bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyte Flux at a Biomaterial-Tissue Interface over Time: Implications for Sensors for Type 1 and 2 Diabetes Mellitus
Authors: Ekberg Neda Rajamand , Brismar Kerstin , Malmstedt Jonas , Hedblad Mari-Anne , Adamson Ulf , Ungerstedt Urban , Wisniewski Natalie
Published: January 2014

Objective:

The very presence of an implanted sensor (a foreign body) causes changes in the adjacent tissue that may alter the analytes being sensed. The objective of this study was to investigate changes in glucose availability and local tissue metabolism at the sensor-tissue interface in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

Method:

Microdialysis was used to model implanted sensors. Capillary glucose and subcutaneous (sc) microdialysate analytes were monitored in five T1DM and five T2DM patients. Analytes included glucose, glycolysis metabolites (lactate, pyruvate), a lipolysis metabolite (glycerol), and a protein degradation byproduct (urea). On eight consecutive days, four measurements were taken during a period of steady state blood glucose.

Results:

Microdialysate glucose and microdialysate-to-blood-glucose ratio increased over the first several days in all patients. Although glucose recovery eventually stabilized, the lactate levels continued to rise. These trends were explained by local inflammatory and microvascular changes observed in histological analysis of biopsy samples. Urea concentrations mirrored glucose trends. Urea is neither produced nor consumed in sc tissue, and so the initially increasing urea trend is explained by increased local capillary presence during the inflammatory process. Pyruvate in T2DM microdialysate was significantly higher than in T1DM, an observation that is possibly explained by mitochondrial dysfunction in T2DM. Glycerol in T2DM microdialysate (but not in T1DM) was higher than in healthy volunteers, which is likely explained by sc insulin resistance (insulin is a potent antilipolytic hormone). Urea was also higher in microdialysate of patients with diabetes mellitus compared to healthy volunteers. Urea is a byproduct of protein degradation, which is known to be inhibited by insulin. Therefore, insulin deficiency or resistance may explain the higher urea levels. To our knowledge, this is the first histological evaluation of a human tissue biopsy containing an implanted glucose monitoring device.

Conclusions:

Monitoring metabolic changes at a material-tissue interface combined with biopsy histology helped to formulate an understanding of physiological changes adjacent to implanted glucose sensors. Microdialysate glucose trends were similar over 1-week in T1DM and T2DM; however, differences in other analytes indicated wound healing and metabolic activities in the two patient groups differ. We propose explanations for the specific observed differences based on differential insulin insufficiency/resistance and mitochondrial dysfunction in T1DM versus T2DM.
Utilization of Advanced Modalities in the Management of Diabetic Charcot Neuroarthropathy
Authors: Pappalardo Jennifer , Fitzgerald Ryan
Published: January 2014

Technological advances have allowed reconstructive foot and ankle surgeons greater opportunity to provide significant limb salvage options to those patients who present with significant lower extremity deformity due to diabetic Charcot neuroarthropathy. Paradigms that promote the utilization of these advanced modalities have demonstrated significant improved limb salvage outcomes in this challenging patient population and have consequently improved the quality of life for patients. The purpose of this review is to discuss current concepts in Charcot reconstruction.
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.
Use of Sugar on the Healing of Diabetic Ulcers: A Review
Authors: Biswas Atanu , Bharara Manish , Hurst Craig , Gruessner Rainer , Armstrong David , Rilo Horacio
Published: January 2014

With the advent of several innovative wound care management tools, the choice of products and treatment modalities available to clinicians continues to expand. High costs associated with wound care, especially diabetic foot wounds, make it important for clinician scientists to research alternative therapies and optimally incorporate them into wound care protocols appropriately. This article reviews using sugar as a treatment option in diabetic foot care and provides a guide to its appropriate use in healing foot ulcers. In addition to a clinical case study, the physiological significance and advantages of sugar are discussed.
Analysis of the Nova Stat Strip® Glucose Meter for Real-Time Blood Glucose Determinations during Glucose Clamp Studies: “Don't Swap Horses in Midstream”
Authors: Heinemann Lutz
Published: January 2014

