BG Measurements Research Articles

655-P: Evaluation of Accuracy and Longevity of an Implantable CGM System through 365 Days

Background: The PROMISE Clinical Trial, conducted to assess safety and accuracy of a 180-day implantable CGM System, had 43 subjects implanted with a modified sensor containing sacrificial boronic acid (SBA) to reduce the degradation of the boronic acid glucose-binding moieties. In-home use to 365 days was monitored in a 30 subject SBA sub-study. Methods: Accuracy of sensor glucose (SG) measurements produced by an algorithm emulator was compared to YSI model 2300 glucose obtained during in-clinic visits to 180 days. The sub-study compared SG to fingerstick blood glucose (BG, CONTOUR Next One BG meter) 4-7 times/day, from days 1-365 or until sensor retirement. SG values were paired within 5 mins after a BG values in the 30 sensors. MARD for 1-180 days was assessed with both YSI and BG reference methods. MARD by glucose ranges were compared for 1-180 days, 181-365 days and 1-365 days using BG as reference. Results: The MARD for SBA sensors for days 1-180 from in-clinic visits was 8.1% with YSI and 9.5% with BG as reference. The Table shows a comparison of MARD values by glucose ranges for the 3 time periods. Conclusions: There was ∼1.4 percentage point increase in overall MARD obtained when BG measurements were used as the reference value rather than YSI. The extension of the PROMISE Clinical Trial in a subset of subjects implanted with SBA sensors suggests accuracy can be maintained and extended to 365 days and across 40-400 mg/dl glucose ranges. Disclosure A.E.Jacquin: Employee; Senseonics, Other Relationship; BrainScope Company, Inc. L.Al-khawi: None. P.Sanchez: Employee; Senseonics. S.Mohanty: Employee; Senseonics. K.S.Tweden: Employee; Senseonics. F.R.Kaufman: Consultant; Twin Health, Employee; Senseonics.

Role of Betaglycan in TGF-β Signaling and Wound Healing in Human Endometriotic Epithelial Cells and in Endometriosis.

Simple SummaryEndometriosis is a benign female disorder presumably caused by dislocation of endometrial tissue during menstruation most often into the pelvis and is mainly resulting in pain and infertility. Up to date the pathogenesis of endometriosis is still unclear and a non-invasive biomarker not available. One of the cytokines suggested to be involved in the pathogenesis are the transforming growth factor-betas 1-3, which signal via two high-affinity receptors and in the case of transforming growth factor-beta2 also via the co-receptor betaglycan. In this study, we have analyzed the involvement of betaglycan into transforming growth factor-beta signaling and the contribution to biological functions such as wound healing with an in vitro model. We demonstrated an interesting interaction of betaglycan with the transforming growth factor-betas 1-3 and vice versa. Remarkably, the co-receptor betaglycan in its soluble form reduced wound healing as well as secretion of transforming growth factor-betas. Although we found some hints that endocervical mucus levels are different between healthy subjects and cases with endometriosis it was not sufficient for a reliable non-invasive diagnosis of the disease. Taken together, our findings suggest a novel role for betaglycan in the pathogenesis of endometriosis. Endometriosis is characterized by the presence of ectopic endometrium most often in the pelvis. The transforming growth factor-beta (TGF-β) superfamily is also involved in the pathogenesis; however, betaglycan (BG, syn. TGF-β type III receptor) as an important co-receptor was not studied. We analyzed mainly BG ectodomain shedding because released soluble BG (sBG) often antagonizes TGF-β signaling. Furthermore, we studied the role of TGF-βs and BG in wound healing and evaluated the suitability of BG measurements in serum and endocervical mucus for non-invasive diagnosis of endometriosis. Evaluation of the BG shedding and signaling pathways involved as well as wound healing was performed with enzyme-linked immune assays (ELISAs), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), small interfering RNA (siRNA) knockdown, and scratch assays with human endometriotic epithelial cells. TGF-β1/2 stimulation resulted in a significant dose-dependent reduction in BG shedding in endometriotic cells, which was TGF-β/activin receptor-like kinase-5 (ALK-5)/mother against decapentaplegic homolog3 (SMAD3)- but not SMAD2-dependent. Inhibition of matrix metalloproteinases (MMPs) using the pan-MMP inhibitor GM6001 and tissue inhibitor of MMPs (TIMP3) equally attenuated BG shedding, signifying the involvement of MMPs in shedding. Likewise, recombinant BG moderately reduced the secretion of TGF-β1/2 and wound healing of endometriotic cells. TGF-β1 significantly enhanced the secretion of MMP2 and MMP3 and moderately promoted wound healing. In order to evaluate the role of BG in endometriosis, serum (n = 238) and mucus samples (n = 182) were analyzed. Intriguingly, a significant reduction in the levels of sBG in endocervical mucus but not in the serum of endometriosis patients compared to controls was observed. Collectively, these observations support a novel role for BG in the pathophysiology of endometriosis.

