ABSTRACT
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.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin , Humans , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Blood Glucose/drug effects , Blood Glucose/analysis , Adult , Insulin/administration & dosage , Insulin/therapeutic use , Male , Female , Administration, Inhalation , Middle Aged , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Postprandial Period , Insulin Infusion Systems , Insulin, Short-Acting/administration & dosage , Insulin, Short-Acting/therapeutic useABSTRACT
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.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin , Humans , Insulin/therapeutic use , Bionics , Diabetes Mellitus, Type 1/drug therapy , Insulin, Regular, Human , Blood Glucose , Blood Glucose Self-Monitoring/methods , Reproducibility of Results , PancreasABSTRACT
Objective: To evaluate the psychosocial impact and user experience for the insulin-only configuration of iLet bionic pancreas (BP) in persons 6-83 years years of age with type 1 diabetes. Research Design and Methods: In this multicenter, randomized controlled, 13-week trial, 275 adults (221 randomly assigned to the BP group and 54 to the standard of care [SC] group) and 165 youth and their caregivers (112 randomly assigned to the BP group and 53 to the SC group) completed psychosocial questionnaires at baseline, mid-study, and the end of the trial. Results: In all age groups, most participants would recommend using the BP, including those with previous experience using automated insulin delivery devices. Similarly, the vast majority of participants reported a high level of perceived benefits and a low number of perceived burdens. Adult participants reported significant decreases in the fear of hypoglycemia and in diabetes-specific emotional distress, as well as improvements in their perceived well-being. Conclusion: Findings demonstrate acceptability, reduced burden, and positive psychosocial outcomes for adults. Children and teenagers also report high acceptability and reduced burden, but less clear improvements in psychosocial outcomes. Clinical Trial Registration Number: NCT04200313.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin , Child , Adult , Humans , Adolescent , Insulin/therapeutic use , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/psychology , Bionics , Caregivers , Insulin, Regular, Human , Pancreas , Hypoglycemic AgentsABSTRACT
Capillary hemoglobin A1c (HbA1c) collection has grown in importance due to its convenience during situations such as the coronavirus disease 2019 (COVID-19) pandemic and virtual visits. The viability of capillary blood samples as an accurate alternative to venous samples has previously only been assessed in smaller sample sizes. In this brief report, 773 paired capillary and venous samples taken from 258 study participants in the Insulin-Only Bionic Pancreas Trial were analyzed at the University of Minnesota Advanced Research and Diagnostic Laboratory and assessed for HbA1c value congruency. Results showed that 97.7% of the capillary samples were within 5% of their respective venous measurement, and R2 between the two HbA1c sources was 0.95. These results are consistent with previous studies that also reported high concordance between capillary and venous HbA1c values using the same laboratory method, providing further evidence that capillary HbA1c measurements are an accurate alternative to venous measurements. Clinical Trial Registration number: NCT04200313.
Subject(s)
COVID-19 , Insulin , Humans , Bionics , Glycated Hemoglobin , Insulin/therapeutic use , Insulin, Regular, Human , PancreasABSTRACT
The bionic pancreas (BP) is initialized with body weight only and doses insulin autonomously without carbohydrate counting, instead using qualitative meal announcements. In case of device malfunction, the BP generates and continuously updates backup insulin doses for injection or pump users, including long-acting insulin dose, a four-period basal insulin profile, short-acting meal doses, and a glucose correction factor. Following a 13-week trial in type 1 diabetes, participants using the BP (6-83 years) completed 2-4 days, in which they were randomly assigned to their prestudy insulin regimen (N = 147) or to follow BP-provided guidance (N = 148). Glycemic outcomes with BP guidance were similar to those reinstituting their prestudy insulin regimen, with both groups having higher mean glucose and lower time-in-range than while using the BP during the 13-week trial. In conclusion, a backup insulin regimen automatically generated by the BP can be safely implemented if need arises to discontinue use of the BP. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.
