bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Classification of Diabetic Gait Pattern Based on Cluster Analysis of Biomechanical Data
Authors: Sawacha Zimi , Guarneri Gabriella , Avogaro Angelo , Cobelli Claudio 
Published: January 2014

Background: The diabetic foot, one of the most serious complications of diabetes mellitus and a major risk factor for plantar ulceration, is determined mainly by peripheral neuropathy. Neuropathic patients exhibit decreased stability while standing as well as during dynamic conditions. A new methodology for diabetic gait pattern Classification based on cluster analysis has been proposed that aims to identify groups of subjects with similar patterns of gait and verify if three-dimensional gait data are able to distinguish diabetic gait patterns from one of the control subjects. Method: The gait of 20 nondiabetic individuals and 46 diabetes patients with and without peripheral neuropathy was analyzed [mean age 59.0 (2.9) and 61.1(4.4) years, mean body mass index (BMI) 24.0 (2.8), and 26.3 (2.0)]. K-means cluster analysis was applied to classify the subjects' gait patterns through the analysis of their ground reaction forces, joints and segments (trunk, hip, knee, ankle) angles, and moments. Results: Cluster analysis Classification led to definition of four well-separated clusters: One aggregating just neuropathic subjects, one aggregating both neuropathics and non-neuropathics, one including only diabetes patients, and one including either controls or diabetic and neuropathic subjects. Conclusions: Cluster analysis was useful in grouping subjects with similar gait patterns and provided evidence that there were subgroups that might otherwise not be observed if a group ensemble was presented for any specific variable. In particular, we observed the presence of neuropathic subjects with a gait similar to the controls and diabetes patients with a long disease duration with a gait as altered as the neuropathic one.
Modeling the Effects of Subcutaneous Insulin Administration and Carbohydrate Consumption on Blood Glucose
Authors: Percival Matthew W. , Bevier Wendy C. , Wang Youqing , Dassau Eyal , Zisser Howard C. , Jovanovič Lois , Doyle Francis J. 
Published: January 2014

Background: Estimation of the magnitude and duration of effects of carbohydrate (CHO) and subcutaneously administered insulin on blood glucose (BG) is required for improved BG regulation in people with type 1 diabetes mellitus (T1DM). The goal of this study was to quantify these effects in people with T1DM using a novel protocol. Methods: The protocol duration was 8 hours: A 1–3 U subcutaneous (SC) insulin bolus was administered and a 25-g CHO meal was consumed, with these inputs separated by 3–5 hours. The DexCom SEVEN® PLUS continuous glucose monitor was used to obtain SC glucose measurements every 5 minutes and YSI 2300 Stat Plus was used to obtain intravenous glucose measurements every 15 minutes. Results: The protocol was tested on 11 subjects at Sansum Diabetes Research Institute. The intersubject parameter coefficient of variation for the best identification method was 170%. The mean percentages of output variation explained by the bolus insulin and meal models were 68 and 69%, respectively, with root mean square error of 14 and 10 mg/dl, respectively. Relationships between the model parameters and clinical parameters were observed. Conclusion: Separation of insulin boluses and meals in time allowed unique identification of model parameters. The wide intersubject variation in parameters supports the notion that glucose-insulin models and thus insulin delivery algorithms for people with T1DM should be personalized. This experimental protocol could be used to refine estimates of the correction factor and the insulin-to-carbohydrate ratio used by people with T1DM.
Correct Use of a New Reusable Insulin Injection Pen by Patients with Diabetes: A Design Validation Study
Authors: Schwartz Sherwyn 
Published: January 2014