Endocrine Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism. To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes. PubMed and Embase were searched from January 1992 to January 2020. We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non-English-language studies were excluded. Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers. The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations >150 mg/dL [>8.3 mmol/L] and BG concentrations <50 mg/dL [<2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] <4.2 μg/dL [<54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration <18 μg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of <9 μg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation. These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing. We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.

Comparison of Accu Chek Inform II point-of-care test blood glucose meter with Hexokinase Plasma method for a diabetes mellitus population during surgery under general anesthesia

PurposeBlood glucose (BG) concentrations of patients with diabetes mellitus (DM) are monitored during surgery to prevent hypo- and hyperglycemia. Access to point-of-care test (POCT) glucose meters at an operating room will usually provide monitoring at shorter intervals and may improve glycemic control. However, these meters are not validated for patients under general anesthesia.MethodsThis cross-sectional study included 75 arterial BG measurements from 75 patients (71 with DM, mostly insulin dependent) who underwent elective non-cardiac surgery under general anesthesia. Arterial blood samples were taken at least 60 minutes after induction. One drop of blood was used for Accu Chek Inform II (ACI II) POCT BG meter and the residual blood was sent to the clinical laboratory for a Hexokinase Plasma reference method. A Bland–Altman plot was used to visualize the differences between both methods, and correlation was assessed using the intra-class correlation coefficient (ICC).ResultsThe results showed an estimated mean difference of 0.8 mmol/L between ACI II and the reference method, with limits of agreement equal to -0.6 and 2.2 mmol/L. In general, the reference method produced higher values than ACI II. ICC was 0.955 (95% CI 0.634–0.986), P < 0.001, and concordance correlation coefficient (CCC) was 0.955 (95% CI 0.933–0.970).ConclusionArterial BG measurements during surgery in patients with DM under general anesthesia using POCT BG meter are in general lower than laboratory measurements, but the ICC and CCC show a clinically acceptable correlation. We conclude that POCT measurements conducted on arterial specimens using the ACI II provide sufficiently accurate results for glucose measurement during surgery under general anesthesia.

Study protocol for assessing the user acceptance, safety and efficacy of a tablet-based workflow and decision support system with incorporated basal insulin algorithm for glycaemic management in participants with type 2 diabetes receiving home health care: A single-centre, open-label, uncontrolled proof-of-concept study

IntroductionDiabetes management can be especially complex for older adults who receive health care at home. Thus, international guidelines recommend basal-insulin regimens due to simpler handling and low hypoglycaemia risk. A basal-insulin algorithm (including basal-plus) was developed to also include participant's health status and subsequently implemented into a tablet-based workflow and decision support system, GlucoTab@MobileCare. This study protocol describes a proof-of-concept study to investigate user acceptance, safety and efficacy of the GlucoTab@MobileCare system in participants receiving home health care. MethodsThe open-label, single-centre, uncontrolled study will recruit a maximum of ten participants with insulin treated type-2-diabetes (age ≥18 years) who receive home health care. During a three month study period participants will receive basal- or basal-plus-insulin therapy once daily as suggested by the GlucoTab@MobileCare system. Statistical analysis will be conducted on an intention-to-treat basis. The primary endpoint is the percentage of tasks (BG measurements, insulin dose calculations, insulin injections) that were performed according to GlucoTab@MobileCare suggestions relative to the total of suggested tasks. Secondary endpoints include user acceptance, safety and efficacy parameters. The study was approved by the ethics committee and regulatory authorities. Before obtaining written informed consent, all participants will receive oral and written information about all aspects of the study. Results will be published in a peer-reviewed journal and at diabetes and geriatric conferences. DiscussionPotential implications may be improved quality and safety of basal-insulin therapy in older adults as well as support for health-care-providers in daily routine including evidence-based knowledge. Trial registrationGerman Clinical Trials Register (DRKS00015059);

620-P: Improving Glycemic Control in Patients with T2D in Brazil through Tech-Enabled Low-Cost Virtual Monitoring

