bluuebunny/crossref_metadata_2025 huggingface dataset:
Bariatric Surgery and Type 2 Diabetes Mellitus: Surgically Induced Remission
Authors: Tejirian Talar , Jensen Candice , Dutson Erik
Published: January 2014

The relationship between obesity and type 2 diabetes mellitus (T2DM) is well known. Morbidly obese patients with T2DM who undergo bariatric surgery have improvement or remission of their diabetes. Different types of bariatric operations offer varying degrees of T2DM remission. These operations are classified as restrictive, malabsorptive, or a combination of both. The gold-standard operation, known as the Roux-en-Y gastric bypass, is a combination operation.

Most often, improvement of the diabetes is seen within days of the operation. Various theories to explain this rapid change include calorie restriction and hormonal changes from exclusion of the upper gastrointestinal tract. Weight loss accounts for the sustained improvements in glucose control. The patients who benefit the most are those who are early in their disease course.

Having a single treatment for both obesity and T2DM is ideal. As bariatric surgery has become a safe operation when performed by experienced surgeons, it should be considered a treatment for these diseases. The impact it can have on the lives of individual patients and society as a whole is tremendous.
Measuring Glucose Concentrations: Daily Practice, Current and Future Developments
Authors: Heinemann Lutz
Published: January 2014

Self-monitoring of blood glucose (SMBG) by means of modern glucose meters is of relevance for all patients with diabetes. It not only provides important information about the effect of therapeutic interventions on metabolic control, but about the effect of exercise and meals as well. Therefore, it is an essential part of diabetes therapy. However, it has received little interest from academia in the last 10 years. This is in sharp contrast to the massive increase in SMBG use in the last decades and its economic impact on health care systems. Many physicians and patients believe that SMBG and the measurement technologies behind it are a no-brainer nowadays, i.e., that the measurement provides reliable results in practically all cases. In reality, it appears as if patients have only mediocre knowledge about the appropriate handling of the procedure and subsequent therapeutic action. Also, evaluation of the measurement quality of blood glucose meters is not studied adequately in many cases. Such studies should also take into account handling by the patients themselves under daily life conditions. Unfortunately, most of such studies are initiated and sponsored by the manufacturers of blood glucose meters/test strips, and not by an independent institution. In view of the costs and risks combined with SMBG, we should consider that all patients participate in a course that ends with a little examination and provides them with a “driver's license” for this diagnostic measure.
Glucose Sensing Issues for the Artificial Pancreas
Authors: DeVries J. Hans
Published: January 2014

The first retrospective continuous glucose monitor entered the market in 1999. Now that this tool gives online data, the question arises whether it is ready to be incorporated into a closed-loop system. The author discusses the following questions: (1) Is the accuracy of current continuous glucose monitoring (CGM) systems good enough for use in a prototype artificial pancreas system?; (2) How do we assess CGM accuracy?; (3) What is the minimal distance between a continuous glucose monitor and an insulin delivery site in which a CGM can function accurately?; and (4) Does any physiological and instrumental delay associated with continuous glucose monitoring hamper the development of an artificial pancreas?
Use of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Hospital: A Review of One Institution's Experience
Authors: Leonhardi Brenda J. , Boyle Mary E. , Beer Karen A. , Seifert Karen M. , Bailey Marilyn , Miller-Cage Victoria , Castro Janna C. , Bourgeois Peggy B. , Cook Curtiss B.
Published: January 2014

Background:

This article reviews the performance of our hospital's inpatient insulin pump policy.

Methods:

Twenty-five hospital admissions of 21 unique patients receiving outpatient insulin pump therapy were reviewed.

Results:

Between November 1, 2005, and November 30, 2006, there were 25 hospital admissions involving 21 patients receiving outpatient insulin pump therapy. The average age and duration of diabetes among these 21 patients was 50 and 29 years, respectively; 67% were women, 90% had type 1 diabetes, and all were white. The mean length of hospital stay was 4 days, and the average reported length of insulin pump therapy was 4 years. Patients in 16 of the admissions were identified as candidates for continued use of the insulin pump during the hospital stay. Over 90% of patients remaining on the insulin pump had documentation by nursing of the presence of the pump at the time of admission; 100% of the patients had an admission glucose recorded; 88% had a record of signed patient consent; 81% had evidence of completed preprinted insulin pump orders; 75% received a required endocrine consultation; and 75% of cases had documentation of completed bedside flow sheet. A high frequency of both hypoglycemic and hyperglycemic events occurred in the patients; however, no adverse events were related directly to the insulin pump.

