Diabetic Ketoacidosis Events Research Articles

679-P: Costs and Cost-Effectiveness of the FreeStyle Libre System vs. Blood Glucose Self-Monitoring in Patients with Type 2 on MDI Insulin Treatment in Israel

Introduction: Frequent glucose monitoring is essential to obtaining glucose control. We assessed the costs and cost-effectiveness of using the FreeStyle Libre® Flash Continuous Glucose Monitoring system (FSL) compared to self-monitoring of blood glucose (SMBG) in people with type 2 diabetes treated with multiple daily insulin injections (T2D MDI) from a healthcare payer perspective in Israel. Methods: We calculated the incremental cost per quality adjusted life year (QALY) gained. Glucose monitoring costs are based on actual costs of FreeStyle Libre®, strips and lancets, assuming full adherence to monitoring. Severe hypoglycemic events (SHE) and diabetic ketoacidosis (DKA) costs are based on real-world data from Israel and the Israeli Ministry of Health list price. Costs are presented in Israeli Shekel (ILS) and $US. The incidence rates of SHE and DKA are based on real-world data from a large cohort of patients in France. Due to the short time horizon of this analysis, we assumed no mortality differences between the two monitoring alternatives. Utility increments for the use of CGM vs. SMBG, decrease in HbA1C and disutility for SHE and DKA events are based on estimates from the literature. The analysis was conducted over a 5-year time horizon, applying an annual discount rate of 3% on costs and outcomes. One way sensitivity analyses were performed on difference in costs. Results: FreeStyle Libre® use is associated with a cost increase of ILS 27,021 ($US 8,444) and an increase of 0.26 QALYs, generating an incremental cost-effectiveness ratio of ILS 103,977 ($US 32,493) per QALY gained. These results are highly sensitive to changes in costs of glucose monitoring. Conclusion: Assuming a willingness to pay threshold of $US 43,600 per QALY gained (GDP per capita in Israel in 2020) , the FreeStyle Libre® system is a highly cost-effective glucose monitoring alternative to SMBG for T2D MDI patients in Israel. Disclosure D.Greenberg: Advisory Panel; Abbott Diabetes, Consultant; Geffen Medical, Israel.

510-P: DKA Prevention on Insulin Pumps: Lessons Learned from a Large Pediatric Pump Practice

While the Type 1 Diabetes Exchange data noted that diabetic ketoacidosis (DKA) is more common in those utilizing injection regimens than insulin pumps, DKA remains a risk for pump users, as it can precipitously develop if insulin infusion is interrupted. We sought to obtain more recent DKA admission data in T1D youth using insulin pumps and the impact of CGM on DKA rates. Methods: We characterized DKA data in insulin pump users from episodes between 12/20 and 6/2021 in an academic pediatric endocrine practice in which 68% were pump users. Results: Among 591 pump patients aged <25 years (y) , 28 events occurred (3.16 events per 100 patient-y. Mean age was 13.6±3.4y; 85.7% were 12-19y old. More events were in males (60.7%) , 53.6% were white, 71.4% non-Hispanic. Mean HbA1c was 10.22.3%, diabetes duration 6.1±4.0y, and 57.1% used CGM; 28.6% of patients were new to pump therapy (<1y) .Admission pH levels ranged between 7.0-7.31, with 28.6% of events classified as “moderate” and 46.4% as “severe.” Average length of stay was 2.0±0.7 days. While there was no significant difference in pH levels, CGM wearers had higher admission bicarbonate values (11.8 vs. 9.3, p=0.04) . Clinicians assessed the cause of DKA to be related to concurrent illness (10.7%) , insulin omission (14.3%) , pump infusion site failure (57.1%) or other pump malfunctions (14.3%) . For most (60.7%) , this was the first documented DKA event. Alcohol consumption was a contributing factor in only one event. Conclusions: DKA events were relatively uncommon; most episodes occurred in adolescents in poor diabetes control. Notably, most events could have been avoided if users followed standard trouble shooting guidelines. Thus, education on DKA prevention should be reinforced at each visit, particularly for teens on pumps with higher A1c levels. Moreover, while CGM wearers had higher admission bicarbonate values, over 50% of those hospitalized for DKA wore a CGM, suggesting even pump users using CGM require frequent reinforcement of DKA prevention education. Disclosure E.Doyle: None. S.A.Weinzimer: Consultant; Dompé, Research Support; Abbott Diabetes, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc. W.V.Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited.

