Protein Ingestion in Reducing the Risk of Late-Onset Post-Exercise Hypoglycemia: A Pilot Study in Adolescents and Youth with Type 1 Diabetes.

Dietary protein causes dose-dependent hyperglycemia in individuals with type 1 diabetes (T1D). This study investigated the effect of consuming 50 g of protein on overnight blood glucose levels (BGLs) following late-afternoon moderate-intensity exercise. Six participants (3M:3F) with T1D, HbA1c 7.5 ± 0.8% (58.0 ± 8.7 mmol/mol) and aged 20.2 ± 3.1 years exercised for 45 min at 1600 h and consumed a protein drink or water alone at 2000 h, on two separate days. A basal insulin euglycemic clamp was employed to measure the mean glucose infusion rates (m-GIR) required to maintain euglycemia on both nights. The m-GIR on the protein and water nights during the hypoglycemia risk period and overnight were 0.27 ± 043 vs. 1.60 ± 0.66 mg/kg/min (p = 0.028, r = 0.63) and 0.51 ± 0.16 vs. 1.34 ± 0.71 mg/kg/min (p = 0.028, r = 0.63), respectively. Despite ceasing intravenous glucose infusion on the protein night, the BGLs peaked at 9.6 ± 1.6 mmol/L, with a hypoglycemia risk period mean of 7.8 ± 1.5 mmol/L compared to 5.9 ± 0.4 mmol/L (p = 0.028) on the water night. The mean plasma glucagon levels were 51.5 ± 14.1 and 27.2 ± 10.1 ng/L (p = 0.028) on the protein and water night, respectively. This suggests that an intake of protein is effective at reducing the post-exercise hypoglycemia risk, potentially via a glucagon-mediated stimulation of glucose production. However, 50 g of protein may be excessive for maintaining euglycemia.

Reproducibility of plasma glucose responses to moderate-intensity exercise in individuals with type 1 diabetes.

AIM: To examine the within-person variability in plasma glucose responses to moderate-intensity morning exercise in young individuals with type 1 diabetes after overnight fasting and under basal insulin conditions. METHODS: In this pilot study, eight participants completed 40 min of moderate-intensity exercise at 60% V̇O2 peak on three separate days. The within-person standard deviation (SDw) in plasma glucose response was analysed both during and 1 h after exercise using the two visits per participant most closely matched by pre-exercise plasma glucose level. RESULTS: When the two closest matched visits per individual were included for analysis, mean (±SD) change in plasma glucose level was -1.8 ± 1.1 mmoL/L during exercise and -0.6 ± 1.0 mmoL/L during recovery, with the SDw of these changes being 0.5 mmol (95% CI 0.2, 0.8) during exercise and 0.8 mmoL/L (95% CI 0.4, 1.3) during recovery. The median intra-individual difference in plasma glucose level change was 0.3 mmoL/L [IQR 0.1, 0.7] during exercise and 0.8 mmoL/L [IQR 0.4, 1.0] during recovery. CONCLUSION: Within-person plasma glucose responses to moderate-intensity exercise may be reproducible under fasting and basal insulin conditions and similar pre-exercise plasma glucose levels. This finding may assist the design of future studies investigating both the reproducibility of glycaemic responses to exercise and blood glucose management for individuals with type 1 diabetes.

Effects of Dietary Fat and Protein on Glucoregulatory Hormones in Adolescents and Young Adults With Type 1 Diabetes.