Proper performance of glucose clamps is critically dependent on reliable blood glucose (BG) measurements. A number of requirements have to be fulfilled by a system that aims to replace the laboratory devices that are currently in use. Many more aspects need to be taken into account besides the accuracy of BG measurement. It might very well be that the BG meter studied by Rabiee and colleagues in this issue of Journal of Diabetes Science and Technology fulfills most or all of such requirements; however, these aspects have to be tested more thoroughly before one switches from an established measurement method to the Nova Stat Strip® glucometer.
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.
Enhancing Clinical Islet Transplantation through Tissue Engineeering Strategies
Authors: Giraldo Jaime A. , Weaver Jessica D. , Stabler Cherie L.
Published: January 2014

Clinical islet transplantation (CIT), the infusion of allogeneic islets within the liver, has the potential to provide precise and sustainable control of blood glucose levels for the treatment of type 1 diabetes. The success and long-term outcomes of CIT, however, are limited by obstacles such as a nonoptimal transplantation site and severe inflammatory and immunological responses to the transplant. Tissue engineering strategies are poised to combat these challenges. In this review, emerging methods for engineering an optimal islet transplantation site, as well as novel approaches for improving islet cell encapsulation, are discussed.
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.
We Need Tighter Regulatory Standards for Blood Glucose Monitoring, but They Should Be for Accuracy Disclosure
Authors: Ginsberg Barry H.
Published: January 2014

Regulatory interest has focused on the accuracy of blood glucose monitoring systems. Currently, almost all systems meet the International Organization for Standardization (ISO) 15197 clinical standard (=95% of the values within 20% of the reference for values above 75 mg/dl and within 15 mg/dl below that level). Should the systems have to meet one of the extended ISO standards of 15%, 10%, or even 5%? There is a wide variety of people with diabetes doing glucose monitoring, and the majority do not need better accuracy. Indeed, when selecting an insulin dose, the inaccuracy of the glucose reading has little effect compared with the inaccuracy in counting carbohydrates and the variability in insulin absorption. It might be far better to evaluate the accuracy in a standard method and provide the accuracy values on a standard label. Patients and health care providers could then select the monitoring system that best meets their needs.
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.
Analysis of the NovoPen® Echo for the Delivery of Insulin: A Comparison of Usability, Functionality, and Preference among Pediatric Subjects, Their Parents, and Health Care Professionals
Authors: Reynholds Carey , Antal Zoltan
Published: January 2014

In the current issue of Journal of Diabetes Science and Technology, Dr. Olsen and colleagues analyzed the attitudes of children, their caregivers, and health care professional towards the usability, functionality, and preference of the NovoPen® Echo (Novo Nordisk Inc., Princeton, NJ). A comparison is made to two other insulin pen devices with half-unit increment capability—the NovoPen Junior and the HumaPen® Luxura® (Eli Lilly and Company, Indianapolis, IN). Their results support the idea that the NovoPen Echo has the highest overall satisfaction among pen devices capable of delivering half-unit increments, is equally simple to assemble and inject, and has the added benefit of a simple recall memory function. A major concern is their finding that fewer adolescents dialed a dose correctly with NovoPen Echo than with the other two pens tested. Furthermore, the true test in validating their claims of the importance of this device lays in future studies, which should be undertaken to demonstrate that a preferred delivery device actually leads to improved compliance in children and adolescents with type 1 diabetes.
Analysis of Point-of-Care and Over-the-Counter Testing Methods for Hemoglobin A1c: How Good Do They Need to Be?
Authors: Little Randie R.
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Chang and colleagues evaluate the performance of the A1CNow® SELFCHECK device for measurement of hemoglobin A1c (HbA1c). The authors discuss the potential advantages of point-of-care (POC) HbA1c testing and also mention the importance of accuracy and precision and provide some data to document the device's performance. There are specific criteria for HbA1c method evaluation and proficiency testing used by the National Glycohemoglobin Standardization Program and the College of American Pathologists. Chang and colleagues mention these criteria but chose wider performance limits for their evaluation of the A1cNow SELFCHECK. Given the available data on the relationship between HbA1c and risk for complications, assay method performance is a vital consideration when HbA1c results, including those from POC methods, are used in the management of patients with diabetes. In this issue of Journal of Diabetes Science and Technology, Chang and colleagues evaluate the performance of the A1CNow® SELFCHECK device for measurement of hemoglobin A1c (HbA1c). The authors discuss the potential advantages of point-of-care (POC) HbA1c testing and also mention the importance of accuracy and precision and provide some data to document the device's performance. There are specific criteria for HbA1c method evaluation and proficiency testing used by the National Glycohemoglobin Standardization Program and the College of American Pathologists. Chang and colleagues mention these criteria but chose wider performance limits for their evaluation of the A1cNow SELFCHECK. Given the available data on the relationship between HbA1c and risk for complications, assay method performance is a vital consideration when HbA1c results, including those from POC methods, are used in the management of patients with diabetes.
Analysis of Institutional Blood Glucose Surveillance
Authors: Boaz Mona , Landau Zohar , Wainstein Julio
Published: January 2014

