Hypoglycemic treatment of diabetic patients in the Emergency Department

Objectives: To analyze if the hypoglycemic therapy prescribed in the Emergency Department adapts to the consensus recommendations available, as well as to assess its clinical impact. Methods: A descriptive observational study, which included patients awaiting hospital admission, who were in the Observation Ward of the Emergency Department and had been previously diagnosed with diabetes mellitus, and were receiving treatment with hypoglycemic drugs at home. The management of antidiabetic treatment and its clinical impact were assessed. Results: 78 patients were included. At admission to the Emergency Department, treatment was modified for 91% of patients, and omitted for 9%. The most prescribed treatment was sliding scale insulin (68%). The treatments prescribed coincided in a 16.7% with the recommendations by the Spanish Society of Emergency Medicine. After intervention by the Pharmacist, the omission descended to 1.3%, and the adaptation to the recommendations increased to 20.5%. Comparing patients whose treatment coincided with the recommendations and those who did not, the clinical impact was respectively: mean glycemia at 24 hours: 138.3 ± 49.5 mg/dL versus 182.7 ± 97.1 mg/dL (p = 0.688); mean rescues with insulin lispro: ± 1.6 versus 1.5 ± 1.8 (p = 0.293); mean units of insulin lispro administered: 4.6 ± 12.7 IU versus 6.6 ± 11.3 IU (p = 0.155). Conclusions: We found antidiabetic prescriptions to have a low adaptation to consensus recommendations. These results are in line with other studies, showing an abuse of sliding scale regimen as single hypoglycemic treatment.

Targeting histone deacetylases for the treatment of disease : Epigenetics Review Series

The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular 'code' recognized and used by non-histone proteins to regulate specific chromatin functions. One modification, which has received significant attention, is that of histone acetylation. The enzymes that regulate this modification are described as lysine acetyltransferases or KATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The pro-inflammatory environment is increasingly being recognized as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential and current development of histone deacetylases for the treatment of diseases for which a pro-inflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the pro-inflammatory environment. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Histone deacetylase inhibitors target diabetes via chromatin remodeling or as chemical chaperones?

Globally, obesity and diabetes (particularly type 2 diabetes) represents a major challenge to world health. Despite decades of intense research efforts, the genetic basis involved in diabetes pathogenesis & conditions associated with obesity are still poorly understood. Recent advances have led to exciting new developments implicating epigenetics as an important mechanism underpinning diabetes and obesity related disease. One epigenetic mechanism known as the "histone code" describes the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as lysine acetyltransferases or KATs and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. Some of the known inhibitors of HDACs (HDACi) have also been shown to act as "chemical chaperones" to alleviate diabetic symptoms. In this review, we discuss the available evidence concerning the roles of HDACs in regulating chaperone function and how this may have implications in the management of diabetes. © 2009 Bentham Science Publishers Ltd.

Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes

Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 P×-9, odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. © 2011 Nature America, Inc. All rights reserved.

Pharmacist review prevents evolving metformin-associated lactic acidosis

What is known There is controversy surrounding the risk of metformin and the development of lactic acidosis. There have been no reports of a pharmacist preventing a patient developing metformin-associated lactic acidosis. Objectives Our objective was to report on a pharmacist potentially preventing an evolving case of metformin-associated lactic acidosis (MALA). Case description A patient who had been having episodes of nausea and vomiting for a year was referred for a home medicines review (HMR) by his general practitioner. The pharmacist who conducted the HMR suspected that the patient's symptoms could have been due to metformin. It was recommended to measure the serum lactate level and suspend metformin. Our patient was found to have a high lactate level and was referred to the emergency department by his general practitioner. Recovery was prompt with symptomatic support and cessation of metformin. What is new This appears to be the first case reported in the literature of a pharmacist recognizing an evolving case of MALA. Conclusion Although the incidence of MALA is rare, health professionals should be aware of the initial symptoms of lactic acidosis, especially in elderly patients with risk factors, to prevent a fatal lactic acidosis event.

Catalytic ring hydrogenation of benzoic acid with supported transition metal catalysts in scCO(2)

The ring hydrogenation of benzoic acid to cyclohexanecarboxylic acid over charcoal-supported transition metal catalysts in supercritical CO2 medium has been studied in the present work. The cyclohexanecarboxylic acid can be produced efficiently in supercritical CO2 at the low reaction temperature of 323 K. The presence of CO2 increases the reaction rate and several parameters have been discussed.

STAR 3 randomized controlled trial to compare sensor-augmented insulin pump therapy with multiple daily injections in the treatment of type 1 diabetes: research design, methods, and baseline characteristics of enrolled subjects.

