Applying technologies to simplify strategies for exercise in type 1 diabetes.

Challenges and fears related to managing glucose levels around planned and spontaneous exercise affect outcomes and quality of life in people living with type 1 diabetes. Advances in technology, including continuous glucose monitoring, open-loop insulin pump therapy and hybrid closed-loop (HCL) systems for exercise management in type 1 diabetes, address some of these challenges. In this review, three research or clinical experts, each living with type 1 diabetes, leverage published literature and clinical and personal experiences to translate research findings into simplified, patient-centred strategies. With an understanding of limitations in insulin pharmacokinetics, variable intra-individual responses to aerobic and anaerobic exercise, and the features of the technologies, six steps are proposed to guide clinicians in efficiently communicating simplified actions more effectively to individuals with type 1 diabetes. Fundamentally, the six steps centre on two aspects. First, regardless of insulin therapy type, and especially needed for spontaneous exercise, we provide an estimate of glucose disposal into active muscle meant to be consumed as extra carbohydrates for exercise ('ExCarbs'; a common example is 0.5 g/kg body mass per hour for adults and 1.0 g/kg body mass per hour for youth). Second, for planned exercise using open-loop pump therapy or HCL systems, we additionally recommend pre-emptive basal insulin reduction or using HCL exercise modes initiated 90 min (1-2 h) before the start of exercise until the end of exercise. Modifications for aerobic- and anaerobic-type exercise are discussed. The burden of pre-emptive basal insulin reductions and consumption of ExCarbs are the limitations of HCL systems, which may be overcome by future innovations but are unquestionably required for currently available systems.

Associations between daily step count classifications and continuous glucose monitoring metrics in adults with type 1 diabetes: analysis of the Type 1 Diabetes Exercise Initiative (T1DEXI) cohort.

AIMS/HYPOTHESIS: Adults with type 1 diabetes should perform daily physical activity to help maintain health and fitness, but the influence of daily step counts on continuous glucose monitoring (CGM) metrics are unclear. This analysis used the Type 1 Diabetes Exercise Initiative (T1DEXI) dataset to investigate the effect of daily step count on CGM-based metrics. METHODS: In a 4 week free-living observational study of adults with type 1 diabetes, with available CGM and step count data, we categorised participants into three groups-below (<7000), meeting (7000-10,000) or exceeding (>10,000) the daily step count goal-to determine if step count category influenced CGM metrics, including per cent time in range (TIR: 3.9-10.0 mmol/l), time below range (TBR: <3.9 mmol/l) and time above range (TAR: >10.0 mmol/l). RESULTS: A total of 464 adults with type 1 diabetes (mean±SD age 37±14 years; HbA1c 48.8±8.1 mmol/mol [6.6±0.7%]; 73% female; 45% hybrid closed-loop system, 38% standard insulin pump, 17% multiple daily insulin injections) were included in the study. Between-participant analyses showed that individuals who exceeded the mean daily step count goal over the 4 week period had a similar TIR (75±14%) to those meeting (74±14%) or below (75±16%) the step count goal (p>0.05). In the within-participant comparisons, TIR was higher on days when the step count goal was exceeded or met (both 75±15%) than on days below the step count goal (73±16%; both p<0.001). The TBR was also higher when individuals exceeded the step count goals (3.1%±3.2%) than on days when they met or were below step count goals (difference in means -0.3% [p=0.006] and -0.4% [p=0.001], respectively). The total daily insulin dose was lower on days when step count goals were exceeded (0.52±0.18 U/kg; p<0.001) or were met (0.53±0.18 U/kg; p<0.001) than on days when step counts were below the current recommendation (0.55±0.18 U/kg). Step count had a larger effect on CGM-based metrics in participants with a baseline HbA1c ≥53 mmol/mol (≥7.0%). CONCLUSIONS/INTERPRETATION: Our results suggest that, compared with days with low step counts, days with higher step counts are associated with slight increases in both TIR and TBR, along with small reductions in total daily insulin requirements, in adults living with type 1 diabetes. DATA AVAILABILITY: The data that support the findings reported here are available on the Vivli Platform (ID: T1-DEXI; https://doi.org/10.25934/PR00008428 ).

Real World Interstitial Glucose Profiles of a Large Cohort of Physically Active Men and Women.

