OBJECTIVE To compare glucose control with hybrid closed-loop (HCL) when challenged by high intensity exercise (HIE), moderate intensity exercise (MIE), and resistance exercise (RE) while profiling counterregulatory hormones, lactate, ketones, and kinetic data in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This study was an open-label multisite randomized crossover trial. Adults with type 1 diabetes undertook 40 min of HIE, MIE, and RE in random order while using HCL (Medtronic MiniMed 670G) with a temporary target set 2 h prior to and during exercise and 15 g carbohydrates if pre-exercise glucose was <126 mg/dL to prevent hypoglycemia. Primary outcome was median (interquartile range) continuous glucose monitoring time-in-range (TIR; 70–180 mg/dL) for 14 h post–exercise commencement. Accelerometer data and venous glucose, ketones, lactate, and counterregulatory hormones were measured for 280 min post–exercise commencement. RESULTS Median TIR was 81% (67, 93%), 91% (80, 94%), and 80% (73, 89%) for 0–14 h post–exercise commencement for HIE, MIE, and RE, respectively (n = 30), with no difference between exercise types (MIE vs. HIE; P = 0.11, MIE vs. RE, P = 0.11; and HIE vs. RE, P = 0.90). Time-below-range was 0% for all exercise bouts. For HIE and RE compared with MIE, there were greater increases, respectively, in noradrenaline (P = 0.01 and P = 0.004), cortisol (P < 0.001 and P = 0.001), lactate (P ≤ 0.001 and P ≤ 0.001), and heart rate (P = 0.007 and P = 0.015). During HIE compared with MIE, there were greater increases in growth hormone (P = 0.024). CONCLUSIONS Under controlled conditions, HCL provided satisfactory glucose control with no difference between exercise type. Lactate, counterregulatory hormones, and kinetic data differentiate type and intensity of exercise, and their measurement may help inform insulin needs during exercise. However, their potential utility as modulators of insulin dosing will be limited by the pharmacokinetics of subcutaneous insulin delivery.

OBJECTIVE To evaluate glucose control using fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) delivered by the MiniMed Advanced Hybrid Closed-Loop (AHCL) system in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS In this randomized, open-label, crossover study, participants were assigned to receive faster aspart or IAsp in random order. Stages 1 and 2 comprised of 6 weeks in closed loop, preceded by 2 weeks in open loop. This was followed by stage 3, whereby participants changed directly back to the insulin formulation used in stage 1 for 1 week in closed loop. Participants chose their own meals except for two standardized meal tests, a missed meal bolus and late meal bolus. The primary outcome was the percentage of time sensor glucose values were from 70 to 180 mg/dL (time in range [TIR]). RESULTS Twenty-five adults (52% male) were recruited; the median (interquartile range) age was 48 (37, 57) years, and the median HbA_1c was 7.0% (6.6, 7.2) (53 [49, 55] mmol/mol). Faster aspart demonstrated greater overall TIR compared with IAsp (82.3% [78.5, 83.7] vs. 79.6% [77.0, 83.4], respectively; mean difference 1.9% [0.5, 3.3]; P = 0.007). Four-hour postprandial glucose TIR was higher using faster aspart compared with IAsp for all meals combined (73.6% [69.4, 80.2] vs. 72.1% [64.5, 78.5], respectively; median difference 3.5% [1.0, 7.3]; P = 0.003). There was no ketoacidosis or severe hypoglycemia. CONCLUSIONS Faster aspart safely improved glucose control compared with IAsp in a group of adults with well-controlled type 1 diabetes using AHCL. The modest improvement was mainly related to mealtime glycemia. While the primary outcome demonstrated statistical significance, the clinical impact may be small, given an overall difference in TIR of 1.9%.

