Prevalence of nocturnal hypoglycemia in free-living conditions in adults with type 1 diabetes: What is the impact of daily physical activity?

Objective: Studies investigating strategies to limit the risk of nocturnal hypoglycemia associated with physical activity (PA) are scarce and have been conducted in standardized, controlled conditions in people with type 1 diabetes (T1D). This study sought to investigate the effect of daily PA level on nocturnal glucose management in free-living conditions while taking into consideration reported mitigation strategies to limit the risk of nocturnal hyoglycemia in people with T1D. Methods: Data from 25 adults (10 males, 15 females, HbA1c: 7.6 ± 0.8%), 20-60 years old, living with T1D, were collected. One week of continuous glucose monitoring and PA (assessed using an accelerometer) were collected in free-living conditions. Nocturnal glucose values (midnight-6:00 am) following an active day "ACT" and a less active day "L-ACT" were analyzed to assess the time spent within the different glycemic target zones (<3.9 mmol/L; 3.9 - 10.0 mmol/L and >10.0 mmol/L) between conditions. Self-reported data about mitigation strategies applied to reduce the risk of nocturnal hypoglycemia was also analyzed. Results: Only 44% of participants reported applying a carbohydrate- or insulin-based strategy to limit the risk of nocturnal hypoglycemia on ACT day. Nocturnal hypoglycemia occurrences were comparable on ACT night versus on L-ACT night. Additional post-meal carbohydrate intake was higher on evenings following ACT (27.7 ± 15.6 g, ACT vs. 19.5 ± 11.0 g, L-ACT; P=0.045), but was frequently associated with an insulin bolus (70% of participants). Nocturnal hypoglycemia the night following ACT occurred mostly in people who administrated an additional insulin bolus before midnight (3 out of 5 participants with nocturnal hypoglycemia). Conclusions: Although people with T1D seem to be aware of the increased risk of nocturnal hypoglycemia associated with PA, the risk associated with additional insulin boluses may not be as clear. Most participants did not report using compensation strategies to reduce the risk of PA related late-onset hypoglycemia which may be because they did not consider habitual PA as something requiring treatment adjustments.

Is Better Understanding of Management Strategies for Adults With Type 1 Diabetes Associated With a Lower Risk of Developing Hypoglycemia During and After Physical Activity?

BACKGROUND: We aim to determine how knowledge and type 1 diabetes (T1D) management strategies are associated with hypoglycemic risk for physical activity (PA)-induced hypoglycemia among people with T1D (PWT1D). METHODS: One hundred thirty-seven physically active adults with T1D completed diabetes management, PA habits and PA-associated hypoglycemia questionnaire. RESULTS: PA-associated hypoglycemia (during PA, within 1 hour of PA and overnight after PA) was reported by 49% to 61% of respondents, with 18% indicating that they felt inadequately equipped to perform regular PA safely. For during PA, more hypoglycemia was reported by PWT1D with more knowledge of hypoglycemia prevention strategies and those using continuous subcutaneous insulin infusion (CSII) vs multiple injections, those with decreasing basal rate 30 to 60 minutes before PA vs no adjustment before PA, and those taking snacks for unplanned PA vs no snacking. For within 1 hour after PA, more hypoglycemia was reported by PWT1D less knowledgeable about insulin pharmacokinetics and those practicing pre- vs post-dinner PA. For overnight after PA, more hypoglycemia was reported by PWT1D with shorter diabetes duration; CSII users having greater understanding of exercise-induced glucose fluctuations; those reporting reducing nocturnal insulin infusion rates vs no adjustment at night; those engaged in PA for at least 31 minutes; and those engaged in moderate and vigorous PA (vs light PA) as well as regularly performing interval training vs nonregular practice. Glycated hemoglobin and use of continuous glucose monitoring were not associated with any timing of reported PA-associated hypoglycemia. CONCLUSIONS: PA-associated hypoglycemia is common among PWT1D. Greater knowledge of PA and T1D management is not associated with less PA-associated hypoglycemia. Diabetes management confidence could encourage higher tolerance for hypoglycemic risk.

Anticipated Basal Insulin Reduction to Prevent Exercise-Induced Hypoglycemia in Adults and Adolescents Living with Type 1 Diabetes.

