Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis.

CONTEXT: Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce. OBJECTIVE: We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM. METHOD: PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool. RESULTS: A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (-0.09%/mg), weight (-2.2 kg/mg), and TDI (-4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (-0.51% vs -0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse. CONCLUSION: Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.

Are serum cortisol measurements by immunoassays reliable?: A case series.

Routinely used automated immunoassays have been found to give unrealiable measurements of thyroid hormones in the presence of either high or low levels of thyroxine-binding globulin. Thyroid hormones are not the only analytes bound to specific binding proteins that are measured by immunoassays. Preliminary data from a series of cases, comparing IA measurements to those obtained by liquid chromatography-tandem mass spectrometry, reveal for the first time that IA measurements report falsely low (by an average of 27%) serum cortisol concentrations. Initial findings suggest that IA measurements of serum cortisol are affected by high concentrations of corticosteroid binding globulin.

Metabolically Healthy Obesity, Transition to Metabolic Syndrome, and Cardiovascular Risk.

BACKGROUND: Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal follow-up, with inconsistent results. OBJECTIVES: The authors hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of MetS explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality. METHODS: Among 6,809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) the authors used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (≥30 kg/m2) and MetS (International Diabetes Federation consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions. RESULTS: Compared with metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost one-half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.14 to 2.25), compared with those with stable MHO or healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR: 1.62; 95% CI: 1.27 to 2.07; 2 visits, OR: 1.92; 95% CI: 1.48 to 2.49; 3+ visits, OR: 2.33; 95% CI: 1.89 to 2.87; p value for trend <0.001) and MetS mediated approximately 62% (44% to 100%) of the relationship between obesity at any point during follow-up and CVD. CONCLUSIONS: Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.

Emergency department throughput: an intervention.

Shortening emergency department (ED) boarding time and managing hospital bed capacity by expediting the inpatient discharge process have been challenging for hospitals nationwide. The objective of this study is was to explore the effect of an innovative prospective intervention on hospital workflow, specifically on early inpatient discharges and the ED boarding time. The intervention consisted of a structured nursing "admission discharge transfer" (ADT) protocol receiving new admissions from the ED and helping out floor nursing with early discharges. ADT intervention was implemented in a 38-bed hospitalist run inpatient unit at an academic hospital. The study population consisted of 4486 patients (including inpatient and observation admissions) who were hospitalized to the medicine unit from March 2013-March 2014. Of these hospitalizations, 2259 patients received the ADT intervention. Patients' demographics, discharge and ED boarding data were collected for from March 4, 2013 to March 31, 2014 for both intervention and control groups (28 weeks each). Chi-square and unpaired t tests were utilized to compare population characteristics. Poisson regression analysis was conducted to estimate the association between intervention and hospital length of stay adjusted for differences in patient demographics. Mean age of the study population was 58.6 years, 23% were African Americans and 55% were women. A significant reduction in ED boarding time (p < 0.001) and improvement in early (before 2 PM) hospital discharges (p = 0.01) were noticed among patients in the intervention groups. There was a slight but significant reduction in hospital length of stay for observation patients in the intervention group; however, no such difference was noted for inpatient admissions. Our study showed that dedicating nursing resources towards ED-boarded patients and early inpatient discharges can significantly improve hospital workflow and reduce hospital length of stay.

Predictors of response to cardiac resynchronization therapy: A systematic review.

BACKGROUND: Multiple studies have sought to determine variables associated with improved "response" to cardiac resynchronization therapy(CRT). Such variables, however, are often derived from inadequately controlled, single center cohort studies calling external validity into question. We sought to determine predictors of response to CRT-D and CRT-P utilizing the methods of systematic review. METHODS: We searched MEDLINE, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1, 1995, as this is the date of first article reporting use of CRT through October 20, 2014. Paired investigators independently screened search results to assess eligibility. For inclusion, investigators abstracted data sequentially and assessed risk of bias independently. Investigators graded the strength of evidence as a group. RESULTS: We identified 13,015 unique citations of which 11,897 were excluded during the abstract screen. During the full-text screening, we excluded 1118 citations. 12 studies reported in 15 articles were included in this review. A left bundle branch (LBBB) morphology, non-ischemic cardiomyopathy (NICM), and female gender were generally associated with improved outcomes following CRT-D. Sinus rhythm (as compared to atrial fibrillation) and a wider QRS duration were associated with improved outcomes following CRT-D albeit with a lower strength of evidence. There was insufficient evidence to determine predictors of outcomes in patients undergoing CRT-P. CONCLUSIONS: A native LBBB, NICM, female gender, sinus rhythm, and a wider QRS duration are associated with improved outcomes following CRT-D implant.

