bluuebunny/crossref_metadata_2025_split huggingface dataset:
Basal—Prandial Insulin Delivery in Type 2 Diabetes Mellitus via the V-Go™: A Novel Continuous Subcutaneous Infusion Device
Authors: Kapitza Christoph , Fein Seymour , Heinemann Lutz , Schleusener Debra , Levesque Steven , Strange Poul 
Published: January 2014

Background: The V-Go™ is a once-daily disposable device that allows coverage of basal and prandial insulin requirements over a period of 24 hours. The aim of this proof-of-concept study was to evaluate the clinical functionality, safety, and pharmacodynamics of the V-Go delivering insulin aspart and redistributing a single basal dose of insulin glargine as a constant basal infusion supplemented with prandial insulin in subjects with type 2 diabetes mellitus. Methods: In six subjects receiving once-daily subcutaneous (SC) injections of insulin glargine (≥15 U/day) with or without concomitant oral antidiabetic drugs, glargine was discontinued following a 3-day baseline phase. The V-Go was then applied to the lower abdomen of the subjects once daily for 7 days (days 1–3 inpatient, days 4–7 outpatient). Each V-Go provided a continuous 24-hour preset basal infusion rate of insulin aspart (0.6 U/h) and up to three daily prandial doses at mealtimes. Capillary blood glucose concentrations were measured at 11 time points per day during the baseline and inpatient phases and at 4 time points per day during the outpatient phase. Additionally, glucose profiles were measured continuously on all days. Results: The V-Go was well tolerated and operated as anticipated. The mean ± SEM prestudy daily dose of SC insulin glargine was 33.3 ± 13.8 U; the mean daily total insulin aspart dose infused with the V-Go was 31.5 ± 7.5 and 32.3 ± 7.8 U for the inpatient and outpatient periods, respectively. Fasting blood glucose values were similar to those observed at baseline throughout the study, with nonsignificant (NS) reductions in readings collected during the outpatient phase before lunch (−35 ± 27 mg/dl) and before dinner (−38 ± 25 mg/dl). The 2-hour postprandial glucose trended lower from 231 to 195 mg/dl (NS) at breakfast, 234 to 166 mg/dl (NS) at lunch, and 222 to 171 mg/dl (NS) at dinner. Bedtime blood glucose decreased (mean change from baseline −52 ± 21 mg/dl; P = 0.0313), as did nighttime (3:00 AM) measurements (−20 ± 9 mg/dl; P = 0.0313). Overall glycemic control tended to improve, as shown by continuous glucose monitoring changing from 173 to 157 mg/dl ( P = 0.063, NS) and 156 mg/dl ( P = 0.219) during inpatient and outpatient periods, respectively. Glycemic variability assessed by the M value similarly tended to decrease from 33 ± 9 to 25 ± 4 (NS) and 21 ± 4 (NS) for inpatient and outpatient periods, respectively. Conclusions: These first data suggest that use of the V-Go is an attractive alternative to SC insulin injection therapy because metabolic control appears to be maintained or even improved without increasing daily insulin doses.
Randomized Forced Titration to Different Doses of Technosphere® Insulin Demonstrates Reduction in Postprandial Glucose Excursions and Hemoglobin A1c in Patients with Type 2 Diabetes
Authors: Tack Cees J. , Christov Vladimir , de Galan Bastiaan E. , Derwahl Karl-Michael , Klausmann Gerhard , Pelikánová Terezie , Perušičová Jindra , Boss Anders H. , Amin Nikhil , Kramer David , Petrucci Richard , Yu Wen , Yu Wen ,   The 005 Study Group
Published: January 2014

