Utility of Continuous Glucose Monitoring vs. Meal Study in Detecting Hypoglycemia After Gastric Bypass

Context Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose, and relief of symptom when glucose is normalized (Whipple’s triad). Objective To compare the yield of mixed meal test (MMT) and continuous glucose monitoring system (CGMS) in detecting hypoglycemia after gastric bypass surgery (GB). Setting The study was conducted at General Clinical Research Unit, Cincinnati Children’s Hospital (Cincinnati, OH, United States). Methods Glucose profiles were evaluated in 15 patients with documented recurrent clinical hypoglycemia after GB, 8 matched asymptomatic GB subjects, and 9 healthy weight-matched non-operated controls using MMT in a control setting and CGMS under free-living conditions. Results Patients with prior GB had larger glucose variability during both MMT and CGMS when compared to non-surgical controls regardless of their hypoglycemic status. Sensitivity (71 vs. 47 %) and specificity (100 vs. 88 %) of MMT in detecting hypoglycemia was superior to CGMS. Conclusions Our findings indicate that a fixed carbohydrate ingestion during MMT is a more reliable test to diagnose GB-related hypoglycemia compared to CGMS during free-living state.

Sport supplements and the athlete’s gut: a review.

Vigorous or prolonged exercise poses a challenge to gastrointestinal system functioning and is associated with digestive symptoms. This narrative review addresses 1) the potential of dietary supplements to enhance gut function and reduce exercise-associated gastrointestinal symptoms and 2) strategies for reducing gastrointestinal-related side effects resulting from popular sports supplements. Several supplements, including probiotics, glutamine, and bovine colostrum, have been shown to reduce markers of gastrointestinal damage and permeability with exercise. Yet, the clinical ramifications of these findings are uncertain, as improvements in symptoms have not been consistently observed. Among these supplements, probiotics modestly reduced exercise-associated gastrointestinal symptoms in a few studies, suggesting they are the most evidenced-based choice for athletes looking to manage such symptoms through supplementation. Carbohydrate, caffeine, and sodium bicarbonate are evidence-based supplements that can trigger gastrointestinal symptoms. Using glucose-fructose mixtures is beneficial when carbohydrate ingestion is high (>50 g/h) during exercise, and undertaking multiple gut training sessions prior to competition may also be helpful. Approaches for preventing caffeine-induced gastrointestinal disturbances include using low-to-moderate doses (<500 mg) and avoiding/minimizing exacerbating factors (stress, anxiety, other stimulants, fasting). Adverse gastrointestinal effects of sodium bicarbonate can be avoided by using enteric-coated formulations, low doses (0.2 g/kg), or multi-day loading protocols.

Long-term follow-up of a randomized clinical trial comparing glycemic excursion minimization (GEM) to weight loss (WL) in the management of type 2 diabetes

