vitamin-k-semiquinone-radical and Diabetes-Mellitus

Topics: Blood Glucose; Diabetes Mellitus; Humans; Hypoglycemic Agents; Plant Extracts; Plants, Medicinal; Vitamin A; Vitamin K; Vitamins

Diabetes is a serious chronic metabolic disease that causes complications over time, bringing serious public health challenges that affect different countries across the world. The current clinical drugs for diabetes may lead to adverse effects such as hypoglycemia and liver and abdominal distension and pain, which prompt people to explore new treatments for diabetes without side effects. The research objective of this review article is to systematically review studies on vitamins and diabetes and to explain their possible mechanism of action, as well as to assess the role of vitamins as drugs for the prevention and treatment of diabetes. To achieve our objective, we searched scientific databases in PubMed Central, Medline databases and Web of Science for articles, using "vitamin" and "diabetes" as key words. The results of numerous scientific investigations revealed that vitamin levels were decreased in humans and animals with diabetes, and vitamins show promise for the prevention and/or control of diabetes through anti-inflammation, antioxidation and the regulation of lipid metabolism. However, a few studies showed that vitamins had no positive effect on the development of diabetes. Currently, studies on vitamins in the treatment of diabetes are still very limited, and there are no clinical data to clarify the dose-effect relationship between vitamins and diabetes; therefore, vitamins are not recommended as routine drugs for the treatment of diabetes. However, we still emphasize the great potential of vitamins in the prevention and treatment of diabetes, and higher quality studies are needed in the future to reveal the role of vitamins in the development of diabetes.

Topics: Diabetes Mellitus; Dietary Supplements; Humans; Vitamin A; Vitamin K; Vitamins

The prevalence of atrial fibrillation (AF) is increasing as the population ages. AF treatment-related complications also increase markedly in older adults (defined as ≥75 years of age for this review). The older AF population has a high risk of stroke, bleeding, and death. Syncope and fall-related injuries are the most common reasons for nonprescription of oral anticoagulation (OAC), and are more common in older adults when OACs are used with antiarrhythmic drugs. Digoxin may be useful for rate control, but associations with increased mortality limit its use. Beyond rate and rhythm control considerations, stroke prophylaxis is critical to AF management, and the benefits of direct OACs, compared with warfarin, extend to older adults. Invasive procedures such as AF catheter ablation, pacemaker implantation/atrioventricular junction ablation, and left atrial appendage occlusion may be useful in appropriately selected cases. However, older adults have generally been under-represented in clinical trials.

Topics: Accidental Falls; Aged; Alcohol Drinking; Anti-Arrhythmia Agents; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Catheter Ablation; Cognitive Dysfunction; Coronary Artery Disease; Cost-Benefit Analysis; Decision Making, Shared; Dementia; Diabetes Mellitus; Dual Anti-Platelet Therapy; Exercise; Frailty; Heart Failure; Humans; Hypertension; Overweight; Polypharmacy; Primary Prevention; Risk Assessment; Secondary Prevention; Sleep Apnea, Obstructive; Stroke; Vitamin K; Weight Loss

Current guidelines recommend vitamin K antagonists (VKAs) for left ventricular thrombus (LVT) resolution. Direct oral anticoagulants (DOACs) are increasingly evaluated as alternatives to the standard of care in anticoagulation.. We performed a systematic review and meta-analysis to assess the use of DOACs vs VKAs for LVT treatment. The occurrence of LVT resolution, systemic embolism (SE) or stroke, and bleeding events were compared during follow-up using random-effects analysis.. The 5 included studies were all observational (a total of 828 patients). Of these, 284 patients (34%) were treated with DOACs, and 544 (66%) treated with VKAs. Thrombus resolution was similar for both methods (pooled odds ratio [OR], 0.91; 95% CI, 0.47-1.75;. Our systematic review and meta-analysis suggests DOACs were as effective as VKAs for LVT resolution, with a similar risk of systemic embolism/stroke and clinically relevant bleeding. These results, obtained from observational studies, are not definitive and hence randomized controlled trials are needed. Nevertheless, our analysis identifies key experimental features required in future studies.

