bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Glucagon-like Peptide-1 Analog Delivered Orally Reduces Postprandial Glucose Excursions in Porcine and Canine Models
Authors: Eldor Roy , Kidron Miriam , Greenberg-Shushlav Yael , Arbit Ehud 
Published: January 2014

Background: Glucagon-like peptide-1 (GLP-1) and its analogs are associated with a gamut of physiological processes, including induction of insulin release, support of normoglycemia, β-cell function preservation, improved lipid profiles, and increased insulin sensitivity. Thus, GLP-1 harbors significant therapeutic potential for regulating type 2 diabetes mellitus, where its physiological impact is markedly impaired. To date, GLP-1 analogs are only available as injectable dosage forms, and its oral delivery is expected to provide physiological portal/peripheral concentration ratios while fostering patient compliance and adherence. Methods: Healthy, fasting, enterically cannulated pigs and beagle canines were administered a single dose of the exenatide-based ORMD-0901 formulation 30 min before oral glucose challenges. Blood samples were collected every 15 min for evaluation of ORMD-0901 safety and efficacy in regulating postchallenge glucose excursions. Results: Enterically delivered ORMD-0901 was well tolerated by all animals. ORMD-0901 formulations RG3 and AG2 led to reduced glucose excursions in pigs when delivered prior to a 5 g/kg glucose challenge, where area under the curve (AUC)0-120 values were up to 43% lower than in control sessions. All canines challenged with a glucose load with no prior exposure to exenatide, demonstrated higher AUC0-150 values than in their exenatide-treated sessions. Subcutaneous exenatide delivery amounted to a 51% reduction in mean glucose AUC0-150, while formulations AG4 and AG3 prompted 43% and 29% reductions, respectively. Conclusions: When delivered enterically, GLP-1 (ORMD-0901) is absorbed from the canine and porcine gastrointestinal tracts and retains its biological activity. Further development of this drug class in an oral dosage form is expected to enhance diabetes control and patient compliance.
Prevalence of Sleep Abnormalities and Their Association with Metabolic Syndrome among Asian Indians: Chennai Urban Rural Epidemiology Study (CURES − 67)
Authors: Roopa Mahadevan , Deepa Mohan , Indulekha Karunakaran , Mohan Viswanathan 
Published: January 2014

Objective: To estimate the prevalence of sleep abnormalities and their association with glucose intolerance and metabolic syndrome (MS) in the normal-weight urban South Indian population. Methods: This population-based, cross-sectional study was carried out in 358 subjects aged 20–76 years randomly selected from the Chennai Urban Rural Epidemiology Study in South India. A validated questionnaire assessing various sleep abnormalities (snoring, daytime sleepiness, lack of refreshing sleep, and number of hours of sleep) was administered. All subjects underwent an oral glucose tolerance test, and anthropometric biochemical measurements were obtained to assess cardiometabolic risk factors including glucose intolerance. Diabetes risk was assessed using a previously validated Indian Diabetes Risk Score (IDRS). Results: The overall prevalence of snoring and daytime sleepiness was 40% and 59%, respectively. Snorers were more male, older, smokers, and had higher levels of cardiometabolic risk factors. Subjects with daytime sleepiness had higher body mass index (BMI) and abdominal obesity. Both snoring (50.9% vs 30.2%, p < 0.001) and daytime sleepiness (68% vs 49.7%, p < 0.001) were more prevalent among subjects with impaired glucose metabolism compared to those with normal glucose metabolism. Both sleep measures were associated with higher diabetes risk scores, as assessed by the IDRS (snoring: Trend χ2, 11.14, p = 0.001; daytime sleepiness: Trend χ2, 5.12, p = 0.024). Metabolic syndrome was significantly associated with snoring even after adjusting for age, sex, family history of diabetes, physical activity, smoking, and alcohol. Conclusion: The prevalence of snoring and daytime sleepiness is high among urban South Indians and these two sleep measures are associated with glucose intolerance, MS, and higher diabetes risk scores.
The Key to Unlocking the Virtual Body: Virtual Reality in the Treatment of Obesity and Eating Disorders
Authors: Riva Giuseppe 
Published: January 2014

