Risk Factors for Failure of Direct Current Cardioversion in Patients with Type 2 Diabetes Mellitus and Atrial Fibrillation.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a well-recognised risk factor for cardiovascular disease and the prevalence of atrial fibrillation (AF) is higher among patients with T2DM. Direct current cardioversion (DCCV) is an important management option in persistent AF. We sought to determine independent risk factors for immediate and short-term outcomes of DCCV for treatment of AF in patients with T2DM. METHODS: Retrospective outcome analysis of DCCV for persistent AF in 102 T2DM patients compared with 102 controls. RESULTS: DCCV was successful in 68 (66.6%) people with T2DM compared to 86 (84.3%) in the control group (P = 0.003). After initial successful cardioversion, only 38 (37.2%) T2DM patients remained in sinus rhythm compared to 63 (61.8%) in the control group (P = 0.007) at a median follow-up of 74.5 days (IQR 69.4-77.4). Multiple logistic regression analysis showed that the presence of T2DM (P = 0.014), digoxin use (P = 0.01), statin use (P = 0.005), left-atrial size (P = 0.01), and LV ejection fraction (P = 0.008) were independent risk factors for immediate DCCV failure. T2DM (P = 0.034) was an independent risk factor for AF relapse. Among patients with T2DM, previous DCCV (P = 0.033), digoxin use (P = 0.035), left-atrial size (P = 0.01), LV ejection fraction (P = 0.036), and HbA1c (P = 0.011) predicted immediate failure of DCCV whilst digoxin use (P = 0.026) was an independent risk factor for relapse of AF. CONCLUSION: T2DM, higher HbA1c, digoxin treatment, and structural and functional cardiac abnormalities are independent risk factors for immediate DCCV failure and AF relapse.

A comparison of the effects of low- and high-dose atorvastatin on lipoprotein metabolism and inflammatory cytokines in type 2 diabetes: Results from the Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA) randomized trial.

BACKGROUND: Statin therapy is recommended in type 2 diabetes (T2DM) although views on treatment intensity and therapeutic targets remain divided. OBJECTIVES: Our objectives were to compare the effects of high-intensity and moderate-intensity atorvastatin treatment on lipoprotein metabolism and inflammatory markers and how frequently treatment goals are met in high-risk T2DM patients. METHODS: Patients with T2DM and albuminuria (urinary albumin:creatinine ratio >5 mg/mmol, total cholesterol <7 mmol/L, proteinuria <2 g/d, creatinine <200 µmol/L) were randomized to receive atorvastatin 10 mg (n = 59) or 80 mg (n = 60) daily. Baseline and 1-year follow-up data are reported. RESULTS: Patients were at high cardiovascular disease risk (observed combined mortality and nonfatal cardiovascular disease annual event rate 4.8%). The non-high-density lipoprotein cholesterol (HDL-C) goal of <2.6 mmol/L was achieved in 72% of participants receiving high-dose atorvastatin, but only in 40% on low-dose atorvastatin (P < .005). The proportion achieving apolipoprotein B (apoB) <0.8 g/L on high-dose and low-dose atorvastatin was 82% and 70%, respectively (NS). Total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL-C, oxidized LDL, apoB, glyc-apoB, apolipoprotein E, and lipoprotein-associated phospholipase A2 decreased significantly, more so in participants on high-dose atorvastatin. Adiponectin increased and serum amyloid A decreased without dose dependency. Neither dose produced significant changes in HDL-C, cholesterol efflux, high-sensitivity C-reactive protein, glycated hemoglobin, serum paraoxonase-1, lecithin:cholesterol acyltransferase, or cholesteryl ester transfer protein. CONCLUSIONS: High-dose atorvastatin is more effective in achieving non-HDL-C therapeutic goals and in modifying LDL-related parameters. Recommended apoB treatment targets may require revision. Despite the increase in adiponectin and the decrease in serum amyloid A, HDL showed no change in functionality.