Topics: Administration, Oral; Age Factors; Anticoagulants; Diabetes Mellitus; Embolism; Factor Xa Inhibitors; Hemorrhage; Humans; Hypertension; Platelet Aggregation Inhibitors; Sex Factors; Stroke; Thrombosis; Vitamin K

Pathological calcification is a major cause of cardiovascular morbidities primarily in population with chronic kidney disease (CKD), end stage renal diseases (ERSD) and metabolic disorders. Investigators have accepted the fact that vascular calcification is not a passive process but a highly complex, cell mediated, active process in patients with cardiovascular disease (CVD) resulting from, metabolic insults of bone fragility, diabetes, hypertension, dyslipidemia and atherosclerosis. Over the years, studies have revealed various mechanisms of vascular calcification like induction of bone formation, apoptosis, alteration in Ca-P balance and loss of inhibition. Novel clinical studies targeting cellular mechanisms of calcification provide promising and potential avenues for drug development. The interventions include phosphate binders, sodium thiosulphate, vitamin K, calcimimetics, vitamin D, bisphosphonates, Myoinositol hexaphosphate (IP6), Denosumab and TNAP inhibitors. Concurrently investigators are also working towards reversing or curing pathological calcification. This review focuses on the relationship of vascular calcification to clinical diseases, regulators and factors causing calcification including genetics which have been identified. At present, there is lack of any significant preventive measures for calcifications and hence this review explores further possibilities for drug development and treatment modalities.

Topics: Atherosclerosis; Calcimimetic Agents; Calcium; Denosumab; Diabetes Mellitus; Diphosphonates; Dyslipidemias; Enzyme Inhibitors; Homeostasis; Hypertension; Inositol Phosphates; Phosphorus; Renal Insufficiency, Chronic; Thiosulfates; Vascular Calcification; Vitamin D; Vitamin K

In this analysis, we aimed to compare the efficacy and safety of dual therapy (DT) with a non-vitamin K oral anticoagulant (NOAC) and an adenosine diphosphate receptor antagonist (P2Y12 inhibitor) vs triple therapy (TT) with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus (DM) patients with co-existing atrial fibrillation (AF) following percutaneous coronary intervention (PCI).. Medical Literature Analysis and Retrieval System Online (MEDLINE), http://www.ClinicalTrials.gov, Excerpta Medical data BASE (EMBASE), Web of Science, Cochrane Central and Google Scholar were the searched databases. Studies that were randomized trials or observational studies comparing DT vs TT for the treatment of DM patients with co-existing AF following PCI were included in this analysis. The adverse cardiovascular outcomes and bleeding events were the endpoints. This meta-analysis was carried out by the RevMan version 5.4 software. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent data and interpret the analysis.. A total number of 4970 participants were included whereby 2456 participants were assigned to the DT group and 2514 participants were assigned to the TT group. The enrollment period varied from year 2006 to year 2018. Our current results showed that major adverse cardiac events (RR: 1.00, 95% CI: 0.84-1.20; P = .98), mortality (RR: 1.08, 95% CI: 0.78-1.48; P = .66), myocardial infarction (RR: 1.02, 95% CI: 0.74-1.42; P = .90), stroke (RR: 0.94, 95% CI: 0.53-1.67; P = .84) and stent thrombosis (RR: 1.09, 95% CI: 0.56-2.10; P = .80) were similar with DT versus TT in these patients. However, the risks for total major bleeding (RR: 0.66, 95% CI: 0.54-0.82; P = .0001), total minor bleeding (RR: 0.74, 95% CI: 0.64-0.85; P = .0001), Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding (RR: 0.58, 95% CI: 0.35-0.95; P = .03), TIMI defined minor bleeding (RR: 0.62, 95% CI: 0.42-0.92; P = .02), intra-cranial bleeding (RR: 0.34, 95% CI: 0.13-0.95; P = .04) and major bleeding defined by the International Society on Thrombosis and Hemostasis (RR: 0.68, 95% CI: 0.51-0.90; P = .008) were significantly higher with TT.. DT with a NOAC and a P2Y12 inhibitor was associated with significantly less bleeding events without increasing the adverse cardiovascular outcomes when compared to TT with aspirin, a P2Y12 inhibitor and a Vitamin K antagonist for the treatment of DM patients with co-existing AF following PCI. Hence, DT is comparable in efficacy, but safer compared to TT. This interesting hypothesis will have to be confirmed in future studies.

