Showing papers in "Journal of diabetes science and technology in 2008"

Alzheimer's Disease is Type 3 Diabetes—Evidence Reviewed

Abstract: 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.

A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response:

Abstract: In recent years, a variety of devices (drug-eluting stents, artificial organs, biosensors, catheters, scaffolds for tissue engineering, heart valves, etc.) have been developed for implantation into patients. However, when such devices are implanted into the body, the body can react to these in a number of different ways. These reactions can result in an unexpected risk for patients. Therefore, it is important to assess and optimize the biocompatibility of implantable devices. To date, numerous strategies have been investigated to overcome body reactions induced by the implantation of devices. This review focuses on the foreign body response and the approaches that have been taken to overcome this. The biological response following device implantation and the methods for biocompatibility evaluation are summarized. Then the risks of implantable devices and the challenges to overcome these problems are introduced. Specifically, the challenges used to overcome the functional loss of glucose sensors, restenosis after stent implantation, and calcification induced by implantable devices are discussed.

Body Composition Methods: Comparisons and Interpretation:

Abstract: The incidence of obesity in the United States and other developed countries is epidemic. Because the prevalence of comorbidities to obesity, such as type 2 diabetes, has also increased, it is clear there is a great need to monitor and treat obesity and its comorbidities. Body composition assessments vary in precision and in the target tissue of interest. The most common assessments are anthropometric and include weight, stature, abdominal circumference, and skinfold measurements. More complex methods include bioelectrical impedance, dual-energy X-ray absorptiometry, body density, and total body water estimates. There is no single universally recommended method for body composition assessment in the obese, but each modality has benefits and drawbacks. We present here the most common methods and provide guidelines by way of examples to assist the clinician/researcher in choosing methods appropriate to their situation.

A review of the foreign-body response to subcutaneously-implanted devices: the role of macrophages and cytokines in biofouling and fibrosis.

Abstract: The biological response to implanted biomaterials in mammals is a complex series of events that involves many biochemical pathways. Shortly after implantation, fibrinogen and other proteins bind to the device surface, a process known as biofouling. Macrophages then bind to receptors on the proteins, join into multinucleated giant cells, and release transforming growth factor β and other inflammatory cytokines. In response to these signals, quiescent fibroblasts are transformed into myofibroblasts, which synthesize procollagen via activation of Smad mediators. The procollagen becomes crosslinked after secretion into the extracellular space. Mature crosslinked collagen and other extracellular matrix proteins gradually contribute to formation of a hypocellular dense fibrous capsule that becomes impermeable or hypopermeable to many compounds. Porous substrates and angiogenic growth factors can stimulate formation of microvessels, which to some extent can maintain analyte delivery to implanted sensors. However, stimulation by vascular endothelial growth factor alone may lead to formation of leaky, thin-walled, immature vessels. Other growth factors are most probably needed to act upon these immature structures to create more robust vessels. During implantation of foreign bodies, the foreign-body response is difficult to overcome, and thousands of biomaterials have been tested. Biomimicry (i.e., creating membranes whose chemical structure mimics natural cellular compounds) may diminish the response, but as of this writing, it has not been possible to create a stealth material that circumvents the ability of the mammalian surveillance systems to distinguish foreign from self.

Glycemic Variability: The Third Component of the Dysglycemia in Diabetes. Is it Important? How to Measure it?:

Abstract: The dysglycemia of diabetes includes two components: (1) sustained chronic hyperglycemia that exerts its effects through both excessive protein glycation and activation of oxidative stress and (2) acute glucose fluctuations. Glycemic variability seems to have more deleterious effects than sustained hyperglycemia in the development of diabetic complications as both upward (postprandial glucose increments) and downward (interprandial glucose decrements) changes activate the oxidative stress. For instance, the urinary excretion rate of 8-iso-PGF2α, a reliable marker of oxidative stress, was found to be strongly, positively correlated (r = 0.86, p < .001) with glycemic variability assessed from the mean amplitude of glycemic excursions (MAGE) as estimated by continuous glucose monitoring systems (CGMS). These observations therefore raise the question of whether we have the appropriate tools for assessing glycemic variability in clinical practice. From a statistical point of view, the standard deviation (SD) around the mean glucose value appears as the “gold standard.” By contrast, the MAGE index is probably more appropriate for selecting the major glucose swings that are calculated as the arithmetic mean of differences between consecutive peaks and nadirs, provided that the differences be greater than the SD around the mean values. Furthermore, calculating the MAGE index requires continuous glucose monitoring, which has the advantage to detect all isolated upward and downward acute glucose fluctuations. In conclusion, the increasing use of CGMSs will certainly promote better assessment and management of glycemic variability.