Conclusions:

Insulin pump therapy can be safely continued in the hospital setting. While staff compliance with required procedures was high, there was still room for improvement. More data are needed, however, on whether this method of insulin delivery is effective for controlling hyperglycemia in hospitalized patients.
Further Development of Artificial Pancreas: Blocked by Patents?
Authors: Erdin Nils , Robin Franck , Heinemann Lutz , Brandt Derek , Hovorka Roman
Published: January 2014

Patent activity in the field of medical device technology and especially in the area of artificial pancreas development has surged in recent years. According to the search presented in this article, the number of granted U.S. patents in the area of closed-loop glucose control (CLGC) increased from 24 filed in 1991 to 247 filed in 2001. A company active in the area of diabetes technology development will likely need to understand a patent landscape consisting of hundreds of patents. Currently, both in the United States and in Europe, patentability requirements seem to be raised in order to ensure patent quality. However, the current patent landscape reflects the work of the patent offices in the past, as already granted patents are not affected by changes made to the patent grant procedure today.

Regarding the increasing amount of patents and considering the complexity of CLGC systems, the attempt to develop a CLGC system will become more and more venturesome regarding the risk of infringement of already existing patents. The consequence of this situation can be that less innovation takes place.

This article highlights some important general aspects of the patent system, briefly characterizes the current CLGC patent landscape, and illustrates by means of two exemplary patents what one angle of said patent landscape looks like. It is our opinion that, in order to support the rapid development of an artificial pancreas for patients with diabetes, adequate action to lower this hurdle should be undertaken by a consortium of all parties involved (industries, patient organizations, health-care professionals, and institutional payers).
A Review of the Development of a Vehicle for Localized and Controlled Drug Delivery for Implantable Biosensors
Authors: Bhardwaj Upkar , Papadimitrakopoulos Fotios , Burgess Diane J.
Published: January 2014

A major obstacle to the development of implantable biosensors is the foreign body response (FBR) that results from tissue trauma during implantation and the continuous presence of the implant in the body. The in vivo stability and functionality of biosensors are compromised by damage to sensor components and decreased analyte transport to the sensor. This paper summarizes research undertaken by our group since 2001 to control the FBR toward implanted sensors. Localized and sustained delivery of the anti-inflammatory drug, dexamethasone, and the angiogenic growth factor, vascular endothelial growth factor (VEGF), was utilized to inhibit inflammation as well as fibrosis and provide a stable tissue-device interface without producing systemic adverse effects. The drug-loaded polylactic-co-glycolic acid (PLGA) microspheres were embedded in a polyvinyl alcohol (PVA) hydrogel composite to fabricate a drug-eluting, permeable external coating for implantable devices. The composites were fabricated using the freeze-thaw cycle method and had mechanical properties similar to soft body tissue. Dexamethasone-loaded microsphere/hydrogel composites were able to provide anti-inflammatory protection, preventing the FBR. Moreover, concurrent release of dexamethasone with VEGF induced neoangiogenesis in addition to providing anti-inflammatory protection. Sustained release of dexamethasone is required for the entire sensor lifetime, as a delayed inflammatory response developed after depletion of the drug from the composites. These studies have shown the potential of PLGA microsphere/PVA hydrogel-based composites as drug-eluting external coatings for implantable biosensors.
Development of Novel Glucose Sensing Fluids with Potential Application to Microelectromechanical Systems-Based Continuous Glucose Monitoring
Authors: Li Siqi , Huang Xian , Davis Erin N. , Lin Qiao , Wang Qian
Published: January 2014

Background:

We have previously presented a microelectromechanical systems (MEMS) viscometric sensor for continuous glucose monitoring. The sensing fluid used therein was based on protein concanavalin A, which is known to have significant drawbacks, such as immunotoxicity and instability. To address this issue, a stable, biocompatible polymeric sensing fluid has been developed.

Methods:

In the polymeric sensing system, glucose reversibly formed strong ester bonds with the phenylboronic acid moiety on the poly(acrylamide- ran-3-acrylamidophenylboronic acid) (PAA- ran-PAAPBA) polymer backbone, resulting in cross-linking of the copolymers and an increase in the solution viscosity. The copolymers were synthesized via classic free radical copolymerization processes. The viscosity of the PAA- ran-PAAPBA, dissolved in phosphate-buffered saline buffer and in the presence of glucose at physiologically relevant concentrations, was measured by an Ubbelodhe viscometer and a prototype MEMS viscometric device.

Results:

Experimental results showed that the polymer molecular weight and composition depended on the solvent quantity, while the sensing fluid viscosity was determined by the polymer molecular weight and percentage composition of PAAPBA. The study of the temperature effect on viscosity showed that the polymer sensed glucose effectively under physiological conditions, although the high temperature lowered its sensitivity. Through proper adjustment of these parameters, a distinctive viscosity increase was observed when the glucose concentration increased from 0 to 450 mg/dl, which was detectable by our prototype MEMS device.

