Joshua I. Barzilay

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY.

Abbreviations: A1C = hemoglobin A1C AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascular Risk in Diabetes ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure ACEI = angiotensinconverting enzyme inhibitor AGI = alpha-glucosidase inhibitor apo B = apolipoprotein B ARB = angiotensin II receptor blocker ASCVD = atherosclerotic cardiovascular disease BAS = bile acid sequestrant BMI = body mass index BP = blood pressure CHD = coronary heart disease CKD = chronic kidney disease CVD = cardiovascular disease DKA = diabetic ketoacidosis DPP-4 = dipeptidyl peptidase 4 EPA = eicosapentaenoic acid FDA = Food and Drug Administration GLP-1 = glucagon-like peptide 1 HDL-C = high-density-lipoprotein cholesterol LDL-C = low-densitylipoprotein cholesterol LDL-P = low-density-lipoprotein particle Look AHEAD = Look Action for Health in Diabetes NPH = neutral protamine Hagedorn OSA = obstructive sleep apnea SFU = sulfonylurea SGLT-2 = sodium glucose cotrans...

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): clinical center recruitment experience.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized clinical outcome trial of antihypertensive and lipid-lowering therapy in a diverse population (including substantial numbers of women and minorities) of 42,419 high-risk hypertensives aged > or = 55 years with a planned mean follow-up of 6 years. In this paper, we describe our experience in the identification, recruitment, and selection of clinical centers for this large simple trial capable of meeting the recruitment goals outlined for ALLHAT, and we highlight factors associated with clinical center performance. Over 135,000 recruitment brochures were mailed to physicians. Requests for information and application packets were received from 9351 (6.8%) interested investigators. A total of 1053 completed applications were received and 909 sites (86%) were eventually approved to join the trial. Of the approved sites, 278 either later declined participation or were never activated, and 8 were closed within a year for lack of enrollment. The final 623 randomizing centers exceeded the trials recruitment goal to enroll at least 40,000 participants into the trial, although the recruitment period was extended 1.5 years longer than planned. Fewer than a quarter of the sites (22.6%) were recruited from academic medical centers or Department of Veterans Affairs Medical Centers. More than half of the sites (54.7%) were private solo or group practices, which contributed 53% of randomized participants. Community health centers comprised about 8% of the ALLHAT sites and 2.9% were part of health maintenance organizations. More than 22% of the principal investigators reported that they had no previous clinical research experience. In summary, ALLHAT was successful in recruiting a diverse group of clinical centers to achieve its patient recruitment goals.

American Association of Clinical Endocrinologists' Comprehensive Diabetes Management Algorithm 2013 Consensus Statement - Executive Summary

Alan J. Garber, MD, PhD, FACE; Martin J. Abrahamson, MD; Joshua I. Barzilay, MD, FACE; Lawrence Blonde, MD, FACP, FACE; Zachary T. Bloomgarden, MD, MACE; Michael A. Bush, MD; Samuel Dagogo-Jack, MD, FACE; Michael B. Davidson, DO, FACE; Daniel Einhorn, MD, FACP, FACE; W. Timothy Garvey, MD; George Grunberger, MD, FACP, FACE; Yehuda Handelsman, MD, FACP, FACE, FNLA; Irl B. Hirsch, MD; Paul S. Jellinger, MD, MACE; Janet B. McGill, MD, FACE; Jeffrey I. Mechanick, MD, FACE, ECNU, FACN, FACP; Paul D. Rosenblit, MD, PhD, FACE, FNLA; Guillermo E. Umpierrez, MD, FACE; Michael H. Davidson, MD, FACC, FACP, FNLA

Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria

BACKGROUND The new fasting American Diabetes Association (ADA) criteria for the diagnosis of diabetes mellitus rely mainly on fasting blood glucose concentrations and use a lower cut-off value for diagnosis than the WHO criteria. We aimed to assess the sensitivity of these criteria for the detection of cardiovascular disease, the main complication of diabetes mellitus in the elderly. METHODS We did a cross-sectional and prospective analysis of 4515 participants of the Cardiovascular Health Study, an 8 year longitudinal study designed to identify factors related to the onset and course of cardiovascular disease in adults aged at least 65 years. We calculated the prevalence and incidence of cardiovascular disease for the ADA and WHO criteria. FINDINGS There was a higher prevalence of cardiovascular disease among individuals with impaired glucose or newly diagnosed diabetes by both criteria than among those with normal glucose concentrations. However, because fewer individuals had abnormal glucose states by the fasting ADA criteria (22.3%) than by the WHO criteria (46.8%), the number of cases of cardiovascular disease attributable to abnormal glucose states was a third of that attributable by the WHO criteria (53 vs 159 cases per 10,000). For the two sets of criteria, the relative risk for incident cardiovascular disease (mean follow-up 5.9 years) was higher in individuals with impaired glucose and newly diagnosed diabetes than in those with normal glucose. Individuals classified as normal by the fasting ADA criteria had a higher absolute number of incident events (455 of 581 events) than those classified as normal by the WHO criteria (269 of 581 events). Fasting ADA criteria were therefore less sensitive than the WHO criteria for predicting cardiovascular disease among individuals with abnormal glucose (sensitivity, 28% vs 54%). INTERPRETATION The new fasting ADA criteria seem to be less predictive than the WHO criteria for the burden of cardiovascular disease associated with abnormal glucose in the elderly.