T2D remains a global epidemic and has become a major public health concern in Brazil, with almost 17M people living with T2D. Poor glycemic control leads to severe loss in life expectancy, quality of life and increased healthcare expenses. The main challenges to support patients with T2D in developing countries are geographical dispersion and limited budgets. The primary objective of this study is to determine whether the use of a low-cost, 100% virtual patient monitoring program, can improve disease control in patients with T2D in Brazil, using remote diabetes support through Appia’s digital platform connected to a smart BGM, coupled with remote coaches. Methods: Thirty-one participants aged 36-69 years old previously diagnosed with T2D that measure their BG levels at least 2 times per week, were recruited online and enrolled in the program. Most of them were just receiving oral medication treatment. HbA1c was measured at the beginning and at the end of the program. During the 12-week lifestyle modification program, the patients were given an intelligent BGM connected to a mobile app that stores BG measurements in the cloud. Additionally, patients were given access to a remote diabetes coach for personalized content, weekly goals setting and support. Patients did not receive medical intervention outside of their PCP. Results: The mean HbA1c was significantly reduced by 1.11% (95% CI: -1.5754 - -0.7446, p&amp;lt;0.0001) from a starting mean of 8.5% to 7.39% at the end of the program. Total average BG levels dropped from 169 mg/dL to 138 mg/dL with n=2439 readings. Also, the severe hyperglycemic events (&amp;gt;300 mg/dL) were reduced by 51.55%, without increasing level 2 (&amp;lt;54 mg/dL) and 3 hypoglycemic events. Finally, the total number of BG measurements during the program increased by 8.43% in 90 days (from 0.8/day to 0.9/day per patient). Conclusion: The combination of remote diabetes coaching with a smart BGM connected to an app was effective for improving glycemic control in patients with T2D in Brazil. Disclosure M. Carrica: Stock/Shareholder; Self; Appia. F. Valente: Consultant; Spouse/Partner; Sanofi Genzyme. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc. L. Migliano: Employee; Self; Appia. Y. Lorda Dumont: None. J.E. Salles: Board Member; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc.

900-P: HbA1c Is an Insufficient Glucose Control Assessment Tool in Type 1 and Type 2 Treated with Insulin

HbA1c is currently used for assessment of glucose control in type 1 and type 2 diabetes patients treated with different therapeutic regiments. Different conditions besides glucose concentration affect its level and, in many cases, HbA1c is insufficient to present glucose control. In our study we compare representativeness of usually used control assessment tools such HbA1c and multiple daily blood glucose measurements with results derived from CGM record. We studied a group of 106 patients (60 men, 46 women; mean age 58.23±10.81 years), 21 patients with type 1 diabetes (on intensified regimen) and 85 patients with type 2 diabetes (33 - on oral medications, 31 - on pre-mixed insulin, 21 - on intensified insulin regimen). Patients were observed for three-month period - they performed eight-point BG measurements at least three time weekly, HbA1c was measured at the end of this period and continuous glucose monitoring with iProTM was performed for seven days. In oral medication treated group a high positive correlation was found between HbA1c (7.13±0.85%) and average blood glucose level during period of CGM (7.15±1.80mmol/l) (p&amp;lt;0.01) with correlation coefficient were (r1=0.742) (p&amp;lt;0.05). In pre-mixed insulin treated group and type 2 with intensified regimen lower positive correlation was found (7.64±1.40% and 7.69±1.23%, respectively 7.64±1.48mmol/l and 7.60±1.30mmol/l), with r2=0.642 (p&amp;lt;0.01) and r3=0.570 (p&amp;lt;0.05). No correlation was found in type 1 diabetes group (r4=0.083). No correlations were found between HbA1c and number of excursions in other groups. Same trend of correlations was found comparing HbA1c and mean BG level in eight-point profile. We conclude that HbA1c is appropriate assessment tool only in oral treated type 2 diabetes patients. In type 1 and insulin treated type 2 patients HbA1c gives relative information about overall control with no precise presenting of glucose fluctuations and out-of-range values of BG. Disclosure T. Totomirova: None. M. Arnaudova: None. I. Daskalova: None.

