Person-first language in diabetes and obesity scientific publications.

AIMS: We aimed to quantify the use of person-first language (PFL) among scholarly articles focusing on diabetes or obesity. METHODS: PFL and condition-first language (CFL) terms for diabetes and obesity (e.g. diabetic, obese) were identified from existing guidelines and a review of the literature. Exact phrase literature searches were conducted between 2011 and 2020 and results were categorised as PFL, CFL or both. RESULTS: Among diabetes articles, 43% used PFL, 40% used CFL and 17% contained both. Among obesity articles, 0.5% used PFL, 99% used CFL and 0.2% used both. The use of PFL increased by 3% per year for diabetes articles, compared to 117% for obesity articles. The rate of adoption of PFL in diabetes articles was unchanged in 2018-2020 compared to the 3 years prior. CONCLUSIONS: While the use of person-first language in diabetes articles had increased over the review period, its rate of adoption has started to slow. Conversely, the use of PFL in obesity articles is nascent and increasing.

Characteristics and Weight Loss Practices From a Cohort of 20,000 Patients Using Direct-to-Consumer Telehealth: Observational Cross-sectional Study.

BACKGROUND: Despite the increasing prevalence of obesity, the use of pharmacotherapy treatment remains low. Telehealth platforms have the potential to facilitate access to pharmacotherapy interventions, but little is known about telehealth patients. OBJECTIVE: This study describes a large patient population taking Plenity, an oral superabsorbent hydrogel (OSH) used in the treatment of excess weight or obesity (BMI 25-40 kg/m2). The analysis compared differences in weight loss practices and in-person access to obesity care among telehealth patients with preobesity and obesity. METHODS: This was a cross-sectional assessment of a random sample of 20,000 telehealth patients who completed a structured, web-based visit and received at least one prescription of OSH. Patients were eligible to receive care via telehealth if they were adults, were not pregnant, and had a BMI ≥25 kg/m2. During the visit, patients provided baseline health information including comorbidities, diet, and exercise habits. Their zip code of residence was used to determine their proximity to an obesity medicine provider. Descriptive statistical analysis and tests of differences (chi-square and 2-tailed t tests) were used to compare patients with preobesity (BMI 25-29.9 kg/m2) and obesity (BMI 30-40 kg/m2). RESULTS: Most (15,576/20,000, 77.88%) of the cohort were female, with a mean age of 44 (SD 11) years and a mean BMI of 32.4 (SD 4.1) kg/m2. Among the cohort, 32.13% (6426/20,000) had preobesity, and 40.18% (8036/20,000) of all patients had ≥1 weight-related comorbidity. Almost all (19,732/20,000, 98.66%) patients attempted 1 weight loss method before OSH and half (10,067/20,000, 50.34%) tried ≥4 different methods. Exercise and low-calorie diets were the most attempted weight loss methods, and 28.76% (5752/20,000) of patients reported a prior prescription of weight loss medication. Patients with obesity were more likely than patients with preobesity to have previously tried commercial weight loss plans (7294/13,574, 53.74% vs 2791/6426, 43.43%; P<.001), specialized diets (8493/13,574, 62.57% vs 3799/6426, 59.12%; P<.001), over-the-counter supplements (6807/13,574, 50.15% vs 2876/6426, 44.76%; P<.001), and prescription weight loss medications (4407/13,574, 32.47% vs 1345/6426, 20.93%; P<.001). Females were more likely to seek treatment for preobesity (5332/15,576, 34.23% vs 1094/4424, 24.73% male; P<.001) and reported fewer comorbidities (5992/15,576, 38.47% vs 2044/4424, 46.2% male; P<.001), despite >90% of both sexes reporting the belief that excess weight negatively affected their health (14,247/15,576, 91.47% female participants, 4116/4424, 93.04% male participants). Moreover, 29.25% (5850/20,000) of patients lived in the same zip code and 85.15% (17,030/20,000) lived in the same county as an obesity medicine provider. CONCLUSIONS: Data from this large patient cohort supports the potential for telehealth to provide prescriptive weight management treatment to a population seeking care. Patients with preobesity are an undertreated population who actively seek new weight management options. Female participants sought weight management treatment earlier in the disease continuum than males, despite reporting fewer comorbidities.

