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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.

Background Neonatal hypoglycemia is a common and treatable risk factor for neurological impairment. Real-time continuous glucose monitoring (RT-CGM) can show glucose concentration in real time. Using an RT-CGM alarm, physicians can be alerted and intervene in hypoglycemia. No reports, however, have evaluated the reliability of RT-CGM at low glucose levels in infants. This study therefore investigated the difference between blood glucose (BG) and RT-CGM sensor data at low glucose levels and assessed the optimum method of using a hypoglycemic alarm in infants. Methods We enrolled infants whose glycemic management was difficult. We calculated the mean absolute difference (MAD) and mean absolute relative difference (MARD) between BG and RT-CGM sensor data. We compared the MAD and MARD between the low BG fluctuation and high BG fluctuation groups. Results We used RT-CGM for 12 patients (29 times) and investigated 448 pairs of BG and RT-CGM sensor data. The MAD between these pairs was 9.3 ± 8.9 mg/dL, and the MARD was 11.5%. The MAD at low glucose was 7.7 ± 6.0 mg/dL, and the MARD was 16.2%. The MAD and MARD were 6.8 ± 5.4 mg/dL and 7.8% in the low fluctuation group and 10.1 ± 9.5 mg/dL and 12.7% in the high fluctuation group, respectively. Conclusions The difference between BG and RT-CGM sensor data changes with the degree of fluctuation in BG. When physicians set the hypoglycemic alarm, consideration of this difference and a change in the alarm setting according to the degree of fluctuation in BG may be useful.

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.

Autonomic nervous system (ANS) can maintain homeostasis through the coordination of different organs including heart. The change of blood glucose (BG) level can stimulate the ANS, which will lead to the variation of Electrocardiogram (ECG). Considering that the monitoring of different BG ranges is significant for diabetes care, in this paper, an ECG-based technique was proposed to achieve non-invasive monitoring with three BG ranges: low glucose level, moderate glucose level, and high glucose level. For this purpose, multiple experiments that included fasting tests and oral glucose tolerance tests were conducted, and the ECG signals from 21 adults were recorded continuously. Furthermore, an approach of fusing density-based spatial clustering of applications with noise and convolution neural networks (DBSCAN-CNN) was presented for ECG preprocessing of outliers and classification of BG ranges based ECG. Also, ECG's important information, which was related to different BG ranges, was graphically visualized. The result showed that the percentages of accurate classification were 87.94% in low glucose level, 69.36% in moderate glucose level, and 86.39% in high glucose level. Moreover, the visualization results revealed that the highlights of ECG for the different BG ranges were different. In addition, the sensitivity of prediabetes/diabetes screening based on ECG was up to 98.48%, and the specificity was 76.75%. Therefore, we conclude that the proposed approach for BG range monitoring and prediabetes/diabetes screening has potentials in practical applications.

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.

Goat production is central to resource-poor rural livelihoods in the tropics. However, it is constrained by high inbreeding levels and poor access to good quality breeding bucks. In this study, semen extenders differing in egg yolk and energy level were compared in their ability to maintain liquid semen from a tropical goat breed, when stored at physiological (37 °C) or refrigerator (4 °C) temperature. Semen was collected weekly for nine weeks from seven bucks of the Small East African goat breed, diluted in three extenders and incubated at 37 °C or 4 °C for 24 h. The semen parameters: viability, motility and morphology were better preserved when semen was incubated at 4 °C compared to 37 °C across all extenders. Sperm motility after 24 h at 4 °C was 50.4 ± 5.5%, 50.4 ± 6.2% and 54.3 ± 5.4% for Extender 1 (high glucose, 18% egg yolk), Extender 2 (low glucose, 2.5% egg yolk) and Extender 3 (low fructose, no egg yolk), respectively. Extender 2 maintained significantly higher viability values (67.7 ± 2.5%) at 24 h compared to Extenders 3 (59.3 ± 2.1%) and 1 (46.7 ± 4.2%). Normal morphology after 24 h (88.1 ± 3.1% at 4 °C and 85.6 ± 3.1% at 37 °C) fell within the acceptable range for good quality semen. Acceptable quality was maintained within 8 h and up to 24 h from collection for non-frozen goat semen stored at 37 °C and 4 °C temperature, respectively. These results imply that Small East African goat semen diluted in low or non-egg yolk based extenders and stored at refrigerator temperature can be valuable for artificial reproduction of native goats on low resource capacity farms in developing countries.

