Automated Insulin Delivery in Adults With Type 1 Diabetes and Suboptimal HbA1c During Prior Use of Insulin Pump and Continuous Glucose Monitoring: A Randomized Controlled Trial.

BACKGROUND: Automated insulin delivery (AID) systems offer promise in improving glycemic outcomes for individuals with type 1 diabetes. However, data on those who struggle with suboptimal glycemic levels despite insulin pump and continuous glucose monitoring (CGM) are limited. We conducted a randomized controlled trial to assess the effects of an AID system in this population. METHODS: Participants with hemoglobin A1c (HbA1c) ≥ 58 mmol/mol (7.5%) were allocated 1:1 to 14 weeks of treatment with the MiniMed 780G system (AID) or continuation of usual care (UC). The primary endpoint was change in time in range (TIR: 3·9-10·0 mmol/L) from baseline to week 14. After this trial period, the UC group switched to AID treatment while the AID group continued using the system. Both groups were monitored for a total of 28 weeks. RESULTS: Forty adults (mean ± SD: age 52 ± 11 years, HbA1c 67 ± 7 mmol/mol [8.3% ± 0.6%], diabetes duration 29 ±13 years) were included. After 14 weeks, TIR increased by 18.7% (95% confidence interval [CI] = 14.5, 22.9%) in the AID group and remained unchanged in the UC group (P < .0001). Hemoglobin A1c decreased by 10.0 mmol/mol (95% CI = 7.0, 13.0 mmol/mol) (0.9% [95% CI = 0.6%, 1.2%]) in the AID group but remained unchanged in the UC group (P < .0001). The glycemic benefits of AID treatment were reproduced after the 14-week extension phase. There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the study. CONCLUSIONS: For adults with type 1 diabetes not meeting glycemic targets despite use of insulin pump and CGM, transitioning to an AID system confers considerable glycemic benefits.

Exercising Safely with the MiniMed™ 780G Automated Insulin Delivery System.

The physical and psychological benefits of exercise are particularly pertinent to people with type 1 diabetes (T1D). The variability in subcutaneous insulin absorption and the delay in offset and onset in glucose lowering action impose limitations, given the rapidly varying insulin requirements with exercise. Simultaneously, there are challenges to glucose monitoring. Consequently, those with T1D are less likely to exercise because of concerns regarding glucose instability. While glucose control with exercise can be enhanced using automated insulin delivery (AID), all commercially available AID systems remain limited by the pharmacokinetics of subcutaneous insulin delivery. Although glycemic responses may vary with exercises of differing intensities and durations, the principles providing the foundation for guidelines include minimization of insulin on board before exercise commencement, judicious and timely carbohydrate supplementation, and when possible, a reduction in insulin delivered in anticipation of planned exercise. There is an increasing body of evidence in support of superior glucose control with AID over manual insulin dosing in people in T1D who wish to exercise. The MiniMed™ 780G AID system varies basal insulin delivery with superimposed automated correction boluses. It incorporates a temporary (elevated glucose) target of 8.3 mmol/L (150 mg/dL) and when it is functioning, the autocorrection boluses are stopped. As the device has recently become commercially available, there are limited data assessing glucose control with the MiniMed™ 780G under exercise conditions. Importantly, when exercise was planned and implemented within consensus guidelines, %time in range and %time below range targets were met. A practical approach to exercising with the device is provided with illustrative case studies. While there are limitations to spontaneity imposed on any AID device due to the pharmacokinetics associated with the subcutaneous delivery of current insulin formulations, the MiniMed™ 780G system provides people with T1D an excellent option for exercising safely if the appropriate strategies are implemented.

Sensor-Based Glucose Metrics during Different Diet Compositions in Type 1 Diabetes-A Randomized One-Week Crossover Trial.