Topics: 4-Hydroxycoumarins; Aged; Aspirin; Atrial Fibrillation; Diabetes Mellitus; Diabetic Cardiomyopathies; Drug Therapy, Combination; Female; Hematologic Agents; Humans; Indenes; Male; Observational Studies as Topic; Percutaneous Coronary Intervention; Postoperative Complications; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin K

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events. These AF patients may be denied oral anticoagulants, whilst evidence shows that the absolute benefits of oral anticoagulants are greatest in patients at highest risk. NOACs are an alternative to VKAs to prevent stroke in patients with "non-valvular AF", and NOACs may offer a greater net clinical benefit compared with VKAs, particularly in these high-risk patients. Physicians have to learn how to use these drugs optimally in specific settings. We review concrete clinical scenarios for which practical answers are currently proposed for use of NOACs based on available evidence for patients with kidney disease, elderly patients, women, patients with diabetes, patients with low or high body weight, and those with valve disease.

Topics: Administration, Oral; Aging; Anticoagulants; Antithrombins; Atrial Fibrillation; Body Weight; Diabetes Mellitus; Factor Xa Inhibitors; Heart Valve Diseases; Hemorrhage; Humans; Kidney Diseases; Risk Factors; Stroke; Vitamin K

In patients with atrial fibrillation (AF), the safety and efficacy of nonvitamin K antagonist oral anticoagulants (NOACs) vs warfarin according to diabetes mellitus (DM) status are not completely characterized. We performed a meta-analysis to clarify whether in these patients the strategy of oral anticoagulation should be tailored to diabetes status. In this study-level meta-analysis, we included 4 randomized phase III trials comparing NOACs and warfarin in patients with nonvalvular AF; a total of 18 134 patients with DM and 40 454 without DM were overall considered. Incidence of the following outcome measures was evaluated during the follow-up: stroke or systemic embolism, ischemic stroke, major bleeding, intracranial bleeding, and vascular death. Use of NOACs compared with warfarin reduced stroke/systemic embolism in diabetic (Risk Ratios [RR] 0.80, 95% CI 0.68-0.93; P = .004) and nondiabetic patients (RR 0.83, 0.73-0.93; P = .001) (P for interaction .72). No interaction between diabetes status and benefits of NOACs was found for the occurrence of ischemic stroke, major bleeding, or intracranial bleeding (P for interaction >.05 for each comparison). Reduction of vascular death rates with NOACs was significant in diabetic patients (4.97% vs 5.99% with warfarin; RR 0.83, 0.72-0.96; P = .01), in whom absolute the reduction of this outcome measure was higher than in nondiabetics (1.02% vs 0.27%), although no interaction was present (P = .23). Results of this meta-analysis support the safety and efficacy of NOACs compared with warfarin in diabetic patients with nonvalvular AF.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Diabetes Complications; Diabetes Mellitus; Humans; Prognosis; Randomized Controlled Trials as Topic; Safety; Stroke; Vitamin K; Warfarin

The human gastrointestinal tract harbors trillions of bacteria, most of which are commensal and have adapted over time to the milieu of the human colon. Their many metabolic interactions with each other, and with the human host, influence human nutrition and metabolism in diverse ways. Our understanding of these influences has come through breakthroughs in the molecular profiling of the phylogeny and the metabolic capacities of the microbiota. The gut microbiota produce a variety of nutrients including short-chain fatty acids, B vitamins, and vitamin K. Because of their ability to interact with receptors on epithelial cells and subepithelial cells, the microbiota also release a number of cellular factors that influence human metabolism. Thus, they have potential roles in the pathogenesis of metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and cognition, which extend well beyond their traditional contribution to nutrition. This review explores the roles of the gut microbiota in human nutrition and metabolism, and the putative mechanisms underlying these effects.

