levels of dp-ucMGP were measured by ELISA.. In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p<0.0001) with dp-ucMGP levels (β = -0.26, p = 0.045) after integrating effects of height (β = -0.38, p = 0.01), insulin treatment (β = 0.42, p = 0.002), retinopathy treated by laser (β = 0.26, p = 0.02), and total cholesterol levels (β = 0.3, p = 0.03) by multivariable analysis.. The association between diabetic neuropathy and the inactive form of MGP suggests the existence of new pathophysiological pathways to explore. Further studies are needed to determine if dp-ucMGP may be used as a biomarker of sensitive neuropathy. Since dp-ucMGP is a marker of poor vitamin K status, clinical studies are warranted to explore the potential protective effect of high vitamin K intake on diabetic peripheral neuropathy.

Topics: Aged; Biomarkers; Calcium-Binding Proteins; Cohort Studies; Diabetes Mellitus, Type 2; Extracellular Matrix Proteins; Female; Humans; Male; Matrix Gla Protein; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Vitamin K

Objective Recent research has investigated the possible inverse relationship between vitamin K intake and body fat. In addition, an increasing number of studies are supporting a key role for this vitamin in improving lipid profile and insulin sensitivity and reducing the risk of type 2 diabetes mellitus, but little is known about what mechanisms would be involved. Thus, the objective of this study was to investigate the relationship between vitamin K intake (in the form of phylloquinone - PK), body fat, lipid profile and markers of glucose homeostasis in adults and the elderly. Subjects and methods A cross-sectional study with 298 participants (46% men) in the São Paulo Health Survey 2014-2015. Spearman correlations were performed to evaluate the associations between vitamin K intake and the biochemical and body composition measures. Results Among normal-weight male adults (n = 15), PK intake presented a positive correlation with the quantitative insulin sensitivity check index (QUICKI) (r = 0.525; p = 0.045). Among men with high fat mass index (FMI) (n = 101), PK intake had a negative correlation with homeostasis model assessment estimate for β-cell function (HOMA-β) (r = -0.227; p = 0.022). In women with high FMI (n = 122), PK intake had a negative correlation with HOMA-β (r = -0.199, p = 0.032) and insulin (r = -0.207, p = 0.026). No correlations were found between PK intake and lipid profile. Conclusions Our findings support a potential relationship among PK intake, body fat and markers of glucose homeostasis in adults and the elderly.

Topics: Adipose Tissue; Adult; Aged; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose; Homeostasis; Humans; Insulin; Insulin Resistance; Lipids; Male; Vitamin K

The impact of vitamin K in ameliorating diabetes-associated complications, especially those linked with platelet activation and coagulation remains unclear. The current study aims to systematically explore and discuss the available evidence on the impact of vitamin K on the diabetes-cardiovascular disease (CVD)-associated complications.. A systematic review of studies published on the MEDLINE (PubMed), EMBASE, and Google Scholar electronic database will be conducted. The review will include studies published from inception until May 25, 2020, reporting on the effect of vitamin K on CVD-related markers, especially coagulation factors and platelet activation in type 2 diabetes mellitus. Before the full-text screening, all studies will be screened by title, abstract, and keywords. The Downs and Black checklist will be used to assess the quality of the studies. Additionally, the Cochrane collaboration tool will also be used to evaluate the risk of bias across the included studies. Kappa Cohen's calculator will be used to assess the level of agreement between the authors.. This systematic review will not require ethical approval, and the results will be distributed through conference and peer-reviewed publications. Our results will assist current and future research scientists on the potential use of vitamin K as a protective therapy against CVD-related complications.. This protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42020151667.