Conclusions:

We have successfully developed a stable, biocompatible polymeric system for the sensitive detection of glucose. MEMS experiments demonstrated that the sensing fluid was able to sense glucose at different concentrations. This sensing system can potentially enable highly reliable, continuous monitoring of glucose in interstitial fluid from subcutaneous tissue.
German-Translated Norfolk Quality of Life (QOL-DN) Identifies the Same Factors as the English Version of the Tool and Discriminates Different Levels of Neuropathy Severity
Authors: Vinik Etta J. , Paulson James F. , Ford-Molvik Stephanie L. , Vinik Aaron I.
Published: January 2014

Background:

The development and validation of Norfolk QOL-DN, a fiber-specific, quality-of-life tool for diabetic neuropathy, was published previously (Part 1). This study (Part 2) defines the psychometric properties of the German-translated Norfolk QOL-DN in a large multicenter (96 sites) population with neuropathy ranging from minimal to severe, comparing them with those in the origina51 English/American version in a 30-center European/North American population with mild neuropathy; determines the power of the German-translated version in a five-staged diabetic peripheral neuropathy (DPN) German population to discriminate different levels of neuropathy severity; and establishes factors having the greatest impact on QOL.

Methods:

One hundred eighty-six German patients were assessed: asymptomatic of DPN ( n = 40), symptomatic ( n = 46), DN with foot-ulcer history ( n = 32), DN with amputations ( n = 22), and DN amputation history ( n = 46). German-translated Norfolk QOL-DN was administered to 177 patients with staged DN complications. German-translated Norfolk QOL-DN data were compared with QOL-DN data from the European/American study of 379 mild neuropathy patients. Exploratory factor analysis assessed factor structure consistency in the translated instrument. Ordinal regression analysis (polytomous universal model) was used to evaluate the association between factor scores and complication stages.

Results:

The German translation identified the same five factors in more advanced neuropathy as in the English mild neuropathy population. Total QOL scores differed among each of the five neuropathy severity groups [analysis of variance p < 0.001, Tukey-Kramer post hoc, α = 0.05]. Two factors emerged as predictors of impaired QOL and disease severity: physical function/large fiber (Wald X2 = 6.188, p = 0.013) and activities of daily living (ADL)(Wald X2 = 9.098, p = 0.003).

Conclusions:

Norfolk QOL-DN discriminates levels of neuropathy within and between populations. Physical functioning and ADL are the most important determinants of QOL. Early occurrence of orthostasis suggests a redefinition of autonomic neuropathy to be more symptom inclusive.
Twenty-Four Hour Ambulatory Blood Pressure Monitoring in Adolescents with Type 1 Diabetes: Getting Started
Authors: Pellizzari Margaret , Speiser Phyllis W. , Carey Dennis E. , Fort Pavel , Kreitzer Paula M. , Frank Graeme R.
Published: January 2014

Twenty-four hour ambulatory blood pressure monitoring (ABPM) is a valuable tool in the pediatric and adolescent population with type 1 diabetes. It provides useful information not readily available from sporadic clinic blood pressure (BP) measurements and a more reliable estimation of the subject's BP over an extended period of time. Ambulatory blood pressure monitoring is gaining popularity with clinicians and investigators alike. The American Heart Association has recently issued recommendations for the use of ABPM in children and adolescents. We have incorporated ABPM into our adolescent diabetes practice and present useful information for clinicians planning to initiate 24 h ABPM in their clinical practice.
Alzheimer's Disease is Type 3 Diabetes—Evidence Reviewed
Authors: de la Monte Suzanne M. , Wands Jack R.
Published: January 2014

Alzheimer's disease (AD) has characteristic histopathological, molecular, and biochemical abnormalities, including cell loss; abundant neurofibrillary tangles; dystrophic neurites; amyloid precursor protein, amyloid-β (APP-Aβ) deposits; increased activation of prodeath genes and signaling pathways; impaired energy metabolism; mitochondrial dysfunction; chronic oxidative stress; and DNA damage. Gaining a better understanding of AD pathogenesis will require a framework that mechanistically interlinks all these phenomena. Currently, there is a rapid growth in the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration, but this surge of new information is riddled with conflicting and unresolved concepts regarding the potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity to AD pathogenesis. Herein, we review the evidence that (1) T2DM causes brain insulin resistance, oxidative stress, and cognitive impairment, but its aggregate effects fall far short of mimicking AD; (2) extensive disturbances in brain insulin and insulin-like growth factor (IGF) signaling mechanisms represent early and progressive abnormalities and could account for the majority of molecular, biochemical, and histopathological lesions in AD; (3) experimental brain diabetes produced by intracerebral administration of streptozotocin shares many features with AD, including cognitive impairment and disturbances in acetylcholine homeostasis; and (4) experimental brain diabetes is treatable with insulin sensitizer agents, i.e., drugs currently used to treat T2DM. We conclude that the term “type 3 diabetes” accurately reflects the fact that AD represents a form of diabetes that selectively involves the brain and has molecular and biochemical features that overlap with both type 1 diabetes mellitus and T2DM.
Contributions of Mathematical Modeling of Beta Cells to the Understanding of Beta-Cell Oscillations and Insulin Secretion
Authors: Pedersen Morten Gram
Published: January 2014