CONTEXT: Dietary fat and protein impact postprandial hyperglycemia in people with type 1 diabetes, but the underlying mechanisms are poorly understood. Glucoregulatory hormones are also known to modulate gastric emptying and may contribute to this effect. OBJECTIVE: Investigate the effects of fat and protein on glucagon-like peptide (GLP-1), glucagon-dependent insulinotropic polypeptide (GIP) and glucagon secretion. METHODS: 2 crossover euglycemic insulin clamp clinical trials at 2 Australian pediatric diabetes centers. Participants were 12-21 years (n = 21) with type 1 diabetes for ≥1 year. Participants consumed a low-protein (LP) or high-protein (HP) meal in Study 1, and low-protein/low-fat (LPLF) or high-protein/high-fat (HPHF) meal in Study 2, all containing 30 g of carbohydrate. An insulin clamp was used to maintain postprandial euglycemia and plasma glucoregulatory hormones were measured every 30 minutes for 5 hours. Data from both cohorts (n = 11, 10) were analyzed separately. The main outcome measure was area under the curve of GLP-1, GIP, and glucagon. RESULTS: Meals low in fat and protein had minimal effect on GLP-1, while there was sustained elevation after HP (80.3 ± 16.8 pmol/L) vs LP (56.9 ± 18.6), P = .016, and HPHF (103.0 ± 26.9) vs LPLF (69.5 ± 31.9) meals, P = .002. The prompt rise in GIP after all meals was greater after HP (190.2 ± 35.7 pmol/L) vs LP (152.3 ± 23.3), P = .003, and HPHF (258.6 ± 31.0) vs LPLF (151.7 ± 29.4), P < .001. A rise in glucagon was also seen in response to protein, and HP (292.5 ± 88.1 pg/mL) vs LP (182.8 ± 48.5), P = .010. CONCLUSION: The impact of fat and protein on postprandial glucose excursions may be mediated by the differential secretion of glucoregulatory hormones. Further studies to better understand these mechanisms may lead to improved personalized postprandial glucose management.

Antidiuretic hormone and the activation of glucose production during high intensity aerobic exercise.

OBJECTIVE: This study aimed to investigate the role that antidiuretic hormone (ADH) may play in the activation of glucose production during high intensity aerobic exercise. MATERIALS/METHODS: This study was part of larger study based on a repeated measures cross-over study design and involved ten adult participants who exercised in the morning at 80 % V̇O2peak for up to 40 min or until exhaustion. During and after exercise, the participants were subjected to a morning euglycaemic/euinsulinaemic clamp while [6,6-2H2]glucose was infused and blood sampled to measure the endogenous rate of glucose appearance (Ra) and ADH levels. RESULTS: The levels of plasma ADH were 1.8 ± 0.2 pmol/L (mean ± SEM) at rest and increased to 10.5 ± 2.1 pmol/L at the end of exercise (mean ± SEM), which lasted 8.5-40 min. In response to exercise, glucose Ra also rose significantly (p < 0.05), but there was no significant association between changes in ADH levels and glucose Ra (r = 0.49; p = 0.150). CONCLUSIONS: Although the significant increase in glucose Ra and ADH levels during high intensity aerobic exercise suggest for the first time that these processes may be causally related, there was no significant association between these variables, maybe because of the small sample size and varying exercise durations. Hence, the importance of the causal role that ADH may play in the exercise-mediated activation of hepatic glucose production warrants further in depth investigations.

Additional Insulin Is Required in Both the Early and Late Postprandial Periods for Meals High in Protein and Fat: A Randomized Trial.

CONTEXT: The pattern and quantity of insulin required for high-protein high-fat (HPHF) meals is not well understood. OBJECTIVE: This study aimed to determine the amount and delivery pattern of insulin required to maintain euglycemia for 5 hours after consuming a HPHF meal compared with a low-protein low-fat (LPLF) meal. METHODS: This randomized crossover clinical trial, conducted at 2 Australian pediatric diabetes centers, included 10 patients (12-21 years of age) with type 1 diabetes for ≥ 1 year. Participants were randomized to HPHF meal (60 g protein, 40 g fat) or LPLF meal (5 g protein, 5 g fat) with identical carbohydrate content (30 g). A modified insulin clamp technique was used to determine insulin requirements to maintain postprandial euglycemia for 5 hours. Total mean insulin requirements over 5 hours were measured. RESULTS: The total mean insulin requirements for the HPHF meal were significantly greater than for the LPLF meal (11.0 [CI 9.2, 12.8] units vs 5.7 [CI 3.8, 7.5] units; P = 0.001). Extra intravenous insulin was required for HPHF: 0 to 2 hours (extra 1.2 [CI 0.6, 1.6] units/h), 2 to 4 hours (extra 1.1 [CI 0.6, 1.6] units/h), and 4 to 5 hours (extra 0.6 [CI 0.1, 1.1] units/h) after the meal. There were marked inter-individual differences in the quantity of additional insulin (0.3 to 5 times more for HPHF) and the pattern of insulin delivery (0%-85% of additional insulin required in the first 2 hours). CONCLUSION: The addition of protein and fat to a standardized carbohydrate meal almost doubled the mean insulin requirement, with most participants requiring half of the additional insulin in the first 2 hours.