Recent advances in therapies utilizing superabsorbent hydrogel technology for weight management: A review.

Long-term therapeutic benefit of treatments for weight management in patients with overweight (also termed preobesity) or obesity may be limited by variable safety, tolerability, and efficacy profiles, and patient adherence to treatment regimens. There is a medical need for nonsystemic treatments that promote weight loss in patients with overweight or early obesity. This report reviews four different approaches of utilizing superabsorbent hydrogel technology for weight management at varying stages of preclinical and clinical development. The first is a nonsystemic, oral superabsorbent hydrogel created from naturally derived building blocks used in foods (cellulose-based), designed to mix homogenously with and change the properties of the ingested meal throughout the gastrointestinal tract (stomach and small intestine). This is the first-in-class to be cleared by the Food and Drug Administration (FDA) to aid in weight-management for adults with BMI of 25-40 kg/m2 in conjunction with diet and exercise. In contrast, the other three approaches in development utilize superabsorbent hydrogel technologies to support an intragastric balloon-like structure, solely occupying space in the stomach and displacing the meal: (1) a pufferfish-inspired device; (2) Epitomee, a pH-sensitive self-expanding hydrogel device; and (3) a light-degradable hydrogel used to control balloon deflation. These new approaches that utilize superabsorbent hydrogel technology offer a wide range of clinical applicability and have the potential to broaden the weight management treatment landscape. Over time, increasing the number of patients treated with superabsorbent hydrogel technologies will provide important information on long-term efficacy and safety.

Oral Superabsorbent Hydrogel (Plenity) for Weight Management.

OBJECTIVE: To describe the mechanism, clinical trial data, adverse effects, and potential role in therapy of an oral superabsorbent hydrogel (OSH) for weight management. DATA SOURCES: A literature search was completed using MEDLINE and Google Scholar using the following search terms: oral superabsorbent hydrogel, Plenity, and Gelesis100 (September 1999 to July 2020). Abstracts and posters were identified from relevant scientific congress archives and published supplements. STUDY SELECTION AND DATA EXTRACTION: All available studies were considered. Only human studies were used for drug interaction, efficacy, and safety data. DATA SYNTHESIS: OSH is a first-in-class, nonsystemic agent for weight management. It is indicated for use in patients with a body mass index (BMI) of 25 to 40 kg/m2 regardless of comorbidity status. OSH functions primarily through space occupancy in the stomach and small intestine. Studies have demonstrated that OSH has modest weight loss efficacy and a favorable safety profile, with no significant difference in overall adverse events compared with placebo. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: OSH is one of the only prescription antiobesity therapeutics (AOTs) that can be utilized in overweight patients with BMI equal to 25 to 30 kg/m2, regardless of comorbidity status. Given its nonsystemic mechanism of action and safety profile, OSH may help shift the focus of weight management toward patients with a lower BMI. CONCLUSIONS: OSH offers a nonsystemic approach to weight management for patients who are diagnosed with overweight or obesity. As an alternative option to current pharmacological AOTs, OSH may address an existing clinical gap in weight management.

CSP01, a Novel Superabsorbent Hydrogel, Reduces Colonic Transit Time in Patients With Chronic Idiopathic Constipation in a Randomized, Double-blind, Controlled Pilot Clinical Trial.

Background/Aims: CSP01 is a novel superabsorbent hydrogel that absorbs gastrointestinal fluids and maintains high viscoelastic properties into the colon, where these fluids are released. Methods: We conducted a single-center, randomized, double-blind, parallel-group, placebo-controlled pilot study comparing change in colonic transit time (CTT) among patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) treated for 21 days with either CSP01 hydrogel, active control (carboxymethylcellulose [CMC]) or placebo. CTT was measured using wireless motility capsule transit testing at pre-treatment and end-of-treatment. The primary endpoint was change in CTT. Results: Forty subjects (20 CSP01, 11 CMC, 9 placebo) were enrolled and 38 completed the study. There was no significant change in mean CTT by treatment group (P = 0.297). In the placebo group, CTT increased by 15.3 minutes between baseline and end of treatment, increased by 366.4 minutes for CMC, and decreased by 727.4 minutes for CSP01. In post hoc analyses among those with CIC, mean CTT decreased by 1079 minutes for CSP01 (P = 0.025 compared to placebo), 919 minutes for CMC (P = 0.117 compared to placebo) and increased by 1113 minutes for placebo. Among patients with IBS-C, there was no significant difference in change in CTT for any treatment group. One subject in the CSP01 arm developed back pain attributed to constipation and withdrew without a second CTT measurement; there were no other adverse events. Conclusion: CSP01 significantly decreased CTT compared to placebo among patients with CIC, but not in patients with IBS-C.

