bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Local Blood Flow by Warming the Application Site: Beneficial Effects on Postprandial Glycemic Excursions
Authors: Freckmann Guido , Pleus Stefan , Haug Cornelia , Bitton Gabriel , Nagar Ron
Published: January 2014

The absorption profile of rapid-acting insulin analogs delivered subcutaneously is slow compared with physiological insulin. Shorter time to peak and shorter duration of insulin action are important steps toward reducing high postprandial blood glucose concentrations in diabetes therapy and are critical for the development of a closed-loop insulin delivery system. Many attempts have been made to develop more rapid-acting insulins. Since the 1950s, different approaches, such as jet injectors and sprinkler needles, which try to increase the absorption areas of injected insulin, have been developed; however, none of them are commonly used in diabetes therapy. Massage and heat increase tissue blood perfusion and, thereby, the absorption of subcutaneously applied insulin. The main focus of this article is a novel device that allows local application of heat to human skin. The device can be connected to a regular insulin pump. This device could demonstrate a significant effect on insulin absorption and postprandial glucose excursions in multiple clinical trials.
Screening for Diabetic Cardiac Autonomic Neuropathy Using a New Handheld Device
Authors: Gulichsen Elisabeth , Fleischer Jesper , Ejskjaer Niels , Eldrup Ebbe , Tarnow Lise
Published: January 2014

Background:

Cardiac autonomic neuropathy (CAN) is a serious complication of longstanding diabetes and is associated with an increased morbidity and reduced quality of life in patients with diabetes. The present study evaluated the prevalence of CAN diagnosed by reduced heart rate variability (HRV) using a newly developed device in a large, unselected, hospital-based population of patients with diabetes.

Methods:

The study examined 323 patients consisting of 206 type 1 diabetes (T1DM) patients and 117 type 2 diabetes (T2DM) patients. The new handheld prototype Vagus™ was used to screen for CAN. Three different standardized cardiac reflex tests were performed to calculate HRV: 30:15 ratio, E:I ratio, and the Valsalva maneuver. An abnormal HRV in one test is indicative of early CAN, and if two or more tests show abnormal HRV, the diagnosis of CAN is established.

Results:

In total, 86% of examined patients completed all three tests. Each test was completed by more than 90% of the patients. The prevalence of established CAN was 23%, whereas 33% of the patients had early signs of CAN. The prevalence was higher in T2DM patients (27.8%) than in T1DM patients (20.6 %), p = .02. Patients with CAN were older and had a longer duration of diabetes, higher systolic blood pressure, more nephropathy and retinopathy, and a higher vibration threshold.

Conclusions:

Cardiac autonomic neuropathy is frequent in both T2DM and T1DM patients, especially in those with other late diabetes complications. Screening for CAN with the new device is feasible.
Risk Factors for Inpatient Hypoglycemia during Subcutaneous Insulin Therapy in Non-Critically Ill Patients with Type 2 Diabetes
Authors: Farrokhi Farnoosh , Klindukhova Olena , Chandra Prakash , Peng Limin , Smiley Dawn , Newton Christopher , Pasquel Francisco , Fereira Maria E. , Umpierrez Guillermo
Published: January 2014

Objective:

We aimed to determine risk factors associated with hypoglycemia during subcutaneous insulin therapy in non-critically ill patients with type 2 diabetes.

Methods:

We conducted an analysis of three randomized control trials using basal/bolus regimen and regular sliding scale insulin (SSI) in patients with diabetes admitted to medical and surgical settings.

Results:

We analyzed medical records of 261 general medicine and 211 noncardiac surgery patients treated with basal/ bolus regimen with glargine/glulisine ( n = 169), detemir/aspart ( n = 67), neutral protamine Hagedorn/regular ( n = 63), or with SSI ( n = 173). The overall frequency of mild and severe hypoglycemia (<70 and <40 mg/dl) was 19% and 2%, respectively. During treatment, medical patients experienced a higher number of hypoglycemia than surgical patients (23% versus 13%; p = .005), but the rate of severe hypoglycemia was similar between groups (1.9% versus 1.9%; p = not significant). Increasing age, impaired kidney function (glomerular filtration rate < 60 ml/min), total daily insulin dose, and type of insulin regimen (basal/bolus versus SSI) during hospitalization were important contributors for hypoglycemia in both medical and surgical patients. Among these variables, increasing age and type of insulin regimen (basal/bolus versus SSI) were found to be independent predictors of hypoglycemic events.

Conclusions:

Mild hypoglycemic events are common during subcutaneous insulin therapy in medical and surgical patients with type 2 diabetes. Increasing age, impaired renal function, daily insulin dose, and insulin regimen (basal/bolus versus SSI) are important predictors of hypoglycemia during insulin therapy in patients with type 2 diabetes mellitus.
System Accuracy Evaluation of 43 Blood Glucose Monitoring Systems for Self-Monitoring of Blood Glucose according to DIN EN ISO 15197
Authors: Freckmann Guido , Schmid Christina , Baumstark Annette , Pleus Stefan , Link Manuela , Haug Cornelia
Published: January 2014

Background:

The accuracy of systems for self-monitoring of blood glucose is important, as reliable measurement results are a prerequisite for therapeutic decisions.

