bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Monitoring of Blood Glucose in Type 1 Diabetes Patients with Insufficient Metabolic Control: Focused Self-Monitoring of Blood Glucose Intervention Can Lower Glycated Hemoglobin A1C
Authors: Skeie Svein , Kristensen Gunn B. B. , Carlsen Siri , Sandberg Sverre
Published: January 2014

Objective:

Little attention has been given and few studies have been published focusing on how to optimize self-monitoring of blood glucose (SMBG) use to monitor daily therapy for persons with type 1 diabetes mellitus. This study was designed to evaluate the effect on glycated hemoglobin (A1C) of a structured intervention focused on SMBG in type 1 diabetes patients with insufficient metabolic control (A1C ≥ 8%) using a randomized clinical trial design.

Method:

One hundred fifty-nine outpatients with type 1 diabetes on multiple injection therapy with insulin and A1C ≥8% were recruited and randomized to one group receiving a focused, structured 9-month SMBG intervention ( n = 59) and another group receiving regular care based on guidelines ( n = 64).

Results:

Glycated hemoglobin values (mean % ± standard deviation) at study start was similar: 8.65 ± 0.10 in the intervention group and 8.61 ± 0.09 in the control group. The two groups were comparable (age, gender, body mass index, complication rate, and treatment modality) at study start and had mean diabetes duration and SMBG experience of 19 and 20 years, respectively. At study end, there was decrease in A1C in the intervention group ( p < .05), and the A1C was 0.6% lower compared with the control group (p < .05). No increase in the number of minor or major hypoglycemia episodes was observed in the intervention group during the study period.

Conclusions:

A simple, structured, focused SMBG intervention improved metabolic control in patients with longstanding diabetes type 1 and A1C ≥ 8%. The intervention was based on general recommendations, realistic in format, and can be applied in a regular outpatient setting.
Changes in Diabetes Distress Related to Participation in an Internet-Based Diabetes Care Management Program and Glycemic Control
Authors: Fonda Stephanie J. , McMahon Graham T. , Gomes Helen E. , Hickson Sara , Conlin Paul R.
Published: January 2014

Background:

This article investigated how changes in diabetes distress relate to receiving care management through an Internet-based care management (IBCM) program for diabetes and level of participation in this program. Further, it examined the relationship between diabetes distress and changes in glycemic control.

Methods:

We enrolled patients of the Veterans Affairs Boston Healthcare System with diabetes who had hemoglobin A1c (HbA1c) levels of ≥9.0%. Subjects were randomized to usual care ( n = 52) or IBCM ( n = 52) for 1 year. We measured diabetes distress at baseline and quarterly thereafter using the Problem Areas in Diabetes (PAID) questionnaire. Glycemic control was determined by baseline and quarterly HbA1c. For subjects randomized to IBCM, we measured participation by observing frequency and consistency of their usage of the IBCM patient portal over 12 months. Linear mixed models were used to analyze THE data.

Results:

PAID scores declined over time for both treatment groups. Among subjects randomized to IBCM, the decline in PAID scores over time was significant for sustained users of the IBCM patient portal but not for nonusers. Moreover, subjects whose usage of the patient portal was sustained throughout the study had lower PAID scores at baseline. With respect to changes in glycemic control, HbA1c reduced individual differences in PAID scores by 44%; a lower baseline HbA1c was associated with lower baseline PAID scores, and over time, the decrease in HbA1c was associated with further decreases in the PAID score.

Conclusions:

Participation in IBCM varies by initial diabetes distress, with people with less distress participating more. For people who participate, IBCM further mitigates diabetes distress. There is also a relationship between achievements in glycemic control and subsequent lowering of diabetes distress. Future research should identify how to maximize fit between patient needs and the provisions of IBCM, with the aim of increasing patient engagement in the active management of their health using this care modality. A key to maximizing fit might be first addressing metabolic control aggressively and then using IBCM for sustainment of health.
Comparison of the Dose Accuracy of Prefilled Insulin Pens
Authors: Weise Alexander , Pfützner Johannes W. , Borig Julia , Pfützner Anna M. , Safinowski Michael , Hänel Heike , Musholt Petra B. , Pfützner Andreas
Published: January 2014

Background:

Prefilled insulin pens have become a convenient and accurate way for diabetes patients to inject insulin. Their ease of use has helped to reduce the resistance of patients with type 1 diabetes and type 2 diabetes in the United States and Europe toward initiation of insulin therapy. This study compared the dosing accuracy of two prefilled insulin pens (the SoloStar® from Sanofi Aventis, Berlin, Germany, and the Next Generation [NG] FlexPen® from Novo Nordisk, Mainz, Germany).

Methods:

The dosing accuracy was tested for both pens with 24 × 10 international units of insulin (IU) and 9 × 30 IU injection volumes to investigate whether the pens comply within the acceptable International Organization for Standardization (ISO) limits of 10% (±1 IU) for 10 IU and 5% (±1.5 IU) for 30 IU. The doses were applied each with a new needle strictly according to the instructions for use of the pen manufacturers. A sensitive pharmaceutical balance was used for the assessment of the applied volumes, and the results were corrected for the specific density of the insulin formulations. We used 18 insulin pens (from two different production lots each) for the two volumes, respectively, resulting in a total of 432 doses per pen with 10 IU and 162 doses per pen with 30 IU.

