Background and Aims

While real-time continuous glucose monitoring (RT-CGM) has been associated with greater glycemic improvement than traditional blood glucose monitoring (BGM) in T2D, little is known about the differential impact on glucose monitoring satisfaction over time in this population.

Methods

The MOBILE randomized controlled trial documented significantly greater glycemic benefits in RT-CGM (Dexcom™ G6 CGM System®) T2D participants (n=108) than BGM T2D participants (n=57). To compare change in satisfaction over time between RT-CGM and BGM users, participants completed three subscales of the Glucose Monitoring Satisfaction Survey (T2-GMSS): Openness, Emotional Burden and Behavioral Burden, at baseline and 8 months.

Results

Openness rose over time in both groups (ps<.01), though improvement was significantly greater in the RT-CGM (3.06 ± 0.78 to 3.83 ± 0.71) vs. BGM group (3.01 ± 0.78 to 3.37 ± 0.71), resulting in a moderate-to-large between-group effect size at 8 months (d=.67, p<.001). Emotional and Behavioral Burden fell in both groups (ps<.01), with no significant between-group differences. Change over time in all three subscales was associated in the expected direction with HbA1c improvements (rs=0.39-0.47, ps<.001).

Conclusions

Both study arms evidenced significant gains in all three aspects of glucose monitoring satisfaction. However, RT-CGM users reported significantly greater improvement than BGM users along one of those dimensions, Openness, which represents how the monitoring system may unblock rather than constrain one’s lifestyle. This is consistent with previous research illustrating how RT-CGM can enhance one’s comfort and confidence with trying out new foods and activities, thereby allowing individuals to feel less restricted.

Background and Aims

Despite the centennial of insulin’s discovery by Frederick Banting, Charles Best, and colleagues at the University of Toronto in 1921, half of the people living with diabetes worldwide cannot access or afford it. The aim of this study is to present contemporary data concerning out-of-pocket expenses (OoPEs), the extent of insulin and supply underuse, and the degree of financial coverage people with type 1 diabetes (T1D) are experiencing across the world.

Methods

A web-based, cross-sectional survey was conducted from August to December 2020. The analysis included comparisons between responses from countries with no, partial, and full healthcare coverage.

Results

1,066 participants from 64 countries took part in the study. ~25% of respondents reported having underused insulin at least once within the last year due to perceived cost. A significant correlation was observed between OoPEs and reported household income for respondents with partial healthcare coverage. 63.2% of participants reported disruption of insulin supplies and 25.3% reported an increase of prices related to the COVID-19 pandemic.

Conclusions

This study confirms previous reports of ~25% of people in the United States with T1D using less insulin and/or fewer supplies at least once in the last year due to cost, a trend associated with the extent of healthcare coverage. Similar trends were observed in some middle/low income countries. Moreover, patients reported an increase in insulin prices and disruption of supplies during the COVID-19 pandemic. This study highlights the importance of self-reported OoPEs and its association with underuse/rationing of insulin.

Background and Aims

Previous studies have shown clinical benefits in patients who used professional Continuous Glucose Monitor (CGM). However, the effect of professional CGM use in non-insulin Type-2 Diabetes (T2D) patients having poor glycemic control in real world settings has not been studied. We examined the association between HbA1c and professional CGM in T2D patients with poor glycemic control using multiple non-insulin therapies.

Methods

This retrospective analysis used healthcare claims data from Optum^® Clinformatics,^® comprised of commercial and Medicare Advantage members between 01-January 2018 to 31-October 2020. T2D patients ≥ 18 years of age were identified using ICD-9/ICD-10 codes having an HbA1c between 7.8–10.5%, using ≥ 2 non-insulin therapies, with no prior CGM or professional CGM use, and 6-months of continuous enrollment pre and post index date. Index date was defined as acquisition of professional CGM identified through CPT codes 95250 and 95251. The outcome was mean HbA1c change between baseline and up to 6-months post-index date.

