AFREZZA PRE-MEAL BOLUS REDUCES EARLY GLYCEMIC EXCURSION DURING HYBRID CLOSED LOOP TREATMENT
- Alfonso Galderisi, United States of America
- Nathan Cohen, United States of America
- Peter Calhoun, United States of America
- Marc Breton, United States of America
- Kristen Kraemer, United States of America
- Melinda Zgorski, United States of America
- Lori Carria, United States of America
- Eda Cengiz, United States of America
Abstract
Background and Aims
Background. Optimizing post-prandial glycemic control during closed-loop (CL) treatment remains a challenge given the delays in insulin absorption and action. We aimed to investigate the effect of ultra-fast acting Afrezza inhaled insulin on improving post-prandial blood glucose control during hybrid closed loop (HCL) treatment in young adults with type 1 diabetes.
Methods
Methods: We conducted an inpatient, three-way, randomized crossover meal study to assess the efficacy and safety of Afrezza at a low(AL) and a high dose(AH) as compared to a rapid-acting insulin(RAI) pre-meal bolus during Diabetes-Assistant-HCL treatment. The 11 participants received two sequential meals on three study days with RAI, AH(rounded up available Afrezza dose) or AL(rounded down Afrezza dose). The primary efficacy outcome was the peak postprandial plasma glucose (PPG) level calculated by pooling data for four hours after the start of each meal.
Results
Results: The mean PPG for the RAI control arm and AHwere similar (185±50mg/dL vs. 195±46mg/dL, respectively; p=0.45), while it was higher for meals using AL(208±54mg/dL, p=0.04). The AHachieved significantly lower early PPG level than the RAI arm (30 min; p<0.001), and improvement in PPG waned at 120 and 180 min (p=0.02).
Conclusions
Conclusions: Afrezza (AH) pre-meal bolus reduced the early glycemic excursion and improved PPG during HCL compared to RAI pre-meal bolus. The improvement in PPG has not been sustained after the end of Afrezza glucodynamic action at 120m.
EFFICACY AND SAFETY COMPARISON BETWEEN U-100 REGULAR HUMAN INSULIN AND RAPID ACTING INSULIN WHEN DELIVERED BY V-GO WEARABLE INSULIN DELIVERY DEVICE IN TYPE 2 DIABETES
- Pablo Mora, United States of America
- David R. Sutton, jr., United States of America
- Ashwini Gore, United States of America
- Bantwal S. Baliga, United States of America
- Rebecca F. Goldfaden, United States of America
- Carla Nikkel, United States of America
- John Sink ii, United States of America
- Beverley Adams-huet, United States of America
Abstract
Background and Aims
Increasing insulin prices have led to a renewed debate to determine if Rapid Acting Insulin (RAI) analogs offer an advantage over less expensive Regular Human Insulins (RHI). Meta-analyses have shown RAI analogs offer no advantage over RHI; however, to our knowledge, no data exists when delivered via continuous subcutaneous infusion. V-Go® is a 24-hr wearable patch-like insulin delivery device providing a preset continuous basal rate of insulin and on-demand bolus dosing. This study compared the efficacy and safety of RAI versus RHI when delivered by V-Go.
Methods
This multi-center prospective, randomized, parallel, non-inferiority 14-week study was conducted in a T2DM population in the United States. Patients administering RAI with V-Go were randomized to continue RAI or switch to RHI. Primary endpoint assessed non-inferiority for the between group net difference in A1C derived from a mixed model analysis; non-inferiority margin=0.4%. Between group differences from baseline for hypoglycemia (based on three 7point glucose profiles), insulin total daily dose (TDD) and weight were evaluated as secondary endpoints.
Results
One hundred thirteen patients (59 RHI and 54 RAI) were evaluated. Baseline characteristics were similar between cohorts. Change in A1C favored RHI and non-inferiority to RAI was demonstrated. Absolute change in the % of patients with documented hypoglycemia from pre-randomization to the end of study was not statistically different between groups (RHI +5.1% vs RAI +5.6%). Between group differences for TDD and weight were not statistically different.
Conclusions
Patients administering RAI with V-Go can safely switch to RHI delivery with V-Go and maintain similar glycemic control.
TECHNOSPHERE INSULIN PROVIDES BETTER EARLY POSTPRANDIAL GLUCOSE CONTROL THAN SUBCUTANEOUS RAPID-ACTING ANALOGUE
Abstract
Background and Aims
In a recent study (STAT, NCT03143816), patients with type 1 diabetes (T1D) treated with Technosphere Insulin (TI) demonstrated better early postprandial glucose (PPG) control than those on subcutaneous (SC) insulin aspart. The average daily dose of TI in patients who took TI as directed in the protocol was twice that of insulin aspart (40.5 vs 20.6 U). Despite the higher dose, the TI group experienced less time in hypoglycemia than the insulin aspart group. These results prompted a retrospective analysis of mixed-meal tolerance tests (MMTTs) conducted in T1D to further evaluate the 2:1 dosing ratio.