Results:

Both pens showed a very good performance, which was better for the 10 IU dose than in comparative previous studies. The NG FlexPen (mean absolute percent deviation 10 IU/30 IU: 1.63 ± 0.84%/1.23 ± 0.76%) was even more accurate than the SoloStar (2.11 ± 0.92%/1.54 ± 0.84%, p > .001/ p > .05 versus the NG FlexPen). Only 0.2% of the doses were outside the ISO limit at 10 IU, with the NG FlexPen (0.6% at 30 IU). The corresponding figures for the SoloStar were 0.4% and 1.8%, respectively.

Conclusions:

A direct head-to-head comparison of the two prefilled insulin pens with a standardized protocol resulted in a more stable dosing accuracy of both pens as compared to previous investigations. In this investigation, the NG FlexPen was more accurate than the SoloStar at both tested doses.
A Review of Health Literacy and Diabetes: Opportunities for Technology
Authors: Boren Suzanne Austin
Published: January 2014

Background:

The objective of this study was to assess the published literature on health literacy and diabetes, as well as identify opportunities for technology to strengthen information skills and modify behavior to improve diabetes health outcomes.

Methods:

Medline (1990–2008), the Cumulative Index to Nursing and Allied Health Literature (1990–2008), and the Education Resources Information Center (1990–2008) were searched, and reference lists from included articles were reviewed to identify additional studies. Articles were included that presented measures of literacy or numeracy specific to diabetes, examined associations between health literacy and diabetes outcomes, or tested a health literacy intervention among persons with diabetes.

Results:

Twenty-four articles were included in this review. Five articles reported on measures of literacy or numeracy specific to diabetes. Thirteen of the fifteen cross-sectional studies (87%) associated limited health literacy with poorer diabetes outcomes. Two of the four (50%) health literacy intervention studies lead to improved health outcomes.

Conclusions:

The cross-sectional studies provide evidence of an association between health literacy and diabetes outcomes; however, there is a need to design and test strategies to improve diabetes health outcomes that consider health literacy. Information and communication technology opportunities could help to mediate the effect that limited health literacy has on diabetes-related health outcomes.
Requirements for Calibration in Noninvasive Glucose Monitoring by Raman Spectroscopy
Authors: Lipson Jan , Bernhardt Jeff , Block Ueyn , Freeman William R. , Hofmeister Rudy , Hristakeva Maya , Lenosky Thomas , McNamara Robert , Petrasek Danny , Veltkamp David , Waydo Stephen
Published: January 2014

Background:

In the development of noninvasive glucose monitoring technology, it is highly desirable to derive a calibration that relies on neither person-dependent calibration information nor supplementary calibration points furnished by an existing invasive measurement technique (universal calibration).

Method:

By appropriate experimental design and associated analytical methods, we establish the sufficiency of multiple factors required to permit such a calibration. Factors considered are the discrimination of the measurement technique, stabilization of the experimental apparatus, physics-physiology-based measurement techniques for normalization, the sufficiency of the size of the data set, and appropriate exit criteria to establish the predictive value of the algorithm.

Results:

For noninvasive glucose measurements, using Raman spectroscopy, the sufficiency of the scale of data was demonstrated by adding new data into an existing calibration algorithm and requiring that (a) the prediction error should be preserved or improved without significant re-optimization, (b) the complexity of the model for optimum estimation not rise with the addition of subjects, and (c) the estimation for persons whose data were removed entirely from the training set should be no worse than the estimates on the remainder of the population. Using these criteria, we established guidelines empirically for the number of subjects (30) and skin sites (387) for a preliminary universal calibration. We obtained a median absolute relative difference for our entire data set of 30 mg/dl, with 92% of the data in the Clarke A and B ranges.

Conclusions:

Because Raman spectroscopy has high discrimination for glucose, a data set of practical dimensions appears to be sufficient for universal calibration. Improvements based on reducing the variance of blood perfusion are expected to reduce the prediction errors substantially, and the inclusion of supplementary calibration points for the wearable device under development will be permissible and beneficial.
Eliminating the Blood: Ongoing Outbreaks of Hepatitis B Virus Infection and the Need for Innovative Glucose Monitoring Technologies
Authors: Thompson Nicola D. , Perz Joseph F.
Published: January 2014

Background:

As part of routine diabetes care, capillary blood is typically sampled using a finger-stick device and then tested using a handheld blood glucose meter. In settings where multiple persons require assistance with blood glucose monitoring, opportunities for bloodborne pathogen transmission may exist.

Methods:

Reports of hepatitis B virus (HBV) infection outbreaks in the United States that have been attributed to blood glucose monitoring practices were reviewed and summarized.

Results:

Since 1990, state and local health departments investigated 18 HBV infection outbreaks, 15 (83%) in the past 10 years, that were associated with the improper use of blood glucose monitoring equipment. At least 147 persons acquired HBV infection during these outbreaks, 6 (4.1%) of whom died from complications of acute HBV infection. Outbreaks appear to have become more frequent in the past decade, primarily affecting long-term care residents with diabetes. Each outbreak was attributed to glucose monitoring practices that exposed HBV-susceptible persons to blood-contaminated equipment that was previously used on HBV-infected persons. The predominant unsafe practices were the use of spring-loaded finger-stick devices on multiple persons and the sharing of blood glucose testing meters without cleaning and disinfection between uses.

