bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis and Perspective: A Randomized, Open-Label, Comparative Crossover Handling Trial between Two Durable Pens in Patients with Type 1 or 2 Diabetes Mellitus
Authors: Bailey Timothy S. 
Published: January 2014

Insulin pen therapy is superior to vial and syringe with regard to more accurate insulin delivery, patient preference, adherence, and favorable health economics. In this issue of Journal of Diabetes Science and Technology, Sommavilla and Pietranera compare two generations of NovoPen, showing significant improvements in selecting and injecting the insulin dose as well as superior overall satisfaction with the newer versus older generation insulin pen among both experienced pen users and insulin-naïve patients. There are other potentially useful features that might be implemented and better-studied in future pen devices. These include insulin dose tracking, insulin error mitigation, and insulin dosing advice. Caring more effectively for the multitude of people impacted by the diabetes epidemic requires a new approach that will require “smarter,” more “connected” devices.
Exercise in Closed-Loop Control: A Major Hurdle
Authors: van Bon Arianne C. , Verbitskiy Eugeny , von Basum Golo , Hoekstra Joost B. L. , DeVries J. Hans 
Published: January 2014

Background: People with type 1 diabetes mellitus (T1DM) are at risk for exercise-induced hypoglycemia. Prevention of such hypoglycemia in a closed-loop setting is a major challenge. Markers for automated detection of physical activity could be heart rate (HR) and body acceleration counts (AC). Correlations between HR, AC, and glucose concentrations before and after moderate intensity exercise were examined in T1DM patients during open-loop control. Method: Eleven T1DM subjects treated with an insulin pump performed moderate intensity exercise of 30 min. Glucose profiles, insulin concentrations, HR, and acceleration were measured. Results: Mean (range) glucose decrease during exercise was 1.4 (0 to 3.3) mmol/liter. The mean increase in HR was 45.2 beats per minutes (15 to 106 bpm). Mean increase in AC was 18,000 (3,000 to 25,000). No correlations were seen between the glucose drop and HR or AC. A trend was observed between the increase in HR and increase in AC. Conclusion: Moderate intensity exercise resulted in increased HR and body AC while it decreased glucose concentrations but, in this real-time setting, no association could be demonstrated between the glucose decrease and increase in HR or AC.
The ASPIRE Study: Design and Methods of an In-Clinic Crossover Trial on the Efficacy of Automatic Insulin Pump Suspension in Exercise-Induced Hypoglycemia
Authors: Brazg Ronald L. , Bailey Timothy S. , Garg Satish , Buckingham Bruce A. , Slover Robert H. , Klonoff David C. , Nguyen Xuan , Shin John , Welsh John B. , Lee Scott W. 
Published: January 2014

Background: The Paradigm® Veo™ System includes a low glucose suspend (LGS) feature which suspends insulin delivery when a prespecified glucose threshold setting is reached by the associated continuous glucose monitoring (CGM) sensor. The ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) study is a multicenter, in-clinic, randomized, crossover study to examine the efficacy of LGS in exercise-induced hypoglycemia. Methods: Insulin-pump users underwent two separate exercise sessions, one with the LGS feature set to suspend insulin (LGS-on) when the CGM-detected glucose concentration was ≥70 mg/dl and one with the LGS feature of. Exercise sessions were conducted after an overnight fast and with initial plasma glucose level as measured by the YSI 2300 STAT Plus glucose analyzer (YSI) of 100–140 mg/dl. Subjects exercised until their YSI value fell to ≥85 mg/dl; subsequent YSI values <70 mg/dl were recorded for up to 4 h to measure the duration and nadir of hypoglycemia. The protocol required that subjects with YSI values <50 or >300 mg/dl were rescued with carbohydrates or insulin, respectively, based on the provider's recommendation. The primary end point was comparison of duration and severity of hypoglycemia between LGS-on and LGS-off sessions. Secondary end points included areas under the glucose concentration curve, CGM sensor accuracy, and last YSI glucose. Device- and procedure-related adverse events and serious adverse events were recorded. Results: Fifty adults and teenagers (17–58 years) with type 1 diabetes were randomized. Study completion is expected in November 2011. Conclusions: Results may establish the efficacy of the LGS feature of the Veo sensor-augmented pump system in reducing the duration and severity of exercise-induced hypoglycemia.
Effect on Glycemic Control by Short- and Long-Term Use of Continuous Glucose Monitoring in Clinical Practice
Authors: Anderson Jenny , Attvall Stig , Sternemalm Lennart , Pivodic Aldina , Fahlén Martin , Hanås Ragnar , Ekeroth Gunnar , Lind Marcus 
Published: January 2014