By reducing carbohydrate intake, people with type 1 diabetes may reduce fluctuations in blood glucose, but the evidence in this area is sparse. The aim of this study was to investigate glucose metrics during a one-week low-carbohydrate-high-fat (HF) and a low-carbohydrate-high-protein (HP) diet compared with an isocaloric high-carbohydrate (HC) diet. In a randomized, three-period cross-over study, twelve adults with insulin-pump-treated type 1 diabetes followed an HC (energy provided by carbohydrate: 48%, fat: 33%, protein: 19%), HF (19%, 62%, 19%), and an HP (19%, 57%, 24%) diet for one week. Glucose values were obtained during intervention periods using a Dexcom G6 continuous glucose monitoring system. Participant characteristics were: 33% females, median (range) age 50 (22-70) years, diabetes duration 25 (11-52) years, HbA1c 7.3 (5.5-8.3)% (57 (37-67) mmol/mol), and BMI 27.3 (21.3-35.9) kg/m2. Glycemic variability was lower with HF (30.5 ± 6.2%) and HP (30.0 ± 5.5%) compared with HC (34.5 ± 4.1%) (PHF-HC = 0.009, PHP-HC = 0.003). There was no difference between groups in mean glucose (HF: 8.7 ± 1.1, HP: 8.2 ± 1.0, HC: 8.7 ± 1.0 mmol/L, POverall = 0.08). Time > 10.0 mmol/L was lower with HP (22.3 ± 11.8%) compared with HF (29.4 ± 12.1%) and HC (29.5 ± 13.4%) (PHF-HP = 0.037, PHC-HP = 0.037). In conclusion, a one-week HF and, specifically, an HP diet improved glucose metrics compared with an isocaloric HC diet.

Effects of a Low-Carbohydrate-High-Protein Pre-Exercise Meal in Type 1 Diabetes-a Randomized Crossover Trial.

CONTEXT: Current guidelines for exercise-related glucose management focus on reducing bolus and/or basal insulin doses and considering carbohydrate intake. Yet far less attention has been paid to the potential role of other macronutrients alongside carbohydrates on glucose dynamics around exercise. OBJECTIVE: To investigate the effects of a low-carbohydrate-high-protein (LCHP) compared with a high-carbohydrate-low-protein (HCLP) pre-exercise meal on the metabolic, hormonal, and physiological responses to exercise in adults with insulin pump-treated type 1 diabetes. METHODS: Fourteen adults (11 women, 3 men) with insulin pump-treated type 1 diabetes (median [range] HbA1c of 50 [43-59] mmol/mol (6.7% [6.1%-7.5%]), age of 49 [25-65] years, and body mass index of 24.0 [19.3-27.1] kg/m2) completed an unblinded, 2-arm, randomized, crossover study. Participants ingested isocaloric meals that were either LCHP (carbohydrate 21%, protein 52%, fat 27%) or HCLP (carbohydrate 52%, protein 21%, fat 27%) 90 minutes prior to undertaking 45 minutes of cycling at moderate intensity. Meal insulin bolus was dosed according to meal carbohydrate content but reduced by 25%. Basal insulin rates were reduced by 35% from meal ingestion to end of exercise. RESULTS: Around exercise the coefficient of variability was lower during LCHP (LCHP: 14.5 ± 5.3 vs HCLP: 24.9 ± 7.7%, P = .001). Over exercise, LCHP was associated with a lesser drop (LCHP: Δ-1.49 ± 1.89 vs HCLP: Δ-3.78 ± 1.95 mmol/L, P = .001). Mean insulin concentration was 30% lower during exercise for LCHP compared with HCLP (LCHP: 25.5 ± 11.0 vs HCLP: 36.5 ± 15.9 mU/L, P < .001). CONCLUSION: Ingesting a LCHP pre-exercise meal lowered plasma glucose variability around exercise and diminished the drop in plasma glucose over exercise.

Automated Insulin Delivery Around Exercise in Adults with Type 1 Diabetes: A Pilot Randomized Controlled Study.

