Effect of inpatient electroencephalography on clinical decision making.

CONTEXT: Routine inpatient electroencephalography (EEG) is commonly used as a diagnostic and therapeutic decision-making tool in the care of patients with a wide spectrum of conditions. Previous investigations on EEG use have focused on current guidelines or specific clinical presentations. OBJECTIVE: To assess the effect of EEGs on clinical diagnosis and management of disease in adult inpatients in a community hospital. METHODS: Medical records of adult patients who underwent EEG between October 2008 and June 2009 in a single general community hospital were retrospectively reviewed. Data were collected for comorbidities, diagnoses, and management. Findings from EEGs were classified as normal, abnormal, or uninterpretable and according to whether they resulted in a change in diagnosis or management, supported clinical decision making and resulted in no change in diagnosis or management, or did not contribute to diagnosis or management. RESULTS: A total of 200 medical records were reviewed; 110 (55%) were for male patients and 90 (45%) were for female patients, with a mean (range) age of 60 (18-96) years. The most common pre-EEG diagnoses were altered mental status (52 [26%]) and seizure (48 [24%]). Of all EEGs, 115 (57.5%) had findings that were normal, 83 (41.5%) had findings that were abnormal, and 2 (1%) had findings that were uninterpretable. No EEGs had findings that resulted in a change in diagnosis or management, 8 EEGs (4%) had findings that supported clinical decision making and resulted in no change in diagnosis or management, and 192 EEGs (96%) had findings that did not contribute to diagnosis or management. CONCLUSION: In this study, inpatient EEGs rarely contributed to clinical decision making and in no case resulted in a change in diagnosis or management. These findings warrant future research on the effectiveness of inpatient EEGs for a wide breadth of clinical inpatient diagnoses.

Effect of vitamin D replacement on insulin sensitivity in subjects with vitamin D deficiency.

BACKGROUND AND OBJECTIVE: Low vitamin D levels correlate with measures of insulin resistance and prevalence of diabetes mellitus, but there are limited and conflicting data on changes in insulin resistance after vitamin D replacement. The objective of the current study was to examine whether vitamin D replacement improves insulin sensitivity. METHODS: In this randomized double-blind placebo-controlled study, 12 healthy subjects with plasma 25-hydroxy vitamin D (25[OH]D) levels of less than 20 ng/mL were treated with ergocalciferol, 50,000 units, orally once a week for 8 weeks or matching placebo. The main outcome measure was insulin-stimulated glucose infusion rate during the last 20 minutes of a hyperinsulinemic-euglycemic glucose clamp study. RESULTS: At baseline, plasma 25(OH)D levels were similar between the ergocalciferol and placebo groups (13.3 ± 3.8 and 15.7 ± 2.4 ng/mL, respectively; P = 0.3) but were higher in the ergocalciferol group at 8 weeks (18.8 ± 5 vs 12.5 ± 2.2 ng/mL; P = 0.02). Glucose infusion rate was similar between the 2 groups both at baseline and after 8 weeks of treatment. Changes in plasma 25(OH)D levels did not correlate with change in glucose infusion rate. CONCLUSION: Administration of ergocalciferol, 50,000 units, weekly for 8 weeks in subjects with low vitamin D levels improves 25(OH)D levels but does not improve insulin sensitivity.

Common patient concerns about the use of glucagon-like peptide-1 receptor agonists in diabetes mellitus management.

The authors present a case of a 46-year-old woman with type 2 diabetes mellitus who has been on a treatment regimen involving diet, exercise, and metformin. After 2 years of treatment, she has a body mass index of 35 and a glycosylated hemoglobin level of 8.0%, and this level is increasing. Her physician recommends adding a glucagon-like peptide-1 (GLP-1) receptor agonist to her treatment regimen, prompting her to ask several questions. The authors present these questions along with proposed answers, highlighting the practical application of GLP-1 receptor agonists in the context of common patient concerns.

