Timothy S. Bailey

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY - CLINICAL PRACTICE GUIDELINES FOR DEVELOPING A DIABETES MELLITUS COMPREHENSIVE CARE PLAN - 2015

The American Association of Clinical Endocrinologists/American College of Endocrinology Medical Guidelines for Clinical Practice are systematically developed statements to assist healthcare professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances. Abbreviations: A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACCORD = Action to Control Cardiovascu...

One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial

Aim:  The aim of this study was to compare the efficacy and safety of once‐daily human glucagon‐like peptide‐1 analogue liraglutide with dipeptidyl peptidase‐4 inhibitor sitagliptin, each added to metformin, over 52 weeks in individuals with type 2 diabetes.

Reduction in Duration of Hypoglycemia by Automatic Suspension of Insulin Delivery: The In-Clinic ASPIRE Study

BACKGROUND The efficacy of automatic suspension of insulin delivery in induced hypoglycemia among subjects with type 1 diabetes was evaluated. SUBJECTS AND METHODS In this randomized crossover study, subjects used a sensor-augmented insulin pump system with a low glucose suspend (LGS) feature that automatically stops insulin delivery for 2 h following a sensor glucose (SG) value ≤70 mg/dL. Subjects fasted overnight and exercised until their plasma glucose (measured with the YSI 2300 STAT Plus™ glucose and lactate analyzer [YSI Life Sciences, Yellow Springs, OH]) value reached ≤85 mg/dL on different occasions separated by washout periods lasting 3-10 days. Exercise sessions were done with the LGS feature turned on (LGS-On) or with continued insulin delivery regardless of SG value (LGS-Off). The order of LGS-On and LGS-Off sessions was randomly assigned. YSI glucose data were used to compare the duration and severity of hypoglycemia from successful LGS-On and LGS-Off sessions and to estimate the risk of rebound hyperglycemia after pump suspension. RESULTS Fifty subjects attempted 134 sessions, 98 of which were successful. The mean±SD hypoglycemia duration was less during LGS-On than during LGS-Off sessions (138.5±76.68 vs. 170.7±75.91 min, P=0.006). During LGS-On compared with LGS-Off sessions, mean nadir YSI glucose was higher (59.5±5.72 vs. 57.6±5.69 mg/dL, P=0.015), as was mean end-observation YSI glucose (91.4±41.84 vs. 66.2±13.48 mg/dL, P<0.001). Most (53.2%) end-observation YSI glucose values in LGS-On sessions were in the 70-180 mg/dL range, and none was >250 mg/dL. CONCLUSIONS Automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia without causing rebound hyperglycemia.

Accuracy of the Enlite 6-day glucose sensor with guardian and Veo calibration algorithms.

OBJECTIVE This study investigates the accuracy of a newly developed, next-generation subcutaneous glucose sensor, evaluated for 6-day use. RESEARCH DESIGN AND METHODS Seventy-nine subjects (53 men, 26 women) with type 1 diabetes and 18 subjects (14 men, four women) with type 2 diabetes completed a three-center, prospective, sensor accuracy study. The mean age for the group was 42.2±15.0 years (mean±SD), ranging from 18 to 71 years, with a mean glycosylated hemoglobin level of 7.6±1.5%, ranging from 5.5% to 14%. Subjects wore Enlite™ sensors (Medtronic Diabetes, Northridge, CA) in the abdominal and buttocks region for two separate 7-day periods and calibrated with a home-use blood glucose meter. Subjects participated in an in-clinic testing day where frequent sampled plasma glucose samples were acquired every 15 min for 10 h. Sensor data was retrospectively processed with Guardian(®) REAL-Time (Medtronic) and Paradigm(®) Veo™ (Medtronic) calibration routines, and accuracy metrics were calculated for each algorithm and sensor location. Physiological time lag for each measurement site was calculated. RESULTS Based on 6,404 plasma-sensor glucose paired points, the Enlite sensor with Veo calibration algorithm produced a mean absolute relative difference of 13.86% with 97.3% of points within the A+B zones of the Clarke error grid. Threshold-only alarms detected 90.1% of hypoglycemia and 90% of hyperglycemia. Mean time lag measured at the abdominal region was 7.94±6.48 min compared with 11.70±6.71 min (P<0.0001) at the buttocks area. CONCLUSIONS The Enlite sensor accurately measures glucose when compared with gold standard laboratory measurements over its 6-day use. Sensors placed in the buttocks region exhibited greater time lags than sensors placed in the abdomen.