Methods:

This system accuracy evaluation study was performed according to DIN EN ISO 15197:2003 for 43 Conformité Européenne (CE)-labeled blood glucose (BG) monitoring systems. Measurement results of each system were compared with results of the designated comparison method (manufacturer's measurement procedure): glucose oxidase method (YSI 2300 glucose analyzer) or hexokinase method (Hitachi 917/ cobas 501).

Results:

Complete assessment according to the International Organization for Standardization (ISO) standard was performed for 34 out of 43 systems, and 27 (79.4%) meet the requirements of the standard, i.e., ≥95% of their results showed at least the minimum acceptable accuracy. For 9 of the 43 systems, complete accuracy assessment was not performed due to an oxygen sensitivity (manufacturer's labeling). The bias (according to Bland and Altman) of all 43 evaluated systems ranged from −14.1% to +12.4%.

Conclusions:

From the 34 systems completely assessed, 7 systems did not fulfill the minimal accuracy requirements of the ISO standard. The CE mark apparently does not guarantee that all BG systems provide accuracy according to the standard. Because inaccurate systems bear the risk of false therapeutic decisions, regular and standardized evaluation of BG meters and test strips should be requested in order to ensure adherence to quality standards.
Lot-to-Lot Variability of Test Strips and Accuracy Assessment of Systems for Self-Monitoring of Blood Glucose according to ISO 15197
Authors: Baumstark Annette , Pleus Stefan , Schmid Christina , Link Manuela , Haug Cornelia , Freckmann Guido
Published: January 2014

Background:

Accurate and reliable blood glucose (BG) measurements require that different test strip lots of the same BG monitoring system provide comparable measurement results. Only a small number of studies addressing this question have been published.

Methods:

In this study, four test strip lots for each of five different BG systems [Accu-Chek® Aviva (system A), FreeStyle Lite® (system B), GlucoCheck XL (system C), Pura™/mylife™ Pura (system D), and OneTouch® Verio ™ Pro (system E)] were evaluated with procedures according to DIN EN ISO 15197:2003. The BG system measurement results were compared with the manufacturer's measurement procedure (glucose oxidase or hexokinase method). Relative bias according to Bland and Altman and system accuracy according to ISO 15197 were analyzed. A BG system consists of the BG meter itself and the test strips.

Results:

The maximum lot-to-lot difference between any two of the four evaluated test strip lots per BG system was 1.0% for system E, 2.1% for system A, 3.1% for system C, 6.9% for system B, and 13.0% for system D. Only two systems (systems A and B) fulfill the criteria of DIN EN ISO 15197:2003 with each test strip lot.

Conclusions:

Considerable lot-to-lot variability between test strip lots of the same BG system was found. These variations add to other sources of inaccuracy with the specific BG system. Manufacturers should regularly and effectively check the accuracy of their BG meters and test strips even between different test strip lots to minimize risk of false treatment decisions.
Outcomes of Community-Dwelling Adults without Diabetes Mellitus Who Require Ambulance Services for Hypoglycemia
Authors: Parsaik Ajay K. , Carter Rickey E. , Myers Lucas A. , Dong Ming , Basu Ananda , Kudva Yogish C.
Published: January 2014

Objective:

We evaluate the prevalence, etiology, and outcomes of hypoglycemia requiring emergency medical services (EMS) in patients without diabetes mellitus (non-DM).

Methods:

We reviewed medical records of all ambulance calls for non-DM with blood glucose <70 mg/dl in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2009.

Results:

A total of 131 patients (age 51 ± 19 years; 54 % females) made 142 EMS calls, while 10 patients made repeated calls. Causes of hypoglycemia were critical illness (42; 32%), alcohol and polysubstance use (36; 27.5 %), insulinoma/ bariatric surgery (10; 8%), restricted oral intake (7; 5%), and multiple factors (3; 27.5 %). Patients with alcohol and polysubstance abuse were younger ( p = .002). A total of 54 patients had additional hypoglycemia predisposing comorbidities/factors [adrenal insufficiency (2), end-stage renal disease (11) and chronic liver disease (7), beta blockers use (34), and pentamidine use (1)]. Repeated calls and emergency room transportation were similar, but hospitalization varied across the etiologies, with the lowest proportion in the multiple-factor-related hypoglycemia group ( p = .01). Duration of follow-up was 1.28 (interquartile range 0.13–2.70) years. A total of 38 patients died, and age-adjusted mortality varied across different etiologies ( p < .001), with highest among critically ill. Cancer caused the highest number of deaths (7/38; 18%), while 1 death was due to hypoglycemia.

Conclusions:

There were multiple etiologies for hypoglycemic episodes in community-dwelling non-DM that required EMS. Critical illness, multifactorial causes, and alcohol/polysubstance abuse were common causes. Hospitalization and mortality were higher with critical illnesses.
Robust Fault Detection System for Insulin Pump Therapy Using Continuous Glucose Monitoring
Authors: Herrero Pau , Calm Remei , Vehí Josep , Armengol Joaquim , Georgiou Pantelis , Oliver Nick , Tomazou Christofer
Published: January 2014

Background:

The popularity of continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, as a way to deliver insulin more physiologically and achieve better glycemic control in diabetes patients has increased. Despite the substantiated therapeutic advantages of using CSII, its use has also been associated with an increased risk of technical malfunctioning of the device, which leads to an increased risk of acute metabolic complications, such as diabetic ketoacidosis. Current insulin pumps already incorporate systems to detect some types of faults, such as obstructions in the infusion set, but are not able to detect other types of fault such as the disconnection or leakage of the infusion set.