OBJECTIVE Exercising while fasted with type 1 diabetes facilitates weight loss; however, the best strategy to maintain glucose stability remains unclear. RESEARCH DESIGN AND METHODS Fifteen adults on continuous subcutaneous insulin infusion completed three sessions of fasted walking (120 min at 45% VO_2max) in a randomized crossover design: 50% basal rate reduction, set 90 min pre-exercise (−90_min50%_BRR); usual basal rate with carbohydrate intake of 0.3 g/kg/h (CHO-only); and combined 50% basal rate reduction set at exercise onset with carbohydrate intake of 0.3 g/kg/h (Combo). RESULTS Combo had a smaller change in glucose (5 ± 47 mg/dL) versus CHO-only (−49 ± 61 mg/dL, P = 0.03) or −90_min50%_BRR (−34 ± 45 mg/dL). The −90_min50%_BRR strategy produced higher β-hydroxybutyrate levels (0.4 ± 0.3 vs. 0.1 ± 0.1 mmol/L) and greater fat oxidation (0.51 ± 0.2 vs. 0.39 ± 0.1 g/min) than CHO-only (both P < 0.05). CONCLUSIONS All strategies examined produced stable glycemia for fasted exercise, but a 50% basal rate reduction, set 90 min pre-exercise, eliminates carbohydrate needs and enhances fat oxidation better than carbohydrate feeding with or without a basal rate reduction set at exercise onset.

OBJECTIVE To investigate physiological responses to cardiopulmonary exercise (CPX) testing in adults with type 1 diabetes compared with age-, sex-, and BMI-matched control participants without type 1 diabetes. RESEARCH DESIGN AND METHODS We compared results from CPX tests on a cycle ergometer in individuals with type 1 diabetes and control participants without type 1 diabetes. Parameters were peak and threshold variables of VO₂, heart rate, and power output. Differences between groups were investigated through restricted maximum likelihood modeling and post hoc tests. Differences between groups were explained by stepwise linear regressions (P < 0.05). RESULTS Among 303 individuals with type 1 diabetes (age 33 [interquartile range 22; 43] years, 93 females, BMI 23.6 [22; 26] kg/m², HbA_1c 6.9% [6.2; 7.7%] [52 (44; 61) mmol/mol]), VO_2peak (32.55 [26.49; 38.72] vs. 42.67 ± 10.44 mL/kg/min), peak heart rate (179 [170; 187] vs. 184 [175; 191] beats/min), and peak power (216 [171; 253] vs. 245 [200; 300] W) were lower compared with 308 control participants without type 1 diabetes (all P < 0.001). Individuals with type 1 diabetes displayed an impaired degree and direction of the heart rate-to-performance curve compared with control participants without type 1 diabetes (0.07 [−0.75; 1.09] vs. 0.66 [−0.28; 1.45]; P < 0.001). None of the exercise physiological responses were associated with HbA_1c in individuals with type 1 diabetes. CONCLUSIONS Individuals with type 1 diabetes show altered responses to CPX testing, which cannot be explained by HbA_1c. Intriguingly, the participants in our cohort were people with recent-onset type 1 diabetes; heart rate dynamics were altered during CPX testing.

OBJECTIVE To reduce exercise-associated hypoglycemia, individuals with type 1 diabetes on continuous subcutaneous insulin infusion typically perform basal rate reductions (BRRs) and/or carbohydrate feeding, although the timing and amount of BRRs necessary to prevent hypoglycemia are unclear. The goal of this study was to determine if BRRs set 90 min pre-exercise better attenuate hypoglycemia versus pump suspension (PS) at exercise onset. RESEARCH DESIGN AND METHODS Seventeen individuals completed three 60-min treadmill exercise (∼50% of VO_2peak) visits in a randomized crossover design. The insulin strategies included 1) PS at exercise onset, 2) 80% BRR set 90 min pre-exercise, and 3) 50% BRR set 90 min pre-exercise. RESULTS Blood glucose level at exercise onset was higher with 50% BRR (191 ± 49 mg/dL) vs. 80% BRR (164 ± 41 mg/dL; P < 0.001) and PS (164 ± 45 mg/dL; P < 0.001). By exercise end, 80% BRR showed the smallest drop (−31 ± 58 mg/dL) vs. 50% BRR (−47 ± 50 mg/dL; P = 0.04) and PS (−67 ± 41 mg/dL; P < 0.001). With PS, 7 out of 17 participants developed hypoglycemia versus 1 out of 17 in both BRR conditions (P < 0.05). Following a standardized meal postexercise, glucose rose with PS and 50% BRR (both P < 0.05), but failed to rise with 80% BRR (P = 0.16). Based on interstitial glucose, overnight mean percent time in range was 83%, 83%, and 78%, and time in hypoglycemia was 2%, 1%, and 5% with 80% BRR, 50% BRR, and PS, respectively (all P > 0.05). CONCLUSIONS Overall, a 50–80% BRR set 90 min pre-exercise improves glucose control and decreases hypoglycemia risk during exercise better than PS at exercise onset, while not compromising the postexercise meal glucose control.