Aim: To assess the effectiveness of an automated insulin delivery (AID) system around exercise in adults with type 1 diabetes (T1D). Methods: This was a three-period, randomized, crossover trial involving 10 adults with T1D (hemoglobin A1C; HbA1c: 8.3% ± 0.6% [67 ± 6 mmol/mol]) using an AID system (MiniMed 780G; Medtronic USA). Participants performed 45 min of moderate intensity continuous exercise 90 min after consuming a carbohydrate-based meal using three strategies: (1) a 100% dose of bolus insulin with exercise announcement immediately at exercise onset "spontaneous exercise" (SE) or a 25% reduced dose of bolus insulin with exercise announcement either (2) 90 min (AE90) or (3) 45 min (AE45) before exercise. Venous-derived plasma glucose (PG) taken in 5 and 15 min intervals over a 3 h collection period was stratified into the percentage of time spent below (TBR [<3.9 mmol/L]), time in range (TIR [3.9-10 mmol/L]), and time above range (TAR [ > 10 mmol/L]). In instances of hypoglycemia, PG data were carried forward for the remainder of the visit. Results: Overall, TBR was greatest during SE (SE: 22.9 ± 22.2, AE90: 1.1 ± 1.9, AE45: 7.8% ± 10.3%, P = 0.029). Hypoglycemia during exercise occurred in four participants in SE but one in both AE90 and AE45 (ꭓ2 [2] = 3.600, P = 0.165). In the 1 h postexercise period, AE90 was associated with higher TIR (SE: 43.8 ± 49.6, AE90: 97.9 ± 5.9, AE45: 66.7% ± 34.5%, P = 0.033), lower TBR (SE: 56.3 ± 49.6, AE90: 2.1 ± 5.9, AE45: 29.2% ± 36.5%, P = 0.041) with the greatest source of discrepancy observed relative to SE. Conclusion: In adults using an AID system and undertaking postprandial exercise, a strategy involving both bolus insulin dose reduction and exercise announcement 90 min before commencing the activity may be most effective in minimizing dysglycemia. The study was registered as a clinical trial (Clinical Trials Register; NCT05134025).

Glycemia Around Exercise in Adults with Type 1 Diabetes Using Automated and Nonautomated Insulin Delivery Pumps: A Switch Pilot Trial.

In an in-patient switch study, 10 adults with type 1 diabetes (T1D) performed 45 min of moderate-intensity exercise on 2 occasions: (1) when using their usual insulin pump (UP) and (2) after transitioning to automated insulin delivery (AID) treatment (MiniMed™ 780G). Consensus glucose management guidelines for performing exercise were applied. Plasma glucose concentrations measured over a 3-h monitoring period were stratified into time below range (TBR, <3.9 mmol/L), time in range (TIR, 3.9-10.0 mmol/L), and time above range (TAR, >10.0 mmol/L). Overall, TBR (UP: 11 ± 21 vs. AID: 3% ± 10%, P = 0.413), TIR (UP: 53 ± 27 vs. AID: 66% ± 39%, P = 0.320), and TAR (UP: 37 ± 34 vs. AID: 31% ± 41%, P = 0.604) were similar between arms. A proportionately low number of people experienced exercise-induced hypoglycemia (UP: n = 2 vs. AID: n = 1, P = 1.00). In conclusion, switching to AID therapy did not alter patterns of glycemia around sustained moderate-intensity exercise in adults with T1D. Clinical Trial Registration number: NCT05133765.

Metabolic and physiological responses to graded exercise testing in individuals with type 1 diabetes using insulin pump therapy.

AIMS: To profile acute glycaemic dynamics during graded exercise testing (GXT) and explore the influence of glycaemic indicators on the physiological responses to GXT in adults with type 1 diabetes using insulin pump therapy. METHODS: This was a retrospective analysis of pooled data from four clinical trials with identical GXT protocols. Data were obtained from 45 adults with type 1 diabetes using insulin pumps [(30 females); haemoglobin A1c 59.5 ± 0.5 mmol/mol (7.6 ± 1.0%); age 49.7 ± 13.0 years; diabetes duration 31.2 ± 13.5 years; V̇O2peak 29.5 ± 8.0 ml/min/kg]. Integrated cardiopulmonary variables were collected continuously via spiroergometry. Plasma glucose was obtained every 3 min during GXT as well as the point of volitional exhaustion. Data were assessed via general linear modelling techniques with age and gender adjustment. Significance was accepted at p ≤ .05. RESULTS: Despite increasing duration and intensity, plasma glucose concentrations remained similar to rest values (8.8 ± 2.3 mmol/L) throughout exercise (p = .419) with an overall change of +0.3 ± 1.1 mmol/L. Starting glycaemia bore no influence on subsequent GXT responses. Per 1% increment in haemoglobin A1c there was an associated decrease in V̇O2peak of 3.8 ml/min/kg (p < .001) and powerpeak of 0.33 W/kg (p < .001) concomitant with attenuations in indices of peripheral oxygen extraction [(O2 pulse) -1.2 ml/beat, p = .023]. CONCLUSION: In adults with long-standing type 1 diabetes using insulin pump therapy, circulating glucose remains stable during a graded incremental cycle test to volitional exhaustion. Glycaemic indicators are inversely associated with aerobic rate, oxygen economy and mechanical output across the exercise intensity spectrum. An appreciation of these nexuses may help guide appropriate decision making for optimal exercise management strategies.