Methods:

In this article, we propose utilizing a validated robust model-based fault detection technique, based on interval analysis, for detecting disconnections of the insulin infusion set. For this purpose, a previously validated metabolic model of glucose regulation in type 1 diabetes mellitus (T1DM) and a continuous glucose monitoring device were used. As a first step to assess the performance of the presented fault detection system, a Food and Drug Administration-accepted T1DM simulator was employed.

Results:

Of the 100 in silico tests (10 scenarios on 10 subjects), only two false negatives and one false positive occurred. All faults were detected before plasma glucose concentration reached 300 mg/dl, with a mean plasma glucose detection value of 163 mg/dl and a mean detection time of 200 min.

Conclusions:

Interval model-based fault detection has been proven ( in silico) to be an effective tool for detecting disconnection faults in sensor-augmented CSII systems. Proper quantification of the uncertainty associated with the employed model has been observed to be crucial for the good performance of the proposed approach.
The Impact of Mobile Monitoring Technologies on Glycosylated Hemoglobin in Diabetes: A Systematic Review
Authors: Baron Justine , McBain Hayley , Newman Stanton
Published: January 2014

Background:

A new development in the field of telehealth is the use of mobile health technologies (mhealth) to help patients record and track medical information. Mhealth appears particularly advantageous for conditions that require intense and ongoing monitoring, such as diabetes, and where people are of working age and not disabled. This review aims to evaluate the evidence for the effectiveness of mhealth interventions in diabetes management on glycosylated hemoglobin.

Method:

A comprehensive search strategy was developed and applied to eight electronic databases to identify studies that investigated the clinical effectiveness of mobile-based applications that allowed patients to record and send their blood glucose readings to a central server. The eligibility of 8543 papers was assessed against the selection criteria, and 24 papers were reviewed. All studies reviewed were assessed for quality using a standardized quality assessment tool.

Results:

Results for patients with type 1 and type 2 diabetes were examined separately. Study variability and poor reporting made comparison difficult, and most studies had important methodological weaknesses. Evidence on the effectiveness of mhealth interventions for diabetes was inconsistent for both types of diabetes and remains weak.
Diabetic Autonomic Imbalance and Glycemic Variability
Authors: Fleischer Jesper
Published: January 2014

Diabetic autonomic neural imbalance is a severe complication of long-term diabetes patients and may progress to diabetic autonomic neuropathy (DAN). The prevalence of DAN is reported to be between 20 and 70%, depending on the studies. The pathogenesis of DAN remains unresolved. However, emerging evidence suggests that glycemic variability (GV) may be associated with autonomic imbalance in patients with both type 1 and type 2 diabetes. As symptoms are initially weak and uncharacteristic, the condition often remains undiagnosed until late manifestations present themselves. Predominant symptoms may include nausea, vomiting, gastroparesis, involuntary diarrhea, postural hypotension, voiding difficulties, and sexual dysfunction.

Analyzing the patterns of heart rate variability carries the potential for detection of autonomic imbalance in the subclinical and asymptomatic stages. In this context, GV may affect the sympathovagal balance by increasing oxidative stress and proinflammatory cytokines. Establishing a GV risk profile could therefore be important in determining risk factors in diabetes patients. This review addresses the issues above and in particular the possible association between diabetic autonomic imbalance and GV.
Simultaneous Noninvasive Clinical Measurement of Lens Autofluorescence and Rayleigh Scattering Using a Fluorescence Biomicroscope
Authors: Burd John , Lum Stephen , Cahn Frederick , Ignotz Keith
Published: January 2014

Background:

Lens autofluorescence increases with the age of the subject, and the fluorophores responsible are associated with cataract, retinopathy, and other complications of diabetes. We built a scanning confocal lens fluorescence biomicroscope suitable for routine clinical measurement of lens autofluorescence and light scattering and report data from 127 healthy subjects.

Method:

The fluorescence biomicroscope focuses a beam of light from a blue light-emitting diode on the lens and measures fluorescent green light and blue scattered light using a sensitive silicon photomultiplier. The system includes a target fixation light and a video camera for alignment and automatic pupil tracking. Under software control, a volume of measurement is scanned from behind the posterior lens capsule, through the lens to the aqueous humor, and then back again. Software computes the average ratio of lens autofluorescence to scattered light in the central portion of the lens. Self-reported healthy nondiabetic subjects were examined by an optometrist; if their eyes were healthy and without significant cataract, they were entered into the study.

Results:

Valid lens autofluorescence data were collected from 127 subjects between 21 and 70 years of age. A linear model for lens autofluorescence intensity with age was highly statistically significant, and the improvement in fit for higher-order polynomial models was not statistically significant. The ratio of lens autofluorescence to light scatter was also calculated; regression analysis showed significant curvature for the relationship of the fluorescence ratio to age, so a nonlinear model was used to estimate the mean ratio of autofluorescence to scatter and its prediction intervals as a function of age.

