Hyperglycemia-related anxiety during competition in an elite athlete with type 1 diabetes: A case report.

AIM: Managing blood glucose (BG) levels during intense physical activity is challenging for elite athletes with type 1 diabetes (T1D), as it can lead to unpredictable hyper- or hypoglycemia, which can affect performance. This case study presents an 18-year-old male hockey goalie with hyperglycemia-related anxiety during competition and its impact on his T1D management. METHODS: Mixed-methods approach, incorporating qualitative data from an unstructured interview and responses from the Hyperglycemia Avoidance Scale along with quantitative data retrieved from Diasend and laboratory results. RESULTS: The athlete experiences physical and cognitive symptoms during hyperglycemia, affecting his performance. Hyperglycemia-related anxiety influences insulin dosage adjustments and eating habits on game days. Glycemic variability analysis reveals lower BG levels during game time. CONCLUSION: Hyperglycemia-related anxiety leads to modified therapeutic and lifestyle regimens on competition day. Tailored treatment programs are needed for elite athletes with T1D and hyperglycemia-related anxiety.

Efficacy and safety of lemborexant in subjects previously treated with placebo for 6 months in a randomized phase 3 study.

OBJECTIVE/BACKGROUND: To examine the effects of lemborexant (LEM) 5 mg (LEM5) or LEM 10 mg (LEM10) following extended placebo treatment. This post-hoc analysis used subject-reported sleep outcomes data from a phase 3 trial. PATIENTS/METHODS: The subjects in these post-hoc analyses were randomized to placebo for 6 months (Time Period [TP]1) in Study E2006-G000-303 (SUNRISE-2; NCT02952820). Following placebo exposure, subjects were re-randomized to LEM5 or LEM10 for another 6 months (TP2). Subject-reported sleep outcomes derived from sleep diaries included sleep onset latency (sSOL), wake after sleep onset (sWASO), sleep efficiency (sSE), and total sleep time (sTST). Magnitude and change rate in parameters were assessed for 7 days before/after initial randomization to placebo and 7 days before/after re-randomization to LEM (6 months later). Month 6 placebo non-responders were assessed for LEM response in TP2 using predetermined responder definitions. Safety was monitored throughout the study. RESULTS: Overall, 321 subjects received placebo; 258 re-randomized subjects received LEM5 (n = 133) and LEM10 (n = 125). Subjective sleep outcomes improved during TP1 with approximately 62 subjects (∼20%) exhibiting a sustained placebo response. Upon re-randomization to LEM, all measures showed an additional incremental benefit, most prominently in sSOL and sTST. Among Month 6 placebo non-responders, 11%-15% subsequently responded to LEM as assessed at Month 12. The safety profile was similar between treatment periods and treatment groups. CONCLUSIONS: These data suggest that even when insomnia symptoms have improved over time with placebo treatment, additional and sustained clinical gains in sleep outcomes are possible with active treatment using lemborexant.

Efficacy and safety of lemborexant in midlife women with insomnia disorder.

OBJECTIVE: Insomnia is common in midlife women. The efficacy and safety of lemborexant (LEM), a competitive dual orexin receptor antagonist, was assessed for 12 months in a subgroup of midlife women (age, 40-58 y) from Study E2006-G000-303 (Study 303; SUNRISE-2). METHODS: This was a randomized, double-blind, placebo (PBO)-controlled (first 6 mo) study of adults with insomnia disorder ( N = 949). During treatment period 1 (TP1), participants received PBO or LEM 5 mg (LEM5) or 10 mg (LEM10). During TP2 (second 6 mo), LEM participants continued their assigned dose; PBO participants were rerandomized to LEM5 or LEM10. Assessments included patient-reported sleep- and fatigue-related measures and treatment-emergent adverse events. RESULTS: The midlife female subgroup comprised 280 of 949 participants (TP1: PBO, n = 90 of 318 [28.3%]; LEM5, n = 82 of 316 [25.9%]; LEM10, n = 108 of 315 [34.3%]). At 6 months, median changes from baseline in subjective sleep-onset latency (in minutes) were -17.9, -20.7, and - 30.4 for PBO, LEM5, and LEM10 (vs PBO: LEM5, P = not significant; LEM10, P = 0.0310). At 6 months, mean changes from baseline in subjective wake after sleep onset (in minutes) were -37.0 (59.6), -50.1 (74.5), and -54.5 (65.4) for PBO, LEM5, and LEM10 (vs PBO: LEM5 and LEM10, P = not significant), with benefits sustained through 12 months. Greater decreases from baseline (improvement) in Insomnia Severity Index total score and Fatigue Severity Scale total score were seen with LEM versus PBO at 6 months; benefits continued through 12 months. Most treatment-emergent adverse events were mild to moderate in severity. CONCLUSIONS: Consistent with the total population, subjective sleep parameters improved, and improvement was sustained over time in midlife women. LEM was well tolerated, suggesting that LEM may be a potential treatment option for midlife women with insomnia.

