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Objective: Recent consensus statements strongly advocate downloading and interpreting continuous glucose data for diabetes management in patients with type 1 or 2 diabetes. Supplementing periodic glycated hemoglobin (A1C) testing with intermittent continuous glucose monitoring (CGM) using a standardized report form known as the ambulatory glucose profile (AGP) is an evolving standard of care. The rationale for this approach and its implementation with a recently approved novel monitoring technology are explored., Methods: Search of the medical literature, professional guidelines, and real-world evidence guided this introduction of an integrative practice framework that uses AGP in conjunction with intermittent flash continuous glucose monitoring (FCGM) as a supplement to A1C testing., Results: The combination of intermittent continuous glucose pattern analysis, standardized glucose metrics, and a readily interpretable data report has the potential to practically extend the recognized benefits of CGM to more patients and clarify the relationship between A1C and average glucose levels in individual cases., Conclusion: Novel FCGM technologies portend greater use of continuous forms of glucose monitoring and wider adoption of AGP report analysis. Additional formal and empirical evidence is needed to more fully characterize best practice., Abbreviations: A1C = glycated hemoglobin; AGP = ambulatory glucose profile; CGM = continuous glucose monitoring; FCGM = flash continuous glucose monitoring; IQR = interquartile range; SMBG = self-monitoring of blood glucose.

This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position and consensus statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician., Abbreviations: BPCIA = Biologics Price Competition and Innovation Act; FDA = Food and Drug Administration; FFDC = Federal Food Drug and Cosmetics Act; PHS = Public Health Services Act; TE = therapeutic equivalence.

Decreasing glycated hemoglobin (A1C) is the primary goal of current diabetes management due to intervention studies in type 1 and type 2 diabetes associating levels <7.0% (53 mmol/mol) with lower complication risk. Strategic self-monitoring of blood glucose (SMBG) is also recommended to achieve greater time in range, with fewer extremes of hypo- or hyperglycemia. Unlike A1C, SMBG can distinguish among fasting, prandial, and postprandial hyperglycemia; uncover glycemic variability, including potentially dangerous hypoglycemia; and provide feedback to patients about the effects of behavior and medication on glycemic control. However, it has the drawback of capturing only static glucose readings and users are often dependent on time-pressed clinicians to interpret numerous data points. A novel flash continuous glucose monitoring (FCGM) device used for a single 2-week period with a readily interpretable data report know as the ambulatory glucose profile (AGP) has the potential to overcome limitations of conventional technologies, with less cost and greater convenience. This review summarizes the rationale for using intermittent FCGM as a supplement to A1C in primary care, and provides a stepwise approach to interpreting the AGP visual display for efficient individualized therapy.

Aims: We compared cystatin C in youth with versus without diabetes and determined factors associated with cystatin C in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D)., Methods: Youth (ages 12-19years) without diabetes (N=544) were ascertained from the NHANES Study 2000-2002 and those with T1D (N=977) and T2D (N=168) from the SEARCH for Diabetes in Youth Study. Adjusted means of cystatin C concentrations were compared amongst the 3 groups. Next, we performed multivariable analyses within the T1D and T2D SEARCH samples to determine the association between cystatin C and race, sex, age, diabetes duration, HbA1c, fasting glucose, and BMI., Results: Adjusted cystatin C concentrations were statistically higher in NHANES (0.85mg/L) than in either the T1D (0.75mg/L) or T2D (0.70mg/L) SEARCH groups (P<0.0001). Fasting glucose was inversely related to cystatin C only in T1D (P<0.001) and BMI positively associated only in T2D (P<0.01) while HbA1c was inversely associated in both groups., Conclusions: Cystatin C concentrations are statistically higher in youth without diabetes compared to T1D or T2D, however the clinical relevance of this difference is quite small, especially in T1D. In youth with diabetes, cystatin C varies with BMI and acute and chronic glycemic control, however their effects may be different according to diabetes type., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Thanks to significant improvements in the precision, accuracy, and usability of continuous glucose monitoring (CGM), its relevance in both ambulatory diabetes care and clinical research is increasing. In this study, we address the latter perspective and derive provisional reporting recommendations. CGM systems have been available since around the year 2000 and used primarily in people with type 1 diabetes. In contrast to self-measured glucose, CGM can provide continuous real-time measurement of glucose levels, alerts for hypoglycemia and hyperglycemia, and a detailed assessment of glycemic variability. Through a broad spectrum of derived glucose data, CGM should be a useful tool for clinical evaluation of new glucose-lowering medications and strategies. It is the only technology that can measure hyperglycemic and hypoglycemic exposure in ambulatory care, or provide data for comprehensive assessment of glucose variability. Other advantages of current CGM systems include the opportunity for improved self-management of glycemic control, with particular relevance to those at higher risk of or from hypoglycemia. We therefore summarize the current status and limitations of CGM from the perspective of clinical trials and derive suggested recommendations for how these should facilitate optimal CGM use and reporting of data in clinical research.