Impact of Hybrid Closed Loop Therapy on Hypoglycemia Awareness in Individuals with Type 1 Diabetes and Impaired Hypoglycemia Awareness.

Objective: This study evaluated the efficacy of using a hybrid closed loop (HCL) system in restoring hypoglycemia awareness in individuals with impaired awareness of hypoglycemia (IAH). Research Design and Methods: Participants with IAH (Gold score ≥4) were recruited into a randomized crossover pilot study. They participated in two 8-week periods using a HCL system (Medtronic 670G™) (intervention) and standard insulin pump therapy (control). Hyperinsulinemic hypoglycemic clamp studies were undertaken at baseline and at the end of each study period for the evaluation of the counter-regulatory hormonal and symptomatic responses to hypoglycemia. Results: Seventeen participants (mean age [standard deviation] 35.8 years [11.2 years]) were included in the study. Peak epinephrine levels (median, interquartile range [IQR]) in response to hypoglycemia were similar postintervention and control periods; 234.7 pmol/L (109.2; 938.9) versus 188.3 pmol/L (133.7; 402.9), P = 0.233. However, both peak adrenergic and neuroglycopenic symptom scores were higher after intervention; 5.0 (4.5; 9.0) versus 4.0 (4.0; 5.5), P = 0.009, and 8.5 (6.0; 15.0) versus 6.5 (6.0; 7.0) P = 0.014, respectively. Self-reported hypoglycemia awareness improved: median (IQR) Gold score was 4.0 (3.0; 5.5) versus 5.5 (4.5; 6.0); intervention versus control, P = 0.033. Time spent <3.9 and <3.0 mmol/L was lower in the intervention group than in control, P = 0.002. Other patient-reported outcomes (hypoglycemia fear and diabetes treatment satisfaction) did not change. Conclusions: A short-term use of a HCL system failed to demonstrate an improvement in counter-regulatory hormonal responses. However, higher hypoglycemia symptom scores during controlled hypoglycemia, better self-reported hypoglycemia awareness, and less time spent in hypoglycemia suggest the potential benefits of a HCL system in people with IAH. Trial Registration: anzctr.org.au Identifier: ACTRN12616000909426.

Effect of Exercise Intensity on Exogenous Glucose Requirements to Maintain Stable Glycemia At High Insulin Levels in Type 1 Diabetes.

CONTEXT: Under basal insulin levels, there is an inverted U relationship between exercise intensity and exogenous glucose requirements to maintain stable blood glucose levels in type 1 diabetes (T1D), with no glucose required for intense exercise (80% V̇O2 peak), implying that high-intensity exercise is not conducive to hypoglycemia. OBJECTIVE: This work aimed to test the hypothesis that a similar inverted U relationship exists under hyperinsulinemic conditions, with high-intensity aerobic exercise not being conducive to hypoglycemia. METHODS: Nine young adults with T1D (mean ±â€…SD age, 22.6 ±â€…4.7 years; glycated hemoglobin, 61 ±â€…14 mmol/mol; body mass index, 24.0 ±â€…3.3 kg/m2, V̇O2 peak, 36.6 ±â€…8.0 mL·kg-1 min-1) underwent a hyperinsulinemic-euglycemic clamp to maintain stable glycemia (5-6 mmol·L-1), and exercised for 40 minutes at 4 intensities (35%, 50%, 65%, and 80% V̇O2peak) on separate days following a randomized counterbalanced study design. MAIN OUTCOME MEASURES: Glucose infusion rates (GIR) and glucoregulatory hormones levels were measured. RESULTS: The GIR (±â€…SEM) to maintain euglycemia was 4.4 ±â€…0.4 mg·kg-1 min-1 prior to exercise, and increased significantly by 1.8 ±â€…0.4, 3.0 ±â€…0.4, 4.2 ±â€…0.7, and 3.5 ±â€…0.7 mg·kg-1 min-1 during exercise at 35%, 50%, 65%, and 80% V̇O2 peak, respectively, with no significant differences between the 2 highest exercise intensities (P > .05), despite differences in catecholamine levels (P < .05). During the 2-hour period after exercise at 65% and 80% V̇O2 peak, GIRs did not differ from those during exercise (P > .05). CONCLUSIONS: Under hyperinsulinemic conditions, the exogenous glucose requirements to maintain stable glycemia during and after exercise increase with exercise intensity then plateau with exercise performed at above moderate intensity ( > 65% V̇O2 peak). High-intensity exercise confers no protection against hypoglycemia.

Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort.

BACKGROUND: Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant mutations in one of 13 confirmed genes. Estimates of MODY prevalence vary widely, as genetic screening is usually restricted based on clinical features, even in population studies. We aimed to determine prevalence of MODY variants in a large and unselected pediatric diabetes cohort. METHODS: MODY variants were assessed using massively parallel sequencing in the population-based diabetes cohort (n = 1363) of the sole tertiary pediatric diabetes service for Western Australia (population 2.6 million). All individuals were screened, irrespective of clinical features. MODY variants were also assessed in a control cohort (n = 993). RESULTS: DNA and signed consent were available for 821 children. Seventeen children had pathogenic/likely pathogenic variants in MODY genes, two diagnosed with type 2 diabetes, four diagnosed with antibody-negative type 1 diabetes (T1DM), three diagnosed with antibody-positive T1DM, and eight previously diagnosed with MODY. Prevalence of MODY variants in the sequenced cohort was 2.1%, compared to 0.3% of controls. CONCLUSIONS: This is the first comprehensive study of MODY variants in an unselected population-based pediatric diabetes cohort. The observed prevalence, increasing access to rapid and affordable genetic screening, and significant clinical implications suggest that genetic screening for MODY could be considered for all children with diabetes, irrespective of other clinical features.

Glycemia, Treatment Satisfaction, Cognition, and Sleep Quality in Adults and Adolescents with Type 1 Diabetes When Using a Closed-Loop System Overnight Versus Sensor-Augmented Pump with Low-Glucose Suspend Function: A Randomized Crossover Study.

BACKGROUND: We compared glycemia, treatment satisfaction, sleep quality, and cognition using a nighttime Android-based hybrid closed-loop system (Android-HCLS) with sensor-augmented pump with low-glucose suspend function (SAP-LGS) in people with type 1 diabetes. MATERIALS AND METHODS: An open-label, prospective, randomized crossover study of 16 adults (mean [SD] age 42.1 [9.6] years) and 12 adolescents (15.2 [1.6] years) was conducted. All participants completed four consecutive nights at home with Android-HCLS (proportional integral derivative with insulin feedback algorithm; Medtronic) and SAP-LGS. PRIMARY OUTCOME: percent continuous glucose monitoring (CGM) time (00:00-08:00 h) within target range (72-144 mg/dL). Secondary endpoints: percent CGM time above target (>144 mg/dL); below target (<72 mg/dL); glycemic variability (SD); symptomatic hypoglycemia; adult treatment satisfaction; sleep quality; and cognitive function. RESULTS: The primary outcome for all participants was not statistically different between Android-HCLS and SAP-LGS (mean [SD] 59.4 [17.9]% vs. 53.1 [18]%; p = 0.14). Adults had greater percent time within target range (57.7 [18.6]% vs. 44.5 [14.5]%; p < 0.006); less time above target (42.0 [18.7]% vs. 52.6 [16.5]%; p = 0.034); lower glycemic variability (35 [10.7] mg/dL vs. 46 [10.7] mg/dL; p = 0.003); and less (median [IQR]) time below target (0.0 [0.0-0.4]% vs. 0.80 [0.0-3.9]%; p = 0.025). In adolescents, time below target was lower with Android-HCLS vs. SAP-LGS (0.0 [0.0-0.0]% vs. 1.8 [0.1-7.9]%; p = 0.011). Nocturnal symptomatic hypoglycemia was less (1 vs. 10; p = 0.007) in adolescents, but not adults (5 vs. 13; p = 0.059). In adults, treatment satisfaction increased by 10 points (p < 0.02). Sleep quality and cognition did not differ. CONCLUSIONS: Android-HCLS in both adults and adolescents reduced nocturnal hypoglycemia and, in adults, improved overnight time in target range and treatment satisfaction compared with SAP-LGS.