IntroductionWe previously reported the physical, psychological and behavioral 3-month post-treatment results of a randomized controlled trial comparing glycemic excursion minimization (GEM) versus conventional weight loss (WL) therapy in the management of type 2 diabetes (T2D). GEM is a paradigm shift in the lifestyle management of T2D that focuses on reducing postnutrient glucose excursions, rather than reducing weight. We now present the 13-month follow-up results.Research design and methodsThe initial study sample of 172 were 30–80 years old, had T2D for ≤10 years, an HbA1c ≥6.8% (51 mmol/mol), and were not using insulin. Participants were randomized to 6 hours of group treatment, either to WL or one of three versions of GEM. GEM groups differed in degree of blood glucose (BG) feedback provided during treatment: no recommended feedback, systematic capillary BG feedback before and after nutrient intake and physical activity, or continuous glucose monitoring. Since these GEM groups did not differ in pre-post improvement they were combined for initial and current analyses. Of those who completed the 3-month postassessment, 100% and 96% of the WL and GEM participants completed the 13-month follow-up assessment.ResultsPre to follow-up within-group comparisons indicated WL participants sustained improvement in body mass index (BMI) (−0.9±1.4, p=0.001). GEM participants continued to benefit in their HbA1c (−0.5±1.4, p<0.001), BMI (−1±1, p<0.001), high-density lipoprotein (p<0.001), reduction of carbohydrate ingestion (p<0.001), self-monitoring of blood glucose satisfaction (p<0.001) and frequency (p<0.001), diabetes knowledge (p<0.001), diabetes empowerment (p<0.001), and both diabetes distress emotional (p=0.009) and regimen (p=0.001) subscales. Forty-two percent and 52% of WL and GEM participants, respectively, were classified as responders (individuals whose A1c dropped by at least −0.5%), with a mean HbA1c reduction of −1.2% and −1.5%. Neither WL nor GEM responders differed from non-responders in baseline demographics, psychological or disease severity variables. While WL responders could not be predicted, 73% of GEM responders were predicted by post minus pretreatment reductions of HbA1c, diabetes medication and BMI.ConclusionsWhile WL sustained improvement in BMI, GEM sustained benefits across a broad range of physical, behavioral and psychological parameters, beneficial for clinicians and adults with T2D. This may be especially relevant for primary care physicians who manage about 90% of patients with T2D.Trial registration numberNCT03196895.

Comparative impact of dietary carbohydrates on the liver transcriptome in two strains of mice

Excessive long-term consumption of dietary carbohydrates, including glucose, sucrose or fructose, has been shown to have significant impact on genome-wide gene expression, which likely results from changes in metabolic substrate flux. However, there has been no comprehensive study on the acute effects of individual sugars on the genome wide gene expression that may reveal the genetic changes altering signaling pathways, subsequent metabolic processes and ultimately physiological/pathological responses. Considering that gene expressions in response to acute carbohydrate ingestion might be different in nutrient sensitive and insensitive mammals, we conducted comparative studies of genome wide gene expression by deep mRNA sequencing of the liver in nutrient sensitive C57BL/6J and nutrient insensitive BALB/cJ mice. Further to determine the temporal responses, we compared livers from mice in the fasted state and following ingestion of standard laboratory mouse chow supplemented with plain drinking water or water containing 20% glucose, sucrose or fructose. Supplementation with these carbohydrates induced unique extents and temporal changes in gene expressions in a strain specific manner. Fructose and sucrose stimulated gene changes peaked at 3 h postprandial, whereas glucose effects peaked at 12 h and 6 h postprandial in C57BL/6J and BABL/cJ mice, respectively. Network analyses revealed that fructose changed genes were primarily involved in lipid metabolism and were more complex in C57BL/6J than in BALB/cJ mice. These data demonstrate that there are qualitative and quantitative differences in the normal physiological responses of the liver between these two strains of mice and C57BL/6J is more sensitive to sugar intake than BALB/cJ.

Advanced Closed-Loop Control System Improves Postprandial Glycemic Control Compared With a Hybrid Closed-Loop System Following Unannounced Meal

<b>Objective:</b> Meals are a major hurdle to glycemic control in type 1 diabetes (T1D). Our objective was to test a fully-automated closed-loop control (CLC) system in the absence of announcement of carbohydrate ingestion among adolescents with T1D, who are known to commonly omit meal announcement. <p><b>Research Design and Methods: </b>Eighteen adolescents with T1D (age 15.6±1.7 years; HbA1c 7.4%±1.5; 9F/9M) participated in a randomized crossover clinical trial comparing our legacy hybrid CLC system (USS-Virginia) with a novel fully-automated CLC system (RocketAP), during two 46h supervised admissions (each with one announced and one unannounced dinner), following 2 weeks of data collection. Primary outcome was the percent time-in-range 70-180mg/dL (TIR) following the unannounced meal, with secondary outcomes related to additional CGM-based metrics.</p> <p><b>Results: </b> Both TIR and time-in-tight-range 70-140mg/dL (TTR) were significantly higher using RocketAP than using USS-Virginia during the 6h following the unannounced meal (83% [64-93] vs. 53% [40-71]; p=0.004 and 49% [41-59] vs. 27% [22-36]; p=0.002, respectively), primarily driven by reduced time-above-range (TAR >180mg/dL 17% [1.3-34] vs. 47% [28-60]), with no increase in time-below-range (TBR <70mg/dL 0% median for both). RocketAP also improved control following the announced meal (mean difference TBR: -0.7%, TIR: +7%, TTR: +6%), overall (TIR: +5%, TAR: -5%, TTR: +8%), and overnight (TIR: +7%, TTR: +19%, TAR: -5%). RocketAP delivered less insulin overall (78±23U vs. 85±20U, p=0.01)</p> <p><b>Conclusions:</b> A new fully-automated CLC system with automatic prandial dosing was proven to be safe and feasible and outperformed our legacy USS-Virginia in an adolescent population with and without meal announcement.</p>

