Ryan Bailey

This study evaluated the effects of ultra-rapid lispro (URLi) insulin versus insulin lispro on postprandial glucose excursions in 176 individuals with type 1 diabetes using Control-IQ+ technology. Postprandial glycemia differed the most between URLi and lispro at 60 min (mean glucose 166 ± 69 mg/dL vs. 178 ± 70 mg/dL; adjusted mean difference [AMD] = −11 mg/dL; P < 0.001). The URLi had slightly lower mean glucose excursion compared with lispro (AMD = −4 mg/dL; P = 0.001), but the differences between treatments were larger following breakfast (AMD = −9 mg/dL) compared with lunch (AMD = −2 mg/dL) and dinner (AMD = −2 mg/dL). Participants with insulin-to-carbohydrate ratio (ICR) 15 g/U (AMD = 1 mg/dL). In conclusion, compared with insulin lispro, the use of URLi with Control-IQ+ technology modestly improved postprandial glucose excursions with the greatest amount of improvement for breakfast and in those with insulin resistance.

Background: Postmeal hyperglycemia is difficult to avoid even with automated insulin delivery (AID) due to the delayed effect of subcutaneously administered rapid-acting insulin analogs. Inhaled technosphere insulin (TI, Afrezza®) has a more rapid onset of action with the potential to reduce the postmeal glucose rise. We evaluated the effects of a regimen of TI and degludec over 30 weeks. Methods: In total, 123 adults with type 1 diabetes (T1D) participated in a 17-week multicenter randomized controlled trial comparing a regimen of TI plus insulin degludec versus usual care, which consisted predominantly of AID or multiple daily insulin injections (MDI). Interested participants in the TI-degludec group continued this regimen for an additional 13 weeks, with no scheduled visits prior to a final visit at 30 weeks to approximate real-world care. Results: Of the 62 participants in the TI-degludec group, 58 completed the 17-week visit and 45 continued into the extension phase. Prior to the study, 44% were using AID, 9% a sensor-augmented pump without automation, and 47% MDI. Mean HbA1c was 7.6% ± 1.0% at baseline, 7.6% ± 1.0% at 17 weeks, and 7.4% ± 1.0% at 30 weeks. Mean HbA1c change from 17 weeks to 30 weeks was -0.21% (95% confidence interval -0.33% to -0.09%, P < 0.001). HbA1c was Conclusions: HbA1c levels were sustained over 30 weeks using a TI-degludec regimen after switching from AID or MDI. TI should be considered an option for people with T1D.

Objective: To evaluate the safety and explore the efficacy of use of ultra-rapid lispro (URLi, Lyumjev) insulin in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology in children, teenagers, and adults living with type 1 diabetes (T1D). Methods: At 14 U.S. diabetes centers, youth and adults with T1D completed a 16-day lead-in period using lispro in a t:slim X2 insulin pump with Control-IQ 1.5 technology, followed by a 13-week period in which URLi insulin was used in the pump. Results: The trial included 179 individuals with T1D (age 6–75 years). With URLi, 1.7% (3 participants) had a severe hypoglycemia event over 13 weeks attributed to override boluses or a missed meal. No diabetic ketoacidosis events occurred. Two participants stopped URLi use because of infusion-site discomfort, and one stopped after developing a rash. Mean time 70–180 mg/dL increased from 65% ± 15% with lispro to 67% ± 13% with URLi ( P = 0.004). Mean insulin treatment satisfaction questionnaire score improved from 75 ± 13 at screening to 80 ± 11 after 13 weeks of URLi use (mean difference = 6; 95% confidence interval 4–8; P < 0.001), with the greatest improvement reported for confidence avoiding symptoms of high blood sugar. Mean treatment-related impact measure-diabetes score improved from 74 ± 12 to 80 ± 12 ( P < 0.001), and mean TRIM-Diabetes Device (score improved from 82 ± 11 to 86 ± 12 ( P < 0.001). Conclusions: URLi use in the Tandem t:slim X2 insulin pump with Control-IQ 1.5 technology was safe for adult and pediatric participants with T1D, with quality-of-life benefits of URLi use perceived by the study participants. Clinicaltrials.gov registration: NCT05403502.

Aim: The impact of weight gain on insulin dosage and glycemic control in adults with type 1 diabetes (T1D) aged 25 years and older was investigated in the T1D Exchange Registry participants. Methods: Participants were categorized into four groups based on their change in weight from T1D Exchange registry enrollment to year 5: stable weight (−5 to P = 0.005). For this cohort, the mean TDD at year 5 increased from 49 ± 25 to 61 ± 29 U for those who gained ≥20 lb, while decreased from 45 ± 27 to 44 ± 25 U for those with stable weight of −5 to P < 0.001). Among participants with an enrollment HbA1c ≥9.0%, the mean HbA1c at year 5 was statistically insignificant at 8.4% ± 1.3% for those who gained ≥20 lb compared to 9.2% ± 1.7% for those with a stable weight of −5 to P = 0.09). Conclusion: Significant weight gain in adults with T1D who had good to adequate glycemic control was associated with modest deterioration in glucose control despite an increase in TDD. Worsening glucose control may indicate insulin resistance related to weight gain despite significantly increased insulin dosage which was insufficient to maintain adequate glycemic control.