In an article by Anderson and colleagues in this issue of Journal of Diabetes Science and Technology, the 2009 Remote Automated Laboratory System Report describes the use of a proprietary software application in 576 United States hospital benchmark subscribers, permitting blood glucose surveillance. The Program for the Treatment of the Hospitalized Diabetic Patient was initiated at Edith Wolfson Medical Center in 2007 and included an automated glucometer in each inpatient department. Results are transmitted automatically to a central database. Importantly, these data interface with the patient electronic medical record, permitting accurate patient follow-up within and between hospitalizations; the patient response-to-treatment evaluation; identification of secular glucose trends; and interdepartmental and interinstitutional comparisons. The data have been associated with a significant reduction in random blood glucose values. In Israel, the National Diabetes Council has recommended the use of automated institutional glucometers in all hospitals.
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.
The Karlsburg Diabetes Management System: Translation from Research to eHealth Application
Authors: Salzsieder Eckhard , Augstein Petra
Published: January 2014

Background:

Several telemedicine-based eHealth programs exist, but patient-focused personalized decision support (PDS) is usually lacking. We evaluated the acceptance, efficiency, and cost-effectiveness of telemedicine-assisted PDS in routine outpatient diabetes care.

Methods:

Data are derived from the Diabetiva® program of the German health insurance company BKK TAUNUS. Diabetiva offers telemedicine-based outpatient health care in combination with PDS generated by the Karlsburg Diabetes Management System, KADIS®. This retrospective analysis is based on data from the first year of running KADIS-based PDS in routine diabetes care. Participants were insured persons diagnosed with diabetes and cardiovascular diseases. For final analysis, patients were grouped retrospectively as users or nonusers according to physician acceptance or not (based on questionnaires) of the KADIS-based PDS.

Results:

A total of 538 patients participated for more than one year in the Diabetiva program. Of these patients, 289 had complete data sets (two continuous glucose monitoring measurements, two or more hemoglobin A1c (HbA1c) values, and a signed questionnaire) and were included in the final data analysis. Of the physicians, 74% accepted KADIS-based PDS, a rate that was clearly related to HbA1c at the beginning of the observation. If KADIS-based PDS was accepted, HbA1c decreased by 0.4% (7.1% to 6.7%). In contrast, rejection of KADIS-based PDS resulted in an HbA1c increase of 0.5% (6.8% to 7.3%). The insurance company revealed an annual cost reduction of about 900 € per participant in the Diabetiva program.