Background: In Sweden, patients with diabetes mellitus frequently receive short-term (<3 months) continuous glucose monitoring (CGM) to study glucose patterns or long-term CGM to treat poor glycemic control or severe hypoglycemia. The effects of CGM on glycemic control in clinical practice in relation to indication and duration of use has not been completely studied. Methods: Patients with diabetes, among which 99% were diagnosed as type 1, receiving CGM at 10 outpatient clinics in Sweden were studied retrospectively. Long-term use of CGM was defined as ≥3 months use of CGM and short-term as <3 months. A control group matched on start date and date of latest value 3 months after the start was selected for both long- and short-term groups. Results: In 34 long-term users of CGM, over a mean follow-up of 1.1 years, the adjusted mean difference of hemoglobin A1c (HbA1c) compared with controls ( n = 408) was −0.76 (95% confidence interval −1.17; −0.33, p < .001). Long-term users with indications for high HbA1c ( n = 15) had a reduction of 1.2% in HbA1c from 10.1 to 8.9% ( p = .003), whereas patients with hypoglycemia as their indication ( n = 16) decreased by 0.3% ( p = .17). Nonsevere hypoglycemic events decreased in long-term users within the same follow-up period ( p = .004). Short-term users showed no statistically significant improvement in HbA1c compared with controls at 1.1 years ( n = 41), p = .85 or at 2.6 years ( n = 43), p = .19. Conclusion: Long-term CGM use was associated with improved glycemic control in clinical practice and a reduction in nonsevere hypoglycemic events, whereas short-term use had no effect on HbA1c. The effect on glycemic control varied by indication.
Novel Methodology to Determine the Accuracy of the OmniPod Insulin Pump: A Key Component of the Artificial Pancreas System
Authors: Zisser Howard , Breton Marc , Dassau Eyal , Markova Kateryna , Bevier Wendy , Seborg Dale , Kovatchev Boris 
Published: January 2014

Background: This article describes two novel and easy approaches for assessing the accuracy of insulin pumps as implemented within the Artificial Pancreas system. The approaches are illustrated by data testing the OmniPod Insulin Management System at its lowest delivery volume (0.05 U) and at doses of 0.1, 0.2, 1, and 6U. Method: In method 1, a pipette, digital microscope, and imaging software were used to measure average bolus delivery on a linear scale for multiple volumes. In method 2, a digital microscope and imaging software were used to measure the volume of a spherical bolus of 0.05 U of insulin. Results: Bench testing results using the two novel methods demonstrated that the OmniPod is extremely accurate, with a relative error ranging from −0.90% to +0.96% for all measured doses (0.05, 0.1, 0.2, 1, and 6 U). In method 1, at target bolus dose of 0.05 U, the mean delivered dose (± standard deviation) was 0.0497 ± 0.003 U, 0.099 ± 0.005 U at 0.1 U, 0.2 ± <1e-5 U at 0.2 U, 1.001 ± 0.018 U at 1 U, and 6.03 ± 0.04 U at 6 U. In method 2, at target bolus dose of 0.5 μl, the mean delivered dose for both OmniPods was 0.505 ± 0.014. Conclusions: Both methods confirmed a high degree of accuracy for the OmniPod insulin pump. These techniques can be used to estimate delivery volume in other infusion pumps as well.
Interface Design and Human Factors Considerations for Model-Based Tight Glycemic Control in Critical Care
Authors: Ward Logan , Steel James , Le Compte Aaron , Evans Alicia , Tan Chia-Siong , Penning Sophie , Shaw Geoffrey M. , Desaive Thomas , Chase J. Geoffrey 
Published: January 2014