BACKGROUND: Sensor-augmented pump therapy (SAPT) integrates real-time continuous glucose monitoring (RT-CGM) with continuous subcutaneous insulin infusion (CSII) and offers an alternative to multiple daily injections (MDI). Previous studies provide evidence that SAPT may improve clinical outcomes among people with type 1 diabetes. Sensor-Augmented Pump Therapy for A1c Reduction (STAR) 3 is a multicenter randomized controlled trial comparing the efficacy of SAPT to that of MDI in subjects with type 1 diabetes. METHODS: Subjects were randomized to either continue with MDI or transition to SAPT for 1 year. Subjects in the MDI cohort were allowed to transition to SAPT for 6 months after completion of the study. SAPT subjects who completed the study were also allowed to continue for 6 months. The primary end point was the difference between treatment groups in change in hemoglobin A1c (HbA1c) percentage from baseline to 1 year of treatment. Secondary end points included percentage of subjects with HbA1c < or =7% and without severe hypoglycemia, as well as area under the curve of time spent in normal glycemic ranges. Tertiary end points include percentage of subjects with HbA1c < or =7%, key safety end points, user satisfaction, and responses on standardized assessments. RESULTS: A total of 495 subjects were enrolled, and the baseline characteristics similar between the SAPT and MDI groups. Study completion is anticipated in June 2010. CONCLUSIONS: Results of this randomized controlled trial should help establish whether an integrated RT-CGM and CSII system benefits patients with type 1 diabetes more than MDI.

Therapeutic effects of PPARα agonists on diabetic retinopathy in type 1 diabetes models

Retinal vascular leakage, inflammation, and neovascularization (NV) are features of diabetic retinopathy (DR). Fenofibrate, a peroxisome proliferator-activated receptor a (PPARa) agonist, has shown robust protective effects against DR in type 2 diabetic patients, but its effects on DR in type 1 diabetes have not been reported. This study evaluated the efficacy of fenofibrate on DR in type 1 diabetes models and determined if the effect is PPARa dependent. Oral administration of fenofibrate significantly ameliorated retinal vascular leakage and leukostasis in streptozotocin-induced diabetic rats and in Akita mice. Favorable effects on DR were also achieved by intravitreal injection of fenofibrate or another specific PPARa agonist. Fenofibrate also ameliorated retinal NV in the oxygen-induced retinopathy (OIR) model and inhibited tube formation and migration in cultured endothelial cells. Fenofibrate also attenuated overexpression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, and vascular endothelial growth factor (VEGF) and blocked activation of hypoxia-inducible factor-1 and nuclear factor-?B in the retinas of OIR and diabetic models. Fenofibrate's beneficial effects were blocked by a specific PPARa antagonist. Furthermore, Ppara knockout abolished the fenofibrate-induced downregulation of VEGF and reduction of retinal vascular leakage in DR models. These results demonstrate therapeutic effects of fenofibrate on DR in type 1 diabetes and support the existence of the drug target in ocular tissues and via a PPARa-dependent mechanism.

Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes

An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population.

Long-term renal outcomes of patients with type 1 diabetes mellitus and microalbuminuria:an analysis of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort

Microalbuminuria is a common diagnosis in the clinical care of patients with type 1 diabetes mellitus. Long-term outcomes after the development of microalbuminuria are variable.

Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin:a randomized, double-blind, placebo-controlled trial

To evaluate the dose-response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes.

Effect of intensive glycemic control on levels of markers of inflammation in type 1 diabetes mellitus in the diabetes control and complications trial

Type 1 diabetes mellitus is associated with an increased risk of cardiovascular disease (CVD) that is not fully explained by conventional risk factors. The Diabetes Control and Complications Trial (DCCT) showed that intensive diabetes therapy reduced levels of LDL cholesterol and triglycerides but increased the risk of major weight gain, which might adversely affect CVD risk. The present study examined the effect of intensive therapy on levels of several markers of inflammation that have been linked to risk of CVD.

Platelet plasminogen activator inhibitor 1 in patients with type II diabetes

To compare platelet plasminogen activator inhibitor 1 (PAI-1) concentration in type II diabetic patients and healthy control subjects.

Effect of acarbose on biochemical responses and clinical symptoms in dumping syndrome

A dose of 50 mg of acarbose was administered with a standard breakfast to 13 subjects with dumping syndrome. Significant attenuation of hyperglycaemia (p less than 0.01) was observed, and rises in plasma gastric inhibitory polypeptide, insulin and enteroglycagon were reduced (p less than 0.05). Plasma levels of neurotensin, vasoactive intestinal polypeptide and somatostatin were not affected. Dumping score was reduced, but this did not achieve statistical significance. In a longer-term study, 9 patients took acarbose, 50 mg t.i.d., for 1 month. No significant reduction in the number or severity of dumping attacks was observed, but a majority expressed a preference for the drug and some individuals experienced a marked improvement of symptoms.