Background: Individuals with type 2 diabetes mellitus have impairments in early insulin release, resulting in increased postprandial glucose excursions and suboptimal glycemic control. Studies with Technosphere® Insulin (TI) indicate that it has rapid systemic absorption and a short duration of glucose-lowering activity, making it well suited for controlling postprandial glucose levels. Methods: The goal of this phase 2b, prospective, multicenter, double-blind, placebo-controlled study was to characterize the dose response of four different doses (equivalent to 3.6, 7.3, 10.9, and 14.6 U subcutaneous regular human insulin) of prandial TI or Technosphere powder alone administered before each of three meals daily, in combination with insulin glargine over an 11-week treatment period, in patients with type 2 diabetes and suboptimal glycemic control. Conclusions: This study demonstrated that, over 11 weeks, TI plus basal insulin glargine is well tolerated and results in dose-dependent reductions in postprandial glucose and HbA1c levels. Results: The study enrolled 227 patients. In all dose groups, TI demonstrated statistically significant dose-dependent reductions in hemoglobin A1c (HbAlc) versus baseline (−0.4, −0.5, −0.5, and −0.6 for 3.6, 7.3, 10.9, and 14.6 U equivalents, respectively; p < 0.05 in all groups), as well as versus placebo or Technosphere powder alone (−0.40, −0.67, −0.70, and −0.78 for 3.6, 7.3, 10.9, and 14.6 U equivalents, respectively; p < 0.04 in all groups). It reduced the postprandial maximum glucose concentration within each treatment group (statistically significant in all but the TI 3.6 U-equivalent group) and reduced the postprandial area under the glucose curve (statistically significant for the TI 10.9 and 14.6 U-equivalent groups) versus placebo. There were no cases of severe hypoglycemia, while mild/moderate hypoglycemia was observed most frequently in the highest dosage groups, as expected. Rates of cough were low and comparable among all groups. No clinically relevant changes in pulmonary function tests, body weight, or high-resolution computerized axial tomography and magnetic resonance imaging were observed.
Evaluation of the VIA® Blood Chemistry Monitor for Glucose in Healthy and Diabetic Volunteers
Authors: Ganesh Arjunan , Hipszer Brian , Loomba Navdeep , Simon Barbara , Torjman Marc C. , Joseph Jeffrey 
Published: January 2014

Background: Manual methods of blood glucose monitoring are labor-intensive, costly, prone to error, and expose the caregiver to blood. The VIA® blood chemistry monitor for glucose can automatically measure plasma glucose (PG) every 5 minutes for 72 hours using blood sampled from a peripheral vein/artery or a central vein. Methods: VIA performance was evaluated in eight normal and five type 1 diabetic (T1DM) subjects in 15 separate experiments. The VIA device was connected to a peripheral vein and reported a PG value every 5 minutes during each 510-minute experiment. Blood samples were collected manually every 10 minutes and assayed using a HemoCue® β-glucose analyzer (HC). Whole blood HC measurements were corrected to PG values. Paired HC/VIA measurements ( n = 717) were analyzed. Results: Mean PG was 90 ± 14 and 96 ± 12 mg/dl in normal subjects and 194 ± 64 and 173 ± 48 mg/dl in T1DM subject as measured by the HC and VIA, respectively. Clark error grid analysis revealed 86% points in zone A, 11% points in zone B, and 2% points in zone D. Linear regression analysis yielded the following equation: VIA = 0.732 × HC + 30.5 ( r2 = 0.954). Residual analysis revealed a glucose-dependent bias between the HC and the VIA. VIA data were transformed using the linear regression equation to correct for bias. After the correction, the mean absolute relative difference between the VIA and the HC was less than 10%, and 99.6% of data were in zones A and B. The VIA was able to sample blood automatically every 5 minutes for more than 8 hours in the laboratory setting. On average, the VIA reported glucose values for 94% of the samples it attempted to obtain. Conclusions: This study demonstrated that the VIA blood chemistry monitor for glucose can reliably sample blood frequently for a prolonged period of time safely and effectively in diabetic and nondiabetic volunteers. Agreement between the two devices was the closest at normal glucose concentrations. After correcting for a glucose-dependent bias between the devices, the MARD was consistently less than 10% for all glucose ranges.
Automated Blood Sampling and Glucose Sensing in Critical Care Settings
Authors: Kunjan Kislaya , Lloyd Frank P. 
Published: January 2014

Background: Tight glycemic control (TGC) studies in intensive care units (ICU) have shown substantial improvements in clinical outcomes. However, implementation of TGC in ICU practice is partly constrained by the lack of automated continuous blood glucose monitoring systems that can facilitate clinically accurate feedback of glycemic data. The aim of this work is to develop a portable automated blood sampling system for integration with a glucose sensor for use in critical care settings. Methods: Clinical prototypes for glucose sensing in blood were developed based on two distinct technologies: mid-infrared laser absorption spectroscopy and electrochemistry. Concurrently, an automated peripheral venous blood sampling system was developed for integration with the glucose sensing system. Results: The glucose sensing prototypes were validated clinically with various biological samples in a continuous mode. A customized micropump was employed in conjunction with a novel peripheral venous catheter system to automatically sample blood from the subject's forearm. Microvolumes of blood were sampled in continuous and intermittent modes at clinically relevant user-defined frequencies. The clinical feasibility of blood sampling, along with continuous glucose sensing, was demonstrated. Conclusion: Cascade's automated peripheral venous blood sampling system, in combination with a flow-through glucose sensor system, offers several advantages over current state-of-the-art systems. This includes the potential for significantly improved workflow in the ICU, minimal discomfort to the patient, and accurate glucose measurement in whole blood, thus helping achieve tight glycemic control.
Inhaled Technosphere® Insulin in Comparison to Subcutaneous Regular Human Insulin: Time Action Profile and Variability in Subjects with Type 2 Diabetes
Authors: Rave Klaus , Heise Tim , Heinemann Lutz , Boss Anders H. 
Published: January 2014

