Short- and Long-Term Effects on Glucose Control of Nonadherence to Insulin Therapy in People With Type 2 Diabetes An In Silico Study.

BACKGROUND: Strict adherence to multiple daily insulin (MDI) therapy is a cornerstone for the achievement of good glucose control in people with advanced type 2 diabetes (T2D). Here, we aim to in silico assess glucose control in T2D subjects with poor adherence to MDI therapy. METHODS: We tuned the Padova T2D Simulator, originally describing early-stage T2D physiology, around advanced T2D people. One hundred in silico advanced T2D subjects were generated and equipped with optimal MDI therapy: specifically, basal and bolus insulin amounts and injection times were individualized for each subject by applying titration algorithms that iteratively update insulin dose based on glucose deviation from its target. Then, the effect of nonadhering to MDI therapy was assessed using standard glucose control metrics calculated in two 6-month 3-meal/day in silico scenarios: in Scenario 1, subjects received the optimal basal and prandial insulin bolus at each meal; in Scenario 2, subjects received optimal basal insulin and randomly delayed or skipped the prandial insulin bolus in 3 lunches during working days and 1 dinner during weekends. RESULTS: A statistically significant degradation was found in all glucose control outcome metrics in Scenario 2 versus Scenario 1: e.g., percent time above 180 mg/dL increased by 22.2% and glucose management index by 0.2%. CONCLUSIONS: Impaired adherence to MDI therapy in T2D leads to glucose control deteriorations in both short and long terms. Interestingly, short-term hyperglycemia seems being contrasted by residual endogenous insulin secretion, which statistically increased by 3-fold after delayed/skipped insulin boluses compared with optimal ones.

Relationship Between Lipohypertrophy, Glycemic Control, and Insulin Dosing: A Systematic Meta-Analysis.

Background: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.

Assessing Barriers and Adherence to Insulin Injection Technique in People With Diabetes: Development and Validation of New Assessment Tools.

BACKGROUND: The correct injection technique is crucial for people with insulin therapy. However, barriers to insulin injections exist, which can lead to problems with injections. In addition, injection behavior may deviate from recommendations leading to lower adherence to the correct injection technique. We developed two scales to assess barriers and adherence to the correct technique. METHODS: Two item pools were created to assess barriers to insulin injections (barriers scale) and adherence to the correct technique (adherence scale). In an evaluation study, participants completed the two newly created scales, as well as other questionnaires used for criterion validity. Exploratory factor analysis, correlational analysis, and receiver operating characteristics analysis were computed to analyze the validity of the scales. RESULTS: A total of 313 people with type 1 and type 2 diabetes using an insulin pen for insulin injections participated. For the barriers scale, 12 items were selected achieving a reliability of 0.74. The factor analysis revealed three factors namely emotional, cognitive, and behavioral barriers. For the adherence scale, nine items were selected achieving a reliability of 0.78. Both scales showed significant associations with diabetes self-management, diabetes distress, diabetes acceptance, and diabetes empowerment. Receiver operating characteristics analysis showed significant area under the curves for both scales in classifying people with current skin irritations. CONCLUSIONS: Reliability and validity of the two scales assessing barriers and adherence to insulin injection technique were demonstrated. The two scales can be used in clinical practice to identify persons in need of education in insulin injection technique.

In Silico Head-to-Head Comparison of Insulin Glargine 300 U/mL and Insulin Degludec 100 U/mL in Type 1 Diabetes.

Background: Second-generation long-acting insulin glargine 300 U/mL (Gla-300) and degludec 100 U/mL (Deg-100) provide novel basal insulin therapies for the treatment of type 1 diabetes (T1D). Both offer a flatter pharmacokinetic (PK) profile than the previous generation of long-acting insulins, thus improving glycemic control while reducing hypoglycemic events. This work describes an in silico head-to-head comparison of the two basal insulins on 24-h glucose profiles and was used to guide the design of a clinical trial. Materials and Methods: The Universities of Virginia (UVA)/Padova T1D simulator describes the intra-/interday variability of glucose-insulin dynamics and thus provides a robust bench-test for assessing glucose control for basal insulin therapies. A PK model describing subcutaneous absorption of Deg-100, in addition to the one already available for Gla-300, has been developed based on T1D clinical data and incorporated into the simulator. One hundred in silico T1D subjects received a basal insulin dose (Gla-300 or Deg-100) for 12 weeks (8 weeks uptitration, 4 weeks stable dosing) by morning or evening administration in a basal/bolus regimen. The virtual patients were uptitrated to their individual doses with two different titration rules. Results: The last 2-week simulated continuous glucose monitoring data were used to calculate various outcome metrics for both basal insulin treatments, with primary outcome being the percent time in glucose target (70-140 mg/dL). The simulations show no statistically significant difference for Gla-300 versus Deg-100 in the main endpoints. Conclusions: This work suggests comparable glucose control using either Gla-300 or Deg-100 and was used to guide the design of a clinical trial intended to compare second-generation long-acting insulin analogues.