Conclusions:

Our observation of a strongly significant linear regression of fluorescence intensity with age of the subjects agrees with the results from previous studies, as does a nonlinear model for the fluorescence ratio. The fluorescence biomicroscope enables the clinician to identify patients with fluorescence ratio significantly higher than expected for their age.
Operational Challenges and Solutions with Implementation of an Adaptive Seamless Phase 2/3 Study
Authors: Spencer Kimberly , Colvin Kelly , Braunecker Brad , Brackman Marcia , Ripley Joyce , Hines Paul , Skrivanek Zachary , Gaydos Brenda , Geiger Mary Jane
Published: January 2014

A wide variety of operational issues were encountered with the planning and implementation of an adaptive, dose-finding, seamless phase 2/3 trial for a diabetes therapeutic. Compared with a conventional design, significant upfront planning was required, as well as earlier, more integrated cross-functional coordination. The existing infrastructure necessitated greater flexibility to meet the needs of the adaptive design. Rapid data acquisition, analysis, and reporting were essential to support the successful implementation of the adaptive algorithm. Drug supply for nine treatment arms had to be carefully managed across many sites worldwide. Details regarding these key operational challenges and others will be discussed along with resolutions taken to enable successful implementation of this adaptive, seamless trial.
An Adaptive, Dose-Finding, Seamless Phase 2/3 Study of a Long-Acting Glucagon-like Peptide-1 Analog (Dulaglutide): Trial Design and Baseline Characteristics
Authors: Geiger Mary Jane , Skrivanek Zachary , Gaydos Brenda , Chien Jenny , Berry Scott , Berry Donald , Anderson James H.
Published: January 2014

Dulaglutide (dula, LY2189265) is a once-weekly glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus. An adaptive, dose-finding, inferentially seamless phase 2/3 study was designed to support the development of this novel diabetes therapeutic. The study is divided into two stages based on two randomization schemes: A Bayesian adaptive scheme (stage 1) and a fixed scheme (stage 2). Stage 1 of the trial employs an adaptive, dose-finding design to lead to a dula dose-selection decision or early study termination due to futility. If dose selection occurs, the study proceeds to stage 2 to allow continued evaluation of the selected dula doses. At completion, the entire study will serve as a confirmatory phase 3 trial. The final study design is discussed, along with specifics pertaining to the actual execution of this study and selected baseline characteristics of the participants.
Diabetes Connect: An Evaluation of Patient Adoption and Engagement in a Web-Based Remote Glucose Monitoring Program
Authors: Jethwani Kamal , Ling Evelyn , Mohammed Misbah , Myint-U Khinlei , Pelletier Alexandra , Kvedar Joseph C.
Published: January 2014

Background:

We determine whether Diabetes Connect (DC), a Web-based diabetes self-management program, can help patients effectively manage their diabetes and improve clinical outcomes.

Methods:

Diabetes Connect is a 12-month program that allows patients with type 2 diabetes mellitus to upload their blood glucose readings to a database, monitor trends, and share their data with their providers. To examine the impact of the program, we analyzed patient utilization and engagement data, clinical outcomes, as well as qualitative feedback from current and potential users through focus groups.

Results:

We analyzed 75 out of 166 patients. Mean age was 61 years (range 27–87). Patients engaged in DC had an average hemoglobin A1c (HbA1c) change of 1.5%, while nonengaged patients had a HbA1c change of 0.4% ( p = .05). Patients with the best outcomes (HbAlc decline of at least 0.8%) typically took less than 10 days to upload, while patients with the worst outcomes (a rise in HbAlc) took an average of 65 days to upload. Patients with more engaged providers had a better HbA1c change (1.39% versus 0.87%) for practices with an average of 74 versus 30 logins/providers.

Conclusions:

Patient engagement in the program has a positive impact on the outcomes of this collaborative Web-based diabetes self-management tool. Patients who engage early and remain active have better clinical outcomes than unengaged patients. Provider engagement, too, was found critical in engaging patients in DC.
Hypoglycemia-Related Electroencephalogram Changes are Independent of Gender, Age, Duration of Diabetes, and Awareness Status in Type 1 Diabetes
Authors: Remvig Line Sofie , Elsborg Rasmus , Sejling Anne-Sophie , Sørensen Jens Ahm , Snogdal Lena Sønder , Folkestad Lars , Juhl Claus B.
Published: January 2014

Introduction:

Neuroglycopenia in type 1 diabetes mellitus (T1DM) results in reduced cognition, unconsciousness, seizures, and possible death. Characteristic changes in the electroencephalogram (EEG) can be detected even in the initial stages. This may constitute a basis for a hypoglycemia alarm device. The aim of the present study was to explore the characteristics of the EEG differentiating normoglycemia and hypoglycemia and to elucidate potential group differences.

Methods:

We pooled data from experiments in T1DM where EEG was available during both normoglycemia and hypoglycemia for each subject. Temporal EEG was analyzed by quantitative electroencephalogram (qEEG) analysis with respect to absolute amplitude and centroid frequency of the delta, theta, alpha, and beta bands, and the peak frequency of the unified theta-alpha band. To elucidate possible group differences, data were subsequently stratified by age group (± 50 years), gender, duration of diabetes (± 20 years), and hypoglycemia awareness status (normal/impaired awareness of hypoglycemia).

Results:

An increase in the log amplitude of the delta, theta, and alpha band and a decrease in the alpha band centroid frequency and the peak frequency of the unified theta-alpha band constituted the most significant hypoglycemia indicators (all p < .0001). The size of these qEEG changes remained stable across all strata.

