Evaluation of a combined blood glucose monitoring and gaming system (Didget®) for motivation in children, adolescents, and young adults with type 1 diabetes.

The purpose of this study was to assess the performance and acceptability of a blood glucose meter coupled with a gaming system for children, adolescents, and young adults with type 1 diabetes. During an in-clinic visit, duplicate blood samples were tested by subjects (N = 147; aged 5-24 yr) and health care providers (HCPs) to evaluate the accuracy and precision of the Didget® system. Subjects' meter results were compared against Yellow Springs Instruments (YSI) reference results and HCP results using least squares regression and error grid analyses. Precision was measured by average within-subject and within-HCP coefficient of variation (CV). During the home-use component of this study, subjects (n = 58) tested their blood glucose at least two to three times daily for 3-5 d to evaluate routine use of the system. Subjects' meter results showed significant correlations with both YSI (r(2) = 0.94; p < 0.001 for regression slope) and HCP results (r(2) = 0.96; p < 0.001). Average within-subject and within-HCP CVs were 5.9 and 7.2%, respectively. Overall satisfaction was assessed by subjects, their parents or guardians, and HCP surveys. Subject satisfaction with the Didget® system was good to excellent; most subjects found the system easy to use, motivating, and helpful for building good blood glucose monitoring habits. Most HCPs agreed that the system fulfilled a need in diabetes management. In conclusion, the Didget® system was precise and clinically accurate in the hands of children, adolescents, and young adults with type 1 diabetes.

Safety of a Sustainably Produced, Bioengineered, Nature-Identical Salidroside Compound.

Bioactive phytochemicals such as salidroside have been studied to understand the beneficial effects of Rhodiola rosea, an herbaceous plant used in traditional medicine to increase energy and treat a variety of health issues. However, Rhodiola plants are often slow-growing, and many are endangered in their native habitats. Thus, there is a need for safe, alternative supplies of key phytochemicals from Rhodiola. The salidroside subject of this safety study is a synthetic biology product from fermentation of a bioengineered E. coli that produces salidroside. Here, we present comprehensive test results that support the safety of salidroside manufactured via a patented sustainable bioengineering manufacturing process. In vitro bacterial reverse mutation assays with the bioengineered salidroside show no mutagenicity in any of the concentrations tested. In vivo toxicity studies in rats show no adverse effects from the salidroside product. Based on the results of these studies, we conclude that the bioengineered salidroside discussed here is not genotoxic and demonstrates a no-observed-adverse-effect level (NOAEL) at least 2000 mg/kg bw/day in male and female Sprague-Dawley rats. This study supports that the salidroside compound produced using bioengineered E. coli is a viable alternative to salidroside produced from harvested Rhodiola plants for use as a dietary supplement, food ingredient, or potentially as a pharmaceutical product.

Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study.

BACKGROUND: Despite the prognostic value of metabolic syndrome for predicting cardiovascular events, few trials have investigated the effects of statin therapy on cardiovascular morbidity and mortality in patients with the metabolic syndrome. Our post hoc analysis of the Treating to New Targets (TNT) study assessed whether intensive lowering of low-density lipoprotein cholesterol with high-dose atorvastatin therapy results in cardiovascular benefits for patients with both coronary heart disease and the metabolic syndrome. METHODS: The TNT study was a prospective, double blind, parallel-group trial done at 256 sites in 14 countries between April, 1998, and August, 2004, with a median follow-up of 4.9 years. 10,001 patients were enrolled aged 35-75 years with clinically evident coronary heart disease. Our analysis includes 5584 patients with metabolic syndrome based on the 2005 NCEP ATP III criteria. Patients were randomly assigned to receive either atorvastatin 10 mg per day (n=2820) or 80 mg per day (n=2764). The primary outcome measure was time to first major cardiovascular event, defined as death from coronary heart disease, non-fatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or non-fatal stroke. FINDINGS: In patients with coronary heart disease and metabolic syndrome, mean on-treatment low-density lipoprotein cholesterol concentrations at 3 months were 2.6 mmol/L (99.3 mg/dL) with atorvastatin 10 mg, and 1.9 mmol/L (72.6 mg/dL) with atorvastatin 80 mg. At a median follow-up of 4.9 years, major cardiovascular events occurred in 367 (13%) patients receiving atorvastatin 10 mg, compared with 262 (9.5%) receiving atorvastatin 80 mg (hazard ratio 0.71; 95% CI 0.61-0.84; p<0.0001). Irrespective of treatment assignment, significantly more patients with metabolic syndrome (11.3%) had a major cardiovascular event at a median of 4.9 years than those without metabolic syndrome (8.0%; hazard ratio 1.44; 95% CI 1.26-1.64; p<0.0001). This increased risk was significantly reduced by intensive therapy with atorvastatin 80 mg beyond that achieved with atorvastatin 10 mg. INTERPRETATION: These data indicate that patients with coronary heart disease and metabolic syndrome derive incremental benefit from high-dose atorvastatin therapy, irrespective of the presence of diabetes.