Topics: Animals; Bacterial Physiological Phenomena; Carbohydrate Metabolism; Cognition Disorders; Diabetes Mellitus; Energy Metabolism; Epithelial Cells; Fatty Acids, Volatile; Fatty Liver; Fermentation; Food; Gastrointestinal Tract; Humans; Intestinal Absorption; Lipid Metabolism; Metabolic Syndrome; Mice; Minerals; Non-alcoholic Fatty Liver Disease; Nutritional Physiological Phenomena; Obesity; Proteins; Vitamin B Complex; Vitamin K

Arial fibrillation (AF) is the most commonly occurring sustained arrhythmia in the United States and is associated with increased mortality. AF is a risk factor for ischemic stroke, and risk factors for AF include comorbid conditions such as congestive heart failure, diabetes mellitus, older age, hypertension, diabetes, pulmonary disease, and history of stroke, transient ischemic attack, or heart failure. Risk stratification for ischemic stroke in AF patients is based on scoring a group of risk factors that allows for the appropriate tailoring of antithrombotic therapy. The vitamin K antagonists are effective at reducing ischemic stroke rates in medium-risk to high-risk patients and are therefore generally recommended for this group. However, a large proportion of these patients are not treated with vitamin K antagonists because of the potential for adverse outcomes, particularly in elderly patients. New direct thrombin inhibitors and direct Factor Xa inhibitors in development offer the possibility of simplifying treatment and management although offering similar or better efficacy and safety profiles to warfarin. In light of these potential new treatments, the importance and improvement of risk stratification methods and the resulting recommendations in thromboprophylaxis become even more paramount as they make it more likely that medium-risk to high-risk patients can be treated safely.

Topics: Anticoagulants; Antithrombins; Atrial Fibrillation; Chemoprevention; Comorbidity; Diabetes Mellitus; Factor Xa Inhibitors; Fibrinolytic Agents; Heart Failure; Humans; Risk Factors; Stroke; Vitamin K

Recent studies have indicated that osteocalcin, a peptide secreted by osteoblasts, functions as an anti-diabetogenic hormone in mice. Osteocalcin knock out mice exhibit obesity, hyperglycemia, and decreased insulin secretion relative to wild-type mice. Treatment with non-carboxylated osteocalcin upregulates energy expenditure, and ameliorates obesity and diabetes in mouse models of obesity-related diabetes. Of interest, the beneficial effects of osteocalcin were shown to be specific to non-carboxylated osteocalcin. This appears, however, inconsistent with recent clinical studies showing insulin-sensitizing effects of vitamin K, which promotes gamma-carboxylation of osteocalcin. These findings shed new light on the crosstalk between bone and energy expenditure, and lead to new questions. These questions include: (1) Does non-carboxylated osteocalcin exert the beneficial effects in humans?; (2) Does warfarin, a vitamin K antagonist, improve insulin, sensitivity and lower blood glucose levels?; (3) and Do estrogen and bisphosphonate, which reduce circulating osteocalcin, contribute to insulin resistance and obesity? These issues await further investigations.

