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The present study describes the glucose content of 35 Arabian date fruit varieties, that were collected randomly from Saudi Arabian local markets in 2019. Date samples were analyzed for moisture and glucose contents. Using SP-3000nano UV-VIS Spectrophotometer (Optima, japan). In general, the moisture contents ranged from 7.3±0.11 to 29.2±0.13 g/100g fresh weight (FW), with Safawi samples being the highest. Whereas the analyzed date varieties were found to be variable in the glucose content with Rawthanat Alqasim (83.09±0.46 mg/dL) was found to have the highest glucose content , followed by the Sukari Alriyad (80.42±0.47 mg/dL) and Alkhanizi (51.05±0.94 mg/dL) varieties while the others had relatively low glucose contents with Shuqara (24.78±0.57 mg/dL) being the lowest. These information’s can help balancing a healthy diet, specifically for diabetic patients and the effect of glucose consumption in their daily life. And to highlight the different date varieties’ in Saudi arabian as one of the biggest countries in dates production around the world, and compare the differences in their weight and glucose content.

Dual chamber (DC) peritoneal dialysis (PD) dialysates contain fewer glucose degradation products (GDPs), so potentially reducing advanced glycosylation end products (AGEs), which have been reported to increase inflammation and cardiovascular risk. We wished to determine whether use of DC dialysates resulted in demonstrable patient benefits. Biochemical profiles, body composition, muscle strength, and skin autofluorescence measurements of tissue AGEs (SAF) were compared in patients using DC and standard single chamber dialysates. We studied 263 prevalent PD patients from 2 units, 62.4% male, mean age 61.8 ± 16.1 years, 78 (29.7%) used DC dialysates. DC patients were younger (55.9 ± 16.4 vs. 64.2 ± 15.4 years), and more had lower Davies comorbidity score (median 1 (0-1) vs. 1 (0, 2)), slower peritoneal transport (D/P creatinine 0.67 ± 0.12 vs. 0.73 ± 0.13), greater extracellular water-to-total body water (ECW/TBW) ratio (0.46 ± 0.05 vs. 0.42 ± 0.06), all P < .001, whereas there were no differences in the duration of PD (median (IQR) 19 (8-32) vs. 14 (8-23) months), residual renal function (Kt/Vurea 0.71 ± 0.71 vs. 0.87 ± 0.82), urine volume (642 (175-1200) vs. 648 (300-1200) mL/day), hand grip strength (26.9 ± 10.5 vs. 24.9 ± 10.7 kg), C-reactive protein (4(1-10) vs. 4(2-12) mg/L), and SAF (median 3.60 (3.02, 4.40) vs. 3.50 (3.00, 4.23)) AU. In our cross-sectional observational study, we were not able to show a demonstrable advantage for using low GDP dialysates over conventional glucose dialysates, in terms of biochemical profiles, residual renal function, muscle strength, or tissue AGE deposition. More patients using low GDP dialysates were slower peritoneal transporters with higher ECW/TBW ratios.

Aims/Introduction In Japan, an insulin pump with predictive low‐glucose management (PLGM) was launched in 2018. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. The aim of this study was to analyze the safety and efficacy of PLGM in patients treated in a Japanese center. Materials and Methods We carried out a retrospective observational analysis of 16 patients with type 1 diabetes mellitus and one patient after pancreatectomy. They switched from the MiniMed 620G device to the 640G device with PLGM. The primary outcome was the change in the percentage of time in hypoglycemia. The secondary outcome was the change in HbA1c (%) over a period of 3 months. We also explored the presence of “post‐suspend hyperglycemia” with the 640G device. Results After changing to the 640G device, the percentage of time in hypoglycemia (glucose 180 mg/dL) significantly increased from 25.53% (15.78–44.14%) to 32.9% (24.71–45.49%; P = 0.0373). HbA1c significantly increased from 7.6 ± 1.0% to 7.8 ± 1.1% (P = 0.0161). From 1.5 to 4.5 h after the resumption of insulin delivery, the percentage of time in hyperglycemia was 32.23% (24.2–53.75%), but it was significantly lower, 2.78% (0–21.6%), when patients manually restarted the pump within 30 min compared with automatic resumption 31.2% (20–61.66%; P = 0.0063). Conclusions Predictive low‐glucose management is an effective tool for reducing hypoglycemia, but possibly elicits “post‐suspend hyperglycemia.” This information is useful for achieving better blood glucose control in the patients treated with PLGM., An insulin pump with predictive low‐glucose management was launched in 2018 in Japan. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. Predictive low‐glucose management is an effective tool for reducing hypoglycemia, but possibly elicits “post‐suspend hyperglycemia.”

