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Biomedical subjects

Lawrence Blonde

Publications and source records attributed to Lawrence Blonde.

At least 19 recordsLinked to original sources

Reducing cardiovascular disease risk in patients with diabetes: a message from the National Diabetes Education Program.

PURPOSE: To provide nurse practitioners (NPs) a review of current practice guidelines that help clinicians' efforts to reduce the morbidity and mortality associated with diabetes and its major macrovascular complications. DATA SOURCES: This paper presents data from major evidence-based studies and clinical trials that define the scope of the problem, the rationale for risk reduction, and a patient-centered action plan for NPs to effectively manage cardiovascular risk factors in people with diabetes. CONCLUSIONS: NPs are active partners with the National Diabetes Education Program and play a key role in efforts to effectively manage cardiovascular risk factors in people with diabetes and improve their awareness of the link between diabetes and heart disease and stroke. IMPLICATIONS FOR PRACTICE: The action plan to reduce cardiovascular risk in people with diabetes will help NPs to implement the most effective management strategies for medical nutrition therapy, physical activity, and pharmacological therapy required for patient-centered proactive management of hyperglycemia, hypertension, and lipid abnormalities.

Anti-Inflammatory Agents, Non-Steroidal↗

Sildenafil citrate for erectile dysfunction in men with diabetes and cardiovascular risk factors: a retrospective analysis of pooled data from placebo-controlled trials.

OBJECTIVE: Cardiovascular (CV) risk factors are associated with an increased risk of erectile dysfunction (ED). In men with diabetes mellitus (DM), pooled from clinical trials of sildenafil treatment for ED, this retrospective analysis determined efficacy and safety, overall and in subgroups with additional CV risk (i.e., hypertension, dyslipidemia, and smoking). RESEARCH DESIGN AND METHODS: From the manufacturer's database of worldwide research, 12-week data from men with DM were pooled from randomized, double-blind, placebo-controlled trials of flexible-dose sildenafil (25, 50, or 100 mg, PRN) for ED. MAIN OUTCOME MEASURES: Question 3 (achieving an erection), question 4 (maintaining an erection), and the Erectile Function domain of the International Index of Erectile Function; percentage of successful intercourse attempts according to patient event logs; and response to a global efficacy question (GEQ). Differences between groups were determined using logistic regression (percentage of responders according to GEQ) and analysis of covariance (all other outcomes). RESULTS: Inclusion criteria were met by 11 trials and by 974 men with DM and ED who were randomized to placebo (n = 482) and sildenafil (n = 492) within the selected trials. For all outcomes, overall and regardless of additional CV risk, the benefit was greater for sildenafil versus placebo (p < or = 0.0001), including 3-fold more men responding that sildenafil treatment improved their erections (62% vs. 18%) and a more than doubling of the mean +/- standard error percentage of successful sexual intercourse attempts (52.6 +/- 5.0 vs. 22.4 +/- 5.1). Adverse events were mild to moderate and included (sildenafil vs. placebo) headache (5% vs. 2%), flushing (7% vs. 2%), and dyspepsia (4% vs. 0%), which is consistent with the profile in the general population of men treated with sildenafil for ED. CONCLUSION: This retrospective analysis of pooled data showed that sildenafil was well tolerated and improved erectile function and intercourse success in men with ED and DM, regardless of additional CV risk factors.

Adult↗

Adiposopathy: how do diet, exercise and weight loss drug therapies improve metabolic disease in overweight patients?

An increase in bodyweight is generally associated with an increased risk of excessive fat-related metabolic diseases (EFRMD), including Type 2 diabetes mellitus, hypertension and dyslipidemia. However, not all patients who are overweight have EFRMD, and not all patients with EFRMD are significantly overweight. The adipocentric paradigm provides the basis for a unifying, pathophysiological process whereby fat gain in susceptible patients leads to fat dysfunction ('sick fat'), and wherein pathological abnormalities in fat function (adiposopathy) are more directly related to the onset of EFRMD than increases in fat mass (adiposity) alone. But just as worsening fat function worsens EFRMD, improved fat function improves EFRMD. Peroxisome proliferator-activated receptor-gamma agonists increase the recruitment, proliferation and differentiation of preadipocytes ('healthy fat') and cause apoptosis of hypertrophic and dysfunctional (including visceral) adipocytes resulting in improved fat function and improved metabolic parameters associated with EFRMD. Weight loss interventions, such as a hypocaloric diet and physical exercise, in addition to agents such as orlistat, sibutramine and cannabinoid receptor antagonists, may have favorable effects upon fat storage (lipogenesis and fat distribution), nutrient metabolism (such as free fatty acids), favorable effects upon adipose tissue factors involved in metabolic processes and inflammation, and enhanced 'cross-talk' with other major organ systems. In some cases, weight loss therapeutic agents may even affect metabolic parameters and adipocyte function independently of weight loss alone, suggesting that the benefit of these agents in improving EFRMD may go beyond their efficacy in weight reduction. This review describes how adiposopathy interventions may affect fat function, and thus improve EFRMD.

