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Objective: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin., Research Design and Methods: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61)., Results: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group., Conclusions: Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users., (© 2024 by the American Diabetes Association.)

Importance: Continuous glucose monitoring (CGM) has been shown to be beneficial for adults with type 2 diabetes using intensive insulin therapy, but its use in type 2 diabetes treated with basal insulin without prandial insulin has not been well studied., Objective: To determine the effectiveness of CGM in adults with type 2 diabetes treated with basal insulin without prandial insulin in primary care practices., Design, Setting, and Participants: This randomized clinical trial was conducted at 15 centers in the US (enrollment from July 30, 2018, to October 30, 2019; follow-up completed July 7, 2020) and included adults with type 2 diabetes receiving their diabetes care from a primary care clinician and treated with 1 or 2 daily injections of long- or intermediate-acting basal insulin without prandial insulin, with or without noninsulin glucose-lowering medications., Interventions: Random assignment 2:1 to CGM (n = 116) or traditional blood glucose meter (BGM) monitoring (n = 59)., Main Outcomes and Measures: The primary outcome was hemoglobin A1c (HbA1c) level at 8 months. Key secondary outcomes were CGM-measured time in target glucose range of 70 to 180 mg/dL, time with glucose level at greater than 250 mg/dL, and mean glucose level at 8 months., Results: Among 175 randomized participants (mean [SD] age, 57 [9] years; 88 women [50%]; 92 racial/ethnic minority individuals [53%]; mean [SD] baseline HbA1c level, 9.1% [0.9%]), 165 (94%) completed the trial. Mean HbA1c level decreased from 9.1% at baseline to 8.0% at 8 months in the CGM group and from 9.0% to 8.4% in the BGM group (adjusted difference, -0.4% [95% CI, -0.8% to -0.1%]; P = .02). In the CGM group, compared with the BGM group, the mean percentage of CGM-measured time in the target glucose range of 70 to 180 mg/dL was 59% vs 43% (adjusted difference, 15% [95% CI, 8% to 23%]; P < .001), the mean percentage of time at greater than 250 mg/dL was 11% vs 27% (adjusted difference, -16% [95% CI, -21% to -11%]; P < .001), and the means of the mean glucose values were 179 mg/dL vs 206 mg/dL (adjusted difference, -26 mg/dL [95% CI, -41 to -12]; P < .001). Severe hypoglycemic events occurred in 1 participant (1%) in the CGM group and in 1 (2%) in the BGM group., Conclusions and Relevance: Among adults with poorly controlled type 2 diabetes treated with basal insulin without prandial insulin, continuous glucose monitoring, as compared with blood glucose meter monitoring, resulted in significantly lower HbA1c levels at 8 months., Trial Registration: ClinicalTrials.gov Identifier: NCT03566693.

Background: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes., Methods: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA 1c ). The primary outcome was change in HbA 1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527., Findings: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA 1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy)., Interpretation: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use., Funding: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: The objective was to determine the effectiveness of real-time continuous glucose monitoring (CGM) in adults ≥ 60 years of age with type 1 (T1D) or type 2 (T2D) diabetes using multiple daily insulin injections (MDI)., Methods: A multicenter, randomized trial was conducted in the United States and Canada in which 116 individuals ≥60 years (mean 67 ± 5 years) with T1D (n = 34) or T2D (n = 82) using MDI therapy were randomly assigned to either CGM (Dexcom™ G4 Platinum CGM System® with software 505; n = 63) or continued management with self-monitoring blood glucose (SMBG; n = 53). Median diabetes duration was 21 (14, 30) years and mean baseline HbA1c was 8.5 ± 0.6%. The primary outcome, HbA1c at 24 weeks, was obtained for 114 (98%) participants., Results: HbA1c reduction from baseline to 24 weeks was greater in the CGM group than Control group (-0.9 ± 0.7% versus -0.5 ± 0.7%, adjusted difference in mean change was -0.4 ± 0.1%, P < .001). CGM-measured time >250 mg/dL ( P = .006) and glycemic variability ( P = .02) were lower in the CGM group. Among the 61 in the CGM group completing the trial, 97% used CGM ≥ 6 days/week in month 6. There were no severe hypoglycemic or diabetic ketoacidosis events in either group., Conclusion: In adults ≥ 60 years of age with T1D and T2D using MDI, CGM use was high and associated with improved HbA1c and reduced glycemic variability. Therefore, CGM should be considered for older adults with diabetes using MDI.