The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.

Flat oral glucose tolerance test (OGTT) curve is characterized by low glucose levels, seemingly nonresponsive to glucose load. Few studies have explored flat OGTT during pregnancy and have yielded conflicting results, some suggesting risk for fetal growth restriction. This study evaluated the characteristics and perinatal outcomes of women with a flat OGTT during pregnancy. We found that a flat OGTT curve occurs in younger, leaner pregnant women. Also, flat OGTT curve was significantly associated with a male fetus and higher levels of pregnancy-associated plasma protein A at the first-trimester screening. Although flat OGTT can possibly reflect some degree of hyperinsulinemia, it is generally not associated with adverse maternal or neonatal outcomes.

Continuous glucose monitors (CGMs) for the non-invasive monitoring of diabetes are constantly being developed and improved. Although there are multiple biosensing platforms for monitoring glucose available on the market, there is still a strong need to enhance their precision, repeatability, wearability, and accessibility to end-users. Biosensing technologies are being increasingly explored that use different bodily fluids such as sweat and tear fluid, etc., that can be calibrated to and therefore used to measure blood glucose concentrations accurately. To improve the wearability of these devices, exploring different fluids as testing mediums is essential and opens the door to various implants and wearables that in turn have the potential to be less inhibiting to the wearer. Recent developments have surfaced in the form of contact lenses or mouthguards for instance. Challenges still present themselves in the form of sensitivity, especially at very high or low glucose concentrations, which is critical for a diabetic person to monitor. This review summarises advances in wearable glucose biosensors over the past 5 years, comparing the different types as well as the fluid they use to detect glucose, including the CGMs currently available on the market. Perspectives on the development of wearables for glucose biosensing are discussed.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control human β-cell insulin secretion. Here, we examined if HCN channels impact glucagon-like-peptide 1 (GLP-1) receptor modulation of islet Ca2+ handling. We found that Liraglutide (100nM LIRA), a GLP-1 analog, increased mouse β-cell Ca2+ oscillation frequency and cAMP levels in high (11 mM) but not low glucose. Similarly, a subset of human β-cells (65%) show LIRA-induced elevations in Ca2+ oscillation frequency (by 70%, P Disclosure K. E. Zaborska: None. K. L. Jordan: None. P. Dadi: None. M. Dickerson: None. S. M. Graff: None. D. Jacobson: None.

Chronic meningoencephalitis is caused by Cryptococcus neoformans and is treated in many parts of the world with fluconazole (FLC) monotherapy, which is associated with treatment failure and poor outcome. In the host, C. neoformans propagates predominantly under low glucose growth conditions. We investigated whether low glucose, mimicked by growing in synthetic media (SM) with 0.05% glucose (SMlowglu), affects FLC-resistance. A &gt, 4-fold increase in FLC tolerance was observed in seven C. neoformans strains when minimum inhibitory concentration (MIC) was determined in SMlowglu compared to MIC in SM with normal (2%) glucose (SMnlglu). In SMlowglu, C. neoformans cells exhibited upregulation of efflux pump genes AFR1 (8.7-fold) and AFR2 (2.5-fold), as well as decreased accumulation (2.6-fold) of Nile Red, an efflux pump substrate. Elevated intracellular ATP levels (3.2-fold and 3.4-fold), as well as decreased mitochondrial reactive oxygen species levels (12.8-fold and 17-fold), were found in the presence and absence of FLC, indicating that low glucose altered mitochondrial function. Fluorescence microscopy revealed that mitochondria of C. neoformans grown in SMlowglu were fragmented, whereas normal glucose promoted a reticular network of mitochondria. Although mitochondrial membrane potential (MMP) was not markedly affected in SMlowglu, it significantly decreased in the presence of FLC (12.5-fold) in SMnlglu, but remained stable in SMlowglu-growing C. neoformans cells. Our data demonstrate that increased FLC tolerance in low glucose-growing C. neoformans is the result of increased efflux pump activities and altered mitochondrial function, which is more preserved in SMlowglu. This mechanism of resistance is different from FLC heteroresistance, which is associated with aneuploidy of chromosome 1 (Chr1).