Conclusions:

KADIS-based PDS in combination with telemedicine has high potential to improve the outcome of routine outpatient diabetes care.
Creating a Place for Caregivers in Personal Health: The iHealthSpace Copilot Program and Diabetes Care
Authors: Chung Jeanhee , Berkowicz David A. , Ho Benjamin , Jernigan Michael , Chueh Henry
Published: January 2014

Background:

As America's baby boom generation reaches retirement, the number of elders, and, in turn, the number of lay individuals who support them, will continue to increase. With the important services caregivers provide, it is critical that we recognize and provide assistance to the informal caregivers who play this important role in our society. The network of support provisioned by relatives, partners, friends, and neighbors suggests that the dyadic, unidirectional caregiver-care recipient relationship assumed by caregiver research so far and by resources deployed to assist caregivers may be insufficient to ascertain and meet the needs of the care community.

Methods:

In this article, we describe the extension of a Web-based personal health record system, iHealthSpace, for explicitly and openly incorporating caregivers into the care community.

Results:

Using this portal, a set of business rules was implemented to support the creation of custodial accounts. These business rules will be used to create modules that support diabetes care in an adult population.

Conclusions:

We successfully extended an existing patient portal to accommodate the creation of custodial accounts. We will use this portal to assess the impact of custodial access in the care of older patients with diabetes.
“Smart Tattoo” Glucose Biosensors and Effect of Coencapsulated Anti-Inflammatory Agents
Authors: Srivastava Rohit , Jayant Rahul Dev , Chaudhary Ayesha , McShane Michael J.
Published: January 2014

Background:

Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres.

Methods:

The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation.

Results:

The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0–50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site.

Conclusion:

The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as “smart tattoo” glucose sensors with increased functional longevity.
Enhanced Absorption of Nasulin™, an Ultrarapid-Acting Intranasal Insulin Formulation, Using Single Nostril Administration in Normal Subjects
Authors: Stote Robert , Miller Michael , Marbury Thomas , Shi Leon , Strange Poul
Published: January 2014

Background:

This pharmacokinetic (PK) study was designed to investigate the maximum intranasal insulin dose that could be achieved by repeated doses in a single nostril of a nasal spray of recombinant regular human insulin 1% in combination with cyclopentadecalactone (CPE-215) 2%, a compound that enhances absorption of molecules across mucous membranes (Nasulin™, CPEX Pharmaceuticals, Inc.).

Method:

A nine-period crossover study of 8 healthy, nonsmoking subjects (ages 18–50, body mass index <33 kg/m2, weight >70 kg) were studied. In a fasted state, subjects were randomly given 25, 50, and 75 U in a single nostril on the first day and randomly given 50, 75, and 100 U doses utilizing both nostrils on two subsequent days. After a 45-minute PK assessment, subjects were given a meal. To determine the mechanism of enhanced absorption in a single nostril, a second study utilizing 24 subjects under similar conditions received 25 U, placebo (P) that included CPE-215 plus 25 U, and 50 U in a single nostril.

Results:

Single nostril administration revealed enhanced absorption with maximum concentrations (Cmax) of 13, 65, and 96 μU/ml for the 25, 50, and 75 U doses, respectively. Dual nostril administration in two cohorts resulted in Cmax of 31/42, 65/52, and 88/79 μU/ml for the 50, 75, and 100 U, respectively. In the second cohort, Cmax was 23, 19, 56 μU/ml for the 25, P + 25, and 50 U doses, respectively.

Conclusions:

Repeated dosing in a single nostril resulted in enhanced absorption; this was not due to the increased CPE-215 but to the increased insulin administered.
Injection Force of SoloSTAR® Compared with other Disposable Insulin Pen Devices at Constant Volume Flow Rates
Authors: van der Burg Thomas
Published: January 2014

Background:

Injection force is a particularly important practical aspect of therapy for patients with diabetes, especially those who have dexterity problems. This laboratory-based study compared the injection force of the SoloSTAR® insulin pen (SoloSTAR; sanofi-aventis) versus other available disposable pens at injection speeds based on the delivered volume of insulin released at the needle.