Background: The potential clinical benefits of continuous glucose monitoring (CGM) have been recognized for many years, but CGM is used by a small fraction of patients with diabetes. One obstacle to greater use of the technology is the lack of simplified tools for assessing glycemic control from CGM data without complicated visual displays of data., Methods: We developed a simple new metric, the personal glycemic state (PGS), to assess glycemic control solely from continuous glucose monitoring data. PGS is a composite index that assesses four domains of glycemic control: mean glucose, glycemic variability, time in range and frequency and severity of hypoglycemia. The metric was applied to data from six clinical studies for the G4 Platinum continuous glucose monitoring system (Dexcom, San Diego, CA). The PGS was also applied to data from a study of artificial pancreas comparing results from open loop and closed loop in adolescents and in adults., Results: The new metric for glycemic control, PGS, was able to characterize the quality of glycemic control in a wide range of study subjects with various mean glucose, minimal, moderate, and excessive glycemic variability and subjects on open loop versus closed loop control., Conclusion: A new composite metric for the assessment of glycemic control based on CGM data has been defined for use in assessing glycemic control in clinical practice and research settings. The new metric may help rapidly identify problems in glycemic control and may assist with optimizing diabetes therapy during time-constrained physician office visits.

We review clinical instances in which A1C should not be used and reflect on the use of other glucose metrics that can be used, in substitution of or in combination with A1C and SMBG, to tailor an individualized approach that will result in better outcomes and patient empowerment.

Purpose: Options for leveraging available telemedicine technologies, ranging from simple webcams and telephones to smartphone apps and medical-grade wearable sensors, are evolving faster than the culture of clinical research. Until recently, most clinical trials relied on paper-based processes and technology. This cost- and labor-intensive system, while slowly changing, remains an obstacle to new drug development. Alternatives that use existing tools and processes for collecting real-world data in home settings warrant closer examination., Methods: The site-less clinical research organization (CRO) model, whereby pharmacists or other health care professionals provide useful and timely counseling for protocol compliance by regular phone and videoconferencing sessions, is a flexible approach to managing clinical trial participants directly from their homes. An expert panel, including clinical specialists in metabolic or neurodegenerative diseases, health information technology and CRO innovators, and the pharmaceutical industry, met in Dallas, Texas, December 2016, to discuss advancing avenues for site-less CRO and other remote clinical trial practices, taking into account investigator, sponsor, and regulatory perspectives., Findings: Real-time "site-less" management of clinical trials can augment traditional research and development methods by providing data from a broader, more diverse group of patients in real-world practice settings. This methodology also helps to proactively identify safety profile and operational issues. Current use of site-less CRO practices constitutes an important bridge to alternative trial models, including "large simple trials" that strive to answer one or two questions using data derived from representative patient populations treated in typical clinical settings., Implications: Site-less CROs offer a working example of how remote technologies and in-home monitoring methods can address shortcomings of conventional drug development. This model maximizes time and cost, as well as potentially earlier identification of adverse events. Coordinated communication among investigators, sponsors, regulators, and patients will be needed to develop standardized strategies for incorporating site-less CROs into current and future study design., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Increasingly over the past generation, the American healthcare delivery system has received consistently poor marks with regard to public health outcomes and costs. This review by two seasoned diabetes care providers is intended to shed light on the fundamental flaws we believe to underlie that poor performance, and suggest options for better outcomes and cost efficiencies., Recent Findings: Despite major advances in diabetes management medications and tools, overall public health with regard to diabetes outcomes remains poor. Efforts focused on controlling costs appear to be exacerbating the problem., Summary: For chronic diseases like diabetes, fee-for-service care models are fundamentally flawed and predictably fail. We suggest that a major overhaul of the medical economics underlying diabetes care can improve patient outcomes and decrease costs.