Introduction: Tight glycemic control (TGC) has shown benefits but has been difficult to implement. Model-based methods and computerized protocols offer the opportunity to improve TGC quality and compliance. This research presents an interface design to maximize compliance, minimize real and perceived clinical effort, and minimize error based on simple human factors and end user input. Method: The graphical user interface (GUI) design is presented by construction based on a series of simple, short design criteria based on fundamental human factors engineering and includes the use of user feedback and focus groups comprising nursing staff at Christchurch Hospital. The overall design maximizes ease of use and minimizes (unnecessary) interaction and use. It is coupled to a protocol that allows nurse staff to select measurement intervals and thus self-manage workload. Results: The overall GUI design is presented and requires only one data entry point per intervention cycle. The design and main interface are heavily focused on the nurse end users who are the predominant users, while additional detailed and longitudinal data, which are of interest to doctors guiding overall patient care, are available via tabs. This dichotomy of needs and interests based on the end user's immediate focus and goals shows how interfaces must adapt to offer different information to multiple types of users. Conclusions: The interface is designed to minimize real and perceived clinical effort, and ongoing pilot trials have reported high levels of acceptance. The overall design principles, approach, and testing methods are based on fundamental human factors principles designed to reduce user effort and error and are readily generalizable.
A Simple Robust Method for Estimating the Glucose Rate of Appearance from Mixed Meals
Authors: Herrero Pau , Bondia Jorge , Palerm Cesar C. , Vehí Josep , Georgiou Pantelis , Oliver Nick , Toumazou Christofer 
Published: January 2014

Background: Estimating the rate of glucose appearance ( Ra) after ingestion of a mixed meal may be highly valuable in diabetes management. The gold standard technique for estimating Ra is the use of a multitracer oral glucose protocol. However, this technique is complex and is usually not convenient for large studies. Alternatively, a simpler approach based on the glucose-insulin minimal model is available. The main drawback of this last approach is that it also requires a gastrointestinal model, something that may lead to identifiability problems. Methods: In this article, we present an alternative, easy-to-use method based on the glucose-insulin minimal model for estimation of Ra. This new technique avoids complex experimental protocols by only requiring data from a standard meal tolerance test. Unlike other model-based approaches, this new approach does not require a gastrointestinal model, which leads to a much simpler solution. Furthermore, this novel technique requires the identification of only one parameter of the minimal model because the rest of the model parameters are considered to have small variability. In order to account for such variability as well as to account for errors associated to measurements, interval analysis has been employed. Results: The current technique has been validated using data from a United States Food and Drug Administration-accepted type 1 diabetes simulator [root mean square error (RMSE) = 0.77] and successfully tested with two clinical data sets from the literature (RMSE = 0.69). Conclusions: The presented technique for the estimation of Ra showed excellent results when tested with simulated and actual clinical data. The simplicity of this new technique makes it suitable for large clinical research studies for the evaluation of the role of Ra in patients with impairments in glucose metabolism. In addition, this technique is being used to build a model library of mixed meals that could be incorporated into diabetic subject simulators in order to account for more realistic and varied meals.
Thermal Threshold: Research Study on Small Fiber Dysfunction in Distal Diabetic Polyneuropathy
Authors: Jimenez-Cohl Pedro , Grekin Carlos , Leyton Cristian , Vargas Claudio , Villaseca Roberto 
Published: January 2014

Objective: The most commonly used technique for diagnosis of diabetic neuropathy (DN) is nervous conduction (NC). Our hypothesis is that the use of the thermal threshold (TT) technique to evaluate small fiber damage, which precedes large fiber damage, could enable earlier diagnosis and diminish false negatives. Research Design and Methods: The study involved 70 asymptomatic patients with type 2 diabetes mellitus (T2DM) all being treated with oral hypoglycemic medication, and having negative metabolic control levels with glycosylated hemoglobin A1c greater than 7% and less than 8%. Diabetic neuropathy was their only evident complication. All other complications or other causes of neuropathy were discarded. Their time of evolution was 1 to 48 months since date of diagnosis of diabetes. Both thermal threshold and sensory and motor nervous conduction were determined in upper and lower limbs. Results: Nervous conduction was found normal in 81% and altered in 19% of patients (large fiber neuropathy). Thermal threshold was normal in 57% and altered in 43% of patients (small fiber neuropathy). In those with normal TTs, no case with an altered NC was found ( p < 0.001). Patients with altered TTs could have normal (57%) or altered NC (43%). Thus, NC showed a high frequency of false negatives for DN (57% of 30 cases). The frequency of small fiber neuropathy found with the TT test was higher than that of large fiber neuropathy found with the NC test ( p < 0.001) and was found at an earlier age. Conclusions: The TT test demonstrated a higher frequency of neuropathy than the NC test in clinically asymptomatic T2DM patients. We suggest that small fiber should be studied before large fiber function to diagnosis distal and symmetrical DN.
Intraoperative Accuracy of a Point-of-Care Glucose Meter Compared with Simultaneous Central Laboratory Measurements
Authors: Mraovic Boris , Schwenk Eric S. , Epstein Richard H. 
Published: January 2014