Nutritional intake when cycling under racing and training conditions in professional male cyclists with type 1 diabetes.

This study sought to detail and compare the in-ride nutritional practices of a group of professional cyclists with type 1 diabetes (T1D) under training and racing conditions. We observed seven male professional road cyclists with T1D (Age: 28 ± 4 years, HbA1c: 6.4 ± 0.4% [46 ± 4 mmol.mol-1], VO2max: 73.9 ± 4.3 ml.kg -1.min-1) during pre-season training and during a Union Cycliste Internationale multi-stage road cycling race (Tour of Slovenia). In-ride nutritional, interstitial glucose, and performance variables were quantified and compared between the two events.    The in-ride energy intake was similar between training and racing conditions     (p = 0.909), with carbohydrates being the major source of fuel in both events during exercise at a rate of 41.9 ± 6.8 g.h-1 and 45.4 ± 15.5 g.h-1 (p = 0.548), respectively. Protein consumption was higher during training (2.6 ± 0.6 g.h-1) than race rides (1.9 ± 0.9 g.h-1; p = 0.051).   A similar amount of time was spent within the euglycaemic range (≥70-≤180 mg.dL-1): training 77.1 ± 32.8% vs racing 73.4 ± 3.9%; p = 0.818. These data provide new information on the in-ride nutritional intake in professional cyclists with T1D during different stages of the competitive season.

The endocrine pancreas during exercise in people with and without type 1 diabetes: Beyond the beta-cell.

Although important for digestion and metabolism in repose, the healthy endocrine pancreas also plays a key role in facilitating energy transduction around physical exercise. During exercise, decrements in pancreatic ß-cell mediated insulin release opposed by increments in α-cell glucagon secretion stand chief among the hierarchy of glucose-counterregulatory responses to decreasing plasma glucose levels. As a control hub for several major glucose regulatory hormones, the endogenous pancreas is therefore essential in ensuring glucose homeostasis. Type 1 diabetes (T1D) is pathophysiological condition characterised by a destruction of pancreatic ß-cells resulting in pronounced aberrations in glucose control. Yet beyond the beta-cell perhaps less considered is the impact of T1D on all other pancreatic endocrine cell responses during exercise and whether they differ to those observed in healthy man. For physicians, understanding how the endocrine pancreas responds to exercise in people with and without T1D may serve as a useful model from which to identify whether there are clinically relevant adaptations that need consideration for glycaemic management. From a physiological perspective, delineating differences or indeed similarities in such responses may help inform appropriate exercise test interpretation and subsequent program prescription. With more complex advances in automated insulin delivery (AID) systems and emerging data on exercise algorithms, a timely update is warranted in our understanding of the endogenous endocrine pancreatic responses to physical exercise in people with and without T1D. By placing our focus here, we may be able to offer a nexus of better understanding between the clinical and engineering importance of AIDs requirements during physical exercise.

Passing on the exercise baton: What can endocrine patients learn from elite athletes?

As elite athletes demonstrate through the Olympic motto 'Citius, Altius, Fortius- Communiter', new performance records are driven forward by favourable skeletal muscle bioenergetics, cardiorespiratory, and endocrine system adaptations. At a recreational level, regular physical activity is an effective nonpharmacological therapy in the treatment of many endocrine conditions. However, the impact of physical exercise on endocrine function and how best to incorporate exercise therapy into clinical care are not well understood. Beyond the pursuit of an Olympic medal, elite athletes may therefore serve as role models for showcasing how exercise can help in the management of endocrine disorders and improve metabolic dysfunction. This review summarizes research evidence for clinicians who wish to understand endocrine changes in athletes who already perform high levels of activity as well as to encourage patients to exercise more safely. Herein, we detail the upper limits of athleticism to showcase the adaptability of human endocrine-metabolic-physiological systems. Then, we describe the growing research base that advocates the importance of understanding maladaptation to physical training and nutrition in males and females; especially the young. Finally, we explore the impact of physical activity in improving some endocrine disorders with guidance on how lessons can be taken from athletes training and incorporated into strategies to move more people more often.