Low glucose levels during exercise may lead to hypoglycemia, which can have grave consequences in diabetic athletes. Mobile colorimetric wearable biosensors that measure glucose levels in sweat are ideal for self-monitoring as they can utilize the camera in smartphones for signal reading. However, colorimetric biosensors proposed thus far have higher limit of detection (LOD) than electrochemical devices, which makes them unsuitable for detecting hypoglycemia. In this manuscript we describe colorimetric wearable biosensors that detect glucose in sweat with an LOD of 0.01 mM and a dynamic range up to 0.15 mM. The devices are made of filter paper and incorporate a sweat volume sensor and a color chart for signal correction. The biosensors do not suffer from interferences originated by delayed sample readings, or differences in bending angle and sample pH. When applied to volunteers performing an exercise routine, sweat glucose levels corrected with sweat volume measurements correlated well with blood glucose measurements performed with a commercial device. The devices are lightweight and easily disposable. These features, along with the smartphone-based colorimetric readout, makes them promising as "over-the-counter" tests for measuring glucose levels non-invasively during exercise.

Aims/introduction The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients. Materials and methods We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G. Results The area under the curve (AUC) of hypoglycemia of 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided. Conclusions The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption.

Objectives To assess the optimal setting of the predictive low glucose management (PLGM) algorithm for preventing exercise-induced hypoglycemia in adolescents with type 1 diabetes. Methods Thirty-four adolescents, 15 to 20 years, wearing PLGM system, were followed during 3 days exercise during a diabetes camp. PLGM threshold was set at 70 mg/dL between 8 am and 10 pm and 90 mg/dL during 10 pm and 8 am Adolescents were divided into group A and B, with PLGM threshold at 90 and 70 mg/dL, respectively, during exercise. Time spent in hypoglycemia and AUC for time slots 8 am to 1 pm, 1 to 4 pm, 4 to 11 pm, 11 pm to 3 am, 3 to 8 am, in 3 days were compared between groups by Wilcoxon rank sum test. Results We analyzed 31 patients (median age 15.0 years, 58.1% males, median diabetes duration 7.0 years, hemoglobin A1c [HbA1c] 7.1%). No significant difference has been observed in time spent in hypoglycemia between groups using threshold 70 or 90. Time spent in target was similar in both groups, as well as time spent in hypo or hyperglycemia. The trends of blood glucose over the 3 days in the 2 groups over-lapped without significant differences. Conclusions A PLGM threshold of 90 mg/dL during the night was associated with reduced time in hypoglycemia in adolescents doing frequent physical exercise, while maintaining 65.1% time in range during the day. However, a threshold of 70 mg/dL seems to be safe in the duration of the physical exercise. PLGM system in adolescents with type 1 diabetes was effective to prevent hypoglycemia during and after exercise, irrespective of the PLGM thresholds used.

Background: Sensor-integrated pump systems with low-glucose suspend (also known as threshold suspend) functions have markedly transformed the management of type 1 diabetes, but most studies to date have excluded patients at high risk of hypoglycemia. The SMILE study is investigating the efficacy of the MiniMed™ 640G insulin pump with the SmartGuard™ predictive low-glucose management (PLGM) feature in the prevention of hypoglycemia in adults with type 1 diabetes, who are at high risk of hypoglycemia. Methods: SMILE is a prospective, randomized, open-label, controlled trial being undertaken in four European countries and Canada. Following a 2-week run-in phase, eligible participants will be randomized to use either the MiniMed 640G system with continuous glucose monitoring (CGM) and the SmartGuard PLGM feature on continuously for 24 weeks (treatment arm), or the MiniMed 640G without CGM and with blinded continuous glucose measurements between weeks 10-12, 16-18, and 22-24 (control arm). The primary endpoint is the mean number of hypoglycemic events, defined as sensor glucose ≤55 mg/dL (≤3.0 mmol/L) for >20 consecutive minutes. Secondary endpoints include various glycemic indices in the hypoglycemic and hyperglycemic ranges, as well as glycated hemoglobin. Data on patient-reported outcomes such as hypoglycemia awareness and treatment satisfaction will also be collected. Conclusions: It is anticipated that the SMILE study will provide important insights into the effectiveness of SmartGuard technology in adult patients with type 1 diabetes.