The use of continuous glucose monitors (CGMs) in individuals living without diabetes is increasing. The purpose of this study was to profile various CGM metrics around nutritional intake, sleep and exercise in a large cohort of physically active men and women living without any known metabolic disease diagnosis to better understand the normative glycemic response to these common stimuli. A total of 12,504 physically active adults (age 40 ± 11 years, BMI 23.8 ± 3.6 kg/m2; 23% self-identified as women) wore a real-time CGM (Abbott Libre Sense Sport Glucose Biosensor, Abbott, USA) and used a smartphone application (Supersapiens Inc., Atlanta, GA, USA) to log meals, sleep and exercise activities. A total of >1 M exercise events and 274,344 meal events were analyzed. A majority of participants (85%) presented an overall (24 h) average glucose profile between 90 and 110 mg/dL, with the highest glucose levels associated with meals and exercise and the lowest glucose levels associated with sleep. Men had higher mean 24 h glucose levels than women (24 h-men: 100 ± 11 mg/dL, women: 96 ± 10 mg/dL). During exercise, the % time above >140 mg/dL was 10.3 ± 16.7%, while the % time <70 mg/dL was 11.9 ± 11.6%, with the remaining % within the so-called glycemic tight target range (70-140 mg/dL). Average glycemia was also lower for females during exercise and sleep events (p < 0.001). Overall, we see small differences in glucose trends during activity and sleep in females as compared to males and higher levels of both TAR and TBR when these active individuals are undertaking or competing in endurance exercise training and/or competitive events.

Quantifying insulin-mediated and noninsulin-mediated changes in glucose dynamics during resistance exercise in type 1 diabetes.

Exercise can cause dangerous fluctuations in blood glucose in people living with type 1 diabetes (T1D). Aerobic exercise, for example, can cause acute hypoglycemia secondary to increased insulin-mediated and noninsulin-mediated glucose utilization. Less is known about how resistance exercise (RE) impacts glucose dynamics. Twenty-five people with T1D underwent three sessions of either moderate or high-intensity RE at three insulin infusion rates during a glucose tracer clamp. We calculated time-varying rates of endogenous glucose production (EGP) and glucose disposal (Rd) across all sessions and used linear regression and extrapolation to estimate insulin- and noninsulin-mediated components of glucose utilization. Blood glucose did not change on average during exercise. The area under the curve (AUC) for EGP increased by 1.04 mM during RE (95% CI: 0.65-1.43, P < 0.001) and decreased proportionally to insulin infusion rate (0.003 mM per percent above basal rate, 95% CI: 0.001-0.006, P = 0.003). The AUC for Rd rose by 1.26 mM during RE (95% CI: 0.41-2.10, P = 0.004) and increased proportionally with insulin infusion rate (0.04 mM per percent above basal rate, CI: 0.03-0.04, P < 0.001). No differences were observed between the moderate and high resistance groups. Noninsulin-mediated glucose utilization rose significantly during exercise before returning to baseline roughly 30-min postexercise. Insulin-mediated glucose utilization remained unchanged during exercise sessions. Circulating catecholamines and lactate rose during exercise despite relatively small changes observed in Rd. Results provide an explanation of why RE may pose a lower overall risk for hypoglycemia.NEW & NOTEWORTHY Aerobic exercise is known to cause decreases in blood glucose secondary to increased glucose utilization in people living with type 1 diabetes (T1D). However, less is known about how resistance-type exercise impacts glucose dynamics. Twenty-five participants with T1D performed in-clinic weight-bearing exercises under a glucose clamp. Mathematical modeling of infused glucose tracer allowed for quantification of the rate of hepatic glucose production as well as rates of insulin-mediated and noninsulin-mediated glucose uptake experienced during resistance exercise.

Effects of somatostatin receptor type 2 antagonism during insulin-induced hypoglycaemia in male rats with prediabetes.