In-home use of a hybrid closed loop achieves time-in-range targets in preschoolers and school children: Results from a randomized, controlled, crossover trial.

To obtain additional information on the incremental differences between using a sensor-augmented pump (SAP) without automated insulin delivery (AID), using it with predictive low-glucose management (PLGM) or as hybrid closed loop (HCL), in preschool and school children. We conducted a monocentric, randomized, controlled, two-phase crossover study in 38 children aged 2-6 and 7-14 years. The primary endpoint was the percentage of time in range (TIR) of 70-180 mg/dl. Other continuous glucose sensor metrics, HbA1c, patient-related outcomes (DISABKIDS questionnaire, Fear of Hypoglycaemia Survey) and safety events were also assessed. Results from 2 weeks of SAP, 8 weeks of PLGM and 8 weeks of HCL were compared using a paired t-test or Wilcoxon signed-rank test. Overall, we found a high rate of TIR target (>70%) achievement with HCL in preschool (88%) and school children (50%), with average times in Auto Mode of 93% and 87%, respectively. Preschool children achieved a mean TIR of 73% ± 6% (+8% vs. SAP, +6% vs. PLGM) and school children 69% ± 8% (+15% vs. SAP and + 14% vs. PLGM). Overall, HbA1c improved from 7.4% ± 0.9% to 6.9% ± 0.5% (P= .0002). Diabetes burden and worries and fear of hypoglycaemia remained at low levels, without significant changes versus PLGM. No events of severe hypoglycaemia or diabetic ketoacidosis occurred. Preschool children profit from AID at least as much as those aged 7 years and older. To ensure safe use and prescribing modalities, regulatory approval is also required for young children.

Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study

Since there are few treatment options for young people with type 2 diabetes, we aimed to assess the efficacy and safety of dapagliflozin as add-on therapy in children, adolescents, and young adults with type 2 diabetes receiving metformin, insulin, or both. This multicentre, placebo-controlled, double-blind, randomised phase 3 study was undertaken at 30 centres in five countries (Hungary, Israel, Mexico, Russia, and the USA). Participants aged 10-24 years with type 2 diabetes and HbA1c concentration of 6·5-11% (48-97 mmol/mol) were randomly assigned 1:1 to oral dapagliflozin 10 mg or placebo during a 24 week double-blind period, which was then followed by a 28 week open-label safety extension in which all participants received dapagliflozin. Participants and study personnel were masked and participants were randomly assigned treatment (placebo or study drug) using an interactive web and voice response system. The primary outcome was between-group differences in change in HbA1c concentration from baseline to 24 weeks (intention-to-treat analysis). A prespecified sensitivity analysis of the primary outcome was also assessed in the per-protocol population, which included only protocol-compliant participants. This trial is registered with ClinicalTrials.gov, NCT02725593. Between June 22, 2016, and March 15, 2019, 72 participants (19 [26%] of whom were aged 18-24 years) were randomly assigned (39 to dapagliflozin and 33 to placebo). Mean age was 16·1 (SD 3·3) years. In the intention-to-treat analysis, after 24 weeks, mean change in HbA1c concentration was -0·25% (95% CI -0·85 to 0·34; -2·7 [-9·3 to 3·7] mmol/mol) for dapagliflozin and 0·50% (-0·18 to 1·17; 5·5 [-2·0 to 12·8] mmol/mol) for placebo. The between-group difference was -0·75% (95% CI -1·65 to 0·15; -8·2 [-18·0 to 1·6] mmol/mol; p=0·10). In a sensitivity analysis in the per-protocol population (34 in the dapagliflozin group and 26 in the placebo group) after 24 weeks, mean change was -0·51% (-1·07 to 0·05; -5·6 [-11·7 to 0·5] mmol/mol) for dapagliflozin and 0·62% (-0·04 to 1·27; 6·8 [-0·4 to 13·9] mmol/mol) for placebo. The between-group difference was -1·13% (-1·99 to -0·26; -12·4 [-21·8 to -2·8] mmol/mol; p=0·012). Adverse events occurred in 27 (69%) dapagliflozin-assigned participants and 19 (58%) placebo-assigned participants over 24 weeks, and in 29 (74%) participants who received dapagliflozin over 52 weeks. Hypoglycaemia occurred in 11 (28%) dapagliflozin-assigned and six (18%) placebo-assigned participants who received dapagliflozin over 24 weeks and in 13 participants (33%) who received dapagliflozin over 52 weeks; none were considered as serious adverse events. No adverse events of diabetic ketoacidosis occurred. The primary outcome of change in HbA1c concentration was not significant in the intention-to-treat analysis of children, adolescents, and young adults with type 2 diabetes receiving dapagliflozin in addition to standard-of-care treatment. A prespecified sensitivity analysis of protocol-compliant participants showed a significant difference in HbA1c concentration between groups. No new safety signals were identified and there was a low risk of severe hypoglycaemia. AstraZeneca.