Conclusions:

Hypoglycemia-associated EEG changes remain stable across age group, gender, duration of diabetes, and hypoglycemia awareness status. This indicates that it may be possible to establish a general algorithm for hypoglycemia detection based on EEG measures.
Design of the Health Monitoring System for the Artificial Pancreas: Low Glucose Prediction Module
Authors: Harvey Rebecca A. , Dassau Eyal , Zisser Howard , Seborg Dale E. , Jovanovič Lois , Doyle Francis J.
Published: January 2014

Background:

The purpose of this study was to design and evaluate a safety system for the artificial pancreas device system (APDS). Safe operation of the APDS is a critical task, where the safety system is engaged only as needed to ensure reliable operation without positive feedback to the controller.

Methods:

The Health Monitoring System (HMS) was designed as a modular system to ensure the safety of the APDS and the user. It was designed using a large set of ambulatory data and evaluated in silico by inducing hypoglycemia with a missed meal [bolus for a 65 g carbohydrate (CHO) meal] and administering rescue CHOs per HMS alerting. The HMS was validated in-clinic with a real-life challenge of a subject who overdosed insulin prior to admission.

Results:

The HMS was evaluated for clinical use with a 15 min prediction horizon. Retrospectively, 93.5% of episodes were detected with 2.9 false alarms per day. During in silico evaluation, the HMS reduced the time spent <70 mg/dl from 15% to 3%. When the HMS was first tested in-clinic, the subject overdosed ∼3 U of insulin prior to her arrival to a closed-loop session (against protocol). The controller reduced insulin delivery, and the HMS gave four alerts that were successfully received via clinical software and text and multimedia messages. Even with insulin reduction and CHO supplements, hypoglycemia was unavoidable but manageable due to the HMS, confirming that a safety system to detect adverse events is an essential part of the APDS.

Conclusions:

The ability of the HMS to be an effective alert system that provides a safety layer to the APDS controller has been demonstrated in a clinical setting.
Minimizing the Impact of Time Lag Variability on Accuracy Evaluation of Continuous Glucose Monitoring Systems
Authors: Scuffi Cosimo , Lucarelli Fausto , Valgimigli Francesco
Published: January 2014

Background:

Despite all commercially available continuous glucose monitoring (CGM) systems being designed to operate in the extracellular interstitial fluid, and even though there is a well-recognized time lag between the interstitial and the venous compartments, the accuracy of the CGM device readings is still evaluated against the glucose concentration in venous blood (VB) samples, thus resulting in a perceived decrease in accuracy. This article explains how different time lag compensation methods (no compensation, compensation with a fixed delay, compensation with a variable delay based on an intercompartmental diffusional model) have an impact on how CGM accuracy is evaluated.

Methods:

The data set used consisted of 210 CGM/blood glucose data pairs from 18 diabetes subjects (15 type 1 and 3 type 2) selected from a data base collected during two independent clinical trials. All CGM measurements were performed using the GlucoMen®Day CGM system (A. Menarini Diagnostics, Italy), and the reference VB glucose measurements by means of a standard laboratory instrument. For each applied time lag compensation method, the CGM accuracy evaluation was performed as recommended by the POCT05-A consensus guideline.

Results:

The perceived accuracy of the CGM device significantly improved when applying both the fixed or the variable delay compensation method. However, it is worth noting how the variable delay method, which relies on a closer description of the intercompartmental diffusion processes, provided the best perception of the clinical accuracy of the device.

Conclusions:

When assessing the accuracy of a CGM system, a crucial step in data analysis is to account for time lag, which enables minimization of the apparent decline in system accuracy.
A Simple Indian Diabetes Risk Score Could Help Identify Nondiabetic Individuals at High Risk of Non-Alcoholic Fatty Liver Disease (CURES-117)
Authors: Anbalagan Viknesh Prabu , Venkataraman Vijayachandrika , Vamsi Mamilla , Deepa Mohan , Mohan Viswanathan
Published: January 2014

Objective:

We aim to determine whether a simple Indian diabetes risk score (IDRS) is associated with individuals with non-alcoholic fatty liver disease (NAFLD) among nondiabetic Asian Indians.

Methods:

Nondiabetic participants ( n = 409) were selected from the Chennai Urban Rural Epidemiology Study. Mean age was 40 ± 11.9 years, mean body mass index was 23.2 ± 3.9 kg/m2, and 224 (54.8%) were women. The IDRS was classified as high (≥60), medium (30–50), and low (<30) risk. Non-alcoholic atty liver disease was assessed by high-resolution β mode ultrasonography. To determine the factors associated with NAFLD, a univariate analysis was first done and a stepwise logistic regression analysis was done based on the factors associated with NAFLD. Biochemical and anthropometric measurements were obtained using standardized procedures.

Results:

The overall prevalence of NAFLD was 24.7% (101/409 participants), and it was significantly higher among those with a high (30.4%) and medium IDRS (21%) compared with the low IDRS group (15.8%; trend chi square; p = .022). In stepwise logistic regression, IDRS was associated with NAFLD with an adjusted odds ratio of 1.78 (95% confidence interval 1.04–3.06), even after adjusting for potential confounders.

Conclusions:

The IDRS can be used as the initial step to screen individuals at high risk of NAFLD in the community.
Gender Differences in Diabetes Self-Management: A Mixed-Methods Analysis of a Mobile Health Intervention for Inner-City Latino Patients
Authors: Burner Elizabeth , Menchine Michael , Taylor Elena , Arora Sanjay
Published: January 2014

Background:

The benefit of mobile health (mHealth) on diabetes management among low-income, inner-city patients is largely unknown, particularly for Latino patients. TExT-MED (Trial to Examine Text Message for Emergency Department Patients with Diabetes) is a text message-based program designed to improve disease knowledge, self-efficacy, and glycemic control among low-income, inner-city Latinos. In phase I, 23 patients participated in an acceptability and feasibility study. Contrary to our model, there was no increase in knowledge despite increases in self-efficacy and healthy behaviors. In phase II, we performed a mixed-methods analysis to understand how TExT-MED achieved these seemingly contradictory findings.

