bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Susceptibility to Type 2 Diabetes and Implications for Therapy
Authors: Florez Jose C.
Published: January 2014

Since 2000, we have witnessed an explosion of known genetic determinants of type 2 diabetes risk. These findings have seeded the expectation that our ability to make personalized, predictive, therapeutic clinical decisions is imminent. However, the loci discovered to date explain only a small fraction of overall inheritable risk for this disease. In many cases, the reported associations merely signal regions of the genome that are overrepresented in disease versus health but do not identify the causal variants. Well-powered cohort studies have shown that the set of markers detected thus far does not significantly improve individual risk prediction or stratification over common clinical variables, with the possible exception of younger subjects. On the other hand, risk genotypes may help target subgroups for more intensive surveillance or prevention efforts, although whether such a strategy improves patient outcomes and/or is cost-effective should be examined. Similarly, whether genetic information will help guide therapeutic decisions must be tested in adequately designed and rigorously conducted clinical trials.
Effects of Glycemic Load on Metabolic Health and Type 2 Diabetes Mellitus
Authors: Roberts Christian K. , Liu Simin
Published: January 2014

A large body of epidemiologic evidence has demonstrated that the combination of a Western diet and lifestyle is primarily responsible for the increased metabolic disease risk, such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, noted in society today. Thus finding optimal intervention strategies to combat these growing epidemics is imperative. Despite some controversy, a growing body of literature indicates that one aspect of diet that likely affects phenotypic outcomes and metabolic disease risk is the glycemic load (GL). This brief review will provide an overview of the GL concept, discuss epidemiologic work investigating relationships between both GL and metabolic risk factors, as well as intervention studies that have assessed the impact of GL on phenotypic outcomes related to T2DM and cardiovascular disease. Overall, a low dietary GL may be protective against metabolic disease and should be considered as a healthful dietary component.
Environmental Influences on Development of Type 2 Diabetes and Obesity: Challenges in Personalizing Prevention and Management
Authors: Ershow Abby G.
Published: January 2014

Recent epidemic increases in the U.S. prevalence of obesity and diabetes are a consequence of widespread environmental changes affecting energy balance and its regulation. These environmental changes range from exposure to endocrine disrupting pollutants to shortened sleep duration to physical inactivity to excess caloric intake. Overall, we need a better understanding of the factors affecting individual susceptibility and resistance to adverse exposures and behaviors and of determinants of individual response to treatment. Obesity and diabetes prevention will require responding to two primary behavioral risk factors: excess energy intake and insufficient energy expenditure. Adverse food environments (external, nonphysiological influences on eating behaviors) contribute to excess caloric intake but can be countered through behavioral and economic approaches. Adverse built environments, which can be modified to foster more physical activity, are promising venues for community-level intervention. Techniques to help people to modulate energy intake and increase energy expenditure must address their personal situations: health literacy, psychological factors, and social relationships. Behaviorally oriented translational research can help in developing useful interventions and environmental modifications that are tailored to individual needs.
Technologies for Diabetes Genomics
Authors: Mueller Patricia W.
Published: January 2014

The genetic risk for diabetes largely depends on the type of diabetes and the penetrance and severity of the effect of the contributing genes. This ranges from the high-risk mutations of neonatal diabetes and maturity-onset diabetes of the young to the lower, but still significant, risk conferred by common human leukocyte antigen alleles in type 1 diabetes to the still-lower risk conferred by the common variants associated with type 2 diabetes. There are many new molecular technologies, each with their own set of methodological issues, that have been used for genome-wide association studies and that can be used for determining the genetic risk for these various types of diabetes. These technologies include whole genome single nucleotide polymorphism microarrays, high-throughput polymorphism analyzers, next-generation sequencers, and copy-number variant technologies.
A Genomics Study of Type 2 Diabetes Mellitus in U.S. Air Force Personnel
Authors: Lott Lisa
Published: January 2014

The military community is at high risk for type 2 diabetes (T2D), especially as it relates to military beneficiaries, although preventive measures can be implemented to reduce disease onset. This study evaluates the prevalence of risk-associated single nucleotide polymorphisms in patients diagnosed with T2D within active duty, retired military, and military-dependent populations on Lackland Air Force Base compared to nondiabetic controls. Results will be used as a basis of comparison to analyze risk-conferring genotypes in the young, healthy active duty population to generate the prevalence of T2D risk-associated factors in our current and future war fighters. Identifying genetic markers of T2D prior to abnormal glucose control and insulin resistance may ultimately adjust future risk through early detection, healthy lifestyle modifications, and disease management programs.
Improved Glycemic Control through Continuous Glucose Sensor-Augmented Insulin Pump Therapy: Prospective Results from a Community and Academic Practice Patient Registry
Authors: Cohen Ohad , Körner Anna , Chlup Rudolf , Zoupas Christos S. , Ragozin Anton K. , Wudi Krisztina , Bartaskova Dagmar , Pappas Aggelos , Niederland Tamás , Taybani Zoltán , Barák Lubomir , Vazeou Andriani
Published: January 2014

Background:

Conducted by highly experienced investigators with abundant time and resources, phase III studies of continuous glucose sensing (CGS) may lack generalizability to everyday clinical practice.