Mathematical modeling of pancreatic beta cells has contributed significantly to the understanding of the mechanisms involved in glucose-stimulated insulin secretion (GSIS). Early models of insulin secretion built in the 1970s were phenomenological with little biological foundation for the proposed mechanisms. In the 1980s, models focused on identifying the regulation of bursting electrical activity known to be important for insulin secretion. The main result was to reject proposed mechanisms as new data emerged, but important results of the role of cell-to-cell coupling were also established. New models have been proposed that provide possible explanations for the occurrence of various patterns of bursting and calcium oscillations. In addition, modeling has played an important role in comparing competing effects of calcium on both NADH and adenosine 3′-5′-cyclic monophosphate levels. Models including modern cell biological results of the regulation of insulin containing granules and cell heterogeneity have appeared, providing updated versions of the early models proposed in the 1970s. These models, when coupled to electrophysiological- and calcium-based ones, have the prospect to aid in understanding the overall picture of GSIS. In addition, they might be useful for estimating in vivo beta-cell functioning. Beta-cell modeling will likely move closer to clinical applications, where it can be expected to play an important role, as it has and will, in understanding the complex oscillatory phenomena observed in beta cells and islets.
Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose?
Authors: Steil Garry M. , Deiss Dorothee , Shih Judy , Buckingham Bruce , Weinzimer Stuart , Agus Michael S.D.
Published: January 2014

Objective:

Studies showing improved outcomes with tight glycemic control in the intensive care unit (ICU) have resulted in a substantial number of new insulin delivery algorithms being proposed. The present study highlights mechanisms used in the better-known approaches, examines what might be critical differences among them, and uses systems theory to characterize the conditions under which each can be expected to perform best.

Methods:

Algorithm dose (ΔI/ΔG) and step (response to a persistent elevation in glucose) response curves were calculated for written instruction algorithms, developed at the Providence Heart and Vascular Institute (Portland [P] protocol), the University of Washington (UW), and Yale University (Y), together with similar curves for the Glucommander (GM) and proportional integral derivative (PID) computer algorithms. From the simulated curves, different mechanisms used to adjust insulin delivery were identified.

Results:

All algorithms increased insulin delivery in response to persistent hyperglycemia, but the mechanism used altered the algorithm's sensitivity to glucose, or gain, in the GM, UW, and Y protocols, while leaving it unchanged for the P protocol and PID algorithm.

Conclusions:

The increase in insulin delivery in response to persistent hyperglycemia observed with all the algorithms can be expected to bring subjects who respond to insulin to targeted glucose ranges. However, because the PID and P protocols did not alter the insulin delivery response curves, these algorithms can be expected to take longer to achieve target glucose levels in individuals who are insulin resistant and/or are exposed to increased carbohydrate loads (e.g., glucose infusions). By contrast, the GM, UW, and Y algorithms can be expected to adapt to the insulin resistance such that the time to achieve target levels is unchanged if the time for insulin to act does not change. If the insulin resistance is accompanied by a longer time for insulin to act, the UW, Y, and GM algorithms may increase the risk of hypoglycemia. Under these conditions, the longer time required for the PID and P protocols to achieve a target glucose level may be a reasonable trade-off for no increase in the risk of hypoglycemia.
Analysis of Studies That Compare the Dose Accuracy of Prefilled Insulin Pens
Authors: Crowe Daniel
Published: January 2014

Multiple industry-sponsored studies have been published about the accuracy of insulin delivery using prefilled insulin pens. Although the study by Weise and colleagues in this issue of Journal of Diabetes Science and Technology found that the Novo Nordisk device was slightly more accurate than the Sanofi-Aventis device, one can anticipate a Sanofi-Aventis-funded study that may find the opposite, because no internationally acceptable, publicly funded, unbiased scientific organization exists to perform head-to-head comparisons of drugs and devices in an evidence-based manner. Currently, clinicians are left on their own to determine whether a study on this topic was conducted in an accurate, unbiased manner. A fundamental redesign of clinical research could reinvigorate and revolutionize the process by which innovations travel from the bench to the bedside. As we anticipate changes in healthcare in the future, it is imperative that the approval and postmarketing surveillance process is revised to support the practice of true evidence-based medicine.
A Liquid Chromatography/Tandem Mass Spectrometry Method for Determination of 25-Hydroxy Vitamin D2 and 25-Hydroxy Vitamin D3 in Dried Blood Spots: A Potential Adjunct to Diabetes and Cardiometabolic Risk Screening
Authors: Newman Mark S. , Brandon Theodore R. , Groves Margaret N. , Gregory William L. , Kapur Sanjay , Zava David T.
Published: January 2014

Background:

Now emerging as an important risk factor for type 1 diabetes, vitamin D deficiency is also associated with obesity, metabolic syndrome, and type 2 diabetes and has been identified as a potential cardiometabolic risk factor. A simple, accurate screening test for 25-hydroxy vitamin D [25(OH)D] deficiency is needed. We developed a liquid chromatography/tandem mass spectrometry assay for 25-hydroxy vitamin D2 [25(OH)D2] and 25-hydroxy vitamin D3 [25(OH)D3] in dried blood spots.