Incorporating glucagon-like peptide-1 receptor agonists into clinical practice.

Two glucagon-like peptide-1 (GLP-1) receptor agonists are currently approved for use in patients with type 2 diabetes mellitus: exenatide and liraglutide. Both of these injectable agents improve glycemic control as monotherapy or as combination therapy with oral agents. Overall, GLP-1 receptor agonists provide additive effects in dual and triple therapy regimens. In a clinical trial, the use of liraglutide resulted in greater improvements in glycosylated hemoglobin and fasting plasma glucose levels compared to exenatide, although the effects of exenatide on postprandial plasma glucose levels were greater. Clinical trials have also demonstrated statistically significant weight reduction, small beneficial effects on blood pressure, and unchanged lipid profiles with GLP-1 receptor agonists. The author reviews clinical trial data on the use of GLP-1 receptor agonists for patients with type 2 diabetes mellitus, outlines potential contraindications of these agents, and discusses the role of GLP-1 receptor agonists in algorithms for the initiation and advancement of treatment.

Pharmacology of GLP-1 agonists: describing the therapeutic potential to patients.

The pathophysiology of type 2 diabetes mellitus is complex, consisting of far more physiologic defects than simple insulin resistance and ß-cell dysfunction. Our understanding of this progressive disease has moved from a "dual defect" to an "ominous octet" description. This multifactoral concept may explain the difficulty in achieving and maintaining glycemic goals with traditional therapies. Glucagon-like peptide-1 (GLP-1) agonists, which improve insulin secretion, decrease glucagon secretion, increase satiety (and therefore decrease food intake), and may have beneficial effects on ß-cell function, represent an important addition to treatment options. Their glucose-dependent mechanism limits the risk for hypoglycemia, and they are associated with weight loss. Glucagon-like peptide-1 agonists may be used alone in patients intolerant of metformin or in combination with metformin, thiazolidinediones, and sulfonylureas (or in any combination therereof). Concomitant use of dipeptidyl-peptidase-4 inhibitors is not recommended because they have a similar basis of action. Current US Food and Drug Administration indications do not include the concomitant use of GLP-1 agonists with insulin.

Improving outcomes in patients with type 2 diabetes mellitus: practical solutions for clinical challenges.

The incidence and prevalence of type 2 diabetes mellitus (T2DM) in the United States continue to rise, and the disease has become an enormous health concern. While effective glycemic management reduces the risk of diabetes-related complications in patients with T2DM, many patients are unable to reduce their glucose levels to target goals. The authors review key elements in the management of T2DM with an emphasis on achieving and maintaining glycemic control. Strategies are offered to provide practical solutions to the challenges faced by healthcare providers and patients with T2DM. The importance of implementing evidence-based practice guidelines while empowering patients to participate in self-management of their disease is highlighted.

Pathophysiology of type 2 diabetes: targeting islet cell dysfunction.

Type 2 diabetes mellitus (T2DM) continues to be a major health problem worldwide. It is well known that T2DM is a metabolic disorder characterized by hyperglycemia, which arises from insufficient pancreatic insulin secretion, insulin resistance in peripheral tissues, and inadequate suppression of glucagon production. This suppression results in inadequate uptake, storage, and disposal of ingested glucose accompanied by elevated hepatic production of glucose and profound hyperglycemia. Notably, these pathophysiologic processes can progress to a clinically significant degree even in patients with impaired glucose tolerance. As researchers begin to unravel the genetic basis of T2DM, the gradual accumulation of genetic polymorphisms in multiple genes-rather than the mutation of a single "diabetes gene"-appears to be the driving force behind the increase in T2DM risk. Emergent therapies for the management of T2DM include incretin-based agents, which can effectively target two key processes in T2DM by augmenting insulin secretion and inhibiting glucagon production.

Management of progressive type 2 diabetes: role of insulin therapy.