Accuracy evaluation of contour next compared with five blood glucose monitoring systems across a wide range of blood glucose concentrations occurring in a clinical research setting.

BACKGROUND: This study evaluated the accuracy of Contour(®) Next (CN; Bayer HealthCare LLC, Diabetes Care, Whippany, NJ) compared with five blood glucose monitoring systems (BGMSs) across a wide range of clinically occurring blood glucose levels. SUBJECTS AND METHODS: Subjects (n=146) were ≥ 18 years and had type 1 or type 2 diabetes. Subjects' glucose levels were safely lowered or raised to provide a wide range of glucose values. Capillary blood samples were tested on six BGMSs and a YSI glucose analyzer (YSI Life Sciences, Inc., Yellow Springs, OH) as the reference. Extreme glucose values were achieved by glucose modification of the blood sample. System accuracy was assessed by mean absolute difference (MAD) and mean absolute relative difference (MARD) across several glucose ranges, with <70 mg/dL evaluated by MAD as the primary end point. RESULTS: In the low glucose range (<70 mg/dL), MAD values were as follows: Accu-Chek(®) Aviva Nano (Roche Diagnostics, Indianapolis, IN), 3.34 mg/dL; CN, 2.03 mg/dL; FreeStyle Lite(®) (FSL; Abbott Diabetes Care, Inc., Alameda, CA), 2.77 mg/dL; OneTouch(®) Ultra(®) 2 (LifeScan, Inc., Milpitas, CA), 10.20 mg/dL; OneTouch(®) Verio(®) Pro (LifeScan, Inc.), 4.53 mg/dL; and Truetrack(®) (Nipro Diagnostics, Inc., Fort Lauderdale, FL), 11.08 mg/dL. The lowest MAD in the low glucose range, from CN, was statistically significantly lower than those of the other BGMSs with the exception of the FSL. CN also had a statistically significantly lower MARD than all other BGMSs in the low glucose range. In the overall glucose range (21-496 mg/dL), CN yielded the lowest MAD and MARD values, which were statistically significantly lower in comparison with the other BGMSs. CONCLUSIONS: When compared with other BGMSs, CN demonstrated the lowest mean deviation from the reference value (by MAD and MARD) across multiple glucose ranges.

beta-Cell function and insulin sensitivity in early adolescence: association with body fatness and family history of type 2 diabetes mellitus.

The prevalence of type 2 diabetes mellitus (T2DM) among adolescents has increased 5- to 10-fold over the past decade. T2DM results from pancreatic beta-cell dysfunction and insulin resistance. Using rapid iv glucose tolerance testing, we examined beta-cell function and insulin resistance in 72 predominantly Latino eighth grade students (41 males and 31 females; mean +/- sem age, 13.6 +/- 0.1 yr). Thirty-six percent of the children had body mass indexes above the 85th percentile for age and gender, and 50% had a first- or second-degree relative with T2DM. Overweight children were five times more likely to be in the highest quartile for insulin resistance. Children with a family history of T2DM were five times more likely to be in the lowest quartile for insulin secretory capacity, 4.5 times more likely to be in the lowest quartile for glucose disposal, and three times more likely to be in the lowest quartile for insulin resistance. These findings are consistent with a model for the physiology of T2DM in which a familial beta-cell dysfunction is unmasked by increasing insulin resistance secondary to overweight in this predominantly Latino population.

Testing versus guessing blood glucose values: impact on self-care behaviors in type 2 diabetes.