Objective: To determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D)., Research Design and Methods: A randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA 1c ≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% [53 ± 7.7 mmol/mol]); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only ( n = 149) or CGM+BGM ( n = 77) group. The primary outcome was time in range (70-180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%., Results: CGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively ( P < 0.001). Mean time in 70-180 mg/dL was 63 ± 13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group (adjusted difference 0%; one-sided 95% CI -2%). No severe hypoglycemic events occurred in the CGM-only group, and one occurred in the CGM+BGM group., Conclusions: Use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia., (© 2017 by the American Diabetes Association.)

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.

Background: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy., Methods/design: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes., Discussion: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes., Trial Registration: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012.

Aims/hypothesis: The aim of this work was to assess the association between continuous glucose monitoring (CGM) data, HbA1c, insulin-dose-adjusted HbA1c (IDAA1c) and C-peptide responses during the first 2 years following diagnosis of type 1 diabetes., Methods: A secondary analysis was conducted of data collected from a randomised trial assessing the effect of intensive management initiated within 1 week of diagnosis of type 1 diabetes, in which mixed-meal tolerance tests were performed at baseline and at eight additional time points through 24 months. CGM data were collected at each visit., Results: Among 67 study participants (mean age [± SD] 13.3 ± 5.7 years), HbA1c was inversely correlated with C-peptide at each time point (p < 0.001), as were changes in each measure between time points (p < 0.001). However, C-peptide at one visit did not predict the change in HbA1c at the next visit and vice versa. Higher C-peptide levels correlated with increased proportion of CGM glucose values between 3.9 and 7.8 mmol/l and lower CV (p = 0.001 and p = 0.02, respectively) but not with CGM glucose levels <3.9 mmol/l. Virtually all participants with IDAA1c < 9 retained substantial insulin secretion but when evaluated together with CGM, time in the range of 3.9-7.8 mmol/l and CV did not provide additional value in predicting C-peptide levels., Conclusions/interpretation: In the first 2 years after diagnosis of type 1 diabetes, higher C-peptide levels are associated with increased sensor glucose levels in the target range and with lower glucose variability but not hypoglycaemia. CGM metrics do not provide added value over the IDAA1c in predicting C-peptide levels.

Objective: To assess effectiveness of inpatient hybrid closed-loop control (HCLC) followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7 days of diagnosis of type 1 diabetes on the preservation of β-cell function at 1 year., Research Design and Methods: Sixty-eight individuals (mean age 13.3 ± 5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP therapy (intensive group; N = 48) or to the usual-care group treated with multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C-peptide concentrations during mixed-meal tolerance tests at 12 months., Results: Intensive-group participants initiated HCLC a median of 6 days after diagnosis for a median duration of 71.3 h, during which median participant mean glucose concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at 12 months, only 33% of intensive participants averaged sensor use ≥6 days/week. In the usual-care group, insulin pump and CGM use were initiated prior to 12 months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in both groups throughout the study. At 12 months, the geometric mean (95% CI) of C-peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide concentration ≥0.2 pmol/mL (P = 0.30)., Conclusions: In new-onset type 1 diabetes, HCLC followed by SAP therapy did not provide benefit in preserving β-cell function compared with current standards of care.