Topics: Animals; Bone Density Conservation Agents; Diabetes Mellitus; Diphosphonates; Estrogens; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Mice; Obesity; Osteoblasts; Osteocalcin; Vitamin K; Warfarin

Topics: Amino Acids, Branched-Chain; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Agents; Carcinoma, Hepatocellular; Diabetes Mellitus; Humans; Immunotherapy, Adoptive; Interferons; Lamivudine; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Tretinoin; Vitamin K

To elucidate predisposing factors for enlargement of intracerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Cerebral Hemorrhage; Comorbidity; Diabetes Mellitus; Disease Progression; Female; Humans; Hypercholesterolemia; Hypertension; International Normalized Ratio; Liver Diseases; Male; Middle Aged; Platelet Aggregation Inhibitors; Postoperative Complications; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Vitamin K; Warfarin

Medical progress owes a great deal to the fundamental medical sciences and to the application of chemistry, physics and mathematics to medical problems. However, clinical observations and investigations are still of decisive importance in any field of medicine. By a feed-back mechanism they may even stimulate and fertilize fundamental medical sciences. Thus, our knowledge of the blood coagulation mechanism has been considerably enlarged by clinical analysis of hereditary bleeding disorders. - Chemotherapy of neoplastic diseases started from clinical observations during World War I (production of leucopenia by sulfur mustard gas). - Surgical procedures and their consequences have contributed greatly to our knowledge of thyroid function, of the segmental anatomy of the lung, and of the conduction system of the heart. - Observations of side effects of drugs have often enlarged or completely changed their primary clinical indications: from antibacterial sulfonamides, anti-diabetic, antihypertensive and powerful diuretic drugs have been developed, and from histaminics the modern neuroleptics and antidepressants. - Fundamental immunology has been enormously activated by clinical transplantation of kidney and bone marrow. Selective immunological defects in men, real experiments of nature, contributed much to our knowledge of the various types of allergic response. The quality of clinical investigations, particularly of controlled clinical trials, has been considerably improved during the last two decades. Although it is an applied science the reliability of its results is to-day comparable with that of "pure" natural sciences. However, medicine is more than a natural science: examples of outstanding scientists who at the same time were great and human physicians are presented.

Topics: Adrenal Cortex Hormones; Agammaglobulinemia; Arthritis; Cardiac Catheterization; Clinical Trials as Topic; Diabetes Mellitus; Dicumarol; Electroencephalography; Heart Conduction System; Humans; Research Design; Sulfonamides; Thrombosis; Thymus Gland; Thyroid Gland; Vitamin K

Diabetic foot ulcers usually are hard to heal, and amputation is sometimes necessary. Wound bed preparation helps promote the normal healing process, and debridement is fundamental to improving the wound microenvironment. Hydrogel enriched with sodium alginate and vitamins A and E is a new treatment that can aid in debridement and WBP.. This study evaluates the efficacy of the autolytic debridement promoted by hydrogel in the healing of DFU.. This was a single-blind randomized controlled trial with a 12-week follow-up period. Twenty-six patients were randomized into either the control group (cleaning and a simple dressing) or the experimental group (hydrogel treatment). Nineteen patients completed the trial. The wound area, healing, and wound severity classification based on PUSH were evaluated, and microscopic evaluation of the presence of inflammatory infiltrate and collagen production was performed.. The average patient age, duration of the open wound, and presence of diabetes were similar between the groups. The initial wound area was larger in the experimental group than in the control group, however. No statistically significant differences were found in any of the outcomes (lesion area and PUSH subscores) between the groups. Histological analysis demonstrated a reduction in the inflammatory infiltrate in the experimental group; however, there was no increase in collagen production.. The use of enriched hydrogel was found to be of no benefit compared with conventional dressings in the management of DFU.

Topics: Alginates; Bandages, Hydrocolloid; Collagen; Diabetes Mellitus; Diabetic Foot; Humans; Hydrogels; Single-Blind Method; Vitamin A; Vitamin K; Vitamins

