Howard Wolpert

Continuous glucose monitoring and intensive treatment of type 1 diabetes

BACKGROUND The value of continuous glucose monitoring in the management of type 1 diabetes mellitus has not been determined. METHODS In a multicenter clinical trial, we randomly assigned 322 adults and children who were already receiving intensive therapy for type 1 diabetes to a group with continuous glucose monitoring or to a control group performing home monitoring with a blood glucose meter. All the patients were stratified into three groups according to age and had a glycated hemoglobin level of 7.0 to 10.0%. The primary outcome was the change in the glycated hemoglobin level at 26 weeks. RESULTS The changes in glycated hemoglobin levels in the two study groups varied markedly according to age group (P=0.003), with a significant difference among patients 25 years of age or older that favored the continuous-monitoring group (mean difference in change, -0.53%; 95% confidence interval [CI], -0.71 to -0.35; P<0.001). The between-group difference was not significant among those who were 15 to 24 years of age (mean difference, 0.08; 95% CI, -0.17 to 0.33; P=0.52) or among those who were 8 to 14 years of age (mean difference, -0.13; 95% CI, -0.38 to 0.11; P=0.29). Secondary glycated hemoglobin outcomes were better in the continuous-monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference. CONCLUSIONS Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents. (ClinicalTrials.gov number, NCT00406133.)

The effect of continuous glucose monitoring in well-controlled type 1 diabetes.

OBJECTIVE The potential benefits of continuous glucose monitoring (CGM) in the management of adults and children with well-controlled type 1 diabetes have not been examined. RESEARCH DESIGN AND METHODS A total of 129 adults and children with intensively treated type 1 diabetes (age range 8–69 years) and A1C <7.0% were randomly assigned to either continuous or standard glucose monitoring for 26 weeks. The main study outcomes were time with glucose level ≤70 mg/dl, A1C level, and severe hypoglycemic events. RESULTS At 26 weeks, biochemical hypoglycemia (≤70 mg/dl) was less frequent in the CGM group than in the control group (median 54 vs. 91 min/day), but the difference was not statistically significant (P = 0.16). Median time with a glucose level ≤60 mg/dl was 18 versus 35 min/day, respectively (P = 0.05). Time out of range (≤70 or >180 mg/dl) was significantly lower in the CGM group than in the control group (377 vs. 491 min/day, P = 0.003). There was a significant treatment group difference favoring the CGM group in mean A1C at 26 weeks adjusted for baseline (P < 0.001). One or more severe hypoglycemic events occurred in 10 and 11% of the two groups, respectively (P = 1.0). Four outcome measures combining A1C and hypoglycemia data favored the CGM group in comparison with the control group (P < 0.001, 0.007, 0.005, and 0.003). CONCLUSIONS Most outcomes, including those combining A1C and hypoglycemia, favored the CGM group. The weight of evidence suggests that CGM is beneficial for individuals with type 1 diabetes who have already achieved excellent control with A1C <7.0%.

Sensor-Augmented Insulin Pump Therapy: Results of the First Randomized Treat-to-Target Study

BACKGROUND The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring (CGM), compared to using an insulin pump with standard blood glucose monitoring systems. METHODS This 6-month, randomized, multicenter, treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of >or=7.5%. Subjects were randomized to pump therapy with real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood glucose only (control group [CG]). Clinical effectiveness and safety were evaluated. RESULTS A1C levels decreased (P<0.001) from baseline (8.44+/-0.70%) in both groups (SG, -0.71+/-0.71%; CG, -0.56+/-0.072%); however, between-group differences did not achieve significance. SG subjects showed no change in mean hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase (P=0.001) in hypoglycemia AUC during the blinded periods of the study. The between-group difference in hypoglycemia AUC was significant (P<0.0002). Greater than 60% sensor utilization was associated with A1C reduction (P=0.0456). Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the CG group, P=0.04). CONCLUSIONS A1C reduction was no different between the two groups. Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use; however, there was no increase in hypoglycemia AUC or number of events in the SG group. Subjects with greater sensor utilization showed a greater improvement in A1C levels.

Factors predictive of use and of benefit from continuous glucose monitoring in type 1 diabetes.