Method:

Community or academic practices in six Central and Eastern European or Mediterranean countries prospectively established an anonymized registry of consecutive patients with type 1 insulin-dependent diabetes mellitus starting CGS-augmented insulin pump therapy with the Paradigm® X22 (Medtronic MiniMed, Northridge, CA) under everyday conditions, without prior CGS with another device. We compared glycosylated hemoglobin (GHb) values before and after 3 months of CGS and assessed relationships between insulin therapy variables and glycemia-related variables at weeks 1, 4, and 12 of CGS.

Results:

Of 102 enrolled patients, 85 (83%) with complete weeks 1, 4, and 12 sensor data and baseline/3-month GHb data were evaluable. Evaluable patients were ∼54% male and ∼75% adult (mean age, 33.2 ± 16.9 years) with longstanding diabetes and high personal/family education levels. Mean GHb declined significantly after 3 months of CGS (7.55 ± 1.33% at baseline to 6.81 ± 1.08% after 12 weeks, 0.74% absolute decrease, P < 0.001). The absolute GHb reduction correlated significantly ( P < 0.0005) with baseline GHb: larger absolute reductions tended to occur when baseline levels were higher. An increased basal insulin dose as a percentage of the total daily insulin dose and a decreased daily bolus count from week 1 to week 12 of CGS predicted GHb improvement from baseline to week 12.

Conclusions:

CGS-augmented insulin pump therapy appears to improve glycemic control in type 1 diabetes in varied everyday practice settings.
Six-Year Retrospective Follow-Up Study of Safe Screening Intervals for Sight-Threatening Retinopathy in Patients with Diabetes Mellitus
Authors: Soto-Pedre Enrique , Hernaez-Ortega Maria Concepcion , Vázquez José Antonio
Published: January 2014

Background:

We estimate safe screening intervals for sight-threatening diabetic retinopathy (STDR).

Methods:

A 6-year retrospective follow-up study to review screening results of two cohorts of patients with diabetes mellitus (DM) was conducted; a cohort free of diabetic retinopathy (DR) and a cohort with mild nonproliferative diabetic retinopathy (NPDR) at baseline. Patients had been screened by means of a nonmydriatic retinal camera. Baseline age, sex, and diabetes characteristics were also collected. Statistical analysis was based on life-table method of risk estimation.

Results:

A total of 286 patients with DM free of DR and 144 patients with mild NPDR at baseline were included in the study. For patients free of DR, the probability of remaining free of STDR was 97% (95% confidence interval [CI] 94–99%) at the end of the fourth year. In this cohort of patients, those with type 2 DM were more likely to progress to STDR than those who had type 1 DM ( p < .01). For patients with mild NPDR, the probability of remaining free of STDR dropped to 94% (95% CI 88–97%) at the end of the second year, and it was still 100% at the end of the second year for those with a glycated hemoglobin level ≤7.5% at baseline ( p < .05).

Conclusions:

Screening at a 3–4 year interval for diabetes patients free of DR is safe because of their low risk of developing STDR. Patients with mild NPDR require screening at a 1 year interval, or at a 2 year interval with good metabolic control.
A Physiological Model of the Effect of Hypoglycemia on Plasma Potassium
Authors: Christensen Toke Folke , Bækgaard Martin , Dideriksen Jacob Lund , Steimle Kristoffer Lindegaard , Mogensen Mads Lause , Kildegaard Jonas , Struijk Johannes Jan , Hejlesen Ole Kristian
Published: January 2014

Background:

Adrenaline release and excess insulin during hypoglycemia stimulate the uptake of potassium from the bloodstream, causing low plasma potassium (hypokalemia). Hypokalemia has a profound effect on the heart and is associated with an increased risk of malignant cardiac arrhythmias. It is the aim of this study to develop a physiological model of potassium changes during hypoglycemia to better understand the effect of hypoglycemia on plasma potassium.

Method:

Potassium counterregulation to hypokalemia was modeled as a linear function dependent on the absolute potassium level. An insulin-induced uptake of potassium was modeled using a negative exponential function, and an adrenaline-induced uptake of potassium was modeled as a linear function. Functional expressions for the three components were found using published data.

Results:

The performance of the model was evaluated by simulating plasma potassium from three published studies. Simulations were done using measured levels of adrenaline and insulin. The mean root mean squared error (RMSE) of simulating plasma potassium from the three studies was 0.09 mmol/liter, and the mean normalized RMSE was 14%. The mean difference between nadirs in simulated and measured potassium was 0.12 mmol/liter.