Objective: We investigated the effect of two key timings for basal insulin rate reduction on exercise-induced glucose changes and explored the association between circulating insulin concentrations and muscle vasoreactivity. Research Design and Methods: Twenty adults and adolescents performed 60-min exercise sessions (ergocycle) at 60% VO2peak, 240 min after a standardized lunch. In a randomized order, we compared an 80% basal insulin reduction applied 40 min (T-40) or 90 min (T-90) before exercise onset. Near-infrared spectroscopy was used to investigate muscle hemodynamics at vastus lateralis. Glucose and insulin plasma concentrations were measured. Results: Reduction in plasma glucose (PG) level during exercise was attenuated during T-90 versus T-40 strategy (-0.89 ± 1.89 mmol/L vs. -2.17 ± 2.49 mmol/L, respectively; P = 0.09). Linear mixed model analysis showed that PG dropped by an additional 0.01 mM per minute in T-40 versus T-90 (time × strategy interaction, P < 0.05). The absolute number of hypoglycemic events was not different between the two strategies, but they occurred later with T-90. Free insulin tends to decrease more during the pre-exercise period in the T-90 strategy (P = 0.08). Although local muscle vasodilatation (ΔTHb) was comparable between the two strategies, we found that PG dropped more in cases of higher exercise-induced skeletal muscle vasodilatation (ΔTHb × time interaction P < 0.005, e: -0.0086 mM/min and additional mM of ΔTHb). Conclusion: T-90 timing reduced exercise-induced drop in PG and delayed the occurrence of hypoglycemic episodes compared with T-40 timing without a significant reduction in the number of events requiring treatment. Trial registration: ClinicalTrials.gov identifier: NCT03349489.

Minimizing the Risk of Exercise-Induced Glucose Fluctuations in People Living With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion: An Overview of Strategies.

Physical activity (PA) is important for individuals living with type 1 diabetes (T1D) due to its various health benefits. Nonetheless, maintaining adequate glycemic control around PA remains a challenge for many individuals living with T1D because of the difficulty in properly managing circulating insulin levels around PA. Although the most common problem is increased incidence of hypoglycemia during and after most types of PA, hyperglycemia can also occur. Accordingly, a large proportion of people living with T1D are sedentary partly due to the fear of PA-associated hypoglycemia. Continuous subcutaneous insulin infusion (CSII) offers a higher precision and flexibility to adjust insulin basal rates and boluses according to the individual's specific needs around PA practice. Indeed, for physically active patients with T1D, CSII can be a preferred option to facilitate glucose regulation. To our knowledge, there are no guidelines to manage exercise-induced hypoglycemia during PA, specifically for individuals living with T1D and using CSII. In this review, we highlight the current state of knowledge on exercise-related glucose variations, especially hypoglycemic risk and its underlying physiology. We also detail the current recommendations for insulin modulations according to the different PA modalities (type, intensity, duration, frequency) in individuals living with T1D using CSII.

Comparison of two carbohydrate intake strategies to improve glucose control during exercise in adolescents and adults with type 1 diabetes.

BACKGROUND AND AIMS: During aerobic physical activity (PA), hypoglycemia is common in people with type 1 diabetes (T1D). Few studies have compared the effectiveness of different carbohydrate (CHO) intake strategies to prevent PA-induced hypoglycemia. Our objective was to compare the efficacy of two CHO intake strategies, same total amount but different CHO intake timing, to maintain glucose levels in the target range (4.0-10.0 mmol/L) during PA in people with T1D. METHODS AND RESULTS: An open-label, randomized, crossover study in 33 participants (21 adults; 12 adolescents). Participants practiced 60 min PA sessions (ergocyle) at 60% VO2peak 3.5 h after lunch comparing an intake of 0.5 g of CHO per kg of body weight applied in a pre-PA single CHO intake (SCI) or in a distributed CHO intake (DCI) before and during PA. The percentage of time spent in glucose level target range during PA was not different between the two strategies (SCI: 75 ± 35%; DCI: 87 ± 26%; P = 0.12). Hypoglycemia (<4.0 mmol/L) occurred in 4 participants (12%) with SCI compared to 6 participants (18%) with DCI (P = 0.42). The SCI strategy led to a higher increase (P = 0.01) and variability of glucose levels (P = 0.04) compared with DCI. CONCLUSIONS: In people living with T1D, for a 60 min moderate aerobic PA in the post-absorptive condition, a 0.5 g/kg CHO intake helped most participants maintain acceptable glycemic control with both strategies. No clinically significant difference was observed between the SCI and DCI strategies. ClinicalTrials.gov Identifier: NCT03214107 (July 11, 2017).