Results

Data from 15,474 eligible patients were assessed (Professional CGM users, n=677; Non-users, n=14,797). A significant decrease in mean HbA1c from baseline was observed for professional CGM users (-0.78) vs. non-users (-0.32), p <0.0001 (difference-in-differences estimate, -0.50; 95% CI,-0.61 to -0.39; p <0.0001).

Conclusions

Findings suggest T2D patients with poor glycemic control using multiple non-insulin therapies may benefit from professional CGM resulting in reduction in HbA1c over a 6-month period compared to usual care. Professional CGM can inform clinicians about their patients’ glycemic patterns and help to tailor diabetes management strategies for patients.

Background and Aims

The effect of tirzepatide, a novel dual GIP/GLP-1 receptor agonist, vs insulin degludec (IDeg) on liver fat content (LFC) and visceral and abdominal subcutaneous adipose tissue (VAT and ASAT) was assessed with MRI techniques in a subpopulation of participants in the SURPASS-3 trial.

Methods

Insulin-naive participants with type 2 diabetes and Fatty Liver Index ≥60 had an MRI scan performed before randomisation (1:1:1:1) to once-weekly tirzepatide (5, 10, 15 mg) or once-daily IDeg as add-on to metformin with/without sodium-glucose co-transporter-2 inhibitors (SGLT-2i). The primary outcome was the change from baseline in LFC at Week 52 using pooled data from tirzepatide 10/15-mg arms vs IDeg. Secondary outcomes compared the individual tirzepatide doses vs IDeg at Week 52 for LFC, VAT and ASAT volumes; proportions of participants achieving LFC targets.

Results

A total of 296 participants had evaluable MRI data during the study (mean baseline age, 56.2 years; diabetes duration, 8.3 years; HbA_1c, 8.2%; weight, 94.4 kg; BMI, 33.5 kg/m²; 30% on SGLT-2i). The reduction from baseline in LFC at Week 52 was significantly greater for the pooled tirzepatide 10/15-mg arms vs IDeg arm and for all individual tirzepatide doses vs IDeg. The proportions of participants achieving LFC targets were significantly greater in each tirzepatide arm vs IDeg arm. All tirzepatide doses reduced VAT and ASAT volumes at Week 52 while IDeg increased both. The results were similar regardless of the concomitant use of SGLT-2i.

Conclusions

Tirzepatide demonstrated clinically meaningful reductions in LFC and VAT and ASAT volumes compared to IDeg in this SURPASS-3 substudy.

Background and Aims

This study investigated safety and effectiveness outcomes after HCL versus CSII use for six months.

Methods

Participants (n=302, aged 2-80 years) with T1D were randomized to MiniMed™ 670G system HCL or control (CSII without CGM) for six months, after completing a baseline run-in period (~2 weeks). Effectiveness endpoints included difference in A1C, time spent below target range (TBR<70mg/dL), time spent in target range (TIR, 70-180mg/dL) over 24 hours and nighttime, and coefficient of variation (CV). Endpoints were evaluated by baseline HbA1c >8% (Group 1) and baseline HbA1c ≤8% (Group 2) first, then by combined groups (Group 1 and 2). A one-way ANOVA was used to compare HCL and CSII outcomes. Safety endpoints included severe hypoglycemic, diabetic ketoacidosis (DKA) and serious device-related adverse events (AEs).

Results

For each group, HbA1c and TBR<70mg/dL were lower with HCL versus CSII (p<0.001 for both, Table). For the overall group, the nighttime and 24-hour TIR, in addition to CV, were also improved with HCL (p<0.001 for all). Throughout the study period, there was 1 serious device-related AE (HCL), 4 severe hypoglycemic (HCL:0, Control:4) events, and no DKA events.

Conclusions

This large RCT demonstrated significant improvement in glycemic control with HCL therapy over CSII therapy irrespective of baseline HbA1c.This large RCT demonstrated significant improvement in glycemic control with HCL therapy over CSII therapy irrespective of baseline HbA1c.