Diabetes Self-Management Care via Cell Phone: A Systematic Review

Abstract: It is an ongoing challenge to provide care and support that will produce and sustain the desired improvements in the health of persons with a chronic illness such as diabetes. Quality health care requires effective collaboration between clinicians and patients.1,2 Finding novel ways to enhance communication and improve the health of those with chronic diseases is also a continuing part of providing care. Interventions involving automated telephone message systems have been shown to improve knowledge and health outcomes.3–5 Telephone-based interventions have had positive results even among persons of low socioeconomic status and ethnic minorities.6 According to the Cellular Telecommunications and Internet Association, there are over 255 million cell phone subscribers in the United States.7 Although income may seem to be a major barrier in cell phone ownership, every two out of three households in the United States have a cell phone.8 In a survey of those owning a cell phone, 35% said that they use it for text messaging.9 There is a need to examine if the various functions of cell phones, including text messaging, can help with providing better health care and lead to improved health outcomes. Education and information technology are parts of diabetes care that have been studied. There are other reviews on health care telephone technology,10,11 automated telephone messages,4,12 cell phone technology,13 diabetes Web-assisted interventions,14 and diabetes-computerized learning technologies.15 However, no systematic review or meta-analysis of cell phone-based interventions for persons with diabetes and/or obesity exists to our knowledge that analyzes the evidence on the use of cell phones and text messaging interventions to improve health outcomes, processes of care, acceptance by users, and whether it is cost-effective. The objective of this study was to evaluate the evidence on the impact of cell phone interventions in improving health outcomes and/or processes of care for persons with diabetes and/or obesity. We systematically reviewed studies to evaluate the impact of care and support interventions via cell phone in improving health outcomes and processes of care for persons with diabetes and/or obesity.

Hemorheological Disorders in Diabetes Mellitus

Abstract: The objective of the present study is to review hemorheological disorders in diabetes mellitus. Several key hemorheological parameters, such as whole blood viscosity, erythrocyte deformability, and aggregation, are examined in the context of elevated blood glucose level in diabetes. The erythrocyte deformability is reduced, whereas its aggregation increases, both of which make whole blood more viscous compared to healthy individuals. The present paper explains how the increased blood viscosity adversely affects the microcirculation in diabetes, leading to microangiopathy.

Evaluating the efficacy of closed-loop glucose regulation via control-variability grid analysis.

Abstract: Background: Advancements in subcutaneous continuous glucose monitoring and subcutaneous insulin delivery are stimulating the development of a minimally invasive artificial pancreas that facilitates optimal glycemic regulation in diabetes The key component of such a system is the blood glucose controller for which different design strategies have been investigated in the literature In order to evaluate and compare the efficacy of the various algorithms, several performance indices have been proposed Methods: A new tool—control-variability grid analysis (CVGA)—for measuring the quality of closed-loop glucose control on a group of subjects is introduced It is a method for visualization of the extreme glucose excursions caused by a control algorithm in a group of subjects, with each subject presented by one data point for any given observation period A numeric assessment of the overall level of glucose regulation in the population is given by the summary outcome of the CVGA Results: It has been shown that CVGA has multiple uses: comparison of different patients over a given time period, of the same patient over different time periods, of different control laws, and of different tuning of the same controller on the same population Conclusions: Control-variability grid analysis provides a summary of the quality of glycemic regulation for a population of subjects and is complementary to measures such as area under the curve or low/high blood glucose indices, which characterize a single glucose trajectory for a single subject

Analysis, modeling, and simulation of the accuracy of continuous glucose sensors.