Conclusions:

The presented model simulated plasma potassium with good accuracy in a wide range of clinical settings. The limited number of hypoglycemic episodes in the test set necessitates further tests to substantiate the ability of the model to simulate potassium during hypoglycemia. In conclusion, the model is a good first step toward better understanding of changes in plasma potassium during hypoglycemia.
Computing the Risk of Postprandial Hypo- and Hyperglycemia in Type 1 Diabetes Mellitus considering Intrapatient Variability and other Sources of Uncertainty
Authors: García-Jaramillo Maira , Calm Remei , Bondia Jorge , Tarín Cristina , Vehí Josep
Published: January 2014

Objective:

The objective of this article was to develop a methodology to quantify the risk of suffering different grades of hypo- and hyperglycemia episodes in the postprandial state.

Methods:

Interval predictions of patient postprandial glucose were performed during a 5-hour period after a meal for a set of 3315 scenarios. Uncertainty in the patient's insulin sensitivities and carbohydrate (CHO) contents of the planned meal was considered. A normalized area under the curve of the worst-case predicted glucose excursion for severe and mild hypo- and hyperglycemia glucose ranges was obtained and weighted accordingly to their importance. As a result, a comprehensive risk measure was obtained. A reference model of preprandial glucose values representing the behavior in different ranges was chosen by a X2 test. The relationship between the computed risk index and the probability of occurrence of events was analyzed for these reference models through 19,500 Monte Carlo simulations.

Results:

The obtained reference models for each preprandial glucose range were 100, 160, and 220 mg/dl. A relationship between the risk index ranges <10, 10–60, 60–120, and >120 and the probability of occurrence of mild and severe postprandial hyper- and hypoglycemia can be derived.

Conclusions:

When intrapatient variability and uncertainty in the CHO content of the meal are considered, a safer prediction of possible hyper- and hypoglycemia episodes induced by the tested insulin therapy can be calculated.
Antisense Oligonucleotide Therapy in Diabetic Retinopathy
Authors: Hnik Peter , Boyer David S. , Grillone Lisa R. , Clement John G. , Henry Scott P. , Green Ellen A.
Published: January 2014

Diabetic retinopathy is one of the leading causes of blindness in the United States and other parts of the world. Historically, laser photocoagulation and vitrectomy surgery have been used for the treatment of diabetic retinopathy, including diabetic macular edema. Both procedures have proven to be useful under certain conditions but have their limitations. New pathways and processes that promote diabetic retinopathy have been identified, and several new therapeutic approaches are under investigation. These new therapies may be beneficial in the treatment of diabetic retinopathy and include antivascular endothelial growth factor agents, corticosteroids, and therapies that may potentially target a number of additional diabetic retinopathy-related factors and processes, including antisense oligonucleotides. Second-generation antisense oligonucleotides, such as iCo-007, may offer a significant advantage in the treatment of diabetic retinopathy by downregulating the signal pathways of multiple growth factors that seem to play a critical role in the process of ocular angiogenesis and vascular leakage. Benefits of such molecules are expected to include the specificity of the kinase target and an extended half-life, resulting in less frequent intravitreal drug administration, resistance to molecule degradation, and a good safety profile.
The Effect of Reduced Somatosensation on Standing Balance: A Systematic Review
Authors: Kars H. J. J. (Cojanne) , Hijmans Juha M. , Geertzen Jan H. B. , Zijlstra Wiebren
Published: January 2014

The objective of this review is to identify and review publications describing the impact of reduced somatosensation on balance. Based on knowledge of the association between specific somatosensory loss and deterioration of balance, conclusions can be made about role of somatosensation in standing balance.

A systematic literature review is presented in which publications from the years 1993 through 2007 were searched in Medline and Embase. Medical Subject Headings (MESH) terms and free text words (related to balance, somatosensory loss, and lower limb) were used to perform the searches. Fifteen articles were selected for detailed review based on predetermined inclusion criteria, and three of the included articles described the effect of experimentally reduced somatosensation on balance in healthy subjects. Ten of the articles described balance in diabetic neuropathy (DN). The last two included articles described balance in Charcot-Marie-Tooth (CMT) disease type 1A (CMT1A) or type 2 (CMT2).

The literature indicates that the tactile sensation is reduced in DN, CMT1A, and CMT2 and when the plantar surface of the feet was hypothermically anesthetized. Joint motion sensation seems to be impaired in patients with DN, and passive joint position sensation appears to be reduced in healthy subjects with anesthesia of ankle and foot from prolonged ischemia. This reduced somatosensation seems to have a negative effect on balance in patients with DN and CMT2; however, this appeared not to be the case in patients with CMT1A and in healthy subjects.
Analysis: Continuous Glucose Monitoring during Intensive Insulin Therapy
Authors: Mraovic Boris
Published: January 2014