AIMS: To examine if glucagon counterregulatory defects exist in a rat model of prediabetes (pre-T2D) and to assess if a selective somatostatin receptor 2 antagonist (SSTR2a), ZT-01, enhances the glucagon response to insulin-induced hypoglycaemia. MATERIALS AND METHODS: Hyperglycaemia was induced in 8- to 9-week-old male, Sprague-Dawley rats via 7 weeks of high-fat diet followed by a single, low-dose intraperitoneal injection of streptozotocin (30 mg/kg). After 2 weeks of basal insulin therapy (0-4 U/d insulin glargine, administered subcutaneously [SC]) to facilitate partial glycaemic recovery and a pre-T2D phenotype, n = 17 pre-T2D and n = 10 normal chow-fed control rats underwent the first of two hypoglycaemic treatment-crossover experiments, separated by a 1-week washout period. On each experimental day, SSTR2a (3 mg/kg ZT-01, SC) or vehicle was administered 1 hour prior to insulin-induced hypoglycaemia (insulin aspart, 6 U/kg, SC). RESULTS: Glucagon counterregulation was marginally reduced with the induction of pre-T2D. Treatment with SSTR2a raised peak plasma glucagon levels and glucagon area under the curve before and after insulin overdose in both and pre-T2D rats. Blood glucose concentration was elevated by 30 minutes after SSTR2a treatment in pre-T2D rats, and hypoglycaemia onset (≤3.9 mmol/L) was delayed by 15 ± 12 minutes compared with vehicle (P < 0.001), despite similar glucose nadirs in the two treatment groups (1.4 ± 0.3 mmol/L). SSTR2a treatment had no effect on blood glucose levels in the control group or on the hypoglycaemia-induced decline in plasma C-peptide levels in either group. CONCLUSIONS: Treatment with an SSTR2a increases glucagon responsiveness and delays the onset of insulin-induced hypoglycaemia in this rat model of pre-T2D where only a modest deficiency in glucagon counterregulation exists.

Weight management in young adults with type 1 diabetes: The advancing care for type 1 diabetes and obesity network sequential multiple assignment randomized trial pilot results.

AIMS: Co-management of weight and glycaemia is critical yet challenging in type 1 diabetes (T1D). We evaluated the effect of a hypocaloric low carbohydrate, hypocaloric moderate low fat, and Mediterranean diet without calorie restriction on weight and glycaemia in young adults with T1D and overweight or obesity. MATERIALS AND METHODS: We implemented a 9-month Sequential, Multiple Assignment, Randomized Trial pilot among adults aged 19-30 years with T1D for ≥1 year and body mass index 27-39.9 kg/m2 . Re-randomization occurred at 3 and 6 months if the assigned diet was not acceptable or not effective. We report results from the initial 3-month diet period and re-randomization statistics before shutdowns due to COVID-19 for primary [weight, haemoglobin A1c (HbA1c), percentage of time below range <70 mg/dl] and secondary outcomes [body fat percentage, percentage of time in range (70-180 mg/dl), and percentage of time below range <54 mg/dl]. Models adjusted for design, demographic and clinical covariates tested changes in outcomes and diet differences. RESULTS: Adjusted weight and HbA1c (n = 38) changed by -2.7 kg (95% CI -3.8, -1.5, P < .0001) and -0.91 percentage points (95% CI -1.5, -0.30, P = .005), respectively, while adjusted body fat percentage remained stable, on average (P = .21). Hypoglycaemia indices remained unchanged following adjustment (n = 28, P > .05). Variability in all outcomes, including weight change, was considerable (57.9% were re-randomized primarily due to loss of <2% body weight). No outcomes varied by diet. CONCLUSIONS: Three months of a diet, irrespective of macronutrient distribution or caloric restriction, resulted in weight loss while improving or maintaining HbA1c levels without increasing hypoglycaemia in adults with T1D.

Is There an Optimal Time of Day for Exercise? A Commentary on When to Exercise for People Living With Type 1 or Type 2 Diabetes.

Exercise is a cornerstone of diabetes self-care because of its association with many health benefits. Several studies that have explored the best time of day to exercise to inform clinical recommendations have yielded mixed results. For example, for people with prediabetes or type 2 diabetes, there may be benefits to timing exercise to occur after meals, whereas people with type 1 diabetes may benefit from performing exercise earlier in the day. One common thread is the health benefits of consistent exercise, suggesting that the issue of exercise timing may be secondary to the goal of helping people with diabetes establish an exercise routine that best fits their life.