Abstract: Background:Continuous glucose monitors (CGMs) collect a detailed time series of consecutive observations of the underlying process of glucose fluctuations. To some extent, however, the high temporal resolution of the data is accompanied by increased probability of error in any single data point. Due to both physiological and technical reasons, the structure of these errors is complex and their analysis is not straightforward. In this article, we describe some of the methods needed to obtain a description of the sensor error that is detailed enough for simulation.Methods:Data were provided by Abbott Diabetes Care and included two data sets collected by the FreeStyle Navigator™ CGM: The first set consisted of 1032 time series of glucose readings from 136 patients with type 1 diabetes and parallel time series of reference blood glucose (BG) collected via self-monitoring at irregular intervals. The average duration of a time series was 5 days; the total number of sensor-reference data pairs was approximately ...

A Review of Glycated Albumin as an Intermediate Glycation Index for Controlling Diabetes

Abstract: Introduction:This article reviews glycated albumin (GA) as a potential intermediate-term glycation index to fill the gap between self-monitoring of blood glucose (SMBG) and hemoglobin A1c testing i...

Anti-inflammatory polymeric coatings for implantable biomaterials and devices.

Abstract: Synthetic polymer coatings are used extensively in modern medical devices and implants because of their material versatility and processability. These coatings are designed for specific applications by controlling composition and physical and chemical properties, and they can be formed into a variety of complex structures and shapes. However, implantation of these materials into the body elicits a strong inflammatory host response that significantly limits the integration and biological performance of devices. Biomaterial-mediated inflammation is a complex reaction involving protein adsorption, leukocyte recruitment and activation, secretion of inflammatory mediators, and fibrous encapsulation of the implant. Significant research efforts have focused on modifying material properties using various anti-inflammatory polymeric surface coatings to generate more biocompatible implants. This minireview provides a brief background on the events of biomaterial-mediated inflammation and highlights various approaches used for modifying material surfaces to modulate inflammatory responses. These include both passive and active strategies, such as nonfouling surface treatments and delivery of anti-inflammatory agents, respectively. Novel approaches will be needed to extend the in vivo lifetime and performance of devices and reduce the need for multiple implantation surgeries.

Development of a neural network for prediction of glucose concentration in type 1 diabetes patients.

Abstract: Background:A major difficulty in the management of diabetes is the optimization of insulin therapies to avoid occurrences of hypoglycemia and hyperglycemia. Many factors impact glucose fluctuations...

Finger Pricking and Pain: A Never Ending Story:

Abstract: Without finger pricking, no self-measurement of blood glucose (SMBG) is possible. However, the number of scientific studies dealing with this topic, which is highly relevant for patients, is surprisingly small. This is in sharp contrast to the number of papers about blood glucose meters and SMBG in general. This article highlights a number of aspects that are relevant when it comes to finger pricking and pain. There is a clear improvement in the technology employed in the many different lancing devices that are on the market nowadays; however, no good head-to-head comparison study has been performed to date. The invention of novel devices for finger pricking will most likely bring more attention to this topic.

The failure of exubera: are we beating a dead horse?

Abstract: Inhalation of insulin appears to have become an alternative for the subcutaneous injection of insulin for the time being. However, the recent withdrawal of one product that had already reached the marketplace or others that were close to approval raised severe concerns about the future of the pulmonary route for insulin administration. In view of the progress made with respect to the size of the inhaler and the many other options that would improve the pharmacodynamic properties of inhaled insulin, patient acceptance of this innovative approach, and (hopefully) a reduction in cost, we should begin with an open discussion about the future of inhaled insulin in order to avoid its premature death. This commentary discusses many of the advantages and disadvantages of inhaled insulin from the view of the patients, diabetologists, scientists, pharmaceutical industry, health care payers, and politicians. It is hoped that this unusual approach allows keeping an open mind about this interesting route of drug administration.

DUROS technology delivers peptides and proteins at consistent rate continuously for 3 to 12 months.