Method:

We performed a qualitative analysis of focus groups with patients from phase I. We explored patients' receipt of health information from TExT-MED and other information sources. We used these qualitative findings to perform a mixed-methods analysis of the outcomes from phase I, reanalyzing the quantitative measures of self-efficacy, diabetes knowledge, and healthy behaviors.

Results:

We conducted two focus groups, one in English and one in Spanish. Through qualitative analysis, we found gender differences in information sources, dietary self-efficacy, and desired educational content. Applying this knowledge, we re-stratified phase I outcomes by gender and found differential changes in diabetes knowledge, self-efficacy, and behaviors. Men had increased self-efficacy while women showed increased knowledge.

Conclusions:

The efficacy of mHealth on diabetes management was affected by gender. Specifically, men and women differ in their dietary self-efficacy, information sources, and desired topics in future mHealth interventions. To achieve maximal impact, future mHealth interventions should be mindful of this gender difference.
Changing Prescribing Patterns of Type 2 Diabetes Medications from 2002–2010: An Electronic Health Record-Based Evaluation
Authors: Mehta Sanjeev N. , Goldfine Allison B. , Abrahamson Martin J. , DiVincenzo Richard , Laffel Lori M. B.
Published: January 2014

Background:

The implementation of electronic health records (EHRs) may support evaluations of health care delivery, such as the prescription of newly approved medications, to adults with diabetes. We aimed to evaluate prescribing patterns of thiazolidinediones and novel glucose-lowering drug classes using electronic prescribing data contained in an outpatient EHR from 2002–2010.

Methods:

We identified adults with type 2 diabetes seen from 2002–2010 who were newly prescribed rosiglitazone (ROSI), pioglitazone (PIO), or a novel glucose-lowering drug class (other). The annual number of new prescriptions and their relative percentages (per 1000 patients) were calculated.

Results:

From 2002–2010, 6209 patients with type 2 diabetes were newly prescribed 8858 eligible medications. In 2006, ROSI and PIO accounted for 44% and 37% of new prescriptions, respectively. After 2007, the relative percentage of new ROSI prescriptions declined more rapidly than PIO prescriptions, falling to 7% and 47% of peak levels, respectively, by 2010. By 2010, the relative percentages of new ROSI, PIO, and other prescriptions were 2%, 18%, and 80%, respectively.

Conclusions:

Evaluations of EHR data represent a cost-effective method for evaluating diabetes medications with new Food and Drug Administration warnings or indications. Validation of demographic and clinical data will expand the scope of EHR-based evaluations of health care delivery and outcomes for adults with diabetes.
Performance Variability of Seven Commonly Used Self-Monitoring of Blood Glucose Systems: Clinical Considerations for Patients and Providers
Authors: Brazg Ronald L. , Klaff Leslie J. , Parkin Christopher G.
Published: January 2014

Background:

Blood glucose data are frequently used in clinical decision making, thus it is critical that self-monitoring of blood glucose (SMBG) systems consistently provide accurate results. Concerns about SMBG accuracy have prompted the development of newly proposed International Organization for Standardization (ISO) standards: ≥95% of individual glucose results shall fall within ±15 mg/dl of the results of the manufacturer's reference procedure at glucose concentrations <100 mg/dl and within ±15% for values >100 mg/dl. We evaluated seven marketed systems against the current and proposed ISO criteria (criterion A).

Method:

Capillary blood samples were collected from 100 subjects and tested on seven systems: Accu-Chek Aviva Plus, Advocate Redi-Code, Element, Embrace, Prodigy Voice, TRUEbalance, and WaveSense Presto. Results were compared with manufacturer's documented reference system, YSI or perchloric acid hexokinase; three different strip lots from each system were tested on each subject, in duplicate.

Results:

Compared against current ISO criteria (≥95% within ±15 mg/dl for values <75 mg/dl and ±20% for values ≥75 mg/dl) the Accu-Chek Aviva Plus, Element, and WaveSense Presto systems met accuracy criteria. However, only the Accu-Chek Aviva Plus met the proposed ISO criteria (criterion A) in all three lots. The other six systems failed to meet the criteria in at least two of the three lots, showing lot-to-lot variability, high/low bias, and variations due to hematocrit.

Conclusions:

Inaccurate SMBG readings can potentially adversely impact clinical decision making and outcomes. Clinicians can reduce controllable variables by prescribing accurate SMBG systems. Adherence to the proposed ISO criteria should enhance patient safety by improving the accuracy of SMBG systems.
Self-Adjustment of Insulin Dose Using Graphically Depicted Self-Monitoring of Blood Glucose Measurements in Patients with Type 1 Diabetes Mellitus
Authors: Reichel Andreas , Rietzsch Hannes , Ludwig Barbara , Röthig Katrin , Moritz Annette , Bornstein Stefan R.
Published: January 2014

Background:

There is a need for patients to be able to adjust their insulin doses accurately and independently during continuous subcutaneous insulin infusion (CSII) therapy in order to avoid glycemic excursions and improve glycemic control. Use of new technology has the potential to aid patients in visualizing their circadian patterns and improving their understanding of data provided by self-monitored blood glucose (SMBG) measurements.