Background: This study assessed time action profile and within- and between-subject variability of inhaled Technosphere® Insulin (TI) compared with subcutaneous regular human insulin (sc RHI). Methods: Thirteen subjects with type 2 diabetes (age 56 ± 7 years, body mass index 30.4 ± 3.0 kgm−2; hemoglobin A1c 6.9 ± 0.9%; mean ± SD) participated in this six-period crossover isoglycemic glucose clamp study. In randomized order, each subject received three single doses of TI and sc RHI on separate study days. Results: Inhalation of TI resulted in a higher maximum serum insulin concentration (858 vs 438 pmol·liter−1; p = 0.0001) and shorter intervals to maximum insulin concentration (17 vs 135 minutes; p = 0.0001) than sc RHI. Overall, 48 units of TI and 24 units of sc RHI provided comparable 3-hour insulin exposure (INS area under the curve0–3 h55.8 vs 60.0 nmol·min·liter−1, respectively). Time to maximum metabolic effect was shorter (79 vs 293 minutes; p < 0.0001), and percentage of glucose disposal during the first 3 hours was higher for TI compared with sc RHI (59 vs 27%). Within-subject variabilities of insulin exposure following inhalation of TI for 2 and 3 hours and end of study period were 19, 18, and 16% as compared with 27, 25, and 15% after sc RHI injection ( p = not significant). Conclusion: Technosphere Insulin has a more rapid onset of action than sc RHI. About 60% of the glucose-lowering effect of TI occurs during the first 3 hours after application. In contrast, <30% of the glucose-lowering effect of sc RHI occurs in this period. Technosphere Insulin demonstrated a lower intrasubject variability during the 3-hour postprandial period, without reaching statistical significance.
Cardiometabolic Risk Factors Assessed by a Finger Stick Dried Blood Spot Method
Authors: Kapur Sanjay , Kapur Sonia , Zava David 
Published: January 2014

Background: Cardiovascular and metabolic risk factors are gaining attention as potential indicators for intervention in the prevention and treatment of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Blood spot technology offers an efficient, convenient method to measure these risk factors in an at-risk population. Simple and convenient methods to assess cardiometabolic risk factors will allow clinicians to formulate treatment strategies for effective prevention and management of these conditions. Method: Insulin and high sensitivity C-reactive protein (hs-CRP) were measured in dried blood spot and corresponding serum samples using conventional commercial serum kits based on a direct sandwich ELISA technique. The triglyceride assay involved enzymatic hydrolysis of triglycerides by lipase to glycerol and free fatty acids. The glycerol produced was then measured by coupled enzyme reactions. Blood spot assays were modified from previously published methods to give improved accuracy and turnaround time. Results: Blood spot levels correlated well with serum levels of hs-CRP ( r = 0.99), triglycerides (fasting, r = 0.95; nonfasting, r = 0.94), and insulin (fasting, r = 0.93; nonfasting, r = 0.97). Conclusion: Blood spot testing for insulin, hs-CRP, and triglycerides may be helpful in the cardiometabolic screening or monitoring of patients at risk of developing CVD, T2DM, or metabolic syndrome.
Use of a Computerized Intravenous Insulin Algorithm within a Nurse-Directed Protocol for Patients Undergoing Cardiovascular Surgery
Authors: Davidson Paul C. , Steed R. Dennis , Bode Bruce W. , Hebblewhite Harry R. , Prevosti Louis , Cheekati Vasundhara 
Published: January 2014