Results of the Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial, intensive insulin therapy (IIT), and use of a continuous glucose sensor in intensive care units (ICU) were analyzed. The NICE-SUGAR trial was unable to determine if optimal intensive insulin therapy decreases mortality. Continuous glucose monitoring (CGM) technology has the potential to improve glycemic control with low glucose variability and low incidence of hypoglycemia. Interstitial fluid CGM may not be useful in perioperative and ICU settings. Studies evaluating the accuracy and reliability of CGM devices, based on a whole blood sample in perioperative and ICU settings, are needed. Once a reliable CGM sensor for ICU use is identified, a large, prospective, controlled, multicenter study could determine if optimal IIT with a low or zero incidence of hypoglycemic events improves mortality.:
Glucose Meters: A Review of Technical Challenges to Obtaining Accurate Results
Authors: Tonyushkina Ksenia , Nichols James H.
Published: January 2014

Glucose meters are universally utilized in the management of hypoglycemic and hyperglycemic disorders in a variety of healthcare settings. Establishing the accuracy of glucose meters, however, is challenging. Glucose meters can only analyze whole blood, and glucose is unstable in whole blood. Technical accuracy is defined as the closeness of agreement between a test result and the true value of that analyte. Truth for glucose is analysis by isotope dilution mass spectrometry, and frozen serum standards analyzed by this method are available from the National Institute of Standards and Technology. Truth for whole blood has not been established, and cells must be separated from the whole blood matrix before analysis by a method like isotope dilution mass spectrometry. Serum cannot be analyzed by glucose meters, and isotope dilution mass spectrometry is not commonly available in most hospitals and diabetes clinics to evaluate glucose meter accuracy. Consensus standards recommend comparing whole blood analysis on a glucose meter against plasma/serum centrifuged from a capillary specimen and analyzed by a clinical laboratory comparative method. Yet capillary samples may not provide sufficient volume to test by both methods, and venous samples may be used as an alternative when differences between venous and capillary blood are considered. There are thus multiple complexities involved in defining technical accuracy and no clear consensus among standards agencies and professional societies on accuracy criteria. Clinicians, however, are more concerned with clinical agreement of the glucose meter with a serum/plasma laboratory result. Acceptance criteria for clinical agreement vary across the range of glucose concentrations and depend on how the result will be used in screening or management of the patient. A variety of factors can affect glucose meter results, including operator technique, environmental exposure, and patient factors, such as medication, oxygen therapy, anemia, hypotension, and other disease states. This article reviews the challenges involved in obtaining accurate glucose meter results.
Progress in Development of an Artificial Pancreas
Authors: Klonoff David C. , Cobelli Claudio , Kovatchev Boris , Zisser Howard C.
Published: January 2014

This issue of Journal of Diabetes Science and Technology contains a collection of 12 original articles describing the latest advances in the development of algorithms for controlling insulin delivery in an artificial pancreas. Algorithms presented in this issue are affected by numerous quantifiable factors, including insulin pharmacokinetics, timing of meal carbohydrate appearance, meal size, amount of exercise, presence of stress, day-to-day variations in insulin sensitivity, insulin time-activity profiles, accuracy of glucose monitor calibration, metabolic profiles of both adults and neonates, and risks of hypoglycemia/hyperglycemia. These articles present theoretical advances in insulin delivery algorithms from modeled in silico patients, as well as clinical data from actual patients who have used closed loop systems. The novel approaches described in these articles are expected to bring us much closer to realization of a commercially available closed loop system for controlling glucose levels in patients with diabetes.
Probabilistic Evolving Meal Detection and Estimation of Meal Total Glucose Appearance
Authors: Cameron Fraser , Niemeyer Günter , Buckingham Bruce A.
Published: January 2014

Background:

Automatic compensation of meals for type 1 diabetes patients will require meal detection from continuous glucose monitor (CGM) readings. This is challenged by the uncertainty and variability inherent to the digestion process and glucose dynamics as well as the lag and noise associated with CGM sensors. Thus any estimation of meal start time, size, and shape is fundamentally uncertain. This uncertainty can be reduced, but not eliminated, by estimating total glucose appearance and using new readings as they become available.

Method:

In this article, we propose a probabilistic, evolving method to detect the presence and estimate the shape and total glucose appearance of a meal. The method is unique in continually evolving its estimates and simultaneously providing uncertainty measures to monitor their convergence. The algorithm operates in three phases. First, it compares the CGM signal to no-meal predictions made by a simple insulin-glucose model. Second, it fits the residuals to potential, assumed meal shapes. Finally, it compares and combines these fits to detect any meals and estimate the meal total glucose appearance, shape, and total glucose appearance uncertainty.

Results:

We validate the performance of this meal detection and total glucose appearance estimation algorithm both separately and in cooperation with a controller on the Food and Drug Administration-approved University of Virginia/Padova Type I Diabetes Simulator. In cooperation with a controller, the algorithm reduced the mean blood glucose from 137 to 132 mg/dl over 1.5 days of control without any increased hypoglycemia.

Conclusion:

This novel, extensible meal detection and total glucose appearance estimation method shows the feasibility, relevance, and performance of evolving estimates with explicit uncertainty measures for use in closed-loop control of type 1 diabetes.
New Approaches to Display of Self-Monitoring of Blood Glucose Data
Authors: Rodbard David
Published: January 2014

Background:

There is a need for improved methods for display and analysis of self-monitoring of blood glucose (SMBG) data to facilitate identification of clinical problems, assist the clinician in the interpretation of daily patterns and longitudinal trends, serve as a guide to locating the most important segments of logbook data, and permit rapid analysis of the patient's pattern of glucose monitoring.