Trends in Type 1 Diabetic Ketoacidosis During COVID-19 Surges at 7 US Centers: Highest Burden on non-Hispanic Black Patients.

ContextThe impact of the COVID-19 pandemic on individuals with type 1 diabetes remains poorly defined.ObjectiveWe examined United States trends in diabetic ketoacidosis (DKA) among individuals with type 1 diabetes (T1D) during the COVID-19 pandemic at 7 large US medical centers and factors associated with these trends.MethodsWe compared DKA events among children and adults with T1D during COVID-19 surge 1 (March-May 2020) and COVID-19 surge 2 (August-October 2020) to the same periods in 2019. Analysis was performed using descriptive statistics and chi-square tests.ResultsWe found no difference in the absolute number of T1D patients experiencing DKA in 2019 vs 2020. However, a higher proportion of non-Hispanic Black (NHB) individuals experienced DKA in 2019 than non-Hispanic White (NHW) individuals (44.6% vs 16.0%; P < .001), and this disparity persisted during the COVID-19 pandemic (48.6% vs 18.6%; P < .001). DKA was less common among patients on continuous glucose monitor (CGM) or insulin pump in 2020 compared to 2019 (CGM: 13.2% vs 15.0%, P < .001; insulin pump: 8.0% vs 10.6%, P < .001). In contrast to annual DKA totals, a higher proportion of patients had DKA during COVID-19 surges 1 and 2 compared to the same months in 2019 (surge 1: 7.1% vs 5.4%, P < .001; surge 2: 6.6% vs 5.7%, P = .001).ConclusionDKA frequency increased among T1D patients during COVID-19 surges with highest frequency among NHB patients. DKA was less common among patients using CGM or insulin pumps. These findings highlight the urgent need for improved strategies to prevent DKA among patients with T1D—not only under pandemic conditions, but under all conditions—especially among populations most affected by health inequities.

Evaluation of Extended Infusion Set Performance in Adults with Type 1 Diabetes: Infusion Set Survival Rate and Glycemic Outcomes from a Pivotal Trial

Background:Standard insulin infusion sets (IISs) are to be replaced every 2 to 3 days to avoid complications and diabetic ketosis due to set failure. This pivotal trial evaluated the safety and performance of a new extended-wear infusion set (EIS) when used for 7 days by adults with type 1 diabetes (T1D).Methods:This single-arm, nonrandomized trial enrolled adults (18–80 years of age) with T1D, who used their own MiniMed™ 670G system with insulin lispro or insulin aspart and the EIS for up to 7 days, across 12 consecutive wears. Safety endpoints included incidence of serious adverse events (SAEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), severe hypoglycemia (SevHypo), severe hyperglycemia (SevHyper), diabetic ketoacidosis (DKA), and skin infection. The EIS failure rate due to unexplained hyperglycemia (i.e., suspected occlusion), the overall EIS survival rate, glycemic control outcomes (i.e., A1C, mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered, and satisfaction with the EIS were determined.Results:The intention to treat population (n = 259, 48% men, 45.0 ± 14.1 years) wore a total of 3041 EIS devices. No SADE, UADE, or DKA events was reported. Overall rates of SAEs, SevHypo, SevHyper, and skin infection were 3.8, 2.5, 104.1, and 20.1 events per 100 participant-years. The rate of EIS failure due to unexplained hyperglycemia at the end of day 7 was 0.1% (95% confidence interval [CI]: 0.03–0.51) and 0.4% (95% CI: 0.16–1.00) for insulin lispro and aspart use, respectively. Overall EIS survival rate at the end of day 7 was 77.8% (95% CI: 76.2–79.3), glycemic control did not change, and participants reported greater satisfaction with the EIS compared with standard IISs worn before the study (P < 0.001).Conclusions:This investigation demonstrates that the EIS, when worn for up to 7 days, was safe and rated with high satisfaction, without adversely affecting glycemic control in adults with T1D.Clinical Trial Registration number: NCT04113694 (https://clinicaltrials.gov/ct2/show/NCT04113694).

Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial

Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. In a multicentre, multinational, parallel randomised controlled trial, participants aged 6-18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0-10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference -3·5 mmol/mol (95% CI -6·5 to -0·5 [-0·32 percentage points, -0·59 to -0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26-53]), but consistently high with CamAPS FX (93% [88-96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. National Institute of Diabetes and Digestive and Kidney Diseases.

Effectiveness of continuous glucose monitoring in maintaining glycaemic control among people with type 1 diabetes mellitus: a systematic review of randomised controlled trials and meta-analysis.

The aim of this work was to assess the effectiveness of continuous glucose monitoring (CGM) vs self-monitoring of blood glucose (SMBG) in maintaining glycaemic control among people with type 1 diabetes mellitus. Cochrane Library, PubMed, Embase, CINAHL, Scopus, trial registries and grey literature were searched from 9 June 2011 until 22 December 2020 for RCTs comparing CGM intervention against SMBG control among the non-pregnant individuals with type 1 diabetes mellitus of all ages and both sexes on multiple daily injections or continuous subcutaneous insulin infusion with HbA1c levels, severe hypoglycaemia and diabetic ketoacidosis (DKA) as outcomes. Studies also included any individual or caregiver-led CGM systems. Studies involving GlucoWatch were excluded. Risk of bias was appraised with Cochrane risk of bias tool. Meta-analysis and meta-regression were performed using Review Manager software and R software, respectively. Heterogeneity was evaluated using χ2 and I2 statistics. Overall effects and certainty of evidence were evaluated using Z statistic and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) software. Twenty-two studies, involving 2188 individuals with type 1 diabetes, were identified. Most studies had low risk of bias. Meta-analysis of 21 studies involving 2149 individuals revealed that CGM significantly decreased HbA1c levels compared with SMBG (mean difference -2.46mmol/mol [-0.23%] [95% CI -3.83, -1.08], Z = 3.50, p=0.0005), with larger effects experienced among higher baseline HbA1c >64mmol/mol (>8%) individuals (mean difference -4.67mmol/mol [-0.43%] [95% CI -6.04, -3.30], Z = 6.69, p<0.00001). However, CGM had no influence on the number of severe hypoglycaemia (p=0.13) and DKA events (p=0.88). Certainty of evidence was moderate. CGM is superior to SMBG in improving glycaemic control among individuals with type 1 diabetes in the community, especially in those with uncontrolled glycaemia. Individuals with type 1 diabetes with HbA1c >64mmol/mol (>8%) are most likely to benefit from CGM. Current findings could not confer a concrete conclusion on the effectiveness of CGM on DKA outcome as DKA incidences were rare. Current evidence is also limited to outpatient settings. Future research should evaluate the accuracy of CGM and the effectiveness of CGM across different age groups and insulin regimens as these remain unclear in this paper. Registration no. CRD42020207042. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Incidence of diabetic ketoacidosis during Ramadan compared with non-fasting months in King Saud Medical City, Riyadh, Saudi Arabia.

Ramadan in Islam is the ninth month of the Muslim calendar and the holy month of fasting. In the fasting state, there is the danger of the blood glucose levels becoming too high when normal levels of medication are not taken. This can lead to diabetic ketoacidosis (DKA). The risk of diabetic emergencies, including DKA, is thought to be higher during Ramadan fasting due to metabolic changes and alterations in food habits. We aim to assess the incidence of DKA during Ramadan and perform a comparison pre and post month of Ramadan. This is a retrospective study that involves all adults who were admitted with DKA to King Saud Medical City in Riyadh, Saudi Arabia. We explored the relationship of admissions to Ramadan and compared it to the month before (Sha'aban) and the month after (Shawwal). During the duration of the study, 51 patients with DKA were admitted to the hospital. Nineteen patients in Ramadan (37.3%), eight patients in Sha'aban (15.7%), and 24 patients in Shawwal (47%). This shows a significant increment in Ramadan compared to Sha'aban, and more increment in Shawwal (P = 0.019). The most common precipitating factor for diabetic ketoacidosis during Ramadan and Sha'aban is missing insulin dose, while infections are considered the main stimulating agent in Shawwal. There was an increase in the incidence of DKA episodes in Ramadan compared with the preceding month, but fewer DKA events compared to Shawwal, which might indicate that Ramadan fasting is a potential risk factor for DKA.