Insulin is an effective treatment for achieving tight glycemic control and improving clinical outcomes in patients with diabetes. While insulin therapy is required from the onset of diagnosis in type 1 disease, its role in type 2 diabetes requires consideration as to when to initiate and advance therapy. In this article, we review a case study that unfolds over 5 years and discuss the therapeutic decision points, initiation and advancement of insulin regimens, and analyze new data regarding the advantages and disadvantages of tight management of glucose levels.

Achieving glycemic control: cornerstone in the treatment of patients with multiple metabolic risk factors.

The control of glycosylated hemoglobin (HbA(1c)) levels is crucial to the successful treatment of patients with diabetes mellitus (T2DM). Glycemic control is a cornerstone for reducing end-organ disease, and HbA(1c) is the benchmark for defining glucose control over long durations. The author reviews available information from published clinical trials regarding the benefits of tight glycemic control in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). He notes that published data support the use of tight glucose control for reducing risks of retinopathy, nephropathy, and neuropathy in both patients with T1DM and patients with T2DM. He also notes that early aggressive insulin management of younger individuals with T1DM led to reductions in the incidence of myocardial infarction (MI), stroke, and death. However, published data do not clearly support benefits of tight glucose control for the prevention of cardiovascular events in older patients with long-standing T2DM. The author also reviews recommended treatments for achieving and maintaining glycemic control in patients. He concludes that the most successful treatment requires that physicians encourage patients to actively participate in the management of their own disease, and that physicians provide patients with opportunities to learn the cornerstones of effective therapy.

Aggressively managing type 2 diabetes mellitus, hyperlipidemia, and bone loss.

Physicians have many options available for treating patients with type 2 diabetes mellitus (T2DM). Making decisions on types of pharmaceuticals to use and when to introduce them into the treatment regimen can be a complex process. In addition, nutrition and exercise must be considered in any comprehensive treatment plan. The author describes the case of an African American woman with uncontrolled T2DM, obesity, hyperlipidemia, low bone mass, menopausal symptoms, stage 3 chronic kidney disease, distal sensory neuropathy, and background retinopathy. An aggressive, comprehensive treatment plan developed for this patient included pharmaceuticals (triple oral therapy: metformin, pioglitazone hydrochloride, and sitagliptin phosphate), nutrition counseling (with a registered, licensed dietician), and exercise. Treatment led to substantial improvements in the patient's daytime glucose level, glycosylated hemoglobin level, and body weight at 3-month follow-up. Further interventions were needed to address the patient's hyperlipidemia and low bone mass. The author offers physician guidelines for making decisions on glycemic control for patients with T2DM and for managing hyperlipidemia. He also strongly recommends incorporating nutrition counseling by registered, licensed dietitians and exercise (preferably of a weight-bearing nature) into treatment plans for patients with T2DM, hyperlipidemia, and low bone mass.

Islet cell dysfunction in progression to diabetes mellitus.

The epidemic of type 2 diabetes mellitus is increasing in most nations. This illness is a major cause of cardiovascular disease, stroke, blindness, renal failure, and amputations. Because available interventions have failed to show durability, new modes of therapy need to be directed at the underlying causes of abnormal glucose metabolism. The development of such modes of therapy will require an improved understanding of how the beta-cell mass compensates for changes in insulin resistance and why beta cells lose the capacity to secrete insulin. In addition, new therapeutic modalities need to address alpha-cell dysregulation, because the inability to suppress glucagon production results in ongoing elevated levels of hepatic glucose.

Insulin therapy for maximal glycemic control in type 2 diabetes mellitus.

Type 2 diabetes mellitus is on the rise, yet glycemic control continues to elude patients-and their physicians. During the past decade, the use of insulin monotherapy has decreased while the use of oral antidiabetic agents (either alone or in combination with insulin injections) has increased. The continued prevalence of the disorder, changes in prescribing patterns, and recent data indicating that only one third of patients with type 2 diabetes mellitus achieve glycemic control underscore the need for physicians to reevaluate the clinical management of this now common disorder. Insulin analogs provide flexibility in the delivery of insulin therapy for this population. Although potential barriers and complications to initiation exist, patients should understand that achieving and maintaining glycemic control reduces the risk of long-term complications as a result of type 2 diabetes mellitus. Physicians are encouraged to actively identify and address patient concerns about this treatment modality.