Recent studies have found low-normal potassium (K) to be associated with increased diabetes risk. We sought to verify these associations in a multi-ethnic US cohort; and to determine if these associations extend to US Hispanics and Asian-Americans.. We analyzed data from Multi-Ethnic Study of Atherosclerosis (MESA) participants who were free-of-diabetes at baseline. We examined cross-sectional associations between measures of K-serum, dietary, and urine-with fasting glucose and HOMA-IR. We examined longitudinal associations between K and diabetes risk over 8 years.. In multivariable models, compared to those with higher serum K (≥4.5mmol/L), those with lower serum K (<4.0mmol/L) had significantly higher fasting glucose [1.3 mg/dL (95%CI 0.2, 2.4), P-value = 0.03]. Incident diabetes developed in 1281 of 5415 at-risk participants. In minimally-adjusted models, we found inverse associations between serum and dietary K and diabetes risk. Compared to those with higher serum K, those with lower serum K had an HR (95% CI) of incident diabetes of 1.23 (1.04, 1.47), P-value = 0.02. However, these associations were attenuated in fully-adjusted models. We found no significant interaction between potassium and ethnicity.. In this multi-ethnic cohort, we found a significant inverse association between serum K and fasting glucose but no significant association with longer-term diabetes risk. This inverse association between potassium and glucose must be studied further to understand the physiology and its potential impact on chronic health.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Potassium; Risk Factors; United States; Vitamin K

The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial.. We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding.. The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients.. The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF.

Topics: Administration, Oral; Aged; Atrial Fibrillation; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Embolism; Factor Xa Inhibitors; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Stroke; Treatment Outcome; Vitamin K

Medical progress owes a great deal to the fundamental medical sciences and to the application of chemistry, physics and mathematics to medical problems. However, clinical observations and investigations are still of decisive importance in any field of medicine. By a feed-back mechanism they may even stimulate and fertilize fundamental medical sciences. Thus, our knowledge of the blood coagulation mechanism has been considerably enlarged by clinical analysis of hereditary bleeding disorders. - Chemotherapy of neoplastic diseases started from clinical observations during World War I (production of leucopenia by sulfur mustard gas). - Surgical procedures and their consequences have contributed greatly to our knowledge of thyroid function, of the segmental anatomy of the lung, and of the conduction system of the heart. - Observations of side effects of drugs have often enlarged or completely changed their primary clinical indications: from antibacterial sulfonamides, anti-diabetic, antihypertensive and powerful diuretic drugs have been developed, and from histaminics the modern neuroleptics and antidepressants. - Fundamental immunology has been enormously activated by clinical transplantation of kidney and bone marrow. Selective immunological defects in men, real experiments of nature, contributed much to our knowledge of the various types of allergic response. The quality of clinical investigations, particularly of controlled clinical trials, has been considerably improved during the last two decades. Although it is an applied science the reliability of its results is to-day comparable with that of "pure" natural sciences. However, medicine is more than a natural science: examples of outstanding scientists who at the same time were great and human physicians are presented.

Topics: Adrenal Cortex Hormones; Agammaglobulinemia; Arthritis; Cardiac Catheterization; Clinical Trials as Topic; Diabetes Mellitus; Dicumarol; Electroencephalography; Heart Conduction System; Humans; Research Design; Sulfonamides; Thrombosis; Thymus Gland; Thyroid Gland; Vitamin K

Topics: Clinical Trials as Topic; Diabetes Mellitus; Diabetic Retinopathy; Humans; Inositol; Rutin; Vitamin K

Topics: Diabetes Complications; Diabetes Mellitus; Humans; Vitamin K

It remains unknown whether higher dietary intake of antioxidant vitamins could reduce the harmful effects of air pollution on incident diabetes mellitus.. A total of 156,490 participants free of diabetes mellitus in the UK Biobank data were included in this analysis. Antioxidant vitamin intake was measured using a 24-h food intake questionnaire, and results were categorized as sufficient or insufficient according to the British Recommended Nutrient Intake. Exposure to fine particles (PM. A total of 4271 incident diabetes mellitus cases were identified during a median follow-up of 11.7 years. Compared with participants with insufficient intake of antioxidant vitamins, those with sufficient consumption had a weaker association between air pollution (PM. Our study suggests that ambient air pollution is one important risk factor of diabetes mellitus, and sufficient intake of antioxidant vitamins may reduce such adverse effects of air pollution on diabetes mellitus.