Background and Aims

Undetected nocturnal hypoglycemia is a problem in insulin-treated people with T2D that can lead to hypoglycemia unawareness and anxiety. The aim was to develop a prediction algorithm to warn people at risk at bedtime.

Methods

CGM data was collected from 67 insulin-treated people with T2D (NCT01819129). Data was structured into 24-hour periods and labelled as nocturnal hypoglycemia or not depending on whether fifteen consecutive minutes were spent below 3.0 mmol/L during the following night (00.01-05.59). The periods were divided into ‘last night’ (00.01-05.59), ‘morning’ (06.00-09.00), ‘day’ (06.00-00.00), and ‘evening’ (21.00-00.00) for predictor extraction. Periods were required below 20% missing data in each interval, and people without periods with nocturnal hypoglycemia were excluded. The minimum value, maximum value, range, slope (linear regression), glycemic variability percentage, standard deviation, variance, and mean were extracted for each interval as potential predictors. A relative variant for each predictor was calculated by subtracting the mean of previous periods, resulting in 64 potential predictors. Forward selection was used to select informative predictors, and a logistic regression model was trained and validated using 5-fold cross-validation to predict 24-hour periods resulting in nocturnal hypoglycemia.

Results

Preprocessing identified 30 patients with 60/496 periods resulting in nocturnal hypoglycemia. Forward selection revealed that the optimal predictor combination was minimum value (evening), minimum value (day), mean (evening), and relative maximum value (day), which provided an averaged area under the receiver operating characteristics curve of 0.78 (p<0.001) (Figure 1).

Conclusions

The algorithm was able to predict 24-hour periods resulting in nocturnal hypoglycemia and could prevent such cases.

Background and Aims

Insulin therapy should be individualized for users’ unique treatment goals. The Omnipod 5 System provides automated insulin delivery (AID) with customizable glucose targets from 110-150mg/dL (6.1-8.3mmol/L). This analysis assessed system performance at specific glucose targets during the 3-month pivotal study in very young children (aged 2-5.9y) with type 1 diabetes (T1D).

Methods

Participants with A1C<10% (86mmol/mol) used the AID system for 3 months at home after a 14-day standard therapy (ST) phase. Glucose targets from 110-150mg/dL (6.1-8.3mmol/L) in 10mg/dL (0.55mmol/L) increments were programmable by time of day. Primary safety and efficacy endpoints, respectively, were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), and sensor glucose percent time in target range (TIR) (70-180mg/dL, 3.9-10.0mmol/L) during AID at each glucose target compared with ST.

Results

Participants (N=80), aged (mean±SD) 4.7±1.0y with T1D duration 2.3±1.1y, had a total daily dose (TDD) of 13.7±4.4units (range 5.3-27.1units) and baseline A1C of 7.4±1.0% (57±10.9mmol/mol) (range 5.4-10.2%, 36-88mmol/mol). TIR improved during the AID phase with all targets, while time <70mg/dL (<3.9mmol/L) remained low at the 110mg/dL (6.1mmol/L) target and decreased with all other targets (Table). There was no correlation between time-weighted average target and age (r=-0.02) or TDD (r=0.05), (both p>0.05). There were no SH or DKA episodes.

Conclusions

The Omnipod 5 System was safely used by a large cohort of very young children with T1D at glucose targets from 110-150mg/dL (6.1-8.3mmol/L). The 110mg/dL (6.1mmol/L) and 120mg/dL (6.7mmol/L) targets were used most often, at a combined 75% of the time.

Background and Aims

Time in range (TIR; glucose of 70-180 mg/dL) overcomes some of the limitations of HbA1c in the individual assessment of glycemic control. This study evaluates whether TIR is associated with the presence of chronic complications in a real-world population of people with type 1 diabetes (T1D).