In Silico Examination of Initiation of Long-Acting Insulin Analogs Toujeo Compared to Lantus Under 3 Dosing Titration Rules in Virtual Type 2 Diabetes Subjects.

BACKGROUND: Despite the benefits and clinical necessity of insulin treatment in type 2 diabetes (T2D), healthcare providers are reluctant to initiate insulin, and patients are reluctant to start it for several reasons, one of these being the complexity of insulin treatment. Patients and their healthcare providers can benefit from titration algorithms (TAs) or rules that assist with the initiation and titration of insulin, performing the calculations that are needed to safely initiate and conservatively adjust. METHODS: The primary objective for this in silico study was to examine the effectiveness of 3 dose TAs (1-3) for optimization of basal insulin glargine (Gla-100 and Gla-300). In the simulations, 100 virtual subjects with T2D were included (50% men, age 62 ± 3 years, HbA1c 8.1% ± 2.9%, body weight 94 ± 16 kg). Subjects were studied under each TA (TA1 and TA2 fasting blood glucose [FBG] targets 90-130 mg/dL, TA3 FBG target 110-150 mg/dL). Initial dose of both insulins was based on 0.2 U/kg body weight. During 3 months, subjects reported their FBG to the LTHome web-based dose guidance system with a rules engine to safely guide long-acting insulin titration and maintenance. Subjects followed dose recommendations to reach designated FBG target ranges. RESULTS: All subjects reached stable doses under all TAs with both Gla-100 and Gla-300 insulin, and 93 or more of the 100 subjects, depending on the assigned TA, achieved the target FBG range within the 3-month simulation for all TAs. Mean FBG was lowered (Gla-100: 155 ± 40 to 118 ± 11 mg/dL with TA1 and TA2 and 132 ± 12 mg/dL for TA3; Gla-300: 125 ± 14 with TA1 and TA2 and 134 ± 15 mg/dL with TA3). Calculated HbA1c improved from 8.1% ± 2.9% to 7.1% ± 2.5% for TA1 and TA2 and 7.5% ± 2.5% for TA3, a reduction of 0.9% and 0.6% over 3 months for both insulins. Three subjects on Gla-100 and one subject on Gla-300 experienced mild hypoglycemia. CONCLUSION: All TAs delivered safe dose recommendations with minimal hypoglycemia, leading to a stable glucose control in the majority of subjects.

More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized Head-to-Head BRIGHT Trial.

OBJECTIVE: To compare insulin glargine 300 units/mL (Gla-300) versus insulin degludec 100 units/mL (IDeg-100) in this first head-to-head randomized controlled trial. RESEARCH DESIGN AND METHODS: BRIGHT (NCT02738151) was a multicenter, open-label, active-controlled, two-arm, parallel-group, 24-week, noninferiority study in insulin-naive patients with uncontrolled type 2 diabetes. Participants were randomized 1:1 to evening dosing with Gla-300 (N = 466) or IDeg-100 (N = 463), titrated to fasting self-monitored plasma glucose of 80-100 mg/dL. The primary end point was HbA1c change from baseline to week 24. Safety end points included incidence and event rates of hypoglycemia. RESULTS: At week 24, HbA1c improved similarly from baseline values of 8.7% (72 mmol/mol) in the Gla-300 group and 8.6% (70 mmol/mol) in the IDeg-100 group to 7.0% (53 mmol/mol)-least squares mean difference -0.05% (95% CI -0.15 to 0.05) (-0.6 mmol/mol [-1.7 to 0.6])-demonstrating noninferiority of Gla-300 versus IDeg-100 (P < 0.0001). Hypoglycemia incidence and event rates over 24 weeks were comparable with both insulins, whereas during the active titration period (0-12 weeks) the incidence and rate of anytime (24-h) confirmed hypoglycemia (≤70 and <54 mg/dL) were lower with Gla-300. Both insulins were properly titrated and exhibited no specific safety concerns. CONCLUSIONS: Gla-300 and IDeg-100 provided similar glycemic control improvements with relatively low hypoglycemia risk. Hypoglycemia incidence and rates were comparable with both insulins during the full study period but lower in favor of Gla-300 during the titration period. The choice between these longer-acting basal insulins may be determined by factors such as access and cost, alongside clinical considerations.