2459-PUB: Clinical Characteristics and Management of Patients with Type 1 Diabetes—A National Population-Based Spanish Study (SED1)

Introduction: Little is known about the clinical characteristics and management of type 1 diabetes (T1D) in Spain from a national perspective. To sort this lack of information out the Spanish Diabetes Society (SED) promoted a national population-based audit study. (SED1 Study). Material and Methods: Observational, cross-sectional study of a nationally representative sample of patients with DM1 in 78 Spanish sites, including children and adults. Results: A total of 647 participants were included: Aged 36.5+14.4 years (7.6% &amp;lt; 14), 55,3% female, 97.2% Caucasian, time since diagnosis 17.9±12.0 years and a BMI of 24.7±4.4 kg/m2 (40.2% &amp;gt; 25; 12.1% ≥30). 75.0% of the population had secondary or university studies. 20.2% of patients were active smokers and 48.7% had any type of comorbidity, mainly dyslipidemia (25.8%). Any kind of retinopathy and nephropathy was present in 19.3 and 5.9% of patients. Regarding disease management, 75.9% used basal-bolus insulin therapy, 20.4% pump therapy, half of patients used insulin/carbohydrate ratio (ICR), performed 3.0±0.9 blood glucose measurements/day (BG) and 24.9% used continuous-glucose monitoring. Mean last-year HbA1c was 7.6±1.2% (&amp;lt; 7%, 30.6%). The univariate logistic regression indicated that, HbA1c value was determined negatively by BG measurements (-0.045, p=0.03) and frequency of use of ICR (-0.236, p=0.008) and positively by disease duration (0.011, p=0.002) and lack of adherence to diet counseling (0.788, p=0.0001). Conclusion: The management and type of treatment of T1D in Spain is similar to other western countries. There is still a substantial proportion of patients not reaching the recognized A1c target and with either overweight or obesity. Some factors related to T1D management prevent a greater effectiveness of treatment. Disclosure F. Gomez-Peralta: Advisory Panel; Self; Abbott, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. E. Menéndez-Torre: None. S. Conde Barreiro: Other Relationship; Self; Lilly Diabetes, Sanofi. I. Conget: None. A. Novials: None. Funding Sanofi

951-P: A Clinical Decision Support System for Basal-Bolus Insulin Therapy Is Moving to Hospital Routine Care: Efficacy, Safety, and Usability Confirmed

Glycemic goals of inpatients should consider the prevention of hypoglycemia and hyperglycemia. To achieve glycemic control in the hospital, guidelines recommend basal-bolus insulin therapy as the preferred method for treatment of persistent hyperglycemia and the use of clinical decision support systems. The aim of this study was to investigate the efficacy, safety and usability of the GlucoTab® decision support system in hospital routine care of non-critically ill patients with type 2 diabetes at 3 general wards of a university medical center. In total, 150 patients with type 2 diabetes requiring insulin therapy (56 female, age 68 ± 11 years, HbA1c 77 ± 24 mmol/mol, diabetes duration 15 ± 11 years, BMI 30 ± 6 kg/m2, length of hospital stay 9 ± 7 days) were treated with basal-bolus insulin therapy guided by GlucoTab®, a mobile decision support system providing automated workflow tasks and suggestions for insulin dosing to nurses and physicians. In total 4879 capillary blood glucose values (BG) were documented. By using the GlucoTab® system in routine care, a mean daily BG of 159 ± 32 mg/dl could be achieved. 68.8% of all BG measurements were in the acceptable range (70-&amp;lt;180 mg/dl). The percentage of BG values &amp;lt;40, &amp;lt;70 and ≥300 mg/dl was 0.02%, 2.2% and 2.3%, respectively. Health care professional’s adherence to the suggested insulin doses (n=7407) and workflow tasks (n=9927) was high (&amp;gt;93% and 91%, respectively). The study confirmed that the GlucoTab® system supports a safe, efficacious and user-friendly glycemic management of basal-bolus insulin therapy in hospital routine care. Further research will include decision support for alternative therapy types for patients with less stringent goals to prevent hypoglycemia in hospital routine care. Disclosure K.M. Lichtenegger: None. F. Aberer: None. A.C. Tuca: None. K. Donsa: Stock/Shareholder; Self; decide Clinical Software GmbH. B. Höll: Employee; Self; decide Clinical Software GmbH. L. Schaupp: None. J. Plank: None. P. Beck: Employee; Self; decide Clinical Software GmbH. Stock/Shareholder; Self; decide Clinical Software GmbH. F. Fruhwald: None. T.R. Pieber: Advisory Panel; Self; ADOCIA, Arecor Limited, AstraZeneca, Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Novo Nordisk A/S. J.K. Mader: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Prediktor Medical, Roche Diabetes Care, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Dexcom, Inc., Novo Nordisk Inc. Stock/Shareholder; Self; decide Clinical Software GmbH. Funding Research Studio Austria "GlucoTab“ (844737)

Study on the blood glucose management with controlled goal feed in Malaysian critically ill patients