Objective: To determine the safety and efficacy of a change in blood glucose (BG) control protocol from a single target to 2 targets based on diabetes mellitus (DM) status and glycated hemoglobin A1C (A1C) in a cohort of critically ill patients., Methods: This investigation includes 1,979 patients admitted to a single intensive care unit (ICU) between September 16, 2013 and September 15, 2015. The BG target was 90 to 120 mg/dL in the PRE era and 80 to 140 mg/dL for patients without diabetes (NON) and with DM with A1C <7% and 110 to 160 mg/dL for DM with A1C ≥7% (TIGHT and LOOSE protocols) in the POST era. The primary efficacy outcome was the observed:expected (O:E) mortality ratio., Results: Among NON, the mean BG was slightly lower in the POST era: 118 (106-132) versus 115 (101-120) mg/dL (P = .0003). Among DM, the mean BG was 139 (123-160) mg/dL in the PRE era versus 136 (119-149) and 159 (138-171) mg/dL for TIGHT and LOOSE in the POST era (P = .0668 and .0001, respectively). Overall, 11.0% and 11.8% of patients had at least 1 BG level <70 mg/dL in the 2 eras (P = .68). The O:E mortality ratios for NON and DM for the PRE and POST eras were 0.75 versus 0.74 (P = .51) and 0.69 versus 0.52 (P<.001) respectively, and among DM with A1C ≥7% were 0.74 versus 0.52 (P = .004)., Conclusion: This hypothesis-generating investigation suggests the need for additional prospective interventional studies assessing the outcomes of patients randomized to personalized glucose targets., Abbreviations: APACHE = Acute Physiology and Chronic Health Evaluation A1C = glycated hemoglobin A1C BG = blood glucose CV = co-efficient of variation DM = diabetes mellitus ICU = intensive care unit LOS = length of stay NON = patients without DM O:E = observed: expected.

Background: Real-time continuous glucose monitoring (RTCGM) may help in the management of individuals with type 1 diabetes mellitus (T1DM); however, the evidence supporting its use is unclear. The available meta-analyses on this topic use aggregate data which weaken inference., Objective: Individual patient data were obtained from randomized controlled trials (RCTs) to conduct a meta-analysis and synthesize evidence about the effect of RTCGM on glycosylated haemoglobin (HbA1c), hypoglycaemic events and time spent in hypoglycaemia in T1DM., Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus through January 2015. We included RCTs that enrolled individuals with T1DM and compared RTCGM vs control group. A two-step regression model was used to pool individual patient data., Results: We included 11 RCTs at moderate risk of bias. Meta-analysis suggests that the use of RTCGM is associated with a statistically significant but modest reduction in HbA1c (-0·276; 95% confidence interval -0·465 to -0·087). The improvements in HbA1c were primarily seen in individuals over age 15 years. We were unable to identify a statistically significant difference in time spent in hypoglycaemia or the number of hypoglycaemic episodes although these analyses were imprecise and warrant lower confidence. There was no difference between males and females., Conclusion: RTCGM in T1DM is associated with a reduction in HbA1c primarily in individuals over 15 years of age. We were unable to identify a statistically significant difference in the time spent in hypoglycaemia or the incidence of hypoglycaemic episodes., (© 2016 John Wiley & Sons Ltd.)