Method:

Blood spots were collected by finger stick simultaneously with serum samples obtained by venipuncture from healthy volunteers. Disks punched from the dried blood spots were sonicated with an internal standard solution of deuterated 25(OH)D3 (26,26,26,27,27,27-d6). Methanol was added to precipitate proteins prior to extraction with hexane. The extracted samples were dried and reconstituted in 50:50 methanol:H2O before injection into a Varian 320-MS TQ mass spectrometer.

Results:

Blood spot assay precision was good over the reportable range: interassay coefficients of variation were 13, 13, and 11% at concentrations of 14, 26, and 81 ng/ml, respectively, for 25-hydroxy vitamin D3 and 12% at 23 ng/ml for 25(OH)D2. The 25(OH)D3 assay was linear from 3.5 to 75 ng/ml (R > 0.99). Blood spot and serum values showed excellent correlation for 25(OH)D2 ( R = 0.90, n = 54) and 25(OH)D3 ( R = 0.91, n = 83).

Conclusions:

This blood spot assay for 25(OH)D2 and 25(OH)D3 provides a convenient and cost-effective alternative to serum assays and can be automated. This may be valuable in large-scale screening for risk of type 1 diabetes, for cardiometabolic risk screening, and for monitoring vitamin D supplementation.
The Potential Use of Radio Frequency Identification Devices for Active Monitoring of Blood Glucose Levels
Authors: Moore Bert
Published: January 2014

Imagine a diabetes patient receiving a text message on his mobile phone warning him that his blood glucose level is too low or a patient's mobile phone calling an emergency number when the patient goes into diabetic shock.

Both scenarios depend on automatic, continuous monitoring of blood glucose levels and transmission of that information to a phone. The development of advanced biological sensors and integration with passive radio frequency identification technologies are the key to this. These hold the promise of being able to free patients from finger stick sampling or externally worn devices while providing continuous blood glucose monitoring that allows patients to manage their health more actively. To achieve this promise, however, a number of technical issues need to be addressed.
Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations
Authors: Lehmann Eldon D. , Tarín Cristina , Bondia Jorge , Teufel Edgar , Deutsch Tibor
Published: January 2014

Introduction:

AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described.

Methods:

This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done.

Discussion:

The methodology to be adopted for implementing the generic absorption model within AIDA has been overviewed, and the first plasma insulin profiles based on this approach have been demonstrated. Ideas for future work and development are discussed. It is expected that an updated release of AIDA (v4.5), based on this collaborative approach, will become available for free—in due course—via the www.2aida.org Web site. Readers who wish to be informed when the new software is launched can join the very low volume AIDA announcement list by sending a blank email note to subscribe@2aida.org .

Results:

Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as well as for insulin doses up to 50 IU.
Improving Access to Eye Care: Teleophthalmology in Alberta, Canada
Authors: Ng ManCho , Nathoo Nawaaz , Rudnisky Chris J. , Tennant Matthew T. S.
Published: January 2014

Background:

Diabetic retinopathy in Alberta and throughout Canada is common, with a prevalence up to 40% in people with diabetes. Unfortunately, due to travel distance, time, and expense, a third of patients with diabetes do not receive annual dilated eye examinations by ophthalmologists, despite universal health care access. In an effort to improve access, a teleophthalmology program was developed to overcome barriers to eye care. Prior to clinical implementation, teleophthalmology technology was clinically validated for the identification of treatable levels of diabetic retinopathy.

Method:

Patients undergoing a teleophthalmology assessment underwent stereoscopic digital retinal photographs following pupillary dilation. Digital images were then packaged into an encrypted password-protected compressed file for uploading onto a secure server. Images were digitally unpackaged for review as a stereoscopic digital slide show and graded with a modified Early Treatment Diabetic Retinopathy Study algorithm. Reports were then generated automatically as a PDF file and sent back to the referring physician.

Results:

Teleophthalmology programs in Alberta have assessed more than 5500 patients (9016 visits) to date. Nine hundred thirty patients have been referred for additional testing or treatment. Approximately 2% of teleophthalmology assessments have required referral for in-person examination due to ungradable image sets, most commonly due to cataract, corneal drying, or asteroid hyalosis.

Conclusions:

In Alberta and throughout Canada, many patients with diabetes do not receive an annual dilated eye examination. Teleophthalmology is beneficial because patients can be assessed within their own communities. This decreases the time to treatment, allows treated patients to be followed remotely, and prevents unnecessary referrals. Health care costs may be reduced by the introduction of comprehensive teleophthalmology examinations by enabling testing and treatment to be planned prior to the patient's first visit.
Variation in the Frequency of Hemoglobin A1c (HbA1c) Testing: Population Studies Used to Assess Compliance with Clinical Practice Guidelines and Use of HbA1c to Screen for Diabetes
Authors: Lyon Andrew W. , Higgins Trefor , Wesenberg James C. , Tran David V. , Cembrowski George S.
Published: January 2014

Background:

The volume of hemoglobin A1c (HbA1c) testing has increased dramatically over the past decade and few studies have attempted to determine how the test is used. The goals of this study were to evaluate the frequency of HbA1c testing in regional populations to assess the extent of screening for diabetes and to determine if the HbA1c testing intervals of known diabetic patients were consistent with clinical practice guidelines.