Methods:

We developed prototype software to display SMBG data in a two-dimensional color-coded array: Time of day is displayed on the horizontal axis; date or sequential day is displayed on the vertical axis. Each glucose value is shown by a color-coded symbol categorizing it as “very high,” “high,” “within target range,” “low,” or “very low.” The number of categories and their ranges can be defined by the user, and different target ranges and limits for the categories can be used for different times of day. Placing the cursor over any observation activates a “pop-up box” showing the date, day of week, time of day, glucose value, and ancillary information. Several options and variations are available.

Results:

This new type of display is compact, serves as a guide to assist the physician in locating the most important segments of the logbook, and permits display of glucose data from 90 or more days in a chart as small as 4 by 4 inches. This analysis permits rapid identification of measurements that are above or below the target range and facilitates rapid evaluation of patterns observed on different days or days of the week.

Conclusion:

These new approaches complement other popular graphical displays by conveying information efficiently and effectively to the physician, other health care providers, the patient, and family caregivers in a new and novel, concise, standardized yet flexible format.
Institutional Blood Glucose Monitoring System for Hospitalized Patients: An Integral Component of the Inpatient Glucose Control Program
Authors: Boaz Mona , Landau Zohar , Matas Zipora , Wainstein Julio
Published: January 2014

Background:

The ability to measure patient blood glucose levels at bedside in hospitalized patients and to transmit those values to a central database enables and facilitates glucose control and follow-up and is an integral component in the care of the hospitalized diabetic patient.

Objective:

The goal of this study was to evaluate the performance of an institutional glucometer employed in the framework of the Program for the Treatment of the Hospitalized Diabetic Patient (PTHDP) at E. Wolfson Medical Center, Holon, Israel.

Methods:

As part of the program to facilitate glucose control in hospitalized diabetic patients, an institutional glucometer was employed that permits uploading of data from stands located in each inpatient department and downloading of that data to a central hospital-wide database. Blood glucose values from hospitalized diabetic patients were collected from August 2007 to October 2008. The inpatient glucose control program was introduced gradually beginning January 2008.

Results:

During the follow-up period, more than 150,000 blood glucose measures were taken. Mean glucose was 195.7 ± 99.12 mg/dl during the follow-up period. Blood glucose values declined from 206 ± 105 prior to PTHDP (August 2007–December 2007) to 186 ± 92 after its inception (January 2008–October 2008). The decline was associated significantly with time ( r = 0.11, p < 0.0001). The prevalence of blood glucose values lower than 60 mg/dl was 1.48% [95% confidence interval (CI) 0.36%] prior to vs 1.55% (95% CI 0.37%) following implementation of the PTHDP. Concomitantly, a significant increase in the proportion of blood glucose values between 80 and 200 mg/dl was observed, from 55.5% prior to program initiation vs 61.6% after program initiation ( p < 0.0001).

Conclusions:

The present study was designed to observe changes in institution-wide glucose values following implementation of the PTHDP. Information was extracted from the glucometer system itself. Because the aforementioned study was not a clinical trial, we cannot rule out that factors other than introduction of the program could explain some of the variability observed. With these limitations in mind, it nevertheless appears that the PTHDP, of which the institutional glucometer is an integral, essential component, was associated with improved blood glucose values in the hospitalized diabetic patient.
E-Prescribing: Clinical Implications for Patients with Diabetes
Authors: Smith Marie , Dang Devra , Lee Jennifer
Published: January 2014

With the recent Center for Medicare and Medicaid Services and stimulus package incentives for health information technology, many clinicians are expected to adopt or enhance their use of e-prescribing systems. E-prescribing has nearly eradicated medication errors resulting from prescriber handwriting interpretations, yet several other patient-care and workflow benefits still remain a promise. As prescribers select or update their e-prescribing systems (whether stand-alone or integrated with electronic health records), close attention is needed to the e-prescribing application features and level of clinical decision support to avoid clinical blind spots, including incomplete or inaccurate patient medication lists, poor drop-down menu or screen design, and lack of clinically relevant and actionable drug interaction and drug allergy alerts. This article presents three case studies that highlight common e-prescribing problems involving diabetes patients.
Hyperglycemia in Critical Illness: A Review
Authors: Brealey David , Singer Mervyn
Published: January 2014