OBJECTIVE: To assess differences between estimated blood glucose values and those measured on a blood glucose meter and the impact on self-care behavior in type 2 diabetes. RESEARCH DESIGN AND METHODS: Subjects ≥18 years with type 2 diabetes (N = 297) attending a Taking Control of Your Diabetes conference were asked questions about diabetes management and to estimate their current blood glucose. Study staff tested subjects' blood glucose on a meter. After seeing the result, subjects were again asked questions on diabetes management. CLINICAL TRIAL REGISTRATION: NCT01453413. MAIN OUTCOME MEASURE: The percentage of subject blood glucose estimations that were outside ISO 15197:2003 accuracy criteria (>±15 mg/dL or >±20% of meter glucose values). RESULTS: Nearly half (46%) of subjects estimated blood glucose values outside ISO 15197:2003 accuracy criteria. Time since last blood glucose test, time since last meal, testing frequency, and A1C did not have an effect on differences between estimated blood glucose values and meter results. In the questionnaire before blood glucose testing, most subjects strongly agreed, agreed, or neither agreed nor disagreed that 'I make decisions about my diabetes, such as my food intake or my insulin dose even when I do not test my blood sugar' (71%) and 'My body tells me without testing if my blood sugar is low or high' (77%). After blood glucose testing, 99% of subjects strongly agreed, agreed, or neither agreed nor disagreed that 'Knowing my blood sugar by checking could help me make different diabetes decisions'. CONCLUSIONS: Self-monitoring of blood glucose is an important component of diabetes self-management. Testing rather than guessing blood glucose values is important to obtain accurate results and inform people with type 2 diabetes to make effective, appropriate diabetes management decisions. A potential limitation of this study is that the subject population may not be representative of the general population of people with diabetes; however, the conference setting may attract a more motivated population, which could underestimate the magnitude of the results.

Active assistance technology reduces glycosylated hemoglobin and weight in individuals with type 2 diabetes: results of a theory-based randomized trial.

BACKGROUND: Type 2 diabetes is an individual health challenge requiring ongoing self-management. Remote patient reporting of relevant health parameters and linked automated feedback via mobile telephone have potential to strengthen self-management and improve outcomes. This research involved development and evaluation of a mobile telephone-based remote patient reporting and automated telephone feedback system, guided by health behavior change theory, aimed at improving self-management and health status in individuals with type 2 diabetes. SUBJECTS AND METHODS: This research comprised a randomized controlled trial. Inclusion criteria were diagnosis of type 2 diabetes, elevated glycosylated hemoglobin (HbA1c) levels (range, 6.5-11%) or use of oral diabetes medication, and 30-70 years of age. Intervention subjects (n=24) participated in remote patient reporting of health status parameters and linked health behavior change feedback. Control participants (n=24) received standard of care including diabetes education and healthcare provider counseling. Patients were followed for approximately 10 months. RESULTS: Intervention participants achieved, compared with controls and controlling for baseline, a significantly greater mean reduction in HbA1c of -0.40% (95% confidence interval [CI] -0.67% to -0.14%) versus 0.036% (95% CI -0.23% to 0.30%) (P<0.03) and significantly greater weight reduction of -2.1 kg (95% CI -3.6 to -0.6 kg) versus 0.4 kg (95% CI -1.1 to 1.9 kg). Nonsignificant trends for greater intervention compared with control improvement in systolic and diastolic blood pressure were observed. CONCLUSIONS: Sophisticated information technology platforms for remote patient reporting linked with theory-based health behavior change automated feedback have potential to improve patient outcomes in type 2 diabetes and merit scaled-up research efforts.

Performance of a new blood glucose monitoring system in the hands of intended users.

BACKGROUND: This study assessed the performance of a blood glucose monitoring system (BGMS) in development that uses a new generation of blood glucose test strips with capillary and venous blood in the hands of its intended users, people with diabetes and healthcare professionals (HCPs). SUBJECTS AND METHODS: In total, 93 subjects ≥ 18 years old (median age, 33 years) with type 1 (78%) or type 2 (22%) diabetes participated. Untrained subjects performed self-test fingersticks using a Microlet(®)2 lancing device (Bayer HealthCare LLC, Diabetes Care, Tarrytown, NY) followed by testing of their own capillary blood on the BGMS. HCPs performed fingersticks (using a Tenderlett(®) lancing device [International Technidyne Corp., Edison, NJ]) and venipunctures on subjects and tested both capillary and venous samples from subjects on the BGMS. All BGMS results were compared with Yellow Springs Instruments (YSI) (YSI Life Sciences, Inc., Yellow Springs, OH) laboratory results. Analytical accuracy was assessed according to International Organization for Standardization (ISO) 15197:2003 guidelines (i.e., within ± 15 mg/dL or ± 20% of the YSI results for samples with glucose concentrations < 75 mg/dL and ≥ 75 mg/dL, respectively) and more stringent criteria (i.e., within ± 15 mg/dL or ± 15% of the YSI results for samples with glucose concentrations < 100 mg/dL and ≥ 100 mg/dL, respectively). RESULTS: Overall, 98.9% (180/182) of subject Microlet2 capillary fingerstick results, 99.5% (182/183) of HCP Tenderlett capillary fingerstick results, and 100% (186/186) of venous results met current ISO criteria and more stringent criteria. The average hematocrit was 44%, with values ranging from 32% to 52%. CONCLUSIONS: Test results from both capillary fingerstick and venous samples with a new BGMS in development met current accuracy guidelines as well as proposed tighter criteria.