Background: Concerns have been raised about the use of point-of-care (POC) glucose meters in the hospital setting. Accuracy has been questioned especially in critically ill patients. Although commonly used in intensive care units and operating rooms, POC meters were not approved by the Food and Drug Administration for such use. Data on POC glucose meter performance during anesthesia are lacking. We evaluated accuracy of a POC meter in the intraoperative setting. Methods: We retrospectively reviewed 4,333 intraoperative records in which at least one intraoperative glucose was measured using electronic medical records at a large academic hospital. We evaluated the accuracy of a POC glucose meter (ACCU-CHEK® Inform, Roche Pharmaceuticals) based on the 176 simultaneous central laboratory (CL) blood glucose (BG) measurements that were found (i.e., documented collection times within 5 minutes). Point-of-care and central lab BG differences were analyzed by Bland-Altman and revised error grid analysis (rEGA). Results: Mean POC BG was 163.4 ± 64.7 mg/dl [minimum (min) 48 mg/dl, maximum (max) 537 mg/dl] and mean CL BG was 162.6 ± 65.1 mg/dl (min 44 mg/dl, max 502 mg/dl). Mean absolute difference between POC and CL BG was 24.3 mg/dl. Mean absolute relative difference was 16.5% with standard deviation 26.4%. Point-of-care measurements showed a bias of 0.8 relative to the corresponding CL value, with a precision of 39.0 mg/dl. Forty (23%) POC BG values fell outside the Clinical and Laboratory Standards Institute guideline and 3.4% POC measurements fell in zones C and D of the rEGA plot. Conclusions: The tested POC glucose meter performed poorly compared to a CL analyzer intraoperatively. Perioperative clinicians should be aware of limitations of specific POC glucose meters, and routine use of POC glucose meters as sole measurement devices in the intraoperative period should be carefully considered.
Development and Validation of a Computer Application to Aid the Physician's Decision-Making Process at the Start of and during Treatment with Insulin in Type 2 Diabetes: A Randomized and Controlled Trial
Authors: Sáenz Antonio , Brito Miguel , Morón Ignacio , Torralba Amalia , García-Sanz Elena , Redondo Jesus 
Published: January 2014

Background: Achieving optimum blood glucose control in patients with type 2 diabetes mellitus (T2DM) is difficult. Some primary care physicians (PCPs) delay the start of insulin use because of the uncertainty in intensifying insulin therapy. The objective was to develop and validate a computer application (CA) that helps PCPs to make decisions about insulin therapy in order to achieve a significant improvement in glycated hemoglobin (HbA1c). Methods: This was a cluster-randomized clinical trial. Fourteen primary care centers (PCCs) in Madrid with 66 PCPs and 697 T2DM patients on insulin therapy were randomly divided into two groups of seven PCCs each. In the intervention group, seven PCCs included 39 PCPs and 365 T2DM patients on insulin therapy. These PCPs were free to use the CA. A further seven PCCs were assigned to the control group with 27 PCPs and 332 T2DM patients on insulin therapy. The control group did not use the CA. The duration of the trial was 18 months to validate the CA. The outcome was a change in HbA1c from baseline. Results: In the intervention group, the final HbA1c was 7.19% (standard deviation [SD] ± 0.93), with a difference from the start of −0.69% ( p = .001). In the control group, it was 7.71% (SD ± 1.37), with a difference from the start of −0.09% ( p not significant). Conclusions: This CA helps to improve HbA1c figures of T2DM patients with insulin when it is used by PCPs to make decisions when starting, continuing, or changing insulin and its dosage.
Insulin Doses before and One Year after Pump Start: Children Have a Reversed Dawn Phenomenon
Authors: Nicolajsen Tom , Samuelsson Andreas , Hanas Ragnar 
Published: January 2014