Background: This article describes our experience with inpatient hybrid closed-loop control (HCLC) initiated shortly after the diagnosis of type 1 diabetes in a randomized trial designed to assess the effectiveness of inpatient HCLC followed by outpatient sensor-augmented pump (SAP) therapy on the preservation of β-cell function., Subjects and Methods: Forty-eight individuals with newly diagnosed type 1 diabetes and positive pancreatic autoantibodies (7.8-37.7 years old) received inpatient HCLC therapy for up to 93 h, initiated within 7 days of diagnosis., Results: On initiation of HCLC, mean glucose concentration was 240±100 mg/dL. During the first day of HCLC, median of the participant's mean glucose concentrations fell rapidly to 146 mg/dL, a level of control that was sustained on Days 2 and 3 (138 mg/dL and 139 mg/dL, respectively). By Day 3, the median percentage of glucose values >250 and <60 mg/dL was <1%. During the first 2 weeks of SAP treatment at home, the median participant mean glucose level was 126 mg/dL (interquartile range, 117, 137 mg/dL), and the median percentage of values between 71 and 180 mg/dL was 85% (interquartile range, 80%, 90%)., Conclusions: Inpatient HCLC followed by outpatient SAP therapy can provide a safe and effective means to rapidly reverse glucose toxicity and establish near-normal glycemic control in patients with newly diagnosed type 1 diabetes.

Despite improvements for management of type 1 diabetes (T1D), patients have difficulty achieving glycated hemoglobin (A1c) levels recommended by the Diabetes Control and Complications Trial (DCCT). Two multicenter randomized trials were conducted to evaluate benefit of using a continuous glucose monitor (CGM) with standard glucose monitoring for T1D management. The primary study evaluated benefits of CGM in 322 patients with A1c >7.0%. The secondary study evaluated 129 patients with A1c <7.0%. In the primary study, CGM resulted in improvements in A1c at 6 m in subjects >25 years, but not those <25. However, all subjects using CGM regularly showed benefit. Improved A1c did not come with increased severe hypoglycemia as seen in the DCCT, and benefit was sustained over 1 year. In the secondary study, CGM use helped subjects maintain target A1c levels with reduced exposure to biochemical hypoglycemia. The data collected allowed for other analyses of important factors in T1D management.

Objective: To determine exposure to hyper- and hypoglycemia using blinded continuous glucose monitoring (CGM) profiles in youth with type 1 diabetes (T1D) with residual β-cell function during the first year of insulin treatment., Research Design and Methods: Blinded, 3-7 day CGM profiles were obtained in 16 short-term T1D patients (age 8-18 years, T1D duration 6-52 weeks) who had peak C-peptide levels ranging from 0.46 to 1.96 nmol/L during a mixed-meal tolerance test. Results in this short-term group were compared with those in 34 patients with well-controlled, longer-term T1D (duration ≥5 years), matched for age and A1C with the short-term T1D group, and with those in 26 age-matched nondiabetic individuals., Results: Despite matching for A1C, and therefore similar mean sensor glucose levels in the two T1D groups, short-term T1D participants had a lower frequency of hypoglycemia (0.3 vs. 7.6%, P < 0.001), a trend toward less hyperglycemia (17 vs. 32%, P = 0.15), and a greater percentage in the target range (median 77 vs. 60%, P = 0.02). Indeed, the percentage of sensor glucose levels ≤70 mg/dL in the short-term T1D group (0.3%) did not differ from those in the nondiabetic group (1.7%, P = 0.73). The coefficient of variation of sensor glucose levels (an index of glucose variability) was lower in short-term vs. longer-term T1D participants (27 vs. 42%, respectively, P < 0.001)., Conclusions: In youth with short-term T1D who retain residual β-cell function, there is negligible exposure to hypoglycemia and lower glucose variability than in youth with well-controlled T1D of longer duration.

Objectives: To describe the interrelationships of glycemic control measures: hemoglobin A1c (HbA1c), glycated albumin, fructosamine, 1,5-anhydroglucitrol (1,5-AG), and continuous glucose monitoring (CGM) in children and adolescents with type 1 diabetes., Methods: In total, 26 subjects of age 4-17 had HbA1c measurement followed within 14 d by three laboratory measures of glycemia and the collection of CGM glucose data (N = 21)., Results: Glycated albumin and fructosamine levels had a higher correlation with each other than with HbA1c. The correlation of 1,5-AG with HbA1c was lower (absolute r value = 0.25). All four measures had a similar degree of correlation with CGM-measured mean glucose (absolute r value = 0.50-0.56) and with hyperglycemic area under the curve (AUC) at 180 mg/dL (0.50-0.60)., Conclusion: Each of the four measures (i.e., HbA1c, glycated albumin, fructosamine, and 1,5-AG) had a similar correlation with mean glucose and hyperglycemic AUC-180. 1,5-AG did not correlate with hyperglycemic AUC-180 better than did HbA1c., (© 2011 John Wiley & Sons A/S.)