Monitoring the Comparative Safety of SGLT2i vs GLP-1 RA in Older Adults With Type 2 Diabetes by Frailty Status

Using Medicare (4/2013-12/2017), we conducted 9 sequential analyses of patients with type 2 diabetes initiating SGLT2i vs. GLP1-RA mimicking the accrual of new data every 6 months to monitor SGLT2i safety with respect to diabetic ketoacidosis (DKA) since their U.S. approval. For each analysis, we estimated cumulative HRs (95% CIs) after 1:1 propensity score matching on >70 covariates comparing treatments within frail and non-frail patients. By analysis 1, SGLT2i were associated with a higher DKA rate vs. GLP-1RA in both frail and non-frail patients, but results were highly imprecise due to few events. With the accrual of more DKA events, precision of the estimates continued to improve through analysis 9 [HR=2.95 (95% CI, 1.19-7.31)] in frail patients; [HR=1.77 (1.15, 2.75)] in non-frail patients], with sufficiently precise estimates by analysis 6 in frail patients [HR=2.80 (95% CI, 1.03, 7.61)] and by analysis 7 in non-frail patients [HR=1.62 (95% CI, 1.01, 2.57)].

Improved HbA1c and reduced glycaemic variability after 1-year intermittent use of flash glucose monitoring

Flash glucose monitoring (FGM) was introduced in China in 2016, and it might improve HbA1c measurements and reduce glycaemic variability during T1DM therapy. A total of 146 patients were recruited from October 2018 to September 2019 in Liaocheng. The patients were randomly divided into the FGM group or self-monitoring blood glucose (SMBG) group. Both groups wore the FGM device for multiple 2-week periods, beginning with the 1st, 24th, and 48th weeks for gathering data, while blood samples were also collected for HbA1c measurement. Dietary guidance and insulin dose adjustments were provided to the FGM group patients according to their Ambulatory Glucose Profile (AGP) and to the SMBG group patients according to their SMBG measurements taken 3–4 times daily. All of the participants underwent SMBG measurements on the days when not wearing the FGM device. At the final visit, HbA1c, time in range (TIR), duration of hypoglycaemia and the number of diabetic ketoacidosis (DKA) events were taken as the main endpoints. There were no significant difference in the baseline characteristics of the two groups. At 24 weeks, the HbA1c level of the FGM group was 8.16 ± 1.03%, which was much lower than that of the SMBG group (8.68 ± 1.01%) (p = 0.003). The interquartile range (IQR), mean blood glucose (MBG), and the duration of hypoglycaemia in the FGM group also showed significant declines, compared with the SMBG group (p < 0.05), while the TIR increased in the FGM group [(49.39 ± 17.54)% vs (42.44 ± 15.49)%] (p = 0.012). At 48 weeks, the differences were more pronounced (p < 0.01). There were no observed changes in the number of episodes of DKA by the end of the study [(0.25 ± 0.50) vs (0.28 ± 0.51), p = 0.75]. Intermittent use of FGM by T1DM patients can improve their HbA1c and glycaemic control without increasing the hypoglycaemic exposure in insulin-treated individuals with type 1 diabetes in an developing country.

Safety and Glycemic Outcomes During the MiniMed™ Advanced Hybrid Closed-Loop System Pivotal Trial in Adolescents and Adults with Type 1 Diabetes.