Hyperglycemia is commonplace in the critically ill patient and is associated with worse outcomes. It occurs after severe stress (e.g., infection or injury) and results from a combination of increased secretion of catabolic hormones, increased hepatic gluconeogenesis, and resistance to the peripheral and hepatic actions of insulin. The use of carbohydrate-based feeds, glucose containing solutions, and drugs such as epinephrine may exacerbate the hyperglycemia. Mechanisms by which hyperglycemia cause harm are uncertain. Deranged osmolality and blood flow, intracellular acidosis, and enhanced superoxide production have all been implicated. The net result is derangement of endothelial, immune and coagulation function and an association with neuropathy and myopathy. These changes can be prevented, at least in part, by the use of insulin to maintain normoglycemia.
Perioperative and Critical Illness Dysglycemia—Controlling the Iceberg
Authors: Keegan Mark T. , Goldberg Michael E. , Torjman Marc C. , Coursin Douglas B.
Published: January 2014

Patients with dysglycemia related to known or unrecognized diabetes, stress hyperglycemia, or hypoglycemia in the presence or absence of exogenous insulin routinely require care during the perioperative period or critical illness. Recent single and multicenter studies, a large multinational study, and three meta-analyses evaluated the safety of routine tight glycemic control (80–110 mg/dl) in critically ill adults. Results led to a call for more modest treatment goals (initiation of insulin at a blood glucose >180 mg/dl with a goal of ∼150 mg/dl). In this symposium, an international group of multidisciplinary experts discusses the role of tight glycemic control, glucose measurement technique and its accuracy, glucose variability, hypoglycemia, and innovative methods to facilitate glucose homeostasis in this heterogeneous patient population.
Glycemic Control in the Burn Intensive Care Unit: Focus on the Role of Anemia in Glucose Measurement
Authors: Mann Elizabeth A. , Mora Alejandra G. , Pidcoke Heather F. , Wolf Steven E. , Wade Charles E.
Published: January 2014

Glycemic control with intensive insulin therapy (IIT) has received widespread adoption secondary to findings of improved clinical outcomes and survival in the burn population. Severe burn as a model for trauma is characterized by a hypermetabolic state, hyperglycemia, and insulin resistance. In this article, we review the findings of a burn center research facility in terms of understanding glucose management. The conferred benefits from IIT, our findings of poor outcomes associated with glycemic variability, advantages from preserved diurnal variation of glucose and insulin, and impacts of glucometer error and hematocrit correction factor are discussed. We conclude with direction for further study and the need for a reliable continuous glucose monitoring system. Such efforts will further the endeavor for achieving adequate glycemic control in order to assess the efficacy of target ranges and use of IIT.
Glycemic Control and Organ Transplantation
Authors: Marvin Michael R. , Morton Vicki
Published: January 2014

A discussion of hyperglycemia during organ transplantation is a broad topic that includes patients with a known history of diabetes pretransplant, those at risk for post-transplant diabetes, those with stress-induced hyperglycemia, those with hyperglycemia related to immunosuppressive therapy, and hyperglycemia in the deceased organ donor. In contrast to the plethora of articles and studies describing perioperative and critical care management of hyperglycemia in cardiac, trauma, and medical/surgical intensive care unit patients, relatively few published articles in the field of organ transplantation can be found. This article consists of a review of available literature in the form of publications and abstracts, and a preliminary report of the authors' work with liver transplantation and deceased organ donors.
Usability, Participant Acceptance, and Safety of a Prefilled Insulin Injection Device in a 3-Month Observational Survey in Everyday Clinical Practice in Australia
Authors: Carter John , Beilin Jonathan , Morton Adam , De Luise Mario
Published: January 2014

Background:

SoloSTAR® (SOL; sanofi-aventis, Paris, France) is a prefilled insulin pen device for the injection of insulin glargine and insulin glulisine. This is the first Australian survey to determine its usability, participant acceptance, and safety in clinical practice.

Methods:

A 3-month, nonrandomized, noncomparative, observational survey in Australia was conducted in individuals with diabetes. Participants were given SOL pens containing glargine, the instruction leaflet, and a toll-free helpline number. Training was offered to all participants. Safety data, including product technical complaints (PTCs), were gathered from ongoing feedback given by the participant or health care professional (HCP) and by independent interviews conducted 6–10 weeks after study start.

Results:

Some 2674 people consented to take part across 93 sites (150 HCPs), and 2029 participated in interviews. Of these, 52.6% had type 1 diabetes, 16.3% had manual dexterity problems, and 15.5% had poor eyesight not corrected by glasses. At the time of interview, 96.8% of participants were still using SOL. None of the eight PTCs reported were due to technical defects; most were related to handling errors. Some 62 participants reported 77 adverse events; none were related to a PTC. The vast majority of participants (95.4%) were “very satisfied” or “satisfied” with using SOL, and 89.7% of the participants had no questions or concerns using SOL on a daily basis. Similar positive findings were reported by participants with manual or dexterity impairments.

Conclusions:

In this survey of everyday clinical practice, SOL had a good safety profile and was very well accepted by participants.
Mobile Phone Technology for Children with Type 1 and Type 2 Diabetes: A Parent Survey
Authors: Pena Venessa , Watson Alice J. , Kvedar Joseph C. , Grant Richard W.
Published: January 2014

Purpose:

The novel application of information technology has the potential to improve care for children with diabetes. We surveyed parents of children with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) to (1) identify their concerns related to their children's diabetes and (2) assess the relationship between these concerns and parental attitudes toward a glucometer integrated into a mobile phone that could provide parents and health care providers with a child's real-time glucose readings via text message and a secure Web site.