Clinical Accuracy of a Continuous Glucose Monitoring System With an Advanced Algorithm

Background: We assessed the performance of a modified Dexcom G4 Platinum system with an advanced algorithm, in comparison with frequent venous samples measured on a laboratory reference (YSI) during a clinic session and in comparison to self-monitored blood glucose (SMBG) during home use. Methods: Fifty-one subjects with diabetes were enrolled in a prospective multicenter study. Subjects wore 1 sensor for 7-day use and participated in one 12-hour in-clinic session on day 1, 4, or 7 to collect YSI reference venous glucose every 15 minutes and capillary SMBG test every 30 minutes. Carbohydrate consumption and insulin dosing and timing were manipulated to obtain data in low and high glucose ranges. Results: In comparison with the laboratory reference method (n = 2,263) the system provided a mean and median absolute relative differences (ARD) of 9.0% and 7.0%, respectively. The mean absolute difference for CGM was 6.4 mg/dL when the YSIs were within hypoglycemia ranges (≤ 70 mg/dL). The percentage in the clinically accurate Clarke error grid A zone was 92.4% and in the benign error B zone was 7.1%. Majority of the sensors (73%) had an aggregated MARD in reference to YSI ≤ 10%. The MARD of CGM-SMBG for home use was 11.3%. Conclusions: The study showed that the point and rate accuracy, clinical accuracy, reliability, and consistency over the duration of wear and across glycemic ranges were superior to current commercial real-time CGM systems. The performance of this CGM is reaching that of a self-monitoring blood glucose meter in real use environment.

Accuracy of the SEVEN® Continuous Glucose Monitoring System: Comparison with Frequently Sampled Venous Glucose Measurements

Background: The purpose of this study was to compare the accuracy of measurements obtained from the DexCom™ SEVEN® system with Yellow Springs Instrument (YSI) laboratory measurements of venous blood glucose. Methods: Seventy-two subjects with insulin-requiring diabetes, aged 18–71, were enrolled in a multicenter, prospective single-arm study. All participants wore the SEVEN continuous glucose monitoring (CGM) system for one, 7-day wear period. Calibration with capillary finger stick measurements was performed 2 hours after sensor insertion and once every 12 hours thereafter. A subset of subjects (28) wore two systems simultaneously to assess precision. All subjects participated in one, 10-hour in-clinic session on day 1, 4, or 7 of the study to compare CGM measurements against a laboratory method (YSI analyzer) using venous measurements taken once every 20 minutes. Carbohydrate consumption and insulin dosing were adjusted in order to obtain a broad range of glucose values. Results: Comparison of CGM measurements with the laboratory reference method (n = 2318) gave mean and median absolute relative differences (ARDs) of 16.7 and 13.2%, respectively. The percentage was 70.4% in the clinically accurate Clarke error grid A zone and 27.5% in the benign error B zone. Performance of the SEVEN system was consistent over time with mean and median ARD lowest on day 7 as compared to YSI (13.3 and 10.2%, respectively). Average sensor time lag was 5 minutes. Conclusions: Measurements of the DexCom SEVEN system were found to be consistent and accurate compared with venous measurements made using a laboratory reference method over 7 days of wear.

