bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerating and Improving the Consistency of Rapid-Acting Analog Insulin Absorption and Action for Both Subcutaneous Injection and Continuous Subcutaneous Infusion Using Recombinant Human Hyaluronidase
Authors: Muchmore Douglas B. , Vaughn Daniel E. 
Published: January 2014

Rapid-acting insulin analogs were introduced to the market in the 1990s, and these products have improved treatment of diabetes by shortening the optimum delay time between injections and meals. Compared with regular human insulin, rapid-acting insulin formulations also reduce postprandial glycemic excursions while decreasing risk of hypoglycemia. However, the current prandial products are not fast enough for optimum convenience or control. Recombinant human hyaluronidase (rHuPH20) has been used to increase the dispersion and absorption of other injected drugs, and in the case of prandial insulin analogs, it confers both ultrafast absorption and action profiles. Animal toxicology studies have demonstrated excellent tolerability of rHuPH20, and human studies, involving over 60,000 injections of prandial insulin + rHuPH20 to date, have similarly shown excellent safety and tolerability. Studies using rapid-acting analog insulin with rHuPH20 have included clinic-based pharmacokinetic and glucodynamic euglycemic glucose clamp studies, test meal studies, and take-home treatment studies. Administration methods have included subcutaneous injection of coformulations of rapid-acting insulin + rHuPH20 as well as continuous subcutaneous infusion of coformulations or use of pretreatment of newly inserted infusion sets with rHuPH20 followed by standard continuous subcutaneous insulin infusion therapy. These studies have demonstrated acceleration of insulin absorption and action along with improvement in postprandial glycemic excursions and reduction in hypoglycemia risks. Further, rHuPH20 reduces intrasubject variability of insulin absorption and action and provides greater consistency in absorption and action profiles over wear time of an infusion set. Further studies of rHuPH20 in the take-home treatment setting are underway.
First Clinical Evaluation of a New Long-Term Subconjunctival Glucose Sensor
Authors: Müller Achim Josef , Knuth Monika , Nikolaus Katharina Sibylle , Herbrechtsmeier Peter 
Published: January 2014

Background: To evaluate the feasibility of an implantable subconjunctival glucose monitoring system (SGMS) for glucose monitoring in humans, we investigated the in vivo performance of the sensor in a clinical trial with five patients. Methods: The new SGMS consists of an implantable ocular mini implant (OMI) and a hand-held fluorescence photometer. The implantable subconjunctival glucose sensor is composed of a fluorescence resonance energy transfer system based on Concanavalin A chemistry, embedded in a nelfilcon polymer hydrogel disk. Blood glucose changes in humans were induced by oral glucose intake and insulin injections. Results: The in vivo response of the new SGMS was tested in a first human clinical study with five diabetes patients. The OMI was well tolerated in the eyes of the patients. The SGMS exhibited high correlation coefficients (>0.88) with blood glucose changes and a good stability of the sensor response to glucose for the study period of 2 weeks. Lag times were in the range of 5–10 min. A total of 98% of all data pairs was in the clinical acceptable ranges A and B of the consensus error grid. Conclusions: For the first time, the possibility to measure glucose in vivo in the subconjunctival interstitial fluid for a period of 2 weeks was demonstrated in a human clinical trial.
Insulin Pump Therapy in the Perioperative Period: A Review of Care after Implementation of Institutional Guidelines
Authors: Boyle Mary E. , Seifert Karen M. , Beer Karen A. , Mackey Patricia , Schlinkert Richard T. , Stearns Joshua D. , Cook Curtiss B. 
Published: January 2014

Background: An institutional policy was previously established for patients with diabetes on insulin pump therapy undergoing elective surgical procedures. Method: Electronic medical records were reviewed to assess documentation of insulin pump status and glucose monitoring during preoperative, intraoperative, and postanesthesia care unit (PACU) phases of care. Results: Twenty patients with insulin pumps underwent 23 procedures from March 1 to December 31, 2011. Mean (standard deviation) age was 58 (13) years, mean diabetes duration was 28 (17) years, and mean duration of insulin pump therapy was 7 (6) years. Nearly all cases (86%) during the preoperative phase had the presence of the device documented—an improvement over the 64% noted in data collected before the policy. Intraoperatively, 13 cases (61%) had the presence of the pump documented, which was higher than the 28% before implementation of the policy. However, documentation of pump status was found in only 38% in the PACU and was actually less than the 60% documented previously. Over 90% of cases had glucose checked in the preoperative area and the PACU, and only 60% had it checked intraoperatively, which was nearly identical to the percentages seen before policy implementation. No adverse events occurred when insulin pump therapy was continued. Conclusions: Although some processes still require improvement, preliminary data suggest that the policy for perioperative management of insulin pumps has provided useful structure for care of these cases. The data thus far indicate that insulin pump therapy can be continued safely during the perioperative period.
The Relationships between Common Measures of Glucose Meter Performance
Authors: Wilmoth Daniel R. 
Published: January 2014