Subject(s)
Diabetes Mellitus, Type 1 , Pancreas, Artificial , Humans , Insulin/therapeutic use , Hypoglycemic Agents/therapeutic use , Bionics , Blood Glucose , Diabetes Mellitus, Type 1/drug therapy , Insulin, Regular, Human/therapeutic use , Pancreas , Glucose , Insulin Infusion SystemsABSTRACT
Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) using fast-acting insulin aspart (Fiasp®) in adults with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized trial, 275 adults with T1D (18-83 years old, baseline HbA1c 5.3%-14.9%) were randomly assigned 2:2:1 to use the BP with fast-acting insulin aspart (BP-F group, N = 114), BP with aspart or lispro (BP-A/L group, N = 107), or a control group using their standard-care insulin delivery (SC group, N = 54) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. The BP-F versus SC comparison was considered primary and BP-F versus BP-A/L secondary. Results: Mean ± standard deviation (SD) HbA1c decreased from 7.8% ± 1.2% at baseline to 7.1% ± 0.6% at 13 weeks with BP-F versus 7.6% ± 1.2% to 7.5% ± 0.9% with SC (adjusted difference = -0.5%, 95% CI -0.7 to -0.3, P < 0.001). CGM-measured percent time <54 mg/dL over 13 weeks with BP-F was noninferior to SC (adjusted difference = 0.00%, 95% CI -0.07 to 0.05, P < 0.001 for noninferiority based on a prespecified noninferiority limit of 1%). Over 13 weeks, mean time in range 70-180 mg/dL (TIR) increased by 14% (3.4 h/day) and mean CGM glucose was reduced by 18 mg/dL with BP-F compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and the SD of CGM glucose all favored BP-F compared with SC (P < 0.001). Differences between BP-F and BP-A/L were minimal, with no difference in HbA1c at 13 weeks (adjusted difference = -0.0%, 95% CI -0.2 to 0.1, P = 0.67) or mean glucose (adjusted difference = -2.0 mg/dL, 95% CI -4.3 to 0.4, P = 0.10). Mean TIR was 2% greater with BP-F than BP-A/L (95% CI 1 to 4, P = 0.005), but the percentages of participants improving TIR by ≥5% were not significantly different (P = 0.49) and there were no significant differences comparing BP-F versus BP-A/L across nine patient-reported outcome surveys. The rate of severe hypoglycemia events did not differ among the three groups. Conclusions: In adults with T1D, HbA1c was improved with the BP using fast-acting insulin aspart compared with standard care without increasing CGM-measured hypoglycemia. However, the effect was no better than the reduction observed with the BP using aspart or lispro. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.
Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Adolescent , Adult , Aged , Aged, 80 and over , Bionics , Blood Glucose , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Aspart/therapeutic use , Insulin Lispro , Middle Aged , Pancreas , Young AdultABSTRACT
Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) using insulin aspart or insulin lispro in adults with type 1 diabetes (T1D). Methods: In this multicenter, randomized, controlled trial, 161 adults with T1D (18-79 years old, baseline HbA1c 5.5%-13.1%, 32% using multiple daily injections, 27% using a pump without automation, 5% using a pump with predictive low glucose suspend, and 36% using a hybrid closed loop system before the study) were randomly assigned 2:1 to use the BP (N = 107) with insulin aspart or insulin lispro (BP group) or a standard-of-care (SC) control group (N = 54) using their usual insulin delivery plus continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 7.6% ± 1.2% at baseline to 7.1% ± 0.6% at 13 weeks with BP versus 7.6% ± 1.2% to 7.5% ± 0.9% with SC (adjusted difference = -0.5%, 95% confidence interval -0.6% to -0.3%, P < 0.001). Over 13 weeks, mean time in range 70-180 mg/dL (TIR) increased by 11% (2.6 h/d) and mean CGM glucose was reduced by 16 mg/dL with BP compared with SC (P < 0.001). Improvement in these metrics was seen during the first day of BP use and by the end of the first week reached levels that remained relatively stable through 13 weeks. Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose all favored the BP group (P < 0.001). The CGM-measured hypoglycemia was low at baseline (median time <54 mg/dL of 0.21% [3 min/d] for the BP group and 0.11% [1.6 min/d] for the SC group) and not significantly different between groups over the 13 weeks (P = 0.51 for time <70 mg/dL and 0.33 for time <54 mg/dL). There were 7 (6.5% of 107 participants) severe hypoglycemic events in the BP group and 2 events in the SC group (1.9% of 54 participants, P = 0.40). Conclusions: In adults with T1D, use of the BP with insulin aspart or insulin lispro improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.
Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Adolescent , Adult , Aged , Bionics , Blood Glucose/analysis , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Aspart , Insulin Lispro , Insulin, Regular, Human , Middle Aged , Pancreas , Young AdultABSTRACT
Objective: To evaluate a transition from standard-of-care (SC) management of type 1 diabetes (any insulin delivery method including hybrid closed-loop systems plus real-time continuous glucose monitoring [CGM]) to use of the insulin-only configuration of the iLet® bionic pancreas (BP) in 90 adults and children (age 6-71 years). Research Design and Methods: After the SC group completed the randomized controlled trial (RCT) portion of the Insulin-Only BP Pivotal Trial, 90 of the 107 participants participated in a 13-week study using the BP. The key outcomes were change from baseline in HbA1c and CGM metrics after 13 weeks on the BP. Results: Using the BP, mean HbA1c decreased from 7.7% ± 1.0% (61 ± 10.9 mmol/mol) at baseline to 7.1% ± 0.6% (54 ± 6.6 mmol/mol) at 13 weeks (mean change -0.55% ± 0.72% [-6 ± 7.9 mmol/mol], P < 0.001), time in range 70-180 mg/dL increased by 12.0% ± 12.5% (from 53% ± 17% to 65% ± 9%, P < 0.001), and mean glucose decreased by -18 ± 23 mg/dL (from 182 ± 32 to 164 ± 15 mg/dL, P < 0.001). The higher the baseline HbA1c level, the greater the change in HbA1c. Results were similar in the adult (N = 42) and pediatric (N = 48) cohorts. Time <70 mg/dL decreased from baseline over the 13 weeks by -0.50% ± 1.86% (P = 0.02), and time <54 mg/dL was similar (change from baseline -0.08% ± 0.59%, P = 0.24). Two severe hypoglycemia events (in same participant) and one diabetic ketoacidosis event occurred. Conclusions: Glycemic control improved after adult and pediatric participants in the SC arm in the Insulin-Only BP Pivotal Trial transitioned to use of the BP. Improvement using the BP was of similar magnitude to that observed during the RCT. ClinicalTrials.gov number, NCT04200313.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin , Adolescent , Adult , Aged , Bionics , Blood Glucose , Blood Glucose Self-Monitoring/methods , Child , Diabetes Mellitus, Type 1/drug therapy , Glucose , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Infusion Systems , Insulin, Regular, Human/therapeutic use , Middle Aged , Pancreas , Young AdultABSTRACT
Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.2%; 35% using multiple daily injections, 36% using an insulin pump without automation, 4% using an insulin pump with low glucose suspend, and 25% using a hybrid closed-loop system before the study) were randomly assigned 2:1 to use BP (n = 112) with insulin aspart or insulin lispro (BP group) or to a control group (n = 53) using their personal standard care insulin delivery (SC group) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 8.1% ± 1.2% at baseline to 7.5% ± 0.7% at 13 weeks with BP versus 7.8% ± 1.1% at both baseline and 13 weeks with SC (adjusted difference = -0.5%, 95% CI -0.7% to -0.2%, P < 0.001). Participants with baseline HbA1c ≥9.0% (n = 34) decreased mean HbA1c from 9.7% ± 0.8% to 7.9% ± 0.6% after 13 weeks with BP compared with 9.7% ± 0.5% to 9.8% ± 0.8% with SC. Over 13 weeks, mean time in range (TIR) 70-180 mg/dL increased by 10% (2.4 h per day) and mean CGM glucose was reduced by 15 mg/dL with BP compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose favored BP (P < 0.001). Time <54 mg/dL was low at baseline (median 0.2%) and not significantly different between groups over 13 weeks (P = 0.24). A severe hypoglycemia event occurred in 3 (2.7%) participants in the BP group and in 1 (1.9%) in the SC group. Conclusions: In youth 6-17 years old with T1D, use of insulin-only configuration of BP improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Improvement in glycemic metrics was most pronounced in participants with high baseline HbA1c levels. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.
Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Adolescent , Bionics , Blood Glucose/analysis , Blood Glucose Self-Monitoring , Child , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Aspart/therapeutic use , Insulin Infusion Systems , Insulin Lispro/therapeutic use , Insulin, Regular, Human/therapeutic use , PancreasABSTRACT
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<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).
Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin Aspart , Insulin Infusion Systems , Insulin Lispro , Adolescent , Adult , Aged , Bionics/instrumentation , Blood Glucose/analysis , Blood Glucose Self-Monitoring/instrumentation , Blood Glucose Self-Monitoring/methods , Child , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin/administration & dosage , Insulin/adverse effects , Insulin/therapeutic use , Insulin Aspart/administration & dosage , Insulin Aspart/adverse effects , Insulin Aspart/therapeutic use , Insulin Infusion Systems/adverse effects , Insulin Lispro/administration & dosage , Insulin Lispro/adverse effects , Insulin Lispro/therapeutic use , Middle Aged , Young AdultABSTRACT
The publisher of Diabetes Technologies & Therapeutics officially withdraws the Just Accepted version of the article entitled, "Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial," by Laurel H Messer, et al. (epub 28 Jun 2022; DOI: 10.1089/dia.2022.0201) due to its erroneous release before being finalized. The correct version will be republished in due course. The publisher extends its sincerest apologies to the authors of the article and to the journal's readership for this regrettable mishap.
ABSTRACT
OBJECTIVE: To explore the effect of discontinuing continuous glucose monitoring (CGM) after 8 months of CGM use in adults with type 2 diabetes treated with basal without bolus insulin. RESEARCH DESIGN AND METHODS: This multicenter trial had an initial randomization to either real-time CGM or blood glucose monitoring (BGM) for 8 months followed by 6 months in which the BGM group continued to use BGM (n = 57) and the CGM group was randomly reassigned either to continue CGM (n = 53) or discontinue CGM with resumption of BGM for glucose monitoring (n = 53). RESULTS: In the group that discontinued CGM, mean time in range (TIR) 70-180 mg/dL, which improved from 38% before initiating CGM to 62% after 8 months of CGM, decreased after discontinuing CGM to 50% at 14 months (mean change from 8 to 14 months -12% [95% CI -21% to -3%], P = 0.01). In the group that continued CGM use, little change was found in TIR from 8 to 14 months (baseline 44%, 8 months 56%, 14 months 57%, mean change from 8 to 14 months 1% [95% CI -11% to 12%], P = 0.89). Comparing the two groups at 14 months, the adjusted treatment group difference in mean TIR was -6% (95% CI -16% to 4%, P = 0.20). CONCLUSIONS: In adults with type 2 diabetes treated with basal insulin who had been using real-time CGM for 8 months, discontinuing CGM resulted in a loss of about one-half of the initial gain in TIR that had been achieved during CGM use.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Adult , Blood Glucose , Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic useABSTRACT
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.
Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/drug therapy , Glycemic Control/methods , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Aged , Confidence Intervals , Diabetes Mellitus, Type 2/blood , Female , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Patient Satisfaction , Postprandial Period , Sample Size , Time Factors , Treatment OutcomeABSTRACT