Conclusion:

Hepatitis B virus infection outbreaks associated with blood glucose monitoring have occurred with increasing regularity in the Unites States and may represent a growing but under-recognized problem. Advances in technology, such as the development of blood glucose testing meters that can withstand frequent disinfection and noninvasive glucose monitoring methods, will likely prove useful in improving patient safety.
Toward an Agent-Based Patient—Physician Model for the Adoption of Continuous Glucose Monitoring Technology
Authors: Verella J. Tipan , Patek Stephen D.
Published: January 2014

Health care is a major component of the U.S. economy, and tremendous research and development efforts are directed toward new technologies in this arena. Unfortunately few tools exist for predicting outcomes associated with new medical products, including whether new technologies will find widespread use within the target population. Questions of technology adoption are rife within the diabetes technology community, and we particularly consider the long-term prognosis for continuous glucose monitoring (CGM) technology.

We present an approach to the design and analysis of an agent model that describes the process of CGM adoption among patients with type 1 diabetes mellitus (T1DM), their physicians, and related stakeholders. We particularly focus on patient—physician interactions, with patients discovering CGM technology through word-of-mouth communication and through advertising, applying pressure to their physicians in the context of CGM device adoption, and physicians, concerned about liability, looking to peers for a general level of acceptance of the technology before recommending CGM to their patients.

Repeated simulation trials of the agent-based model show that the adoption process reflects the heterogeneity of the adopting community. We also find that the effect of the interaction between patients and physicians is colored by the nature of the environment as defined by the model parameters.

We find that, by being able to represent the diverse perspectives of different types of stakeholders, agent-based models can offer useful insights into the adoption process. Models of this sort may eventually prove to be useful in helping physicians, other health care providers, patient advocacy groups, third party payers, and device manufacturers understand the impact of their decisions about new technologies.
Mathematical Modeling Research to Support the Development of Automated Insulin-Delivery Systems
Authors: Steil Garry M. , Reifman Jaques
Published: January 2014

The world leaders in glycemia modeling convened during the Eighth Annual Diabetes Technology Meeting in Bethesda, Maryland, on 14 November 2008, to discuss the current practices in mathematical modeling and make recommendations for its use in developing automated insulin-delivery systems. This report summarizes the collective views of the 25 participating experts in addressing the following four topics: current practices in modeling efforts for closed-loop control; framework for exchange of information and collaboration among research centers; major barriers for the development of accurate models; and key tasks for developing algorithms to build closed-loop control systems. Among the participants, the following main conclusions and recommendations were widely supported: Physiologic variance represents the single largest technical challenge to creating accurate simulation models. A Web site describing different models and the data supporting them should be made publically available, with funding agencies and journals requiring investigators to provide open access to both models and data. Existing simulation models should be compared and contrasted, using the same evaluation and validation criteria, to better assess the state of the art, understand any inherent limitations in the models, and identify gaps in data and/or model capability.
Hemoglobin A1c Point-of-Care Assays; A New World with a Lot of Consequences!
Authors: Lenters-Westra Erna , Slingerland Robbert J.
Published: January 2014

Background:

Point-of-care instruments for the measurement of hemoglobin A1c (HbA1c) may improve the glycemic control of people with diabetes by providing a rapid result if the performance of the instruments used is acceptable. A 0.5% HbA1c difference between successive results is considered a clinically relevant change. With this in mind, the In2it from Bio-Rad and the DCA Vantage from Siemens were evaluated according to Clinical and Laboratory Standards Institute (CLSI) protocols.

Methods:

The CLSI protocols EP-5 and EP-9 were applied to investigate precision, accuracy, and bias. The bias was compared with three certified secondary reference measurement procedures. Differences between capillary and venous blood were investigated by an end-user group consisting of nurse practitioners at a diabetes care center.

Results:

At HbA1c levels of 5.1 and 11.2%, total coefficients of variation (CV) for the In2it were 4.9 and 3.3%, respectively, and for the DCA Vantage were 1.7 to 1.8% and 3.7 to 5.5% depending on the lot number of the cartridges. Method comparisons showed significant lot number-dependent results for the In2it and the DCA Vantage compared with the three reference methods. No overall difference was observed between capillary and venous blood for both methods.

Conclusion:

Performance results of the In2it and the DCA Vantage showed variable and lot number-dependent results. To maintain the interlaboratory CV of 5% for HbA1c, the Clinical Laboratory Improvement Amendments rules for waived point-of-care instruments should be revised. An obligation for participating in external quality schemes and taking adequate action should be considered for POC instruments that perform poorly.
Communication Plays a Critical Role in Web-Based Monitoring
Authors: Levine Betty A. , Turner Jeanine Warisse , Robinson James D. , Angelus Pamela , Hu Tang Ming-Jye
Published: January 2014

Background:

Patient-health care practitioner (HCP) interaction via a Web-based diabetes management system may increase patient monitoring of their blood glucose (BG) levels.