Background: Glucose meter performance is commonly measured in several different ways, including the relative bias and coefficient of variation (CV), the total error, the mean absolute relative deviation (MARD), and the size of the interval around the reference value that would be necessary to contain a meter measurement at a specified probability. This fourth measure is commonly expressed as a proportion of the reference value and will be referred to as the necessary relative deviation. A deeper understanding of the relationships between these measures may aid health care providers, patients, and regulators in comparing meter performances when different measures are used. Methods: The relationships between common measures of glucose meter performance were derived mathematically. Results: Equations are presented for calculating the total error, MARD, and necessary relative deviation using the reference value, relative bias, and CV when glucose meter measurements are normally distributed. When measurements are also unbiased, the CV, total error, MARD, and necessary relative deviation are linearly related and are therefore equivalent measures of meter performance. Conclusions: The relative bias and CV provide more information about meter performance than the other measures considered but may be difficult for some audiences to interpret. Reporting meter performance in multiple ways may facilitate the informed selection of blood glucose meters.
Feasibility of a Bihormonal Closed-Loop System to Control Postexercise and Postprandial Glucose Excursions
Authors: Van Bon Arianne C. , Jonker Lisanne D. , Koebrugge Rob , Koops Robin , Hoekstra Joost B. L. , DeVries J. Hans 
Published: January 2014

Background: The aim of this pilot study was to test the feasibility of a bihormonal (glucagon and insulin) closed-loop (CL) system by challenging the system with two meals and 30 min exercise. Methods: Ten patients with type 1 diabetes treated with continuous subcutaneous insulin infusion underwent a standardized protocol on three different occasions: 40 g carbohydrate breakfast followed 2 h later by 30 min of moderate-intensity exercise, followed 1.5 h later by a standardized 60 g carbohydrate lunch. An open-loop (OL) day served as control, the first CL day as tuning experiment, and the second CL day to compare with OL. Results: The overall mean venous glucose was similar: 9 (5.4–13.5) mmol/liter in OL versus 8.7 (6.4–11.0) mmol/liter in CL, p = .74. The postbreakfast glucose concentrations tended to be lower in OL than in CL [9.5 (4.3–13.3) versus 11.4 (7–16.2) mmol/liter; p = .07] and higher in OL than in CL postlunch [9.4 (6.0–14.9) versus 7.7 (5.5–9.0) mmol/liter, p = .15]. The postexercise glucose concentrations were similar in OL and CL: 7.5 (4.6–13) versus 8.2 (5.5–13.1) mmol/liter; p = .45. In those patients coming in with baseline glucose above 7 mmol/liter, there was initial overinsulinization in CL. During OL, two hypoglycemic episodes occurred compared with four hypoglycemic episodes in three participants during CL. Glucagon seemed mostly effective in preventing hypoglycemia. Conclusions: Overall, CL glucose control was comparable to OL control, but there was overinsulinization in those patients with baseline glucose above 7 mmol/liter.
Effect of Insulin Feedback on Closed-Loop Glucose Control: A Crossover Study
Authors: Ruiz Jessica L. , Sherr Jennifer L. , Cengiz Eda , Carria Lori , Roy Anirban , Voskanyan Gayane , Tamborlane William V. , Weinzimer Stuart A. 
Published: January 2014