Adipose Tissue↗

What are incretins, and how will they influence the management of type 2 diabetes?

OBJECTIVE: To review the pathophysiology of type 2 diabetes (T2DM), the role of incretins, the potential of incretin-based therapies to address unmet therapeutic needs in T2DM, and the potential impact this will have on the contribution of managed care pharmacy to diabetes therapy. SUMMARY: Diabetes, the fifth leading cause of death by disease in the United States, costs approximately $132 billion per year in direct and indirect medical expenses. According to the Centers for Disease Control and Prevention.s National Health and Nutrition Examination Survey, a majority of diabetes patients do not achieve target A1C levels with their current treatment regimens. Advances in understanding the pathophysiologic abnormalities underlying the metabolic dysfunctions associated with T2DM are leading to the development of new treatment approaches and new therapeutic classes of drugs. Novel incretin-based therapies currently available, and in late-stage development, are among those showing the greatest promise for addressing the unmet needs of traditional therapies.

Adenosine Deaminase↗

Current evidence regarding the value of self-monitored blood glucose testing.

Many people with diabetes are falling short of attaining or maintaining glycemic goals. Self-monitoring of blood glucose (SMBG) is among the many strategies proposed to address the problem. SMBG complements hemoglobin A1c (HbA1c) testing by providing specific information regarding the effects of diet, exercise, and medications on glycemia. Although the importance of self-monitoring is appreciated for insulin-using patients, evidence is still emerging in support of self-monitoring for patients with type 2 diabetes managed with oral agents or diet. Evaluating the available evidence requires a good understanding of the study design and methodology. Although several clinical trials involving SMBG have been insufficiently powered to detect clinically meaningful differences in HbA1c, recent meta-analyses have reproducibly supported the benefit of self-monitoring in non-insulin-treated patients. Although additional work is needed to establish optimal frequency and timing of SMBG, these studies can serve as a basis for conservative recommendations to guide patients and their healthcare providers.

Blood Glucose↗

Current challenges in diabetes management.

The burden of diabetes on the health care system mandates efforts to more optimally treat those with the disease and to prevent its development in those at risk. Early and intensive intervention in patients with diabetes reduces the risk of microvascular and macrovascular complications and disease progression. Current challenges in diabetes management include: (1) optimizing the use of currently available therapies to ensure adequate glycemic, blood pressure, and lipid control and to reduce complications; (2) educating patients on diabetes self-management; (3) improving patient adherence to lifestyle and pharmacologic interventions; (4) reducing barriers to the early use of insulin; and (5) improving the delivery of health care to people with chronic conditions.

Blood Glucose↗

Metabolic issues in patients with severe mental illness.

This article reviews the epidemiology of weight gain and diabetes mellitus in general and in patients with severe mental illness in particular. Body mass index is defined, and possible predictors for weight gain in patients receiving antipsychotic medications are also enumerated. Information on risk of association with type 2 diabetes mellitus is described, as well as information on dyslipidemias within the rubric of the metabolic syndrome. Recent consensus panel reports and their recommendations for ongoing patient monitoring are reviewed. The issue of switching antipsychotic medication in the context of a developing metabolic disorder is discussed with regard to appropriately balancing risk and benefits. Collaborative treatment between a psychiatrist and an endocrinologist is encouraged. The primary care physician may be required to fulfill both roles.

Antipsychotic Agents↗

Real-world trials to answer real-world questions.

Currently, there is a discrepancy between clinical trials designed to assess the efficacy and safety of a new medication under investigation and the real-life questions that need to be addressed regarding the clinical use of the medication by patients, healthcare professionals and society. The data necessary to obtain regulatory approval may be of limited relevance to policy makers when calculating economic parameters such as value for money or cost effectiveness. 'Real-world' studies examine questions relevant to health policy and reimbursement. There are many different forms of clinical trials, but in designing trials incorporating realistic budget impact estimates the important issue is to ensure we are asking a sensible question and attempting to answer it with an appropriate experimental design. As an example, a real-world trial currently underway that examines scenarios of introducing inhaled insulin into clinical practice is described.

Clinical Trials as Topic↗

Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study.