Topics: Air Pollutants; Air Pollution; Antioxidants; Cohort Studies; Diabetes Mellitus; Eating; Environmental Exposure; Humans; Nitrogen Dioxide; Particulate Matter; Vitamin A; Vitamin K; Vitamins

Topics: Arteries; Bone Density; Calcification, Physiologic; Diabetes Mellitus; Humans; Vitamin K

Topics: Arteries; Bone Density; Calcification, Physiologic; Diabetes Mellitus; Humans; Vitamin K

The efficacy and safety of oral anticoagulation (OAC) using the vitamin K antagonists (VKA) are closely associated with the quality of anticoagulation, reflected by time in therapeutic range (TTR). The SAMe-TT2R2 is a risk score developed to predict the quality of anticoagulation control among VKA users. To analyse the quality of anticoagulation and its clinical determinants based on different methods in a prospective cohort of atrial fibrillation patients on VKA treatment participating in the multicentre Spanish observational registry FANTASIIA.. Estimated TTR was calculated from Rosendaal, direct method, international normalized ratio variability, and NICE criteria. Time in therapeutic range values were compared for those patients with a SAMe-TT2R2 score 0-2 and >2. One thousand four hundred and seventy patients were analysed (56.4% male, mean age 74.1 ± 9.5 years). Mean TTR was 61.5 ± 25.1 with Rosendaal and 64.7 ± 24.2 with direct method. There was a high correlation between both methods (ρ = 0.805). The prevalence of poor anticoagulation control was 55%. Diabetes mellitus [odds ratio (OR) 1.38; P = 0.008], peripheral artery disease (PAD, OR 1.62; P = 0.048), and HAS-BLED (OR 1.13; P = 0.022) were independently associated with TTR < 70%. SAMe-TT2R2 score 0-2 had a higher mean TTR than patients with SAMe-TT2R2 >2 (P = 0.044), with a specificity of > 90% for predicting TTR < 70%. Patients with TTR < 70% had higher risk of events (21.7 vs. 16.8%; P = 0.021).. In a multicentre prospective registry, 55% of AF patients had poor anticoagulation control with diabetes mellitus, PAD, and HAS-BLED being independently associated with TTR < 70%. A high SAMe-TT2R2 scores had a high specificity for predicting a TTR < 70% as an indicator of poor quality anticoagulation.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Comorbidity; Diabetes Mellitus; Female; Humans; International Normalized Ratio; Male; Odds Ratio; Peripheral Arterial Disease; Prevalence; Prospective Studies; Registries; Risk Factors; Spain; Stroke; Vitamin K

To determine the temporal trend in poorly-controlled anticoagulated patients.. A longitudinal study was conducted on a non-unselected sample of all patients seen in a health centre over a period of 3 years (2011-2013). Patients who received anti-vitamin K anticoagulation for at least 6 months due to non-valvular atrial fibrillation were selected, obtaining a final sample of 130 patients.. The mean age of the sample was 77.0±1.5 years and 53.1% were male. The prevalence of hypertension and diabetes mellitus was 90% and 33.8%, respectively, and 11.5% and 14.6% had had heart failure or a stroke, respectively. The mean number of medications taken by patients was 7.6±0.6. The prevalence of insufficient control of time in therapeutic range, calculated by Rosendaal, was 60.2% in 2011, 54.2% in 2010, and 43.4% in 2012. On analysing the time in the therapeutic range in patients with impaired control in the first quarter of follow-up, it was observed to remain low in subsequent years: 69.7% vs 55%, P=.0005, in 2011; 71.9% vs 59.3%, P=.0015 in 2012; and 74.7% vs 60%, P=.0005 in 2013.. Our study shows that patients with inadequate time in therapeutic range have a tendency to stay in poor control, suggesting the need for early clinical decisions in patients on anticoagulants, taking into account the prognosis and economic costs of atrial fibrillation and treatment.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Longitudinal Studies; Male; Primary Health Care; Retrospective Studies; Stroke; Time Factors; Vitamin K