Background: Studies of closed-loop control (CLC) in patients with type 1 diabetes (T1D) consistently demonstrate improvements in glycemic control as measured by increased time-in-range (TIR) 70-180 mg/dL. However, clinical predictors of TIR in users of CLC systems are needed. Materials and Methods: We analyzed data from 100 children aged 6-13 years with T1D using the Tandem Control-IQ CLC system during a randomized trial or subsequent extension phase. Continuous glucose monitor data were collected at baseline and during 12-16 weeks of CLC use. Participants were stratified into quartiles of TIR on CLC to compare clinical characteristics. Results: TIR for those in the first, second, third, and fourth quartiles was 54%, 65%, 71%, and 78%, respectively. Lower baseline TIR was associated with lower TIR on CLC (r = 0.69, P < 0.001). However, lower baseline TIR was also associated with greater improvement in TIR on CLC (r = -0.81, P < 0.001). During CLC, participants in the highest versus lowest TIR-quartile administered more user-initiated boluses daily (8.5 ± 2.8 vs. 5.8 ± 2.6, P < 0.001) and received fewer automated boluses (3.5 ± 1.0 vs. 6.0 ± 1.6, P < 0.001). Participants in the lowest (vs. the highest) TIR-quartile received more insulin per body weight (1.13 ± 0.27 vs. 0.87 ± 0.20 U/kg/d, P = 0.008). However, in a multivariate model adjusting for baseline TIR, user-initiated boluses and insulin-per-body-weight were no longer significant. Conclusions: Higher baseline TIR is the strongest predictor of TIR on CLC in children with T1D. However, lower baseline TIR is associated with the greatest improvement in TIR. As with open-loop systems, user engagement is important for optimal glycemic control.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin Infusion Systems , Adolescent , Blood Glucose , Blood Glucose Self-Monitoring , Child , Diabetes Mellitus, Type 1/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic useABSTRACT
Introduction: Hybrid closed-loop systems increase time-in-range (TIR) and reduce glycemic variability. Person-reported outcomes (PROs) are essential to assess the utility of new devices and their impact on quality of life. This article focuses on the PROs for pediatric participants (ages 6-13 years) with type 1 diabetes (T1D) and their parents during a trial using the Tandem Control-IQ system, which was shown to increase TIR and improve other glycemic metrics. Research Design and Methods: One hundred and one children 6 to 13 years old with T1D were randomly assigned to closed-loop control (CLC) or sensor-augmented pump (SAP) in a 16-week randomized clinical trial with extension to 28 weeks during which the SAP group crossed over to CLC. Health-related quality of life and treatment satisfaction measures were obtained from children and their parents at baseline, 16 weeks, and 28 weeks. Results: Neither the children in the CLC group nor their parents had statistically significant changes in PRO outcomes compared with the SAP group at the end of the 16-week randomized controlled trial and the 28-week extension. Parents in the CLC group reported nonsignificant improvements in some PRO scores when compared with the SAP group at 16 weeks, which were sustained at 28 weeks. Sleep scores for parents improved from "poor sleep quality" to "adequate sleep quality" between baseline and 16 weeks, however, the change in scores was not statistically different between groups. Conclusions: Children with T1D who used the Control-IQ system did not experience increased burden compared with those using SAP based on person-reported outcomes from the children and their parents. Clinical Trials Registration: NCT03844789.
Subject(s)
Diabetes Mellitus, Type 1 , Quality of Life , Adolescent , Blood Glucose , Blood Glucose Self-Monitoring , Child , Diabetes Mellitus, Type 1/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Infusion Systems , Parents , Personal SatisfactionABSTRACT
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 <54 mg/dL <1% compared with 14% when using SAP (P = 0.03). Substantial improvement in TIR was seen after the 1st day of CLC. Time <70 mg/dL decreased from 1.80% to 1.34% (P < 0.001). In the CLC-CLC cohort, mean TIR increased from 53 ± 17% prerandomization to 67 ± 10% during the RCT and remained reasonably stable at 66 ± 10% through the 12 weeks post-RCT. No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either cohort. CONCLUSIONS: This further evaluation of the Control-IQ CLC system supports the findings of the preceding RCT that use of a closed-loop system can safely improve glycemic control in children 6-13 years old with type 1 diabetes from the 1st day of use and demonstrates that these improvements can be sustained through 28 weeks of use.