Aims/hypothesis Hypoglycaemia is a major barrier to good glucose control in type 1 diabetes. Frequent hypoglycaemic episodes impair awareness of subsequent hypoglycaemic bouts. Neural changes underpinning awareness of hypoglycaemia are poorly defined and molecular mechanisms by which glial cells contribute to hypoglycaemia sensing and glucose counterregulation require further investigation. The aim of the current study was to examine whether, and by what mechanism, human primary astrocyte (HPA) function was altered by acute and recurrent low glucose (RLG). Methods To test whether glia, specifically astrocytes, could detect changes in glucose, we utilised HPA and U373 astrocytoma cells and exposed them to RLG in vitro. This allowed measurement, with high specificity and sensitivity, of RLG-associated changes in cellular metabolism. We examined changes in protein phosphorylation/expression using western blotting. Metabolic function was assessed using a Seahorse extracellular flux analyser. Immunofluorescent imaging was used to examine cell morphology and enzymatic assays were used to measure lactate release, glycogen content, intracellular ATP and nucleotide ratios. Results AMP-activated protein kinase (AMPK) was activated over a pathophysiologically relevant glucose concentration range. RLG produced an increased dependency on fatty acid oxidation for basal mitochondrial metabolism and exhibited hallmarks of mitochondrial stress, including increased proton leak and reduced coupling efficiency. Relative to glucose availability, lactate release increased during low glucose but this was not modified by RLG. Basal glucose uptake was not modified by RLG and glycogen levels were similar in control and RLG-treated cells. Mitochondrial adaptations to RLG were partially recovered by maintaining euglycaemic levels of glucose following RLG exposure. Conclusions/interpretation Taken together, these data indicate that HPA mitochondria are altered following RLG, with a metabolic switch towards increased fatty acid oxidation, suggesting glial adaptations to RLG involve altered mitochondrial metabolism that could contribute to defective glucose counterregulation to hypoglycaemia in diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-018-4744-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

We thank Seibold (1) for his interest in our randomized study comparing real-time CGM (rtCGM) and intermittently scanned CGM (isCGM) in patients with type 1 diabetes (T1D) and normal hypoglycemia awareness during physical activity and over the subsequent home phase (2). We acknowledge the challenges associated with using outcomes from the isCGM (FreeStyle Libre) and rtCGM (Guardian Connect Mobile) devices in our study. Nevertheless, we disagree that this disqualifies any comparisons. It does, however, stimulate further discussion. We agree that different sensors may have different performance characteristics, especially at low glucose range (3). However, there are more similarities in hyperglycemia (3). In fact, rtCGM was superior to isCGM not only in hypoglycemia but also in hyperglycemia (>10.0 mmol/L [>180 mg/dL] …

Impaired awareness of hypoglycaemia (IAH) affects between 25% and 30% of all people with type 1 diabetes (T1D) and markedly increases risk of severe hypoglycaemia. This greatly feared complication of T1D impairs quality of life and has a recognised morbidity. People with T1D have an increased propensity to hypoglycaemia as a result of fundamental physiological defects in their ability to respond appropriately to a fall in blood glucose levels. With repeated exposure to low glucose, many then develop a condition referred to as IAH, where there is a reduced ability to perceive the onset of hypoglycaemia and take appropriate corrective action. The management of individuals with IAH relies initially on its identification in the clinic through a detailed exploration of the frequency of hypoglycaemia and an assessment of the individual’s ability to recognise these episodes. In this review article, we will address the clinical strategies that may help in the management of the patient with IAH once identified, who may or may not also suffer from problematic hypoglycaemia. The initial focus is on how to identify such patients and then on the variety of approaches involving educational programmes and technological approaches that may be taken to minimise hypoglycaemia risk. No single approach can be advocated for all patients, and it is the role of the health care professional to identify the clinical strategy that best enables their patient to achieve this goal.