Effectiveness of a Predictive Algorithm in the Prevention of Exercise-Induced Hypoglycemia in Type 1 Diabetes.

BACKGROUND: Sensor-augmented pump therapy (SAPT) with a predictive algorithm to suspend insulin delivery has the potential to reduce hypoglycemia, a known obstacle in improving physical activity in patients with type 1 diabetes. The predictive low glucose management (PLGM) system employs a predictive algorithm that suspends basal insulin when hypoglycemia is predicted. The aim of this study was to determine the efficacy of this algorithm in the prevention of exercise-induced hypoglycemia under in-clinic conditions. METHODS: This was a randomized, controlled cross-over study in which 25 participants performed 2 consecutive sessions of 30 min of moderate-intensity exercise while on basal continuous subcutaneous insulin infusion on 2 study days: a control day with SAPT alone and an intervention day with SAPT and PLGM. The predictive algorithm suspended basal insulin when sensor glucose was predicted to be below the preset hypoglycemic threshold in 30 min. We tested preset hypoglycemic thresholds of 70 and 80 mg/dL. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia with plasma glucose <63 mg/dL or plasma glucose <50 mg/dL) and was compared in both control and intervention arms. RESULTS: Results were analyzed in 19 participants. In the intervention arm with both thresholds, only 6 participants (32%) required treatment for hypoglycemia compared with 17 participants (89%) in the control arm (P = 0.003). In participants with a 2-h pump suspension on intervention days, the plasma glucose was 84 ± 12 and 99 ± 24 mg/dL at thresholds of 70 and 80 mg/dL, respectively. CONCLUSIONS: SAPT with PLGM reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting.

Prevention of Insulin-Induced Hypoglycemia in Type 1 Diabetes with Predictive Low Glucose Management System.

BACKGROUND: Sensor-augmented pump therapy (SAPT) with algorithms to predict impending low blood glucose and suspend insulin delivery has the potential to reduce hypoglycemia exposure. The aim of this study was to determine whether predictive low glucose management (PLGM) system is effective in preventing insulin-induced hypoglycemia in controlled experiments. METHODS: Two protocols were used to induce hypoglycemia in an in-clinic environment. (A) Insulin bolus: Insulin was administered as a manual bolus through the pump. (B) Increased basal insulin: Hypoglycemia was induced by increasing basal rates overnight to 180%. For both protocols, participants were randomized and studied on 2 separate days; a control day with SAPT alone and an intervention day with SAPT and PLGM activated. The predictive algorithm was programmed to suspend basal insulin infusion when sensor glucose was predicted to be <80 mg/dL in 30 min. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia or plasma glucose <50 mg/dL) and was compared in both control and intervention arms. RESULTS: With insulin bolus, 24/28 participants required hypoglycemia treatment with SAPT alone compared to 5/28 participants when PLGM was activated (P ≤ 0.001). With increased basal rates, all the eight SAPT-alone participants required treatment for hypoglycemia compared to only one with SAPT and PLGM. There was no post pump-suspend hyperglycemia with insulin bolus (P = 0.4) or increased basal rates (P = 0.69) in participants with 2-h pump suspension on intervention days. CONCLUSIONS: SAPT with PLGM reduced the requirement for hypoglycemia treatment following insulin-induced hypoglycemia in an in-clinic setting.

Effect of Exercise Intensity on Glucose Requirements to Maintain Euglycemia During Exercise in Type 1 Diabetes.