A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.

OBJECTIVE: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥  27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges.

BACKGROUND: Lipodystrophy (LD; non-human immunodeficiency virus [HIV]-associated) syndromes are a rare body of disorders for which true prevalence is unknown. Prevalence estimates of rare diseases are important to increase awareness and financial resources. Current qualitative and quantitative estimates of LD prevalence range from ~0.1 to 90 cases/million. We demonstrate an approach to quantitatively estimate LD prevalence (all, generalized, and partial) through a search of 5 electronic medical record (EMR) databases and 4 literature searches. METHODS: EMR and literature searches were conducted from 2012 to 2014. For the EMR database searches (Quintiles, IMS LifeLink, General Electric Healthcare, and Humedica EMR), LD cases were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 272.6 (United Kingdom General Practice Research Database used other diagnostic codes to identify LD) plus additional LD-associated clinical characteristics (patients with HIV or documented HIV treatment were excluded). Expert adjudication of cases was used for the Quintiles database only. Literature searches (PubMed and EMBASE) were conducted for each of the 4 major LD subtypes. Prevalence estimates were determined by extrapolating the total number of cases identified for each search to the database population (EMR search) and European population (literature search). RESULTS: The prevalence range of all LD across all EMR databases was 1.3-4.7 cases/million. For the adjudicated Quintiles search, the estimated prevalence of diagnosed LD was 3.07 cases/million (95% confidence interval [CI], 2.30-4.02), 0.23 cases/million (95% CI, 0.06-0.59) and 2.84 cases/million (95% CI, 2.10-3.75) for generalized lipodystrophy (GL) and partial lipodystrophy (PL), respectively. For all literature searches, the prevalence of all LD in Europe was 2.63 cases/million (0.96 and 1.67 cases/million for GL and PL, respectively). CONCLUSION: LD prevalence estimates are at the lower range of previously established numbers, confirming that LD is an ultra-rare disease. The establishment of diagnostic criteria and coding specific to the 4 major LD subtypes and future studies/patient registries are needed to further refine our estimates.

In silico design of optimal ratio for co-administration of pramlintide and insulin in type 1 diabetes.

BACKGROUND: The ability to simulate in silico experiments is crucial for fast and cost-effective preliminary studies prior to clinical trials. We present an in silico approach to the design of optimal pramlintide-to-insulin (P/I) ratios, using our computer simulator of the human metabolic system, with a population of virtual adult type 1 diabetes mellitus patients and with individual parameters modified to account for the dynamic effects of pramlintide. MATERIALS AND METHODS: A model of pramlintide action on gastric emptying was built using data of 15 type 1 diabetes mellitus subjects studied twice with a standardized dual-tracer meal on placebo and pramlintide, which was incorporated in our type 1 diabetes simulator. Extensive in silico experiments on 100 virtual subjects were performed to optimize the co-administration of pramlintide and insulin prior to its submission to clinical trials; several P/I ratios were tested in terms of efficacy, in attenuating postprandial hyperglycemia, and in hypoglycemia safety. RESULTS: In silico experiments estimated the optimal P/I ratio to be 9 µg of pramlintide per unit (U) of insulin. Additional simulations narrowing the investigated range indicated that P/I ratios of 8 and 10 µg/U would achieve similar performance. Moreover, simulation results suggested that in clinical trials, insulin boluses should be reduced by approximately 21% at a P/I ratio of 9 µg/U to account for the effects of pramlintide and avoid postprandial hypoglycemia. CONCLUSIONS: We can assert that a valid simulation model of pramlintide action was developed, leading to in silico estimation of optimal pramlintide:insulin co-administration ratio. Clinical trials will confirm (or adjust) this initial estimation.