Stress-induced hyperglycaemia is commonly occurred in the intensive care unit (ICU). It is known that the intensive insulin therapy (IIT) has successfully managed the blood glucose level within the targeted band. However, modifications on the current practice need to be considered to minimize the risk of hypoglycaemia and mortality. Thus, the aim of this study is to assess the performance of a new practice known as Stochastic Targeted (STAR) Protocol in managing blood glucose levels in Malaysia ICU setting. STAR is a tablet-computer based protocols that provides patient-specific glucose control framework accounting for patient variability with a stochastically derived maximum 5% risk of hypoglycaemia events. A retrospective 92 non-diabetes patient’s data who underwent IIT were identified. Patient’s blood glucose levels, exogenous insulin and nutrition inputs including patient demographics were extracted from the ICU charts to create virtual patients by using physiologically mathematical model. Three trials were simulated with controlled goal feed (GF) and without GF. Only one type of nutrition is considered in this study which is Glucerna. The outcomes will be compared in terms of %BG within the targeted band of 4.4 to 10.0 mmol/L, the total number of BG measurements, and the % of severe hypoglycaemia. The results indicate that STAR virtual trial with controlled GF reduced the risk of hypoglycaemia to 3% and the clinical burden up to 1630 hours while maintaining BG within the targeted band. The total number of BG measurements also decreased to 5384 from 7038. Thus, the implementation of STAR protocol in the Malaysia ICU is beneficial and it is proven safe while aiding nurses and physicians in reducing the clinical burden and medical cost in treating stress-induce hyperglycaemia in the demanding ICU setting.

Intermittently Scanned Continuous Glucose Monitoring (isCGM)—Examination in Pediatric Patients With and Without Ketoacidosis

The isCGM (FreeStyle Libre “flash”) is approved in a number of countries for use in adults, but has had minimal study in pediatric groups and no reports of its use during ketoacidosis. This study in pediatric patients sought to compare paired samples from this isCGM to the Accucheck Aviva glucose monitor under conditions of varying glucose levels and varying degrees of ketoacidosis. Twelve hyperglycemic T1D patients, ages 6-16 years, were studied with a minimum of 6 paired comparisons in each condition: 3 with ketoacidosis (pH 7.2-7.3) and one with severe ketoacidosis (pH &amp;lt;7.2), and all others nonketotic. Up to a 15% measurement difference between BG and tissue glucose measurements for BG &amp;gt; 100 mg/dL, or an absolute difference of 15 mg/dL for BG &amp;lt; 100 mg/dL, were considered within target range. Blood glucose levels ranged from 35 to 556 mg/dl (1.94-30.89 mmol/L) and pH levels 6.9 to 7.6. Mean absolute relative differences (MARD, isCGM vs. Accucheck paired measurements) were: 426 non-ketoacidotic with BG &amp;gt;100 mg/dL: MARD of 11.77% with 69.2% of values within a 15% difference; 96 non-ketoacidotic with BG &amp;lt; 100 mg/dL: MARD of 12.4% with 78.1% within 15%; 17 ketoacidotic with BG&amp;gt;100 mg/dL: MARD of 12.42% with 70.6% within 15%; and 6 severely ketoacidotic: MARD of 22.68% with 16.7% within 15%, constituting a major difference with severe ketoacidosis. Clarke Error Grid Analysis for results with non-ketoacidotic values with BG &amp;lt;=79 mg/dL: 93% in Zone A and 7% in Zone B; ketoacidotic values: 94.11% in Zone A and 5.88% in Zone B; and severely ketoacidotic values: 50% in Zone A and 50% in Zone B. Of the 545 paired comparisons obtained, only 17 were obtained during ketosis and 6 during severe ketoacidosis. These results show that this “flash” isCGM and BG measurements determined by Accucheck Aviva are highly concordant, however, the major differences observed during severe ketoacidosis urge caution in interpreting the blood glucose levels under this condition. Disclosure G.A. Bou: None. M. Wurm: None. B.C. Hansen: None. K. Schwab: None.