Effect of Extended-Release Niacin on High-Density Lipoprotein (HDL) Functionality, Lipoprotein Metabolism, and Mediators of Vascular Inflammation in Statin-Treated Patients.

BACKGROUND: The aim of this study was to explore the influence of extended-release niacin/laropiprant (ERN/LRP) versus placebo on high-density lipoprotein (HDL) antioxidant function, cholesterol efflux, apolipoprotein B100 (apoB)-containing lipoproteins, and mediators of vascular inflammation associated with 15% increase in high-density lipoprotein cholesterol (HDL-C). Study patients had persistent dyslipidemia despite receiving high-dose statin treatment. METHODS AND RESULTS: In a randomized double-blind, placebo-controlled, crossover trial, we compared the effect of ERN/LRP with placebo in 27 statin-treated dyslipidemic patients who had not achieved National Cholesterol Education Program-ATP III targets for low-density lipoprotein cholesterol (LDL-C). We measured fasting lipid profile, apolipoproteins, cholesteryl ester transfer protein (CETP) activity, paraoxonase 1 (PON1) activity, small dense LDL apoB (sdLDL-apoB), oxidized LDL (oxLDL), glycated apoB (glyc-apoB), lipoprotein phospholipase A2 (Lp-PLA2), lysophosphatidyl choline (lyso-PC), macrophage chemoattractant protein (MCP1), serum amyloid A (SAA) and myeloperoxidase (MPO). We also examined the capacity of HDL to protect LDL from in vitro oxidation and the percentage cholesterol efflux mediated by apoB depleted serum. ERN/LRP was associated with an 18% increase in HDL-C levels compared to placebo (1.55 versus 1.31 mmol/L, P<0.0001). There were significant reductions in total cholesterol, triglycerides, LDL cholesterol, total serum apoB, lipoprotein (a), CETP activity, oxLDL, Lp-PLA2, lyso-PC, MCP1, and SAA, but no significant changes in glyc-apoB or sdLDL-apoB concentration. There was a modest increase in cholesterol efflux function of HDL (19.5%, P=0.045), but no change in the antioxidant capacity of HDL in vitro or PON1 activity. CONCLUSIONS: ERN/LRP reduces LDL-associated mediators of vascular inflammation, but has varied effects on HDL functionality and LDL quality, which may counter its HDL-C-raising effect. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01054508.

Interrupting the natural history of diabetes mellitus: lifestyle, pharmacological and surgical strategies targeting disease progression.

In recent decades we have seen a surge in the incidence of diabetes in industrialized nations; a threat which has now extended to the developing world. Type 2 diabetes is associated with significant microvascular and macrovascular disease, with considerable impact on morbidity and mortality. Recent evidence has cast uncertainty on the benefits of very tight glycaemic goals in these individuals. The natural history of disease follows an insidious course from disordered glucose metabolism in a pre-diabetic state, often with metabolic syndrome and obesity, before proceeding to diabetes mellitus. In the research setting, lifestyle, pharmacological and surgical intervention targeted against obesity and glycaemia has shown that metabolic disturbances can be halted and indeed regressed if introduced at an early stage of disease. In addition to traditional anti-diabetic medications such as the glinides, sulphonylureas and the glitazones, novel therapies manipulating the endocannabinoid system, neurotransmitters, intestinal absorption and gut hormones have shown dual benefit in weight loss and glycaemic control normalisation. Whilst these treatments will not and should not replace lifestyle change, they will act as invaluable adjuncts for weight loss and aid in normalising the metabolic profile of individuals at risk of diabetes. Utilizing novel therapies to prevent diabetes should be the focus of future research, with the aim of preventing the challenging microvascular and macrovascular complications, and ultimately cardiovascular death.

Dapagliflozin: a review on efficacy, clinical effectiveness and safety.