Effect of caloric restriction with or without physical activity on body composition and epicardial fat in type 2 diabetic patients: A pilot randomized controlled trial.

BACKGROUND AND AIMS: There is debate over the independent and combined effects of caloric restriction (CR) and physical activity (PA) on reduction in fat mass and in epicardial fat thickness. We compared the impact of a similar energy deficit prescription by CR or by CR combined with PA on total fat mass, epicardial fat thickness, and cardiometabolic profile in individuals with type 2 diabetes. METHODS AND RESULTS: In this 16-week randomized controlled study, 73 individuals were randomly enrolled to receive: 1) a monthly motivational phone call (Control), 2) a caloric deficit of -700 kilocalories/day (CR), or 3) a caloric deficit of -500 kilocalories/day combined with a PA program of -200 kilocalories/day (CR&PA). Total fat mass, epicardial fat, and cardiometabolic profile were measured at baseline and after 16 weeks. While comparable weight loss occurred in both intervention groups (-3.9 ± 3.5 kg [CR], -5.1 ± 4.7 kg [CR&PA], -0.2 ± 2.9 kg [Control]), changes in total fat mass were significantly different between all groups (-2.4 ± 2.9 kg [CR], -4.5 ± 3.4 kg [CR&PA], +0.1 ± 2.1 kg [Control]; p < 0.05) as well as epicardial fat thickness (-0.4 ± 1.6 mm [CR], -1.4 ± 1.4 mm [CR&PA], +1.1 ± 1.3 mm [Control]; p < 0.05). There were no significant differences in trends for cardiometabolic parameters improvement between groups. CONCLUSIONS: For a similar energy deficit prescription and comparable weight loss, the combination of CR&PA provides a greater reduction in fat mass and epicardial fat thickness than CR alone in individuals with comparable weight loss and with a similar energy deficit prescription. These results, however, do not translate into significant improvements in cardiometabolic profiles. CLINICALTRIALS. GOV IDENTIFIER: NCT01186952.

A single-blind, randomised, crossover study to reduce hypoglycaemia risk during postprandial exercise with closed-loop insulin delivery in adults with type 1 diabetes: announced (with or without bolus reduction) vs unannounced exercise strategies.

AIMS/HYPOTHESIS: For individuals living with type 1 diabetes, closed-loop insulin delivery improves glycaemic control. Nonetheless, maintenance of glycaemic control during exercise while a prandial insulin bolus remains active is a challenge even to closed-loop systems. We investigated the effect of exercise announcement on the efficacy of a closed-loop system, to reduce hypoglycaemia during postprandial exercise. METHODS: A single-blind randomised, crossover open-label trial was carried out to compare three strategies applied to a closed-loop system at mealtime in preparation for exercise taken 90 min after eating at a research testing centre: (1) announced exercise to the closed-loop system (increases target glucose levels) in addition to a 33% reduction in meal bolus (A-RB); (2) announced exercise to the closed-loop system and a full meal bolus (A-FB); (3) unannounced exercise and a full meal bolus (U-FB). Participants performed 60 min of exercise at 60% [Formula: see text] 90 min after eating breakfast. The investigators were not blinded to the interventions. However, the participants were blinded to the sensor glucose readings and to the insulin infusion rates throughout the intervention visits. RESULTS: The trial was completed by 37 adults with type 1 diabetes, all using insulin pumps: mean±SD, 40.0 ± 15.0 years of age, HbA1c 57.1 ± 10.8 mmol/mol (7.3 ± 1.0%). Reported results were based on plasma glucose values. During exercise and the following 1 h recovery period, time spent in hypoglycaemia (<3.9 mmol/l; primary outcome) was reduced with A-RB (mean ± SD; 2.0 ± 6.2%) and A-FB (7.0 ± 12.6%) vs U-FB (13.0 ± 19.0%; p < 0.0001 and p = 0.005, respectively). During exercise, A-RB had the least drop in plasma glucose levels: A-RB -0.3 ± 2.8 mmol/l, A-FB -2.6 ± 2.9 mmol/l vs U-FB -2.4 ± 2.7 mmol/l (p < 0.0001 and p = 0.5, respectively). Comparison of A-RB vs U-FB revealed a decrease in the time spent in target (3.9-10 mmol/l) by 12.7% (p = 0.05) and an increase in the time spent in hyperglycaemia (>10 mmol/l) by 21% (p = 0.001). No side effects were reported during the applied strategies. CONCLUSIONS/INTERPRETATION: Combining postprandial exercise announcement, which increases closed-loop system glucose target levels, with a 33% meal bolus reduction significantly reduced time spent in hypoglycaemia compared with the other two strategies, yet at the expense of more time spent in hyperglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT0285530 FUNDING: JDRF (2-SRA-2016-210-A-N), the Canadian Institutes of Health Research (354024) and the Fondation J.-A. DeSève chair held by RR-L.