Background: Closed-loop (CL) insulin delivery systems utilizing proportional-integral-derivative (PID) controllers have demonstrated susceptibility to late postprandial hypoglycemia because of delays between insulin delivery and blood glucose (BG) response. An insulin feedback (IFB) modification to the PID algorithm has been introduced to mitigate this risk. We examined the effect of IFB on CL BG control. Methods: Using the Medtronic ePID CL system, four subjects were studied for 24 h on PID control and 24 h during a separate admission with the IFB modification (PID + IFB). Target glucose was 120 mg/dl; meals were served at 8:00 AM, 1:00 PM, and 6:00 PM and were identical for both admissions. No premeal manual boluses were given. Reference BG excursions, defined as incremental glucose rise from premeal to peak, and postprandial BG area under the curve (AUC; 0–5 h) were compared. Results are reported as mean ± standard deviation. Results: The PID + IFB control resulted in higher mean BG levels compared with PID alone (153 ± 54 versus 133 ± 56 mg/dl; p < .0001). Postmeal BG excursions (114 ± 28 versus 114 ± 47 mg/dl) and AUCs (285 ± 102 versus 255 ± 129 mg/dl/h) were similar under both conditions. Total insulin delivery averaged 57 ± 20 U with PID versus 45 ± 13 U with PID + IFB ( p = .18). Notably, eight hypoglycemic events (BG < 60 mg/dl) occurred during PID control versus none during PID + IFB. Conclusions: Addition of IFB to the PID controller markedly reduced the occurrence of hypoglycemia without increasing meal-related glucose excursions. Higher average BG levels may be attributable to differences in the determination of system gain (Kp) in this study. The prevention of postprandial hypoglycemia suggests that the PID + IFB algorithm may allow for lower target glucose selection and improved overall glycemic control.
GlucoMen Day Continuous Glucose Monitoring System: A Screening for Enzymatic and Electrochemical Interferents
Authors: Lucarelli Fausto , Ricci Francesco , Caprio Felice , Valgimigli Francesco , Scuffi Cosimo , Moscone Danila , Palleschi Giuseppe 
Published: January 2014

Background: While most of the common drugs with the potential to interfere with continuous glucose monitoring (CGM) systems are accessible over the counter and can be assumed by CGM patients without medical supervision, many other chemicals are frequently used to treat critically ill patients. Continuous glucose monitoring reading accuracy may also be compromised in patients characterized by abnormally high concentrations of physiological interferents. In this article, 22 species selected from endogenous and exogenous chemicals were screened as possible interferents of GlucoMen®Day (GMD), the new microdialysis-based CGM system from A. Menarini Diagnostics. Method: Interference testing was performed according to the EP7-A2 guideline (Clinical and Laboratory Standards Institute 2005). Interference was evaluated at two levels of glucose, with each interferent additionally tested at two concentrations. Furthermore, two configurations of the GMD disposable sensor kit—one designed for subcutaneous application, the other for direct intravascular CGM—were challenged with interferent-spiked serum and blood samples, respectively. Results: With the exception of dopamine (however, at very high, nonphysiological concentrations), no interference was observed for all the tested substances. Interestingly, none of the common electrochemical interferents (including ascorbic acid, acetaminophen, and salicylic acid, which represent the major specificity issue for the competing CGM systems) significantly affected the system's output. Conclusions: These results provide clear insights into the advantages offered by the use of a microdialysis-based CGM system that additionally relies on the detection of hydrogen peroxide at low operating potential. GlucoMen Day may become the CGM system of choice for those patients who require either regular administration of drugs or their glycemia to be tightly controlled in the intensive care unit or similar environments.
Mobile Health Applications to Assist Patients with Diabetes: Lessons Learned and Design Implications
Authors: Årsand Eirik , Frøisland Dag Helge , Skrøvseth Stein Olav , Chomutare Taridzo , Tatara Naoe , Hartvigsen Gunnar , Tufano James T. 
Published: January 2014