Methods:

A three-center, nonrandomized, prospective feasibility study of 109 Native Americans with poorly controlled type 1 diabetes mellitus and type 2 diabetes mellitus were recruited from Alabama, Idaho, and Arizona. The study intervention included the use of a Web-based diabetes management application (MyCareTeam®) that allowed timely interaction between patients and HCPs. Information about diabetes, nutrition, and exercise was also available. Finally, patients were able to provide BG readings to their HCP via the MyCareTeam system.

Results:

As a result, 59.6% of the patients sent one or more messages to their HCP, 92.67% received one or more messages from their HCP, and 78.89% received one or more person-centered messages from their HCP. Additionally, the number of times a patient logged into the system and the frequency with which they tested their blood sugar were correlated with (a) the number of messages sent to their HCP, (b) the total number of messages received from their HCP, and (c) the number of person-centered messages received from their HCP. Thus patients who sent more messages also tested their BG more frequently, as measured by the number of BG readings uploaded from their meter to the MyCareTeam database. Person-centered messages seem to be particularly important to motivating the patient to monitor their BG levels and use the Web-based system.

Conclusions:

These results suggest that patient—HCP interaction and, in particular, more personalized interactions increases patient frequency of BG monitoring.
Cleveland Clinic Cardiovascular Intensive Care Unit Insulin Conversion Protocol
Authors: Olansky Leann , Sam Sharon , Lober Cheryl , Yared Jean-Pierre , Hoogwerf Byron
Published: January 2014

Background:

The importance of near-normal blood glucose in the immediate postoperative period is generally accepted and is best achieved in the perioperative period with a constant intravenous (IV) infusion of insulin. This requires intensive nursing only achievable in an intensive care unit (ICU) setting. Glucose management after transfer to a regular nursing floor (RNF) has not been studied systematically. In August 2006, the Cleveland Clinic began using long-acting insulin glargine as the insulin infusion was terminated in the ICU.

Methods:

This prospective analysis examined all patients receiving IV insulin infusion after cardiothoracic surgery in a 1 month period. The analyses evaluated the safety and efficacy of a protocol using a transition to subcutaneous insulin glargine of 50% of the calculated 24 h requirement at the end of the ICU insulin infusion protocol in preparation for transfer to the RNF.

Results:

Only 1 patient in 99 developed hypoglycemia, and no patient suffered severe hypoglycemia (glucose < 40 mg/dl), while the majority (70%) had euglycemia (glucose between 70 and 150 mg/dl).

Conclusions:

This approach was both safe—as there was very little hypoglycemia (1 patient in 99)—and effective, as blood sugar was well controlled in most subjects. Efficacy for achieving euglycemia was 70%. Efficacy was likely reduced because of the upper limit of insulin glargine dosage imposed by some providers as a safety consideration. Although there was a physician option to override, the maximum protocol dose of 30 U was rarely exceeded, leading to inadequate dosing in some subjects who required high insulin infusion rates in the ICU.
Clinical Update on Optimal Prandial Insulin Dosing Using a Refined Run-to-Run Control Algorithm
Authors: Zisser Howard , Palerm Cesar C. , Bevier Wendy C. , Doyle Francis J. , Jovanovic Lois
Published: January 2014

Background:

This article provides a clinical update using a novel run-to-run algorithm to optimize prandial insulin dosing based on sparse glucose measurements from the previous day's meals. The objective was to use a refined run-to-run algorithm to calculate prandial insulin-to-carbohydrate ratios (I:CHO) for meals of variable carbohydrate content in subjects with type 1 diabetes (T1DM).

Method:

The open-labeled, nonrandomized study took place over a 6-week period in a nonprofit research center. Nine subjects with T1DM using continuous subcutaneous insulin infusion participated. Basal insulin rates were optimized using continuous glucose monitoring, with a target fasting blood glucose of 90 mg/dl. Subjects monitored blood glucose concentration at the beginning of the meal and at 60 and 120 minutes after the start of the meal. They were instructed to start meals with blood glucose levels between 70 and 130 mg/dl. Subjects were contacted daily to collect data for the previous 24-hour period and to give them the physician-approved, algorithm-derived I:CHO ratios for the next 24 hours. Subjects calculated the amount of the insulin bolus for each meal based on the corresponding I:CHO and their estimate of the meal's carbohydrate content. One- and 2-hour postprandial glucose concentrations served as the main outcome measures.

Results:

The mean 1-hour postprandial blood glucose level was 104 ± 19 mg/dl. The 2-hour postprandial levels (96.5 ± 18 mg/dl) approached the preprandial levels (90.1 ± 13 mg/dl).

Conclusions:

Run-to-run algorithms are able to improve postprandial blood glucose levels in subjects with T1DM.
Can Technology Improve Adherence to Long-Term Therapies?
Authors: Reach Gérard
Published: January 2014

Background:

Therapeutic nonadherence is defined as the lack of equivalence between the behavior of the patients and their prescribed medical treatment. Consequences of nonadherence include not only health outcomes, but also cost saving. Thus, this issue gets paramount importance in contemporary medicine.