Methods:

Two years of HbA1c results were extracted from laboratory information systems in four regions of the province of Alberta that represent urban, mixed urban-rural, and rural populations. HbA1c testing frequencies and the proportions of nondiabetic patients undergoing HbA1c tests were derived.

Results:

Approximately 60% of HbA1c tests in each region were done on patients who had only a single test during the 2-year interval. Testing of nondiabetic patients accounted for 24% of HbA1c tests and varied by region. While the cumulative frequency distributions of HbA1c test intervals resembled each other, detailed analyses of the frequency distributions depicted broad multimodal peaks and regional variations that suggest a great deal of heterogeneity among practices. The most common HbA1c testing interval was 3 months ± 3 weeks in each region and is consistent with the 3-month test interval target in a clinical practice guideline.

Conclusions:

HbA1c testing is being performed on a substantial proportion of nondiabetic patients. On average, patients with diabetes in Alberta receive 1.5 HbA1c tests per year. However, we observed regional differences in the frequency of testing and variation in compliance with clinical practice guidelines.
The Correlation of Hemoglobin A1c to Blood Glucose
Authors: Sikaris Ken
Published: January 2014

The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of “average blood glucose” as though “blood glucose” were itself a simple idea. When we consider all the blood glucose forms—arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting—we can start to see that this is not a simple issue.

Nevertheless, it seems as though HbA1c correlates to any single glucose measurement. Having more than one measurement and taking those measurements in the preceding month improves the correlation further. In particular, by having glucose measurements that reflect both the relatively lower overnight glucose levels and measurements that reflect the postprandial peaks improves not only our ability to manage diabetes patients, but also our understanding of how HbA1c levels are determined. Modern continuous glucose monitoring (CGM) devices may take thousands of glucose results over a week. Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c.

The ability to relate HbA1c to average glucose may become a popular method for reporting HbA1c, eliminating current concerns regarding differences in HbA1c standardization. Hemoglobin A1c expressed as an average glucose may be more understandable to patients and improve not only their understanding, but also their ability to improve their diabetes management.
Noninvasive Ultrasonic Glucose Sensing with Large Pigs (∼200 Pounds) Using a Lightweight Cymbal Transducer Array and Biosensors
Authors: Park Eun-Joo , Werner Jacob , Beebe Joshua , Chan Samantha , Smith Nadine Barrie
Published: January 2014

Background:

To prevent complications in diabetes, the proper management of blood glucose levels is essential. Since conventional glucose meters require pricking fingers or other areas of the skin, a noninvasive method for monitoring blood glucose levels is desired. Using a lightweight cymbal transducer array, this study was conducted to noninvasively determine the glucose levels of pigs having a similar size to humans.

Method:

In vivo experiments using eight pigs (∼200 pounds) were performed in five groups. A cymbal array with four biosensors was attached to the axillary area of the pig. The array was operated at 20 kHz at special peak-temporal peak intensity (Isptp) equal to 50 or 100 mW/cm2 for 5, 10, or 20 minutes. After the ultrasound exposure, glucose concentrations of the interstitial fluid were determined using biosensors. For comparison, glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter.

Result:

In comparison, glucose levels determined by a cymbal array and biosensor system were close to those measured by a glucose meter. After a 20-minute ultrasound exposure at Isptp = 100 mW/cm2, the average glucose level determined by the ultrasound system was 175 ± 7 mg/dl, which is close to 166 ± 5 mg/dl measured by the glucose meter.

Conclusion:

Results indicate the feasibility of using a cymbal array for noninvasive glucose sensing on pigs having a similar size to humans. Further studies on the ultrasound conditions, such as frequency, intensity, and exposure time, will be continued for effective glucose sensing.
Analysis of the Performance of the Software/Hardware Product MyDiaBase+RxChecker for Assessing Treatment Regimens
Authors: Petrasek Danny , Bidner Marissa
Published: January 2014

In 2008, the Action to Control Cardiovascular Risk in Diabetes trial was halted due to an unexpected number of deaths in the intensive treatment group (aiming for hemoglobin A1c levels less than 6%). Hypoglycemic episodes were thought by some to be a contributing cause, underscoring again the challenge of maintaining tight control while avoiding dangerous excursions into hypoglycemic territory. Albisser and colleagues present a set of articles in this issue of Journal of Diabetes Science and Technology that describe a clinical product developed specifically for this timeless clinical conundrum.
Review of Fructosyl Amino Acid Oxidase Engineering Research: A Glimpse into the Future of Hemoglobin A1c Biosensing
Authors: Ferri Stefano , Kim Seungsu , Tsugawa Wakako , Sode Koji
Published: January 2014