A randomized controlled trial of one bag vs. two bag system of fluid delivery in children with diabetic ketoacidosis: Experience from a developing country

PurposeTo compare one vs. two bag system with respect to blood glucose variability (BGV), time for resolution of acidosis and incidence of hypoglycemia, hypokalemia, and cerebral edema in children with diabetic ketoacidosis (DKA). Material and methodsIn an open labelled randomized controlled trial, thirty consecutive patients ≤12years with DKA were randomized to either one (n=15) or two bag (n=15) system of intravenous fluid delivery. The two bags had similar electrolyte but differing dextrose concentration (none vs. 12.5%) and changing the rate of fluid, delivered different dextrose concentrations. BGV was primary outcome while hypoglycemia (blood glucose, BG<50mg/dL), hypokalemia (serum potassium<3.5mEq/L), time to resolution of acidosis and cerebral edema were secondary outcomes. ResultsThe one and two bag systems had similar BGV parameters; median hourly absolute BG change (mg/dL) [44 (30–74.5) vs. 36 (31–49); p=0.54], mean of standard deviation of BG measurements [65.1 (25.1) vs. 65.5 (26.8); p=0.96] and median number of undesirable events (hourly blood sugar change ≥50mg/dL) [4.5 (1.75–6.0) vs. 5.0 (3.0–8.0); p=0.31]. The incidence of hypoglycemia [42.9% (n=6) vs. 26.7% (n=4); p=0.45] and hypokalemia [64% (n=9) vs. 67% (n=10); p=0.23], and mean (SD) time to resolution of acidosis [20.3 (14.8) and 20.3 (7.0); p=0.59] were similar in both the groups. None had cerebral edema. ConclusionsThe one and two bag systems were similar to each other with respect to BGV, incidence of complications and time to resolution of acidosis.

Hypoglycemia Rates After Restriction of High-Dose Glargine in Hospitalized Patients

Hypoglycemia remains one of the main challenges of insulin therapy. To reduce insulin-related hypoglycemia at our institution, we restricted inpatient ordering of high glargine doses (≥0.5 U/kg/day) to endocrine staff in May 2013. This retrospective cohort study assesses its effect on hypoglycemia and glycemic control within 48 hours of admission (ADM). We identified 692 adult patients hospitalized at Boston Medical Center who received glargine upon ADM from November 1, 2012 through April 30, 2013 as the pre-intervention group, and 651 adult patients admitted between November 1, 2013 and April 30, 2014 as the postintervention group. Demographics, medical history, home insulin regimen, concurrent oral diabetes medications or glucocorticoid administration, ADM serum creatinine, all blood glucose levels (BG) ≤48 hours of ADM, and hemoglobin A1c values ≤3 months were assessed. Hypoglycemia was defined as BG ≤70 mg/dL, and hyperglycemia as BG ≥200 mg/dL. Multivariable regression models assessed potential associations between covariates and incidence of hypoglycemia and average BG ≤48 hours of ADM. Demographics were similar between groups. Significantly less patients received high-dose glargine in the post-intervention group (5.2% vs. 0.3%, P<.001). Incidences of hypoglycemia were significantly lower in the postintervention group (20.9% vs. 17.8%, P<.001 per ADM; 3.4% vs. 2.3%, P = .001 per BG measurements [BGM]). Mean BG levels ≤48 hours of ADM and incidence of hyperglycemia were not significantly different. The adjusted incident rate ratio of hypoglycemia was 0.63 per ADM and 0.74 per BGM in the postintervention group compared to the pre-intervention group (P = .001 and P = .063, respectively). We found that implementation of a restriction on high doses of glargine resulted in lower rates of hypoglycemia without worsening glycemic control. ADM = admission BG = blood glucose BGM = blood glucose measurements BMC = Boston Medical Center BMI = body mass index EMR = electronic medical record HgbA1c = hemoglobin A1c IRR = incidence rate ratio NPH = neutral protamine Hagedorn TDD = total daily dose T2D = type 2 diabetes.

The Individual Meal Pattern

in Mean BG but significantly different from all other strata. We might say that each subject is imprisoned in his/her own stratum and maintains a steady meal pattern to maintain a steady BG. Figure 1 shows Mean BGs in increasing sequence: The high Mean BGs are associated with insulin resistance. These assessments on Mean BG were taken before any training on Initial Hunger (IH) and again after 5 months from training. I was criticized by ASN for assessments based on portable devices. Portable devices are unreliable. When I started my long research, I considered single BG measurements as inconsistent and the BG wavering destitute any meaning to the measurements. The liver delivers glucose into blood every 12 minutes. Physical activity, a gram of sugar, a heavy concern, all increase BG. We do not know the onset of the post-absorptive period, that also declines lowly, slowly. I retained that we could better rely on the mean of many measurements during a period. Single measurements were incorporated in collective, weekly assessments (Mean BG). At recruitment, the BG means of 120 investigated subjects showed SDs of 5 to 10 mg/dL that corresponded to confidence limits of 3.84 mg/dL at P < 0.05. We could stratify the 120 subjects in ten small strata. Each stratum contained subjects without differences