Method:

The aim of this article is to discuss the relationships between technology and adherence by asking the following three questions. (1) How can technology be used to monitor patient adherence? (2) Considering the mechanisms of nonadherence in chronic diseases, is there room for technology in interventions aimed to improve patient adherence? (3) What about adherence to technology in diabetes care?

Results and Conclusion:

Technology may help improve adherence to long-term therapies by (1) giving a concrete representation of adherence rewards, (2) overcoming immediate obstacles to adherence, such as the fear of hypoglycemia, and (3) providing an opportunity for patient-doctor conversations. This assumes, however, that both the patient and the doctor are convinced that technologies are useful.
EyePACS: An Adaptable Telemedicine System for Diabetic Retinopathy Screening
Authors: Cuadros Jorge , Bresnick George
Published: January 2014

Background:

Annual retinal screening of patients with diabetes is the standard clinical practice to prevent visual impairment and blindness from diabetic retinopathy. Telemedicine-based diabetic retinopathy screening (DRS) in primary care settings can effectively detect sight-threatening retinopathy and significantly increase compliance with annual retinal exams. EyePACS is a license-free Web-based DRS system designed to simplify the process of image capture, transmission, and review. The system provides a flexible platform for collaboration among clinicians about diabetic retinopathy.

Methods:

Primary clinic personnel (i.e., nursing, technical, or administrative staff) are trained and certified by the EyePACS program to acquire retinal images from standard digital retinal cameras. Relevant clinical data and eight high-resolution images per patient (two external and six retinal images) are encrypted and transmitted to a secure Internet server, using a standard computer and Web browser. Images are then interpreted by certified EyePACS reviewers or local eye care providers who are certified through the EyePACS Retinopathy Grading System. Reports indicating retinopathy level and referral recommendations are transmitted back to primary care providers through the EyePACS Web site or through interfaces between EyePACS and Health Level 7-compliant electronic medical records or chronic disease registries.

Results:

The pilot phase of the EyePACS DRS program in California (2005–2006) recorded 3562 encounters. Since 2006, EyePACS has been expanded to over 120 primary care sites throughout California and elsewhere recording over 34,000 DRSs. The overall rate of referral is 8.21% for sight-threatening retinopathy and 7.83% for other conditions (e.g., cataract and glaucoma).

Conclusion:

The use of license-free Web-based software, standard interfaces, and flexible protocols has allowed primary care providers to adopt retinopathy screening with minimal effort and resources.
Technosphere® Insulin: Defining the Role of Technosphere Particles at the Cellular Level
Authors: Angelo Robert , Rousseau Kathleen , Grant Marshall , Leone-Bay Andrea , Richardson Peter
Published: January 2014

Background:

Technosphere® Insulin (TI) is a novel inhalation powder for the treatment of diabetes mellitus. Technosphere Insulin delivers insulin with an ultra rapid pharmacokinetic profile that is distinctly different from all other insulin products but similar to natural insulin release. Such rapid absorption is often associated with penetration enhancers that disrupt cellular integrity.

Methods:

Technosphere Insulin was compared to a panel of known penetration enhancers in vitro using the Calu-3 lung cell line to investigate the effects of TI on insulin transport.

Results:

Measures of tight junction integrity such as transepithelial electrical resistance, Lucifer yellow permeability, and F-actin staining patterns were all unaffected by TI. Cell viability and plasma membrane integrity were also not affected by TI. In contrast, cells treated with comparable (or lower) concentrations of penetration enhancers showed elevated Lucifer yellow permeability, disruption of the F-actin network, reduced cell viability, and compromised plasma membranes.

Conclusions:

These results demonstrate that TI is not cytotoxic in an in vitro human lung cell model and does not function as a penetration enhancer. Furthermore, TI does not appear to affect the transport of insulin across cellular barriers.
Oral Insulin and Buccal Insulin: A Critical Reappraisal
Authors: Heinemann Lutz , Jacques Yves
Published: January 2014

Despite the availability of modern insulin injection devices with needles that are so sharp and thin that practically no injection pain takes place, it is still the dream of patients with diabetes to, for example, swallow a tablet with insulin. This is not associated with any pain and would allow more discretion. Therefore, availability of oral insulin would not only ease insulin therapy, it would certainly increase compliance. However, despite numerous attempts to develop such a “tablet” in the past 85 years, still no oral insulin is commercially available. Buccal insulin is currently in the last stages of clinical development by one company and might become available in the United States and Europe in the coming years (it is already on the market in some other countries). The aim of this review is to critically describe the different approaches that are currently under development. Optimal coverage of prandial insulin requirements is the aim with both routes of insulin administration (at least with most approaches). The speed of onset of metabolic effect seen with some oral insulin approaches is rapid, but absorption appears to be lower when the tablet is taken immediately prior to a meal. With all approaches, considerable amounts of insulin have to be applied in order to induce therapeutically relevant increases in the metabolic effect because of the low relative biopotency of buccal insulin. Unfortunately, the number of publications about clinical-experimental and clinical studies is surprisingly low. In addition, there is no study published in which the variability of the metabolic effect induced (with and without a meal) was studied adequately. In summary, after the failure of inhaled insulin, oral insulin and buccal insulin are hot candidates to come to the market as the next alternative routes of insulin administration.
Are Current Insulin Pumps Accessible to Blind and Visually Impaired People?
Authors: Burton Darren M. , Uslan Mark M. , Blubaugh Morgan V. , Clements Charles W.
Published: January 2014

Background:

In 2004, Uslan and colleagues determined that insulin pumps (IPs) on the market were largely inaccessible to blind and visually impaired persons. The objective of this study is to determine if accessibility status changed in the ensuing 4 years.