Hollow Ni-Al-Mn triple layered hydroxide (HLTH) nanocomposite is used for developing a sensitive nonenzymatic electrochemical glucose sensor. Electrochemical studies of HLTH modified nickel foam (NF) possess a remarkable sensing activity towards glucose oxidation with a wide range of detection from 0.015 mM to 8 mM. The sensors show a superior sensitivity of 2.253 mA mM−1 cm−2 with a low glucose detection limit of 1.49 μM (S/N = 3). The fast response time of electrode is

Background/aim Prevention of hypoglycemia remains a major challenge in diabetic management, despite the introduction of modern insulin pumps in daily clinical practice. The Low Glucose Suspend (LGS) and the newer Predictive Low Glucose Management (PLGM) systems incorporated in the Medtronic insulin pumps have shown promising results in prevention of hypoglycemia. Our aim was to evaluate the effect of the 2 systems relative to the frequency of clinically significant hypoglycemia in Type 1 diabetes (T1DM). In addition, we investigated the events preceding clinically significant hypoglycemia episodes. Methods A cross-sectional study was conducted in 30 T1DM patients using the MiniMed 640G vs. 30 using the MiniMed Veo sensor-augmented insulin pump. All data was recorded during patients’ normal daily activity and living conditions. The patients were matched for age and duration of diabetes. Results PLGM use was associated with lower incidence of clinically significant hypoglycemia (1.9±1.4 vs. 3.6±1.9 episodes per week), along with reduced exposure to hypoglycemia. The data indicated that both pump systems are effective in preventing severe hypoglycemic episodes. In both groups the most common events preceding hypoglycemic episodes included adjustment of hyperglycemia, basal rate increase and miscalculation of carbohydrates. Conclusions The results indicated that the use of the Minimed 640G pump system can help reduce the frequency of clinically significant hypoglycemia. Management of hyperglycemia must be addressed in diabetes education programs in order to encourage proper adjustment of high blood glucose levels. Future studies would be useful in exploring the details of the events preceding hypoglycemia episodes in insulin pump users.

Objective: To discuss the effect of EGFR-mTOR signal way in the adaption of cervical carcinoma cell in low glucose and high lactic acid. Methods: Hela cells were cultured in four conditions: normal glucose (NG, glucose 10 mmol/L), low glucose (LG, glucose 3 mmol/L), high lactic acid (HL, lactic acid 2.5 mmol/L) and low glucose and high lactic acid (LGHL, glucose 10 mmol/L, lactic acid 2.5 mmol/L). Growth inhibitory rate of Hela cell was determined by CCK-8; Flow cytometry (FCM) was performed to evaluate the cell cycle; Results: Compared with the rate in NG, the rate in low glucose and high lactic acid was significantly increased (P < 0.01). Compared with the rate in NG, the rate of G1/G0 was increased in HL and in LGHL (P < 0.01, P < 0.01); the rate of G1/G0 in LG didn't have significant difference; the rates of G2/M in HL and in LGHL were decreased, and the G2/M rate in LG was increased, but all of them had no statistically significant. The rates of S were decreased in HL, LG and LGHL (P < 0.05, no statistically significant, P < 0.05). The expression level of EGFR mRNA in Hela was decreased and the level of mTOR mRNA was increased in HL (both had no statistically significant), when compared with the levels in NG. The expression level of EGFR mRNA was decreased (P < 0.05) and the level of mTOR mRNA was a little increased (no statistically significant) in LG; while the EGFR and mTOR expression levels were increased in LGHL (P < 0.05). Conclusion: Low glucose and high lactic acid environment is conducive to Hela cell survival, and can promote the expression of EGFR and mTOR.