Effects of postprandial exercise on blood glucose levels in adults with type 1 diabetes: a review.

People with type 1 diabetes experience challenges in managing blood glucose around exercise. Previous studies have examined glycaemic responses to different exercise modalities but paid little attention to participants' prandial state, although this is an important consideration and will enhance our understanding of the effects of exercise in order to improve blood glucose management around activity. This review summarises available data on the glycaemic effects of postprandial exercise (i.e. exercise within 2 h after a meal) in people with type 1 diabetes. Using a search strategy on electronic databases, literature was screened until November 2022 to identify clinical trials evaluating acute (during exercise), subacute (≤2 h after exercise) and late (>2 h to ≤24 h after exercise) effects of postprandial exercise in adults with type 1 diabetes. Studies were systematically organised and assessed by exercise modality: (1) walking exercise (WALK); (2) continuous exercise of moderate intensity (CONT MOD); (3) continuous exercise of high intensity (CONT HIGH); and (4) interval training (intermittent high-intensity exercise [IHE] or high-intensity interval training [HIIT]). Primary outcomes were blood glucose change and hypoglycaemia occurrence during and after exercise. All study details and results per outcome were listed in an evidence table. Twenty eligible articles were included: two included WALK sessions, eight included CONT MOD, seven included CONT HIGH, three included IHE and two included HIIT. All exercise modalities caused consistent acute glycaemic declines, with the largest effect size for CONT HIGH and the smallest for HIIT, depending on the duration and intensity of the exercise bout. Pre-exercise mealtime insulin reductions created higher starting blood glucose levels, thereby protecting against hypoglycaemia, in spite of similar declines in blood glucose during activity between the different insulin reduction strategies. Nocturnal hypoglycaemia occurred after higher intensity postprandial exercise, a risk that could be diminished by a post-exercise snack with concomitant bolus insulin reduction. Research on the optimal timing of postprandial exercise is inconclusive. In summary, individuals with type 1 diabetes exercising postprandially should substantially reduce insulin with the pre-exercise meal to avoid exercise-induced hypoglycaemia, with the magnitude of the reduction depending on the exercise duration and intensity. Importantly, pre-exercise blood glucose and timing of exercise should be considered to avoid hyperglycaemia around exercise. To protect against late-onset hypoglycaemia, a post-exercise meal with insulin adjustments might be advisable, especially for exercise in the evening or with a high-intensity component.

The Effect of Starting Blood Glucose Levels on Serum Electrolyte Concentrations during and after Exercise in Type 1 Diabetes.

Fear of hypoglycemia is a major exercise barrier for people with type 1 diabetes (PWT1D). Consequently, although guidelines recommend starting exercise with blood glucose (BG) concentration at 7-10 mmol/L, PWT1D often start higher, potentially affecting hydration and serum electrolyte concentrations. To test this, we examined serum and urine electrolyte concentrations during aerobic exercise (cycling 45 min at 60%VO2peak) in 12 PWT1D (10F/2M, mean ± SEM: age 29 ± 2.3 years, VO2peak 37.9 ± 2.2 mL·kg-1·min-1) with starting BG levels: 8-10 (MOD), and 12-14 (HI) mmol/L. Age, sex, and fitness-matched controls without diabetes (CON) completed one exercise session with BG in the normal physiological range. Serum glucose was significantly higher during exercise and recovery in HI versus MOD (p = 0.0002 and p < 0.0001, respectively) and in MOD versus CON (p < 0.0001). During exercise and recovery, MOD and HI were not significantly different in serum insulin (p = 0.59 and p = 0.63), sodium (p = 0.058 and p = 0.08), potassium (p = 0.17 and p = 0.16), calcium (p = 0.75 and 0.19), and magnesium p = 0.24 and p = 0.09). Our findings suggest that exercise of moderate intensity and duration with higher BG levels may not pose an immediate risk to hydration or serum electrolyte concentrations for PWT1D.