Aims and Hypothesis: The optimal duration and frequency of short-term continuous glucose monitoring (CGM) to reflect long-term glycemia have not been determined. The Juvenile Diabetes Research Foundation CGM randomized trials provided a large dataset of longitudinal CGM data for this type of analysis., Methods: The analysis included 185 subjects who had 334 3-month intervals of CGM data meeting specific criteria. For various glucose indices, correlations (r²) were computed for the entire 3-month interval versus selected sampling periods ranging from 3 to 15 days. Other computed agreement measures included median relative absolute difference, values within ± 10% and ± 20% of full value, and median absolute difference., Results: As would be expected, the more days of glucose data that were sampled, the higher the correlation with the full 3 months of data. For 3 days of sampling, the r² value ranged from 0.32 to 0.47, evaluating mean glucose, percentage of values 71-180 mg/dL, percentage of values > 180 mg/dL, percentage of values ≤ 70 mg/dL, and coefficient of variation; in contrast, for 15 days of sampling, the r² values ranged from 0.66 to 0.75. The results were similar when the analysis intervals were stratified by age group (8-14, 15-24, and ≥ 25 years), by baseline hemoglobin A1c level (< 7.0% and ≥ 7.0%), and by CGM device type., Conclusions and Interpretation: Our data suggest that a 12-15-day period of monitoring every 3 months may be needed to optimally assess overall glucose control. Shorter periods of sampling can be useful, but the correlation with 3-month measures of glycemic control is lower.

Objective: To determine the relationship between mean sensor glucose concentrations and hemoglobin A(1c) (HbA(1c)) values measured in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications laboratory at the University of Minnesota in a cohort of subjects with type 1 diabetes from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized trial., Research Design and Methods: Near-continuous glucose sensor data (≥ 4 days/week) were collected for 3 months before a central laboratory-measured HbA(1c) was performed for 252 subjects aged 8-74 years, the majority of whom had stable HbA(1c) values (77% within ± 0.4% of the patient mean)., Results: The slope (95% CI) for mean sensor glucose concentration (area under the curve) versus a centrally measured HbA(1c) was 24.4 mg/dL (22.0-26.7) for each 1% change in HbA(1c), with an intercept of -16.2 mg/dL (-32.9 to 0.6). Although the slope did not vary with age or sex, there was substantial individual variability, with mean sensor glucose concentrations ranging from 128 to 187 mg/dL for an HbA(1c) of 6.9-7.1%. The root mean square of the errors between the actual mean sensor glucose concentration versus the value calculated using the regression equation was 14.3 mg/dL, whereas the median absolute difference was 10.1 mg/dL., Conclusions: There is substantial individual variability between the measured versus calculated mean glucose concentrations. Consequently, estimated average glucose concentrations calculated from measured HbA(1c) values should be used with caution.

Background: The use of continuous glucose monitoring (CGM) in the pediatric population is not well characterized. We have evaluated the use of CGM over a 12-month interval in youth with type 1 diabetes (TID) and have provided a description of CGM use., Methods: Eighty subjects 8-17 years old with T1D and baseline hemoglobin A1c (HbA1c) >or=7.0% used CGM as part of a 6-month randomized trial and subsequent 6-month extension study. Outcomes included frequency of CGM use, HbA1c levels, rate of severe hypoglycemia, and a CGM satisfaction scale., Results: Seventy-six (95%) of 80 subjects were using CGM after 6 months (median use = 5.5 days/week) compared with 67 (84%) after 12 months (median use = 4.0 days/week). The 17 subjects using CGM >or=6 days/week in month 12 had substantially greater improvement from baseline in HbA1c than did the 63 subjects using CGM <6 days/week in month 12 (mean change - 0.8 +/- 0.6% vs. +0.1 +/- 0.7%, P < 0.001). They also reported greater satisfaction with use of CGM (P = 0.001). The incidence of severe hypoglycemic events was low during the 12 months of the study irrespective of the amount of CGM use., Conclusions: In youth with T1D, frequency of use decreases over time. Individuals who use CGM on a near-daily basis can have substantial improvement in glycemic control.