CONTEXT: No recommendations exist to inform the carbohydrate amount required to prevent hypoglycemia associated with exercise of different intensities in individuals with type 1 diabetes (T1D). OBJECTIVE: The relationship between exercise intensity and carbohydrate requirements to maintain stable euglycemia in individuals with T1D remains to be determined. It was predicted that an "inverted-U" relationship exists between exercise intensity and the amount of glucose required to prevent hypoglycemia during exercise at basal insulinemia. Our objective was to investigate this relationship and elucidate the underlying glucoregulatory mechanisms. DESIGN, PARTICIPANTS, AND INTERVENTION: We subjected nine individuals (mean ± SD age, 21.5 ± 4.0 years; duration of disease, 11.4 ± 6.4 years; glycated hemoglobin, 7.9 ± 0.8% [60 mmol/mol]; body mass index, 25.4 ± 5.5 kg/m(2); VO2peak, 34.8 ± 5.1 mL·kg(-1)·min(-1); and lactate threshold, 59.9 ± 5.9% VO2peak) with T1D to a euglycemic clamp, whereby euglycemia was maintained by infusing basal insulin rates with concomitant infusion of [6,6-(2)H2]glucose for determining glucose kinetics. Glucose was infused to maintain euglycemia during and for 2 hours after exercise of different intensities (35, 50, 65, and 80% VO2peak). MAIN OUTCOME MEASURES: The glucose infusion rate (GIR), levels of glucoregulatory hormones, and rates of endogenous glucose appearance and disappearance were compared between conditions. RESULTS: The mean GIR to maintain euglycemia during exercise increased with intensity up to 50% (4.0 ± 1.6 g/h; P < .05) and 65% (4.1 ± 1.7 g/h), but no glucose was required at 80% VO2peak. Glucose rate of appearance and disappearance increased with intensity and, together with plasma catecholamines, reached higher levels at 80% VO2peak. CONCLUSION: Our findings support the predicted inverted-U relationship between exercise intensity and glucose requirement. However, the relationship between iv and oral glucose requirements needs to be investigated to translate these GIR data to clinical practice.

Effect of antecedent moderate-intensity exercise on the glycemia-increasing effect of a 30-sec maximal sprint: a sex comparison.

This study investigated whether a prior bout of moderate-intensity exercise attenuates the glycemia-increasing effect of a maximal 30-sec sprint. A secondary aim was to determine whether the effect of antecedent exercise on the glucoregulatory response to sprinting is affected by sex. Participants (men n = 8; women n = 7) were tested on two occasions during which they either rested (CON) or cycled for 60-min at a moderate intensity of ~65% V ˙ O 2 peak (EX) before performing a 30-sec maximal cycling effort 195 min later. In response to the sprint, blood glucose increased to a similar extent between EX and CON trials, peaking at 10 min of recovery, with no difference between sexes (P > 0.05). Blood glucose then declined at a faster rate in EX, and this was associated with a glucose rate of disappearance (R d) that exceeded the glucose rate of appearance (R a) earlier in EX compared with CON, although the overall glucose R a and R d profile was higher in men compared with women (P < 0.05). The response of growth hormone was attenuated during recovery from EX compared with CON (P < 0.05), with a lower absolute response in women compared with men (P < 0.05). The response of epinephrine and norepinephrine was also lower in women compared with men (P < 0.05) but similar between trials. In summary, a prior bout of moderate-intensity exercise does not affect the magnitude of the glycemia-increasing response to a 30-sec sprint; however, the subsequent decline in blood glucose is more rapid. This blood glucose response is similar between men and women, despite less pronounced changes in glucose R a and R d, and a lower response of plasma catecholamines and growth hormone to sprinting in women.

Antecedent hypoglycaemia does not diminish the glycaemia-increasing effect and glucoregulatory responses of a 10 s sprint in people with type 1 diabetes.