CONTINUOUS GLUCOSE MONITORING: A CONSENSUS CONFERENCE OF THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY

OBJECTIVE/METHODS Barriers to continuous glucose monitoring (CGM) use continue to hamper adoption of this valuable technology for the management of diabetes. The American Association of Clinical Endocrinologists and the American College of Endocrinology convened a public consensus conference February 20, 2016, to review available CGM data and propose strategies for expanding CGM access. RESULTS Conference participants agreed that evidence supports the benefits of CGM in type 1 diabetes and that these benefits are likely to apply whenever intensive insulin therapy is used, regardless of diabetes type. CGM is likely to reduce healthcare resource utilization for acute and chronic complications, although real-world analyses are needed to confirm potential cost savings and quality of life improvements. Ongoing technological advances have improved CGM accuracy and usability, but more innovations in human factors, data delivery, reporting, and interpretation are needed to foster expanded use. The development of a standardized data report using similar metrics across all devices would facilitate clinician and patient understanding and utilization of CGM. Expanded CGM coverage by government and private payers is an urgent need. CONCLUSION CGM improves glycemic control, reduces hypoglycemia, and may reduce overall costs of diabetes management. Expanding CGM coverage and utilization is likely to improve the health outcomes of people with diabetes. ABBREVIATIONS A1C = glycated hemoglobin AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ASPIRE = Automation to Simulate Pancreatic Insulin Response CGM = continuous glucose monitoring HRQOL = health-related quality of life ICER = incremental cost-effectiveness ratio JDRF = Juvenile Diabetes Research Foundation MARD = mean absolute relative difference MDI = multiple daily injections QALY = quality-adjusted life years RCT = randomized, controlled trial SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR = Sensor-Augmented Pump Therapy for A1C Reduction T1D = type 1 diabetes T2D = type 2 diabetes.

Accuracy and Acceptability of the 6-Day Enlite Continuous Subcutaneous Glucose Sensor

OBJECTIVE This study evaluated the performance and acceptability of the Enlite(®) glucose sensor (Medtronic MiniMed, Inc., Northridge, CA). SUBJECTS AND METHODS Ninety adults with type 1 or type 2 diabetes wore two Enlite sensors on the abdomen and/or buttock for 6 days and calibrated them at different frequencies. On Days 1, 3, and 6, accuracy was evaluated by comparison of sensor glucose values with frequently sampled plasma glucose values collected over a 12-h period. Accuracy was assessed at different reference glucose concentrations and during times when absolute glucose concentration rates of change were <1, 1-2, and >2 mg/dL/min. The sensors ability to detect hypoglycemia or hyperglycemia was evaluated with simulated alerts. Subject satisfaction was evaluated with a 7-point Likert-type questionnaire, with a score of 7 indicating strong agreement. RESULTS With abdomen sensors under actual-use calibration (mean, 2.8 ± 0.9 times/day), the overall mean (median) absolute relative difference (ARD) values between sensor and reference values were 13.6% (10.1%); the corresponding buttock sensor ARD values were 15.5% (10.5%). With abdomen sensors under minimal calibration (mean, 1.2 ± 0.9 times/day), the mean (median) ARD values were 14.7% (10.8%). Mean ARD values of abdomen sensors at rates of change of <1, 1-2, and >2 mg/dL/min were 13.6%, 12.9%, and 16.3%, respectively. With abdomen sensors, 79.5% and 94.1% of hypoglycemic and hyperglycemic events, respectively, were correctly detected; 81.9% and 94.9% of hypoglycemic and hyperglycemic alerts, respectively, were confirmed. The failure rates for abdomen and buttock sensors were 19.7% and 13.9%, respectively. Mean responses to survey questions for all subjects related to comfort and ease of use were favorable. CONCLUSIONS The Enlite sensor provided accurate data at different glucose concentrations and rates of change. Subjects found the sensor comfortable and easy to use.

Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes: The SWITCH 1 Randomized Clinical Trial.