Methods

Sensor-measured TIR and the occurrence of microvascular (diabetic retinopathy [DR], diabetic nephropathy [DN], diabetic peripheral neuropathy [DPN]) and macrovascular complications in 812 people with T1D were analyzed cross-sectionally. Binary logistic regression was used to evaluate the contribution of TIR to the presence of chronic complications, after correction for sex, age, diabetes duration, BMI, blood pressure, lipid profile, smoking, lipid lowering and antihypertensive therapy.

Results

Mean TIR was 52.7 ± 15.2%. Overall, 46.1% had at least one microvascular complication (34.5% DR, 23.9% DN, 16% DPN) and 16.6% suffered from any macrovascular complication. The prevalence of at least one microvascular complication (p for trend <0.001), DR (p for trend <0.001) and DN (p for trend =0.036) decreased with increasing TIR quartiles (figure 1). The odds ratio of having at least one microvascular complication, DR, DN, DPN or any macrovascular complication per 1% increase in TIR was 0.969 (95%CI: 0.957-0.982, p<0.001), 0.959 (95%CI: 0.945-0.974, p<0.001), 0.981 (95%CI: 0.967-0.995, p=0.008), 0.980 (95%CI: 0.964-0.997, p=0.019) and 0.975 (95%CI: 0.958-0.992, p=0.005) respectively.

Conclusions

TIR is inversely associated with the presence of chronic diabetes complications. These data add validity to the use of TIR as key measure of glycemic control and endpoint of clinical trials, in addition to HbA1c.

Background and Aims

Hybrid Closed Loop (HCL) systems improve time in range 70-180 mg/dL (TIR) but not all users meet the TIR target of ≥70%. This study developed a model to predict attainment of the consensus TIR target after 12-months of HCL use based on baseline and 1-month data among Tandem Control-IQ (CIQ) users.

Methods

Data from 162 youth (7.6±1.4 yrs., 45.7%F, 7.6%±1.4% HbA1c) who began using the CIQ HCL system were included. Lasso model selection was used to develop a predictive model for meeting the TIR goal after 12 months of use. The lasso is a single-step alternative to stepwise selection and includes covariates maximizing area under the curve (AUC) rather than using significance testing. Candidate factors included sex, age, diabetes duration, baseline HbA1c, race/ethnicity, insurance status, history of pump and continuous glucose monitor (CGM) use, and scores on psychosocial questionnaires, as well as percent CGM use, percent TIR, number of meal boluses/day, and percent HCL use at 1-month.

Results

Factors retained in the final model included 1-month TIR, meal boluses/day, and Hypoglycemia Fear Survey Helplessness/Worry About Low Blood Glucose score. The model had very good predictive ability with AUC of 0.84 (Figure). Internal 5-fold cross validation was also very good with an average AUC of 0.803±0.014.

Conclusions

Our prognostic model using clinically accessible baseline, early device-use and psychosocial data can strongly predict users who will meet therapeutic targets with HCL technology. This model may be useful in early identification of barriers so as to promote early intervention prior to behaviors becoming ingrained.

Background and Aims

Older adults with type 1 diabetes (T1D) have distinct characteristics that can make optimising glycaemic control challenging. We hypothesised that hybrid closed-loop is safe and more effective than sensor-augmented pump (SAP) therapy in older adults with T1D.

Methods

In a multicentre, multinational (UK and Austria), randomised, crossover study, adults aged 60 years and over with T1D using insulin pump therapy underwent two 16-week periods comparing hybrid closed-loop (CamAPS FX) and SAP therapy in random order. The primary endpoint was the proportion of time sensor glucose was in target range between 3.9 and 10.0mmol/L. ClinicalTrials.gov NCT04025762.