Methods
In study MKC-TI-009 (NCT00308308), patients with T1D underwent 1 to 3 MMTTs. There were 1326 evaluable PPG profiles: 674 MMTTs from 261 patients on insulin aspart and 652 MMTTs from 264 patients on TI.
Results
On average, the area under the PPG excursion curve (PPGE AUC) decreased with increasing dose, and the mean (standard error [SE]) ratio of the insulin aspart slope to the TI slope was 2.1 (0.3), consistent with the results of STAT. This was confirmed when doses of TI 8, 16, and 24 U were compared with mean (SE) insulin aspart doses of 4 (1), 8 (1), and 12 (1) U, respectively (Figure). 
Conclusions
The TI PPGE curves confirm TI has an earlier onset and shorter duration of action, whereas the insulin aspart PPGE curves tend to drop below baseline in the late postprandial period, reflecting a longer duration of action. The timing of hypoglycemia (levels 1 and 2) follows the pattern of PPGEs.
REDUCED NUMBER OF HYPOGLYCAEMIC EVENTS OBSERVED IN CHILDREN AFTER INTRODUCING CONNECTED INSULIN PENS
Abstract
Background and Aims
Combining insulin injection and continuous blood glucose monitoring (CGM) data has been shown to improve glycaemic control in adults with T1DM. In children and adolescents with T1DM, insulin management is often challenging despite the importance of avoiding hypoglycaemia and hyperglycaemia. This population could therefore potentially also benefit from a connected insulin pen. This study aimed to describe glycaemic parameters following introduction of a connected insulin pen in a paediatric population.
Methods
In this non-interventional study, conducted at three Swedish diabetes clinics, connected pens containing basal and/or bolus insulin were prescribed to children and adolescents with T1DM. Injection and CGM data were recorded via the Glooko cloud system either at home or during routine clinic visits. CGM data were used to determine incidence of hypoglycaemia (<3.0 mmol/L), time-in-range (TIR), time-in-hypoglycaemia (TIHypo) and time-in-hyperglycaemia (TIHyper).
Results
In total, 39 children and adolescents used the connected pens with CGM for up to 633 days (average 409 days). Compared with baseline, the incidence of hypoglycaemia had decreased by 12% at 6 months (95% C.I. [-27; 7], p=0.19) and by 31% after 12 months (95% C.I: [-44; -16], p<0.001). A corresponding decrease was observed in TIHypo after 12 months (p=0.03) whereas TIR and TIHyper were not significantly affected. Basal insulin dose increased over time; bolus dose was unchanged.
Conclusions
These real-world findings suggest that the use of connected insulin pens in a paediatric population with T1DM may help to reduce hypoglycaemic events and TIHypo and to support dose optimisation.
A NOVEL METHODOLOGY TO ASSESS METABOLIC FLEXIBILITY AND MITOCHONDRIAL FUNCTION IN ORDER TO PRESCRIBE PERSONALIZED EXERCISE TO INDIVIDUALS WITH OBESITY AND DIABETES.
Abstract
Background and Aims
Mitochondrial dysfunction (MtD) and metabolic inflexibility are hallmarks of obesity and type 2 diabetes (T2D). Exercise as medicine is a reality and along with nutrition, the most effective way to prevent obesity and T2D. Our JDRF group recently published new exercise guidelines for individuals with T1D1. However, it is necessary to improve and personalize exercise prescription. Measuring substrate utilization and lactate during exercise could be a valid method to assess metabolic flexibility and mitochondrial function in order to prescribe individualized exercise programs.
Methods
25 Endurance athletes (EA), 25 moderately active individuals (MA) and 20 individuals with obesity and T2D (OB/T2D) performed a graded exercise test to exhaustion. Lactate ([La-]), as well as fat and carbohydrate oxidation (FATox and CHOox) were measured throughout the test. Comparisons and correlations between [La-] and FATox observed were done by means of a Student t-test. Statistical significance was set at p<0.001.
Results
At a same relative exercise intensity, FATox was significantly higher in EA and MA than in OB/T2D (p<0.0001). [La-] was significantly lower in EA and MA compared to OB/T2D (p<0.0001). Correlations between FATox and [La-] in all the 3 groups was high, r=-0.95, p<0.0001 in EA, r=-0.96, p<0.00001 in MA and r=-0.93, p<0.001 in OB/T2D.
Conclusions
Lactate highly correlates with fat metabolism during exercise across different populations. The measurement of blood lactate concentration and FATox during exercise provides an indirect method to assess metabolic flexibility and mitochondrial function in individuals in order to prescribe individualized exercise programs to target obesity and T2D.