Type 1 Diabetes and the Menstrual Cycle: Where/How Does Exercise Fit in?

Regular exercise is associated with substantial health benefits for individuals with type 1 diabetes (T1D). However, the fear of hypoglycemia (low blood glucose) due to activity-induced declines in blood glucose levels acts as a major barrier to partaking in exercise in this population. For females with T1D, hormonal fluctuations during the menstrual cycle and their effects on blood glucose levels can act as an additional barrier. The impact that these cyclic changes may have on blood glucose and insulin needs and the consequent risk of hypoglycemia during or after exercise are still unknown in this population. Therefore, in this narrative review, we gathered existing knowledge about the menstrual cycle in T1D and the effects of different cyclic phases on substrate metabolism and glucose response to exercise in females with T1D to increase knowledge and understanding around exercise in this underrepresented population. This increased knowledge in such an understudied area can help to better inform exercise guidelines for females with T1D. It can also play an important role in eliminating a significant barrier to exercise in this population, which has the potential to increase activity, improve mental health and quality of life, and decrease the risk of diabetes-related complications.

Systematic Review and Meta-analysis of Blood Glucose Response to High-intensity Interval Exercise in Adults With Type 1 Diabetes.

OBJECTIVES: Exercise-induced hyperglycemia is recognized in type 1 diabetes (T1D) clinical guidelines, but its association with high-intensity intermittent exercise (HIIE) in acute studies is inconsistent. In this meta-analysis, we examined the available evidence of blood glucose responses to HIIE in adults with T1D. The secondary, aim was to examine predictors of blood glucose responses to HIIE. We hypothesized that there would be no consistent effect on blood glucose from HIIE, unless examined in the context of participant prandial status. METHODS: We conducted a literature search using key words related to T1D and HIIE. Studies were required to include at least 6 participants with T1D with a mean age >18 years, involve an HIIE intervention, and contain pre- and postexercise measures of blood glucose. Analyses of extracted data were performed using a general inverse variance statistical method with a random effects model and a weighted multiple regression. RESULTS: Nineteen interventions from 15 reports were included in the analysis. A mean overall blood glucose decrease of -1.3 mmol/L (95% confidence interval [CI], -2.3 to -0.2 mmol/L) was found during exercise, albeit with high heterogeneity (I2=84%). When performed after an overnight fast, exercise increased blood glucose by +1.7 mmol/L (95% CI, 0.4 to 3.0 mmol/L), whereas postprandial exercise decreased blood glucose by -2.1 mmol/L (95% CI, -2.8 to -1.4 mmol/L), with a statistically significant difference between groups (p<0.0001). No associations with fitness (p=0.4), sex (p=0.4), age (p=0.9), exercise duration (p=0.9), or interval duration (p=0.2) were found. CONCLUSION: The effect of HIIE on blood glucose is inconsistent, but partially explained by prandial status.

The Resistance Exercise in Already Active Diabetic Individuals (READI) Randomized Clinical Trial.