Aims: To evaluate the long-term safety and efficacy of a simplified basal-bolus regimen of once-daily insulin degludec/insulin aspart (IDegAsp) with additional IAsp vs. a standard basal-bolus insulin regimen of insulin detemir (IDet) with IAsp in adults with Type 1 diabetes., Methods: This was an open-label trial comprising a 26-week core phase followed by a 26-week extension phase. Participants were randomized to IDegAsp once daily at the main meal and IAsp at remaining meals (IDegAsp+IAsp), or IDet (once or twice daily) and IAsp at all meals (IDet+IAsp). Insulins were titrated to target plasma glucose of < 5 mmol/l (< 90 mg/dl) at pre-breakfast (IDegAsp and IDet) and at pre-meal (IAsp)., Results: After 52 weeks, the overall confirmed hypoglycaemia rate was 31.8 episodes/patient-years of exposure (PYE) with IDegAsp+Asp and 36.7 episodes/PYE with IDet+IAsp, and the rate of nocturnal confirmed hypoglycaemia was significantly lower with IDegAsp+Asp than with IDet+IAsp (3.1 vs. 5.4 episodes/PYE, respectively; P < 0.05). Adverse event rates were comparable between groups. Mean HbA 1c decreased from baseline by 0.7% (IDegAsp+IAsp) and 0.6% (IDet+IAsp), achieving 60 or 61 mmol/mol (7.6% or 7.7%, respectively), at Week 52. The mean total daily insulin dose was lower with IDegAsp+IAsp than with IDet+IAsp (ratio: 0.87; 95% CI 0.79-0.95; P = 0.0026)., Conclusions: Once-daily treatment with IDegAsp and IAsp as bolus insulin for remaining meals was associated with significantly lower risk of nocturnal confirmed hypoglycaemia, improved glycaemic control and showed non-inferiority compared with IDet+IAsp, the standard of care in Type 1 diabetes., (© 2016 The Authors Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Importance: The majority of individuals with type 1 diabetes do not meet recommended glycemic targets., Objective: To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections., Design, Setting, and Participants: Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5% (58 mmol/mol) treated with multiple daily insulin injections., Interventions: Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks., Main Outcomes and Measures: Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied., Results: Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA1c was 8.6% (70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92% (63 mmol/mol) during continuous glucose monitoring use and 8.35% (68 mmol/mol) during conventional treatment (mean difference, -0.43% [95% CI, -0.57% to -0.29%] or -4.7 [-6.3 to -3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia., Conclusions and Relevance: Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Further research is needed to assess clinical outcomes and longer-term adverse effects., Trial Registration: clinicaltrials.gov Identifier: NCT02092051.

Background: Hypoglycemia is a major concern in older adults with type 1 diabetes (T1D) and there is limited knowledge in this population. We examined data from 199 adults, ≥60 years of age, who participated in a T1D Exchange study assessing factors associated with severe hypoglycemia (SH) in older adults with T1D: 100 with SH in the prior year and 99 with no SH in prior 3 years (mean age 68; mean diabetes duration 40 years; 47% female; 92% non-Hispanic white). Hypoglycemia was assessed with up to 14 days of blinded continuous glucose monitoring (CGM). Linear regression models were performed to assess the association between biochemical hypoglycemia [defined as percentage of time below specific cutoffs (<70/60/50 mg/dL)] and various factors., Results: Overall, participants had CGM values <70 mg/dL for a median of 91 min per day. On 53% of days, glucose levels continuously were <70 mg/dL for ≥20 min. Hypoglycemia was found to be strongly associated with glucose variability (r = 0.76; P < 0.001). Time spent in hypoglycemia was greater in those who were younger (P = 0.004), had shorter diabetes duration (P = 0.008), lower HbA1c (P < 0.001), and undetectable C-peptide (P = 0.001), but did not differ by insulin method, education level, number of blood glucose checks per day, cognition, activities of daily living, or fear of hypoglycemia., Innovation: This study adds valuable data on the frequency of hypoglycemia in older adults with T1D., Conclusion: Future studies need to focus on how to prevent hypoglycemia in this vulnerable population of older adults with long-standing T1D.

Objective: To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes., Participants: The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline., Evidence: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies., Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines., Conclusions: Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.

Objective: To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes., Research Design and Methods: A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin., Results: Mean baseline glycated hemoglobin (HbA1c) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6 mmol/mol]; 1.2 mg: -0.22% [2.4 mmol/mol]; 0.6 mg: -0.23% [2.5 mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis >1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01)., Conclusions: In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg., (© 2016 by the American Diabetes Association.)

Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To understand the decisional practices of anesthesia providers in managing intraoperative glucose levels., Design: This is a retrospective cohort study., Setting: Operating rooms in an academic medical center., Patients: Adult patients undergoing surgery., Intervention: Intraoperative blood glucose management based on an institutional protocol., Measurements: Glucose management data was extracted from electronic medical records to determine compliance to institutional glucose management protocol that prescribes hourly glucose measurements and insulin doses to maintain glucose levels between 100 to 140mg/dL. Effect of patient and surgery specific factors on compliance to glucose management protocol was explored., Main Results: In 1903 adult patients compliances to hourly glucose measurements was 72.5% and correct insulin adjustments was 12.4%. Insulin was under-dosed compared to the prescribed value by a mean of 0.85U/h (95% CI 0.76-0.95). Multivariate analysis showed that compliance to hourly glucose measurements decreased with increasing length of the procedure (OR=0.92 per hour, 95% CI 0.89-0.95) but increased with ASA status codes (OR=1.25 per ASA unit, 95% CI=1.06-1.49). Greater compliance to correct insulin adjustment was found in diabetic patients compared with non-diabetic patients (OR=1.31, 95% CI 1.09-1.55). On average, providers administered progressively more insulin with an additional 0.11U/h (95% CI=0.00-0.21] for every additional 10kg/m(2) of BMI and 0.20U/h (95% CI=0.01-0.39) less in diabetic patients than in non-diabetic patients. With the above practice pattern, the mean±SD of glucose level was 158±36mg/dL. Hypoglycemic (<60mg/dL) incident rate was 0.1% (9/8301 measurements) while hyperglycemic (>180mg/dL) incident rate was 28%. Glucose levels were within the target range (100-140mg/dL) only 28% of the time., Conclusions: Low compliance and considerable variability in initiating and following institutional glucose management protocol were observed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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.