Methods:

Five IPs on the market in 2008 were acquired and analyzed for key accessibility traits such as speech and other audio output, tactual nature of control buttons, and the quality of visual displays. It was also determined whether or not a blind or visually impaired person could independently complete tasks such as programming the IP for insulin delivery, replacing batteries, and reading manuals and other documentation.

Results:

It was found that IPs have not improved in accessibility since 2004. None have speech output, and with the exception of the Animas IR 2020, no significantly improved visual display characteristics were found. Documentation is still not completely accessible.

Conclusion:

Insulin pumps are relatively complex devices, with serious health consequences resulting from improper use. For IPs to be used safely and independently by blind and visually impaired patients, they must include voice output to communicate all the information presented on their display screens. Enhancing display contrast and the size of the displayed information would also improve accessibility for visually impaired users. The IPs must also come with accessible user documentation in alternate formats.
The Personalized Medicine for Diabetes Meeting Summary Report
Authors: Klonoff David C.
Published: January 2014

Personalized medicine for diabetes is a potential method to specifically identify people who are at high risk of developing type 2 diabetes based on a combination of personal history, family history, physical examination, circulating biomarkers, and genome. High-risk individuals can then be referred to lifestyle programs for risk reduction and disease prevention. Using a personalized medicine approach, a patient with already-diagnosed type 2 diabetes can be treated individually based on information specific to that individual. The field of personalized medicine for diabetes is rapidly exploding. Diabetes Technology Society convened the Personalized Medicine for Diabetes (PMFD) Meeting March 19–20, 2009 in San Francisco. The meeting was funded through a contract from the US Air Force. Diabetes experts from the military, government, academic, and industry communities participated. The purpose was to reach a consensus about PMFD in type 2 diabetes to (a) establish screening programs, (b) diagnose cases at an early stage, and (c) monitor and treat the disease with specific measures. The group defined what a PMFD program should encompass, what the benefits and drawbacks of such a PMFD program would be, and how to overcome barriers. The group reached six conclusions related to the power of PMFD to improve care of type 2 diabetes by resulting in (1) better prediction, (2) better prophylactic interventions, (3) better treatments, and (4) decreased cardiovascular disease burden. Additional research is needed to demonstrate the benefits of this approach. The US Air Force is well positioned to conduct research and develop clinical programs in PMFD.
Genetics Factors Contributing to Type 2 Diabetes across Ethnicities
Authors: Elbein Steven C.
Published: January 2014

Type 2 diabetes mellitus (T2DM) is among the many common diseases with a strong genetic component, but until recently, the variants causing this disease remained largely undiscovered. With the ability to interrogate most of the variation in the genome, the number of genetic variants has grown from 2 to 19 genes, many with multiple variants. An additional three genes are associated primarily with fasting glucose rather than T2DM. Despite the plethora of new markers, the individual effect is uniformly small, and the cumulative effect explains little of the genetic risk for T2DM. Furthermore, the success is largely restricted to European populations. Despite success in mapping genes in Asian populations, success in United States minorities, particularly African Americans, has been limited. The genetic findings highlight the role of the β cell in diabetes pathogenesis, but much remains to be discovered before genetic prediction and individualized medicine can become a reality for this disease.
Pharmacogenetics for Type 2 Diabetes: Practical Considerations for Study Design
Authors: Vella Adrian
Published: January 2014

There is a relative dearth of studies designed to elucidate genetic variation that can explain differences in the response to diabetes pharmacotherapy. When designing such studies, appropriate consideration of the various nongenetic variables that can affect the treatment response is necessary. In addition, disease stage and prior pharmacotherapy also influence drug efficacy. Selecting the appropriate genetic variant to test in such studies is also important, and common variants (known to be functional or otherwise) in a given candidate locus should be tested for the effect on the treatment response. Finally, an appropriate measure of treatment response is necessary to enable detection of pharmacogenetic effects. Perhaps prior to undertaking such studies, smaller studies utilizing well-characterized, homogenous populations with normal glucose tolerance or prediabetes (to avoid the problem of disease effects on treatment response) and surrogate measures of response such as insulin secretion should be completed.
Personalized Medicine in Diabetes: Regulatory Considerations
Authors: Harper Courtney C.
Published: January 2014

Personalized medicine has become a topic of great interest because of its potential to improve patient care and optimize therapeutic strategy. The U.S. Food and Drug Administration (FDA) is interested in promoting personalized medicine, whenever appropriate, to protect and promote the public health. The ability to better diagnose, screen, and manage patients with diabetes in order to individualize care should lead to better health outcomes and a large benefit to public health. This article describes FDA regulatory considerations for devices intended for use as personalized medicine tools for the diagnosis and treatment of patients with diabetes.
Noninvasive Optical Screening for Diabetes
Authors: Ediger Marwood N. , Olson Byron P. , Maynard John D.
Published: January 2014

Background:

Advanced glycation end products (AGEs) are implicated in the complications of diabetes. Advanced glycation end products also accumulate in the skin and are sensitive biomarkers for the risk of developing diabetes and related complications. Some AGEs fluoresce and can be measured noninvasively by optical spectroscopy.