Current practice of hypoglycemia management in the ED

PurposeTo characterize hypoglycemia management and identify characteristics associated with refractory (need for additional treatment following initial management) and recurrent (adequate initial treatment followed by blood glucose [BG] ≤50 mg/dL) hypoglycemia. MethodsRetrospective review of adult emergency department (ED) patients who presented to a large academic medical center with hypoglycemia (BG ≤ 50 mg/dL) between January 2011 and July 2015. Data collection focused on BG measurements and treatment practices. Data are reported using descriptive statistics, Wilcoxon rank sum, and χ2 analysis as appropriate. ResultsTwo hundred forty-four patients were included (mean age, 59 ± 18.7 years; weight, 85 ± 24.3 kg). Patients arriving via prehospital care (n = 124) were assessed faster in the ED (median, 25 minutes; interquartile range [IQR], 10-40 minutes) compared with ambulatory arrival (median, 43 minutes; IQR, 17-95 minutes; P = .0018). There were 174 patients with a BG ≤ 50 mg/dL in the ED. Of those, 108 (62.1%) were treated with intravascular bolus dextrose/intramuscular glucagon and 21 patients (12%) did not receive any treatment or food. The overall median time to treatment after identification of hypoglycemia was 12 minutes (IQR, 6-27.8 minutes); treatment was administered faster after bedside point-of-care testing assessment compared with when serum samples resulted (11 [IQR, 6-23.5] minutes vs 25 [IQR, 10.75-42.5] minutes, respectively; P = .015). The overall time to repeat BG was obtained 22 (IQR, 8-44) minutes after bolus treatment, but this interval increased with subsequent measurements. Refractory or recurrent hypoglycemia occurred in 30.3% of patients. Mean initial BG was lower in the subset of patients who developed refractory hypoglycemia compared with those who did not (35.1 ± 9.8 vs 37.6 ± 10.2 mg/dL, P = .079), although not statistically significant. Patients with recurrent hypoglycemia were also less likely to receive dextrose containing intravenous fluids compared with those without recurrent hypoglycemia (P = .028). Infection was the only associated characteristic with refractory or recurrent hypoglycemia (P = .021). ConclusionsOverall, 12% of patients did not receive treatment for hypoglycemia in the ED with a BG ≤ 50 mg/dL. Time to treatment after identification was faster when identified by care testing vs serum sample result. Time to repeat BG in the ED was relatively quick, but did increase over time. About one-third of patients had refractory or recurrent hypoglycemia and infection was associated with this occurrence. Lack of dextrose containing intravenous fluid was associated with the incidence of recurrent hypoglycemia.

Nonlinear model predictive glycemic control of critically ill patients using online identification of insulin sensitivity.

In critically ill patients suffering from hyperglycemia, it has been recently shown that mortality and morbidity can be reduced by keeping blood glucose within the range of 80-110 mg/dL. However, maintaining glycemia within such range is difficult due to the time variability in insulin sensitivity in critically ill patients. In this paper, we propose a novel glycometabolism model of critically ill patients with an insulin sensitivity parameter and develop a nonlinear model predictive glycemic control system with online identification of insulin sensitivity at one-hour intervals. Simulation results show that our system keeps 70% of BG measurements within the range of 80-110 mg/dL without any severe hypoglycemic incidents, which indicates the effectiveness and safety of our system.

Accuracy and performance of continuous glucose monitors in athletes

Abstract Continuous glucose monitoring (CGM) devices, with their 1-5 minute measurement interval, allow blood glucose dynamics to be captured more frequently and less invasively than traditional measures of blood glucose concentration (BG). These devices are primarily designed for the use in type 1 and type 2 diabetic patients to aid BG regulation. However, because of their increased measurement frequency and reduced invasiveness CGM devices have been recently applied to other subject cohorts, such as intensive care patients and neonates. One unexamined cohort is athletes. Continuous monitoring of an athlete's BG has the potential to increase race performance, speed recovery, and aid training, as BG can reflect metabolic and inflammatory conditions. However, before these benefits can be realized the accuracy and performance of CGM devices in active athletes must be evaluated. Two Ipro2 CGM devices (Medtronic Minimed, Northridge, CA, USA) were inserted into an athlete (resting HR 50 beats per minute (bpm), training 10-17hrs per week). Two fasting exercise tests were carried out 3 days apart, involving 2 hours of continuous exercise and a glucose bolus at the end of the 2 hours. Reference BG measurements were taken regularly. These tests were then repeated while the athlete was sedentary, HR