OBJECTIVE: Metformin, a biguanide antihyperglycemic medication, lowers blood glucose in patients with type 2 diabetes with minimal risk of hypoglycemia. Most common side effects include diarrhea, nausea and vomiting. Extended-release metformin (Glucophage XR)*, a once-daily tablet using the patented GelShield Diffusion System release mechanism, may be better tolerated than immediate-release metformin (Glucophage). This retrospective chart review examined the overall gastrointestinal (GI) tolerability of both formulations. RESEARCH DESIGN AND METHODS: Patient charts were reviewed and data were collected from October 2001 to May 2002. Adult patients with type 2 diabetes started on extended-release metformin (metformin-XR) or switched from immediate-release metformin to metformin-XR within the previous 2 years were eligible for inclusion in the metformin-XR cohort. Patients started on immediate-release metformin within the previous 2 years were eligible for inclusion in the immediate-release metformin cohort. Previous experience of GI side effects while taking immediate-release metformin did not prevent inclusion in either cohort, though patients with significant underlying GI disease or moderate to severe hepatic or renal impairment were excluded. GI tolerability was assessed during the first year of treatment with immediate-release metformin or metformin-XR. Primary endpoints were overall GI tolerability and frequency of diarrhea during the first year of treatment. RESULTS: A total of 471 patients' charts were reviewed and data were collected from four diabetes clinics; 310 (metformin-XR) and 158 (immediate-release metformin) eligible patients were included. Patients were, on average, 56 years old, and overweight (mean body mass index 33 kg/m2). The majority of patients were Caucasian (50%), Hispanic (24%) or Black (19%). Mean daily doses were 1258 mg (range 500-2500 mg) for metformin-XR and 1282 mg (range 500-2550 mg) for immediate-release metformin. About 25% of the metformin-XR cohort had been switched from immediate-release metformin due to a history of GI adverse events (AE). Despite this, the frequency of any GI AE was similar between metformin-XR and immediate release metformin (11.94 vs. 11.39%, p = 0.86). The incidence of individual GI AE also did not differ significantly between cohorts. In a cohort of 205 patients started on immediate-release metformin and switched to metformin-XR, the frequency of any GI AE was 26.34% (while taking immediate release metformin; n = 205) vs. 11.71% (after switching to metformin-XR; n = 205) (p = 0.0006) and the frequency of diarrhea was 18.05% (while taking immediate-release metformin) vs. 8.29% (after switching to metformin-XR) (p = 0.0084). CONCLUSIONS: In this retrospective chart review, patients switched from immediate-release metformin to metformin-XR experienced fewer GI side effects on comparable doses of the extended-release metformin.

Administration, Oral↗

Efficacy and safety of inhaled insulin (exubera) compared with subcutaneous insulin therapy in patients with type 2 diabetes: results of a 6-month, randomized, comparative trial.

OBJECTIVE: Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections. RESEARCH DESIGN AND METHODS: Patients were randomized to 6 months' treatment with either premeal inhaled insulin plus a bedtime dose of Ultralente (n = 149) or at least two daily injections of subcutaneous insulin (mixed regular/NPH insulin; n = 150). The primary efficacy end point was the change in HbA1c from baseline to the end of study. RESULTS: HbA1c decreased similarly in the inhaled (-0.7%) and subcutaneous (-0.6%) insulin groups (adjusted treatment group difference: -0.07%, 95% CI -0.32 to 0.17). HbA1c < 7.0% was achieved in more patients receiving inhaled (46.9%) than subcutaneous (31.7%) insulin (odds ratio 2.27, 95% CI 1.24-4.14). Overall hypoglycemia (events per subject-month) was slightly lower in the inhaled (1.4 events) than in the subcutaneous (1.6 events) insulin group (risk ratio 0.89, 95% CI 0.82-0.97), with no difference in severe events. Other adverse events, with the exception of increased cough in the inhaled insulin group, were similar. No difference in pulmonary function testing was seen. Further studies are underway to assess tolerability in the longer term. Insulin antibody binding increased more in the inhaled insulin group. Treatment satisfaction was greater in the inhaled insulin group. CONCLUSIONS: Inhaled insulin appears to be effective, well tolerated, and well accepted in patients with type 2 diabetes and provides glycemic control comparable to a conventional subcutaneous regimen.

Administration, Inhalation↗

Thiazolidinediones in the treatment of managed care patients with type 2 diabetes.

Insulin resistance and progressive beta-cell failure are fundamental defects in type 2 diabetes. Treatments that improve insulin sensitivity and beta-cell function can improve these defects and improve glycemic control. The thiazolidinediones (TZDs) improve insulin sensitivity, fasting and postprandial plasma glucose levels, and glycosylated hemoglobin (HbA1c) levels. These agents can be used as monotherapy, and they have been successfully combined with other antidiabetic therapies. The TZDs have also been associated with improvements in various cardiovascular risk factors, including hypertension, the dyslipidemic profile often observed in patients with diabetes or insulin resistance, aspects of endothelial dysfunction, abnormal hemostasis, and levels of several inflammatory markers. Studies are currently under way to evaluate the effects of TZDs on cardiovascular event rates. Accumulating evidence suggests that TZDs may enhance or preserve beta-cell function and thus may have a more durable therapeutic effect than some of the other oral antidiabetic agents. Using TZDs as monotherapy or as a component of combination therapy will contribute to improved glycemic control and should reduce the risk of diabetic complications. A number of studies have shown that a strategy of aggressive use of pharmacologic agents to achieve glycemic control is associated with cost benefits.

Animals↗