Should all diabetic patients receive statins?

Diabetes is known to play a causal role in promoting both microvascular and macrovascular complications. Reducing rates of end-organ damage has been a key objective of multiple clinical trials. In addition to the roles of glycemic and blood pressure control, it is evident that lipid reduction via statin therapy independently helps to reduce the risk of primary and secondary vascular events. This effect seems to remain intact across a broad range of lipid levels, suggesting additional mechanisms for efficacy of statin medications beyond cholesterol reduction. The demonstrated safety and data from recent trials lend support to the argument that all people with diabetes should be started on statin therapy regardless of their cholesterol level. It is also plausible that treating the underlying mechanisms of vascular dysfunction, inflammation, and injury so prevalent in diabetic patients would have similar implications for the patient identified as having insulin resistance or metabolic syndrome.

Management of diabetes in the real world: tight control of glucose metabolism.

This clinical review looks at tight control of blood glucose with oral agents and insulin in adults and children with type 2 diabetes mellitus. It includes recommendations based on the treatment algorithms from the Texas Diabetes Council. The focus is on specific indications for selecting initial monotherapy, early dual therapy, or combination oral therapy. Discussion includes glycemic targets and times to goal along with recommendations for insulin management that depend on patient stratification as "treatment naive" or "combination oral agent failures" (defined as A1c value < or = 9.5% or > 9.5%). This presentation also includes protocols for once-daily injections, multidose insulin injections, and intensive insulin therapy (physiologic insulin delivery) as well as discussion of starting doses, titration schedules, optimum basal bolus insulin regimen, and calculation of insulin augmentation.

Combination therapy for dyslipidemia.

In the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines, the emphasis of lipid-lowering therapy is placed on reaching target plasma low-density lipoprotein cholesterol (LDL-C) levels in order to reduce the risk for coronary heart disease (CHD). Although therapeutic lifestyle changes can have a positive effect on LDL-C levels, the ATP III recognizes that a majority of patients with dyslipidemia will also require drug therapy to achieve lipid targets. Currently, only a small percentage of patients, including those with CHD, are reaching goal. Early aggressive use of the effective lipid-lowering agents currently available is critical to achieve target lipid levels in a greater number of patients. Use of drug combinations further enhances the likelihood of achieving target lipid levels. Ideally, the combination of therapeutic modalities used both the endogenous and exogenous pathways of cholesterol synthesis to reduce the amount produced in the body, as well as the amount absorbed from the diet. This article reviews the pharmacotherapeutic effects of combination therapy, summarizes the strengths and weaknesses of current lipid-lowering drug combinations, and identifies the potential impact of the novel cholesterol absorption inhibitor ezetimibe on the LDL-C treatment algorithm.

Strategies for optimizing lipid treatment outcomes.

The relationship between increased levels of cholesterol and elevated risk for coronary heart disease (CHD) has been described in many epidemiologic and well-designed prospective trials. Since first being elucidated by the Coronary Primary Prevention Trial, reducing levels of blood cholesterol results in a corresponding reduction in CHD risk has been demonstrated by numerous trials. The evidence now indicates that cholesterol reduction by any number of means confers up to a 35% reduction in total mortality, coronary mortality, coronary artery procedures, stroke, and other CHD-related events. This article reviews data that demonstrate cholesterol reduction decreases CHD risk, discusses current and emerging treatment modalities, and describes the methods healthcare practitioners can use to enhance lipid treatment outcomes. It also identifies educational tools that can be used to empower patients to improve their compliance and become actively involved in reducing their CHD risk.