INTRODUCTION: The prevalence of type 2 diabetes mellitus has reached epidemic proportions. Progressive deterioration in glycaemic control and the current limitations of existing therapies such as weight gain and hypoglycaemia led us to welcome the first of a new class of drugs. Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a novel mode of therapy independent of insulin secretion or action. By blocking glucose reabsorption in the kidney they lead to an increase in urinary glucose excretion with reduction in plasma glucose levels. AREAS COVERED: In this article, we will review inhibition of SGLT2 as a novel strategy for the treatment of type 2 diabetes mellitus with dapagliflozin . PubMed and MEDLINE were searched for literature published up to July 2012, for efficacy, clinical effectiveness and safety reports of dapagliflozin. EXPERT OPINION: Improvement in glycaemic control with a low risk of hypoglycaemia, concomitant weight loss and the potential of lowering of blood pressure make SGLT2 inhibition an attractive approach using dapagliflozin therapy. Many SGLT2 inhibitors are undergoing Phase III clinical trials and more are in Phase I and II clinical trials.

Extended-release niacin with laropiprant : a review on efficacy, clinical effectiveness and safety.

INTRODUCTION: Although treatment with statins reduces cardiovascular (CV) events in patients with dyslipidemia, a residual 60 - 70% CV risk remains. This CV risk may be inversely related to high-density lipoprotein-cholesterol (HDL-C). Interest in niacin has re-emerged because of its HDL-C raising effects. The flushing associated with niacin which has previously affected patient compliance can now be significantly blocked with laropiprant (LRPT). AREAS COVERED: This review aims to assess the efficacy, clinical effectiveness and safety of extended-release niacin (ERN) with LRPT. The authors searched PubMed and MEDLINE for literature published between January 2006 and November 2011, for efficacy, clinical effectiveness and safety reports of ERN with LRPT. EXPERT OPINION: Niacin has been shown to prevent CV events, reduce mortality and has beneficial effects on vascular endothelial function. Evidence suggests that this is due to its broad-spectrum lipid altering properties, including lowering lipoprotein (a) (Lp(a)), and its pleiotropic actions. While side effects associated with niacin have limited its use in the past, the extended-release formulations and co-administration of LRPT have increased its tolerability, particularly by reducing flushing. The authors advise that ERN should be used in patients with a high risk of cardiovascular disease, who have failed to reach conventional targets.

The role of the renin-angiotensin system blocking in the management of atrial fibrillation.

OBJECTIVE: To review current available evidence for the role of renin-angiotensin system blockade in the management of atrial fibrillation. METHOD: We conducted a PubMed and Medline literature search (January 1980 through July 2011) to identify all clinical trials published in English concerning the use of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers for primary and secondary prevention of atrial fibrillation. We also discussed renin-angiotensin system and its effects on cellular electrophysiology. CONCLUSION: The evidence from the current studies discussed does not provide a firm definitive indication for the use of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers in the primary or secondary prevention of atrial fibrillation. Nevertheless, modest benefits were observed in patients with left ventricular dysfunction. In view of the possible benefits and the low incidence of side-effects with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, they can be given to patients with recurrent AF, specifically those with hypertension, heart failure and diabetes mellitus.

Role of aspirin in the primary prevention of cardiovascular disease in diabetes mellitus: a meta-analysis.

OBJECTIVE: To evaluate the benefits of aspirin in people with diabetes mellitus for the primary prevention of cardiovascular disease. RESEARCH DESIGN/METHODS: We searched MEDLINE and Cochrane database for randomized, controlled trials of aspirin in people with diabetes and no cardiovascular disease. Relative risks were determined using random-effects meta-analysis. MAIN OUTCOME MEASURES: Risk reduction of aspirin compared with control groups for major cardiovascular events. RESULTS: Six trials consisting of 7374 patients with diabetes showed no benefits of aspirin compared with non-aspirin users with regard to overall mortality, risk reduction (relative risk (RR) = 0.96, 95% CI 0.78 - 1.18, p = 0.71), major cardiovascular events (RR = 0.90, 95% CI 0.78 - 1.05, p = 0.17) and myocardial infarction (RR = 0.95, 95% CI 0.76 - 1.18, p = 0.63). Risk of major bleeding in the aspirin compared with the non-aspirin group was not significant (RR = 2.49, 95% CI 0.70 - 8.84, p = 0.16). CONCLUSIONS: Aspirin therapy did not reduce the risk of cardiovascular events. Existing trials were limited by small patient numbers and low cardiovascular event rates. The use of aspirin cannot be routinely recommended for primary prevention of cardiovascular events in diabetes.