Method:

Four different prefilled disposable pens were tested: SoloSTAR containing insulin glargine; FlexPen® and the Next Generation FlexPen® (NGFP) (Novo Nordisk), both containing insulin detemir; and KwikPen® containing insulin lispro (Eli Lilly). All pens were investigated using the maximum dispense volume for each pen type [80 units (U) for SoloSTAR; 60 U for the other pens], from the free needle tip dispensing into a beaker. Twenty pens of each type were fitted with the recommended needles and tested at two dose speeds (6 and 10 U/s); each pen was tested twice.

Results:

Mean plateau injection force and maximum injection force were consistently lower with SoloSTAR compared with FlexPen, NGFP, and KwikPen at both injection speeds tested. An injection speed of 10 U/s was associated with higher injection force compared with 6 U/s for all the pens tested ( p < .001).

Conclusions:

SoloSTAR stands out because of its low injection force, even when compared with newer insulin pen devices such as the KwikPen and NGFP. This may enable patients, especially those with dexterity problems, to administer insulin more easily and improve management of their diabetes.
Analysis of the Injection Force of Solostar® Compared with other Disposable Insulin Pen Devices at Constant Volume Flow Rates
Authors: Carter Alan W.
Published: January 2014

Insulin pen devices have greatly enhanced the portability and accessibility to insulin therapy for millions of people with diabetes. Comparison research data should be reviewed thoroughly.

In this issue of Journal of Diabetes Science and Technology, the study presented by Thomas van der Burg is balanced in number of samples tested, same tensile meter, and identical units per second delivery rate into an open beaker. Mean plateau force of SoloSTAR® and KwikPen® were Significantly lower. KwikPen and SoloSTAR utilized 5-mm length 31-gauge (G) needles vs 6-mm 31G needles for FlexPen® and Next Generation FlexPen®, perhaps skewing results in favor of shorter needles instead of device design.

Individual understanding of correct insulin use, appropriate self-monitoring of blood glucose, vision and dexterity capability, and affordability of therapy must be considered first. SoloSTAR holds one unique market advantage, delivery of up to 80 units of insulin per injection.
Evaluation of Dexterity in Insulin-Treated Patients with Type 1 and Type 2 Diabetes Mellitus
Authors: Pfützner Julia , Hellhammer Juliane , Musholt Petra , Pfützner Anke H. , Böhnke Jan , Hero Torsten , Amann-Zalan Ildiko , Ganz Manfred , Forst Thomas , Pfützner Andreas
Published: January 2014

Background:

Daily routine for insulin-treated patients with diabetes mellitus requires correct performance of self-monitoring of blood glucose and insulin injections several times a day. Dexterity skills may play an important role in the performance efficacy of these procedures.

Methods:

We collected data of insulin-treated (>10 years) patients with different age ranges [healthy controls, 14 female/11 male, age (mean ± standard deviation) 55 ± 7 years; type 1 diabetes mellitus (T1DM) patients, 12/13, 45 ± 9 years, disease duration 23.9 ± 6.5 years; T2DM patients, 8/17, 64 ± 6 years, 16.2 ± 6.9 years; T2DM patients (>70 years of age), 9/16, 75 ± 4 years, 19.7 ± 7.0 years]. After assessment of neuropathy (temperature, pain, and vibration perception), the patients participated in two dexterity test batteries [Jebsen-Taylor hand-function test (JHFT) and motoric performance series (MPS)].

Results:

Patients with type 2 diabetes showed disturbed vibration perception as compared to the other groups. The dexterity results were influenced by age to a large extent. Older T2DM patients performed worst in the majority of the subtests (e.g., JHFT, writing nondominant hand: Control, 40.8 ± 11.7 s; T1DM, 46.3 ± 50.9 s, not significant versus control; old T2DM, 68.1 ± 29.5 s, p < .05; young T2DM, 52.5 ± 26.2 s, p < .05). Patients with type 1 diabetes showed similar JHFT and MPS results than the 10-year-older control subjects and performed outside of the age-dependent normal reference range.

Conclusions:

Manual skills and dexterity differed between the groups, and age-corrected reduced skills were common in both T1DM and T2DM patients in this study. Our findings underline the importance of considering dexterity and manual skills when designing medical devices for patients with diabetes mellitus.