warfarin and Hyperglycemia

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

The aim of this article was to describe (i) the epidemiology and outcomes of stroke relating to diabetes; (ii) the pathophysiology of diabetes as a risk factor for stroke; (iii) the management of acute stroke in patients with diabetes; (iv) the evidence of primary and secondary prevention of stroke in patients with diabetes; and (v) the risk of new-onset diabetes using older antihypertensive agents. The combination of diabetes and stroke disease is a major cause of morbidity and mortality worldwide. Evidence from large clinical trials performed in patients with diabetes supports the need for aggressive and early intervention to target patients' cardiovascular (CV) risks in order to prevent the onset, recurrence and progression of acute stroke. Identification of at-risk patients with diabetes and metabolic syndrome has also allowed the delivery of early and effective intervention to reduce stroke risks, while active treatment during the acute phase of stroke will reduce long-term neurological and functional deficits. While the ongoing debate on the risk benefits of different antihypertensive, lipid-lowering and antiplatelet agents should not detract clinicians from pursuing aggressive CV risk reduction, the application of evidence-based medicine specifically in patients with diabetes will facilitate the use of appropriate agents to improve clinical outcomes. The overall management of patients with diabetes and acute stroke or at risk of secondary stroke should also include multifactorial intervention that not only targets patient's CV risk but also includes behavioural, lifestyle and, where appropriate, surgical intervention.

Topics: Anticoagulants; Carotid Stenosis; Diabetic Angiopathies; Dyslipidemias; Endarterectomy, Carotid; Humans; Hyperglycemia; Hypertension; Platelet Aggregation Inhibitors; Risk Factors; Smoking Cessation; Stroke; Warfarin

Topics: Adipose Tissue; Anticoagulants; Blood Glucose; C-Reactive Protein; Conflict of Interest; Disease Outbreaks; Female; Health Care Reform; Humans; Hyperglycemia; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Mass Screening; MicroRNAs; Overweight; Social Support; Warfarin

Observations by pharmacists monitoring anticoagulated patients suggested that patients with diabetes often require more frequent international normalized ratio (INR) monitoring than patients without diabetes. The purpose of this investigation was to examine the association between glycemic control and therapeutic anticoagulation control.. Patients with diabetes who were receiving warfarin therapy monitored by the Kaiser Permanente of Colorado Clinical Pharmacy Anticoagulation Service were eligible for inclusion. Patients were included if they had a diagnosis of diabetes mellitus type 1 or 2, aged > or =18 years, and had initiated anticoagulant therapy > or =120 days before their most recent hemoglobin A1C measurement. The primary outcome was the correlation between hemoglobin A1C value and percent of time in the patient-specific INR range. Multivariate analysis was undertaken to regress percent of time in INR range on an A1C value > or =8.0 while adjusting for other possible explanatory variables.. A total of 911 patients with diabetes were included in the study. Subjects with an A1C value > or =8.0 had similar characteristics as those subjects with an A1C value < 8.0. Correlation analysis revealed no relationship between percent of time spent in INR range and A1C value (Spearman Correlation Coefficient = 0.012, p = 0.805). Multivariate analysis revealed no relationship between percent of time spent in INR range and A1C value > or =8.0 (Odds Ratio = 1.00; 95% Confidence Interval = 0.99, 1.01) when adjusting for possible explanatory variables.. For patients with diabetes on warfarin anticoagulation therapy, there is no association between glycemic control and therapeutic anticoagulation control. However, anticoagulation therapy providers should manage these patients with the same diligence and care as patients without diabetes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Angiopathies; Drug Interactions; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Warfarin

Warfarin increases mortality of intracerebral hemorrhage (ICH). The authors investigated whether this effect reflects increased baseline ICH volume at presentation or increased ICH expansion.. Subjects were drawn from an ongoing prospective cohort study of ICH outcome. The effect of warfarin on baseline ICH volume was studied in 183 consecutive cases of supratentorial ICH age > or = 18 years admitted to the emergency department over a 5-year period. Baseline ICH volume was determined using computerized volumetric analysis. The effect of warfarin on ICH expansion (increase in volume > or = 33% of baseline) was analyzed in 70 consecutive cases in whom ICH volumes were measured on all subsequent CT scans up to 7 days after admission. Multivariable analysis was used to determine warfarin's influence on baseline ICH, ICH expansion, and whether warfarin's effect on ICH mortality was dependent on baseline volume or subsequent expansion.. There was no effect of warfarin on initial volume. Predictors of larger baseline volume were hyperglycemia (p < 0.0001) and lobar hemorrhage (p < 0.0001). Warfarin patients were at increased risk of death, even when controlling for ICH volume at presentation. Warfarin was the sole predictor of expansion (OR 6.2, 95% CI 1.7 to 22.9) and expansion in warfarin patients was detected later in the hospital course compared with non-warfarin patients (p < 0.001). ICH expansion showed a trend toward increased mortality (OR 3.5, 95% CI 0.7 to 8.9, p = 0.14) and reduced the marginal effect of warfarin on ICH mortality.. Warfarin did not increase ICH volume at presentation but did raise the risk of in-hospital hematoma expansion. This expansion appears to mediate part of warfarin's effect on ICH mortality.

Topics: Adult; Aged; Anticoagulants; Apolipoproteins E; Cerebral Hemorrhage; Cohort Studies; Disease Progression; Female; Genotype; Hematoma; Hospital Mortality; Humans; Hyperglycemia; Hypertension; Life Tables; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Radiography; Risk; Treatment Outcome; Warfarin