Due to the increasing demand and interest of the consumers of bracatinga honeydew honey, it becomes important to know its characteristics in order to guarantee the quality of this dark honey. It is also necessary to investigate possible parameters that easily determine their differentiation from other honeys, thus guaranteeing their authenticity. Therefore, in the present study, the physicochemical characteristics and the reducing/scavenging proprieties of 16 bracatinga (Mimosa scabrella Bentham) honeydew honey samples and 25 blossom honey (different botanical origin) samples from Santa Catarina, Brazil, were investigated. Bracatinga honeydew honeys were defined by its high free acidity, electrical conductivity and reducing/scavenging capacity, and low glucose content.Still, these specific parameters allowed the differentiation between bracatinga honeydew honeys and blossom honeys, from the of principal component analysis, contributing to the differentiation of these honeys.

Objective: To explore on the antitumor effect of gefitinib and rapamycin and possible mechanism in normal glucose and high lactic acid microenvironment. Methods: Hela cells are cultured in six conditions: the normal glucose group (NG, glucose 3 mmol/L); the normal glucose + gefitinib group (NGG, glucose 3 mmol/L, gefitinib 2.67 μmol/L); the normal glucose + rapamycin group (NGR, glucose 3 mmol/L, rapamycin 2.67 μmol/L); the high lactate group (NGHL, glucose 3 mmol/L, lactic acid 2.5 mmol/L); the normal glucose + high lactate + gefitinib group (NGHLG, glucose 3 mmol/L, lactic acid 2.5 mmol/L, gefitinib 2.67μmol/L); the normal glucose + high lactate + rapamycin group (NGHLG, glucose 10 mmol/L, lactic acid 2.5 mmol/L, rapamycin 2.67μmol/L). Growth inhibitory rate of Hela cell is determined by CCK-8; Flow cytometry (FCM) is performed to evaluate the cell cycle; The annexin V-phycoerythrin/Propidium Iodide (annexin V-PE/PI) staining combined with flow cytometry is used to examine the cell cycle and apoptosis of Hela cells. Results: Under normal glucose with gefitinib or rapamycin environment, the apoptosis rate of Hela cells is higher than that of the normal glucose group. But the cell apoptosis rate of the gefitinib or rapamycin group decreases in high lactic acid and normal glucose, which is lower than that of the normal glucose and high lactate. Combined with the results of cell cycle, compared with the normal glucose group, percentage of Hela cells in G1/G0 phase increases significantly, the proportion of S phase cells decreases significantly in high lactic acid environment. In the normal glucose and gefitinib environment, Hela cells in G1/G0 phase and S phase are slightly higher than the proportion of normal glucose group, and G2/M phase cells are mild lower than the proportion of normal glucose group. Under the environment of high lactate and normal glucose, the percentage of G1/G0 and S phase cells in the gefitinib increase. As for rapamycin, normal glucose and high lactic acid environment makes cells stay in G1/G0 phase. The presence of rapamycin in the environment of normal sugar and high lactate makes more cells stay in G1/G0 or G2/M phase. Conclusion: Normal glucose and high lactic acid environment is conducive to Hela cell survival, and can promote the expression of EGFR and mTOR. Gefitinib is an antagonist of EGFR and rapamycin is an inhibitor of mTOR.

Point-of-care (POC) diagnostics have shown excellent potential in rapid biological analysis and health/disease monitoring. Here, we introduce a versatile, cost-effective, flexible, and wearable POC biomarker patch for effective sweat collection and health monitoring. We design and fabricate channels/patterns on filter paper using wax printing technology, which can direct sweat to collection and biomarker detection zones on the proposed platform. The detection zones are designed to measure the amount of collected sweat, in addition to measuring the sweat pH, and glucose (a potential diabetic biomarker), and lactate concentrations. It is significantly challenging to measure glucose in human sweat by colorimetric methods due to the extremely low glucose levels found in this medium. However, we overcame this issue by effectively engineering our wearable biosensor for optimal intake, storage, and evaporation of sweat. Our design concentrates the colorant (indicator) into a small detection zone and significantly increases the sensitivity for the sweat glucose sensing reactions. The device can thus detect glucose in physiological glucose concentration range of 50-300 μM. This cost-effective and wearable biosensor can provide instant in situ quantitative results for targets of interest, such as glucose, pH, and lactate, when coupled with the imaging and computing functionalities of smartphones. Meanwhile, it is also feasible to extract the air-dried sweat from the storage zone for further ex situ measurements of a broader portfolio of biomarkers, leading to applications of our wearable biosensor in personalized nutrition and medicine.

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.