Purpose: Insulin infusion sets (IISs) are an essential component of safe and effective insulin pump therapy. Establishing best practices for their use has been impeded by a lack of formal study and limited resources for clinician and patient education. Recent innovations in IIS science promise to change this status quo by increasing awareness of such problems as unexplained hyperglycemia and infusion set occlusion., Methods: In August 2015, a panel of diabetologists and certified diabetes educators from various disciplines was convened to reconsider IIS-related complications of pump therapy, to better characterize infusion set factors affecting patient experience, and to update priorities for optimizing current technologies. Actionable guidelines were provided for addressing common issues, including skin reactions, site rotation and set changes, dislodgment of the infusion set, and partial or complete blockage of the catheter. These issues may underlie episodes of IIS failure and/or unexplained hyperglycemia., Conclusion: Development of practical tools and standardized guidelines for empowering patients to prevent, diagnose, and troubleshoot IIS problems that contribute to unexplained hyperglycemia will be necessary to realize the full benefit of insulin pump therapy along the continuum of diabetes education., (© 2016 The Author(s).)

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for patients with hematological malignancies. However, is associated with substantial rates of morbidity and mortality. We and others have shown that malglycemia is associated with adverse transplant outcome. Therefore, improving glycemic control may improve transplant outcome. In this prospective study we evaluated the feasibility of using Glucommander (a Computer-Guided Glucose Management System; CGGM) in order to achieve improved glucose control in hospitalized HCT patients. Nineteen adult patients contributed 21 separate instances on CGGM. Patients were on CGGM for a median of 43 h. Median initial blood glucose (BG) on CGGM was 244 mg/dL, and patients on 20 study instances reached the study BG target of 100-140 mg/dL after a median of 6 h. After BG reached the target range, the median average BG level per patient was 124 mg/dL. Six patients had a total of 10 events of BG <70 mg/dL (0.9% of BG measurements), and no patients experienced BG level <40 mg/dL. The total estimated duration of BG <70 mg/dL was 3 h (0.2% of the total CGGM time). In conclusion, our study demonstrates that stringent BG control in HCT patients using CGGM is feasible.

Manual calculation of bolus insulin dosages can be challenging for individuals treated with multiple daily insulin injections (MDI) therapy. Automated bolus calculator capability has recently been made available via enhanced blood glucose meters and smartphone apps. Use of this technology has been shown to improve glycemic control and reduce glycemic variability without changing hypoglycemia; however, the clinical utility of app-based bolus calculators has not been demonstrated. Moreover, recent evidence challenges the safety and efficacy of these smartphone apps. Although the ability to automatically calculate bolus insulin dosages addresses a critical need of MDI-treated individuals, this technology raises concerns about efficacy of treatment and the protection of patient safety. This article discusses key issues and considerations associated with automated bolus calculator use., (© 2016 Diabetes Technology Society.)

Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM., Methods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples., Results: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P < .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P < .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P < .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82., Conclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges., (© 2016 Diabetes Technology Society.)

Poor perioperative glycemic management can lead to negative surgical outcome. Improved compliance to glucose control protocol could lead to better glucose management. An Anesthesia Information Management System based decision support system-Smart Anesthesia Manager™ (SAM) was used to generate real-time reminders to the anesthesia providers to closely adhere to our institutional glucose management protocol. Compliance to hourly glucose measurements and correct insulin dose adjustments was compared for the baseline period (12 months) without SAM and the intervention period (12 months) with SAM decision support. Additionally, glucose management parameters were compared for the baseline and intervention periods. A total of 1587 cases during baseline and 1997 cases during intervention met the criteria for glucose management (diabetic patients or non-diabetic patients with glucose level >140 mg/dL). Among the intervention cases anesthesia providers chose to use SAM reminders 48.7 % of the time primarily for patients who had diabetes, higher HbA1C or body mass index, while disabling the system for the remaining cases. Compliance to hourly glucose measurement and correct insulin doses increased significantly during the intervention period when compared with the baseline (from 52.6 to 71.2 % and from 13.5 to 24.4 %, respectively). In spite of improved compliance to institutional protocol, the mean glucose levels and other glycemic management parameters did not show significant improvement with SAM reminders. Real-time electronic reminders improved intraoperative compliance to institutional glucose management protocol though glycemic parameters did not improve even when there was greater compliance to the protocol.