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 >or=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 >or=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.

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 >or=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 >or=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 >or=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.

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 < or =70 mg/dl, A1C level, and severe hypoglycemic events. RESULTS At 26 weeks, biochemical hypoglycemia (< or =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 < or =60 mg/dl was 18 versus 35 min/day, respectively (P = 0.05). Time out of range (< or =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%.

Objective: For continuous glucose sensors to improve the treatment of children with type 1 diabetes (T1D), they must be accurate, comfortable to wear, and easy to use. We conducted a pilot study of the FreeStyle Navigator Continuous Glucose Monitoring System (Abbott Diabetes Care) to examine the feasibility of daily use of a continuous glucose monitor (CGM) in an extended ambulatory setting., Methods: Following a 13-wk trial of daily Navigator use, 45 children with T1D [10.7 +/- 3.7 yr, range 4.6-17.6, 24 using insulin pumps; continuous subcutaneous insulin infusion (CSII) and 21 using glargine-based multiple daily injections (MDI)] used the Navigator for an additional 13 wk., Results: Navigator use was initially slightly higher in the CSII users than in the MDI users but declined similarly in both groups by 22-26 wk. After 26 wk, 11 (46%) of 24 CSII users and 7 (33%) of 21 MDI users were using the CGM at least 5 d a week. No baseline demographic or clinical factors were predictive of the amount of sensor use at 26 wk. However, Navigator use during weeks 1-13 and scores on a CGM satisfaction survey at 13 wk were predictive of use in weeks 22-26., Conclusions: CGM was generally well-tolerated in children with T1D for more than 6 months, and early acceptance of CGM was predictive of extended use of the device. Although many subjects and parents found CGM valuable, the declining usage over time underscores the need to develop new technologies and strategies to increase acceptance, effectiveness, and long-term use of these devices in youth with T1D.

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.), (2008 Massachusetts Medical Society)

Background: There are no published guidelines for use of real-time continuous glucose monitoring data by a patient; we therefore developed the DirecNet Applied Treatment Algorithm (DATA). The DATA provides algorithms for making diabetes management decisions using glucose values: (i) in real time which include the direction and rate of change of glucose levels, and (ii) retrospectively based on downloaded sensor data., Objective: To evaluate the use and effectiveness of the DATA in children with diabetes using a real-time continuous glucose sensor (the FreeStyle Navigator)., Subjects: Thirty children and adolescents (mean +/- standard deviation age = 11.2 +/- 4.1 yr) receiving insulin pump therapy., Methods: Subjects were instructed on use of the DATA and were asked to download their Navigator weekly to review glucose patterns. An Algorithm Satisfaction Questionnaire was completed at 3, 7, and 13 wk., Results: At 13 wk, all of the subjects and all but one parent thought that the DATA gave good, clear directions for insulin dosing, and thought the guidelines improved their postprandial glucose levels. In responding to alarms, 86% of patients used the DATA at least 50% of the time at 3 wk, and 59% reported doing so at 13 wk. Similar results were seen in using the DATA to adjust premeal bolus doses of insulin., Conclusions: These results show the feasibility of implementing the DATA when real-time continuous glucose monitoring is initiated and support its use in future clinical trials of real-time continuous glucose monitoring.

Objective: To evaluate the accuracy and precision of the FreeStyle Navigator continuous glucose monitoring system in children with type 1 diabetes., Research Design and Methods: In 30 children with type 1 diabetes (mean age 11.2 +/- 4.1 years), the Navigator glucose values were compared with reference serum glucose values of blood samples obtained in an inpatient clinical research center and measured in a central laboratory using a hexokinase enzymatic method and in an outpatient setting with a FreeStyle meter. Median absolute difference (AD) and median relative absolute difference (RAD) were computed for sensor-reference and sensor-sensor pairs., Results: The median AD and RAD were 17 mg/dl and 12%, respectively, for 1,811 inpatient sensor-reference pairs and 20 mg/dl and 14%, respectively, for 8,639 outpatient pairs. The median RAD between two simultaneous Navigator measurements (n = 1,971) was 13%. Ninety-one percent of sensors in the inpatient setting and 81% of sensors in the outpatient setting had a median RAD < or = 20%., Conclusions: The Navigator's accuracy does not yet approach the accuracy of current-generation home glucose meters, but it is sufficient to believe that the device has the potential to be an important adjunct to treatment of youth with type 1 diabetes.