Glycated proteins, particularly glycated hemoglobin A1c, are important markers for assessing the effectiveness of diabetes treatment. Convenient and reproducible assay systems based on the enzyme fructosyl amino acid oxidase (FAOD) have become attractive alternatives to conventional detection methods. We review the available FAOD-based assays for measurement of glycated proteins as well as the recent advances and future direction of FAOD research. Future research is expected to lead to the next generation of convenient, simple, and economical sensors for glycated protein, ideally suited for point-of-care treatment and self-monitoring applications.
Data Mining Technologies for Blood Glucose and Diabetes Management
Authors: Bellazzi Riccardo , Abu-Hanna Ameen
Published: January 2014

Data mining is the process of selecting, exploring, and modeling large amounts of data to discover unknown patterns or relationships useful to the data analyst. This article describes applications of data mining for the analysis of blood glucose and diabetes mellitus data. The diabetes management context is particularly well suited to a data mining approach. The availability of electronic health records and monitoring facilities, including telemedicine programs, is leading to accumulating huge data sets that are accessible to physicians, practitioners, and health care decision makers. Moreover, because diabetes is a lifelong disease, even data available for an individual patient may be massive and difficult to interpret. Finally, the capability of interpreting blood glucose readings is important not only in diabetes monitoring but also when monitoring patients in intensive care units. This article describes and illustrates work that has been carried out in our institutions in two areas in which data mining has a significant potential utility to researchers and clinical practitioners: analysis of (i) blood glucose home monitoring data of diabetes mellitus patients and (ii) blood glucose monitoring data from hospitalized intensive care unit patients.
Closing the Circle of Care with New Firmware for Diabetes: MyDiaBase+RxChecker
Authors: Albisser A. Michael , Alejandro Rodolfo , Sperlich Marianne , Ricordi Camillo
Published: January 2014

Background:

Satisfactory glycemic control, meeting American Diabetes Association recommendations, is difficult to achieve. Technologically, this is most likely because the circle of care is incomplete. Many have suggested that the introduction of information technology may remedy the situation. However, previous attempts have not succeeded. Recognizing this, we evolved firmware that supports and links both the patient at home and their care providers in the clinic.

Firmware Design and Methods:

The device includes software and a database, all contained in a standard USB flash drive. At home, patients use the database portion of the device (MyDiaBase). It fully complements their diabetes education while capturing pertinent self-management information by tracking self-monitored blood glucose data, body weight, medication dosing, physical activity, diet, lifestyle, and stress. In the clinic, providers use the RxChecker program to perform prescription checks that are based on their patients' outcomes data, thereby effectively closing the circle of care.
Usefulness of Point-of-Care Testing in the Treatment of Diabetes in an Underserved Population
Authors: Leal Sandra , Soto-Rowen Marisa
Published: January 2014

Background:

The purpose of this article was to communicate our experience with point-of-care testing (POCT) using Bayer's A1CNow+® device to test glycated hemoglobin (A1C) in the management of diabetes and to share the observations of our quality control efforts.

Methods:

Forty-seven patients' POCT samples were compared with laboratory samples to determine the validity of the POCT sample being drawn. Data collected represent a 10-month time period that were drawn on-site with the following distribution: 36 samples were drawn the same day, 7 samples were drawn 1 day later, 3 samples were drawn within 3 days, and 1 sample was drawn 4 days later. Although all samples were collected on-site, some of the samples were sent to other local branches of nationally recognized laboratories for analysis.

Results:

The range of A1C results for the POCT group was 5.6 to >13%. The range of A1C results for the laboratory-drawn group was 5 to 12.6%. Twenty-four patients had laboratory results that read lower than the result obtained in the clinic, with an A1C range of 5 to 12.6%, and two patients had laboratory results that read exactly the same as the result obtained in the clinic when using POCT. These two individuals had A1C results of 9.1 and 12.6%. Analysis of data collected determined an r value of 0.918 demonstrating agreement between the POCT samples and the laboratory samples.

Conclusions:

POCT with the A1CNow+ is an effective, economical tool for use in a pharmacist-based diabetes clinic that serves a high-risk underserved population. POCT allows the pharmacist the ability to use on-site results to inform patients of their progress, modify their therapy immediately with an immediate face-to-face opportunity to assure understanding, and provide a self-management goal.
A Strategy for Analyzing Gene—Nutrient Interactions in Type 2 Diabetes
Authors: Wise Carolyn , Kaput Jim
Published: January 2014