International audience; The main objective of diabetes control is to correct hyperglycaemia while avoiding hypoglycaemia, especially in insulin-treated patients. Fear of hypoglycaemia is a hurdle to effective correction of hyperglycaemia because it promotes under-dosing of insulin. Strategies to minimise hypoglycaemia include education and training for improved hypoglycaemia awareness and the development of technologies to allow their early detection and thus minimise their occurrence. Patients with impaired hypoglycaemia awareness would benefit the most from these technologies. The purpose of this systematic review is to review currently available or in-development technologies that support detection of hypoglycaemia or hypoglycaemia risk, and identify gaps in the research. Nanomaterial use in sensors is a promising strategy to increase the accuracy of continuous glucose monitoring devices for low glucose values. Hypoglycaemia is associated with changes on vital signs, so electrocardiogram and encephalogram could also be used to detect hypoglycaemia. Accuracy improvements through multivariable measures can make already marketed galvanic skin response devices a good noninvasive alternative. Breath volatile organic compounds can be detected by dogs and devices and alert patients at hypoglycaemia onset, while near-infrared spectroscopy can also be used as a hypoglycaemia alarms. Finally, one of the main directions of research are deep learning algorithms to analyse continuous glucose monitoring data and provide earlier and more accurate prediction of hypoglycaemia. Current developments for early identification of hypoglycaemia risk combine improvements of available 'needle-type' enzymatic glucose sensors and noninvasive alternatives. Patient usability will be essential to demonstrate to allow their implementation for daily use in diabetes management.

Understanding proteomic changes in the ischemic penumbra are crucial to rescue those salvageable cells and reduce the damage of an ischemic stroke. Since the penumbra region is dynamic with heterogeneous cells/tissues, tissue sampling from animal models of stroke for the molecular study is a challenge. In this study, cultured hippocampal HT22 cells under hypoxia treatment for 17.5 h with 0.69 mM low glucose (H+LG) could mimic ischemic penumbral cells since they had much higher cell viability and viable cell number compared to hypoxia without glucose (H-G) treatment. To validate established cell-based ischemic penumbral model and understand the beneficial effects of low glucose (LG), quantitative proteomics analysis was performed on H+LG, H-G, and normoxia with normal 22 mM glucose (N+G) treated cells. We identified 427 differentially abundant proteins (DAPs) between H-G and N+G and further identified 105 DAPs between H+LG and H-G. Analysis of 105 DAPs revealed that LG promotes cell survival by activating HIF1 alpha to enhance glycolysis; preventing the dysregulations of extracellular matrix remodeling, cell cycle and division, and antioxidant and detoxification; as well as attenuating inflammatory reaction response, protein synthesis and neurotransmission activity. Our results demonstrated that this established cell-based system could mimic penumbral conditions and can be used for molecular studies. National Institute of General Medical SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [SC1GM111178-01A1] This work was supported by grants from the National Institute of General Medical Sciences (SC1GM111178-01A1) to JX.

Our aim was to assess the potential of flash glucose monitoring (FGM) for diagnostic workup of suspected post-bariatric hypoglycaemia (PBH). Patients (N = 13) with suspected PBH underwent a food and symptoms diary (FSD) record along with FGM over 14 days. Targeted data analysis confirmed the occurrence of low glucose events in parallel to meal-triggered symptoms. Glycaemic variability, as assessed by Mean Absolute Glucose change (MAG change), was increased, while a higher risk of glycaemic excursions towards both hyper and hypoglycaemia (ADRRFGMGT) was observed in those with more frequent and severe hypoglycaemia. The herein described hypoglycaemia risk index (LBGIFGMGT) with a cut-off value of 4.6 showed to have 100% sensitivity and 100% specificity for PBH. This pilot proof-of-concept study highlighted that FSD coupled with FGM followed by targeted data analysis, provides relevant insights towards PBH diagnosis and grading in a user-friendly and easy to implement study protocol. Furthermore, LBGIFGMGT demonstrated to be an excellent index for PBH diagnosis. The unexpected improvement of glucose profile noticed along the monitoring time also unravels a possible application for PBH management. The authors thank the patients who have participated in the study for trusting the clinical team on the off-label approach endeavoured towards the management of their condition. The authors also acknowledge Rita Magalhães, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal, and Henrique Vasconcelos, Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal for technical assistance with software. UMIB is funded by FCT (UID/MULTI/0215/2016, UID/MULTI/0215/2019, UIDB/00215/2020 and UIDP/00215/2020)