CONTEXT: Resistance exercise training (strength training) and aerobic exercise training are both recommended for people with type 1 diabetes, but it is unknown whether adding resistance exercise provides incremental benefits in people with this condition who already perform aerobic exercise regularly. OBJECTIVE: This work aimed to evaluate the incremental effect of resistance training on glycated hemoglobin A1c (HbA1c), fitness, body composition, and cardiometabolic risk factors in aerobically active people with type 1 diabetes. METHODS: The Resistance Exercise in Already-active Diabetic Individuals (READI) trial (NCT00410436) was a 4-center, randomized, parallel-group trial. After a 5-week run-in period with diabetes management optimization, 131 aerobically active individuals with type 1 diabetes were randomly assigned to resistance exercise (n = 71, intervention-INT) or control (n = 60, CON) for 22 additional weeks. Both groups maintained their aerobic activities and were provided dietary counseling throughout. Exercise training was 3 times per week at community-based facilities. The primary outcome was HbA1c, and secondary outcomes included fitness (peak oxygen consumption, muscle strength), body composition (anthropometrics, dual-energy x-ray absorptiometry, computed tomography), and cardiometabolic risk markers (lipids, apolipoproteins). Assessors were blinded to group allocation. RESULTS: There were no significant differences in HbA1c change between INT and CON. Declines in HbA1c (INT: 7.75 ± 0.10% [61.2 ± 1.1 mmol/mol] to 7.55 ± 0.10% [59 ± 1.1 mmol/mol]; CON: 7.70 ± 0.11% [60.7 ± 1.2 mmol/mol] to 7.57 ± 0.11% [59.6 ± 1.3 mmol/mol]; intergroup difference in change -0.07 [95% CI, -0.31 to 0.18]). Waist circumference decreased more in INT than CON after 6 months (P = .02). Muscular strength increased more in INT than in CON (P < .001). There were no intergroup differences in hypoglycemia or any other variables. CONCLUSION: Adding resistance training did not affect glycemia, but it increased strength and reduced waist circumference, in aerobically active individuals with type 1 diabetes.

Reassessing the evidence: prandial state dictates glycaemic responses to exercise in individuals with type 1 diabetes to a greater extent than intensity.

Recent guidelines suggest that adding anaerobic (high intensity or resistance) activity to an exercise session can prevent blood glucose declines that occur during aerobic exercise in individuals with type 1 diabetes. This theory evolved from earlier study data showing that sustained, anaerobic activity (high intensity cycling) increases blood glucose levels in these participants. However, studies involving protocols where anaerobic (high intensity interval) and aerobic exercise are combined have extremely variable glycaemic outcomes, as do resistance exercise studies. Scrutinising earlier studies will reveal that, in addition to high intensity activity (intervals or weight lifting), these protocols had another common feature: participants were performing exercise after an overnight fast. Based on these findings, and data from recent exercise studies, it can be argued that participant prandial state may be a more dominant factor than exercise intensity where glycaemic changes in individuals with type 1 diabetes are concerned. As such, a reassessment of study outcomes and an update to exercise recommendations for those with type 1 diabetes may be warranted.

Comparison of Nocturnal Glucose After Exercise Among Dual-Hormone, Single-Hormone Algorithm-Assisted Insulin Delivery System and Usual Care in Adults and Adolescents Living with Type 1 Diabetes: A Pooled Analysis.

Background: Available studies comparing the efficacy of dual-hormone (DH)-algorithm-assisted insulin delivery (AID), single-hormone (SH)-AID and usual care on postexercise overnight glucose in people with type 1 diabetes (T1D) have had different outcomes. By pooling data from all available studies, we aim to draw stronger conclusions. Methods: Data were pooled from two three-arm, open-label, randomized, controlled, crossover studies. Forty-one adults [median (Q1, Q3) age: 34.0 years (29.5, 51.0), mean HbA1c: 7.5% ± 1.0%] and 17 adolescents with T1D [age: 14.0 (13.0, 16.0), HbA1c: 7.8% ± 0.8%] underwent DH-AID, SH-AID, and usual care. Each intervention involved evening aerobic exercise (60-min). The primary outcome, time in range% (TIR%) overnight (00:00-06:00) postexercise based on continuous glucose monitoring, was compared among treatments using linear mixed effect model or generalized linear mixed model. Results: Among adults, mean TIR% was 94.0% ± 11.9%, 83.1% ± 20.5%, and 65.1% ± 37.0% during DH-AID, SH-AID, and usual care intervention, respectively (P < 0.05 for all between-group comparisons). DH-AID was superior to SH-AID and usual care, and SH-AID was superior to usual care regarding hypoglycemia and hyperglycemia prevention, but not glycemic variability. Among adolescents, DH-AID and SH-AID reduced dysglycemia, but not glycemic variability, better than usual care. Glycemic outcomes were similar between DH-AID and SH-AID. Conclusion: AID systems allow improved postexercise nocturnal glycemic management than usual care for both adults and adolescents. DH-AID was better than SH-AID among adults, but not adolescents.