Methods:

A 24-week crossover study was performed in 25 patients with type 1 diabetes mellitus using CSII and SMBG. Patients were randomized either to entering blood glucose data into handwritten logbooks or to using the Accu-Chek SmartPix information management system (IMS) coupled with instructions from a training manual to aid interpretation of the IMS readings. Patients analyzed these chart readings every 2 weeks, and outpatient visits were scheduled for both arms every 6 weeks.

Results:

There was a significantly lower mean overall blood glucose level with the IMS compared with use of a logbook (139 ± 16.2 versus 150 ± 19.8 mg/dl; Δ = 10.8 mg/dl; p < .01), and a significantly higher proportion of blood glucose values was in the target range compared with use of a logbook (43.6% versus 38.5%; p < .001). Hypoglycemic events were also significantly lower with the IMS compared with logbooks (3.7 fewer events/6 weeks; p < .05). There was no significant difference between groups in the daily frequency of SMBG measurements.

Conclusions:

The use of an IMS, coupled with an easily understood training manual, enables patients to improve glycemic control by performing accurate and timely self-adjustments to their insulin regimens.
In Silico Evaluation of an Artificial Pancreas Combining Exogenous Ultrafast-Acting Technosphere Insulin with Zone Model Predictive Control
Authors: Lee Justin J. , Dassau Eyal , Zisser Howard , Harvey Rebecca A. , Jovanovič Lois , Doyle Francis J.
Published: January 2014

Background:

Because of the slow pharmacokinetics of subcutaneous (SC) insulin, avoiding postprandial hyperglycemia has been a major challenge for an artificial pancreas (AP) using SC insulin without a meal announcement.

Methods:

A semiautomated AP with Technosphere® Insulin (TI; MannKind Corporation, Valencia, CA) was designed to combine pulmonary and SC insulin. Manual inhalation of 10 U ultrafast-absorbing TI at mealtime delivers the first, or cephalic, phase of insulin, and an SC insulin pump controlled by zone model predictive controller delivers second-phase and basal insulin. This AP design was evaluated on 100 in silico subjects from the University of Virginia/Padova metabolic simulator using a protocol of two 50 g carbohydrate (CHO) meals and two 15 g CHO snacks.

Results:

Simulation analysis shows that the semiautomated AP with TI provides 32% and 16% more time in the controller target zone (80–140 mg/dl) during the 4 h postprandial period, with 39 and 20 mg/dl lower postprandial blood glucose peak on average than the pure feedback AP and the AP with manual feed-forward SC bolus, respectively. No severe hypoglycemia (<50 mg/dl) was observed in any cases.

Conclusions:

The semiautomated AP with TI provides maximum time in the clinically accepted region when compared with pure feedback AP and AP with manual feed-forward SC bolus. Furthermore, the semiautomated AP with TI provides a flexible operation (optional TI inhalation) with minimal user interaction, where the controller design can be tailored to specific user needs and abilities to interact with the device.
Technical Challenges and Clinical Outcomes of Using a Closed-Loop Glycemic Control System in the Hospital
Authors: Okabayashi Takehiro , Kozuki Akihito , Sumiyoshi Tatsuaki , Shima Yasuo
Published: January 2014

According to large randomized trials, results suggest that maintaining normoglycemia postoperatively through tight glycemic control (TGC) and intensive insulin therapy (IIT) can improve surgical outcomes as well as reduce mortality and morbidity in critically ill patients. However, trials examining the effects of TGC have had conflicting results. Systematic reviews and meta-analyses have also led to differing conclusions. The main reason these clinical trials and meta-analyses show negative results for TGC is the high incidence of hypoglycemia induced by IIT. This could not be prevented because there is no reliable technique that can avoid this condition during IIT. The development of accurate, continuous blood glucose monitoring devices and closed-loop systems for computer-assisted blood glucose control in the intensive care unit (ICU) will probably help avoid hypoglycemia in these situations.

The STG closed-loop glycemic control system was introduced to our department to be used and evaluated for strict serum glucose control with no hypoglycemic episodes during IIT in the surgical ICU, to reduce the workload of ICU nurses, and to decrease incidents related to the management of blood glucose levels according to manual conventional venous infusion insulin therapy. The goal of our team was to use the STG closed-loop glycemic control system for perioperative TGC in surgical patients to solve the complications of IIT and reduce risk of hypoglycemia. The challenge at our hospital demonstrated that the STG closed-loop glycemic control system can be expected to achieve TGC with no occurrence of hypoglycemia induced by IIT after surgery.
An Overview of Canadian and U.S. Approaches to Drug Regulation and Responses to Postmarket Adverse Drug Reactions
Authors: Cheung Richard Y. , Goodwin Sarah H.
Published: January 2014

Over the years, drug products, including those indicated for diabetes, have been withdrawn from the marketplace because of quality concerns and/or severe adverse drug reactions. While the drug regulatory process is designed to detect, among other things, adverse drug reactions before a drug receives marketing authorization, for various reasons, premarket detection of all potential adverse reactions associated with a drug may not be possible. As such, regulatory authorities must also react to and manage adverse reactions identified at the postmarket stage. In this article, we provide a general overview of drug regulation in Canada and the United States and consider an example of a drug indicated for the treatment of diabetes and how newly identified potential safety concerns were managed in the postmarket environment.
As the Pendulum Swings—Medical Products Class Actions Litigation in Canada: Recent Developments
Authors: Pliszka Peter J. , Armstrong Sarah J.
Published: January 2014