Background: Several studies have shown the benefits of tight glycemic control in the intensive care unit. A large hospital became concerned about certain deficiencies in the management of glucose control in conjunction with cardiovascular surgery. A multidisciplinary steering committee was formed, which implemented a glycemic protocol, the subject of this study. Methods: The glycemic protocol is a perioperative, nurse-directed program that incorporates the computerized intravenous (IV) insulin algorithm, Glucommander. Upon admission, hemoglobin A1c and blood glucose (BG) were tested, and patients were screened for previously diagnosed diabetes. This information was used to determine if preoperative insulin will be used, if the patient will be transitioned post-IV to subcutaneous (SC) basal-bolus insulin, and if insulin will be prescribed on discharge. IV insulin was initiated perioperatively in known diabetes cases or if one BG value >140 mg/dl or two BG values >110 mg/dl within 24 hours before or during surgery. The target range was 90 to 120 mg/dl. Results: In the 9 months after protocol implementation, 93% of the patients had no BG value >200 mg/dl during the first 48 hours postoperatively. In the 6 months of study data, there were 457 patients. The mean time to target range was 3.0 hours. The mean IV insulin run time was 37 hours. The mean BG value was 107 mg/dl. Only 2% of patients had transient BG <50 mg/dl, and no BG values were >40 mg/dl. Of the patients, 52% were transitioned to SC basal-bolus, and 26% were discharged on insulin. Conclusions: The Glucommander earned high respect from the nurses for the way it scheduled BG tests and eliminated the calculation time and calculation errors associated with manual methods. The protocol was highly effective in normalizing glucose without hypoglycemia. The multidisciplinary steering committee proved to be a good approach to implementing a glycemic protocol.
An Internet Service Supporting Quality Assessment of Inpatient Glycemic Control
Authors: Thomas Prem , Inzucchi Silvio E. 
Published: January 2014

Background: Several studies have linked the maintenance of normoglycemia in acutely ill inpatients with improved clinical outcomes. We previously proposed a few standard definitions for monitoring inpatient glycemic control, or “glucometrics.” In clinical practice, limited data management resources for developing and refining measurement protocols can slow quality improvement efforts. With regard to glucometrics, there are few baseline data regarding the quality of hospital glycemic management. Furthermore, there are no reliable methods for hospitals to gauge the progress of their quality improvement efforts. Methods: We built a novel Web application that calculates glucometrics on anonymized blood glucose data files uploaded by registered users. This Web site also collects many key characteristics of the users and institutions utilizing the service. This application will allow us to pool data from several institutions to calculate aggregate glucometrics, providing baseline data for quality improvement efforts and ongoing metrics for institutions to gauge their progress. Results: The application, accessible at http://metrics.med.yale.edu , has already drawn visitors from several countries. A number of users have registered formally, and some have begun to upload institutional glucose data. The application delivers detailed glucometrics reports to registered users, complete with visual displays. Quality improvement staff from large health systems have been the predominant users. Conclusions: We have created an open access Web application to facilitate quality monitoring and improvement efforts—as well as clinical research—regarding inpatient glycemic management. If employed widely, this application could help establish national performance standards for glycemic control.
In Silico Simulation of Long-Term Type 1 Diabetes Glycemic Control Treatment Outcomes
Authors: Wong Xing-Wei , Chase J. Geoffrey , Hann Christopher E. , Lotz Thomas F. , Lin Jessica , Le Compte Aaron J. , Shaw Geoffrey M. 
Published: January 2014

Objectives: The goals of this study were to develop (1) a safe and effective protocol for the clinical control of type 1 diabetes using conventional self-monitoring blood glucose (SMBG) measurements and multiple daily injections with insulin analogues, and (2) an in silico simulation tool of type 1 diabetes to predict long-term glycemic control outcomes of clinical interventions. Methods: The virtual patient method was used to develop a simulation tool for type 1 diabetes using data from a type 1 diabetes patient cohort ( n = 40). The tool was used to test the adaptive protocol (AC) and a conventional intensive insulin therapy (CC) against results from a representative control cohort. Optimal and suboptimal basal insulin replacements were evaluated as a function of SMBG frequency in conjunction with the (AC and CC) prandial control protocols. Results: In long-term glycemic control, the AC protocol significantly decreased hemoglobin A1c in conditions of suboptimal basal insulin replacement for SMBG frequencies ≥6/day, and reduced the occurrence of mild and severe hypoglycemia by 86–100% over controls, over all SMBG frequencies in conditions of optimal basal insulin. Conclusions: A simulation tool to predict long-term glycemic control outcomes from clinical interventions has been developed to test a novel, adaptive control protocol for type 1 diabetes. The protocol is effective and safe compared to conventional intensive insulin therapy and controls. As fear of hypoglycemia is a large psychological barrier to glycemic control, the AC protocol may represent the next evolution of intensive insulin therapy to deliver increased glycemic control with increased safety. Further clinical or experimental validation is needed to fully prove the concept.
FlexPen® and KwikPen™ Prefilled Insulin Devices: A Laboratory Evaluation of Ergonomic and Injection Force Characteristics
Authors: Ignaut Debra A. , Opincar Michael , Lenox Sheila 
Published: January 2014