Association of sex hormones with carotid artery distensibility in men and postmenopausal women: multi-ethnic study of atherosclerosis.

The decline in carotid distensibility with age is steeper in women than in men, however, the correlates of this sex difference are not known. We examined the association of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone-binding globulin, in 2783 postmenopausal women and 2987 men aged 45 to 84 years at the Multi-Ethnic Study of Atherosclerosis baseline examination. Carotid artery lumen diameters by ultrasound and brachial artery blood pressures were measured at systole and diastole. Regression models to determine the association of carotid distensibility coefficient and lumen diameter with sex-specific quartiles of sex hormones were adjusted for age, race, height, weight, diabetes mellitus, current smoking, antihypertensive medication use, total and high-density lipoprotein cholesterol levels, and hormone replacement therapy in women. A higher DC indicates a more distensible vessel. In women, higher dehydroepiandrosterone (P=0.008) and lower sex hormone-binding globulin (P=0.039) were associated with lower distensibility; higher dehydroepiandrosterone and lower estradiol were associated with smaller carotid diameters. In men, higher Bio-T (P=0.009) and lower estradiol (P=0.007) were associated with greater distensibility and also with smaller diameters (P=0.012 and 0.002, respectively). An androgenic internal milieu is associated with lesser carotid distensibility and diameter remodeling in women, but the opposite is true for men. Higher levels of estradiol are associated with smaller carotid diameters in both the sexes. Future longitudinal and experimental studies are needed to reveal the mechanism and clinical consequences of these associations.

Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis intensive glucose control in type 2 diabetes.

BACKGROUND: Aggressive glycemic control has been hypothesized to prevent renal disease in patients with type 2 diabetes mellitus. A systematic review was conducted to summarize the benefits of intensive vs conventional glucose control on kidney-related outcomes for adults with type 2 diabetes. METHODS: Three databases were systematically searched (January 1, 1950, to December 31, 2010) with no language restrictions to identify randomized trials that compared surrogate renal end points (microalbuminuria and macroalbuminuria) and clinical renal end points (doubling of the serum creatinine level, end-stage renal disease [ESRD], and death from renal disease) in patients with type 2 diabetes receiving intensive glucose control vs those receiving conventional glucose control. RESULTS: We evaluated 7 trials involving 28 065 adults who were monitored for 2 to 15 years. Compared with conventional control, intensive glucose control reduced the risk for microalbuminuria (risk ratio, 0.86 [95% CI, 0.76-0.96]) and macroalbuminuria (0.74 [0.65-0.85]), but not doubling of the serum creatinine level (1.06 [0.92-1.22]), ESRD (0.69 [0.46-1.05]), or death from renal disease (0.99 [0.55-1.79]). Meta-regression revealed that larger differences in hemoglobin A1c between intensive and conventional therapy at the study level were associated with greater benefit for both microalbuminuria and macroalbuminuria. The pooled cumulative incidence of doubling of the serum creatinine level, ESRD, and death from renal disease was low (<4%, <1.5%, and <0.5%, respectively) compared with the surrogate renal end points of microalbuminuria (23%) and macroalbuminuria (5%). CONCLUSIONS: Intensive glucose control reduces the risk for microalbuminuria and macroalbuminuria, but evidence is lacking that intensive glycemic control reduces the risk for significant clinical renal outcomes, such as doubling of the serum creatinine level, ESRD, or death from renal disease during the years of follow-up of the trials.

Acute changes in N-terminal pro-B-type natriuretic peptide during hospitalization and risk of readmission and mortality in patients with heart failure.