During the relatively short history of class proceedings in Canada, developers and manufacturers of medical devices and pharmaceuticals (“medical products”), including medical products designed for patients with diabetes, have found themselves at the receiving end of a significant number of class action claims. As a result, medical products litigation has become the battleground for some of the most significant developments in Canadian class actions law. This article provides a broad overview of some of the most significant developments. The authors pay particular attention to developments regarding the test for class action certification and consider whether high-profile dismissals of certification motions represent a trend toward raising the threshold for plaintiffs seeking to obtain certification of a proposed class action. The authors also consider a decision arising out of a lengthy class action common issues trial in which the medical device company was victorious. In the authors' view, the class action pendulum in Canada, particularly as it relates to medical products claims, remains in motion. It behooves all affected players to keep their eye on this ball with rapt attention to see where it may move next.
Protecting the Rights of School Children with Diabetes
Authors: Wood James M.
Published: January 2014

School children with diabetes are facing increasing difficulties in receiving care during the school day. Despite the existence of federal statutes ensuring their rights to a free, appropriate public education, many school districts throughout the country do little, if anything, to ensure that their condition is treated throughout the school day. The chronic shortage of school nurses has resulted in hardships on families, relatives, and friends to ensure that care, including insulin, is timely and appropriately provided. While many states have taken measures to provide care by unlicensed trained volunteers, efforts to accomplish this in California have resulted in prolonged litigation. A variety of nursing organizations oppose all efforts to train unlicensed volunteers, arguing that such is not permitted by California law. The issue is unresolved and currently pending in the California Supreme Court.
Clinical Implications and Economic Impact of Accuracy Differences among Commercially Available Blood Glucose Monitoring Systems
Authors: Budiman Erwin S. , Samant Navendu , Resch Ansgar
Published: January 2014

Background:

Despite accuracy standards, there are performance differences among commercially available blood glucose monitoring (BGM) systems. The objective of this analysis was to assess the potential clinical and economic impact of accuracy differences of various BGM systems using a modeling approach.

Methods:

We simulated additional risk of hypoglycemia due to blood glucose (BG) measurement errors of five different BGM systems based on results of a real-world accuracy study, while retaining other sources of glycemic variability. Using data from published literature, we estimated an annual additional number of required medical interventions as a result of hypoglycemia. We based our calculations on patients with type 1 diabetes mellitus (T1DM) and T2DM requiring multiple daily injections (MDIs) of insulin in a U.S. health care system. We estimated additional costs attributable to treatment of severe hypoglycemic episodes resulting from BG measurement errors.

Results:

Results from our model predict an annual difference of approximately 296,000 severe hypoglycemic episodes from BG measurement errors for T1DM (105,000 for T2DM MDI) patients for the estimated U.S. population of 958,800 T1DM and 1,353,600 T2DM MDI patients, using the least accurate BGM system versus patients using the most accurate system in a U.S. health care system. This resulted in additional direct costs of approximately $339 million for T1DM and approximately $121 million for T2DM MDI patients per year.

Conclusion:

Our analysis shows that error patterns over the operating range of BGM meter may lead to relevant clinical and economic outcome differences that may not be reflected in a common accuracy metric or standard. Further research is necessary to validate the findings of this model-based approach.
Feasibility of Adjacent Insulin Infusion and Continuous Glucose Monitoring via the Medtronic Combo-Set
Authors: O'Neal David N. , Adhya Sumona , Jenkins Alicia , Ward Glenn , Welsh John B. , Voskanyan Gayane
Published: January 2014

Background:

Subcutaneously infused insulin may interfere with the function of nearby glucose-sensing electrodes and vice versa. The prototype of the Combo-Set device (Medtronic) incorporates a subcutaneous insulin delivery catheter and continuous glucose monitoring (CGM) sensor assembled on the same platform and separated by 11 mm. We aim to evaluate Combo-Set's insulin delivery and glucose-sensing functions.

Methods:

Ten subjects with type 1 diabetes wore a Combo-Set and a Sof-Sensor inserted subcutaneously in contralateral abdominal areas connected to iPro recorders (Medtronic) for 53.25 ± 0.75 h (mean ± standard deviation). The Combo-Set delivered insulin diluent except during meal tests on days 1 and 3 when insulin lispro was delivered as a meal bolus and postmeal basal. Venous plasma samples were collected at the following time points from meal start: 0, 30, 60, 120, and 180 min for insulin measurements. The accuracy of the Combo-Set sensors was evaluated and compared with that of the Sof-Sensor, with each referenced against capillary glucose values (Contour Link Meter, Bayer).

Results:

Accuracy of the Combo-Set sensor was comparable to that of the Sof-Sensor. Clarke error grid analysis showed that 97% of Combo-Set and 93% of Sof-Sensor values were in the A+B regions ( p = .20, not significant). The Combo-Set showed the expected postbolus peak insulin time (67 ± 9 min, mean ± standard error). One “no delivery” alarm occurred during the 21 patient days of use.

Conclusion:

A device providing for simultaneous adjacent placement of an insulin infusion catheter and a CGM sensor is feasible and functions within acceptable limits. The low “no delivery” alarm rate was similar to that of other infusion sets.