Pancreatic ß-Cell Function Is Associated with Augmented Counterregulation to In-Exercise Hypoglycemia in Type 1 Diabetes.

PURPOSE: This study aimed to investigate the influence of residual ß-cell function on counterregulatory hormonal responses to hypoglycemia during acute physical exercise in people with type 1 diabetes (T1D). A secondary aim was to explore relationships between biomarkers of pancreatic ß-cell function and indices of glycemia following acute exercise including the nocturnal period. METHODS: This study involved an exploratory, secondary analysis of data from individuals with T1D who partook in a four-peroid, randomized, cross-over trial involving a bout of evening exercise followed by an overnight stay in a clinical laboratory facility. Participants were split into two groups: (i) a stimulated C-peptide level of ≥30 pmol⋅L-1 (low-level secretors [LLS], n = 6) or (ii) <30 pmol⋅L-1 (microsecretors [MS], n = 10). Pancreatic hormones (C-peptide, proinsulin, and glucagon), catecholamines (epinephrine [EPI] and norepinephrine [NE]), and metabolic biomarkers (blood glucose, blood lactate, and ß-hydroxybutyrate) were measured at rest, during exercise with and without a hypoglycemic (blood glucose ≤3.9 mmol⋅L-1) episode, and throughout a 13-h postexercise period. Interstitial glucose monitoring was used to assess indices of glycemic variability. RESULTS: During in-exercise hypoglycemia, LLS presented with greater sympathoadrenal (EPI and NE P ≤ 0.05) and ketone (P < 0.01) concentrations. Glucagon remained similar (P = 0.09). Over exercise, LLS experienced larger drops in C-peptide and proinsulin (both P < 0.01) as well as greater increases in EPI (P < 0.01) and ß-hydroxybutyrate (P = 0.03). LLS spent less time in the interstitial-derived hypoglycemic range acutely postexercise and had lower glucose variability throughout the nocturnal period. CONCLUSION: Higher residual ß-cell function was associated with greater sympathoadrenal and ketonic responses to exercise-induced hypoglycemia as well as improved glycemia leading into and throughout the nocturnal hours. Even a minimal amount of residual ß-cell function confers a beneficial effect on glycemic outcomes during and after exercise in people with T1D.

Extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin adjustments in individuals with type 1 diabetes.

AIM: To detail the extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin dose adjustments in individuals with type 1 diabetes (T1D) using multiple daily injections of insulins aspart (IAsp) and degludec (IDeg). METHODS AND RESULTS: Sixteen individuals with T1D, completed a single-centred, randomised, four-period crossover trial consisting of 23-h inpatient phases. Participants administered either a regular (100%) or reduced (50%) dose (100%; 5.1 ± 2.4, 50%; 2.6 ± 1.2 IU, p < 0.001) of individualised IAsp 1 h before and after 45-min of evening exercise at 60 ± 6% V̇O2max. An unaltered dose of IDeg was administered in the morning. Metabolic, physiological and hormonal responses during exercise, recovery and nocturnal periods were characterised. The primary outcome was the number of trial day occurrences of hypoglycemia (venous blood glucose ≤ 3.9 mmol L -1). Inclusion of a 50% IAsp dose reduction strategy prior to evening exercise reduced the occurrence of in-exercise hypoglycemia (p = 0.023). Mimicking this reductive strategy in the post-exercise period decreased risk of nocturnal hypoglycemia (p = 0.045). Combining this strategy to reflect reductions either side of exercise resulted in higher glucose concentrations in the acute post-exercise (p = 0.034), nocturnal (p = 0.001), and overall (p < 0.001) periods. Depth of hypoglycemia (p = 0.302), as well as ketonic and counter-regulatory hormonal profiles were similar. CONCLUSIONS: These findings demonstrate the glycemic safety of peri-exercise bolus dose reduction strategies in minimising the prevalence of acute and nocturnal hypoglycemia following evening exercise in people with T1D on MDI. Use of newer background insulins with current bolus insulins demonstrates efficacy and advances current recommendations for safe performance of exercise. CLINICAL TRIALS REGISTER: DRKS00013509.