Efficacy and safety of lemborexant over 12 months in Asian adults with insomnia disorder.

Study objectives: Lemborexant (LEM) is a dual orexin receptor antagonist approved for treating adults with insomnia. We analyzed the efficacy (subjective sleep outcomes) and safety of LEM over 12 months in the subgroup of Asian subjects from Study E2006-G000-303 (Study 303). Methods: Study 303 was a 12-month, randomized, placebo-controlled (first 6 months), double-blind, parallel-group, phase 3 study of adults with insomnia disorder. During the 6-month Period 1, subjects were randomized (1:1:1) to placebo, LEM 5 mg (LEM5), or LEM 10 mg (LEM10); LEM subjects continued treatment in the following 6-month Period 2. Outcome measures included subject-reported (subjective) sleep onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), total sleep time (sTST), Insomnia Severity Index (ISI), and Patient Global Impression-Insomnia version (PGI-I). Treatment-emergent adverse events (TEAEs) were assessed. Results: Overall, 178 Asian subjects (Japanese, n = 161; Chinese, n = 4; other Asian, n = 13) were included. Greater decreases in sSOL and sWASO and increases in sSE and sTST from baseline were observed with LEM vs placebo at 6 months; LEM benefits were sustained through 12 months. Greater decreases in ISI total score were seen with LEM vs placebo at 6 months; improvements from baseline with LEM continued through 12 months. For each PGI-I item, LEM-treated subjects had more positive medication effects than placebo-treated subjects at 6 months; these effects were maintained with LEM in Period 2. TEAEs were generally mild to moderate. Conclusions: LEM improved subjective sleep parameters and was well-tolerated in Asian subjects with insomnia disorder over 12 months. Clinical trial registration: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

Improvement in fatigue and sleep measures with the dual orexin receptor antagonist lemborexant in adults with insomnia disorder.

OBJECTIVE: Fatigue is a common symptom in patients with insomnia. This analysis evaluated whether treatment of nighttime symptoms of insomnia with a dual orexin receptor antagonist, lemborexant, might also reduce fatigue. METHODS: Analyses were conducted of two phase 3 studies of subjects with insomnia disorder. Subjects received placebo, lemborexant 5 mg, or lemborexant 10 mg in the 12-month (6 months placebo-controlled) Study E2006-G000-303 (Study 303: SUNRISE-2) of adults (N = 949; full analysis set [FAS]), and the 1-month, placebo- and active-controlled Study E2006-G000-304 (Study 304; SUNRISE-1) of older adults (females ≥55 years, males ≥65 years) (N = 1006; FAS). Fatigue was assessed using the Fatigue Severity Scale (FSS). Patient-reported sleep onset and maintenance endpoints were analyzed using data from electronic sleep diaries. RESULTS: Lemborexant significantly reduced subject-reported fatigue versus placebo over a 6-month treatment period (FSS total score least-squares mean treatment difference of -2.50 for 5 mg and -2.56 for 10 mg of lemborexant; p < 0.05 for both). This reduction was sustained over 12 months of lemborexant in both the overall population and in subjects with clinically meaningful fatigue (FSS total score ≥36) at baseline. Improvements in fatigue over time positively correlated with improvements in sleep onset and maintenance parameters. Improvements in sleep quality were evident as early as 1 week after lemborexant treatment, whereas longer-term treatment (>1 month) may be needed for improvements in insomnia-related fatigue. CONCLUSIONS: In addition to improving sleep onset and sleep maintenance in subjects with insomnia disorder, lemborexant provides further benefit by reducing daytime fatigue. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02952820 and https://clinicaltrials.gov/ct2/show/NCT02783729. ABBREVIATIONS: DSM-5 = Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; FSS = Fatigue Severity Scale; ICSD-3 = International Classification of Sleep Disorders, Third Edition; LSM = least squares mean; sSE = subjective sleep efficiency; sSOL = subjective sleep onset latency; sTST = subjective total sleep time; sWASO = subjective sleep after wake onset.

Impact of lemborexant treatment on insomnia severity: analyses from a 12-month study of adults with insomnia disorder.