Background: Automated insulin delivery systems improve glycemic control including time spent in, below and above range (TIR, TBR and TAR, respectively) in people with T1D. A next generation system, the MiniMedTM AHCL system, that offers a target set point (SP) of 100 or 120mg/dL, autocorrects to 120mg/dL every 5 mins and has fewer Auto Mode exits, was evaluated. Methods: A 16-site, single-arm, in-home trial of the AHCL system in 39 adolescents (14-21yrs) and 118 adults (≥22yrs) with T1D was conducted. After a baseline period of sensor-integrated pump, HCL feature, or predictive low glucose feature use (~14 days), the AHCL feature was enabled with a 100 or 120mg/dL SP for ~45 days and then the other SP for ~45 days. Study endpoints included safety events, change in A1C, sensor glucose (SG), %TIR, %TBR and %TAR. Results: There were no DKA or severe hypoglycemia episodes during the study period. Auto Mode was used ≥95% of the time; autocorrection was 22% of daily bolus. The table shows outcomes (mean±SD) for the overall group and each age group at baseline and study period (100 and 120mg/dL SP), and at the 100mg/dL SP. Best glycemic results (SG of 141±8.8mg/dL, TIR of 78.8±5.5% and TBR of 2.6±2.0%; N=29) were seen with a 100mg/dL SP and active insulin time of 120 minutes. Conclusion: These pivotal trial data demonstrate that AHCL is safe and significantly improved A1C and SG in subjects aged ≥14 years with T1D. Disclosure A.L. Carlson: Consultant; Self; Medtronic. Research Support; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S, Sanofi, UnitedHealth Group. B.W. Bode: Advisory Panel; Self; Medtronic, Novo Nordisk A/S. Consultant; Self; Eli Lilly and Company, Medtronic, Novo Nordisk A/S. Research Support; Self; Abbott, Advance, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, National Institutes of Health, Nova Biomedical, Novo Nordisk A/S, Provention Bio, Inc., Sanofi, Senseonics. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., MannKind Corporation, Medtronic, Novo Nordisk A/S, Sanofi, Senseonics. Stock/Shareholder; Self; Aseko. R.L. Brazg: None. M.P. Christiansen: Research Support; Self; Abbott, Ascensia Diabetes Care, Biolinq, Dexcom, Inc., Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk A/S, Sanofi-Aventis, Senseonics, ViroMed Laboratories, Xeris Pharmaceuticals, Inc. S.K. Garg: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Diagnostics France. Research Support; Self; Dexcom, Inc., Eli Lilly and Company, Medtronic. K. Kaiserman: Advisory Panel; Self; Medtronic. Consultant; Self; Medtronic. Research Support; Self; Medtronic. Speaker’s Bureau; Self; Medtronic. M. Kipnes: None. D.R. Liljenquist: None. A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Cecelia Health. Consultant; Self; Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi, T1D Exchange. D.I. Shulman: Advisory Panel; Self; Medtronic. K.K. Singh: None. R.H. Slover: None. J. Thrasher: Advisory Panel; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Board Member; Self; Medtronic. Consultant; Self; Medtronic. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Medtronic, Mylan, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Medtronic, Sanofi. X. Chen: Employee; Self; Medtronic. B. Grosman: Employee; Self; Medtronic. S.W. Lee: Employee; Self; Medtronic. L.J. Lintereur: Employee; Self; Medtronic. M. Liu: Employee; Self; Medtronic. N. Parikh: None. A.S. Rhinehart: Employee; Self; Glytec, Medtronic. Stock/Shareholder; Self; Dexcom, Inc., Glytec, Lexicon Pharmaceuticals, Inc., MannKind Corporation, Tandem Diabetes Care. F. Peng: None. A. Roy: Employee; Self; Medtronic. J. Shin: Employee; Self; Medtronic. D. Wu: None. R. Vigersky: Employee; Self; Medtronic.