AIMS/HYPOTHESIS: A 10 s sprint has been reported to provide a means to prevent acute post-exercise hypoglycaemia in young adults with type 1 diabetes because of its glycaemia-raising effect, but it is unclear whether this effect is impaired by antecedent hypoglycaemia. The purpose of this study was to investigate whether antecedent hypoglycaemia impairs the glycaemia-raising effect of a 10 s sprint in individuals with type 1 diabetes. METHODS: Eight individuals underwent a hyperinsulinaemic-hypoglycaemic or hyperinsulinaemic-euglycaemic clamp on two separate mornings. Thereafter, the participants underwent a basal insulin-euglycaemic clamp before performing a 10 s sprint on a cycle ergometer. The levels of blood glucose and glucoregulatory hormones and rates of glucose appearance (Ra) and disappearance (Rd) were compared between conditions. RESULTS: During the morning clamps, blood glucose levels were significantly different between conditions of hypoglycaemia (2.8 ± 0.1 mmol/l) and euglycaemia (5.4 ± 0.2 mmol/l; p < 0.001). Mean glycaemia prior to sprinting was similar (5.6 ± 0.4 and 5.5 ± 0.3 mmol/l for hypoglycaemic and euglycaemic conditions, respectively; p = 0.83). In response to the afternoon sprint, the pattern of increase in blood glucose levels did not differ between conditions, reaching similar maximal levels 45 min after exercise (6.5 ± 0.4 and 6.6 ± 0.3 mmol/l, respectively; p = 0.43). The early post-exercise patterns in glucose Ra and Rd and increases in plasma adrenaline (epinephrine), growth hormone and cortisol levels did not differ between conditions. CONCLUSIONS/INTERPRETATION: Hypoglycaemia in the morning does not diminish the glycaemia-raising effect of an afternoon 10 s sprint in young adults with type 1 diabetes, suggesting that sprinting is a useful strategy for opposing hypoglycaemia, regardless of prior hypoglycaemia.

Acute hyperglycaemia does not alter nitric oxide-mediated microvascular function in the skin of adolescents with type 1 diabetes.

PURPOSE: We assessed the impact of an acute bout of hyperglycaemia on nitric oxide (NO)-mediated microvascular function in the skin of adolescents with type 1 diabetes (T1DM). METHODS: Twelve subjects (12-18 years) with T1DM were randomised into a control (n = 6) or hyperglycaemia (n = 6) group. Hyperinsulinaemic clamps were used to manipulate blood glucose level (BGL). Following a baseline period, where all subjects were euglycaemic (20 min), the experimental phase began. During the experimental phase, BGL was elevated to 16.7 ± 0.9 mmol L(-1) in the hyperglyceamic group, while it was maintained at euglycaemia (5.5 ± 0.1 mmol L(-1)) in the control group. Simultaneously, cutaneous microvascular function (% max cutaneous vascular conductance, CVC%) was assessed using laser Doppler fluxometry following stimulation of skin blood flow using localised heating (42 °C). To determine the NO contribution to skin blood flow, two microdialysis sites were assessed, one perfused with Ringers and the other with the NO blocker, NG-monomethyl-L-arginine (L-NMMA). RESULTS: In the hyperglycaemic group, acute increase in BGL was not associated with changes in skin blood flow (CVC% 82.4 ± 8.7% at 5.5 ± 0.1 mmol L(-1) vs 79.5 ± 9.1% at 16.7 ± 0.9 mmol L(-1), unpaired t tests, P = 0.588) or the contribution of NO to vasodilation. CONCLUSIONS: These results suggest that, in our group of adolescents with type 1 diabetes, acute hyperglycaemia did not affect skin microvascular NO-mediated function.

A 10-s sprint performed after moderate-intensity exercise neither increases nor decreases the glucose requirement to prevent late-onset hypoglycemia in individuals with type 1 diabetes.