Type 2 diabetes mellitus (T2DM), like all chronic diseases, results from interactions between multiple genes and multiple environmental factors. Nevertheless, many research studies focus on either nutrition or genetic factors independently of each other. The challenges of analyzing gene—nutrient interactions in T2DM are the (i) genetic heterogeneity in humans, (ii) complexity of environmental factors, particularly dietary chemicals, and (iii) diverse physiologies that produce the same apparent disease. Many of these variables are not accounted for in the design or study of T2DM or, indeed, most chronic diseases, although exceptions are noteworthy. Establishing experimental paradigms to analyze the complexity of these interactions and physiologies is challenging, but possible. This article provides a strategy to extend nutrigenomic experimental strategies to include early environmental influences that may promote adult-onset disease.
Circulating Biomarkers of Glycemia in Diabetes Management and Implications for Personalized Medicine
Authors: True Mark W.
Published: January 2014

Personalized medicine represents a new model in how the medical community approaches disease management. Rather than managing those with a particular diagnosis according to an established guideline, the personalized medicine model seeks to identify unique characteristics within each patient that can serve as a basis for disease characterization and specialized treatment. This article reviews several circulating biomarkers of glycemia that are used in the medical management of diabetes, to include hemoglobin A1c, fructosamine, and 1,5-anhydroglucitol. Within the discussion, specific attention is paid to areas in which biomarker results do not correlate with anticipated results based on actual mean glycemia. Variability between actual and anticipated results of the various biomarker tests represents opportunities to identify previously undefined subcategories of diabetes and groups of patients that fit into these subcategories. Finally, research areas are proposed for these subcategories that would further promote the field of personalized medicine in diabetes.
Waist Circumference Threshold Values for Type 2 Diabetes Risk
Authors: Friedl Karl E.
Published: January 2014

Adult gains in body weight, excess adiposity, and intra-abdominal fat have each been associated with risk for type 2 diabetes mellitus (T2DM), forming the basis for preventive medicine guidelines and actuarial predictions using practical indices of weight (e.g., body mass index [BMI]) and waist circumference (WC). As obesity-related disease spreads beyond affluent western countries, application of WC thresholds to other populations has highlighted issues of their generalizability. For example, U.S. national health goals based on BMI < 25 kg/m2 and WC < 89 cm (women) and <102 cm (men) differ considerably with a recent law in Japan mandating intervention for older adults with WC exceeding 90 cm (women) and 85 cm (men). The U.S. military has also faced issues of generalizability of WC-based adiposity standards that are fair and achievable. Data from many studies indicate that WC is a reliable biomarker for T2DM risk, suggesting that, for adult men and women, action thresholds should be more stringent than current U.S. guidelines, and it would not be harmful to set worldwide targets somewhere below 90 cm for men and women, regardless of weight status. Medical technology has provided many great insights into disease, including modern imaging technologies that have differentiated fat depots that have the greatest influence on T2DM, but ultimately, an inexpensive measuring tape provides the most useful and cost-effective preventive measure for T2DM today. At some point in the future, a Star Trek-like abdominal body fat “tricorder” noninvasive assessment of tissue composition may provide an advantage over abdominal girth.
Gastric Electrical Stimulation with the TANTALUS® System in Obese Type 2 Diabetes Patients: Effect on Weight and Glycemic Control
Authors: Sanmiguel Claudia P. , Conklin Jeffrey L. , Cunneen Scott A. , Barnett Philip , Phillips Edward H. , Kipnes Mark , Pilcher John , Soffer Edy E.
Published: January 2014

Background:

The TANTALUS® System is an investigational device that consists of an implantable pulse generator connected to gastric electrodes. The system is designed to automatically detect when eating starts and only then deliver sessions of gastric electrical stimulation (GES) with electrical pulses that are synchronized to the intrinsic antral slow waves. We report the effect of this type of GES on weight loss and glucose control in overweight/obese subjects with type 2 diabetes mellitus (T2DM). This study was conducted under a Food and Drug Administration/Institutional Review Board-approved investigational device exemption.

Method:

Fourteen obese T2DM subjects on oral antidiabetes medication were enrolled and implanted laparoscopically with the TANTALUS System (body mass index 39 ± 1 kg/m2, hemoglobin A1c [HbA1c] 8.5 ± 0.2%). Gastric electrical stimulation was initiated four weeks after implantation. Weight, HbA1c, fasting blood glucose, blood pressure, and lipid levels were assessed during the study period.

Results:

Eleven subjects reached the 6-month treatment period endpoint. Gastric electrical stimulation was well tolerated by all subjects. In those patients completing 6 months of therapy, HbA1c was reduced significantly from 8.5 ± 0.7% to 7.6 ± 1%, p < .01. Weight was also significantly reduced from 107.7 ± 21.1 to 102.4 ± 20.5 kg, p < .01. The improvement in glucose control did not correlate with weight loss ( R2 = 0.05, p = .44). A significant improvement was noted in blood pressure, triglycerides, and cholesterol (low-density lipoprotein only).

Conclusions:

Short-term therapy with the TANTALUS System improves glucose control, induces weight loss, and improves blood pressure and lipids in obese T2DM subjects on oral antidiabetes therapy.