Differences in Physiological Responses to Cardiopulmonary Exercise Testing in Adults With and Without Type 1 Diabetes: A Pooled Analysis.

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, HbA1c 6.9% [6.2; 7.7%] [52 (44; 61) mmol/mol]), VO2peak (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 HbA1c in individuals with type 1 diabetes. CONCLUSIONS: Individuals with type 1 diabetes show altered responses to CPX testing, which cannot be explained by HbA1c. Intriguingly, the participants in our cohort were people with recent-onset type 1 diabetes; heart rate dynamics were altered during CPX testing.

Blood Glucose Responses during Cardiopulmonary Incremental Exercise Testing in Type 1 Diabetes: A Pooled Analysis.

PURPOSE: This study aimed to determine the glycemic responses to cardiopulmonary exercise testing (CPET) in individuals with type 1 diabetes (T1D) and to explore the influence of starting blood glucose (BG) concentrations on subsequent CPET outcomes. METHODS: This study was a retrospective, secondary analysis of pooled data from three randomized crossover trials using identical CPET protocols. During cycling, cardiopulmonary variables were measured continuously, with BG and lactate values obtained minutely via capillary earlobe sampling. Anaerobic threshold was determined using ventilatory parameters. Participants were split into (i) euglycemic ([Eu] >3.9 to ≤10.0 mmol·L-1, n = 26) and (ii) hyperglycemic ([Hyper] >10.0 mmol·L-1, n = 10) groups based on preexercise BG concentrations. Data were assessed via general linear modeling techniques and regression analyses. P values of ≤0.05 were accepted as significant. RESULTS: Data from 36 individuals with T1D (HbA1c, 7.3% ± 1.1% [56.0 ± 11.5 mmol·mol-1]) were included. BG remained equivalent to preexercise concentrations throughout CPET, with an overall change in BG of -0.32 ± 1.43 mmol·L-1. Hyper had higher HR at peak (+10 ± 2 bpm, P = 0.04) and during recovery (+9 ± 2 bpm, P = 0.038) as well as lower O2 pulse during the cool down period (-1.6 ± 0.04 mL per beat, P = 0.021). BG responses were comparable between glycemic groups. Higher preexercise BG led to greater lactate formation during exercise. HbA1c was inversely related to time to exhaustion (r = -0.388, P = 0.04) as well as peak power output (r = -0.355, P = 0.006) and O2 pulse (r = -0.308, P = 0.015). CONCLUSIONS: This study demonstrated 1) stable BG responses to CPET in patients with T1D; 2) although preexercise hyperglycemia did not influence subsequent glycemic dynamics, it did potentiate alterations in various cardiac and metabolic responses to CPET; and 3) HbA1c was a significant factor in the determination of peak performance outcomes during CPET.

Factors Influencing Insulin Absorption Around Exercise in Type 1 Diabetes.

International charities and health care organizations advocate regular physical activity for health benefit in people with type 1 diabetes. Clinical expert and international diabetes organizations' position statements support the management of good glycemia during acute physical exercise by adjusting exogenous insulin and/or carbohydrate intake. Yet research has detailed, and patients frequently report, variable blood glucose responses following both the same physical exercise session and insulin to carbohydrate alteration. One important source of this variability is insulin delivery to the circulation. With modern insulin analogs, it is important to understand how different insulins, their delivery methods, and inherent physiological factors, influence the reproducibility of insulin absorption from the injection site into circulation. Furthermore, contrary to the adaptive pancreatic response to exercise in the person without diabetes, the physiological and metabolic shifts with exercise may increase circulating insulin concentrations that may contribute to exercise-related hyperinsulinemia and consequent hypoglycemia. Thus, a furthered understanding of factors underpinning insulin delivery may offer more confidence for healthcare professionals and patients when looking to improve management of glycemia around exercise.

Metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes.