Obesity and eating disorders are usually considered unrelated problems with different causes. However, various studies identify unhealthful weight-control behaviors (fasting, vomiting, or laxative abuse), induced by a negative experience of the body, as the common antecedents of both obesity and eating disorders. But how might negative body image—common to most adolescents, not only to medical patients—be behind the development of obesity and eating disorders? In this paper, I review the “allocentric lock theory” of negative body image as the possible antecedent of both obesity and eating disorders. Evidence from psychology and neuroscience indicates that our bodily experience involves the integration of different sensory inputs within two different reference frames: egocentric (first-person experience) and allocentric (third-person experience). Even though functional relations between these two frames are usually limited, they influence each other during the interaction between long- and short-term memory processes in spatial cognition. If this process is impaired either through exogenous (e.g., stress) or endogenous causes, the egocentric sensory inputs are unable to update the contents of the stored allocentric representation of the body. In other words, these patients are locked in an allocentric (observer view) negative image of their body, which their sensory inputs are no longer able to update even after a demanding diet and a significant weight loss. This article discusses the possible role of virtual reality in addressing this problem within an integrated treatment approach based on the allocentric lock theory.
Automated Near-Continuous Glucose Monitoring Measured in Plasma Using Mid-Infrared Spectroscopy
Authors: Jax Thomas , Heise Tim , Nosek Leszek , Gable Jennifer , Lim Gene , Calentine Christopher 
Published: January 2014

Objective: There are increasing calls for a precise, automated system to enable tight glycemic control and to avoid hypoglycemia in an intensive care unit setting. OptiScan Biomedical has developed a glucose monitor based on mid-infrared spectroscopy that withdraws blood samples (120 μl) and measures plasma glucose. The goal of this study was to validate the performance of the OptiScan Model 5000 over a wide range of glycemic levels in patients. Research Design and Methods: Sixty people with type 1 ( n = 18) or type 2 ( n = 42) diabetes who were otherwise healthy were connected to OptiScanners. Their blood glucose concentrations were kept in a euglycemic, hypoglycemic (<75 mg/dl), and hyperglycemic (>180 mg/dl) range by intravenous administrations of insulin and glucose. OptiScanner venous blood samples were automatically withdrawn every 15 minutes. Reference measurements were done using the YSI 2300 glucose analyzer. Results: The aggregate data points (1155 paired readings) were within International Organization for Standardization standards, with 98.6% of the glucose values within ±20% above 75 mg/dl and ±15 mg/dl below this value. A Clarke error grid analysis showed a total of 1139 points (98.6%) in zone A. Points outside of A exceeded the A zone boundary by an average of 4.3%. The r2 was 0.99. The total coefficient for variance was 6.4%. Conclusions: These results show that the OptiScanner is highly accurate in healthy patients with diabetes across a wide range of glucose values. Mid-infrared spectroscopy may become the method of choice for highly accurate, high frequency, automated glucose measurements and may thus enable better glycemic control in critically ill patients.
Accuracy Performance of the Medtronic NexSensor® for 6 Days in an Inpatient Setting Using Abdomen and Buttocks Insertion Sites
Authors: Peoples Tim , Bailey Timothy , Brazg Ronald , Zisser Howard C. , Janowski Bob , Huang Suiying , Talbot Cary , Yang Qingqing 
Published: January 2014

Background: Users of continuous glucose monitoring are concerned with product accuracy and choice of insertion site. The Medtronic NexSensor® was evaluated for accuracy during 6 days of wear when inserted in the abdomen and buttocks areas. Methods: Adults (ages 18–75) with type 1 diabetes wore two sensors simultaneously for 6 days, one each inserted in the abdomen and buttocks. Subjects underwent a frequent blood sampling study for 12 hours, during which time reference blood glucose values were obtained every 15 minutes and compared to sensor values. Results: Sixty-three subjects were enrolled, and 61 subjects completed the study. The mean agreement rate between sensor and blood glucose values was 75.5% [95% confidence interval (CI), 69.5, 81.4] at the abdomen site, 73.8% (95% CI, 68.8, 78.8) at the buttocks site, and 75.6% (95% CI, 70.8, 80.4) when sensor and reference data were combined between sites. Over 90% of paired sensor-reference values on Clarke error grids were within the A and B ranges. The mean absolute relative differences were 17.1% at the abdomen site, 16.5% at the buttocks site, and 16.8% when sites were combined. Conclusion: The NexSensor was accurate for inpatient, frequent-sample testing for 6 days when inserted into the abdomen and buttocks. The results of this study also provide evidence that both the abdomen and buttocks are suitable as sensor insertion sites.
Indian Diabetes Risk Score Helps to Distinguish Type 2 from Non-Type 2 Diabetes Mellitus (GDRC-3)
Authors: Sharma Kunal M. , Ranjani Harish , Nguyen Ha , Shetty Shuba , Datta Manjula , Narayan K. M. Venkat , Mohan Viswanathan 
Published: January 2014