Abstract: Background: DUROS ® delivery technology consists of sterile, nonbiodegradable, single-use devices for continuous, subcutaneous administration of therapeutic molecules at steady rates. DUROS delivery technology is capable of delivering a wide range of therapeutic molecules for durations ranging from 3 to 12 months. Administration of therapy via DUROS devices may facilitate patient compliance with treatment since the DUROS device does not require self-injections. Consistent delivery of drug levels within a targeted therapeutic window achievable with DUROS delivery technology avoids exposure to high initial drug concentrations that can result from bolus injections and that may be associated with certain adverse drug effects. Methods: Several approaches have been taken to assess the suitability of DUROS devices for delivery of the therapeutic molecules leuprolide acetate, glucagon-like peptide-1 (GLP-1), and omega interferon (omega IFN). Testing includes determining protein stability and measuring in vitro protein release rates. Results: Three peptides or proteins were formulated into either a solution (leuprolide) or Intarcia's proprietary DUROS suspension formulation (GLP-1, omega IFN) and filled into DUROS devices. The devices demonstrated reliable start-up and continuous steady drug delivery in in vitro studies. Stability of the molecules was maintained for 3 years at 37°C (leuprolide), 2 years at 30°C (omega IFN), or 6 months at 37°C (GLP-1). Patients in clinical studies of a 1-year DUROS device found the device to be comfortable and convenient. Conclusions: Multiple studies demonstrated that peptides or proteins remain stable in DUROS devices and that delivery at a steady rate can be achieved over a wide range of delivery rates.

Modular Artificial β-Cell System: A Prototype for Clinical Research

Abstract: Background:The quest toward an artificial β-cell has been accelerating, propelled by recent technological advances in subcutaneous glucose sensors and insulin pumps. The development and clinical testing of algorithms involves several challenges: communication and data transfer between a sensor and a pump via computer, a human interface presenting real-time information to the physician, safety issues when an automated system is used to administer insulin, and an architecture that supports different sensors, pumps, and control algorithms. These challenges were addressed in the development of a modular artificial β-cell system for clinical research.Methods:The developmental environment of MATLAB® (The MathWorks, Inc., Natick, MA) allowed the flexible implementation of communication protocols for different sensors and pumps. The system has a plug-and-play option for the control algorithm and a human interface that presents and logs the data, enforces protocol safety rules, and facilitates physician oversight....

Reliability of lightguide spectrophotometry (O2C) for the investigation of skin tissue microvascular blood flow and tissue oxygen supply in diabetic and nondiabetic subjects.

Abstract: Background and Aims: Skin microvascular assessment has progressed to an important evaluation in patients with diabetes mellitus. This study was done to evaluate a new device using micro-lightguide spectrophotometry in the assessment of skin microvascular function. Material and Methods: Twenty nondiabetic subjects (age 46.6 ± 14.8 years; mean ± SD) and 20 diabetic patients (age 59.4 ± 8.4 years) participated in repeated microvascular measurements using micro-lightguide spectrophotometry. This technique allows simultaneous, noninvasive measurement of microvascular blood flow and hemoglobin oxygenation (SO 2) at the same anatomical area in different tissue layers. A skin probe was placed on nonhairy skin at the thenar eminence of the left hand for the measurement of SO2, and the postischemic reactive hyperemia response (PRH) was measured in skin and underlying muscle tissue. Results: Repeated measurements in PRH revealed a good correlation at the superficial skin layer ( r = 0.97, p < 0.0001) with a coefficient of variation at 9.2 ± 1.7% and at the superficial muscle layer ( r = 0.80, p < 0.0002) with a coefficient of variation at 9.7 ± 1.5%. A slightly weaker correlation was observed for the SO 2 measurement at the skin layer (r = 0.69 ± p < 0.0001) with a coefficient of variation at 17.5 ± 3.8% and at the muscle layer ( r = 0.48; p = 0.0016) with a coefficient of variation at 18.1 ± 10.5%. Conclusions: Lightguide spectrophotometry is an easy, noninvasive, and reliable method for simultaneous measurement of superficial microvascular blood flow by laser Doppler fluxmetry and skin oxygenation by spectrophotometry. Further studies are required to clarify the validity of these measures in special patient populations such as diabetes mellitus with specified microvascular complications.

Inhaled Technosphere insulin in comparison to subcutaneous regular human insulin: time action profile and variability in subjects with type 2 diabetes.