Advanced meter features improve postprandial and paired self-monitoring of blood glucose in individuals with diabetes: results of the Actions with the CONTOUR Blood Glucose Meter and Behaviors in Frequent Testers (ACT) study.

BACKGROUND: This study evaluated whether education and use of the advanced meter features of the CONTOUR(®) (Bayer HealthCare LLC, Diabetes Care, Tarrytown, NY) blood glucose monitoring system (BGMS) affect the frequency and pattern of blood glucose testing in insulin-using subjects with diabetes who routinely perform self-monitoring of blood glucose (SMBG). SUBJECTS AND METHODS: Insulin-using subjects with type 1 or type 2 diabetes were enrolled in this 6-month, multicenter, prospective study and randomized to one of two groups. The basic meter features group (BMF group) received basic instruction in the use of the BGMS, whereas the advanced meter features group (AMF group) also received training in the use of advanced features, including the meal marker and audible reminder, and were instructed to use these features. Both groups received education on the importance of postprandial testing. RESULTS: The AMF group (n=105) had significantly greater average weekly postprandial blood glucose testing than the BMF group (n=106) at each follow-up visit (P<0.001) and significantly increased the frequency of paired blood glucose testing (P<0.001) as well. In both groups, glycated hemoglobin decreased significantly as postprandial testing frequency increased (P<0.05). Subject reports indicated that use of advanced features made postmeal SMBG considerably easier to remember, helped them better understand how to make decisions on their own, and increased their confidence in meal choices. CONCLUSIONS: Study findings showed that advanced features of the CONTOUR BGMS increased structured testing as measured by postprandial and paired SMBG and were perceived as useful by patients.

Understanding self-monitoring of blood glucose among individuals with type 1 and type 2 diabetes: an information-motivation-behavioral skills analysis.

PURPOSE: To evaluate self-monitoring of blood glucose (SMBG) information deficits, motivational obstacles, and behavioral skills limitations in individuals with type 1 and type 2 diabetes, and to assess the relationship of these deficits with SMBG frequency. METHODS: Individuals with type 1 (n = 208; 103 male, 105 female) and type 2 (n = 218; 107 male, 111 female) diabetes participated in an online survey assessing SMBG information, motivation, behavioral skills, and behavior. RESULTS: A substantial proportion of participants scored as SMBG uninformed, unmotivated, and unskilled on specific assessment items. SMBG information, motivation, and behavioral skills deficits were significantly correlated with SMBG frequency, such that individuals with type 1 or type 2 diabetes, who were less informed, less motivated, and less behaviorally skilled, reported lower frequency of SMBG. CONCLUSION: Common and consequential SMBG information, motivation, and behavioral skills deficits were present, and patients with these gaps were less likely to test frequently. Clinical education focusing on relevant SMBG information, motivation to act, and behavioral skills for acting effectively may be a priority.

Performance evaluation and labeling comprehension of a new blood glucose monitoring system with integrated information management.