Aim: The aim of this study was to investigate whether the Indian Diabetes Risk Score (IDRS) could assist in classifying type 2 diabetes mellitus (T2DM) and non-T2DM among patients attending clinics in India. Methods: Patient records from 2006 through 2009 were taken from the clinical database of a tertiary care diabetes hospital in Chennai, Southern India. A total of 8747 patients with diabetes, diagnosed by a physician either as type 1 diabetes mellitus (T1DM), T2DM, or other types were included for analysis. The IDRS, based on age, abdominal obesity, family history of diabetes, and physical activity, was calculated for each patient at first visit to our clinic. Receiver operating characteristic (ROC) curves were generated to obtain optimal IDRS cut points for predicting T2DM and non-T2DM. Results: Of the 8747 patient records analyzed, 204 (2.3%) were classified as non-T2DM and 8543 (97.7%) as T2DM. In ROC analysis, an IDRS ≥60 [area under the curve (AUC), 0.894; sensitivity, 83.8%; specificity, 81.0%] was predictive of T2DM, while an IDRS <60 (AUC, 0.882; sensitivity, 79.9%; specificity, 83.8%) was predictive of non-T2DM. Conclusions: The IDRS, a simple, cost-effective risk score, can assist in classifying T2DM versus non-T2DM among clinic patients in India.
Using Web Technology to Support Population-Based Diabetes Care
Authors: Cunningham Scott , McAlpine Ritchie , Leese Graham , Brennan Geraldine , Sullivan Frank , Connacher Alan , Waller Annalu , Boyle Douglas I. R. , Greene Stephen , Wilson Elaine , Emslie-Smith Alistair , Morris Andrew D. 
Published: January 2014

Background: Managed clinical networks have been used to coordinate chronic disease management across geographical regions in the United Kingdom. Our objective was to review how clinical networks and multidisciplinary team-working can be supported by Web-based information technology while clinical requirements continually change. Methods: A Web-based population information system was developed and implemented in November 2000. The system incorporates local guidelines and shared clinical information based upon a national dataset for multispecialty use. Automated data linkages were developed to link to the master index database, biochemistry, eye screening, and general practice systems and hospital diabetes clinics. Web-based data collection forms were developed where computer systems did not exist. The experience over the first 10 years (to October 2010) was reviewed. Results: The number of people with diabetes in Tayside increased from 9694 (2.5% prevalence) in 2001 to 18,355 (4.6%) in 2010. The user base remained stable (~400 users), showing a high level of clinical utility was maintained. Automated processes support a single point of data entry with 10,350 clinical messages containing 40,463 data items sent to external systems during year 10. The system supported quality improvement of diabetes care; for example, foot risk recording increased from 36% in 2007 to 73.3% in 2010. Conclusions: Shared-care datasets can improve communication between health care service providers. Web-based technology can support clinical networks in providing comprehensive, seamless care across a geographical region for people with diabetes. While health care requirements evolve, technology can adapt, remain usable, and contribute significantly to quality improvement and working practice.
Quality of Life and Objective Measures of Diabetic Neuropathy in a Prospective Placebo-Controlled Trial of Ruboxistaurin and Topiramate
Authors: Boyd Amanda , Casselini Carolina , Vinik Etta , Vinik Aaron 
Published: January 2014