Methods:

Noninvasive screening for diabetes has been evaluated in an 18-site study involving a cohort of 2793 subjects meeting American Diabetes Association-based screening criteria. Subjects were measured with a specialized skin fluorimeter and also received traditional blood glucose and glycated hemoglobin tests.

Results:

Retrospective results indicated that the noninvasive technology measuring dermal fluorescence is more sensitive at detecting abnormal glucose tolerance than either fasting plasma glucose or glycated hemoglobin A1C.

Conclusions:

These results suggest that noninvasive measurement of dermal fluorescence may be an effective tool to identify individuals at risk for diabetes and its complications. The noninvasive technology yields immediate results, and since measuring dermal fluorescence requires no blood draws or patient fasting, the instrument may be well suited for opportunistic screening.
Ethical Issues of Predictive Genetic Testing for Diabetes
Authors: Haga Susanne B.
Published: January 2014

With the rising number of individuals affected with diabetes and the significant health care costs of treatment, the emphasis on prevention is key to controlling the health burden of this disease. Several genetic and genomic studies have identified genetic variants associated with increased risk to diabetes. As a result, commercial testing is available to predict an individual's genetic risk. Although the clinical benefits of testing have not yet been demonstrated, it is worth considering some of the ethical implications of testing for this common chronic disease. In this article, I discuss several issues that should be considered during the translation of predictive testing for diabetes, including familial implications, improvement of risk communication, implications for behavioral change and health outcomes, the Genetic Information Nondiscrimination Act, direct-to-consumer testing, and appropriate age of testing.
A Feasibility Study of Bihormonal Closed-Loop Blood Glucose Control Using Dual Subcutaneous Infusion of Insulin and Glucagon in Ambulatory Diabetic Swine
Authors: El-Khatib Firas H. , Jiang John , Damiano Edward R.
Published: January 2014

Background:

We sought to test the feasibility and efficacy of bihormonal closed-loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of insulin and glucagon, a model-predictive control algorithm for determining insulin dosing, and a proportional-derivative control algorithm for determining glucagon dosing.

Methods:

Thirteen closed-loop experiments (∼7–27 h in length) were conducted in six ambulatory diabetic pigs weighing 26–50 kg. In all experiments, venous BG was sampled through a central line in the vena cava. Efficacy was evaluated in terms of the controller's ability to regulate BG in response to large meal disturbances (∼5 g of carbohydrate per kilogram of body mass per meal) based only on regular frequent venous BG sampling and requiring only the subject's weight for initialization.

Results:

Closed-loop results demonstrated successful BG regulation to normoglycemic range, with average insulin-to-carbohydrate ratios between ∼1:20 and 1:40 U/g. The total insulin bolus doses averaged ∼6 U for a meal containing ∼6 g per kilogram body mass. Mean BG values in two 24 h experiments were ∼142 and ∼155 mg/dl, with the total daily dose (TDD) of insulin being ∼0.8–1.0 U per kilogram of body mass and the TDD of glucagon being ∼0.02–0.05 mg. Results also affirmed the efficacy of SC doses of glucagon in staving off episodic hypoglycemia.

Conclusions:

We demonstrate the feasibility of bihormonal closed-loop BG regulation using a control system that employs SC infusion of insulin and glucagon as governed by an algorithm that reacts only to BG without any feedforward information regarding carbohydrate consumption or physical activity. As such, this study can reasonably be regarded as the first practical implementation of an artificial endocrine pancreas that has a hormonally derived counterregulatory capability.
Screening for Diabetic Retinopathy Using Computer Vision and Physiological Markers
Authors: Hann Christopher E. , Revie James A. , Hewett Darren , Chase J. Geoffrey , Shaw Geoffrey M.
Published: January 2014

Background:

Hyperglycemia and diabetes result in vascular complications, most notably diabetic retinopathy (DR). The prevalence of DR is growing and is a leading cause of blindness and/or visual impairment in developed countries. Current methods of detecting, screening, and monitoring DR are based on subjective human evaluation, which is also slow and time-consuming. As a result, initiation and progress monitoring of DR is clinically hard.

Methods:

Computer vision methods are developed to isolate and detect two of the most common DR dysfunctions—dot hemorrhages (DH) and exudates. The algorithms use specific color channels and segmentation methods to separate these DR manifestations from physiological features in digital fundus images. The algorithms are tested on the first 100 images from a published database. The diagnostic outcome and the resulting positive and negative prediction values (PPV and NPV) are reported. The first 50 images are marked with specialist determined ground truth for each individual exudate and/or DH, which are also compared to algorithm identification.

Results:

Exudate identification had 96.7% sensitivity and 94.9% specificity for diagnosis (PPV = 97%, NPV = 95%). Dot hemorrhage identification had 98.7% sensitivity and 100% specificity (PPV = 100%, NPV = 96%). Greater than 95% of ground truth identified exudates, and DHs were found by the algorithm in the marked first 50 images, with less than 0.5% false positives.