Accuracy and Performance of Continuous Glucose Monitors in Athletes

Continuous glucose monitoring (CGM) devices, with their 1-5 minute measurement interval, allow blood glucose dynamics to be captured more frequently and less invasively than traditional measures of blood glucose concentration (BG). These devices are primarily designed for the use in type 1 and type 2 diabetic patients to aid BG regulation. However, because of their increased measurement frequency and reduced invasiveness CGM devices have been recently applied to other subject cohorts, such as intensive care patients and neonates. One unexamined cohort is athletes. Continuous monitoring of an athlete's BG has the potential to increase race performance, speed recovery, and aid training, as BG can reflect metabolic and inflammatory conditions. However, before these benefits can be realized the accuracy and performance of CGM devices in active athletes must be evaluated.Two Ipro2 CGM devices (Medtronic Minimed, Northridge, CA, USA) were inserted into an athlete (resting HR 50 beats per minute (bpm), training 10-17hrs per week). Two fasting exercise tests were carried out 3 days apart, involving 2 hours of continuous exercise and a glucose bolus at the end of the 2 hours. Reference BG measurements were taken regularly. These tests were then repeated while the athlete was sedentary, HR < 80bmp. CGM devices agree well with each other and reference measurements during rigorous exercise with a median [IQR] MARD of 7.3 [5.4 - 10.9] %. During sedentary periods the accuracy of the CGM trace compared to reference measurements was reduced, 25.1 [16.9 35.4] %. However the good agreement between the sensors is maintained. This decrease in accuracy is likely related to the fact interstitial fluid is not actively pumped like blood. It relies on muscle movement to circulate and mix. Thus, it can be expected that during exercise more accurate results are seen as the rigorous movement allows rapid mixing and equilibrium between the blood and interstitial fluid.

β-Glucan Antigenemia Anticipates Diagnosis of Blood Culture–Negative Intraabdominal Candidiasis

Life-threatening intraabdominal candidiasis (IAC) occurs in 30 to 40% of high-risk surgical intensive care unit (ICU) patients. Although early IAC diagnosis is crucial, blood cultures are negative, and the role of Candida score/colonization indexes is not established. The aim of this prospective Fungal Infection Network of Switzerland (FUNGINOS) cohort study was to assess accuracy of 1,3-β-d-glucan (BG) antigenemia for diagnosis of IAC. Four hundred thirty-four consecutive adults with abdominal surgery or acute pancreatitis and ICU stay 72 hours or longer were screened: 89 (20.5%) at high risk for IAC were studied (68 recurrent gastrointestinal tract perforation, 21 acute necrotizing pancreatitis). Diagnostic accuracy of serum BG (Fungitell), Candida score, and colonization indexes was compared. Fifty-eight of 89 (65%) patients were colonized by Candida; 29 of 89 (33%) presented IAC (27 of 29 with negative blood cultures). Nine hundred twenty-one sera were analyzed (9/patient): median BG was 253 pg/ml (46-9,557) in IAC versus 99 pg/ml (8-440) in colonization (P < 0.01). Sensitivity and specificity of two consecutive BG measurements greater than or equal to 80 pg/ml were 65 and 78%, respectively. In recurrent gastrointestinal tract perforation it was 75 and 77% versus 90 and 38% (Candida score ≥ 3), 79 and 34% (colonization index ≥ 0.5), and 54 and 63% (corrected colonization index ≥ 0.4), respectively. BG positivity anticipated IAC diagnosis (5 d) and antifungal therapy (6 d). Severe sepsis/septic shock and death occurred in 10 of 11 (91%) and 4 of 11 (36%) patients with BG 400 pg/ml or more versus 5 of 18 (28%, P = 0.002) and 1 of 18 (6%, P = 0.05) with BG measurement less than 400 pg/ml. β-Glucan decreased in IAC responding to therapy and increased in nonresponse. BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture-negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.

5thAnnual Symposium on Self-Monitoring of Blood Glucose (SMBG) Applications and Beyond, May 3–5, 2012, Dublin, Ireland

International experts in the fields of diabetes, diabetes technology, endocrinology, and pediatrics gathered for the 5th Annual Symposium on Self-Monitoring of Blood Glucose (SMBG) Applications and Beyond. The aim of this meeting was to continue setting up a global network of experts in this field and provide an international platform for exchange of ideas to improve life for people with diabetes. In line with previous editions, the 2012 meeting comprised a comprehensive scientific program, parallel interactive workshops, pros and cons debates, and a keynote. All these discussions were intended to help identifying gaps and areas where further scientific work and clinical studies are needed.