Abstract: Background: This study assessed time action profile and within- and between-subject variability of inhaled Technosphere ® Insulin (TI) compared with subcutaneous regular human insulin (sc RHI). Methods: Thirteen subjects with type 2 diabetes (age 56 ± 7 years, body mass index 30.4 ± 3.0 kg·m -2 ; hemoglobin A1c 6.9 ± 0.9%; mean ± SD) participated in this six-period crossover isoglycemic glucose clamp study. In randomized order, each subject received three single doses of TI and sc RHI on separate study days. Results: Inhalation of TI resulted in a higher maximum serum insulin concentration (858 vs 438 pmol·liter -1 ; p = 0.0001) and shorter intervals to maximum insulin concentration (17 vs 135 minutes; p = 0.0001) than sc RHI. Overall, 48 units of TI and 24 units of sc RHI provided comparable 3-hour insulin exposure (INS area under the curve0-3 h 55.8 vs 60.0 nmol·min·liter -1 , respectively). Time to maximum metabolic effect was shorter (79 vs 293 minutes; p < 0.0001), and percentage of glucose disposal during the first 3 hours was higher for TI compared with sc RHI (59 vs 27%). Within-subject variabilities of insulin exposure following inhalation of TI for 2 and 3 hours and end of study period were 19, 18, and 16% as compared with 27, 25, and 15% after sc RHI injection (p = not significant). Conclusion: Technosphere Insulin has a more rapid onset of action than sc RHI. About 60% of the glucose-lowering effect of TI occurs during the first 3 hours after application. In contrast, <30% of the glucose-lowering effect of sc RHI occurs in this period. Technosphere Insulin demonstrated a lower intrasubject variability during the 3-hour postprandial period, without reaching statistical significance.

Biocompatibility and immune acceptance of adult porcine islets transplanted intraperitoneally in diabetic NOD mice in calcium alginate poly-L-lysine microcapsules versus barium alginate microcapsules without poly-L-lysine.

Abstract: Background:If alginate microcapsules are to be used clinically for therapeutic cell transplants, capsule formulations must be designed to enhance optimal biocompatibility and immune acceptance.Meth...

Consensus report of the coalition for clinical research-self-monitoring of blood glucose.

Abstract: The Coalition for Clinical Research—Self-Monitoring of Blood Glucose Scientific Board, a group of nine academic clinicians and scientists from the United States and Europe, convened in San Francisco, California, on June 11–12, 2008, to discuss the appropriate uses of self-monitoring of blood glucose (SMBG) and the measures necessary to accurately assess the potential benefit of this practice in noninsulin-treated type 2 diabetes mellitus (T2DM). Thirteen consultants from the United States, Europe, and Canada from academia, practice, and government also participated and contributed based on their fields of expertise. These experts represent a range of disciplines that include adult endocrinology, pediatric endocrinology, health education, mathematics, statistics, psychology, nutrition, exercise physiology, and nursing. This coalition was organized by Diabetes Technology Management, Inc. Among the participants, there was consensus that: 1. protocols assessing the performance of SMBG in noninsulin treated T2DM must provide the SMBG intervention subjects with blood glucose (BG) goals and instructions on how to respond to BG data in randomized controlled trials (RCTs); 2. intervention subjects in clinical trials of SMBG-driven interventions must aggressively titrate their therapeutic responses or lifestyle changes in response to hyperglycemia; 3. control subjects in clinical trials of SMBG must be isolated from SMBG-driven interventions and not be contaminated by physician experience with study subjects receiving a SMBG intervention; 4. the best endpoints to measure in a clinical trial of SMBG in T2DM include delta Hemoglobin A1c levels, hyperglycemic events, hypoglycemic events, time to titrate noninsulin therapy to a maximum necessary dosage, and quality of life indices; 5. either individual randomization or cluster randomization may be appropriate methods for separating control subjects from SMBG intervention subjects, provided that precautions are taken to avoid bias and that the sample size is adequate; 6. treatment algorithms for assessing SMBG in T2DM may include a dietary, exercise, and/or medication intervention, which are all titratable according to the SMBG values; 7. the medical literature contains very little information about the performance of SMBG in T2DM from RCTs in which treatment algorithms were used for dysglycemic values; and 8. research on the performance of SMBG in T2DM based on sound scientific principles and clinical practices is needed at this time.

Physical Activity—The Major Unaccounted Impediment to Closed Loop Control:

Abstract: This article presents a mathematical model of glucose homeostasis that is valid during physical activity. Known changes in glucose dynamics during exercise were accounted for in the model, and exercise itself was detected and quantified through heart rate (beats per minute). The model was successfully fit to 21 type 1 diabetic subjects during a hyperinsulemic clamp protocol, and performance of the new model was compared with the standard minimal model of glucose kinetics that it was derived from.

Impact of human factors on clinical protocol performance: a proposed assessment framework and case examples.