Changes in Accuracy of Continuous Glucose Monitoring Using Dexcom G4 Platinum Over the Course of Moderate Intensity Aerobic Exercise in Type 1 Diabetes.

Continuous glucose monitoring (CGM) systems help diabetes management in patients with type 1 diabetes (T1D) but could have lower accuracy during exercise. We aim to evaluate the dynamics of CGM accuracy during exercise in patients with T1D. Secondary analysis of data was carried out on 22 patients with T1D (glycated hemoglobin [HbA1c]: 7.3% ± 1.0%, diabetes duration: 23 ± 13 years), who did three exercise sessions (45 min at 60% VO2max on an ergocycle, 3 h postmeal) with paired Dexcom G4 Platinum, and capillary glucose values that were collected every 5 min. Dexcom accuracy was evaluated using sensor bias (SB) and absolute relative difference (ARD). For dynamics of SB analysis, data pairs following hypoglycemia correction were excluded. The analyzed data included 792 pairs (594 during 66 exercise sessions, 198 at rest before exercise). Median ARD was 8.44 (5.35-12.13)% at rest and increased to 16.77 (10.75-26.72)% during exercise (P < 0.001). During exercise, mean SB values evolved from T0 minutes = 5.95 ± 16.04 mg/dL (exercise start); T5 = 9.55 ± 16.40; T10 = 13.51 ± 18.02; T15 = 15.32 ± 20.36; T20 = 17.30 ± 18.92; T25 = 19.46 ± 17.48; T30 = 21.08 ± 19.64; T35 = 19.10 ± 20.36; T40 = 19.82 ± 20.18; and T45 = 18.02 ± 20.90 (exercise end). CGM overestimated capillary at a mean SB of 14.23 ± 16.76 mg/dL over the whole exercise session. CGM accuracy decreased during moderate aerobic exercise as previously described. However, the trend to overestimate capillary glucose was maintained at relatively stable values within 15 min of exercise initiation, which could help patients in their clinical decisions. Similar analyses would be needed for other types of exercise.

Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial.

AIMS/HYPOTHESIS: The aim of this study was to assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared with the single-hormone (insulin alone) artificial pancreas during two types of exercise. METHODS: An open-label randomised crossover study comparing both systems in 17 adults with type 1 diabetes (age, 37.2 ± 13.6 years; HbA1c, 8.0 ± 1.0% [63.9 ± 10.2 mmol/mol]) during two exercise types on an ergocycle and matched for energy expenditure: continuous (60% [Formula: see text] for 60 min) and interval (2 min alternating periods at 85% and 50% [Formula: see text] for 40 min, with two 10 min periods at 45% [Formula: see text] at the start and end of the session). Blocked randomisation (size of four) with a 1:1:1:1 allocation ratio was computer generated. The artificial pancreas was applied from 15:30 hours until 19:30 hours; exercise was started at 18:00 hours and announced 20 min earlier to the systems. The study was conducted at the Institut de recherches cliniques de Montréal. RESULTS: During single-hormone control compared with dual-hormone control, exercise-induced hypoglycaemia (plasma glucose <3.3 mmol/l with symptoms or <3.0 mmol/l regardless of symptoms) was observed in four (23.5%) vs two (11.8%) interventions (p = 0.5) for continuous exercise and in six (40%) vs one (6.25%) intervention (p = 0.07) for interval exercise. For the pooled analysis (single vs dual hormone), the median (interquartile range) percentage time spent at glucose levels below 4.0 mmol/l was 11% (0.0-46.7%) vs 0% (0-0%; p = 0.0001) and at glucose levels between 4.0 and 10.0 mmol/l was 71.4% (53.2-100%) vs 100% (100-100%; p = 0.003). Higher doses of glucagon were needed during continuous (0.126 ± 0.057 mg) than during interval exercise (0.093 ± 0.068 mg) (p = 0.03), with no reported side-effects in all interventions. CONCLUSIONS/INTERPRETATION: The dual-hormone artificial pancreas outperformed the single-hormone artificial pancreas in regulating glucose levels during announced exercise in adults with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01930110 FUNDING: : Société Francophone du Diabète and Diabète Québec.