Background: The Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN) is a validated comprehensive questionnaire designed to capture the entire spectrum of DN related to large fiber, small fiber, and autonomic neuropathy not captured in existing instruments. We aimed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers. Methods: Sixty patients with DN were allocated to treatment on ruboxistaurin (RBX) ( n = 18), topiramate (TPX) ( n = 18), or placebo ( n = 18). QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period. Results: Total QOL scores improved significantly in the active treatment groups (RBX −9.56 ± 4.13; TPX −12.22 ± 2.76) but not in placebo (−5.56 ± 3.49). There were differences in nerve function improvement between treatments. Neurological symptom scores (NSS) improved with TPX from 5.5 (2.3) to 4.3 (0.65) ( p = .007), sensory scores improved with TPX from 15.5 (1.79) to 8.3 (1.19) ( p < .001), motor scores did not change, and sensory and motor impairment scores improved with TPX from 18.8 (2.15) to 12.1 (1.71) ( p = .003). Total neuropathy scores (TNS) improved with TPX from 24.35 (2.61) to 16.35 (2.02) ( p = .001). Neuropathy total symptom score−6 (NTSS−6) changes were significant for both treatments: RBX 4.38 (0.75) to 1.49 (0.38) ( p < .001) and TPX 7.57 (1.3) to 4.26 (0.95) ( p = .036). Changes in QOL-DN large fiber subscores correlated (Spearman's rank) significantly with changes in NTSS-6 ( r = 0.55; p < .0001), NSS ( r = 0.31; p < .04), neuropathy impairment score (NIS) ( r = 0.35; p < .02), and TNS ( r = 0.48; p < .0006). Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores ( r = 0.40; p < .005) and intraepidermal nerve fiber density (IENFD) ( r = −0.29; p < .05). Conclusion: Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures. The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains. Correlations were found between objective measures of neuropathy and total QOL, but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures.
Elevated Intact Proinsulin Levels are Indicative of Beta-Cell Dysfunction, Insulin Resistance, and Cardiovascular Risk: Impact of the Antidiabetic Agent Pioglitazone
Authors: Pfützner Andreas , Forst Thomas 
Published: January 2014

Background: Insulin resistance (IR) and deterioration of beta-cell secretion are main features in the development of type 2 diabetes, which is reflected in increasing serum intact proinsulin levels in later disease stage. Introduction of stable assays that are able to distinguish between intact proinsulin and its specific and unspecific cleavage products has resulted in the finding that serum intact proinsulin values can serve as a direct marker for beta-cell dysfunction, are a highly specific indicator of IR, and can predict cardiovascular risk. Method: Determination of fasting intact proinsulin may be used to monitor and optimize antidiabetic therapeutic approaches. Our study group has been involved in a variety of clinical studies investigating drug effects on beta-cell secretory capacity, IR, and intact proinsulin levels. One focus was on the impact of insulin-sensitizing therapy with pioglitazone on the pancreatic beta-cell load. Results: Treatment with pioglitazone resulted in significant decreases in elevated proinsulin levels in type 2 diabetes patients. This effect was independent from glycemic control. Conclusions: Measurement of fasting intact proinsulin values allows a staging of beta-cell dysfunction and evaluation of IR, thus providing an interesting diagnostic tool for both selection of appropriate therapy and monitoring of treatment success.
Efficacy of Continuous Glucose Monitoring in Improving Glycemic Control and Reducing Hypoglycemia: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Gandhi Gunjan Y. , Kovalaske Michelle , Kudva Yogish , Walsh Kristin , Elamin Mohamed B. , Beers Melody , Coyle Cathy , Goalen Melissa , Murad Mohammad Safwan , Erwin Patricia J. , Corpus Joshua , Montori Victor M. , Murad M. Hassan 
Published: January 2014