Severe hypoglycemia (SH) is an acute complication of diabetes with potentially adverse clinical and psychosocial consequences. There is little published literature in terms of SH-related adverse events (AEs) in patients with type 1 diabetes (PwT1D) in a real-world setting. We recruited PwT1D who had recently started using the Tandem t:slim X2 insulin pump with Basal-IQ Predictive Low Glucose Suspend (PLGS). Amongst other measures, PwT1D reported SH-related AEs at baseline and then again at 6 months post-assessment (PA). Pre-Post differences were analyzed using Fisher’s exact test. In all, 665 PwT1D were included in the analysis (19% of these were Disclosure H. Singh: Employee; Self; Tandem Diabetes Care. M.L. Manning: Employee; Self; Tandem Diabetes Care. M. McElwee-Malloy: Employee; Self; Tandem Diabetes Care. S. Habif: Employee; Self; Tandem Diabetes Care.

We examined the impact of consuming biscuits with a beverage of powdered mulberry or barley leaves in the afternoon on postprandial glucose levels at dinnertime among young adults. A total of 18 young adults participated in a partially double-blinded, randomized crossover trial over 2 weeks, consuming either: (1) no biscuits, (2) a biscuit, (3) a biscuit with a beverage of powdered mulberry leaves, or (4) a biscuit with a beverage of powdered barley leaves, as an afternoon snack followed by a standardized test dinner. Glucose levels were recorded after each meal. Results showed intake of biscuits with a beverage of mulberry and barley leaves significantly reduced postprandial rises in glucose after their immediate consumption and dinner, though there was no direct relationship between the glucose levels at the two meals. Compared to those with low glucose levels, participants with high glucose levels at dinner showed a stronger second meal effect, that was attributed to the mulberry or barley leaves, and were also more likely to have lean body weights and prefer evenings. Our findings indicate that eating snacks alongside mulberry or barley leaves is an effective way to suppress postprandial glucose levels in young adults with high glucose levels who prefer evenings.

Astrocytes generate robust cytoplasmic calcium signals in response to reductions in extracellular glucose. This calcium signal, in turn, drives purinergic gliotransmission, which controls the activity of catecholaminergic (CA) neurons in the hindbrain. These CA neurons are critical to triggering glucose counter-regulatory responses (CRRs) that, ultimately, restore glucose homeostasis via endocrine and behavioral means. Although the astrocyte low-glucose sensor involvement in CRR has been accepted, it is not clear how astrocytes produce an increase in intracellular calcium in response to a decrease in glucose. Our ex vivo calcium imaging studies of hindbrain astrocytes show that the glucose type 2 transporter (GLUT2) is an essential feature of the astrocyte glucosensor mechanism. Coimmunoprecipitation assays reveal that the recombinant GLUT2 binds directly with the recombinant Gq protein subunit that activates phospholipase C (PLC). Additional calcium imaging studies suggest that GLUT2 may be connected to a PLC-endoplasmic reticular-calcium release mechanism, which is amplified by calcium-induced calcium release (CICR). Collectively, these data help outline a potential mechanism used by astrocytes to convert information regarding low-glucose levels into intracellular changes that ultimately regulate the CRR.

Postbariatric hypoglycemia (PBH) is a complication of bariatric surgery with limited therapeutic options. We developed an event-based system to predict and detect hypoglycemia based on continuous glucose monitor (CGM) data and recommend delivery of minidose liquid glucagon.We performed an iterative development clinical study employing a novel glucagon delivery system: a Dexcom CGM connected to a Windows tablet running a hypoglycemia prediction algorithm and an Omnipod pump filled with an investigational stable liquid glucagon formulation. Meal tolerance testing was performed in seven participants with PBH and history of neuroglycopenia. Glucagon was administered when hypoglycemia was predicted. Primary outcome measures included the safety and feasibility of this system to predict and prevent severe hypoglycemia. Secondary outcomes included hypoglycemia prediction by the prediction algorithm, minimization of time below hypoglycemia threshold using glucagon, and prevention of rebound hyperglycemia.The hypoglycemia prediction algorithm alerted for impending hypoglycemia in the postmeal state, prompting delivery of glucagon (150 μg). After observations of initial incomplete efficacy to prevent hypoglycemia in the first two participants, system modifications were implemented: addition of PBH-specific detection algorithm, increased glucagon dose (300 μg), and a second glucagon dose if needed. These modifications, together with rescue carbohydrates provided to some participants, contributed to progressive improvements in glucose time above the hypoglycemia threshold (75 mg/dL).Preliminary results indicate that our event-based automatic monitoring algorithm successfully predicted likely hypoglycemia. Minidose glucagon therapy was well tolerated, without prolonged or severe hypoglycemia, and without rebound hyperglycemia.