The level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor of adverse events in patients with heart failure. We examined the relation between acute changes in NT-proBNP during a single hospitalization and subsequent mortality and readmission. The data from a cohort of 241 consecutive patients aged ≥ 25 years who had been admitted to an urban tertiary care hospital with a primary diagnosis of heart failure were analyzed. Creatinine and NT-proBNP were measured at admission and at discharge of the first admission. The patient demographics, co-morbidities, and length of stay were collected. The patients were prospectively grouped into 2 categories according to the acute changes in NT-proBNP: a decrease of ≥ 50% or <50% from admission to discharge. The primary composite outcome was readmission or death within 1 year of the first hospital admission. The unadjusted hazard ratio of readmission/death was 1.40 (95% confidence interval 0.97 to 2.01; p = 0.07) for those with a < 50% decrease in NT-proBNP compared to their counterparts with a ≥ 50% decrease. After adjustment for age, gender, race, and admission creatinine and NT-proBNP, the risk of readmission/death was 57% greater for those with a < 50% decrease (hazard ratio 1.57, 95% confidence interval 1.08 to 2.28; p = 0.02). An adjustment for co-morbidity, length of stay, and left ventricular ejection fraction did not significantly change this relation. Reductions in NT-proBNP of < 50% during an acute hospitalization for heart failure might be associated with an increased hazard of readmission/death, independent of age, gender, race, creatinine, admission NT-proBNP, co-morbidities, left ventricular ejection fraction, and length of stay. In conclusion, patients with a < 50% reduction in NT-proBNP might benefit from more intensive medical treatment, monitoring, and follow-up.

Atherosclerotic cardiovascular disease screening in adults: American College Of Preventive Medicine position statement on preventive practice.

CONTEXT: Atherosclerotic cardiovascular diseases, including coronary heart disease (CHD), carotid artery stenosis (CAS), peripheral artery disease (PAD), and abdominal aortic aneurysm (AAA), affect millions of U.S. adults and are leading causes of morbidity and mortality. There is some uncertainty regarding the utility of certain screening tests for prevention of cardiovascular morbidity and mortality. EVIDENCE ACQUISITION: Current guidelines and studies pertaining to CHD, CAS, PAD, and AAA screening in the adult population were reviewed. EVIDENCE SYNTHESIS: CHD risk can be estimated by the Framingham Risk Score (FRS), which is valuable in identifying high-risk asymptomatic adults who may benefit from preventive treatments. There is moderate certainty that the benefits of screening do not outweigh the harms for individuals with asymptomatic CAS. The potential harms associated with routine PAD screening in asymptomatic adults are also likely to exceed benefits. Ultrasonography is a safe, noninvasive, and reliable screening test used to identify AAAs for treatment in men aged >65 years who have ever smoked. CONCLUSIONS: American College of Preventive Medicine (ACPM) recommends CHD risk assessment using the FRS to guide risk-based therapy. ACPM does not recommend routine screening of the general adult population using electrocardiogram, exercise-stress testing, computed tomography scanning, ankle-brachial index, carotid intima medial thickness, or emerging risk factors, including high-sensitivity C-reactive protein (hs-CRP). ACPM does not recommend routine screening of the general adult population for CAS or PAD. ACPM recommends one-time AAA screening in men aged 65-75 years who have ever smoked. Routine AAA screening in women is not recommended.

Usefulness of cystatin C and prognosis following admission for acute heart failure.

Cystatin C is a novel marker of renal function that has been found to predict adverse cardiovascular outcomes in ambulatory patients. The aim of this study was to investigate whether this biomarker predicts the length of hospitalization and adverse outcomes in patients hospitalized for heart failure. Two hundred forty consecutive patients aged > or =25 admitted to Johns Hopkins Hospital with exacerbations of heart failure were prospectively enrolled. Cystatin C levels were measured on admission. Patients were followed for 1 year. The primary outcome measure was the length of hospitalization. Secondary outcomes included all-cause mortality and readmission for heart failure. Cystatin C showed no significant association with the length of hospitalization. Patients in the highest quartile (quartile 4) of cystatin C level were at increased risk for death (hazard ratio 2.07 for quartile 4 vs quartiles 1 to 3, p = 0.01) and death or rehospitalization (hazard ratio 1.61 for quartile 4 vs quartiles 1 to 3, p = 0.01). The association between cystatin C and the combined end point of death or rehospitalization during 1-year follow-up remained significant after adjusting for age, race, gender, co-morbidities, and creatinine. Cystatin C was more predictive of these end points than creatinine, and the combination of cystatin C and creatinine was more predictive than either variable alone. In conclusion, cystatin C may be useful in addition to creatinine for predicting outcomes after admission for acute heart failure exacerbations.