Conclusions:

A direct computer vision approach enabled high-quality identification of exudates and DHs in an independent data set of fundus images. The methods are readily generalizable to other clinical manifestations of DR. The results justify a blinded clinical trial of the system to prove its capability to detect, diagnose, and, over the long term, monitor the state of DR in individuals with diabetes.
An Evaluation of “I, Pancreas” Algorithm Performance In Silico
Authors: Wilinska Malgorzata E. , Nodale Marianna
Published: January 2014

Background:

The objective of this study was to investigate the performance of a newly proposed insulin titrating algorithm to achieve tight glycemic control in the critically ill.

Methods:

A simulation environment with 10 critically ill virtual subjects was employed to evaluate the “I, Pancreas” algorithm proposed by Braithwaite et al. and described in an article in this issue of Journal of Diabetes Science and Technology. The algorithm was coded in MATLAB® and was “plugged in” to a simulation environment to provide glucose control in a 48-hour-long simulated study.

Results:

Mean blood glucose was 6.5 ± 0.4 mmol/liter (118 ± 7.8 mg/dl), percentage of time spent in the target glucose range was 38% (32–44%), and the hyperglycemic index was 0.6 (0.4 −1.0) mmol/liter [11.1 (7.7–18.1) mg/dl]. A single episode of mild hypoglycemia at 3.8 mmol/liter (69 mg/dl) was observed during 480 hours of glucose control.

Conclusion:

In this initial in silico evaluation, the “I, Pancreas” algorithm provided a safe control of glucose in the simulated study and achieved tight glycemic control 38% of the time.
Enhanced Glucose Sensor Linearity Using Poly(Vinyl Alcohol) Hydrogels
Authors: Vaddiraju SanthiSagar , Singh Hardeep , Burgess Diane J. , Jain Faquir C. , Papadimitrakopoulos Fotios
Published: January 2014

Background:

High linearities, sensitivities, and low oxygen dependence constitute prime requisites for electrochemical glucose sensors. However, for implantable sensors the need to control tissue inflammation requires the use of outer membranes that permit inward analyte diffusion while continuously releasing anti-inflammatory drugs and other tissue response-modifying (TRM) agents. We have shown previously that while outer membranes based on layer-by-layer (LBL) assembly enhance linearity, poly(vinyl alcohol)(PVA) hydrogels loaded with TRM-containing microspheres enable a significant reduction in tissue inflammation. This article discusses the amperometric performance of glucose sensors coated with stacked LBL/PVA hydrogel outer membranes.

Methods:

Sensors were fabricated by immobilizing glucose oxidase enzyme on a 50-μm platinum wire followed by deposition of stacked LBL/PVA hydrogel outer membranes. The sensor response to various glucose concentrations was determined by applying 0.7 V vs an Ag/AgCl reference electrode in phosphate-buffered saline (37°C). Michaelis—Menten analysis was performed to quantify sensor performance in terms of linearity ( Kappm,glu) and oxygen dependence ( Kappm,O2/[Glucose]).

Results:

When overlaid onto LBL-assembled outer membranes, PVA hydrogels improved sensor linearity by 60% from 10 to 16 m M of glucose and resulted in a twofold decrease in oxygen dependence.

Conclusions:

Enhancement in the performance of a PVA-coated sensor is attributed to the oxygen-storing capability of PVA hydrogel due to the formation of hydrophobic domains during its freezing and thawing employed to physical cross-link the PVA. Such membranes with the capability to release TRMs continuously while storing oxygen constitute a major improvement over current outer membrane technologies.
A Minimal C-Peptide Sampling Method to Capture Peak and Total Prehepatic Insulin Secretion in Model-Based Experimental Insulin Sensitivity Studies
Authors: Lotz Thomas , Göltenbott Uli , Chase J. Geoffrey , Docherty Paul , Hann Christopher E.
Published: January 2014

Aims and Background:

Model-based insulin sensitivity testing via the intravenous glucose tolerance test (IVGTT) or similar is clinically very intensive due to the need for frequent sampling to accurately capture the dynamics of insulin secretion and clearance. The goal of this study was to significantly reduce the number of samples required in intravenous glucose tolerance test protocols to accurately identify C-peptide and insulin secretion characteristics.

Methods:

Frequently sampled IVGTT data from 12 subjects [5 normal glucose-tolerant (NGT) and 7 type 2 diabetes mellitus (T2DM)] were analyzed to calculate insulin and C-peptide secretion using a well-accepted C-peptide model. Samples were reduced in a series of steps based on the critical IVGTT profile points required for the accurate estimation of C-peptide secretion. The full data set of 23 measurements was reduced to sets with six or four measurements. The peak secretion rate and total secreted C-peptide during 10 and 20 minutes postglucose input and during the total test time were calculated. Results were compared to those from the full data set using the Wilcoxon rank sum to assess any differences.

Results:

In each case, the calculated secretion metrics were largely unchanged, within expected assay variation, and not significantly different from results obtained using the full 23 measurement data set ( P < 0.05).

Conclusions:

Peak and total C-peptide and insulin secretory characteristics can be estimated accurately in an IVGTT from as few as four systematically chosen samples, providing an opportunity to minimize sampling, cost, and burden.