BACKGROUND: This study evaluated performance and product labeling of CONTOUR® USB, a new blood glucose monitoring system (BGMS) with integrated diabetes management software and a universal serial bus (USB) port, in the hands of untrained lay users and health care professionals (HCPs). METHOD: Subjects and HCPs tested subject's finger stick capillary blood in parallel using CONTOUR USB meters; deep finger stick blood was tested on a Yellow Springs Instruments (YSI) glucose analyzer for reference. Duplicate results by both subjects and HCPs were obtained to assess system precision. System accuracy was assessed according to International Organization for Standardization (ISO) 15197:2003 guidelines [within ±15 mg/dl of mean YSI results (samples <75 mg/dl) and ±20% (samples ≥75 mg/dl)]. Clinical accuracy was determined by Parkes error grid analysis. Subject labeling comprehension was assessed by HCP ratings of subject proficiency. Key system features and ease-of-use were evaluated by subject questionnaires. RESULTS: All subjects who completed the study (N = 74) successfully performed blood glucose measurements, connected the meter to a laptop computer, and used key features of the system. The system was accurate; 98.6% (146/148) of subject results and 96.6% (143/148) of HCP results exceeded ISO 15197:2003 criteria. All subject and HCP results were clinically accurate (97.3%; zone A) or associated with benign errors (2.7%; zone B). The majority of subjects rated features of the BGMS as "very good" or "excellent." CONCLUSIONS: CONTOUR USB exceeded ISO 15197:2003 system performance criteria in the hands of untrained lay users. Subjects understood the product labeling, found the system easy to use, and successfully performed blood glucose testing.

Performance of the DIDGET blood glucose monitoring system in children, teens, and young adults.

BACKGROUND: This study evaluated the performance of the DIDGET® blood glucose monitoring system (BGMS) in the hands of its intended users: children, teens, and young adults with diabetes. METHODS: Finger stick capillary blood samples were tested in duplicate by subjects (with parent/guardian assistance, if needed) and health care professionals using the DIDGET BGMS, and results were compared with those obtained using a Yellow Springs Instruments (YSI) glucose analyzer. Modified venous blood samples (i.e., glycolyzed or spiked with glucose) were used to analyze meter performance under extreme glucose concentrations. Accuracy was assessed using International Organization for Standardization (ISO) 15197:2003 guidelines (i.e., 95% of meter results within ±15 mg/dl or ±20% of reference values). RESULTS: A total of 123 subjects aged 4 to 24 years with type 1 or type 2 diabetes were enrolled. The DIDGET meter achieved accuracy according to ISO 15197:2003 criteria: >97% of meter results were within ±15 mg/dl or ±20% of reference values. Regression analyses showed a high degree of correlation between meter and YSI results: coefficient of determination (R(2)) = 98.2% for all samples combined and 97.2% for capillary samples only. Clinical accuracy for combined samples was demonstrated by Parkes consensus error grid analyses; 100% of meter results were in zone A (98.5%) or zone B (1.5%). There was no difference in performance or accuracy across age subsets. Hematocrit values did not affect meter blood glucose results. CONCLUSION: The DIDGET BGMS provided accurate test results across all age ranges in children, teens, and young adults with diabetes.

Evaluation of a novel continuous glucose measurement device in patients with diabetes mellitus across the glycemic range.

BACKGROUND: This glucose clamp study assessed the performance of an electrochemical continuous glucose monitoring (CGM) system for monitoring levels of interstitial glucose. This novel system does not require use of a trocar or needle for sensor insertion. METHOD: Continuous glucose monitoring sensors were inserted subcutaneously into the abdominal tissue of 14 adults with type 1 or type 2 diabetes. Subjects underwent an automated glucose clamp procedure with four consecutive post-steady-state glucose plateau periods (40 min each): (a) hypoglycemic (50 mg/dl), (b) hyperglycemic (250 mg/dl), (c) second hypoglycemic (50 mg/dl), and (d) euglycemic (90 mg/dl). Plasma glucose results obtained with YSI glucose analyzers were used for sensor calibration. Accuracy was assessed retrospectively for plateau periods and transition states, when glucose levels were changing rapidly (approximately 2 mg/dl/min). RESULTS: Mean absolute percent difference (APD) was lowest during hypoglycemic plateaus (11.68%, 14.15%) and the euglycemic-to-hypoglycemic transition (14.21%). Mean APD during the hyperglycemic plateau was 17.11%; mean APDs were 18.12% and 19.25% during the hypoglycemic-to-hyperglycemic and hyperglycemic-to-hypoglycemic transitions, respectively. Parkes (consensus) error grid analysis (EGA) and rate EGA of the plateaus and transition periods, respectively, yielded 86.8% and 68.6% accurate results (zone A) and 12.1% and 20.0% benign errors (zone B). Continuous EGA yielded 88.5%, 75.4%, and 79.3% accurate results and 8.3%, 14.3%, and 2.4% benign errors for the euglycemic, hyperglycemic, and hypoglycemic transition periods, respectively. Adverse events were mild and unlikely to be device related. CONCLUSION: This novel CGM system was safe and accurate across the clinically relevant glucose range.