Improved Glycemic Control in a Patient Group Performing 7-Point Profile Self-Monitoring of Blood Glucose and Intensive Data Documentation: An Open-Label, Multicenter, Observational Study.

INTRODUCTION: Regular self-monitoring of blood glucose (SMBG) is recommended as an integral part of therapy for all patients with diabetes treated with insulin. In the current study, the effects on glycemic control of taking 7-point SMBG profiles and using a diabetes management system (DMA) on a smartphone were investigated. METHODS: In a 12-week, open-label, multicenter, observational study, 51 patients [26 with type 1 diabetes mellitus (T1DM) and 25 with type 2 diabetes mellitus (T2DM)] were instructed to perform SMBG at least seven times a day using DMA combined with the iBGStar ® SMBG system. HbA1c was measured at regular visits to the study sites. Patients reviewed and managed their data as well as their treatment on their own and there were no further assistance or treatment recommendations. Adverse events (AEs) were recorded throughout. RESULTS: Overall, mean (SD) change from baseline in HbA1c at week 12 was -0.46 (0.57)% [-5 (6) mmol/mol (p < 0.0001)]. The change in HbA1c was observed in patients with T1DM [-0.27 (0.45)% (-3 [5] mmol/mol; p = 0.0063)] and T2DM [-0.65 (0.62)% (-7 [7] mmol/mol; p < 0.0001)]. The change in HbA1c was not correlated with an increased number of hypoglycemic events (blood glucose less than 55 mg/dL). The majority of AEs were symptomatic hypoglycemic events (42 events; nine patients). CONCLUSIONS: Glycemic control can be improved, without receiving any recommendations or advice on insulin dose, by performing daily 7-point SMBG profiles and using electronic documentation with a smartphone app. These results must be confirmed in a larger controlled trial, but they already strengthen the importance of structured SMBG in diabetes therapy. FUNDING: Sanofi.

Strengths and Limitations of New Approaches for Graphical Presentation of Blood Glucose Monitoring System Accuracy Data.

Graphical presentation of blood glucose monitoring systems' (BGMSs) accuracy typically includes difference plots (DPs). Recently, 3 new approaches were presented: radar plots (RPs), rectangle target plots (RTPs), and surveillance error grids (SEGs). BGMS data were modeled based on 3 scenarios that can be encountered in real life to highlight strengths and limitations of these approaches. Detailed assessment of BGMS data may be easier in plots with individual data points (DPs, RPs, SEGs), whereas RTPs may facilitate display of large amounts of data or comparison of BGMS. SEGs have the advantage of assessing clinical risk. The selection of a specific type depends mostly on the kind of information sought (eg, accuracy in specific concentration intervals, lot-to-lot variability, clinical risk) as there is no "absolute best" approach.

Real-World Data Collection Regarding Titration Algorithms for Insulin Glargine in Patients With Type 2 Diabetes Mellitus.