Background: The optimal number/timing of calibrations entered into the CGMS (Medtronic MiniMed, Northridge, CA) continuous glucose monitoring system have not been previously described., Methods: Fifty subjects with Type 1 diabetes mellitus (10-18 years old) were hospitalized in a clinical research center for approximately 24 h on two separate days. CGMS and OneTouch Ultra meter (LifeScan, Milpitas, CA) data were obtained. The CGMS was retrospectively recalibrated using the Ultra data varying the number and timing of calibrations. Resulting CGMS values were compared against laboratory reference values., Results: There was a modest improvement in accuracy with increasing number of calibrations. The median relative absolute deviation (RAD) was 14%, 15%, 13%, and 13% when using three, four, five, and seven calibration values, respectively (P < 0.001). Corresponding percentages of CGMS-reference pairs meeting the International Organisation for Standardisation criteria were 66%, 67%, 71%, and 72% (P < 0.001). Nighttime accuracy improved when daytime calibrations (pre-lunch and pre-dinner) were removed leaving only two calibrations at 9 p.m. and 6 a.m. (median difference, -2 vs. -9 mg/dL, P < 0.001; median RAD, 12% vs. 15%, P = 0.001). Accuracy was better on visits where the average absolute rate of glucose change at the times of calibration was lower. On visits with average absolute rates <0.5, 0.5 to <1.0, 1.0 to <1.5, and >or=1.5 mg/dL/min, median RAD values were 13% versus 14% versus 17% versus 19%, respectively (P = 0.05)., Conclusions: Although accuracy is slightly improved with more calibrations, the timing of the calibrations appears more important. Modifying the algorithm to put less weight on daytime calibrations for nighttime values and calibrating during times of relative glucose stability may have greater impact on accuracy.

Objective: To examine the acute glucose-lowering effects of aerobic exercise in children and adolescents with type 1 diabetes., Research Design and Methods: Fifty children and adolescents with type 1 diabetes (ages 10 to <18 years) were studied during exercise. The 75-min exercise session consisted of four 15-min periods of walking on a treadmill to a target heart rate of 140 bpm and three 5-min rest periods. Blood glucose and plasma glucagon, cortisol, growth hormone, and norepinephrine concentrations were measured before, during, and after exercise., Results: In most subjects (83%), plasma glucose concentration dropped at least 25% from baseline, and 15 (30%) subjects became hypoglycemic (< or = 60 mg/dl) or were treated for low glucose either during or immediately following the exercise session. The incidence of hypoglycemia and/or treatment for low glucose varied significantly by baseline glucose, occurring in 86 vs. 13 vs. 6% of subjects with baseline values <120, 120-180, and >180 mg/dl, respectively (P < 0.001). Exercise-induced increases in growth hormone and norepinephrine concentrations were marginally higher in subjects whose glucose dropped < or = 70 mg/dl. Treatment of hypoglycemia with 15 g of oral glucose resulted in only about a 20-mg/dl rise in glucose concentrations., Conclusions: In youth with type 1 diabetes, prolonged moderate aerobic exercise results in a consistent reduction in plasma glucose and the frequent occurrence of hypoglycemia when preexercise glucose concentrations are <120 mg/dl. Moreover, treatment with 15 g of oral glucose is often insufficient to reliably treat hypoglycemia during exercise in these youngsters.