Self-management is critical to achieving diabetes treatment goals. Mobile phones and Bluetooth® can support self-management and lifestyle changes for chronic diseases such as diabetes. A mobile health (mHealth) research platform—the Few Touch Application (FTA)—is a tool designed to support the self-management of diabetes. The FTA consists of a mobile phone-based diabetes diary, which can be updated both manually from user input and automatically by wireless data transfer, and which provides personalized decision support for the achievement of personal health goals. Studies and applications (apps) based on FTAs have included: (1) automatic transfer of blood glucose (BG) data; (2) short message service (SMS)-based education for type 1 diabetes (T1DM); (3) a diabetes diary for type 2 diabetes (T2DM); (4) integrating a patient diabetes diary with health care (HC) providers; (5) a diabetes diary for T1DM; (6) a food picture diary for T1DM; (7) physical activity monitoring for T2DM; (8) nutrition information for T2DM; (9) context sensitivity in mobile self-help tools; and (10) modeling of BG using mobile phones. We have analyzed the performance of these 10 FTA-based apps to identify lessons for designing the most effective mHealth apps. From each of the 10 apps of FTA, respectively, we conclude: (1) automatic BG data transfer is easy to use and provides reassurance; (2) SMS-based education facilitates parent-child communication in T1DM; (3) the T2DM mobile phone diary encourages reflection; (4) the mobile phone diary enhances discussion between patients and HC professionals; (5) the T1DM mobile phone diary is useful and motivational; (6) the T1DM mobile phone picture diary is useful in identifying treatment obstacles; (7) the step counter with automatic data transfer promotes motivation and increases physical activity in T2DM; (8) food information on a phone for T2DM should not be at a detailed level; (9) context sensitivity has good prospects and is possible to implement on today's phones; and (10) BG modeling on mobile phones is promising for motivated T1DM users. We expect that the following elements will be important in future FTA designs: (A) automatic data transfer when possible; (B) motivational and visual user interfaces; (C) apps with considerable health benefits in relation to the effort required; (D) dynamic usage, e.g., both personal and together with HC personnel, long-/short-term perspective; and (E) inclusion of context sensitivity in apps. We conclude that mHealth apps will empower patients to take a more active role in managing their own health.
Treatment of Diabetes Prior to and after Bariatric Surgery
Authors: Thorell Anders , Hagström-Toft Eva 
Published: January 2014

The number of patients undergoing bariatric surgery for morbid obesity is increasing. Type 2 diabetes is common among patients undergoing bariatric surgery. The effect of bariatric surgery on glycemia is profound in patients with diabetes and might vary between different bariatric surgical procedures. Therefore, almost invariably, there is a need to adjust antidiabetic drug dosages in the postoperative period in order to prevent hypoglycemia. Moreover, preoperatively, very low calorie diet protocols are applied in many centers to facilitate surgery by reducing liver volume. Because low caloric intake will increase insulin sensitivity, there is also a need for dose adjustments of glucose-lowering drugs during this period as well. Guidelines for adjustments of antidiabetic treatment before and after bariatric surgery are scarce. In this article, an overview of different bariatric surgical procedures as well as their effects on diabetes are presented. Recommendations on the perioperative antidiabetic treatment are proposed.
Use of an Intravascular Fluorescent Continuous Glucose Sensor in Subjects with Type 1 Diabetes Mellitus
Authors: Romey Matthew , Jovanoviĉ Lois , Bevier Wendy , Markova Kateryna , Strasma Paul , Zisser Howard 
Published: January 2014

Background: Stress hyperglycemia in the critically ill is associated with increased morbidity and mortality. Continuous glucose monitoring offers a solution to the difficulties of dosing intravenous insulin properly to maintain glycemic control. The purpose of this study was to evaluate an intravascular continuous glucose monitoring (IV-CGM) system with a sensing element based on the concept of quenched fluorescence. Method: A second-generation intravascular continuous glucose sensor was evaluated in 13 volunteer subjects with type 1 diabetes mellitus. There were 21 study sessions of up to 24 h in duration. Sensors were inserted into peripheral veins of the upper extremity, up to two sensors per subject per study session. Sensor output was compared with temporally correlated reference measurements obtained from venous samples on a laboratory glucose analyzer. Results: Data were obtained from 23 sensors in 13 study sessions with 942 paired reference values. Fourteen out of 23 sensors (60.9%) had a mean absolute relative difference ≤ 10%. Eighty-nine percent of paired points were in the clinically accurate A zone of the Clarke error grid and met ISO 15197 performance criteria. Adequate venous blood flow was identified as a necessary condition for accuracy when local sensor readings are compared with venous blood glucose. Conclusions: The IV-CGM system was capable of achieving a high level of glucose measurement accuracy. However, superficial peripheral veins may not provide adequate blood flow for reliable indwelling blood glucose monitoring.
Pilot Study of a Prototype Minimally Invasive Intradermal Continuous Glucose Monitor
Authors: Weinstock Ruth S. , Bristol Suzan , Armenia Andrew , Gesswein A. Chris , Bequette B. Wayne , Willis John P. 
Published: January 2014