Advanced Closed-Loop Control System Improves Postprandial Glycemic Control Compared With a Hybrid Closed-Loop System Following Unannounced Meal

<b>Objective:</b> Meals are a major hurdle to glycemic control in type 1 diabetes (T1D). Our objective was to test a fully-automated closed-loop control (CLC) system in the absence of announcement of carbohydrate ingestion among adolescents with T1D, who are known to commonly omit meal announcement. <p><b>Research Design and Methods: </b>Eighteen adolescents with T1D (age 15.6±1.7 years; HbA1c 7.4%±1.5; 9F/9M) participated in a randomized crossover clinical trial comparing our legacy hybrid CLC system (USS-Virginia) with a novel fully-automated CLC system (RocketAP), during two 46h supervised admissions (each with one announced and one unannounced dinner), following 2 weeks of data collection. Primary outcome was the percent time-in-range 70-180mg/dL (TIR) following the unannounced meal, with secondary outcomes related to additional CGM-based metrics.</p> <p><b>Results: </b> Both TIR and time-in-tight-range 70-140mg/dL (TTR) were significantly higher using RocketAP than using USS-Virginia during the 6h following the unannounced meal (83% [64-93] vs. 53% [40-71]; p=0.004 and 49% [41-59] vs. 27% [22-36]; p=0.002, respectively), primarily driven by reduced time-above-range (TAR >180mg/dL 17% [1.3-34] vs. 47% [28-60]), with no increase in time-below-range (TBR <70mg/dL 0% median for both). RocketAP also improved control following the announced meal (mean difference TBR: -0.7%, TIR: +7%, TTR: +6%), overall (TIR: +5%, TAR: -5%, TTR: +8%), and overnight (TIR: +7%, TTR: +19%, TAR: -5%). RocketAP delivered less insulin overall (78±23U vs. 85±20U, p=0.01)</p> <p><b>Conclusions:</b> A new fully-automated CLC system with automatic prandial dosing was proven to be safe and feasible and outperformed our legacy USS-Virginia in an adolescent population with and without meal announcement.</p>

Advanced Closed Loop Control System Improves Postprandial Glycemic Control Compared to a Hybrid Closed-Loop System Following Unannounced Meal