Objective: To examine the effect of exercise on overnight hypoglycemia in children with type 1 diabetes mellitus (T1DM)., Study Design: At 5 clinical sites, 50 subjects with T1DM (age 11 to 17 years) were studied in a clinical research center on 2 separate days. One day included an afternoon exercise session on a treadmill. On both days, frequently sampled blood glucose levels were measured at the DirecNet central laboratory. Insulin doses were similar on both days., Results: During exercise, plasma glucose levels fell in almost all subjects; 11 (22%) developed hypoglycemia. Mean glucose level from 10 pm to 6 am was lower on the exercise day than on the sedentary day (131 vs 154 mg/dL; P=.003). Hypoglycemia developed overnight more often on the exercise nights than on the sedentary nights (P=.009), occurring on the exercise night only in 13 (26%), on the sedentary night only in 3 (6%), on both nights in 11 (22%), and on neither night in 23 (46%). Hypoglycemia was unusual on the sedentary night if the pre-bedtime snack glucose level was>130 mg/dL., Conclusions: These findings indicate that overnight hypoglycemia after exercise is common in children with T1DM and support the importance of modifying diabetes management after afternoon exercise to reduce the risk of hypoglycemia.

Background: The objective of this study was to assess how the accuracy of the FreeStyle Flash (Abbott Diabetes Care, Alameda, CA) meter compares with that of the One Touch Ultra (Lifescan, Milpitas, CA) home glucose meter (HGM)., Research Design and Methods: Fifty children with type 1 diabetes (T1D), 10-17 years old, were admitted for two separate 24-h periods to assess the effect of exercise on subsequent nocturnal hypoglycemia. Resulting data were used in a preplanned analysis of the accuracy of the Ultra and FreeStyle HGMs. Glucose levels were measured throughout the day and night and every 15-20 min during a standardized exercise protocol. Reference samples were assayed in a central laboratory using a hexokinase enzymatic method. These reference glucose measurements were paired with HGM values from venous blood obtained within +/- 5 min., Results: The median relative absolute difference was 5% for both the Ultra and FreeStyle HGMs, and the percentages of pairs meeting the International Organisation for Standardization criteria were 99% and 98%, respectively. The FreeStyle tended to read slightly higher than the reference method (median difference = +3 mg/dL; P < 0.001), and there was trend in this direction for the Ultra (median difference = +2 mg/dL, P = 0.15). Sensitivities for detection of hypoglycemia (reference < or = 60 and HGM < or = 70 mg/dL) were 96% and 100% for the Ultra and FreeStyle, respectively, and corresponding false-positive rates were both 5%., Conclusions: In a controlled clinical setting using venous blood samples, both the Ultra and FreeStyle meters demonstrated a high degree of accuracy compared with the laboratory reference over a broad range of glucose concentrations in children with T1D.

Objective: We previously reported the results of an inpatient accuracy study in children with type 1 diabetes using the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge, CA). During the course of that study, a new process was implemented for manufacturing the CGMS sensor. Accuracy from the resulting modified sensor used by only 14 children was significantly better than the original version [median relative absolute difference (RAD), 11% vs. 19%; P < 0.001]. Baseline data from a subsequent outpatient study provide an opportunity to further assess the accuracy of the modified sensor in a much larger sample of children with type 1 diabetes., Research Design and Methods: As part of a randomized trial to assess the utility of the GlucoWatch G2 Biographer (Cygnus, Inc., Redwood City, CA), 200 children with type 1 diabetes were instructed to wear a CGMS for 48-72 h in an outpatient setting at baseline. Glucose measurements from a OneTouch UltraSmart (Lifescan, Inc., Milpitas, CA) home glucose meter were downloaded and used as reference values to calculate accuracy measures., Results: The overall median RAD was 12%. Accuracy was better during hyperglycemia than during hypoglycemia (median RAD, 10% vs. 20%; P < 0.001) and on optimal versus non-optimal days but did not vary significantly by the number of calibrations entered., Conclusions: These data confirm the improved accuracy previously reported for the modified version of the CGMS sensor.