Treatment with exenatide once weekly or twice daily for 30 weeks is associated with changes in several cardiovascular risk markers.

BACKGROUND: Cyslipidemia and type 2 diabetes are two of the most significant risk factors for the development of cardiovascular disease. Measurement of lipoprotein subclasses provides important information about derangements in lipid metabolism and helps refine cardiovascular risk assessment. Exenatide, a glucagon-like peptide 1 receptor agonist, improved glycemic control, obesity, hypertension, and dyslipidemia in patients with type 2 diabetes in clinical trials. METHODS: In the DURATION-1 trial, patients with type 2 diabetes were treated with exenatide once weekly or twice daily for 30 weeks. This post hoc analysis evaluated the impact of exenatide on lipoprotein subclasses in 211 DURATION-1 patients using vertical auto profile methodology and the Statistical Package for the Social Sciences general linear model adjusted for glycosylated hemoglobin (HbA(1c)) and weight. RESULTS: Baseline lipids and high sensitivity C-reactive protein were normal overall based on the standard lipid panel. Once-weekly exenatide reduced apolipoprotein B and the apolipoprotein B to apolipoprotein A1 ratio (P < 0.05), independent of glycemic improvement and weight loss. A significant shift in lipoprotein pattern away from small, dense low-density lipoprotein-4 cholesterol was also observed (P < 0.05). Exenatide once weekly increased high-density lipoprotein-2 cholesterol, even after adjustment for changes in HbA(1c) and weight (P < 0.05). Triglycerides, very low-density lipoprotein cholesterol, and high sensitivity C-reactive protein were reduced with both the once-weekly and twice-daily exenatide regimens (P < 0.05). CONCLUSION: In this post hoc analysis, exenatide significantly improved a number of cardiovascular risk markers. Continuous exenatide exposure with exenatide once weekly elicited a greater response than did immediate-release exenatide twice daily, generally independent of glycemic improvement and weight loss. Thus, in addition to improving glycemic control, exenatide induced favorable changes in lipid and lipoprotein metabolism and decreased systemic inflammation.

WITHDRAWN: Dieting to reduce body weight for controlling hypertension in adults.

BACKGROUND: As early as the 1920's, researchers noted a relationship between caloric restriction, weight loss and a decreased incidence of hypertension (Terry 1922, Preble 1923, Bauman 1928, Master 1929). In 1988 a meta-analysis of aggregate data from 12 prospective studies, including 5 randomized controlled trials (RCTs), found that on average each 1 kilogram decrease in body weight in obese hypertensive patients was associated with a 2.4 mm Hg systolic and 1.5 mm Hg diastolic decrease in blood pressure (Staessen 1988). Blood pressure reductions were not dependent upon degree of baseline obesity.This review aims to: 1) update the work of Staessen (Staessen 1988) looking specifically at randomized controlled trials, and 2) assess whether any of the trials assess effects of weight-reducing diets on clinical outcomes such as quality of life, morbidity or mortality. OBJECTIVES: Evaluate whether weight-loss diets are more effective than regular diets or other antihypertensive therapies in controlling blood pressure and preventing morbidity and mortality in hypertensive adults. SEARCH STRATEGY: MEDLINE and The Cochrane Library were searched through November 1997. Trials known to experts in the field were included through June 1998. SELECTION CRITERIA: For inclusion in the review, trials were required to meet each of the following criteria: 1) randomized controlled trials with one group assigned to a weight-loss diet and the other group assigned to either normal diet or antihypertensive therapy; 2) ambulatory adults with a mean blood pressure of at least 140 mm Hg systolic and/or 90 mm Hg diastolic; 3) active intervention consisting of a calorie-restricted diet intended to produce weight loss (excluded studies simultaneously implementing multiple lifestyle interventions where the effects of weight loss could not be disaggregated); and 4) outcome measures included weight loss and blood pressure. DATA COLLECTION AND ANALYSIS: Studies were dual abstracted by two independent reviewers using a standardized form designed specifically for this review. The primary mode of analysis was qualitative; graphs of effect sizes for individual studies were also used. MAIN RESULTS: Eighteen trials were found. Only one small study of inadequate power reported morbidity and mortality outcomes. None addressed quality of life or general well being issues. In general, participants assigned to weight-reduction groups lost weight compared to control groups.Six trials involving 361 participants assessed a weight-reducing diet versus a normal diet. The data suggested weight loss in the range of 4% to 8% of body weight was associated with a decrease in blood pressure in the range of 3 mm Hg systolic and diastolic. Three trials involving 363 participants assessed a weight-reducing diet versus treatment with antihypertensive medications. These suggested that a stepped-care approach with antihypertensive medications produced greater decreases in blood pressure (in the range of 6/5 mm Hg systolic/diastolic) than did a weight-loss diet. Trials that allowed adjustment of participants' antihypertensive regimens suggested that patients required less intensive antihypertensive drug therapy if they followed a weight-reducing diet. Data was insufficient to determine the relative efficacy of weight-reduction versus changes in sodium or potassium intake or exercise. AUTHORS' CONCLUSIONS: Weight-reducing diets in overweight hypertensive persons can affect modest weight loss in the range of 3-9% of body weight and are probably associated with modest blood pressure decreases of roughly 3 mm Hg systolic and diastolic. Weight-reducing diets may decrease dosage requirements of persons taking antihypertensive medications.