Importance Hypoglycemia, common in patients with type 1 diabetes, is a major barrier to achieving good glycemic control. Severe hypoglycemia can lead to coma or death. Objective To determine whether insulin degludec is noninferior or superior to insulin glargine U100 in reducing the rate of symptomatic hypoglycemic episodes. Design, Setting, and Participants Double-blind, randomized, crossover noninferiority trial involving 501 adults with at least 1 hypoglycemia risk factor treated at 84 US and 6 Polish centers (January 2014-January 12, 2016) for two 32-week treatment periods, each with a 16-week titration and a 16-week maintenance period. Interventions Patients were randomized 1:1 to receive once-daily insulin degludec followed by insulin glargine U100 (n = 249) or to receive insulin glargine U100 followed by insulin degludec (n = 252) and randomized 1:1 to morning or evening dosing within each treatment sequence. Main Outcomes and Measures The primary end point was the rate of overall severe or blood glucose-confirmed (<56 mg/dL) symptomatic hypoglycemic episodes during the maintenance period. Secondary end points included the rate of nocturnal symptomatic hypoglycemic episodes and proportion of patients with severe hypoglycemia during the maintenance period. The noninferiority criterion for the primary end point and for the secondary end point of nocturnal hypoglycemia was defined as an upper limit of the 2-sided 95% CI for a rate ratio of 1.10 or lower; if noninferiority was established, 2-sided statistical testing for superiority was conducted. Results Of the 501 patients randomized (mean age, 45.9 years; 53.7% men), 395 (78.8%) completed the trial. During the maintenance period, the rates of overall symptomatic hypoglycemia were 2200.9 episodes per 100 person-years’ exposure (PYE) in the insulin degludec group vs 2462.7 episodes per 100 PYE in the insulin glargine U100 group for a rate ratio (RR) of 0.89 (95% CI, 0.85-0.94; P < .001 for noninferiority; P < .001 for superiority; rate difference, −130.31 episodes per 100 PYE; 95% CI, −193.5 to −67.16). The rates of nocturnal symptomatic hypoglycemia were 277.1 per 100 PYE in the insulin degludec group vs 428.6 episodes per 100 PYE in the insulin glargine U100 group, for an RR of 0.64 (95% CI, 0.56-0.73; P < .001 for noninferiority; P < .001 for superiority; rate difference, −61.94 episodes per 100 PYE; 95% CI, −83.85 to −40.03). A lower proportion of patients in the insulin degludec than in the insulin glargine U100 group experienced severe hypoglycemia during the maintenance period (10.3%, 95% CI, 7.3%-13.3% vs 17.1%, 95% CI, 13.4%-20.8%, respectively; McNemar P = .002; risk difference, −6.8%; 95% CI, −10.8% to −2.7%). Conclusions and Relevance Among patients with type 1 diabetes and at least 1 risk factor for hypoglycemia, 32 weeks’ treatment with insulin degludec vs insulin glargine U100 resulted in a reduced rate of overall symptomatic hypoglycemic episodes. Trial Registration clinicaltrials.gov Identifier: NCT02034513

Clinical practice guidelines for healthy eating for the prevention and treatment of metabolic and endocrine diseases in adults: cosponsored by the American Association of Clinical Endocrinologists/the American College of Endocrinology and the Obesity Society: executive summary.

J. Michael Gonzalez-Campoy, MD, PhD, FACE1; Sachiko T. St. Jeor, PhD, RD2; Kristin Castorino, DO3; Ayesha Ebrahim, MD, FACE4; Dan Hurley, MD, FACE5; Lois Jovanovic, MD, MACE6; Jeffrey I. Mechanick, MD, FACP, FACN, FACE, ECNU7; Steven M. Petak, MD, JD, MACE, FCLM8; Yi-Hao Yu, MD, PhD, FACE9; Kristina A. Harris10; Penny Kris-Etherton, PhD, RD11; Robert Kushner, MD12; Maureen Molini-Blandford, MPH, RD13; Quang T. Nguyen, DO14; Raymond Plodkowski, MD15; David B. Sarwer, PhD16; Karmella T. Thomas, RD17