OBJECTIVE/BACKGROUND: Evaluate changes in insomnia severity in subjects with moderate to severe insomnia (Insomnia Severity Index [ISI] score ≥15) treated for 12 months nightly with lemborexant. PATIENTS/METHODS: This phase 3 randomized study comprised two 6-month treatment periods. In Period 1, 949 subjects were randomized to placebo, lemborexant 5 mg (LEM5) or 10 mg (LEM10). In Period 2, placebo subjects were rerandomized to LEM5 or LEM10; subjects initially randomized to lemborexant continued their assigned treatment. Insomnia severity was assessed using baseline ISI and 1-, 3-, 6-, 9-, and 12-month post-treatment scores. RESULTS: Mean ISI scores improved significantly across treatment groups and disease severities, with greater decreases from baseline in the LEM5 and LEM10 versus placebo groups at months 1 (-7.1, -7.2, -5.2, respectively), 3 (-8.6, -8.9, -6.1, respectively), and 6 (-9.9, -9.8, -7.2 respectively); ISI score improvements were maintained with LEM5 and LEM10 at months 9 (-11.1 and -11.2, respectively) and 12 (-11.5 and -11.2, respectively). At months 1, 3, and 6, significantly more treatment responders (≥7-point ISI score decrease from baseline) were observed with LEM5 (44%-57%) and LEM10 (44%-52%) versus placebo (30%-41%). At months 1, 3, and 6, more remitters (ISI total score <10 and < 8) were observed with LEM5 (30%-44% and 22%-34%, respectively) and LEM10 (31%-41% and 22%-31%, respectively) versus placebo (18%-28% and 11%-21%, respectively). CONCLUSIONS: Lemborexant significantly reduced insomnia severity for 12 months and increased clinically meaningful response and remission rates versus placebo. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.

"How we do it": A qualitative study of strategies for adopting an exercise routine while living with type 1 diabetes.

Introduction: For people living with type 1 diabetes (T1D) the challenge of increasing daily physical activity (PA) is compounded by the increased risks of hypoglycemia and glucose variability. Little information exists on the lived experience of overcoming these barriers and adopting and maintaining an active lifestyle while living with T1D. Research Design and Methods: We conducted a patient-led qualitative study consisting of semi-structured interviews or focus groups with 22 individuals at least 16 years old living with T1D. We used existing patient co-researcher networks and snowball sampling to obtain a sample of individuals who reported being regularly physically active and had been diagnosed with T1D for at least one year. We used an interpretive description analysis to generate themes and strategies associated with maintaining an active lifestyle while living with T1D. We involved patient co-researchers in study design, data collection, and interpretation. Results: 14 self-identified women and 8 self-identified men (ages 19-62, median age 32 years) completed the study, led by either a researcher, or a patient co-researcher and research assistant regarding their strategies for maintaining an active lifestyle. We identified five themes that facilitate regular sustained PA: (1) Structure and organization are important to adopt safe PA in daily life "I can't do spontaneous exercise. I actually need a couple hours of warning minimum"; (2) Trial and error to learn how their body responds to PA and food "Once you put the time and effort into learning, you will have greater success"; (3) Psychosocial aspects of PA "…because it's not just your body, it's your soul, it's your mind that exercise is for"; (4) Diabetes technology and (5) Education and peer support. Strategies to overcome barriers included (1) Technology; (2) Integrating psychosocial facilitators; (3) Insulin and carbohydrate adjustments; and (4) Planning for exercise. Conclusions: Living an active lifestyle with T1D is facilitated by dedicated structure and organization of routines, accepting the need for trial and error to understand the personalized glycemic responses to PA and careful use of food to prevent hypoglycemia. These themes could inform clinical practice guidelines or future trials that include PA interventions.

Can Resistance Exercise Be a Tool for Healthy Aging in Post-Menopausal Women with Type 1 Diabetes?