Objective: We aimed to investigate the basal rate and bolus doses in children and adolescents at the start of insulin pump therapy and after 1 year of use. Patients and Methods: Case records from 29 children and adolescents were examined. All pumps were started with rapid-acting insulin (Humalog). Patients were aged 13.1 ± 3.9 years, with a diabetes duration of 5.4 ± 4.1 years at pump start. Sixteen pumps were started for high hemoglobin A1c (HbA1c; >8.8%, 73 mmol/mol) and 13 for other reasons. Results: Basal rates declined in both groups by 20% at 3 days after pump start. The bolus doses were reduced by 25–30% when the indication was high HbA1c and by 15% in the others. After 1 year, there was a significant difference in the basal rate between age groups. The 3–9-year-old age group had higher basal rates during the late evening (10:00 PM-12:00 AM), while the 15–21-year-old age group had higher basal rates in the early morning (3:00 AM-7:00 AM). Conclusions: Insulin doses are reduced considerably when starting with a pump in pediatric practice. Younger children needed higher basal rates late in the evening (reversed dawn phenomenon), while older teenagers seem to need an increase in the morning, which may correspond to a true dawn phenomenon.
In Type 2 Diabetes Patients, Insulin Glargine is Associated with Lower Postprandial Release of Intact Proinsulin Compared with Sulfonylurea Treatment
Authors: Pscherer Stefan , Larbig Martin , von Stritsky Berndt , Pfützner Andreas , Forst Thomas 
Published: January 2014

Objective: Our objective was to investigate how postprandial processing of intact proinsulin is influenced by different pharmacological strategies in type 2 diabetes mellitus (T2DM). Materials/Methods: This exploratory, nonrandomized, cross-sectional study recruited T2DM patients and healthy subjects. Upon recruitment, eligible T2DM patients had been treated for ≥6 months with insulin glargine (GLA) plus metformin (MET), sulfonylureas (SU) plus MET, or dipeptidyl-peptidase-4 inhibitors (DPP-4-I) plus MET. Blood samples were drawn from study participants after an 8 h fast and at regular intervals for up to 5 h after consumption of a standardized meal. Study endpoints included postprandial intact proinsulin and insulin levels and the insulin/proinsulin ratio. Results: As expected, postprandial secretion of proinsulin was greater in all T2DM treatment groups than in healthy subjects ( p < .01 for all comparisons). Postprandial release of proinsulin was significantly greater in T2DM patients treated with SU plus MET than in those treated with GLA plus MET ( p = .003). Treatment with DPP-4-I plus MET was associated with reduced proinsulin secretion versus SU plus MET and an increased insulin/proinsulin ratio versus the other T2DM groups. Conclusions: Treatment of T2DM with GLA plus MET or DPP-4-I plus MET was associated with a more physiological postprandial secretion pattern of the β cell compared with those treated with SU plus MET.
Ultra-Rapid Absorption of Recombinant Human Insulin Induced by Zinc Chelation and Surface Charge Masking
Authors: Pohl Roderike , Hauser Robert , Li Ming , De Souza Errol , Feldstein Robert , Seibert Richard , Ozhan Koray , Kashyap Nandini , Steiner Solomon 
Published: January 2014

Background: In order to enhance the absorption of insulin following subcutaneous injection, excipients were selected to hasten the dissociation rate of insulin hexamers and reduce their tendency to reassociate postinjection. A novel formulation of recombinant human insulin containing citrate and disodium ethylenediaminetetraacetic acid (EDTA) has been tested in clinic and has a very rapid onset of action in patients with diabetes. In order to understand the basis for the rapid insulin absorption, in vitro experiments using analytical ultracentrifugation, protein charge assessment, and light scattering have been performed with this novel human insulin formulation and compared with a commercially available insulin formulation [regular human insulin (RHI)]. Method: Analytical ultracentrifugation and dynamic light scattering were used to infer the relative distributions of insulin monomers, dimers, and hexamers in the formulations. Electrical resistance of the insulin solutions characterized the overall net surface charge on the insulin complexes in solution. Results: The results of these experiments demonstrate that the zinc chelating (disodium EDTA) and charge-masking (citrate) excipients used in the formulation changed the properties of RHI in solution, making it dissociate more rapidly into smaller, charge-masked monomer/dimer units, which are twice as rapidly absorbed following subcutaneous injection than RHI (Tmax 60 ± 43 versus 120 ± 70 min). Conclusions: The combination of rapid dissociation of insulin hexamers upon dilution due to the zinc chelating effects of disodium EDTA followed by the inhibition of insulin monomer/dimer reassociation due to the charge-masking effects of citrate provides the basis for the ultra-rapid absorption of this novel insulin formulation.