Background: Insulin pen devices are currently being used by approximately half of insulin users worldwide. ClikSTAR® (sanofi-aventis) is a novel reusable insulin pen for injecting either long-acting insulin glargine or short-acting insulin glulisine. The objective of this study was to demonstrate that individuals with diabetes could use the ClikSTAR pen correctly. Methods: In this open-label, single-center study, people with diabetes delivered three 40 U insulin doses after receiving training from a diabetes specialist (group A, n = 256) or after self-training (group B, n = 47). Administration of a dose of 75–115% of the intended dose was considered successful. Adverse events (AEs) and product technical complaints (PTCs) were recorded. Results: In group A (68% females, 93% Hispanic ethnicity, 97% type 2 diabetes mellitus, mean ± standard deviation age 52 ± 11 years, diabetes duration 11 ± 7 years), half of the participants had prior experience in using insulin pen devices. All except one participant (99.6%) in group A successfully delivered three insulin doses. The lower one-tailed 95% confidence limit for the success rate (98.2%) was higher than the predefined target of 90%. Demographic/baseline characteristics were similar in group B, but 70% had not previously used an injection pen. Group B also showed success; 93.6% of participants successfully completed three dose deliveries. No AEs were reported, although one participant (0.4%) in group A reported one PTC during the training period that was due to a blocked needle. Conclusions: This study successfully validated the ClikSTAR pen for use by individuals with diabetes.
The Sardinian Way to Type 1 Diabetes
Authors: Songini Marco , Lombardo Cira 
Published: January 2014

Sardinia and Finland are the “hottest” areas for type 1 diabetes mellitus (T1DM) worldwide. Its genetic and epidemiological background make Sardinia an ideal region for investigating environmental, immunological, and genetic factors related to the etiopathogenesis of T1DM. Consequently, in 1990, the Insulin-Dependent Diabetes Mellitus Sardinia Project was launched in order to map the geographical distribution of T1DM in the island and to investigate preclinical phases of T1DM in a large cohort of people genetically at risk. The final goal would be to design models of prediction and to formulate safe preventive measures, especially addressed to the general population living in areas at high risk.
Factors Influencing the Effectiveness of Glucagon for Preventing Hypoglycemia
Authors: Castle Jessica R. , Engle Julia M. , Youssef Joseph El , Massoud Ryan G. , Ward W. Kenneth 
Published: January 2014

Background: Administration of small, intermittent doses of glucagon during closed-loop insulin delivery markedly reduces the frequency of hypoglycemia. However, in some cases, hypoglycemia occurs despite administration of glucagon in this setting. Methods: Fourteen adult subjects with type 1 diabetes participated in 22 closed-loop studies, duration 21.5 ± 2.0 h. The majority of subjects completed two studies, one with insulin + glucagon, given subcutaneously by algorithm during impending hypoglycemia, and one with insulin + placebo. The more accurate of two subcutaneous glucose sensors was used as the controller input. To better understand reasons for success or failure of glucagon to prevent hypoglycemia, each response to a glucagon dose over 0.5 μg/kg was analyzed ( n = 19 episodes). Results: Hypoglycemia occurred in the hour after glucagon delivery in 37% of these episodes. In the failures, estimated insulin on board was significantly higher versus successes (5.8 ± 0.5 versus 2.9 ± 0.5 U, p < .001). Glucose at the time of glucagon delivery was significantly lower in failures versus successes (86 ± 3 versus 95 ± 3 mg/dl, p = .04). Sensor bias (glucose overestimation) was highly correlated with starting glucose ( r = 0.65, p = .002). Prior cumulative glucagon dose was not associated with success or failure. Conclusion: Glucagon may fail to prevent hypoglycemia when insulin on board is high or when glucagon delivery is delayed due to overestimation of glucose by the sensor. Improvements in sensor accuracy and delivery of larger or earlier glucagon doses when insulin on board is high may further reduce the frequency of hypoglycemia.
In Vitro and in Vivo Evaluation of Native Glucagon and Glucagon Analog (MAR-D28) during Aging: Lack of Cytotoxicity and Preservation of Hyperglycemic Effect
Authors: Ward W. Kenneth , Massoud Ryan G. , Szybala Cory J. , Engle Julia M. , Youssef Joseph El , Carroll Julie M. , Roberts Charles T. , DiMarchi Richard D. 
Published: January 2014