Background: Advances in insulin pen technology continue to improve the usability of these devices for patients with diabetes. In this study, ergonomic features and injection force, as measured by glide force (GF) and glide force variability (GFV), were evaluated for the new Humalog® Mix75/25 KwikPen™ (KwikPen) and compared with the NovoLog® Mix 70/30 FlexPen® (FlexPen). Methods: Fifty prefilled insulin pen devices (25 of each type) were measured for diameter at the cartridge holder and dose window, length and weight with cap attached, and thumb reach at 30 and 60 units. GF was also determined for 100 devices (50 of each type); GFV at 30 and 60 unit doses was calculated for the plateau portion of the force curve based on the minimum and maximum force measured in that portion of the curve. Results: While FlexPen was lighter in weight than KwikPen, and presented a slightly smaller diameter at the cartridge holder and dose window, KwikPen had a shorter overall pen length compared to FlexPen, with a shorter thumb reach at both the 30- and 60-unit dose settings. The maximum GF for KwikPen was less than FlexPen at both the 30-unit (3.42 vs 5.36 lb, p <0.0001) and 60-unit doses (3.61 vs 5.62, p <0.0001). KwikPen GFV was lower across both doses (mean difference: −0.46 lb at 30 units, −0.44 lb at 60 units; p <0.0001 for both). Conclusions: While FlexPen was lighter with a slightly smaller cartridge holder and dose window diameter, KwikPen was shorter in length with less thumb reach than FlexPen. KwikPen also demonstrated lower GF and GFV, resulting in a smoother injection profile than FlexPen. These features of KwikPen's design and function may offer important advantages for the user during insulin administration.
Use of Continuous Glucose Monitoring to Estimate Insulin Requirements in Patients with Type 1 Diabetes Mellitus during a Short Course of Prednisone
Authors: Bevier Wendy C. , Zisser Howard C. , Jovanovič Lois , Finan Daniel A. , Palerm Cesar C. , Seborg Dale E. , Doyle Francis J. 
Published: January 2014

Background: Insulin requirements to maintain normoglycemia during glucocorticoid therapy and stress are often difficult to estimate. To simulate insulin resistance during stress, adults with type 1 diabetes mellitus (T1DM) were given a three-day course of prednisone. Methods: Ten patients (7 women, 3 men) using continuous subcutaneous insulin infusion pumps wore the Medtronic Minimed CGMS® (Northridge, CA) device. Mean (standard deviation) age was 43.1 (14.9) years, body mass index 23.9 (4.7) kg/m2, hemoglobin A1c 6.8% (1.2%), and duration of diabetes 18.7 (10.8) years. Each patient wore the CGMS for one baseline day (day 1), followed by three days of self-administered prednisone (60 mg/dl; days 2–4), and one post-prednisone day (day 5). Results: Analysis using Wilcoxon signed rank test (values are median [25th percentile, 75th percentile]) indicated a significant difference between day 1 and the mean of days on prednisone (days 2–4) for average glucose level (110.0 [81.0, 158.0] mg/dl vs 149.2 [137.7, 168.0] mg/dl; p = .022), area under the glucose curve and above the upper limit of 180 mg/dl per day (0.5 [0, 8.0] mg/dl·d vs 14.0 [7.7, 24.7] mg/dl·d; p = .002), and total daily insulin dose (TDI), (0.5 [0.4, 0.6] U/kg·d vs 0.9 [0.8, 1.0] U/kg·d; p = .002). In addition, the TDI was significantly different for day 1 vs day 5 (0.5 [0.4, 0.6] U/kg·d vs 0.6 [0.5, 0.8] U/kg·d; p = .002). Basal rates and insulin boluses were increased by an average of 69% (range: 30–100%) six hours after the first prednisone dose and returned to baseline amounts on the evening of day 4. Conclusions: For adults with T1DM, insulin requirements during prednisone induced insulin resistance may need to be increased by 70% or more to normalize blood glucose levels.