Background Predictive alerts for impending hypoglycemic events enable persons with type 1 diabetes to take preventive actions and avoid serious consequences. Objective This study aimed to develop a prediction model for hypoglycemic events with a low false alert rate, high sensitivity and specificity, and good generalizability to new patients and time periods. Methods Performance improvement by focusing on sustained hypoglycemic events, defined as glucose values less than 70 mg/dL for at least 15 minutes, was explored. Two different modeling approaches were considered: (1) a classification-based method to directly predict sustained hypoglycemic events, and (2) a regression-based prediction of glucose at multiple time points in the prediction horizon and subsequent inference of sustained hypoglycemia. To address the generalizability and robustness of the model, two different validation mechanisms were considered: (1) patient-based validation (model performance was evaluated on new patients), and (2) time-based validation (model performance was evaluated on new time periods). Results This study utilized data from 110 patients over 30-90 days comprising 1.6 million continuous glucose monitoring values under normal living conditions. The model accurately predicted sustained events with >97% sensitivity and specificity for both 30- and 60-minute prediction horizons. The false alert rate was kept to Conclusions Providing alerts focused on sustained events instead of all hypoglycemic events reduces the false alert rate and improves sensitivity and specificity. It also results in models that have better generalizability to new patients and time periods.

Aims/Introduction Overproduction of reactive oxygen species (ROS) in endothelial cells (ECs) plays a pivotal role in endothelial dysfunction. Mitochondrial ROS (mtROS) is one of the key players in the pathogenesis of diabetic vascular complications. Hypoglycemia is linked to increased ROS production and vascular events; however, the underlying mechanisms remain unclear. In the present study, we aimed to determine whether and how low glucose (LG) mediates mtROS generation in ECs, and to examine the impact of LG-induced mtROS on endothelial dysfunction. Materials and Methods Metabolomic profiling, cellular oxygen consumption rate, mtROS, endothelial nitric oxide synthase phosphorylation, and the expression of vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 were evaluated in bovine aortic ECs. Results We found that LG increased mtROS generation in ECs; which was suppressed by overexpression of manganese superoxide dismutase. Comprehensive metabolic analysis using capillary electrophoresis-mass spectrometry and oxygen consumption rate assessment showed that the pathway from fatty acid to acetyl-CoA through fatty acid oxidation was upregulated in ECs under LG conditions. In addition, etomoxir, a specific inhibitor of the free fatty acid transporter, decreased LG-induced mtROS production. These results suggested that LG increased mtROS generation through activation of fatty acid oxidation. We further revealed that LG inhibited endothelial nitric oxide synthase phosphorylation, and increased the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. These effects were suppressed either by overexpression of manganese superoxide dismutase or by treatment with etomoxir. Conclusions The activation of fatty acid oxidation followed by mtROS production could be one of the causes for endothelial dysfunction during hypoglycemia.

Neonatal hypoglycaemia is common, and screening and treatment of babies considered at risk is widespread, despite there being little reliable evidence upon which to base management decisions. Although there is now evidence about which babies are at greatest risk, the threshold for diagnosis, best approach to treatment and later outcomes all remain uncertain. Recent studies suggest that treatment with dextrose gel is safe and effective and may help support breast feeding. Thresholds for intervention require a wide margin of safety in light of information that babies with glycaemic instability and with low glucose concentrations may be associated with a higher risk of later higher order cognitive and learning problems. Randomised trials are urgently needed to inform optimal thresholds for intervention and appropriate treatment strategies.