Background: The majority of individuals with type 1 diabetes today have glucose levels exceeding guidelines. The primary aim of this study was to evaluate whether continuous glucose monitoring (CGM), using the Dexcom G4 stand-alone system, improves glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections (MDI)., Methods: Individuals with type 1 diabetes and inadequate glycemic control (HbA1c ≥ 7.5% = 58 mmol/mol) treated with MDI were randomized in a cross-over design to the Dexcom G4 versus conventional care for 6 months followed by a 4-month wash-out period. Masked CGM was performed before randomization, during conventional treatment, and during the wash-out period to evaluate effects on hypoglycemia, hyperglycemia, and glycemic variability. Questionnaires were used to evaluate diabetes treatment satisfaction, fear of hypoglycemia, hypoglycemia confidence, diabetes-related distress, overall well-being, and physical activity during the different phases of the trial. The primary endpoint was the difference in HbA1c at the end of each treatment phase., Results: A total of 205 patients were screened, of whom 161 were randomized between February and December 2014. Study completion is anticipated in April 2016., Conclusions: It is expected that the results of this study will establish whether using the Dexcom G4 stand-alone system in individuals with type 1 diabetes treated with MDI improves glycemic control, reduces hypoglycemia, and influences quality-of-life indicators and glycemic variability., Competing Interests: Declaration of Conflicting Interests: ML has received research grants from AstraZeneca, Dexcom, and Novo Nordisk, been a consultant or received honoraria from Medtronic, Eli Lilly, Pfizer, Abbot Scandinavia, Bayer, Novo Nordisk, and Rubin Medical. ML has participated in advisory boards for Novo Nordisk. WP has served as a consultant for Dexcom and Abbott Diabetes Care. IBH has received research grants from Novo Nordisk, and been a consultant for Abbott Diabetes Care, Roche, and Becton Dickinson. TH has received research funds from Adocia, AstraZeneca, BD, Biocon, Boehringer Ingelheim, Dance Pharmaceuticals, Grünenthal, Eli Lilly, Medtronic, Novo Nordisk, Novartis, Sanofi, and Senseonics. TH has participated in advisory panels for Novo Nordisk and received speaker honoraria and travel grants from Eli Lilly, Mylan, and Novo Nordisk. JB has received honoraria for consulting and/or lecture fees from Abbott Diabetes Care, AstraZeneca, Integrity Applications, Eli Lilly, and Sanofi. SD, NGP, and PM have no conflicts of interest to declare., (© 2016 Diabetes Technology Society.)

Objective: Severe hypoglycemia is common in older adults with long-standing type 1 diabetes, but little is known about factors associated with its occurrence., Research Design and Methods: A case-control study was conducted at 18 diabetes centers in the T1D Exchange Clinic Network. Participants were ≥60 years old with type 1 diabetes for ≥20 years. Case subjects (n = 101) had at least one severe hypoglycemic event in the prior 12 months. Control subjects (n = 100), frequency-matched to case subjects by age, had no severe hypoglycemia in the prior 3 years. Data were analyzed for cognitive and functional abilities, social support, depression, hypoglycemia unawareness, various aspects of diabetes management, C-peptide level, glycated hemoglobin level, and blinded continuous glucose monitoring (CGM) metrics., Results: Glycated hemoglobin (mean 7.8% vs. 7.7%) and CGM-measured mean glucose (175 vs. 175 mg/dL) were similar between case and control subjects. More case than control subjects had hypoglycemia unawareness: only 11% of case subjects compared with 43% of control subjects reported always having symptoms associated with low blood glucose levels (P < 0.001). Case subjects had greater glucose variability than control subjects (P = 0.008) and experienced CGM glucose levels <60 mg/dL for ≥20 min on 46% of days compared with 33% of days in control subjects (P = 0.10). On certain cognitive tests, case subjects scored worse than control subjects., Conclusions: In older adults with long-standing type 1 diabetes, greater hypoglycemia unawareness and glucose variability are associated with an increased risk of severe hypoglycemia. A study to assess interventions to prevent severe hypoglycemia in high-risk individuals is needed., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

This document represents the official position of the American Association of Clinical Endocrinologists and the American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician.