Diabetic endovascular disease: role of coronary artery revascularization.

This century brings a pandemic of diabetes mellitus, with marked increases in early-accelerated atherosclerosis. When asymptomatic patients with diabetes present for evaluation, they have more extensive coronary atherosclerosis, lower ejection fractions, higher rates of previous cardiac events, and more silent ischemia than the normal population. The challenge faced by clinicians is to accurately identify asymptomatic patients with diabetes who have significant coronary ischemia that would benefit from revascularization. Diabetic endovascular disease has all the high-risk features to promote atherosclerosis and coronary occlusion: hyperglycemia-induced endothelial dysfunction, impaired fibrinolysis, increased platelet aggregation, plaque instability, dysfunctional arterial remodeling, and fibrotic and calcified coronary arteries. The optimal revascularization strategy for patients with diabetes is an ongoing debate. The advent of drug-eluting stents has changed the landscape, and some have suggested that the current role of coronary artery bypass grafting may be reduced by as much as 46%. Unfortunately, there is limited evidence from randomized, controlled trials that reflects current practice and could guide clinicians in making the best choices for patients with diabetes and coronary disease. It is hoped that ongoing trials--including Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM), and Coronary Artery Revascularisation in Diabetes (CARDia)--will answer many of the remaining questions. Still, the best treatment includes lifestyle modification and early prevention strategies with global risk reduction.

Exenatide: from the Gila monster to the pharmacy.

OBJECTIVE: To explain the incretin concept and review the pharmacology and clinical utility of exenatide (Byetta-Amylin; Lilly), a new agent for the treatment of patients with type 2 diabetes mellitus, and provide pharmacists with information necessary for counseling patients in the use of exenatide. DATA SOURCES: Review articles, clinical trials, and data on file with the manufacturers. STUDY SELECTION: By the authors. DATA EXTRACTION: By the authors. DATA SYNTHESIS: Exenatide is a synthetic form of a protein found in the saliva of the Gila monster that mimics the action of glucagon-like peptide-1, an incretin important in glucose homeostasis and deficient in patients with diabetes mellitus. Three pivotal clinical trials of exenatide as an add-on therapy in patients with type 2 diabetes mellitus who were unable to achieve glycemic control with maximum doses of metformin, sulfonylurea, or these drugs in combination demonstrated significant reductions in glycosylated hemoglobin (A1C) levels following twice-daily self-injection of exenatide compared with placebo. Weight loss was observed in patients in conjunction with A1C improvement, which occurred without additional patient instruction, intentional caloric deficit, or exercise. Mild-to-moderate nausea was the most common adverse event with exenatide treatment, occurring at the beginning of therapy, lessening over time, and reduced by titration of the dose. CONCLUSION: Exenatide offers a wide range of beneficial glucoregulatory effects, including enhancement of glucose-dependent insulin secretion, restoration of first-phase insulin response, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. These positive effects depend on the patient's understanding of the proper administration technique and timing, the need for continued adherence, and what to do if adverse effects occur, all elements that can be conveyed by pharmacists in their counseling and education of patients with type 2 diabetes mellitus.