Abstract: Background: Hyperglycemia is prevalent in critical care and tight control can save lives Current ad-hoc clinical protocols require significant clinical effort and can often produce highly variable results Thus, tight control remains elusive as there is not enough understanding of the relationship between control performance and protocol design, particularly with regard to how a given protocol is implemented Methods: This article examines the role of human factors and how individuals relate to technological protocols in clinical settings The study consists of an overall brief review that is used to create a first graphical representation of the impact of human factors in clinical medical protocol implementations This initial framework is examined in the context of two similar, but different, case studies—the specialized relative insulin and nutrition tables glycemic control protocol and the TREAT system for antibiotic selection Results: A graphical framework relating the human factors impact on medical protocol implementation is created This framework describes the primary impacts on performance as resulting from clinical burden and protocol transparency Their primary effect is on compliance with the protocol, which directly affects performance and outcome, particularly in long-term studies versus short pilot studies Summary: Compliance is a key element in obtaining the best clinical outcome that a given protocol can provide The issues that most affect compliance are quite often unrelated to the patient or treatment, but are a function of the protocol design and its ability to integrate (by its design) into a given clinical setting A framework for examining these issues in design and in post-hoc assessment is therefore proposed and examined in two brief case studies

Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons.

Abstract: Insulin delivery is a crucial component of a closed-loop system aiming at the development of an artificial pancreas. The intravenous route, which has been used in the bedside artificial pancreas model for 30 years, has clear advantages in terms of pharmacokinetics and pharmacodynamics, but cannot be used in any ambulatory system so far. Subcutaneous (SC) insulin infusion benefits from the broad expansion of insulin pump therapy that promoted the availability of constantly improving technology and fast-acting insulin analog use. However, persistent delays of insulin absorption and action, variability and shortterm stability of insulin infusion from SC-inserted catheters generate effectiveness and safety issues in view of an ambulatory, automated, glucose-controlled, artificial beta cell. Intraperitoneal insulin delivery, although still marginally used in diabetes care, may offer an interesting alternative because of its more-physiological plasma insulin profiles and sustained stability and reliability of insulin delivery.

How Much Do Forgotten Insulin Injections Matter to Hemoglobin A1c in People with Diabetes? A Simulation Study

Abstract: Background: Forgotten or omitted insulin injections are an important contributing factor to poor glycemic control in people with type 1 diabetes. This study uses mathematical modeling and examines the impact on hemoglobin A1c (HbA1c) levels if insulin injections are forgotten. The simulation concerns people with type 1 diabetes on intensive insulin therapy. Methods: Five sets of blood glucose profiles with and without a forgotten injection were obtained. The difference to HbA1c was calculated using an HbA1c estimator on the profiles and was multiplied by the frequency of forgotten events. A frequency of 2.1 forgotten injections per week was found in the literature. Results: Calculations showed that forgetting 2.1 meal-related injections per week would lead to an increase in HbA1c of at least 0.3–0.4% points, and similarly 0.2–0.3% points related to forgotten injections of the long-acting insulin. In case of even more pronounced nonadherence (e.g., if 39% of all injections are forgotten) there is a possible increase of HbA1c of 1.8% points. Conclusions: The magnitude of the possible improvement in HbA1c agrees well with other studies in the relation between adherence and HbA1c levels. The estimated numbers suggest that missing injections are an important reason for suboptimal treatment.

Statistical hypoglycemia prediction.

Abstract: Background:Hypoglycemia presents a significant risk for patients with insulin-dependent diabetes mellitus. We propose a predictive hypoglycemia detection algorithm that uses continuous glucose monitor (CGM) data with explicit certainty measures to enable early corrective action.Method:The algorithm uses multiple statistical linear predictions with regression windows between 5 and 75 minutes and prediction horizons of 0 to 20 minutes. The regressions provide standard deviations, which are mapped to predictive error distributions using their averaged statistical correlation. These error distributions give confidence levels that the CGM reading will drop below a hypoglycemic threshold. An alarm is generated if the resultant probability of hypoglycemia from our predictions rises above an appropriate, user-settable value. This level trades off the positive predictive value against lead time and missed events.Results:The algorithm was evaluated using data from 26 inpatient admissions of Navigator® 1-minute read...