Introduction:This trial assessed safety and effectiveness of an advanced hybrid closed-loop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D).Materials and Methods:This multicenter single-arm study involved an intent-to-treat population of 157 individuals (39 adolescents aged 14–21 years and 118 adults aged ≥22–75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/− predictive low glucose management or Auto Basal was enabled for ∼14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (∼90 days), with glucose target set to 100 or 120 mg/dL for ∼45 days, followed by the other target for ∼45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70–180 mg/dL) and time below range (TBR, <70 mg/dL). Run-in and study phase values were compared using Wilcoxon signed-rank test or paired t-test.Results:Overall group time spent in closed loop averaged 94.9% ± 5.4% and involved only 1.2 ± 0.8 exits per week. Compared with run-in, AHCL reduced A1C from 7.5% ± 0.8% to 7.0% ± 0.5% (<0.001, Wilcoxon signed-rank test, n = 155), TIR increased from 68.8% ± 10.5% to 74.5% ± 6.9% (<0.001, Wilcoxon signed-rank test), and TBR reduced from 3.3% ± 2.9% to 2.3% ± 1.7% (<0.001, Wilcoxon signed-rank test). Similar benefits to glycemia were observed for each age group and were more pronounced for the nighttime (12 AM–6 AM). The 100 mg/dL target increased TIR to 75.4% (n = 155), which was further optimized at a lower active insulin time (AIT) setting (i.e., 2 h), without increasing TBR. There were no severe hypoglycemic or diabetic ketoacidosis events during the study phase.Conclusions:These findings show that the MiniMed AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D. Adjustments in target and AIT settings may further optimize glycemia and improve user experience.Clinical Trial Registration number: NCT03959423.

Flash monitor initiation is associated with improvements in HbA1c levels and DKA rates among people with type 1 diabetes in Scotland: a retrospective nationwide observational study

Aims/hypothesisWe assessed the real-world effect of flash monitor (FM) usage on HbA1c levels and diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH) rates among people with type 1 diabetes in Scotland and across sociodemographic strata within this population.MethodsThis study was retrospective, observational and registry based. Using the national diabetes registry, 14,682 individuals using an FM at any point between 2014 and mid-2020 were identified. Within-person change from baseline in HbA1c following FM initiation was modelled using linear mixed models accounting for within-person pre-exposure trajectory. DKA and SHH events were captured through linkage to hospital admission and mortality data. The difference in DKA and SHH rates between FM-exposed and -unexposed person-time was assessed among users, using generalised linear mixed models with a Poisson likelihood. In a sensitivity analysis, we tested whether changes in these outcomes were seen in an age-, sex- and baseline HbA1c-matched sample of non-users over the same time period.ResultsPrevalence of ever-FM use was 45.9% by mid-2020, with large variations by age and socioeconomic status: 64.3% among children aged <13 years vs 32.7% among those aged ≥65 years; and 54.4% vs 36.2% in the least-deprived vs most-deprived quintile. Overall, the median (IQR) within-person change in HbA1c in the year following FM initiation was −2.5 (−9.0, 2.5) mmol/mol (−0.2 [−0.8, 0.2]%). The change varied widely by pre-usage HbA1c: −15.5 (−31.0, −4.0) mmol/mol (−1.4 [−2.8, −0.4]%) in those with HbA1c > 84 mmol/mol [9.8%] and 1.0 (−2.0, 5.5) mmol/mol (0.1 [−0.2, 0.5]%) in those with HbA1c < 54 mmol/mol (7.1%); the corresponding estimated fold change (95% CI) was 0.77 (0.76, 0.78) and 1.08 (1.07, 1.09). Significant reductions in HbA1c were found in all age bands, sexes and socioeconomic strata, and regardless of prior/current pump use, completion of a diabetes education programme or early FM adoption. Variation between the strata of these factors beyond that driven by differing HbA1c at baseline was slight. No change in HbA1c in matched non-users was observed in the same time period (median [IQR] within-person change = 0.5 [−5.0, 5.5] mmol/mol [0.0 (−0.5, 0.5)%]). DKA rates decreased after FM initiation overall and in all strata apart from the adolescents. Estimated overall reduction in DKA event rates (rate ratio) was 0.59 [95% credible interval (CrI) 0.53, 0.64]) after FM vs before FM initiation, accounting for pre-exposure trend. Finally, among those at higher risk for SHH, estimated reduction in event rates was rate ratio 0.25 (95%CrI 0.20, 0.32) after FM vs before FM initiation.Conclusions/interpretationFM initiation is associated with clinically important reductions in HbA1c and striking reduction in DKA rate. Increasing uptake among the socioeconomically disadvantaged offers considerable potential for tightening the current socioeconomic disparities in glycaemia-related outcomes.Graphical abstract

Rising Rates and Widening Socioeconomic Disparities in Diabetic Ketoacidosis in Type 1 Diabetes in Scotland: A Nationwide Retrospective Cohort Observational Study.