Metastatic breast carcinoma presenting with profound hypocalcemia.

Hypocalcemia is a rare complication of malignancy. We present the case of a 30-year-old lady presenting with a grand mal seizure due to profound hypocalcemia. She was subsequently found to be hypoparathyroid and was diagnosed with metastatic breast carcinoma. Treatment with goserelin and exemestane produced a significant reduction in her tumor load and a correction of her hypocalcemia, which was initially refractory to treatment. We believe this to be the first case of metastatic breast carcinoma actually presenting with hypocalcemia and feel that clinicians should be aware of this rare complication.

Vildagliptin in clinical practice: a review of literature.

Vildagliptin is the second member of the DPP-IV inhibitor class of drugs licensed for the treatment of type 2 diabetes mellitus (T2DM). The novel action of these drugs has promoted a new outlook in the pathobiology of T2DM. This review undertakes to examine the clinical studies published to date, with the aim of evaluating the position of vildagliptin among the drugs that are now available to treat this common dysmetabolic state.

The role of insulin detemir in overweight type 2 diabetes management.

The recent evidence-based shift towards an algorithm of early initiation and aggressive titration of insulin therapy in the management of type 2 diabetes requires the use of an effective insulin formulation that is both safe and acceptable to patients and physicians alike. The advent of the long-acting insulin analogues, insulin detemir and glargine, in the last decade has revolutionized insulin therapy in type 2 diabetes. Their unique pharmacokinetic and pharmacodynamic properties have offered tangible advantage over the conventional intermediate and long-acting insulin preparations in terms of improving glucose control as well as reducing risk of hypoglycemia and weight gain. This review focuses on the pharmacodynamic properties of the long-acting insulin analogue detemir, the outcome of studies on its relative efficacy and safety as well as its proposed place in the management of type 2 diabetes.

Aspirin therapy and primary prevention of cardiovascular disease in diabetes mellitus.

The benefits of aspirin therapy in reducing the subsequent risk of myocardial infarction, stroke and death is well documented in individuals with cardiovascular disease including those with diabetes mellitus (DM). The evidence for aspirin use in primary prevention of cardiovascular events in DM is debatable and meta-analyses do not suggest a proven benefit. Despite the lack of evidence, low-dose aspirin therapy has been recommended by many current diabetes guidelines. This article reviews the results of two recently published large randomized clinical trials that have looked at primary prevention of cardiovascular events using aspirin in patients with DM.

Tight glycaemic control and cardiovascular disease in type 2 diabetes.

The role of tight glycaemic control in reducing cardiovascular events and mortality in type 2 diabetes has not yet been firmly established. Recent clinical trials have yielded unexpected outcomes. This review summarizes the background and outcome of these trials and the implications for management of glycaemia in type 2 diabetes.

The role of the renin angiotensin system blocking in the management of atrial fibrillation.