Study Question: What are the effects of liraglutide, an incretin based treatment, on glycaemic control in people with type 2 diabetes treated with multiple daily insulin injections?, Methods: The study was a randomised, double blind, placebo controlled trial with a parallel group design carried out at 13 hospital based outpatient clinics and one primary care unit in Sweden. Patients were considered eligible for inclusion if they had type 2 diabetes and inadequate glycaemic control (HbA1c concentrations ≥ 58 mmol/mol (7.5%) and ≤ 102 mmol/mol (11.5%)), a body mass index of 27.5-45 kg/m(2), and required multiple daily insulin injections. Overall, 124 participants were randomised 1:1 to subcutaneous liraglutide or placebo by minimisation allocation. The main outcome measure was change in HbA1c level from baseline to week 24., Study Answer and Limitations: Liraglutide was associated with a significant reduction of 16.9 mmol/mol (1.5%) in HbA1c versus 4.6 mmol/mol (0.4%) for placebo, difference -12.3 mmol/mol (95% confidence interval -15.8 to -8.8 mmol/mol; -1.13%, -1.45 to -0.81 mmol/mol). Body weight was significantly reduced in participants in the liraglutide compared with placebo group (3.8 v 0.0 kg, difference -3.8, -4.9 to -2.8 kg), and total daily insulin doses were significantly reduced, by 18.1 units and 2.3 units (difference -15.8, -23.1 to -8.5 units). Reductions in mean and standard deviation of glucose levels estimated by masked continuous glucose monitoring were significantly greater in the liraglutide group than placebo group (-1.9 and -0.5 mmol/L). Neither group experienced severe hypoglycaemic events nor were there any significant differences in symptomatic or asymptomatic non-severe hypoglycaemia (<4.0 or <3.0 mmol/L). The mean number of non-severe symptomatic hypoglycaemic events (<4.0 mmol/L) during follow-up was 1.29 in the liraglutide group and 1.24 in the placebo group (P=0.96). One of the study's limitations was its relatively short duration. Sustained effects of liraglutide have, however, been found over lengthier periods in connection with other treatment regimens. Cardiovascular safety and potential adverse events during longer exposure to liraglutide need to be evaluated. Nausea was experienced by 21 (32.8%) participants in the liraglutide group and 5 (7.8%) in the placebo group and 3 (5%) and 4 (7%) participants in these groups, respectively, had any serious adverse event., What This Study Adds: Adding liraglutide to multiple daily insulin injections in people with type 2 diabetes improves glycaemic control without an increased risk of hypoglycaemia, reduces body weight, and enables patients to lower their insulin doses., Funding, Competing Interests, Data Sharing: This study was an investigator initiated trial, supported in part by Novo Nordisk and InfuCare. Potential competing interests have been reported and are available on the bmj.com., Study Registration: EudraCT 2012-001941-42., (© Lind et al 2015.)

Background: Under controlled conditions, the Dose Safety artificial pancreas (AP) system controller, which utilizes "fuzzy logic" (FL) methodology to calculate and deliver appropriate insulin dosages based on changes in blood glucose, successfully managed glycemic excursions. The aim of this study was to show whether stressing the system with pizza (high carbohydrate/high fat) meals and exercise would reveal deficits in the performance of the Dose Safety FL controller (FLC) and lead to improvements in the dosing matrix., Methods: Ten subjects with type 1 diabetes (T1D) were enrolled and participated in 30 studies (17 meal, 13 exercise) using 2 versions of the FLC. After conducting 13 studies with the first version (FLC v2.0), interim results were evaluated and the FLC insulin-dosing matrix was modified to create a new controller version (FLC v2.1) that was validated through regression testing using v2.0 CGM datasets prior to its use in clinical studies. The subsequent 17 studies were performed using FLC v2.1., Results: Use of FLC v2.1 vs FLC v2.0 in the pizza meal tests showed improvements in mean blood glucose (205 mg/dL vs 232 mg/dL, P = .04). FLC v2.1 versus FLC v2.0 in exercise tests showed improvements in mean blood glucose (146 mg/dL vs 201 mg/dL, P = .004), percentage time spent >180 mg/dL (19.3% vs 46.7%, P = .001), and percentage time spent 70-180 mg/dL (80.0% vs 53.3%, P = .002)., Conclusion: Stress testing the AP system revealed deficits in the FLC performance, which led to adjustments to the dosing matrix followed by improved FLC performance when retested., (© 2015 Diabetes Technology Society.)