Comparison of Two Continuous Glucose Monitoring Systems, Dexcom G4 Platinum and Medtronic Paradigm Veo Enlite System, at Rest and During Exercise.

BACKGROUND: Despite technological advances, the accuracy of continuous glucose monitoring (CGM) systems may not always be satisfactory with rapidly changing glucose levels, as is notable during exercise. We compare the performance of two current and widely used CGM systems, Dexcom G4 Platinum (Dexcom) and Medtronic Paradigm Veo Enlite system (Enlite), during both rest and exercise in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Paired sensor and plasma glucose (PG) values (total of 431 data pairs for Dexcom and 425 for Enlite) were collected from 17 adults (37.3 ± 13.6 years) with T1D. To evaluate and compare the accuracy of sensor readings, criteria involving sensor bias (sensor minus PG levels), absolute relative difference (ARD), and percentage of readings meeting International Organization for Standardization (ISO) criteria were considered. RESULTS: Both Dexcom and Enlite performed equally well during the rest period, with respective mean/median biases of -0.12/-0.02 mmol/L versus -0.18/-0.40 (P = 0.78, P = 0.66) mmol/L and ARDs of 13.77/13.34% versus 12.38/11.95% (P = 0.53, P = 0.70). During exercise, sensor bias means/medians were -0.40/-0.21 mmol versus -0.26/-0.24 mmol/L (P = 0.67, P = 0.62) and ARDs were 22.53/15.13% versus 20.44/14.11% (P = 0.58, P = 0.68) for Dexcom and Enlite, respectively. Both sensors demonstrated significantly lower performance during exercise; median ARD comparison at rest versus exercise for both Dexcom and Enlite showed a P = 0.02. More data pairs met the ISO criteria for Dexcom and Enlite at rest, 73.6% and 76.9% compared with exercise 48.2% and 53.9%. CONCLUSION: Dexcom and Enlite demonstrated comparable overall performances during rest and physical activity. However, a lower accuracy was observed during exercise for both sensors, necessitating a fine-tuning of their performance with physical activity.

A pilot program for physical exercise promotion in adults with type 1 diabetes: the PEP-1 program.

Physical inactivity is highly common in adults with type 1 diabetes (T1D) as specific barriers (i.e., hypoglycemia) may prevent them from being active. The objective of this study was to examine the efficacy of the Physical Exercise Promotion program in type 1 diabetes (PEP-1) program, a group program of physical activity (PA) promotion (intervention) compared with an information leaflet (control), to improve total energy expenditure (TEE) in adults with T1D after 12 weeks. TEE was measured with a motion sensor over a 7-day period at inclusion, after the program (12 weeks) and 1-year after inclusion. The 12 weekly sessions of the program included a 30-min information session (glycemic control and PA) and 60 min of PA. A total of 48 adults, aged 18 to 65 years with a reported PA practice <150 min per week, were recruited (45.8% men; aged 44.6 ± 13.3 years; 8.0% ± 1.1% glycated hemoglobin (A1c)) and randomized in this pilot trial. Ninety percent of participants completed the program and 88% completed the 1-year follow-up. No change was observed for TEE and A1c in both groups. After the 12-week program, the mean peak oxygen uptake increased (14%; p = 0.003) in the intervention group; however, at the 1-year follow-up, it was no longer different from baseline. In the control group, no difference was observed for the peak oxygen uptake. These results suggest that the PEP-1 pilot program could increase cardiorespiratory fitness. However, this benefit is not sustained over a long-term period. The PEP-1 program did not increase TEE in patients with T1D and other strategies remain necessary to counteract physical inactivity in this population.