Topics: Blood Coagulation Disorders; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Meta-Analysis as Topic; Systematic Reviews as Topic; Vitamin K

We compared the risk of bleeding and cardiovascular disease (CVD) events between non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin in people with type 2 diabetes (T2DM).. 862 Incident NOAC users and 626 incident warfarin users with T2DM were identified from within 40 UK general practice (1/4/2017-30/9/2018). Outcomes included incident hospitalisation for bleeding, CVD and re-hospitalisation for CVD within 12 months since first anticoagulant prescription, identified from linked hospitalisation data. A tapered matching method was applied to form comparison cohorts: coarsened exact matching restricted the comparison to areas of sufficient overlap in missingness and characteristics: (i) demographic characteristics; (ii) clinical measurements; (iii) prior bleeding and CVD history; (iv) prescriptions with bleeding; (v) anti-hypertensive treatment(s); (vi) anti-diabetes treatment(s). Entropy balancing sequentially balanced NOAC and warfarin users on their distribution of (i-vi). Weighted logistic regression modelling estimated outcome odds ratios (ORs), using entropy balancing weights from steps i-vi.. The 12-month ORs of bleeding with NOAC (n = 582) vs matched/balanced warfarin (n = 486) were 1.93 (95% confidence interval 0.97-3.84), 2.14 (1.03-4.44), 2.31 (1.10-4.85), 2.42 (1.14-5.14), 2.41 (1.12-5.18), and 2.51 (1.17-5.38) through steps i-vi. ORs for CVD re-hospitalisation was increased with NOAC treatment through steps i-vi: 2.21 (1.04-4.68), 2.13 (1.01-4.52), 2.47 (1.08-5.62), 2.46 (1.02-5.94), 2.51 (1.01-6.20), and 2.66 (1.02-6.94).. Incident NOAC use among T2DM is associated with increased risk of bleeding hospitalisation and CVD re-hospitalisation compared with incident warfarin use. For T2DM, caution is required in prescribing NOACs as first anticoagulant treatment. Further large-scale replication studies in external datasets are warranted.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Comorbidity; Cytarabine; Diabetes Mellitus, Type 2; England; Female; Hemorrhage; Humans; Incidence; Male; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vitamin K; Warfarin

Peripheral artery disease is a common complication among dialyzed patients. Since Vitamin K antagonists promote metastatic calcifications and these are the main determinants of vascular damage, we investigated their role in the development of lower limb ulcers in dialyzed patients. We retrospectively enrolled 316 dialyzed patients, aged 68 ± 15 years, 65% male, 32% diabetic, 43% with ischemic heart disease and followed them for 36 ± 25 months. 60 patients assumed Vitamin K antagonists: they were older, with a higher prevalence of heart disease, at greater risk of death and they developed more ulcers and underwent more lower limb amputations compared to the rest of our cohort. Peripheral artery disease, Vitamin K antagonists and diabetes were independent risk factors for foot lesions. In addition, Vitamin K antagonists were also an independent risk factor for death. Vitamin K antagonists are a potent independent risk factor for the development of the uremic foot syndrome and death.

Topics: Aged; Amputation, Surgical; Anticoagulants; Comorbidity; Diabetes Mellitus, Type 2; Female; Foot Ulcer; Humans; Lower Extremity; Male; Peripheral Arterial Disease; Renal Dialysis; Retrospective Studies; Risk Factors; Uremia; Vitamin K

Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis.. We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis.. We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up.. Treatment with VKA predisposes to the development of calciphylaxis.

Topics: Adult; Aged; Amputation Stumps; Anticoagulants; Arterioles; Calciphylaxis; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Renal Replacement Therapy; Retrospective Studies; Venous Thrombosis; Vitamin K

Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist.. A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment.. The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis.

Topics: Acenocoumarol; Anticoagulants; Diabetes Mellitus, Type 2; Drug Substitution; Female; Heparin, Low-Molecular-Weight; Humans; Hyperalgesia; Leg Ulcer; Middle Aged; Necrosis; Vasculitis; Vitamin K

To investigate the relationship of circulating matrix Gla protein (MGP) species with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic patients.. EPIC-NL is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993-1997), 518 participants were known to have type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The incidence of fatal and nonfatal CVD and CVD subtypes-CHD, peripheral arterial disease (PAD), heart failure, and stroke-were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, physical activity, and history of CVD.. During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95% CI 1.06-1.38), PAD (HRSD 1.32 [95% CI 1.07-1.65]), and heart failure (HRSD 1.75 [95% CI 1.42-2.17]) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 [95% CI 0.94-1.34]) or stroke (HRSD 1.05 [95% CI 0.73-1.49]). Circulating desphospho-carboxylated MGP and circulating total-uncarboxylated MGP levels were not associated with CVD or CVD subtypes.. High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk.