The Impact of Sex, Body Mass Index, Age, Exercise Type and Exercise Duration on Interstitial Glucose Levels during Exercise.

The impact of age, sex and body mass index on interstitial glucose levels as measured via continuous glucose monitoring (CGM) during exercise in the healthy population is largely unexplored. We conducted a multivariable generalized estimating equation (GEE) analysis on CGM data (Dexcom G6, 10 days) collected from 119 healthy exercising individuals using CGM with the following specified covariates: age; sex; BMI; exercise type and duration. Females had lower postexercise glycemia as compared with males (92 ± 18 vs. 100 ± 20 mg/dL, p = 0.04) and a greater change in glycemia during exercise from pre- to postexercise (p = 0.001) or from pre-exercise to glucose nadir during exercise (p = 0.009). Younger individuals (i.e., <20 yrs) had higher glucose during exercise as compared with all other age groups (all p < 0.05) and less CGM data in the hypoglycemic range (<70 mg/dL) as compared with those aged 20-39 yrs (p < 0.05). Those who were underweight, based on body mass index (BMI: <18.5 kg/m2), had higher pre-exercise glycemia than the healthy BMI group (104 ± 20 vs. 97 ± 17 mg/dL, p = 0.02) but similar glucose levels after exercise. Resistance exercise was associated with less of a drop in glycemia as compared with aerobic or mixed forms of exercise (p = 0.008) and resulted in a lower percent of time in the hypoglycemic (p = 0.04) or hyperglycemic (glucose > 140 mg/dL) (p = 0.03) ranges. In summary, various factors such as age, sex and exercise type appear to have subtle but potentially important influence on CGM measurements during exercise in healthy individuals.

ZT-01: A novel somatostatin receptor 2 antagonist for restoring the glucagon response to hypoglycaemia in type 1 diabetes.

AIM: To evaluate the pharmacokinetics and efficacy of a novel somatostatin receptor 2 antagonist, ZT-01, to stimulate glucagon release in rats with type 1 diabetes (T1D). METHODS: The pharmacokinetics of ZT-01 and PRL-2903 were assessed following intraperitoneal or subcutaneous dosing at 10 mg/kg. We compared the efficacy of ZT-01 with PRL-2903 to prevent hypoglycaemia during an insulin bolus challenge and under hypoglycaemic clamp conditions. RESULTS: Within 1 hour after intraperitoneal administration, ZT-01 achieved more than 10-fold higher plasma Cmax compared with PRL-2903. Twenty-four hour exposure was 4.7× and 11.3× higher with ZT-01 by the intraperitoneal and subcutaneous routes, respectively. The median time to reach hypoglycaemia of more than 3.0 mmol/L was 60, 70, and 125 minutes following vehicle, PRL-2903, or ZT-01 administration, respectively. Furthermore, rats receiving ZT-01 had significantly higher glucose nadirs following insulin administration compared with PRL-2903- and vehicle-treated rats. During the hypoglycaemic clamp, ZT-01 increased peak glucagon responses by ~4-fold over PRL-2903. CONCLUSIONS: We conclude that ZT-01 may be effective in restoring glucagon responses and preventing the onset of hypoglycaemia in patients with T1D.

Association between high levels of physical activity and improved glucose control on active days in youth with type 1 diabetes.

BACKGROUND: Sixty minutes per day of at least moderate to vigorous physical activity (MVPA) is recommended for children for a variety of physical and psychological reasons. Adherence to these guidelines is confounded by challenges with glucose control during exercise in type 1 diabetes (T1D). OBJECTIVES: This study examined the potential association between physical activity level on active days and glucose control in youth with T1D. METHODS: Blinded continuous glucose monitors (CGM: Abbott Libre Pro) and physical activity data as measured from a body monitor patch (Metria IH1) were collected for up to 3 weeks in youth aged 9-17 years with T1D. The association between physical activity levels, expressed as mean active metabolic equivalent minutes (MET-minutes) per day, with CGM-based mean glucose, percent time in range (TIR: 70-180 mg/dl), % time above range (TAR) and % time below range (TBR) were assessed using a linear regression model adjusted for age, gender, and baseline HbA1c. RESULTS: Study participants were deemed physically active, as defined by at least 10 min of continuous moderate-to-vigorous activity, on 5.2 ± 1.9 days per week, with a median accumulated physical activity time of 61 [IQR: 37-145] minutes per day. Higher physical activity levels were associated with lower mean glucose levels (r = -0.36; p = 0.02) and lower TAR (r = -0.45; p = 0.002) on active days. Higher activity levels were also associated with greater TIR (r = 0.54; p < 0.001) without being associated with more, or less, TBR. CONCLUSIONS: Higher amounts of physical activity are associated with improvements in TIR without significantly increasing TBR. These data suggest that youth ages 9-17 years with T1D can benefit from a high level of physical activity without undue fear of hypoglycemia.