Incretin mimetics and dipeptidyl peptidase-IV inhibitors: potential new therapies for type 2 diabetes mellitus.

The emergence of the glucoregulatory hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide has expanded our understanding of glucose homeostasis. In particular, the glucoregulatory actions of the incretin hormone GLP-1 include enhancement of glucosedependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. Two approaches have been developed to overcome rapid degradation of GLP-1. One is the use of agents that mimic the enhancement of glucose-dependent insulin secretion, and potentially other antihyperglycemic actions of incretins, and the other is the use of dipeptidyl peptidase-IV inhibitors, which reduce the inactivation of GLP-1, increasing the concentration of endogenous GLP-1. The development of incretin mimetics and dipeptidyl peptidase-IV inhibitors opens the door to a new generation of antihyperglycemic agents to treat several otherwise unaddressed pathophysiologic defects of type 2 diabetes mellitus. We review the physiology of glucose homeostasis, emphasizing the role of GLP-1, the pathophysiology of type 2 diabetes mellitus, the clinical shortcomings of current therapies, and the potential of new therapies -- including the newly approved incretin mimetic exenatide -- that elicit actions similar to those of GLP-1.

The good fat hormone: adiponectin and cardiovascular disease.

New treatments for heart disease continue to be of paramount importance. The newest pandemic facing us is the rise of obesity and diabetes. One new area of research in the field of metabolism is the hormone adiponectin, which is secreted by fat cells. For the most part, this compound seems more likely to be a part of basic science-oriented research; however, it deserves a much closer look. Many compounds such as high-density lipoprotein and others at first were simply markers of disease but later found to be much more important. During this short review, research from basic science to clinical cardiovascular events is discussed in relation to adiponectin.

Thiazolidinediones and cardiovascular disease.

Thiazolidinediones hold promise for reducing cardiovascular events and human atherosclerosis. Similar to statins and angiotensin-converting enzyme inhibitors, peroxisome proliferator activated receptor gamma (PPARgamma) exerts anti-inflammatory and antiatherosclerotic actions in the vessel wall. A number of clinical trials in subjects with or without diabetes have shown that thiazolidinedione therapy can reduce in-stent restenosis and delay progression of atherosclerosis measured by carotid artery ultrasound. PPARgamma directly promotes expression of ATP-binding cassette transporter G1, mediating cellular cholesterol efflux to high-density lipoproteins from macrophages, which may further explain the potential cardiovascular benefit of this class. Whether the benefits observed in animal models will translate in clinical practice is being evaluated in several large, randomized controlled trials.

A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors.

BACKGROUND: In patients with type 2 diabetes mellitus, all therapeutic options should be evaluated for their effect on cardiovascular risk factors, in addition to glycemic control. We conducted a meta-analysis of randomized controlled trials of pioglitazone hydrochloride and rosiglitazone maleate in patients with type 2 diabetes to evaluate their effect on glycemic control, lipids, blood pressure, and weight. METHODS: Randomized controlled trials of patients with type 2 diabetes that compared pioglitazone or rosiglitazone with placebo for 12 weeks were included. Primary analysis was to compare thiazolidinediones with placebo. Secondary analysis was to identify whether treatment with pioglitazone differed from rosiglitazone in any outcomes. We calculated weighted mean differences and 95% confidence intervals. RESULTS: Twenty-three randomized controlled trials were identified. Both thiazolidinediones demonstrated similar hemoglobin A(1c) level decreases of 1.0% to 1.5% and similar increases in body weight of approximately 3.0 kg. Pioglitazone significantly lowered triglyceride level (-40 mg/dL [-0.45 mmol/L]; 95% confidence interval [CI], -53 to -26 mg/dL [-0.60 to -0.29 mmol/L]), increased high-density lipoprotein cholesterol (HDL-C) level (+4.6 mg/dL [+0.12 mmol/L]; 95% CI, 3.6 to 5.5 mg/dL [0.09 to 0.14 mmol/L]), and showed neutral effect on low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels. Rosiglitazone significantly increased HDL-C level (+2.7 mg/dL [+0.07 mmol/L]; 95% CI, 2.0 to 3.4 mg/dL [0.05 to 0.09 mmol/L]), but increased LDL-C level (+15 mg/dL [+0.39 mmol/L]; 95% CI, 13 to 17 mg/dL [0.34 to 0.44 mmol/L]), total cholesterol level (+21 mg/dL [+0.54 mmol/L]; 95% CI, 18 to 25 mg/dL [0.47 to 0.65 mmol/L]), and demonstrated neutral effect on triglyceride level (-1.1 mg/dL [-0.12 mmol/L]; 95% CI, -14 to 12 mg/dL [-0.16 to 0.14 mmol/L]). No data were available on pioglitazone and blood pressure. Rosiglitazone had a neutral effect on systolic (-0.7 mm Hg; 95% CI, -2.6 to 1.1 mm Hg) and diastolic (-0.8 mm Hg; 95% CI, -1.8 to 0.3) blood pressure. CONCLUSIONS: Thiazolidinediones have similar effects on glycemic control and body weight. Pioglitazone produced a more favorable lipid profile. Head-to-head comparative trials as well as longer-term cardiovascular outcome studies are needed to determine whether there are differences in efficacy between the 2 thiazolidinediones.