OBJECTIVE: To determine whether performing a 10-s sprint after moderate-intensity exercise increases the amount of carbohydrate required to maintain euglycemia and prevent late-onset postexercise hypoglycemia relative to moderate-intensity exercise alone. RESEARCH DESIGN AND METHODS: Seven individuals with type 1 diabetes underwent a hyperinsulinemic-euglycemic clamp and performed 30 min of moderate-intensity exercise on two separate occasions followed by either a 10-s maximal sprint effort or no sprint. During the following 8 h, glucose infusion rate to maintain euglycemia and rates of glucose appearance and disappearance were measured continuously. RESULTS: In response to exercise and throughout the 8-h recovery period, there were no differences in glucose infusion rate, blood glucose levels, plasma insulin concentrations, and rates of glucose appearance and disappearance between the two experimental conditions (P > 0.05). CONCLUSIONS: A 10-s sprint performed after 30 min of moderate-intensity exercise does not affect the amount of carbohydrate required to maintain euglycemia postexercise in individuals with type 1 diabetes.

The effect of midday moderate-intensity exercise on postexercise hypoglycemia risk in individuals with type 1 diabetes.

CONTEXT: Exercise increases the risk of hypoglycemia in type 1 diabetes. OBJECTIVE: Recently we reported a biphasic increase in glucose requirements to maintain euglycemia after late-afternoon exercise, suggesting a unique pattern of delayed risk for nocturnal hypoglycemia. This study examined whether this pattern of glucose requirements occurs if exercise is performed earlier in the day. DESIGN, PARTICIPANTS, AND INTERVENTION: Ten adolescents with type 1 diabetes underwent a hyperinsulinemic euglycemic glucose clamp on 2 different occasions during which they either rested or performed 45 minutes of moderate-intensity exercise at midday. Glucose was infused to maintain euglycemia for 17 hours after exercise. MAIN OUTCOME MEASURES: The glucose infusion rate (GIR) to maintain euglycemia, glucose rates of appearance and disappearance, and levels of counterregulatory hormones were compared between conditions. RESULTS: GIRs to maintain euglycemia were not significantly different between groups at baseline (9.8 ± 1.4 and 9.5 ± 1.6 g/h before the exercise and rest conditions, respectively) and did not change in the rest condition throughout the study. In contrast, GIR increased more than 3-fold during exercise (from 9.8 ± 1.4 to 30.6 ± 4.7 g/h), fell within the first hour of recovery, but remained elevated until 11 hours after exercise before returning to baseline levels. CONCLUSIONS: The pattern of glucose requirements to maintain euglycemia in response to moderate-intensity exercise performed at midday suggests that the risk of exercise-mediated hypoglycemia increases during and for several hours after moderate-intensity exercise, with no evidence of a biphasic pattern of postexercise risk of hypoglycemia.

Clinical evaluation of a noninvasive alarm system for nocturnal hypoglycemia.

BACKGROUND: The aim of this study was to evaluate the performance of a prototype noninvasive alarm system (HypoMon) for the detection of nocturnal hypoglycemia. A prospective cohort study evaluated an alarm system that included a sensor belt, a radio frequency transmitter for chest belt signals, and a receiver. The receiver incorporated integrated "real-time" algorithms designed to recognize hypoglycemia "signatures" in the physiological parameters monitored by the sensor belt. METHODS: Fifty-two children and young adults with type 1 diabetes mellitus (T1DM) participated in this blinded, prospective, in-clinic, overnight study. Participants had a mean age of 16 years (standard deviation 2.1, range 12-20 years) and were asked to follow their normal meal and insulin routines for the day of the study. Participants had physiological parameters monitored overnight by a single HypoMon system. Their BG levels were also monitored overnight at regular intervals via an intravenous cannula and read on two independent Yellow Springs Instruments analyzers. Hypoglycemia was not induced by any manipulations of diabetes management, rather the subjects were monitored overnight for "natural" occurrences of hypoglycemia. Performance analyses included comparing HypoMon system alarm times with allowed time windows associated with each hypoglycemic event. RESULTS: The primary recognition algorithm in the prototype alarm system performed at a level consistent with expectations based on prior user surveys. The HypoMon system correctly recognized 8 out of the 11 naturally occurring overnight hypoglycemic events and falsely alarmed on 13 out of the remaining 41 normal nights [sensitivity 73% (8/11), specificity 68% (28/41), positive predictive value 38%,negative predictive value 90%]. CONCLUSION: The prototype HypoMon shows potential as an adjunct method for noninvasive overnight monitoring for hypoglycemia events in young people with T1DM.