Separating insulin-mediated and non-insulin-mediated glucose uptake during and after aerobic exercise in type 1 diabetes.

Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUCEGP) and rate of glucose disappearance (AUCRd) over 45 min from exercise start. A novel application of linear regression of Rd across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUCRd increased 12.45 mmol/L (CI = 10.33-14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01-15.26, P < 0.001) whereas AUCEGP increased 1.66 mmol/L (CI = 1.01-2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81-4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUCEGP increased during intense exercise by 2.14 mmol/L (CI = 0.91-3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUCRd equal to 0.06 mmol/L per % above basal rate (CI = 0.05-0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451.NEW & NOTEWORTHY Separating insulin and non-insulin glucose uptake dynamically during exercise in type 1 diabetes has not been done before. We use a multistep process, including a previously described linear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time.

Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism.

Glucocorticoids (GCs) are hormones that aid the body under stress by regulating glucose and free fatty acids. GCs maintain energy homeostasis in multiple tissues, including those in the liver and skeletal muscle, white adipose tissue (WAT), and brown adipose tissue (BAT). WAT stores energy as triglycerides, while BAT uses fatty acids for heat generation. The multiple genomic and non-genomic pathways in GC signaling vary with exposure duration, location (adipose tissue depot), and species. Genomic effects occur directly through the cytosolic GC receptor (GR), regulating the expression of proteins related to lipid metabolism, such as ATGL and HSL. Non-genomic effects act through mechanisms often independent of the cytosolic GR and happen shortly after GC exposure. Studying the effects of GCs on adipose tissue breakdown and generation (lipolysis and adipogenesis) leads to insights for treatment of adipose-related diseases, such as obesity, coronary disease, and cancer, but has led to controversy among researchers, largely due to the complexity of the process. This paper reviews the recent literature on the genomic and non-genomic effects of GCs on WAT and BAT lipolysis and proposes research to address the many gaps in knowledge related to GC activity and its effects on disease.

The competitive athlete with type 1 diabetes.

Regular exercise is important for health, fitness and longevity in people living with type 1 diabetes, and many individuals seek to train and compete while living with the condition. Muscle, liver and glycogen metabolism can be normal in athletes with diabetes with good overall glucose management, and exercise performance can be facilitated by modifications to insulin dose and nutrition. However, maintaining normal glucose levels during training, travel and competition can be a major challenge for athletes living with type 1 diabetes. Some athletes have low-to-moderate levels of carbohydrate intake during training and rest days but tend to benefit, from both a glucose and performance perspective, from high rates of carbohydrate feeding during long-distance events. This review highlights the unique metabolic responses to various types of exercise in athletes living with type 1 diabetes. Graphical abstract.

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (i.e. before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes. Graphical abstract.

Glucose management for exercise using continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems in type 1 diabetes: position statement of the European Association for the Study of Diabetes (EASD) and of the International Society for Pediatric and Adolescent Diabetes (ISPAD) endorsed by JDRF and supported by the American Diabetes Association (ADA).

Physical exercise is an important component in the management of type 1 diabetes across the lifespan. Yet, acute exercise increases the risk of dysglycaemia, and the direction of glycaemic excursions depends, to some extent, on the intensity and duration of the type of exercise. Understandably, fear of hypoglycaemia is one of the strongest barriers to incorporating exercise into daily life. Risk of hypoglycaemia during and after exercise can be lowered when insulin-dose adjustments are made and/or additional carbohydrates are consumed. Glycaemic management during exercise has been made easier with continuous glucose monitoring (CGM) and intermittently scanned continuous glucose monitoring (isCGM) systems; however, because of the complexity of CGM and isCGM systems, both individuals with type 1 diabetes and their healthcare professionals may struggle with the interpretation of given information to maximise the technological potential for effective use around exercise (ie, before, during and after). This position statement highlights the recent advancements in CGM and isCGM technology, with a focus on the evidence base for their efficacy to sense glucose around exercise and adaptations in the use of these emerging tools, and updates the guidance for exercise in adults, children and adolescents with type 1 diabetes.