The primary objective of this study was to collect data regarding the effectiveness of different dose titration algorithms (TAs) for optimization or initiation of basal insulin supported oral therapy (BOT) in patients with type 2 diabetes. A total of 50 patients were enrolled in this trial (17 women, 33 men, age 63 ± 8 years, HbA1c 7.9 ± 0.8%). The investigator decided on an individual basis to apply any of 4 standard TAs: standard (S: fasting glucose target 90-130 mg/dL, n = 39), standard-fast titration (S-FT: 90-130 mg/dL, larger dose increments at FBG < 180 mg/dl, n = 1), less tight (LT: 110-150 mg/dL, n = 5), and tight (T: 70-100 mg/dL, n = 5). During the next 30 days daily contacts were used to adapt the insulin dose. The majority of all patients (70%) achieved a stable insulin glargine dose within 5 ± 6 days after initiation of the dose titration. HbA1c improved from 7.9 ± 0.8% to 7.5 ± 0.7% (P < .001). In total, 1300 dose decisions were made (1192 according to the TA and 108 by the physicians independently from the TA in 29 patients [58% of study population]). Reasons for TA-overruling dosing decisions were hypoglycemic events (14 mild/4 moderate) in 9 patients. In the majority of these cases (89.8%), the physician recommended continuation of the previous dose or a higher dose. The majority of FBG values were within the respective target range after 4 weeks. In conclusion, the insulin glargine TAs delivered safe dose recommendations with a low risk of hypoglycemia, which successfully led to a stable dose in the vast majority of patients.

Sublingual Immunotherapy with a Five-Grass Pollen Tablet in Adult Patients with Allergic Rhinitis: An Open, Prospective, Noninterventional, Multicenter Study.

BACKGROUND: Although the safety and efficacy of sublingual immunotherapy (SLIT) with a five-grass pollen tablet have been demonstrated in randomized clinical trials (RCTs), these outcomes must always be evaluated in real-life medical practice. METHODS: In a prospective, open-label, noninterventional, "real-life" study in Germany, we evaluated the safety, tolerability, and effectiveness of SLIT with a five-grass pollen tablet in adults with grass-pollen-induced allergic rhinoconjunctivitis. RESULTS: 808 adults were enrolled between September 2008 and December 2009. 35.3% of the participants experienced at least one adverse drug reaction (ADR), the most common of which were mild-to-moderate gastrointestinal and respiratory disorders. Serious ADRs considered causally related to SLIT treatment occurred in four patients. Overall, the five-grass pollen tablet was considered to have good or very good tolerability by most investigators and patients. Treatment was associated with the relief of nasal, ocular, and bronchial symptoms and decreased symptomatic medication use. However, interpretation of clinical improvements was limited by lower atmospheric grass pollen levels during the study season (relative to the preceding season). CONCLUSIONS: In a large population of patients treated in real-life medical practice, SLIT with a five-grass pollen tablet was safe and well tolerated. The patient-reported symptom relief suggests that SLIT was associated with clinical benefits.

Evaluation of a Methodology for Estimating HbA1c Value by a New Glucose Meter.

BACKGROUND: Accuracy/robustness of HbA1c estimation (eA1c) with an algorithm built into the MyStar Extra blood glucose (BG) meter has been demonstrated by in silico testing. We evaluated the performance and use of eA1c in a clinical setting. METHODS: Subjects took the BG meter home for 4 months to obtain eA1c in this open-label, single-center study. Laboratory HbA1c values were obtained approximately every 2 weeks and the corresponding eA1c documented. Subjects completed a questionnaire at study end (NCT01885546). RESULTS: There were 133 enrolled subjects (mean [SD] age 60.0 [15.0] years, 69 males, 104 with diabetes, HbA1c 7.0% [1.4]). A total of 1008 pairs of eA1c and laboratory HbA1c values were available. In subjects with diabetes, 97.5% of the eA1c results fell within ± 20% of the laboratory HbA1c, 95.0% within ± 18%, and 90.7% within ± 15%. When results were limited to the reportable HbA1c range of ≥ 6 to ≤ 10%, 99.3% of eA1c values fell within ± 20% of the laboratory HbA1c, 98.5% within ± 18%, and 96.2% within ± 15% Most subjects agreed/strongly agreed that the eA1c section in the user guide and flash cards was easy to follow (72%), they would use the system to track their eA1c (70%), they found the eA1c tool helpful (79%), and the tool may motivate them to manage their diabetes better (83%). CONCLUSIONS: Accuracy of the eA1c feature in this clinical setting was similar to the performance in silico. The majority of subjects found this tool helpful and agreed it may motivate to manage their diabetes better.

An observational, real-life safety study of a 5-grass pollen sublingual tablet in children and adolescents.