Objective: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication., Research Design and Methods: Cases identified incidentally are described., Results: We identified 13 episodes of SGLT-2 inhibitor-associated euDKA or ketosis in nine individuals, seven with type 1 diabetes and two with type 2 diabetes, from various practices across the U.S. The absence of significant hyperglycemia in these patients delayed recognition of the emergent nature of the problem by patients and providers., Conclusions: SGLT-2 inhibitors seem to be associated with euglycemic DKA and ketosis, perhaps as a consequence of their noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. Patients with type 1 or type 2 diabetes who experience nausea, vomiting, or malaise or develop a metabolic acidosis in the setting of SGLT-2 inhibitor therapy should be promptly evaluated for the presence of urine and/or serum ketones. SGLT-2 inhibitors should only be used with great caution, extensive counseling, and close monitoring in the setting of type 1 diabetes., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

There is no argument that improving mean levels of glycemic control as judged by assays for glycated hemoglobin (HbA(1c)) reduces the risks of microvascular complications and cardiovascular disease events in patients with type 1 and type 2 diabetes. However, observations in some trials have suggested that targeting HbA(1c) to suggested targets may not always result in improved outcomes for people with long-standing type 2 diabetes. The reasons why the glycemic control strategies that primarily use HbA(1c) in these studies did not have predicted outcomes are not clear. Thus, controversy remains as to whether there are glycemic metrics beyond HbA(1c) that can be defined as effective measures that can be used in addition to HbA(1c) to help in assessing the risk of an individual developing diabetes complications. In this regard, the concept of "glycemic variability" (GV) is one metric that has attracted a lot of attention. GV can be simply defined as the degree to which a patient's blood glucose level fluctuates between high (peaks) and low (nadir) levels. The best and most precise way to assess GV is also one that is still debated. Thus, while there is universal agreement that HbA(1c) is the current gold standard for the primary clinical target, there is no consensus as to whether other proposed glycemic metrics hold promise to provide additional clinical data or whether there should be additional targets beyond HbA(1c). Therefore, given the current controversy, we provide a Point-Counterpoint debate on this issue. In the point narrative below, Dr. Hirsch provides his argument that fluctuations in blood glucose as assessed by GV metrics are deleterious and control of GV should be a primary treatment target. In the following counterpoint narrative, Dr. Bergenstal argues that there are better markers to assess the risk of diabetes than GV and provides his consideration of other concepts., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Accuracy of continuous glucose monitoring (CGM) devices in hypoglycemia has been a widely reported shortcoming of this technology. We report the accuracy in hypoglycemia of a new version of the Dexcom (San Diego, CA) G4 Platinum CGM system (software 505) and present results regarding the optimum setting of CGM hypoglycemic alerts., Materials and Methods: CGM values were compared with YSI analyzer (YSI Life Sciences, Yellow Springs, OH) measurements every 15 min. We reviewed the accuracy of the CGM system in the hypoglycemic range using standard metrics. We analyzed the time required for the CGM system to detect biochemical hypoglycemia (70 mg/dL) compared with the YSI with alert settings at 70 mg/dL and 80 mg/dL. We also analyzed the time between the YSI value crossing 55 mg/dL, defined as the threshold for cognitive impairment due to hypoglycemia, and when the CGM system alerted for hypoglycemia., Results: The mean absolute difference for a glucose level of less than 70 mg/dL was 6 mg/dL. Ninety-six percent of CGM values were within 20 mg/dL of the YSI values between 40 and 80 mg/dL. When the CGM hypoglycemic alert was set at 80 mg/dL, the device provided an alert for biochemical hypoglycemia within 10 min in 95% of instances and at least a 10-min advance warning before the cognitive impairment threshold in 91% of instances in the study., Conclusions: Use of an 80 mg/dL threshold setting for hypoglycemic alerts on the G4 Platinum (software 505) may provide patients with timely warning of hypoglycemia before the onset of cognitive impairment, enabling them to treat themselves for hypoglycemia with fast-acting carbohydrates and prevent neuroglycopenia associated with very low glucose levels.