Individual glucose responses to prolonged moderate intensity aerobic exercise in adolescents with type 1 diabetes: The higher they start, the harder they fall.

OBJECTIVE: To evaluate the pattern of change in blood glucose concentrations and hypoglycemia risk in response to prolonged aerobic exercise in adolescents with type 1 diabetes (T1D) that had a wide range in pre-exercise blood glucose concentrations. METHODS: Individual blood glucose responses to prolonged (~60 minutes) moderate-intensity exercise were profiled in 120 youth with T1D. RESULTS: The mean pre-exercise blood glucose concentration was 178 ± 66 mg/dL, ranging from 69 to 396 mg/dL, while the mean change in glucose during exercise was -76 ± 55 mg/dL (mean ± SD), ranging from +83 to -257 mg/dL. Only 4 of 120 youth (3%) had stable glucose levels during exercise (ie, ± ≤10 mg/dL), while 4 (3%) had a rise in glucose >10 mg/dL, and the remaining (93%) had a clinically significant drop (ie, >10 mg/dL). A total of 53 youth (44%) developed hypoglycemia (≤70 mg/dL) during exercise. The change in glucose was negatively correlated with the pre-exercise glucose concentration (R2 = 0.44, P < 0.001), and tended to be greater in those on multiple daily insulin injections (MDI) vs continuous subcutaneous insulin infusion (CSII) (-98 ± 15 vs -65 ± 7 mg/dL, P = 0.05). No other collected variables appeared to predict the change in glucose including age, weight, height, body mass index, disease duration, daily insulin dose, HbA1c , or sex. CONCLUSION: Youth with T1D have variable glycemic responses to prolonged aerobic exercise, but this variability is partially explained by their pre-exercise blood glucose levels. When no implementation strategies are in place to limit the drop in glycemia, the incidence of exercise-associated hypoglycemia is ~44% and having a high pre-exercise blood glucose concentration is only marginally protective.

Metabolic effects of prazosin on skeletal muscle insulin resistance in glucocorticoid-treated male rats.

High-dose glucocorticoids (GC) induce skeletal muscle atrophy, insulin resistance, and reduced muscle capillarization. Identification of treatments to prevent or reverse capillary rarefaction and metabolic deterioration caused by prolonged elevations in GCs would be therapeutically beneficial. Chronic administration of prazosin, an α1-adrenergic antagonist, increases skeletal muscle capillarization in healthy rodents and, recently, in a rodent model of elevated GCs and hyperglycemia. The purpose of this study was to determine whether prazosin administration would improve glucose tolerance and insulin sensitivity, through prazosin-mediated sparing of capillary rarefaction, in this rodent model of increased GC exposure. Prazosin was provided in drinking water (50 mg/l) to GC-treated or control rats (400 mg implants of either corticosterone or a wax pellet) for 7 or 14 days (n = 5-14/group). Whole body measures of glucose metabolism were correlated with skeletal muscle capillarization (C:F) at 7 and 14 days in the four groups of rats. Individual C:F was found to be predictive of insulin sensitivity (r2 = 0.4781), but not of glucose tolerance (r2 = 0.1601) and compared with water only, prazosin treatment decreased insulin values during oral glucose challenge by approximately one-third in corticosterone (Cort)-treated animals. Cort treatment, regardless of duration, induced significant glycolytic skeletal muscle atrophy (P < 0.05), decreased IRS-1 protein content (P < 0.05), and caused elevations in FOXO1 protein expression (P < 0.05), which were unaffected with prazosin administration. In summary, it appears that α1-adrenergic antagonism improves Cort-induced skeletal muscle vascular impairments and reduces insulin secretion during an oral glucose tolerance test, but is unable to improve the negative alterations directly affecting the myocyte, including muscle size and muscle signaling protein expression.