Methods:

We conducted a cross-sectional Web-based survey of parents with children ages 10–19 years (125 with T1DM and 77 with T2DM). Parental concerns were grouped by (1) access to their child's provider, (2) parenting challenges, and (3) knowledge about managing their child's diabetes.

Results:

Parental concerns focused mostly on access to their child's health care provider. Over half of respondents expressed interest in subscribing to a mobile-phone-based service. In multivariate logistic regression models, the odds of being willing to use the service increased if parents had concerns about provider access, a child with T2DM, a college education, or currently subscribed to text messaging. Enthusiasm decreased with increasing annual service cost.

Conclusions:

Study participants—particularly parents with provider access concerns or a child with T2DM—were receptive to adopting novel health technology to help manage their children's diabetes. Adoption of such tools is most likely driven by the unmet needs of parents.
Clinical Evaluation of a Noninvasive Alarm System for Nocturnal Hypoglycemia
Authors: Skladnev Victor N. , Ghevondian Nejhdeh , Tarnavskii Stanislav , Paramalingam Nirubasini , Jones Timothy W.
Published: January 2014

Background:

The aim of this study was to evaluate the performance of a prototype noninvasive alarm system (HypoMon®) for the detection of nocturnal hypoglycemia. A prospective cohort study evaluated an alarm system that included a sensor belt, a radio frequency transmitter for chest belt signals, and a receiver. The receiver incorporated integrated “real-time” algorithms designed to recognize hypoglycemia “signatures” in the physiological parameters monitored by the sensor belt.

Methods:

Fifty-two children and young adults with type 1 diabetes mellitus (T1DM) participated in this blinded, prospective, in-clinic, overnight study. Participants had a mean age of 16 years (standard deviation 2.1, range 12–20 years) and were asked to follow their normal meal and insulin routines for the day of the study. Participants had physiological parameters monitored overnight by a single HypoMon system. Their BG levels were also monitored overnight at regular intervals via an intravenous cannula and read on two independent Yellow Springs Instruments analyzers. Hypoglycemia was not induced by any manipulations of diabetes management, rather the subjects were monitored overnight for “natural” occurrences of hypoglycemia. Performance analyses included comparing HypoMon system alarm times with allowed time windows associated with each hypoglycemic event.

Results:

The primary recognition algorithm in the prototype alarm system performed at a level consistent with expectations based on prior user surveys. The HypoMon system correctly recognized 8 out of the 11 naturally occurring overnight hypoglycemic events and falsely alarmed on 13 out of the remaining 41 normal nights [sensitivity 73% (8/11), specificity 68% (28/41), positive predictive value 38%, negative predictive value 90%].

Conclusion:

The prototype HypoMon shows potential as an adjunct method for noninvasive overnight monitoring for hypoglycemia events in young people with T1DM.
A Review of Standards and Statistics Used to Describe Blood Glucose Monitor Performance
Authors: Krouwer Jan S. , Cembrowski George S.
Published: January 2014

Glucose performance is reviewed in the context of total error, which includes error from all sources, not just analytical. Many standards require less than 100% of results to be within specific tolerance limits. Analytical error represents the difference between tested glucose and reference method glucose. Medical errors include analytical errors whose magnitude is great enough to likely result in patient harm. The 95% requirements of International Organization for Standardization 15197 and others make little sense, as up to 5% of results can be medically unacceptable. The current American Diabetes Association standard lacks a specification for user error. Error grids can meaningfully specify allowable glucose error. Infrequently, glucose meters do not provide a glucose result; such an occurrence can be devastating when associated with a life-threatening event. Nonreporting failures are ignored by standards. Estimates of analytical error can be classified into the four following categories: imprecision, random patient interferences, protocol-independent bias, and protocol-dependent bias. Methods to estimate total error are parametric, nonparametric, modeling, or direct. The Westgard method underestimates total error by failing to account for random patient interferences. Lawton's method is a more complete model. Bland-Altman, mountain plots, and error grids are direct methods and are easier to use as they do not require modeling. Three types of protocols can be used to estimate glucose errors: method comparison, special studies and risk management, and monitoring performance of meters in the field. Current standards for glucose meter performance are inadequate. The level of performance required in regulatory standards should be based on clinical needs but can only deal with currently achievable performance. Clinical standards state what is needed, whether it can be achieved or not. Rational regulatory decisions about glucose monitors should be based on robust statistical analyses of performance.
Compatibility of Insulin Lispro, Aspart, and Glulisine with the Solo™ MicroPump, a Novel Miniature Insulin Pump
Authors: Senesh Gil , Bushi Doron , Neta Avraham , Yodfat Ofer
Published: January 2014

Background:

This study compared the stability of commercially available, rapid-acting insulin in the novel tubeless, skin-adhering Solo™ insulin pump over 6 days at extreme environmental conditions.