Whether advances in the management of type 1 diabetes are reducing rates of diabetic ketoacidosis (DKA) is unclear. We investigated time trends in DKA rates in a national cohort of individuals with type 1 diabetes monitored for 14 years, overall and by socioeconomic characteristics. All individuals in Scotland with type 1 diabetes who were alive and at least 1 year old between 1 January 2004 and 31 December 2018 were identified using the national register (N = 37,939). DKA deaths and hospital admissions were obtained through linkage to Scottish national death and morbidity records. Bayesian regression was used to test for DKA time trends and association with risk markers, including socioeconomic deprivation. There were 30,427 DKA admissions and 472 DKA deaths observed over 393,223 person-years at risk. DKA event rates increased over the study period (incidence rate ratio [IRR] per year 1.058 [95% credibility interval 1.054-1.061]). Males had lower rates than females (IRR male-to-female 0.814 [0.776-0.855]). DKA incidence rose in all age-groups other than 10- to 19-year-olds, in whom rates were the highest, but fell over the study. There was a large socioeconomic differential (IRR least-to-most deprived quintile 0.446 [0.406-0.490]), which increased during follow-up. Insulin pump use or completion of structured education were associated with lower DKA rates, and antidepressant and methadone prescription were associated with higher DKA rates. DKA incidence has risen since 2004, except in 10- to 19-year-olds. Of particular concern are the strong and widening socioeconomic disparities in DKA outcomes. Efforts to prevent DKA, especially in vulnerable groups, require strengthening.

Multicenter Trial of a Tubeless, On-Body Automated Insulin Delivery System With Customizable Glycemic Targets in Pediatric and Adult Participants With Type 1 Diabetes.

OBJECTIVEAdvances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets.RESEARCH DESIGN AND METHODSThis single-arm, multicenter, prospective study enrolled 112 children (age 6–13.9 years) and 129 adults (age 14–70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA1c and percent time in sensor glucose range 70–180 mg/dL (“time in range”).RESULTSA total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P < 0.0001) and in adults by 0.38% (4.2 mmol/mol) (7.16 ± 0.86% to 6.78 ± 0.68% [55 ± 9.4 mmol/mol to 51 ± 7.4 mmol/mol], P < 0.0001). Time in range was improved from standard therapy by 15.6 ± 11.5% or 3.7 h/day in children and 9.3 ± 11.8% or 2.2 h/day in adults (both P < 0.0001). This was accomplished with a reduction in time in hypoglycemia <70 mg/dL among adults (median [interquartile range]: 2.00% [0.63, 4.06] to 1.09% [0.46, 1.75], P < 0.0001), while this parameter remained the same in children. There were three severe hypoglycemia events not attributable to automated insulin delivery malfunction and one diabetic ketoacidosis event from an infusion site failure.CONCLUSIONSThis tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA1c levels and time in target glucose range with a very low occurrence of hypoglycemia.

Screening for Autoantibodies in Type 1 Diabetes: A Call to Action.

• Type 1 diabetes (T1D) is an autoimmune disease that progresses through 3 distinct stages. • T1D can be diagnosed at any age, with a peak incidence at 10-14 years of age. • The incidence of T1D in the United States is rising. • Screening for T1D autoantibodies has positive clinical consequences, including reduction of diabetic ketoacidosis events, improved glycemic control, and positive impact on short- and long-term complications. • Primary care clinicians can play a critical role in promoting islet autoantibody screening.

69-LB: Nonadjunctive Continuous Glucose Monitoring to Control Hypoglycemia (COACH)

Previous studies have been insufficiently powered to assess whether CGM can reduce severe hypoglycemia. The Continuous Monitoring and Control of Hypoglycemia study evaluated nonadjunctive use of the Dexcom CGM system for diabetes management decisions in adults new to CGM. This post-approval 12-month observational study enrolled adults with insulin-requiring diabetes who based diabetes management and insulin dosing decisions on self-monitored blood glucose (SMBG) values for 6 months and then on CGM for 6 months. Per protocol, diabetes management was per usual care. Subjects were queried monthly about hypoglycemic and diabetic ketoacidosis (DKA) events. The primary outcome was change in moderate (requiring third party assistance) and severe (seizure or loss of consciousness) hypoglycemic event frequency between SMBG and CGM phases; secondary outcomes included DKA events. The per-protocol population included all 519 adult subjects who completed the 12-month visit with mean±SD age 50.3±16.1 y, A1C 8.0±1.4%, 32.8% with impaired hypoglycemia awareness, 54.1% male, 66.5% and 33.5% with T1D/T2D, and 29.7% using pumps. Compared to the SMBG phase, the frequency of moderate and severe hypoglycemic events was significantly (p=0.0051) lower during the CGM phase; DKA frequency was also lower (Table). Compared to SMBG, nonadjunctive CGM use reduces rates of severe hypoglycemia and DKA. Disclosure S. Beck: Employee; Self; Dexcom, Inc. C. Kelly: Consultant; Self; Ajinomoto Co., Inc., Dexcom, Inc., Hitachi, Ltd., Vascular Dynamics Inc. N. Njeru: None. J. J. Gorelick: Employee; Self; Dexcom, Inc., Edwards Lifesciences. J. C. Bowers: Employee; Self; Dexcom, Inc. D. A. Price: Employee; Self; Dexcom, Inc.