Lactic Acidosis Rates in Type 2 Diabetes

OBJECTIVE To provide a context for the interpretation of lactic acidosis risk among patients using metformin, we measured rates of lactic acidosis in patients with type 2 diabetes before metformin was approved for use in the U.S. RESEARCH DESIGN AND METHODS Using electronic databases of hospital discharge diagnoses and laboratory results maintained by a large, nonprofit health maintenance organization (HMO), we identified possible lactic acidosis events in three geographically and racially diverse populations with type 2 diabetes. We then reviewed hard-copy clinical records to confirm and describe each event and determine its likely cause(s). RESULTS From <41,000 person-years of experience, we found four confirmed, three possible, and three borderline cases of lactic acidosis. In each case, we identified at least one severe medical condition that could have caused the acidosis. The annual confirmed event rate is similar to published rates of metformin-associated lactic acidosis. CONCLUSIONS Lactic acidosis occurs regularly, although infrequently, among persons with type 2 diabetes, at rates similar to its occurrence among metformin users. The medical conditions with which both metformin-associated and naturally occurring lactic acidosis cooccur are also its potential causes. The observed association between metformin and lactic acidosis may be coincidental rather than causal. This possibility merits further study.

American association of clinical endocrinologists' comprehensive diabetes management algorithm 2013 consensus statement

Alan J. Garber, MD, PhD, FACE; Martin J. Abrahamson, MD; Joshua I. Barzilay, MD, FACE; Lawrence Blonde, MD, FACP, FACE; Zachary T. Bloomgarden, MD, MACE; Michael A. Bush, MD; Samuel Dagogo-Jack, MD, FACE; Michael B. Davidson, DO, FACE; Daniel Einhorn, MD, FACP, FACE; W. Timothy Garvey, MD; George Grunberger, MD, FACP, FACE; Yehuda Handelsman, MD, FACP, FACE, FNLA; Irl B. Hirsch, MD; Paul S. Jellinger, MD, MACE; Janet B. McGill, MD, FACE; Jeffrey I. Mechanick, MD, FACE, ECNU, FACN, FACP; Paul D. Rosenblit, MD, PhD, FACE, FNLA; Guillermo E. Umpierrez, MD, FACE; Michael H. Davidson, MD, FACC, FACP, FNLA

AACE/ACE COMPREHENSIVE DIABETES MANAGEMENT ALGORITHM 2015

George Grunberger, MD, FACP, FACE Yehuda Handelsman, MD, FACP, FNLA, FACE Irl B. Hirsch, MD Paul S. Jellinger, MD, MACE Janet B. McGill, MD, FACE Je rey I. Mechanick, MD, FACP, FACE, FACN, ECNU Paul D. Rosenblit, MD, PhD, FNLA, FACE Guillermo Umpierrez, MD, FACP, FACE Michael H. Davidson, MD, Advisor Martin J. Abrahamson, MD Joshua I. Barzilay, MD, FACE Lawrence Blonde, MD, FACP, FACE Zachary T. Bloomgarden, MD, MACE Michael A. Bush, MD Samuel Dagogo-Jack, MD, DM, FRCP, FACE Michael B. Davidson, DO, FACE Daniel Einhorn, MD, FACP, FACE Je rey R. Garber, MD, FACP, FACE W. Timothy Garvey, MD, FACE TASK FORCE Alan J. Garber, MD, PhD, FACE, Chair AACE/ACE COMPREHENSIVE DIABETES MANAGEMENT ALGORITHM 2015

Coronary artery disease and coronary artery bypass grafting in diabetic patients aged ≥65 years (report from the Coronary Artery Surgery Study [CASS] registry)

A cohort of 317 diabetic patients, aged > or = 65 years, with angiographically proven coronary artery disease, was analyzed and followed for a mean of 12.8 years. Compared with 1,843 age-matched nondiabetic patients, diabetic patients were more likely to (1) have a higher number of coronary occlusions, (2) not be current smokers, (3) have higher systolic but lower diastolic blood pressures, (4) have evidence of peripheral vascular disease, and (5) be women. They did not differ significantly with respect to total cholesterol, family history of coronary artery disease, history of hypertension, or left ventricular hypertrophy. In the total elderly cohort, diabetes was found to be an independent predictor of mortality, conferring a 57.0% increased risk of death. Survival analysis showed that diabetic subjects consistently had higher mortality than nondiabetics. However, the relative survival benefit of coronary artery bypass graft surgery versus medical therapy was comparable in diabetic and nondiabetic patients. Surgical therapy conferred a reduction in mortality of 44%.

Autonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression.

Objective: To investigate prospectively whether autonomic nervous system (ANS) dysfunction and inflammation play a role in the increased cardiovascular disease (CVD)-related mortality risk associated with depression. Methods: Participants in the Cardiovascular Health Study (n = 907; mean age, 71.3 ± 4.6 years; 59.1% women) were evaluated for ANS indices derived from heart rate variability (HRV) analysis (frequency and time domain HRV, and nonlinear indices, including detrended fluctuation analysis (DFA1) and heart rate turbulence). Inflammation markers included C-reactive protein, interleukin-6, fibrinogen, and white blood cell count). Depressive symptoms were assessed, using the 10-item Centers for Epidemiological Studies Depression scale. Cox proportional hazards models were used to investigate the mortality risk associated with depression, ANS, and inflammation markers, adjusting for demographic and clinical covariates. Results: Depression was associated with ANS dysfunction (DFA1, p = .018), and increased inflammation markers (white blood cell count, p = .012, fibrinogen p = .043) adjusting for covariates. CVD-related mortality occurred in 121 participants during a median follow-up of 13.3 years. Depression was associated with an increased CVD mortality risk (hazard ratio, 1.88; 95% confidence interval, 1.23–2.86). Multivariable analyses showed that depression was an independent predictor of CVD mortality (hazard ratio, 1.72; 95% confidence interval, 1.05–2.83) when adjusting for independent HRV and inflammation predictors (DFA1, heart rate turbulence, interleukin-6), attenuating the depression-CVD mortality association by 12.7% (p < .001). Conclusion: Autonomic dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression, but a large portion of the predictive value of depression remains unexplained by these neuroimmunological measures. ANS = autonomic nervous system; LF = low frequency; CI = confidence interval; PNN50 = percent of successive RR interval differences >50 ms; CRP = C-reactive protein; CES-D = Centers for Epidemiological Studies Depression scale; PVC = premature ventricular complex; RMSSD = root mean square successive difference of RR intervals; CHS = Cardiovascular Health Study; CVD = cardiovascular disease; SD = standard deviation; DFA1 = detrended fluctuation analysis; SDNN = standard deviation of the NN intervals; HF = high frequency; HR = hazard ratio; HRT = heart rate turbulence; TO = turbulence onset; HRV = heart rate variability; TS = turbulence slope; VLF = very low frequency; IL-6 = interleukin-6; WBC = white blood cell count.

Adiponectin and Risk of Coronary Heart Disease in Older Men and Women

CONTEXT Despite established insulin-sensitizing and antiatherogenic preclinical effects, epidemiological investigations of adiponectin have yielded conflicting findings, and its relationship with coronary heart disease (CHD) remains uncertain. OBJECTIVE Our objective was to investigate the relationship between adiponectin and CHD in older adults. DESIGN, SETTING, AND PARTICIPANTS This was a case-control study (n = 1386) nested within the population-based Cardiovascular Health Study from 1992--2001. Controls were frequency-matched to cases by age, sex, race, subclinical cardiovascular disease, and center. MAIN OUTCOME MEASURES Incident CHD was defined as angina pectoris, percutaneous or surgical revascularization, nonfatal myocardial infarction (MI), or CHD death. A more restrictive CHD endpoint was limited to nonfatal MI and CHD death. RESULTS Adiponectin exhibited significant negative correlations with baseline adiposity, insulin resistance, dyslipidemia, inflammatory markers, and leptin. After controlling for matching factors, adjustment for waist to hip ratio, hypertension, smoking, alcohol, low-density lipoprotein cholesterol, creatinine, and leptin revealed a modestly increased risk of incident CHD with adiponectin concentrations at the upper end [odds ratio = 1.37 (quintile 5 vs. 1-4), 95% confidence interval 1.02-1.84]. This association was stronger when the outcome was limited to nonfatal MI and fatal CHD (odds ratio = 1.69, 95% confidence interval 1.23-2.32). The findings were not influenced by additional adjustment for weight change, health status, or cystatin C, nor were they abolished by adjustment for potential mediators. CONCLUSIONS This study shows an association between adiponectin and increased risk of first-ever CHD in older adults. Further research is needed to elucidate the basis for the concurrent beneficial and detrimental aspects of this relationship, and under what circumstances one or the other may predominate.