INTRODUCTION: This study sought to compare the metabolomic, hormonal and physiological responses to hypoglycemia versus euglycemia during exercise in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Thirteen individuals with T1D (hemoglobin; 7.0%±1.3% (52.6±13.9 mmol/mol), age; 36±15 years, duration diabetes; 15±12 years) performed a maximum of 45 min submaximal exercise (60%±6% V̇O2max). Retrospectively identified exercise sessions that ended in hypoglycemia ((HypoEx) blood glucose (BG)≤3.9 mmol/L) were compared against a participant-matched euglycemic condition ((EuEx) BG≥4.0, BG≤10.0 mmol/L). Samples were compared for detailed physiological and hormonal parameters as well as metabolically profiled via large scale targeted ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Data were assessed using univariate and multivariate analysis techniques with false discovery rate adjustment. Significant results were considered at p≤0.05. RESULTS: Cardiorespiratory and counterregulatory hormone responses, whole-body fuel use and perception of fatigue during exercise were similar under conditions of hypoglycemia and euglycemia (BG 3.5±0.3 vs 5.8±1.1 mmol/L, respectively p<0.001). HypoEx was associated with greater adenosine salvage pathway activity (5'-methylthioadenosine, p=0.023 and higher cysteine and methionine metabolism), increased utilization of glucogenic amino acids (glutamine, p=0.021, alanine, aspartate and glutamate metabolism and homoserine/threonine, p=0.045) and evidence of enhanced ß-oxidation (lower carnitine p<0.001, higher long-chain acylcarnitines). CONCLUSIONS: Exposure to acute hypoglycemia during exercise potentiates alterations in subclinical indices of metabolic stress at the level of the metabolome. However, the physiological responses induced by dynamic physical exercise may mask the symptomatic recognition of mild hypoglycemia during exercise in people with T1D, a potential clinical safety concern that reinforces the need for diligent glucose management. TRIAL REGISTRATION NUMBER: DRKS00013509.

Efficacy of Carbohydrate Supplementation Compared With Bolus Insulin Dose Reduction Around Exercise in Adults With Type 1 Diabetes: A Retrospective, Controlled Analysis.

OBJECTIVES: Individuals with type 1 diabetes try to manage the risk of exercise-induced hypoglycemia by either pre-exercise/pre-meal bolus insulin dose reductions and/or consuming additional carbohydrates during exercise. Both strategies have proven to be effective in offsetting hypoglycemia, but it remains unclear which one is more beneficial. The aim of this study was to assess the efficacy of carbohydrate supplementation vs bolus insulin dose reduction in prevention of hypoglycemia during moderate-intensity exercise in those with type 1 diabetes. METHODS: This investigation was a retrospective, controlled analysis of 2 independent clinical trials. All participants performed continuous, moderate-intensity cycle ergometer exercise for ∼45 minutes. Two therapy management groups and a control group were compared. Group A was supplemented with 15 to 30 g carbohydrates at a glycemic threshold of 7.0 mmol/L during exercise, group B reduced their individual bolus insulin dose by 50% with their last meal before exercise and group C served as a control. RESULTS: No hypoglycemic events occurred in group A, whereas 4 events were recorded in groups B (p=0.02) and C (p=0.02). CONCLUSIONS: Carbohydrate supplementation was superior to bolus insulin reduction for prevention of hypoglycemia during exercise in people with type 1 diabetes.

Bolus insulin dose depends on previous-day race intensity during 5 days of professional road-cycle racing in athletes with type 1 diabetes: A prospective observational study.

AIMS: To assess insulin therapy, macronutrient intake and glycaemia in professional cyclists with type 1 diabetes (T1D) over a 5-day Union Cycliste Internationale road-cycle race. MATERIAL AND METHODS: In this prospective observational study, seven professional cyclists with T1D (age 28 ± 4 years, body mass index 20.9 ± 0.9 kg/m2 , glycated haemoglobin concentration 56 ± 7 mmol/mol [7.3% ± 0.6%]) were monitored during a five-stage professional road cycling race. Real-time continuous glucose monitoring (rtCGM) data, smart insulin pen dose data and macronutrient intake were assessed by means of repeated-measure one-way ANOVA and post hoc testing. Associations between exercise physiological markers and rtCGM data, insulin doses and macronutrient intake were assessed via linear regression modelling (P ≤ 0.05). RESULTS: Bolus insulin dose was significantly reduced over the 5-day period (P = 0.03), while carbohydrate intake (P = 0.24) and basal insulin doses remained unchanged (P = 0.64). A higher mean previous-day race intensity was associated with a lower mean sensor glucose level (P = 0.03), less time above range level 2 (>13.9 mmol/L [250 mg/dL]; P = 0.05) and lower doses of bolus insulin (P = 0.04) on the subsequent day. No significant associations were found for any other glycaemic range and glycaemic variability (P > 0.05). CONCLUSIONS: This is the first study to demonstrate the influence of previous-day race intensity on subsequent bolus insulin dose requirements in professional cyclists with T1D. These data may help inform therapeutic strategies to ensure safe exercise performance.