ATTD 2021 Invited Speaker Abstracts.

ATTD 2021 Invited Speaker Abstracts.

Frequency of Diabetic Ketoacidosis in Patients with Type1 Diabetes Using FreeStyle Libre: A Retrospective Chart Review.

IntroductionDiabetic ketoacidosis (DKA) is an acute complication associated with poorly managed or undiagnosed diabetes. DKA is associated with significant morbidity, mortality, and healthcare costs, but can be prevented with appropriate management of diabetes. The FreeStyle Libre is flash glucose monitoring device that measures glucose levels in the interstitial subcutaneous tissue and has been shown to reduce HbA1c, time in hypoglycemia and hyperglycemia, as well as improve health-related quality of life.MethodsA retrospective chart review of patients with type 1 diabetes mellitus (T1DM) and recurrent DKA and who initiated FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) was conducted. DKA frequency and severity, glycated hemoglobin (HbA1c), and frequency of blood glucose monitoring were compared between the 2-year period before FreeStyle Libre initiation and the 2-year period after FreeStyle Libre initiation.ResultsA total of 47 patients with T1DM with recurrent DKA were included. FreeStyle Libre was associated with a reduction in the frequency of DKA events, with a mean of 0.2 (standard deviation [SD] 0.4) events per person during the 2 years after FreeStyle Libre initiation versus 2.9 (SD 0.9) during the 2 years before FreeStyle Libre initiation. Severity of DKA events was also reduced, with fewer severe (before mean 0.3 [SD 0.5] versus after 0.0 [SD 0.0]; p < 0.001) DKA events. A reduction in HbA1c (mean 7.4% [SD 0.5] after versus 9.9% [SD 1.2] before [p < 0.001]) and an increase in frequency of blood glucose testing (mean 8.1 scans/day [SD 1.7] after versus 2.2 finger-pricks/day [SD 0.7] at before [p < 0.001]) were also observed.ConclusionFreeStyle Libre is associated with a reduction in the frequency and severity of DKA events, reduction in HbA1c, and increase in frequency of blood glucose testing in patients with T1DM and recurrent DKA. The use of such a glucose monitoring tool can help to reduce the burden of morbidity, mortality, and healthcare costs associated with complications of diabetes.

Disparities in Utilization and Outcomes With Continuous Subcutaneous Insulin Infusion in Young Adults With Type 1 Diabetes

ObjectiveTo evaluate which factors determine utilization patterns and outcomes of continuous subcutaneous insulin infusion (CSII) in young adults with type 1 diabetes. MethodsUtilizing the Optum deidentified electronic health record data set between 2008 to 2018 to perform a retrospective cohort study, we identified 2104 subjects with type 1 diabetes aged 18 to 30 years. We evaluated the effect of race on determining CSII utilization, HbA1c (%), and hospital admission for diabetic ketoacidosis (DKA). Crude and adjusted estimates were computed using logistic regression and linear mixed models. ResultsThere was low CSII utilization among individuals who were Black, Hispanic, male, and those with governmental insurance. These groups also demonstrated higher HbA1c levels. Subjects who were Black, Hispanic, and those with governmental insurance had higher odds of DKA. Even when commercially insured, Black and Hispanic subjects demonstrated higher HbA1c levels, and Black individuals had higher odds of DKA. ConclusionIn a large electronic health record database in the U.S., there was low CSII utilization overall, particularly in Black and Hispanic minorities, despite CSII showing superior HbA1c control without an increase in DKA events.