Topics: Calcium-Binding Proteins; Cardiovascular Diseases; Coronary Disease; Diabetes Mellitus, Type 2; Extracellular Matrix Proteins; Female; Humans; Incidence; Male; Matrix Gla Protein; Middle Aged; Netherlands; Proportional Hazards Models; Prospective Studies; Risk; Vitamin K; Waist-Hip Ratio

To report a case in which the anticoagulation effect of warfarin appeared to have been potentiated by chitosan, probably due to interference with the absorption of vitamin K.. An 83-year-old male with hypertensive cardiovascular disease, type 2 diabetes mellitus, and chronic atrial fibrillation complicated by left atrial thrombus formation was maintained on warfarin 2.5 mg/day. Marked elevation of the international normalized ratio (INR) was noticed after self-medication with chitosan 1200 mg twice daily. He denied taking any other drugs, natural substances, herbal medicines, and nutritional supplements, and stated that he had not changed his dietary habits. After parenteral administration of vitamin K and discontinuation of chitosan, the INR returned to within the target range. However, the patient took chitosan again, and the INR increased to well above the target range. Following strong medical advice, the patient stopped taking chitosan, and the INR remained stable thereafter.. Chitosan is a positively charged polymer that binds to the negatively charged lipids and bile acids in the gastrointestinal tract. It can affect the absorption of vitamins A, D, E, and K. Therefore, the anticoagulation effect of warfarin may be potentiated by chitosan through this mechanism. Use of the Naranjo probability scale revealed that the adverse effect was probably due to chitosan.. The interaction between warfarin and chitosan has not previously been reported. Healthcare professionals should be aware of this potential interaction.

Topics: Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Chitosan; Chronic Disease; Diabetes Mellitus, Type 2; Drug Synergism; Humans; Hypertension; International Normalized Ratio; Male; Self Medication; Thrombosis; Vitamin K; Vitamins; Warfarin

We conducted a cross-sectional examination of the role of serum vitamin K levels as they relate to bone metabolism in elderly women with type II diabetes mellitus (DM). Eighty-five elderly women with type II DM were enrolled. Three fractions of vitamin K, phylloquinone (PK), menaquinone 4 (menatetrenone; MK 4), and menaquinone 7 (MK 7), along with undercarboxylated osteocalcin (UcOC), intact osteocalcin (IOC), urinary deoxypyridinoline (udpd), urinary type I collagen N-telopeptide (NTx), and intact parathyroid hormone (IPTH) were measured. Bone mineral density was measured in the lumbar spine (LSBMD) by dual-energy X-ray absorptiometry (DXA), and T scores or Z scores were calculated. The patients were divided into two groups by T score, under -2.5 (osteoporotic group) and over -2.5 (non-osteoporotic group). UcOC levels in osteoporotics patients were significantly higher than those in the non-osteoporotic group (3.09 +/- 3.94 vs 1.82 +/- 1.76 ng/ml, P = 0.02). The correlation between Z score and logarithmic UcOC/IOC levels in type II DM showed a negative trend ( P = 0.07) and a significantly and negatively association with logarithmic NTx ( r = -0.38; P = 0.001). In osteoporotic DM, the UcOC/IOC ratio was significantly correlated with the Z score ( r = -0.61; P << 0.05). Furthermore, logarithmic UcOC/IOC showed a negative correlation with logarithmic MK 7 ( r = -0.50; P = 0.001). In conclusion, the reduction in LSBMD in elderly women with type II DM may be associated, in part, with a defect in Gamma-glutamylcarboxylation by vitamin K.

Topics: Aged; Biomarkers; Bone Density; Diabetes Mellitus, Type 2; Female; Humans; Osteocalcin; Vitamin K; Vitamin K 2