OBJECTIVE To evaluate factors associated with successful use of continuous glucose monitoring (CGM) among participants with intensively treated type 1 diabetes in the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Randomized Clinical Trial. RESEARCH DESIGN AND METHODS The 232 participants randomly assigned to the CGM group (165 with baseline A1C ≥7.0% and 67 with A1C <7.0%) were asked to use CGM on a daily basis. The associations of baseline factors and early CGM use with CGM use ≥6 days/week in the 6th month and with change in A1C from baseline to 6 months were evaluated in regression models. RESULTS The only baseline factors found to be associated with greater CGM use in month 6 were age ≥25 years (P < 0.001) and more frequent self-reported prestudy blood glucose meter measurements per day (P < 0.001). CGM use and the percentage of CGM glucose values between 71 and 180 mg/dl during the 1st month were predictive of CGM use in month 6 (P < 0.001 and P = 0.002, respectively). More frequent CGM use was associated with a greater reduction in A1C from baseline to 6 months (P < 0.001), a finding present in all age-groups. CONCLUSIONS After 6 months, near-daily CGM use is more frequent in intensively treated adults with type 1 diabetes than in children and adolescents, although in all age-groups near-daily CGM use is associated with a similar reduction in A1C. Frequency of blood glucose meter monitoring and initial CGM use may help predict the likelihood of long-term CGM benefit in intensively treated patients with type 1 diabetes of all ages.

Transitioning From Pediatric to Adult Care A new approach to the post-adolescent young person with type 1 diabetes

Diabetes research and health care have traditionally been divided into two distinct areas for receiving medical care: pediatric and adult. We propose a fresh approach to providing care in which we consider the period of development after high school as a period of “emerging adulthood” for youth with diabetes. We argue that the traditional conceptualization of only two distinct groups of patients misses the unique personal needs of individuals immediately post–high school. We frame this discussion about the needs of these post–high school patients (∼18–30 years of age) within the context of a contemporary theory of post-adolescent development. With this developmental context in hand, we then review psychosocial research on youth with type 1 diabetes. Next we discuss current clinical perspectives and knowledge about the natural course of diabetes during these years. Armed with an understanding of development, psychosocial functioning, and overall health, we then consider the literature regarding transition programs for youth with chronic diseases—both diabetes and other illnesses. We conclude by presenting specific strategies and recommendations to help both pediatric and adult providers care for the transition needs of this vulnerable population of individuals with diabetes. Over the past century, traditional developmental psychology defined the time immediately after adolescence as the “young adult period” (3,4). In contrast, a leading contemporary developmental theorist (1,2) has argued that young adulthood does not begin until youth are in their late twenties or thirties and that the developmental stage between ∼l8 and 25 years defines a period called “emerging adulthood.” Recent cultural trends in America for young people in their twenties lead to delays in assuming adult roles with respect to marriage, parenting, and work. Arnett (2) suggests that todays young people “explore the possibilities available to them in love and work, and move gradually toward making enduring …

Continuous glucose monitoring: an Endocrine Society Clinical Practice Guideline.

OBJECTIVE The aim was to formulate practice guidelines for determining settings where patients are most likely to benefit from the use of continuous glucose monitoring (CGM). PARTICIPANTS The Endocrine Society appointed a Task Force of experts, a methodologist, and a medical writer. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, the Diabetes Technology Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. CONCLUSIONS The Task Force evaluated three potential uses of CGM: 1) real-time CGM in adult hospital settings; 2) real-time CGM in children and adolescent outpatients; and 3) real-time CGM in adult outpatients. The Task Force used the best available data to develop evidence-based recommendations about where CGM can be beneficial in maintaining target levels of glycemia and limiting the risk of hypoglycemia. Both strength of recommendations and quality of evidence were accounted for in the guidelines.

Effect of Continuous Glucose Monitoring on Glycemic Control in Adults With Type 1 Diabetes Using Insulin Injections: The DIAMOND Randomized Clinical Trial.

Importance Previous clinical trials showing the benefit of continuous glucose monitoring (CGM) in the management of type 1 diabetes predominantly have included adults using insulin pumps, even though the majority of adults with type 1 diabetes administer insulin by injection. Objective To determine the effectiveness of CGM in adults with type 1 diabetes treated with insulin injections. Design, Setting, and Participants Randomized clinical trial conducted between October 2014 and May 2016 at 24 endocrinology practices in the United States that included 158 adults with type 1 diabetes who were using multiple daily insulin injections and had hemoglobin A1c (HbA1c) levels of 7.5% to 9.9%. Interventions Random assignment 2:1 to CGM (n = 105) or usual care (control group; n = 53). Main Outcomes and Measures Primary outcome measure was the difference in change in central-laboratory–measured HbA1c level from baseline to 24 weeks. There were 18 secondary or exploratory end points, of which 15 are reported in this article, including duration of hypoglycemia at less than 70 mg/dL, measured with CGM for 7 days at 12 and 24 weeks. Results Among the 158 randomized participants (mean age, 48 years [SD, 13]; 44% women; mean baseline HbA1c level, 8.6% [SD, 0.6%]; and median diabetes duration, 19 years [interquartile range, 10-31 years]), 155 (98%) completed the study. In the CGM group, 93% used CGM 6 d/wk or more in month 6. Mean HbA1c reduction from baseline was 1.1% at 12 weeks and 1.0% at 24 weeks in the CGM group and 0.5% and 0.4%, respectively, in the control group (repeated-measures model P < .001). At 24 weeks, the adjusted treatment-group difference in mean change in HbA1c level from baseline was –0.6% (95% CI, –0.8% to –0.3%; P < .001). Median duration of hypoglycemia at less than <70 mg/dL was 43 min/d (IQR, 27-69) in the CGM group vs 80 min/d (IQR, 36-111) in the control group (P = .002). Severe hypoglycemia events occurred in 2 participants in each group. Conclusions and Relevance Among adults with type 1 diabetes who used multiple daily insulin injections, the use of CGM compared with usual care resulted in a greater decrease in HbA1c level during 24 weeks. Further research is needed to assess longer-term effectiveness, as well as clinical outcomes and adverse effects. Trial Registration clinicaltrials.gov Identifier: NCT02282397