Background: For automated prevention of hypoglycemia, there is a need for glucagon (or an analog) to be sufficiently stable so that it can be indwelled in a portable pump for at least 3 days. However, under some conditions, solutions of glucagon can form amyloid fibrils. Currently, the usage instructions for commercially available glucagon allow only for its immediate use. Methods: In NIH 3T3 fibroblasts, we tested amyloid formation and cytotoxicity of solutions of native glucagon and the glucagon analog MAR-D28 after aging under different conditions for 5 days. In addition, aged native glucagon was subjected to size-exclusion chromatography (SEC). We also studied whether subcutaneous aged Novo Nordisk GlucaGen® would have normal bioactivity in octreotide-treated, anesthetized, nondiabetic pigs. Results: We found no evidence of cytotoxicity from native glucagon or MAR-D28 (up to 2.5 mg/ml) at a pH of 10 in a glycine solvent. We found a mild cytotoxicity for both compounds in Tris buffer at pH 8.5. A high concentration of the commercial glucagon preparation (GlucaGen) caused marked cytotoxicity, but low pH and/or a high osmolarity probably accounted primarily for this effect. With SEC, the decline in monomeric glucagon over time was much lower when aged in glycine (pH 10) than when aged in Tris (pH 8.5) or in citrate (pH 3). Congo red staining for amyloid was very low with the glycine preparation (pH 10). In the pig studies, the hyperglycemic effect of commercially available glucagon was preserved despite aging conditions associated with marked amyloid formation. Conclusions: Under certain conditions, aqueous solutions of glucagon and MAR-D28 are stable for at least 5 days and are thus very likely to be safe in mammals. Glycine buffer at a pH of 10 appears to be optimal for avoiding cytotoxicity and amyloid fibril formation.
Stabilized Glucagon Formulation for Bihormonal Pump Use
Authors: Steiner Solomon S. , Li Ming , Hauser Robert , Pohl Roderike 
Published: January 2014

Background: A promising approach to treat diabetes is the development of an automated bihormonal pump administering glucagon and insulin. A physically and chemically stable glucagon formulation does not currently exist. Our goal is to develop a glucagon formulation that is stable as a clear ungelled solution, free of fibrils at a pH of 7 for at least 7 days at 37 °C. Methods: Experimental glucagon formulations were studied for stability at 25 and 37 °C. Chemical degradation was quantified by reverse phase ultra-performance liquid chromatography. Physical changes were studied using light obscuration and visual observations. Results: Glucagon content of Biodel glucagon and Lilly glucagon at pH 2 and pH 4, as measured by high-performance liquid chromatography at 25 °C, was 100% at 7 days compared to 87% and <7%, respectively. Light obscuration measurements indicated Lilly glucagon at pH 4 formed an opaque gel, while Biodel glucagon formulation remained a clear solution beyond 50 days at 37 °C. Visual observations confirmed these results. Conclusions: Biodel glucagon is a stabilized formulation at physiological pH and remains chemically and physically stable beyond 7 days at 37 °C, suggesting its utility for use in a bihormonal pump.
Contribution of an Intrinsic Lag of Continuous Glucose Monitoring Systems to Differences in Measured and Actual Glucose Concentrations Changing at Variable Rates in Vitro
Authors: Davey Raymond J. , Low Chee , Jones Timothy W. , Fournier Paul A. 
Published: January 2014

Background: Current continuous glucose monitoring (CGM) systems measure glucose levels in the interstitial fluid to estimate blood glucose concentration. A lag time has been observed between CGM system glucose readings and blood glucose levels when glucose levels are changing. Although this lag has been attributed to the time it takes glucose to equilibrate between blood and interstitial fluid compartments, it is unclear to what extent these inaccuracies reflect an intrinsic delay of the device itself. Methods: Four Guardian® REAL-Time CGM systems (CGMSs) (Medtronic Diabetes, Minimed, CA) and eight glucose sensors were tested in glucose solutions prepared in Krebs bicarbonate buffers at 37 °C. Glucose readings obtained from CGMSs were compared with actual glucose concentrations during controlled changes in glucose concentration performed at four rates (30, 90, and 220 mg/dl/hr−1 and an instantaneous change of 110 mg/dl) using a linear gradient maker. Results: Irrespective of the rate and direction of changes in glucose concentration, the readings obtained from CGMSs were significantly different from actual glucose levels. The faster the rise or fall in actual glucose concentration, the more pronounced the mismatch with CGMS glucose readings. Furthermore, the intrinsic lag times (8.3 to 40.1 min) were high enough to account for the lags reported in previous in vivo studies. Conclusions: The lag intrinsic of the CGMS may make a significant contribution to the mismatch between CGM system readings and blood glucose concentrations.
Effect of Short-Term Use of a Continuous Glucose Monitoring System with a Real-Time Glucose Display and a Low Glucose Alarm on Incidence and Duration of Hypoglycemia in a Home Setting in Type 1 Diabetes Mellitus
Authors: Davey Raymond J. , Jones Timothy W. , Fournier Paul A. 
Published: January 2014