Background: The relationship of mean glucose measured with continuous glucose monitoring (CGM) and hemoglobin A1c ( HbA1c) shows considerable variability between individuals with diabetes and may be influenced by race-related factors. Whether the relationship of mean glucose with HbA1c varies according to type 1 diabetes (T1D) or type 2 diabetes (T2D) has not been well evaluated. Methods: Data from 343 participants in four clinical trials (191 with T1D and 152 with T2D) were analyzed. Least squares linear regression models were fit with HbA1c as the dependent variable and mean glucose as the independent variable. Results: Mean age was 57 ± 15 years in the T1D cohort and 58 ± 10 years in the T2D cohort. The T1D cohort was 89% White non-Hispanic, 5% African American, 3% Hispanic, and 3% other or mixed race compared with 52%, 16%, 22%, and 9%, respectively, in the T2D cohort. The relationship between CGM-measured mean glucose and laboratory-measured HbA1c significantly differed between T1D and T2D cohorts, with HbA1c on average being higher with T2D than T1D for the same mean glucose ( P = 0.002). However, this difference was largely attributable to the difference in the proportion of African Americans between T1D and T2D; and after stratifying by race, the mean glucose-HbA1c relationship showed only a small difference between T1D non-African Americans and T2D non-African Americans. The mean glucose-HbA1c relationship appeared similar for White non-Hispanic and Hispanic individuals. Conclusion: HbA1c on average was higher in T2D than T1D for a given mean glucose, but after accounting for race, there was no meaningful difference in the mean glucose-HbA1c relationship comparing T1D and T2D. The mean glucose-HbA1c relationship differs in African American compared with White individuals, but does not appear to differ comparing White non-Hispanic to Hispanic individuals. The published glucose management indicator formula appears to be suitable for both T1D and T2D.

We compared the glucose management indicator (GMI) calculated using 14 days of continuous glucose monitor (CGM) data with GMI calculated using <14 days. Analysis included 581 individuals with type 1 diabetes or type 2 diabetes from five clinical trials. The correlation between the 14- and 7-day GMI was 0.95 and the correlation between 14 days versus 10, 5, and 3 days GMI was 0.98, 0.91, and 0.86, respectively. The percentages of GMI values within 0.3% of the 14-day GMI were 98% with 10-day GMI, 87% with 7-day GMI, 77% with 5-day GMI, and 60% with 3-day GMI. Minimal differences were observed between GMI computed using 14 days of data compared with GMI computed with 7 days. Although 10–14 days of CGM data are preferred for computing GMI, for most patients a satisfactory estimate of HbA1c can be obtained with 7 days of data.

The Medtronic advanced hybrid closed-loop (AHCL) and MiniMed™ 670G hybrid closed-loop (HCL) systems provide the option to temporarily increase the glucose target to 150 mg/dL (8.3 mmol/L). This analysis investigated the efficacy of the AHCL compared with that of the HCL after the use of this setting. Data from 60 participants in the Fuzzy Logic Automated Insulin Regulation (FLAIR) study were used to compare the AHCL and HCL systems after the use of the temporary target (TT), and during analogous periods where this setting was not used. Differences in time in range 70–180 mg/dL between the systems were similar after the use of the TT setting and during analogous non-TT periods (interaction P = 0.87). Similar trends were observed for mean glucose, percentage time >180 mg/dL, and percentage time >250 mg/dL. Differences between AHCL and HCL systems were similar after the use of the TT setting compared with those of non-TT periods. ClinicalTrials.gov NCT03040414

Purpose: The purpose of this study was to evaluate outcomes of Descemet stripping automated endothelial keratoplasty comparing exchange with fresh intermediate-term cold storage solution after lenticule preparation versus reuse of the original solution in the Cornea Preservation Time Study. Methods: In the Cornea Preservation Time Study, 508 donor corneas had lenticules prepared by the eye bank with fresh solution exchange (Fresh group) and 283 with reuse of the original solution (Original group). Storage time for all donors was ≤11 days. Graft success rates, central endothelial cell loss at 3 years, and frequency of positive donor rim cultures were compared between the 2 groups. Results: The 3-year graft success rate (95% confidence interval) was 93.4% (90.7%–95.3%) in the Fresh group and 95.2% (91.8%–97.2%) in the Original group (adjusted hazard ratio for graft failure = 0.64, 95% confidence interval, 0.33–1.24, P = 0.19). The mean percentage endothelial cell loss was significantly greater in the Fresh group versus Original group (45% ± 22% vs. 38% ± 20%, respectively, P = 0.004). Cultures were positive in 4 (1.5%) of 267 donor rims (3 fungal and 1 bacterial) in the Fresh group and in 4 (2.5%) of 158 in the Original group (P = 0.57). There were 2 postoperative infections in the Original group and none in the Fresh group. Conclusions: The use of the original intermediate-term cold storage solution did not reduce the 3-year graft success rate compared with exchanging with fresh solution after lenticule preparation for Descemet stripping automated endothelial keratoplasty, while the frequency of positive donor rim cultures did not significantly differ between groups.

Davidson (1) postulates that the fasting glucose concentration is a good surrogate for time in range (TIR) 70–180 mg/dL, which, as he notes, has been associated

This article reports on the lived experience of Medtronic advanced hybrid closed-loop (AHCL) in comparison to first generation hybrid closed-loop (HCL) in a randomized, open-label, two-period crossover trial. Patient-reported outcome (PROs) measures were administered before randomization and at the end of each study period in 113 adolescents and young adults with type 1 diabetes. Glucose monitoring satisfaction subscales for emotional burden and behavioral burden improved significantly ( P < 0.01) over time with use of AHCL versus HCL and co-occurred with glycemic improvements (reduced percent time above 180 mg/dL during the day and no change in % time less than 54 mg/dL across 24 h) and greater time in Auto Mode. PROs, including distress, technology attitudes, and hypoglycemia confidence, were not different. AHCL use was associated with improved glucose monitoring satisfaction. Satisfaction was greater in those participants who had more appreciable glycemic benefit and stayed in Auto Mode more often. Clinical Trial Registration number: NCT03040414.