Is the use of unfractionated heparin in acute coronary syndrome outmoded?

Because of the key role of thrombin in the pathogenesis of acute coronary syndrome (ACS), the appropriate selection of antithrombotic therapy is important. Unfractionated heparin (UFH) has been the agent of choice for decades. Unfortunately, UFH has a number of limitations related to its pharmacokinetic and pharmacodynamic properties. Low molecular weight heparins (LMWHs) are attractive alternatives to UFH for several reasons, including predictable anticoagulation and ease of administration. Two LMWHs (dalteparin and enoxaparin) have been approved as alternatives to UFH in patients presenting with unstable angina and non-ST-segment elevation myocardial infarction. Randomized, controlled trials, in addition to open-label series, indicate that LMWH can safely be the agent of choice with or without glycoprotein IIb/IIIa in the medical and upstream management of patients with ACS. Although the data are not definitive, several trials suggest that given intravenously, enoxaparin is safe as the sole antithrombotic agent in the catheterization laboratory.

Aggressive medical management of coronary artery disease versus mechanical revascularization.

The treatment of patients with stable angina has three goals: 1) minimize or eliminate ischemia (silent or symptomatic), 2) reduce morbidity, and 3) decrease mortality. Surgical and now angiographic revascularization procedures are increasingly popular approaches to the management of these patients. The results of randomized, controlled trials suggest that revascularization may not improve survival, but is useful to improve symptoms and exercise capacity. However, these trials are of limited value because they do not reflect current state of the art revascularization techniques or optimal medical management. Because many of these studies were conducted more than a decade ago, patients were recruited before the survival benefits of antiplatelet therapy, b-blockers, angiotensin-converting enzyme inhibitors, and aggressive lipid lowering were accepted. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial should help us determine the best approach in these patients. It is a multicenter, randomized trial comparing aggressive medical therapy with aggressive medical therapy with current state of the art percutaneous coronary intervention (PCI) for patients with stable coronary disease. The COURAGE protocol targets global risk reduction emphasizing 1) lifestyle modification, 2) maximal use of drugs to lower blood pressure to Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) VI goals, 3) maximal use of drugs to lower cholesterol to below National Cholesterol Education Program Adult Treatment Panel III goals for secondary prevention, and 4) maximal use of drug to alleviate anginal symptoms with or without the best interventional devices to conduct PCI.

Cardiovascular disease: much more aggressive in patients with type 2 diabetes.

It is estimated that 80% of individuals with type 2 diabetes die of coronary heart disease. Several factors have been found to contribute to the accelerated atherosclerosis present in diabetic patients. These include hyperglycemia-induced endothelial cell dysfunction, impaired fibrinolysis, increased platelet aggregation, and dysfunctional arterial remodeling. The evidence supports that a healthy lifestyle, statin drugs, angiotensin-converting enzyme inhibitors, and aspirin can modify these factors and slow the atherosclerosis process observed in type 2 diabetes. Because of the high prevalence of cardiovascular disease in people with type 2 diabetes, early cardiac testing is indicated. The optimal strategy for coronary revascularization in diabetic patients remains controversial and is discussed in detail in this review.