Subject(s)
Diabetes Mellitus, Type 1 , Hypoglycemia , Adolescent , Blood Glucose , Child , Diabetes Mellitus, Type 1/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Insulin Infusion SystemsABSTRACT
Basal insulin is often prescribed to patients with suboptimally controlled type 2 diabetes (T2D); however, its therapeutic efficacy is inadequate in many. During the MOBILE study's baseline phase, we evaluated 173 participants' continuous glucose monitoring (CGM) data (mean ± SD age 57 ± 9 years; 50% female; HbA1c 9.1% [range 7.1%-11.6%]; 40% using sulphonylureas; 19% using NPH; reported self-monitored blood glucose [SMBG] frequency median 1.0 checks/day) who were using basal, but not prandial insulin. Blinded CGM data were recorded for 10 days prior to randomization. The mean glucose value was 208 ± 47 mg/dL and it was lowest in the early morning. Mean time in the 70-180 mg/dL range was 9.6 ± 6.1 hours/day (40% ± 25%). Hyperglycaemia was extensive with medians of 14.7 (61%) and 5.0 (20.9%) hours/day with glucose greater than 180 and 250 mg/dL, respectively. Hypoglycaemia was infrequent (median [IQR] 0 [0, 4.3] minutes/day [0.0% {0.0%, 0.3%}] with glucose less than 70 mg/dL). Blinded CGM highlights the limitations of infrequent SMBG in basal insulin users with T2D and allows characterization of hyperglycaemia and hypoglycaemia in basal insulin users with suboptimal control. The MOBILE study randomized phase will define the benefits of using real-time CGM compared with SMBG in this population.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Aged , Blood Glucose , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 2/drug therapy , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Insulin , Male , Middle AgedABSTRACT
BACKGROUND: A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes. METHODS: In a 16-week, multicenter, randomized, open-label, parallel-group trial, we assigned, in a 3:1 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. RESULTS: A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop group and from 51±16% to 55±13% in the control group (mean adjusted difference, 11 percentage points [equivalent to 2.6 hours per day]; 95% confidence interval, 7 to 14; P<0.001). In both groups, the median percentage of time that the glucose level was below 70 mg per deciliter was low (1.6% in the closed-loop group and 1.8% in the control group). In the closed-loop group, the median percentage of time that the system was in the closed-loop mode was 93% (interquartile range, 91 to 95). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group. CONCLUSIONS: In this 16-week trial involving children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT03844789.).
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Infusion Pumps, Implantable , Insulin Infusion Systems , Insulin/administration & dosage , Adolescent , Blood Glucose/analysis , Child , Diabetes Mellitus, Type 1/blood , Diabetic Ketoacidosis/etiology , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Injections, Subcutaneous , Insulin/adverse effects , Insulin Infusion Systems/adverse effects , Male , Pancreas, ArtificialSubject(s)
Diabetes Mellitus, Type 1 , Female , Humans , Insulin , Insulin Infusion Systems , PregnancyABSTRACT
OBJECTIVE: To compare glycemic control, quality of life, and pregnancy outcomes of women using insulin pumps and multiple daily injection therapy (MDI) during the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT). RESEARCH DESIGN AND METHODS: This was a prespecified analysis of CONCEPTT involving 248 pregnant women from 31 centers. Randomization was stratified for pump versus MDI and HbA1c. The primary outcome was change in HbA1c from randomization to 34 weeks' gestation. Key secondary outcomes were continuous glucose monitoring (CGM) measures, maternal-infant health, and patient-reported outcomes. RESULTS: At baseline, pump users were more often in stable relationships (P = 0.003), more likely to take preconception vitamins (P = 0.03), and less likely to smoke (P = 0.02). Pump and MDI users had comparable first-trimester glycemia: HbA1c 6.84 ± 0.71 vs. 6.95 ± 0.58% (51 ± 7.8 vs. 52 ± 6.3 mmol/mol) (P = 0.31) and CGM time in target (51 ± 14 vs. 50 ± 13%) (P = 0.40). At 34 weeks, MDI users had a greater decrease in HbA1c (-0.55 ± 0.59 vs. -0.32 ± 0.65%, P = 0.001). At 24 and 34 weeks, MDI users were more likely to achieve target HbA1c (P = 0.009 and P = 0.001, respectively). Pump users had more hypertensive disorders (P = 0.011), mainly driven by increased gestational hypertension (14.4 vs. 5.2%; P = 0.025), and more neonatal hypoglycemia (31.8 vs. 19.1%, P = 0.05) and neonatal intensive care unit (NICU) admissions >24 h (44.5 vs. 29.6%; P = 0.02). Pump users had a larger reduction in hypoglycemia-related anxiety (P = 0.05) but greater decline in health/well-being (P = 0.02). CONCLUSIONS: In CONCEPTT, MDI users were more likely to have better glycemic outcomes and less likely to have gestational hypertension, neonatal hypoglycemia, and NICU admissions than pump users. These data suggest that implementation of insulin pump therapy is potentially suboptimal during pregnancy.