Randomized Forced Titration to Different Doses of Technosphere® Insulin Demonstrates Reduction in Postprandial Glucose Excursions and Hemoglobin A1c in Patients with Type 2 Diabetes

Abstract: Background:Individuals with type 2 diabetes mellitus have impairments in early insulin release, resulting in increased postprandial glucose excursions and suboptimal glycemic control. Studies with ...

Microneedle-based automated therapy for diabetes mellitus.

Abstract: This article discusses the use of microneedles in automated diabetes therapy systems. Advanced bioengineered systems have the potential to close the loop between diagnostic and therapeutic elements of diabetes treatment, thus constituting a “smart” system. Prevalent insulin therapies, and most glucose sensing techniques, involve the transfer of physical entities through the skin. Micromachined needles (microneedles) can achieve this in a noninvasive or minimally invasive manner while contributing various other technological merits. The dynamics of autonomous diabetes therapy systems include highly complex interdependencies between the various physical and biological entities involved, thus warranting multidisciplinary research initiatives. The iterative development of a noninvasive, bioengineered interface such as microneedles necessitates a better understanding of the human skin, its molecular architecture as a polymer film, and its role as a functional biological unit. This review addresses application-specific requirements of a microneedle-based interface system specifically for autonomous diabetes therapy. Key design issues and related parametric interdependencies specific to this application are discussed.

Laboratory-based non-clinical comparison of occlusion rates using three rapid-acting insulin analogs in continuous subcutaneous insulin infusion catheters using low flow rates.

Abstract: Background:Rapid-acting analog insulin is used increasingly for continuous subcutaneous insulin infusion therapy (CSII). As the choice of insulin may be a determinant of catheter occlusion, we compared rates of early and late occlusion of a standard CSII catheter with three insulin analogs in a laboratory-based setting.Methods:Twenty-four pumps were used for the study. Each insulin analog (glulisine, lispro, and aspart) was assigned to eight pumps in a randomized order for each of nine runs of 5-day duration. Pumps were primed to receive a basal dose of 0.1 IU/h with a bolus dose of 2 IU given three times each day. Pumps were placed in an incubator to maintain temperature in the range of 32 to 36 °C.Results:Over the entire study period, there were 48 occlusions. Early occlusions (within 72 hours) occurred during five of the nine runs with no evidence of any difference between insulins (p = .27); there were no occlusions before 48 hours. Over the whole of the 5-day infusion period, the probabilities of ove...

Teleretinal imaging to screen for diabetic retinopathy in the Veterans Health Administration.

Abstract: Diabetes is the leading cause of adult vision loss in the United States and other industrialized countries. While the goal of preserving vision in patients with diabetes appears to be attainable, the process of achieving this goal poses a formidable challenge to health care systems. The large increase in the prevalence of diabetes presents practical and logistical challenges to providing quality care to all patients with diabetes. Given this challenge, the Veterans Health Administration (VHA) is increasingly using information technology as a means of improving the efficiency of its clinicians. The VHA has taken advantage of a mature computerized patient medical record system by integrating a program of digital retinal imaging with remote image interpretation (teleretinal imaging) to assist in providing eye care to the nearly 20% of VHA patients with diabetes. We describe this clinical pathway for accessing patients with diabetes in ambulatory care settings, evaluating their retinas for level of diabetic retinopathy with a teleretinal imaging system, and prioritizing their access into an eye and health care program in a timely and appropriate manner.

Peculiarities of the Continuous Glucose Monitoring Data Stream and Their Impact on Developing Closed-Loop Control Technology

Abstract: Therapeutic advances in type 1 diabetes (T1DM) are currently focused on developing a closed-loop control system using a continuous glucose monitor (CGM), subcutaneous insulin delivery, and a control algorithm. Because a CGM assesses blood glucose indirectly (and therefore often inaccurately), it limits the effectiveness of the controller. In order to improve the quality of CGM data, a series of analyses are suggested. These analyses evaluate and compensate for CGM errors, assess risks associated with glucose variability, predict glucose fluctuation, and forecast hypo- and hyperglycemia. These analyses are illustrated with data collected using the MiniMed CGMS® (Medtronic, Northridge, CA) and Freestyle Navigator™ (Abbott Diabetes Care, Alameda, CA). It is important to remember that traditional statistics do not work with CGM data because consecutive CGM readings are highly interdependent.