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

The percentage of time in therapeutic range (TTR) is a measure of anticoagulation quality with vitamin K antagonists (VKAs). The method most commonly used in clinical trials is the Rosendaal TTR. However, the application of this method in daily practice for clinical decision lacks appropriate instruments. We aimed to evaluate the percentage of tests within the target international normalized ratio (INR) (tests ratio) as a surrogate of Rosendaal TTR. We performed an observational and retrospective study to evaluate the TTR according to the Rosendaal method and tests ratio. We included all outpatients who attended the cardiology anticoagulation clinic of a Portuguese hospital (2011-2013), whose target INR was 2.0-3.0. Three hundred and seventy-seven VKA-treated patients followed for a mean 1.3 years were evaluated. Rosendaal methold and tests ratio significantly correlated (Rho Spearman 0.88, P < 0.001), but the Bland-Altman plot evaluation showed a clinically relevant data dispersion [95% confidence interval (95% CI) -12.9 to 23.1] around a mean difference in TTR -5.1% using the tests ratio method. The linear regression Passing-Bablok confirmed the existence of significant data dispersion and systematic differences. The tests ratio less than 60% had a sensitivity of 91.6%, specificity of 72.3%, positive predictive value (PPV) of 72.2% and negative predictive value (NPV) of 91.6%, for the diagnosis of patients inadequately anticoagulated (Rosendaal TTR <60%). Tests ratio had a c-statistics of 0.94 (95% CI 0.91-0.96). Number of tests in 6 months had a c-statistics of 0.70 (95% CI 0.65-0.75). Tests ratio underestimated TTR in 5% and was not considered equivalent to Rosendaal TTR due to the high variability between methods. Nevertheless, the use of tests ratio less than 60% may be a reasonable option to detect inadequate anticoagulation, as it is a sensitive method and excluded most of the patients with adequate control.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Coagulation; Diabetes Mellitus; Female; Heart Failure; Humans; Hypertension; International Normalized Ratio; Linear Models; Male; Outpatients; Predictive Value of Tests; Retrospective Studies; Stroke; Venous Thromboembolism; Vitamin K

To prevent major hemorrhage during anticoagulation, it is quite important to manage controllable risk factors such as hypertension, diabetes mellitus, smoking habit, and too much alcohol intake. It is also important to avoid dual antithrombotic therapy as long as possible, which increases severe bleeding events. For patients with major bleeding during anticoagulation, we should stop oral medication, stop bleeding by mechanical compression or surgical interventions, and maintain circulation blood volume and blood pressure by appropriate intravenous drip infusion. When intracranial hemorrhage happens, adequate treatment to suppress blood pressure should be provided. Administration of prothrombin complex concentrate (PCC) and vitamin K is effective for urgent reversal of anticoagulation by warfarin. The PCC may be also useful for that by novel oral anticoagulants.

Topics: Administration, Oral; Alcohol Drinking; Anticoagulants; Benzimidazoles; beta-Alanine; Cerebral Hemorrhage; Dabigatran; Diabetes Mellitus; Drug Therapy, Combination; Factor IX; Fibrinolytic Agents; Hemorrhage; Humans; Hypertension; Risk Assessment; Risk Factors; Smoking; Vitamin K; Warfarin

Topics: Blood Coagulation Factors; Diabetes Mellitus; Dicumarol; Drug Incompatibility; Drug Synergism; Humans; Hypoglycemia; Tolbutamide; Vitamin K

Topics: Diabetes Mellitus; Humans; Vitamin A; Vitamin K; Vitamins

Topics: Biochemical Phenomena; Diabetes Mellitus; Esters; Humans; Phosphorus; Phosphorylation; Vitamin A; Vitamin K; Vitamins

Topics: Antifibrinolytic Agents; Diabetes Mellitus; Flavonoids; Hemostatics; Humans; Retinitis; Vitamin K; Vitamins

Topics: Diabetes Mellitus; Humans; Vitamin A; Vitamin K; Vitamins