OBJECTIVE: The objective of the study was to review the current available clinical evidence for the role of renin-angiotensin system (RAS) blockade in the treatment of atrial fibrillation (AF). METHOD: We conducted a Pubmed and Medline literature search (January 1980 through May 2007) to identify all clinical trials published in English involving the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) for preventing the occurrence or recurrence of AF. Discussing pathophysiology and experimental evidence in detail is beyond the scope of this article. CONCLUSION: There is no solid evidence to support using ACE inhibitors or ARBs as antiarrhythmic therapy in patients with AF. However, in view of the possible benefits and the low incidence of side effects with ACE inhibitors and ARBs, they might be given in patients with recurrent AF, particularly if there are other indications for their use such as hypertension, HF, or diabetes mellitus. Possible benefits from pre-treatment argue in favour of using ACE inhibitors and ARB as first-line therapy in patients with hypertension.

Insulin detemir: a new basal insulin analogue.

Basal insulin therapy is an integral part of the intensive management of type 1 diabetes and it is also often used in type 2 diabetes. An ideal insulin regimen in patients with diabetes would mirror the 24-h insulin profile of a non-diabetic person, thereby preventing hyperglycaemia without inducing hypoglycaemia. Until recently, available insulins have pharmacokinetic disadvantages, compared to physiological insulin secretion. Insulin detemir is a new basal insulin analogue recently available for commercial use in the UK. Clinical trials have demonstrated lower fasting plasma glucose levels, lower variability in plasma glucose, predictable action profile and a reduced risk of nocturnal hypoglycaemia and weight gain, compared to conventional basal insulins. This study reviews the properties and potential use of insulin detemir.

Incidence of sight-threatening retinopathy in patients with type 2 diabetes in the Liverpool Diabetic Eye Study: a cohort study.

BACKGROUND: Incidence data on which to base targets and protocols for screening for sight-threatening diabetic retinopathy are few. We aimed to investigate yearly and cumulative incidence of any retinopathy, maculopathy, and sight-threatening diabetic retinopathy in patients with type 2 diabetes in an established systematic programme and to calculate optimum screening intervals according to retinopathy grade at baseline. METHODS: We investigated all patients with type 2 diabetes registered with enrolled general practices (except those who were attending an ophthalmologist) who had retinopathy data available at baseline and at least one further screening event. To screen patients, we used non-stereoscopic three-field mydriatic photography and modified Wisconsin grading. Sight-threatening diabetic retinopathy was defined as moderate preproliferative retinopathy or worse, or clinically significant maculopathy in either or both eyes. FINDINGS: Results were obtained from 20 570 screening events. Yearly incidence of sight-threatening diabetic retinopathy in patients without retinopathy at baseline was 0.3% (95% CI 0.1-0.5) in the first year, rising to 1.8% (1.2-2.5) in the fifth year; cumulative incidence at 5 years was 3.9% (2.8-5.0). Rates of progression to sight-threatening diabetic retinopathy in year 1 by baseline status were: background 5.0% (3.5-6.5), and mild preproliferative 15% (10.2-19.8). For a 95% probability of remaining free of sight-threatening diabetic retinopathy, mean screening intervals by baseline status were: no retinopathy 5.4 years (95% CI 4.7-6.3), background 1.0 years (0.7-1.3), and mild preproliferative 0.3 years (0.2-0.5). INTERPRETATION: A 3-year screening interval could be safely adopted for patients with no retinopathy, but yearly or more frequent screening is needed for patients with higher grades of retinopathy.

Management of amiodarone-induced thyrotoxicosis.

Thyrotoxicosis occurs in up to 3% of people prescribed amiodarone in the UK. The management of amiodarone-induced thyrotoxicosis remains a clinical challenge, as data on optimal treatment from controlled trials are not available. This review will focus on current lines of management.

Painful cutaneous lesions, renal failure and urgent parathyroidectomy.

We describe two patients with end stage renal failure who presented with painful skin lesions, which rapidly progressed to become necrotic and gangrenous. The diagnosis was calciphylaxis, a rare disorder due to calcification and luminal fibrosis of small and medium sized cutaneous and systemic vessels. Both patients had tertiary hyperparathyroidism. An urgent parathyroidectomy was performed on one patient, which relieved her symptoms; the other required local surgery but refused parathyroidectomy and died.