Methods:

Forty-eight pumps for each tested analog were loaded with three different insulin lots and operated at 30 U/day (three sets of 12 pumps) and 15 U/day (one set of 12 pumps) with basal/bolus delivery patterns for 6 days under extreme climatic (37°C, 40% relative humidity) and mechanical (35 strokes/min) stresses. The insulin solutions dispensed were sampled periodically and analyzed for potency, related substances, high molecular weight proteins (HMWP), and preservative content by high-performance liquid chromatography techniques. Biological activity (bioidentity) was demonstrated by an abrupt decrease in blood glucose in rabbits. Solutions were inspected for visual appearance and measured for pH levels.

Results:

During the 6-day sampling period, the potency of all insulin samples was maintained at 95.0–105.0% of the bulk solution concentration of the insulin vials. The levels of HMWP and related substances remained well below labeling limits. The preservative concentration decreased with time but remained bacteriostatic effective. Solutions maintained pH and clarity and were particulate free. The biological activity was verified.

Conclusions:

Insulin analogs lispro, aspart, and glulisine maintained physical, chemical, and biological properties for 6 days when used in the Solo MicroPump device.
The Accuracy of a New Real-Time Continuous Glucose Monitoring Algorithm: An Analysis
Authors: Kovatchev Boris , Breton Marc
Published: January 2014

In this issue of Journal of Diabetes Science and Technology, Keenan and colleagues used archival data from the STAR 1 clinical trial (Medtronic Diabetes) to support the claim that the new Veo™ calibration algorithm improves the accuracy of continuous glucose monitoring, particularly in the critical hypoglycemic range. Extensive data analyses are presented to support this claim; the results are convincing, and the estimated improvement in hypoglycemic detection from 55% for the standard calibration to 82% for the Veo is particularly impressive. We can therefore conclude that the Veo algorithm has the potential to improve the accuracy of hypoglycemia alarms and ultimately contribute to closed-loop control. However, the presented results should be interpreted cautiously because they are based on retrospective analysis and are heavily dependent on the distribution of blood glucose levels observed in a particular data set.
Continuous Glucose Monitoring during Exercise in Patients with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion
Authors: Kapitza Christoph , Hovelmann Ulrike , Nosek Leszek , Kurth Heinz-Joerg , Essenpreis Matthias , Heinemann Lutz
Published: January 2014

Aim:

Exercise is associated with an increased risk of hypoglycemic or hyperglycemic events. The aim of this study was to assess glucose changes during and after physical exercise in patients with type 1 diabetes managed by continuous subcutaneous insulin infusion before and after a 14-day moderate or intense exercise program.

Methods:

Sixteen male patients [hemoglobin A1c 7.3 ± 0.8% (mean ± standard deviation), age 39 ± 11 years, body mass index 26.0 ± 2.7 kg/m2] were enrolled in this single-center, randomized, open-label study. They underwent exercise challenges before and after a 14-day moderate (group A, n = 8) and intense (group B) exercise program. Changes in glucose levels were monitored continuously by means of a microdialysis technique.

Results:

Patients in group A trained less intensively than the patients in group B. The treadmill exercise led to a comparable level of challenge in both patient groups. Neither heart rate nor energy consumption differed within the groups or between the groups. Patients in both groups had a comparable basal insulin infusion rate. Prandial insulin doses were higher pretraining than posttraining in both groups. Identical amounts of additional carbohydrates were consumed by the patients in both groups during the 21 h after the exercise challenge. Glucose profiles recorded showed a wide variability. No differences in the glucose profiles with respect to the training intensity could be observed within and between the groups. Patients in group A tended to spend a shorter period of time in hypoglycemia after the exercise challenge posttraining compared to pretraining, but not the patients in group B. The number of hypoglycemic episodes was not different between the groups.

Conclusions:

The patients with type 1 diabetes exhibit the expected wide variability in glucose profiles before, during, and after physical exercise. Use of continuous glucose monitoring allows handling of this situation without running into the risk of acute metabolic deteriorations.
An Analysis of Dosing Equivalence of Insulin Detemir and Insulin Glargine: More Evidence?
Authors: True Mark W.
Published: January 2014

Current guidelines for the management of type 2 diabetes call for the use of basal insulin when glycemic targets are not achieved. Previous studies have demonstrated noninferiority of insulin detemir, dosed once or twice daily, and insulin glargine, dosed once daily. In this issue of Journal of Diabetes Science and Technology, Dr. Allen King provides additional data of his previously published randomized, double-blinded, crossover trial in which both insulins were restricted to once-daily use. In this trial of 29 patients, 24-hour continuous glucose monitoring profiles (published previously) and dosing requirements (in this publication) were shown to be statistically equivalent between the two insulins. The shortcomings of this trial are its short duration, small number of patients, and potential interference from endogenous insulin. Longer trials with more patients, studying once-daily use of these medications, will help better determine if any significant differences exist.