Background: The objective of this study was to examine whether setting the low glucose alarm of a Guardian® REAL-Time continuous glucose monitoring system (CGMS) to 80 mg/dl for 3 days and providing instructions to users reduce the risk of hypoglycemia under free-living conditions in individuals with type 1 diabetes mellitus (T1DM). Methods: Fourteen participants with T1DM aged 26.1 ± 6.0 years (mean ± standard deviation) were fitted with a CGMS and assigned for 3 days to either an alarm [low and high blood glucose (BG) alarms set at 80 and 200 mg/dl, respectively] or no alarm condition, with each treatment administered to all participants following a counterbalanced design. All participants were given detailed instructions on how to respond appropriately to low glucose alarms. Results: The CGMS with alarm reduced the incidence of hypoglycemia (CGMS readings ≤65 mg/dl) by 44% as well as the time spent below this hypoglycemic threshold by 64% without increasing average BG levels. However, the CGMS with alarm had no effect on the incidence of symptomatic hypoglycemia. Conclusions: Short-term use of the CGMS with alarm, together with appropriate instructions for users, reduces the incidence and duration of hypoglycemia, but only to a limited extent, in part because it overestimates BG in the low glucose range.
Novopen Echo® for the Delivery of Insulin: A Comparison of Usability, Functionality and Preference among Pediatric Subjects, Their Parents, and Health Care Professionals
Authors: Olsen Birthe S. , Lilleøre Søren Kruse , Korsholm Conny Nøhr , Kracht Thorben 
Published: January 2014

Background: Despite advances in insulin pen design and functionality, the selection of pens available for children with diabetes is limited. This study assessed the usability, functionality and attitudes towards NovoPen Echo®, a new durable insulin pen designed for pediatric patients that combines a simple memory function with half-increment dosing, versus NovoPen® Junior and HumaPen® Luxura® HD in pediatric subjects, their parents, and health care professionals (HCPs). Methods: Pens were evaluated in random order during 1:1 interviews in the three target groups (pediatric subjects, parents, and HCPs) in Germany, France, and Canada. Study participants were asked to prepare each pen, perform injections into foam cushions, and provide feedback via a standardized questionnaire. Results: In total, 205 participants were included in the study. On a scale of 1–6 (1 = most favorable; 6 = least favorable regarding overall appearance, shape, colors, thickness and length), NovoPen Echo received the most favorable rating for design and overall appearance (mean ± standard deviation = 1.71 ± 0.79) compared with NovoPen Junior (2.02 ± 0.93) and HumaPen Luxura HD (2.36 ± 1.01). Furthermore, 89% of pediatric subjects and 94% of parents rated the memory function of NovoPen Echo as very easy/easy to use. When asked to rate the pens overall, 80% of participants preferred NovoPen Echo to the other pens ( p < 0.0001). Conclusions: The results demonstrate a high overall level of satisfaction with NovoPen Echo among pediatric subjects, parents, and HCPs. The novel design aspects of NovoPen Echo, namely t1468-he simple memory function, half-increment units and, ease of use and design, may contribute towards promoting treatment adherence, which is essential in the pediatric setting.
Translation of Personalized Decision Support into Routine Diabetes Care
Authors: Augstein Petra , Vogt Lutz , Kohnert Klaus-Dieter , Heinke Peter , Salzsieder Eckhard 
Published: January 2014