Background: The GlucoWatch G2 Biographer (GW2B) (Cygnus, Inc., Redwood City, CA) provides near-continuous monitoring of glucose values in near real time. This device is equipped with two types of alarms to detect hypoglycemia. The hypoglycemia alarm is triggered when the current glucose measurement falls below the level set by the user. The "down alert" alarm is triggered when extrapolation of the current glucose trend anticipates hypoglycemia to occur within the next 20 min., Methods: We used data from an inpatient accuracy study to assess the performance of these alarms. During a 24-h clinical research center stay, 89 children and adolescents with Type 1 diabetes mellitus (3.5-17.7 years old) wore 174 GW2B devices and had frequent serum glucose determinations during the day and night., Results: Sensitivity to detect hypoglycemia (reference glucose < or = 60 mg/dL) during an insulin-induced hypoglycemia test was 24% with the hypoglycemia alarm alone and 88% when combined with the down alert alarm. Overnight sensitivity from 11 p.m. to 6 a.m. was 23% with the hypoglycemia alarm alone and 77% when combined with the down alert alarm. For 16% of hypoglycemia alarms, the reference glucose was above 70 mg/dL for 30 min before and after the time of the alarm. For the two alarm types combined, the corresponding false-positive rate increased to 62%., Conclusions: The down alert alarm substantially improves the sensitivity of the GW2B to detect hypoglycemia at the price of a large increase in the false alarm rate. The utility of these alarms in the day-to-day management of children with diabetes remains to be determined.

Objective: The workup of hypoglycemia requires frequent glucose sampling. We designed these studies to determine if the Continuous Glucose Monitoring System (CGMS) and the GlucoWatch G2 Biographer (GW2B) are sufficiently accurate to use in nondiabetic children. Study design Fifteen healthy children (aged 9-17 years, 11 boys) wore a GW2B and a CGMS during a 24-hour period, and reference serum glucose was measured hourly during the day and half-hourly overnight., Results: Compared with the reference glucose, the median absolute difference in concentrations measured by the GW2B (487 pairs) was 13 mg/dL, and the difference measured by the CGMS was 17 mg/dL (668 pairs), with 30% and 42% of values using the GW2B and CGMS, respectively, deviating >20 mg/dL from the reference value. The GW2B reported values <60 mg/dL in 73% of subjects, the CGMS in 60% of subjects. In none of these episodes was serum glucose truly low. Spurious high glucose concentrations also were observed with the sensors. The mean reference glucose was lowest at 5 am (89 mg/dL) and highest at 11:30 pm (106 mg/dL) during the 24-hour period., Conclusions: Neither the CGMS nor the GW2B is accurate enough to establish population standards of the glycemic profile of healthy children and cannot be recommended in the workup of hypoglycemia in nondiabetic youth.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P

OBJECTIVE: To further evaluate the safety and efficacy of the Control-IQ closed-loop control (CLC) system in children with type 1 diabetes. RESEARCH DESIGN AND METHODS: After a 16-week randomized clinical trial (RCT) comparing CLC with sensor-augmented pump (SAP) therapy in 101 children 6-13 years old with type 1 diabetes, 22 participants in the SAP group initiated use of the CLC system (referred to as SAP-CLC cohort), and 78 participants in the CLC group continued use of CLC (CLC-CLC cohort) for 12 weeks. RESULTS: In the SAP-CLC cohort, mean percentage of time in range 70-180 mg/dL (TIR) increased from 55 ± 13% using SAP during the RCT to 65 ± 10% using CLC (P < 0.001), with 36% of the cohort achieving TIR >70% plus time

Continuous glucose monitors (CGMs) have transformed the way people with type 1 diabetes can self-monitor glucose levels. Past studies have evaluated the accuracy of CGMs in clinic-based studies, but few have analyzed their accuracy in real-world settings. The Insulin-Only Bionic Pancreas Trial provided the opportunity to assess real-world accuracy of the blinded Dexcom G6 Pro sensor over the first 48–60 h of wear using a blood glucose meter (BGM) as a comparator for 1073 CGM–BGM pairs across 53 participants. The mean absolute relative difference (MARD) was 11.0% over a median period of 50 h (range 47–79 h). The MARD was 13.6% in the first 12 h, 10.5% in hours 12–24, and 10.1% after the first 24 h. These results are comparable with accuracy shown previously with laboratory-based measurements and provide real-world evidence of Dexcom G6 Pro accuracy, which improved after the first 12 h and then remained stable thereafter. Clinical Trial Registry: clinicaltrials.gov ; NCT04200313. [ABSTRACT FROM AUTHOR]