<b>Objective:</b> Meals are a major hurdle to glycemic control in type 1 diabetes (T1D). Our objective was to test a fully-automated closed-loop control (CLC) system in the absence of announcement of carbohydrate ingestion among adolescents with T1D, who are known to commonly omit meal announcement. <p><b>Research Design and Methods: </b>Eighteen adolescents with T1D (age 15.6±1.7 years; HbA1c 7.4%±1.5; 9F/9M) participated in a randomized crossover clinical trial comparing our legacy hybrid CLC system (USS-Virginia) with a novel fully-automated CLC system (RocketAP), during two 46h supervised admissions (each with one announced and one unannounced dinner), following 2 weeks of data collection. Primary outcome was the percent time-in-range 70-180mg/dL (TIR) following the unannounced meal, with secondary outcomes related to additional CGM-based metrics.</p> <p><b>Results: </b> Both TIR and time-in-tight-range 70-140mg/dL (TTR) were significantly higher using RocketAP than using USS-Virginia during the 6h following the unannounced meal (83% [64-93] vs. 53% [40-71]; p=0.004 and 49% [41-59] vs. 27% [22-36]; p=0.002, respectively), primarily driven by reduced time-above-range (TAR >180mg/dL 17% [1.3-34] vs. 47% [28-60]), with no increase in time-below-range (TBR <70mg/dL 0% median for both). RocketAP also improved control following the announced meal (mean difference TBR: -0.7%, TIR: +7%, TTR: +6%), overall (TIR: +5%, TAR: -5%, TTR: +8%), and overnight (TIR: +7%, TTR: +19%, TAR: -5%). RocketAP delivered less insulin overall (78±23U vs. 85±20U, p=0.01)</p> <p><b>Conclusions:</b> A new fully-automated CLC system with automatic prandial dosing was proven to be safe and feasible and outperformed our legacy USS-Virginia in an adolescent population with and without meal announcement.</p>

Initiating aerobic exercise with low glycogen content reduces markers of myogenesis but not mTORC1 signaling

Background The effects of low muscle glycogen on molecular markers of protein synthesis and myogenesis before and during aerobic exercise with carbohydrate ingestion is unclear. The purpose of this study was to determine the effects of initiating aerobic exercise with low muscle glycogen on mTORC1 signaling and markers of myogenesis. Methods Eleven men completed two cycle ergometry glycogen depletion trials separated by 7-d, followed by randomized isocaloric refeeding for 24-h to elicit low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate, 1.0 g/kg fat) glycogen. Participants then performed 80-min of cycle ergometry (64 ± 3% VO2peak) while ingesting 146 g carbohydrate. mTORC1 signaling (Western blotting) and gene transcription (RT-qPCR) were determined from vastus lateralis biopsies before glycogen depletion (baseline, BASE), and before (PRE) and after (POST) exercise. Results Regardless of treatment, p-mTORC1Ser2448, p-p70S6KSer424/421, and p-rpS6Ser235/236 were higher (P < 0.05) POST compared to PRE and BASE. PAX7 and MYOGENIN were lower (P < 0.05) in LOW compared to AD, regardless of time, while MYOD was lower (P < 0.05) in LOW compared to AD at PRE, but not different at POST. Conclusion Initiating aerobic exercise with low muscle glycogen does not affect mTORC1 signaling, yet reductions in gene expression of myogenic regulatory factors suggest that muscle recovery from exercise may be reduced.

Effects of two different doses of carbohydrate ingestion on taekwondo-related performance during a simulated tournament

Background Carbohydrate (CHO) ingestion enhances exercise performance; however, the efficacy of CHO intake on repeated bouts of exercise simulating a taekwondo tournament is unknown. Therefore, the purpose was to compare the effects of two different doses of CHO on a sports-specific kicking test during a simulated taekwondo tournament compared to placebo (PLA). Methods In a double-blind, randomized-placebo controlled, cross-over trial, eleven junior male professional taekwondo athletes (age: 16 ± 0.8 years, body mass: 55.3 ± 7.3 kg) ingested one of three solutions: (i) high dose (C45): 45 g of CHO (60 g∙h− 1), (ii) low dose (C22.5): 22.5 g of CHO (30 g∙h− 1; both solutions containing 2:1 glucose:fructose), or a PLA immediately following each kicking test. The kicking test was repeated 5 times, separated by 45 mins of rest, simulating a typical taekwondo competition day. Ratings of perceived exertion (RPE) and gastrointestinal discomfort (GI) scores were collected immediately after, and blood glucose before each test. Results The results revealed that C45 and C22.5 did not improve total, successful, or percentage of successful kicks compared to PLA (p > 0.05). Blood glucose was significantly higher following both CHO conditions compared with PLA across all five tests (p < 0.05). There were no differences between treatments or across tests for RPE (p > 0.05). Conclusion CHO intake, independent of the dose, did not alter taekwondo kick performance during a simulated taekwondo tournament.