Objective: The aim of this study was to evaluate the impact of personalized decision support (PDS) on metabolic control in people with diabetes and cardiovascular disease. Research Design and Methods: The German health insurance fund BKK TAUNUS offers to its insured people with diabetes and cardiovascular disease the possibility to participate in the Diabetiva® program, which includes PDS. Personalized decision support is generated by the expert system KADIS® using self-control data and continuous glucose monitoring (CGM) as its data source. The physician of the participating person receives the PDS once a year, decides about use or nonuse, and reports his/her decision in a questionnaire. Metabolic control of participants treated by use or nonuse of PDS for one year and receiving CGM twice was analyzed in a retrospective observational study. The primary outcome was hemoglobin A1c (HbA1c); secondary outcomes were mean sensor glucose (MSG), glucose variability, and hypoglycemia. Results: A total of 323 subjects received CGM twice, 289 had complete data sets, 97% (280/289) were type 2 diabetes patients, and 74% (214/289) were treated using PDS, resulting in a decrease in HbA1c [7.10 ± 1.06 to 6.73 ± 0.82%; p < .01; change in HbA1c t0- t12months −0.37 (95% confidence interval −0.46 to −0.28)] and MSG (7.7 ± 1.6 versus 7.4 ± 1.2 mmol/liter; p = .003) within one year. Glucose variability was also reduced, as indicated by lower high blood glucose index ( p = .001), Glycemic Risk Assessment Diabetes Equation ( p = .009), and time of hyperglycemia ( p = .003). Low blood glucose index and time spent in hypoglycemia were not affected. In contrast, nonuse of PDS (75/289) resulted in increased HbA1c ( p < .001). Diabetiva outcome was strongly related to baseline HbA1c (HbA1c t0; p < .01) and use of PDS ( p < .01). Acceptance of PDS was dependent on HbA1c t0 ( p = .049). Conclusions: Personalized decision support has potential to improve metabolic outcome in routine diabetes care.
Evaluating the Automated Blood Glucose Pattern Detection and Case-Retrieval Modules of the 4 Diabetes Support System®
Authors: Schwartz Frank L. , Vernier Stanley J. , Shubrook Jay H. , Marling Cynthia R. 
Published: January 2014

Background: We have developed a prototypical case-based reasoning system to enhance management of patients with type 1 diabetes mellitus (T1DM). The system is capable of automatically analyzing large volumes of life events, self-monitoring of blood glucose readings, continuous glucose monitoring system results, and insulin pump data to detect clinical problems. In a preliminary study, manual entry of large volumes of life-event and other data was too burdensome for patients. In this study, life-event and pump data collection were automated, and then the system was reevaluated. Methods: Twenty-three adult T1DM patients on insulin pumps completed the five-week study. A usual daily schedule was entered into the database, and patients were only required to upload their insulin pump data to Medtronic's CareLink® Web site weekly. Situation assessment routines were run weekly for each participant to detect possible problems, and once the trial was completed, the case-retrieval module was tested. Results: Using the situation assessment routines previously developed, the system found 295 possible problems. The enhanced system detected only 2.6 problems per patient per week compared to 4.9 problems per patient per week in the preliminary study ( p = .017). Problems detected by the system were correctly identified in 97.9% of the cases, and 96.1% of these were clinically useful. Conclusions: With less life-event data, the system is unable to detect certain clinical problems and detects fewer problems overall. Additional work is needed to provide device/software interfaces that allow patients to provide this data quickly and conveniently.
Design and Development of a Web-Based Saudi National Diabetes Registry
Authors: Subhani Shazia , Al-Rubeaan Khalid 
Published: January 2014

Background: Given that diabetes is an extremely common disorder in Saudi Arabia, the National Diabetes Registry was designed by King Saud University Hospital Diabetes Center in collaboration with King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia, in the year 2001. The aim of the registry is to identify risk factors related to diabetes and to provide statistics to public health programs and health care professionals for use in planning and evaluation. The registry was designed to provide information on the extent and nature of specific types of diabetes, diabetes complications, and treatment of diabetes in the Kingdom. The registry has been available since 2001, with major collaborations from 26 hospitals as part of Phase I in which 100,000 patient data is to be collected on a regional level from Ar-Riyadh before extending the program to other regions of Saudi Arabia. Methods: The web application was designed using relational database techniques along with on-line help topics to assist users to get acquainted with application functionalities. All Internet forms were designed with validation checks and appropriate messages to ensure quality of data. The security measures established within the application ensure that only authorized users can gain access to the functionalities of the registry at allowed times. Administrative features were designed to manage the registry-related operations easily. Results: The diabetes registry has been in operation for almost 10 years, and around 67,000 patients have been registered to date. The Web-application offers an anytime-anywhere access to the registry's data, removing geographical boundaries and allowing the national registry to provide real-time data entry, updates, reporting, and mapping functionalities more easily. Conclusion: Merging related information in the form of databases can provide improved health care operations through instant access to data, ease of managing complex data structures, and creation of reports to be used by health care planners and hospital administrators.