Objective: We conducted a systematic review and meta-analysis to assess the efficacy of continuous glucose monitoring (CGM) in improving glycemic control and reducing hypoglycemia compared to self-monitored blood glucose (SMBG). Methods: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for randomized trials of adults and children with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed methodological quality, and extracted data. Meta-analytic estimates of treatment effects were generated using a random-effects model. Results: Nineteen trials were eligible and provided data for meta-analysis. Overall, CGM was associated with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean difference (WMD) of −0.27% (95% confidence interval [CI] −0.44 to −0.10)]. This was true for adults with T1DM as well as T2DM [WMD −0.50% (95% CI −0.69 to −0.30) and −0.70 (95% CI, −1.14 to −0.27), respectively]. No significant effect was noted in children and adolescents. There was no significant difference in HbA1c reduction between studies of real-time versus non-real-time devices (WMD −0.22%, 95% CI, −0.59 to 0.15 versus −0.30%, 95% CI, −0.49 to −0.10; p for interaction 0.71). The quality of evidence was moderate due to imprecision, suggesting increased risk for bias. Data for the incidence of severe or nocturnal hypoglycemia were sparse and imprecise. In studies that reported patient satisfaction, users felt confident about the device and gave positive reviews. Conclusion: Continuous glucose monitoring seems to help improve glycemic control in adults with T1DM and T2DM. The effect on hypoglycemia incidence is imprecise and unclear. Larger trials with longer follow-up are needed to assess the efficacy of CGM in reducing patient-important complications without significantly increasing the burden of care for patients with diabetes.
High Sensitivity C-Reactive Protein, Tumor Necrosis Factor-α, Interleukin-6, and Vascular Cell Adhesion Molecule-1 Levels in Asian Indians with Metabolic Syndrome and Insulin Resistance (CURES-105)
Authors: Indulekha Karunakaran , Surendar Jayagopi , Mohan Viswanathan 
Published: January 2014

Aim: The aim of this study was to assess levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and without MS and among MS subjects with and without insulin resistance (IR). Methodology: From the population-based Chennai Urban Rural Epidemiology Study, 334 subjects with MS and 342 subjects without MS were selected. Metabolic syndrome was diagnosed based on modified National Cholesterol Education Program criteria. High-sensitivity C-reactive protein, TNF-α, IL-6, and VCAM-1 were measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR) using the following formula: fasting insulin (μIU/ml) x fasting glucose (mmol/liter)/22.5. Results: Subjects with MS had significantly higher levels of all four inflammatory markers compared to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) ( p < .05), TNF-α (4.47 vs 3.89 pg/ml) ( p < .05), IL-6 (16.22 vs 10.96 pg/ml) ( p < .05), and VCAM-1 (13.8 vs 7.94 pg/ml) ( p < .05). In the total study subjects, hs-CRP ( r = 0.089, p = .047), TNF-α ( r = 0.113, p = .040), IL-6 ( r = 0.176, p = .042), and VCAM-1 ( r = 0.230, p = .06) were significantly correlated with MS. With increasing quartiles of IR, mean levels of hs-CRP ( p for trend <.001) and TNF-α ( p for trend <.05) increased linearly. MS subjects with IR had higher levels of hs-CRP ( p < .001) and TNF-α ( p < .05) compared to MS subjects without IR. Conclusion: In Asian Indians, inflammatory cytokines hs-CRP, TNF-α, IL-6, and VCAM-1 are elevated in subjects with MS while hs-CRP and TNF-α are further elevated in those with MS and IR.
Comparison of Clinically Relevant Technical Attributes of Five Insulin Injection Pens
Authors: Asakura Toshinari 
Published: January 2014

Background: Insulin injection pens are the predominant devices for insulin delivery in Europe and Japan because of their ease of use and convenience. This study compared clinically relevant technical attributes of durable insulin pens that are important to people with diabetes, specifically functions relating to cartridge-fitting, dose-setting, and dose-delivery on NovoPen® 4, ClikStar®, HumaPen Luxura®, Itango®, and Biosulin® Pen. Methods: Frequency components and duration of audible clicks on dose setting and injection were measured using audio equipment when setting and delivering 20 IU of insulin. To assess cartridge-fitting torque, each pen was attached to a torque gauge via the attached needle, and torque was measured with each 180° turn as the cartridge was screwed into the body of the pen. Rotary torque of the dose-setting dial was measured when setting the dose to the maximum dose unit of the pen. Injection force was measured when delivering 20 IU at 5 mm/s in a vertical position and at a tilt of 14.7° from vertical. Results: Audible clicks on dose-setting and dose-delivery were most distinguishable on NovoPen 4, while NovoPen 4 and ClikStar had generally lower cartridge-fitting torque and injection (both vertical and angled) force values. Conclusion: Overall, the results showed that durable insulin pens such as NovoPen 4 have useful features related to assembly, dose-setting, and injection, which may facilitate ease of use for diabetes patients, particularly elderly patients and those with visual and/or manual dexterity impairments.