Due to improvements in diabetes care, people with type 1 diabetes (T1D) are living longer. Studies show that post-menopausal T1D women have a substantially elevated cardiovascular risk compared to those without T1D. As T1D may also accelerate age-related bone and muscle loss, the risk of frailty may be considerable for T1D women. Exercise and physical activity may be optimal preventative therapies to maintain health and prevent complications in this population: They are associated with improvements in, or maintenance of, cardiovascular health, bone mineral density, and muscle mass in older adults. Resistance exercise, in particular, may provide important protection against age-related frailty, due to its specific effects on bone and muscle. Fear of hypoglycemia can be a barrier to exercise in those with T1D, and resistance exercise may cause less hypoglycemia than aerobic exercise. There are currently no exercise studies involving older, post-menopausal women with T1D. As such, it is unknown whether current guidelines for insulin adjustment/carbohydrate intake for activity are appropriate for this population. This review focuses on existing knowledge about exercise in older adults and considers potential future directions around resistance exercise as a therapeutic intervention for post-menopausal T1D women.

Afternoon aerobic and resistance exercise have limited impact on 24-h CGM outcomes in adults with type 1 diabetes: A secondary analysis.

AIMS: This study examined post-exercise glycemic variability in individuals with type 1 diabetes after acute bouts of resistance (RE) and aerobic exercise (AE) compared to a no-exercise day (CON). We hypothesized that exercise days would have greater glucose variability (standard deviation - SD, coefficient of variation - CV), and less time in range (TIR), compared to CON. METHODS: A secondary analysis was conducted on previously collected data. Twelve active participants with type 1 diabetes performed three testing sessions in random order with at least 48 h in between: AE (45-min treadmill run at 60%VO2max), RE (three sets of eight repetitions, seven weight-lifting exercises), and CON (45-min no-exercise control). Interstitial glucose levels were monitored by blinded continuous glucose monitoring (CGM). Glycemic variability was evaluated for 0-6 h, overnight (00:00-06:00) and 24 h after exercise. RESULTS: Mean CGM glucose, TIR, and time above/below range were similar among conditions (P > 0.05). Lower SD (0.8 [0.5-1.1], 1.4 [0.9-2.4]mmol/L, p = 0.009) and CV (11.4 [8.6-15.3], 23.4 [13.7-31.6]%, p = 0.007) were found overnight after AE versus CON. Otherwise, AE and RE had limited impact on post-exercise glycemia. CONCLUSIONS: Acute RE and AE bouts may have limited impact on post-exercise glycemic variability compared to rest in habitually active individuals with type 1 diabetes.

Long-term effectiveness and safety of lemborexant in adults with insomnia disorder: results from a phase 3 randomized clinical trial.

OBJECTIVE/BACKGROUND: Lemborexant is a dual orexin receptor antagonist approved in the United States, Japan, and Canada for the treatment of insomnia in adults. We report effectiveness and safety outcomes in subjects with insomnia who received up to twelve months of continuous lemborexant treatment in Study E2006-G000-303 (Study 303; SUNRISE-2). PATIENTS/METHODS: Study 303 was a twelve-month, global, multicenter, randomized, double-blind, parallel-group, Phase 3 study divided into two treatment periods. In Treatment Period 1 (first six months), subjects (n = 949, Full Analysis Set) were randomized to daily placebo, lemborexant 5 mg (LEM5) or lemborexant 10 mg (LEM10). In Treatment Period 2 (second six months), placebo subjects were rerandomized to LEM5 or LEM10, and subjects randomized to lemborexant continued their assigned treatment (LEM5, n = 251; LEM10, n = 226). Sleep onset and sleep maintenance endpoints were analyzed from daily electronic sleep diary data. Treatment-emergent adverse events (TEAEs) were monitored. RESULTS: For all sleep parameters, the significant benefits observed with LEM5 and LEM10 versus placebo over six months were maintained at twelve months in subjects who received twelve continuous months of treatment. There was no evidence of rebound insomnia or withdrawal in either lemborexant group following treatment discontinuation. Over twelve months of lemborexant treatment, most TEAEs were mild/moderate; the most common TEAEs were nasopharyngitis, somnolence and headache. CONCLUSIONS: LEM5 and LEM10 had significant benefit on sleep onset and sleep maintenance compared with placebo, and importantly, lemborexant effectiveness persisted at twelve months, suggesting that lemborexant may provide long-term benefits for subjects with insomnia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02952820; ClinicalTrialsRegister.eu, EudraCT Number 2015-001463-39.