Results

Thirty-seven participants (mean±SD age 67±5 years, baseline HbA1c 7.4±0.9% [57±10mmol/mol]) were randomised between 4 September 2019 and 2 October 2020. The proportion of time glucose was between 3.9 and 10.0mmol/L was 8.6 percentage points (95% CI 6.2 to 11.0) higher during closed-loop compared to SAP (p<0.001). Time with glucose >10.0mmol/L was 8.4 percentage points lower (95% CI -11.0 to -6.0; p<0.001), mean glucose was 0.7mmol/L lower (95% CI -0.9 to -0.5; p<0.001), and glycated haemoglobin was 0.2% lower (95% CI -0.4 to -0.1; p<0.001) with closed-loop than with SAP. Time in hypoglycaemia (<3.9mmol/L) was similar between periods (p=0.54). Two severe hypoglycaemia events occurred during the SAP period. There were no other treatment related serious adverse events.

Conclusions

Hybrid closed-loop insulin delivery is safe and achieves superior glycaemic control than SAP therapy without increasing the risk of hypoglycaemia in older adults with T1D.

Funding: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Background and Aims

The aim of this study was to compare the efficacy of the currently available Advanced Hybrid Closed Loop (AHCL) technologies, Tandem Control-IQ and Minimed780G, on glycemic control in pediatric and adult patients with Type 1 Diabetes (T1D).

Methods

Continuous glucose monitoring (CGM) data from 90 patients, who upgraded to Minimed780G or Tandem Control-IQsystem and have completed 1-month observation period, were retrospectively analyzed. The two groups were matched and reduced to 32 patients each to minimize the imbalances among basic characteristics. Additionally, an adjustment for baseline HbA1c levels was required.

Results

All 64 matched patients showed a statistically significant improvement of time in range (TIR) (+9.1%, p= 0.001), time above range (TAR) > 250 mg/dl (-9.9%, P=<0.001), standard deviation (SD) (-12.8%, P =0.001) and average glycemia (-22.8%, P=<0.001). Tandem Control-IQ system significantly reduced the frequency of hypoglycemia 70-54 mg/dl, while Minimed 780G increased it (-0.77% vs +0.44% p=0.018).

Conclusions

The use of ACHL systems led to a significant improvement of glycemic control. Minimed 780G appears to be more effective in managing hyperglycemia, while Tandem Control-IQ seems to be more effective in reducing time in hypoglycemia. Understanding the strengths and weaknesses of these devices could be useful to define a customized insulin therapy.

Background and Aims

Background and aims: Evidence from clinical trials have demonstrated the glycemic benefits of hybrid closed-loop insulin delivery systems (HCLS) in children and adults. The primary objective of this study was to provide real-world data on glycemic outcomes and population characteristics in those using HCLS compared to other treatment modalities.

Methods

Methods: Electronic health record data (2019-2021) from the T1D Exchange Quality Improvement (T1DX-QI) Collaborative were analyzed for 15,091 people with T1D. Patients with data on insulin delivery mode [HCLS, sensor augmented pump therapy (SAP), pump only, or multiple daily injections (MDI)], A1c at their most recent clinic visit, and other demographic covariates were included in this analysis. Individuals were classified across insulin delivery groups based on information documented by a healthcare provider at their most recent clinic visit.

Results

Results: In this study population, 744 (5%) were HCLS users, 2,326 (15%) were SAP users, 3,879 (26%) used pump only, and 8,142 (54%) were MDI users. Median (IQR) A1c in the HCLS group was 7.3% (IQR: 6.7,8.0%) compared to 8.0% (IQR: 7.2,9.1%) in the SAP group, 8.3% (IQR: 7.2,10.0%) in the pump only group and 8.7% (IQR: 7.4,10.5%) in the MDI group. Linear mixed models showed HbA1c to be 0.7% lower in the HCLS group compared to SAP, adjusting for age, gender, race/ethnicity and insurance status [Estimated Marginal Mean (95% CI): 7.8% (IQR: 7.3,8.4%) vs 8.7% (IQR: 8.2,9.0%)].

Conclusions

Conclusion: This is a large multi-site real-world study demonstrating significant clinical benefits of HCLS use relative to other insulin treatment options.