Clinical application of emerging sensor technologies in diabetes management: consensus guidelines for continuous glucose monitoring (CGM).

Continuous glucose monitoring (CGM) is an evolving technology poised to redefine current concepts of glycemic control and optimal diabetes management. To date, there are few randomized studies examining how to most effectively use this new tool. Therefore, a group of eight diabetes specialists heard presentations on continuous glucose sensor technology and then discussed their experience with CGM in order to identify fundamental considerations, objectives, and methods for applying this technology in clinical practice. The group concluded that routine use of CGM, with real-time data showing the rate and direction of glucose change, could revolutionize current approaches to evaluating and managing glycemia. The need for such progress is indicated by the growing prevalence of inadequately treated hyperglycemia. Coordinating financial and educational resources and developing clear protocols for using glucose sensor technology are urgent priorities in promoting wide adoption of CGM by patients and health care providers. Finally, researchers, manufacturers, payers, and advocacy groups must join forces on the policy level to create an environment conducive to managing continuous data, measuring outcomes, and formalizing best practices.

Management of diabetes: are doctors framing the benefits from the wrong perspective?

Several large intervention studies have shown that intensive glucose management in diabetic patients can prevent microvascular complications. 1 2 Furthermore, analysis of cost effectiveness in these studies indicates that the lifetime improvement in quality of life and longevity derived from intensive management would outweigh the increased costs of such treatment. 3 4 Nevertheless, tight glycaemic control has proved difficult to achieve in clinical practice. Even patients who have received comprehensive diabetes education and are skilled in self management have difficulty maintaining optimal glycaemic control in the long term. During the four years after completion of the diabetes control and complications trial, the median glycated haemoglobin concentrations of the intensive treatment cohort rose to 7.9% (up from a median value of 7.0-7.2% during the trial).5 Other studies have shown that education on self management of diabetes without interventions to reinforce behavioural change does not lead to sustained improvements in glucose control.6 Many factors can directly and indirectly influence disease management behaviour and metabolic control of people with diabetes. In addition to individual variables (biological and psychological factors), patient behaviour is influenced by transactions within the family system, the broader social and cultural community, and socioeconomic and healthcare system factors.7 In this article we focus on the influence from within the healthcare system—that is, the healthcare providers message about the benefits of optimal glycaemic control—and argue that the message needs to be framed from the perspective of the patient. #### Summary points Because diabetes is a self managed condition, successful models of care must focus on strategies that promote and maintain improved selfcare behaviour New treatment frameworks are needed to enhance the effectiveness of clinicians in promoting behavioural change The message about the benefits of tight glycaemic control needs to be refocused from the perspective of the patient The benefits of intensive …

Sustained benefit of continuous glucose monitoring on A1C, glucose profiles, and hypoglycemia in adults with type 1 diabetes

OBJECTIVE To evaluate long-term effects of continuous glucose monitoring (CGM) in intensively treated adults with type 1 diabetes. RESEARCH DESIGN AND METHODS We studied 83 of 86 individuals ≥25 years of age with type 1 diabetes who used CGM as part of a 6-month randomized clinical trial in a subsequent 6-month extension study. RESULTS After 12 months, median CGM use was 6.8 days per week. Mean change in A1C level from baseline to 12 months was −0.4 ± 0.6% (P < 0.001) in subjects with baseline A1C ≥7.0%. A1C remained stable at 6.4% in those with baseline A1C <7.0%. The incidence rate of severe hypoglycemia was 21.8 and 7.1 events per 100 person-years in the first and last 6 months, respectively. Time per day with glucose levels in the range of 71–180 mg/dl increased significantly (P = 0.02) from baseline to 12 months. CONCLUSIONS In intensively treated adults with type 1 diabetes, CGM use and benefit can be sustained for 12 months.