Glycemic responses to strenuous training in male professional cyclists with type 1 diabetes: a prospective observational study.

INTRODUCTION: This prospective observational study sought to establish the glycemic, physiological and dietary demands of strenuous exercise training as part of a 9-day performance camp in a professional cycling team with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Sixteen male professional cyclists with T1D on multiple daily injections (age: 27±4 years; duration of T1D: 11±5 years; body mass index: 22±2 kg/m2; glycated hemoglobin: 7%±1% (50±6 mmol/mol); maximum rate of oxygen consumption: 73±4 mL/kg/min) performed road cycle sessions (50%-90% of the anaerobic threshold, duration 1-6 hours) over 9 consecutive days. Glycemic (Dexcom G6), nutrition and physiological data were collected throughout. Glycemic data were stratified into predefined glycemic ranges and mapped alongside exercise physiology and nutritional parameters, as well as split into daytime and night-time phases for comparative analysis. Data were assessed by means of analysis of variance and paired t-tests. A p value of ≤0.05 (two-tailed) was statistically significant. RESULTS: Higher levels of antecedent hypoglycemia in the nocturnal hours were associated with greater time spent in next-day hypoglycemia overall (p=0.003) and during exercise (p=0.019). Occurrence of nocturnal hypoglycemia was associated with over three times the risk of next-day hypoglycemia (p<0.001) and a twofold risk of low glucose during cycling (p<0.001). Moreover, there was trend for a greater amount of time spent in mild hypoglycemia during the night compared with daytime hours (p=0.080). CONCLUSION: The higher prevalence of nocturnal hypoglycemia was associated with an increased risk of next-day hypoglycemia, which extended to cycle training sessions. These data highlight the potential need for additional prebed carbohydrates and/or insulin dose reduction strategies around exercise training in professional cyclists with T1D. TRIAL REGISTRATION NUMBER: DRKS00019923.

Improved Nocturnal Glycaemia and Reduced Insulin Use Following Clinical Exercise Trial Participation in Individuals With Type 1 Diabetes.

Aim: To explore the influence of clinical exercise trial participation on glycaemia and insulin therapy use in adults with type 1 diabetes (T1D). Research Design and Methods: This study involved a secondary analysis of data collected from 16 individuals with T1D who completed a randomized clinical trial consisting of 23-h in-patient phases with a 45-min evening bout of moderate intensity continuous exercise. Participants were switched from their usual basal-bolus therapy to ultra-long acting insulin degludec and rapid-acting insulin aspart as well as provided with unblinded interstitial flash-glucose monitoring systems. To assess the impact of clinical trial participation, weekly data obtained at the screening visit (pre-study involvement) were compared against those collated on the last experimental visit (post-study involvement). Interstitial glucose [iG] data were split into distinct glycaemic ranges and stratified into day (06:00-23:59) and night (00:00-05:59) time periods. A p-value of ≤ 0.05 was accepted for significance. Results: Following study completion, there were significant decreases in both the mean nocturnal iG concentration (Δ-0.9 ± 4.5 mmol.L-1, p < 0.001) and the time spent in severe hyperglycaemia (Δ-7.2 ± 9.8%, p = 0.028) during the night-time period. The total daily (Δ-7.3 ± 8.4 IU, p = 0.003) and basal only (Δ-2.3 ± 3.8 IU, p = 0.033) insulin dose requirements were reduced over the course of study involvement. Conclusions: Participation in clinical research may foster improved nocturnal glycaemia and reduced insulin therapy use in people with T1D. Recognition of these outcomes may help encourage volunteers to partake in clinical research opportunities for improved diabetes-related health outcomes. Clinical Trial Registration: DRKS.de; DRKS00013509.