Introduction: The purpose of this study was to assess point accuracy, rate-of-change accuracy, and safety of a prototype, minimally invasive continuous glucose monitoring (CGM) device over a 12 h in-clinic study. The CGM system consisted of a wireless electronics module with a disposable glucose sensor attached to the bottom. The electronics module was affixed to the abdomen using an adhesive pad on the bottom of the disposable sensor housing. Methods: Two CGM sensors were inserted into the abdominal tissue (left and right) of 15 adults aged 26–67 years, 5 with normoglycemia, 5 with type 1 diabetes, and 5 with type 2 diabetes. Over a 12 h period, each participant was fed three meals. Reference venous blood samples were drawn at periodic intervals (12.4 ± 5.3 min), and glucose was measured at the bedside using a laboratory reference method. For each participant, a single plasma equivalent glucose concentration was used for retrospective sensor calibration. Results: A total of 1082 paired data points were obtained from 15 subjects and 25 of 30 sensors. Statistical analysis yielded a mean absolute relative difference of 12.6% and a mean absolute difference of 16.0 mg/dl. Continuous glucose error grid analysis showed the combined point and rate-of-change accuracy was 97.4% in zone A and 1.5% in zone B (98.9% A+B), with 1.1% erroneous readings. Conclusions: The prototype CGM system provided clinically accurate results 98.9% of the time and was well tolerated by participants, with little or no pain and no adverse events.
Acute In Vivo Performance Evaluation of the Fluorescence Affinity Sensor in the Intravascular and Interstitial Space in Swine
Authors: Dutt-Ballerstadt Ralph , Evans Colton , Pillai Arun P. , Gowda Ashok , McNichols Roger , Rios Jesse , Cohn William 
Published: January 2014

Objective: We assessed and compared the performance levels of a fiber-coupled fluorescence affinity sensor (FAS) for glucose detection in the intradermal tissue and intravascular bed during glucose clamping and insulin administration in a large animal model. Research Design and Methods: The FAS (BioTex Inc., Houston, TX) was implanted in interstitial tissue and in the intravenous space in nondiabetic, anesthetized pigs over 6–7 h. For intradermal assessment, a needle-type FAS was implanted in the upper back using a hypodermic needle. For intravenous assessment, the FAS was inserted through a catheter into the femoral artery and vein. Blood glucose changes were induced by infusion of dextrose and insulin through a catheterized ear or jugular vein. Results: Based on retrospective analysis, the mean absolute relative error (MARE) of the sensor in blood and interstitial tissue was 11.9% [standard deviation (SD) = ±9.6%] and 23.8% (SD = ±19.4%), respectively. When excluding data sets from sensors that were affected by exogenous insulin, the MARE for those sensors tested in interstitial tissue was reduced to 16.3% (SD = ±12.5%). Conclusions: The study demonstrated that the performance level of the FAS device implanted in interstitial tissue and blood can be very high. However, under certain circumstances, exogenous insulin caused the glucose concentration in interstitial tissue to be lower than in blood, which resulted in an overall lower level of accuracy of the FAS device. How significant this physiological effect is in insulin-treated persons with diabetes remains to be seen. In contrast, the level of accuracy of the FAS device in blood was very high because of high mass transfer conditions in blood. While the use of the FAS in both body sites will need further validation, its application in critically ill patients looks particularly promising.
Automated Glycemic Pattern Analysis Can Improve Health Care Professional Efficiency and Accuracy
Authors: Katz Laurence B. , Dirani Riad G. , Li Gang , Randoll Randee A. , Mahoney John J. 
Published: January 2014

Background: Health care professionals (HCPs) routinely review handwritten blood glucose (BG) logbooks during office visits of patients with diabetes. Method: In this study, 64 HCPs were asked to assess glycemic patterns and estimate BG averages in six simulated handwritten logbooks. The HCPs then reviewed the pattern logs and averages in six OneTouch® Verio™IQ meters containing corresponding data sets. Results: The average time needed for pattern review was 7.3 min for handwritten logbooks versus 0.9 min using the meter. The total error rate for logbook pattern identification was 43.0% compared with the meter. The mean percentage deviation between HCP estimates of 30-day BG averages and actual values was 14.5%. Conclusions: The meter is associated with faster and more accurate pattern analysis compared with handwritten logbooks.