BACKGROUND: The safety and efficacy of pre- and coseasonal sublingual allergen immunotherapy (SLIT) with a 5-grass pollen sublingual tablet have been demonstrated in a randomized clinical trial (RCT) in children and adolescents. Observational, 'real-life' studies can usefully complement the results of RCTs. METHODS: A prospective, open-label, observational, multicentre post-marketing study of children and adolescents (aged 5-17, with grass pollen-induced allergic rhinitis) treated with the 5-grass pollen sublingual tablet was performed between June 2009 and January 2011 in Germany. Adverse events (AEs) were recorded during consultations with the investigating physicians; AEs judged to have at least a possible causal link to the tablet were classified as adverse drug reactions (ADRs). RESULTS: Eight hundred and forty-nine patients were enrolled (by 207 investigating physicians), 829 (mean ± s.d. age: 10.9 ± 3.3 yr) completed the study without major protocol deviations, and 796 were fully documented with respect to AEs. Ninety-four of the 796 patients (11.8%) experienced at least one ADR on the first day of SLIT and 218 (27.4%) experienced at least one ADR during the study. Four hundred and sixty-six of the 596 ADRs (78.2%) were mild or moderate. The most common ADRs were throat irritation (19.1% of the reactions), oral paresthesia (8.2%), oral pruritus (6.5%) and oedema mouth (6.2%). Serious ADRs occurred in five patients. No epinephrine use was reported. Seventy-six of the 829 patients (9.2%) discontinued SLIT due to AEs. Tolerability was judged to be good or very good by patients (84.7%), parents (87.0%) and investigators (89.7%). CONCLUSIONS: In clinical practice, pre- and coseasonal treatment with a 5-grass pollen sublingual tablet is safe and well tolerated in children and adolescents.

System accuracy evaluation of systems for point-of-care testing of blood glucose: a comparison of a patient-use system with six professional-use systems.

BACKGROUND: Point-of-care testing (POCT) of blood glucose (BG) is performed by medical personnel in clinical settings as well as by patients themselves for self-monitoring of blood glucose (SMBG) at home. We investigated if a system mainly intended for SMBG by people with diabetes, but also suitable for BG measurements by medical personnel, can achieve measurement accuracy on capillary blood samples comparable with professional-use POCT systems. METHODS: System accuracy was evaluated under standardised conditions, following the ISO standard 15197:2003. For each system (one SMBG system with three test strip lots and six professional-use systems), measurement results from capillary blood samples of 100 subjects were compared with a standardised laboratory glucose oxidase method (YSI 2300 glucose analyser). RESULTS: The seven evaluated systems showed 99.5% or 100% of the measurement results within the required system accuracy limits of ISO 15197:2003 (±0.83 mmol/L at BG concentrations <4.2 mmol/L and ±20% at BG concentrations ≥4.2 mmol/L). Applying the more stringent requirements of the revision ISO 15197:2013, the systems showed between 99% and 100% of the measurement results within the accuracy limits (±0.83 mmol/L at BG concentrations <5.55 mmol/L and ±15% at BG concentrations ≥5.55 mmol/L) and between 82% and 98% when even more restrictive limits were applied (±0.56 mmol/L and ±10%, respectively). CONCLUSIONS: Data from this study, which focused on system accuracy, suggest that SMBG systems can achieve system accuracy that is comparable with professional-use systems when measurements are performed on capillary blood samples by trained personnel in a standardised and controlled setting.

Accuracy and robustness of dynamical tracking of average glycemia (A1c) to provide real-time estimation of hemoglobin A1c using routine self-monitored blood glucose data.

BACKGROUND: Laboratory hemoglobin A1c (HbA1c) assays are typically done only every few months. However, self-monitored blood glucose (SMBG) readings offer the possibility for real-time estimation of HbA1c. We present a new dynamical method tracking changes in average glycemia to provide real-time estimation of A1c (eA1c). MATERIALS AND METHODS: A new two-step algorithm was constructed that includes: (1) tracking fasting glycemia to compute base eA1c updated with every fasting SMBG data point and (2) calibration of the base eA1c trace with monthly seven-point SMBG profiles to capture the principal components of blood glucose variability and produce eA1c. A training data set (n=379 subjects) was used to estimate model parameters. The model was then fixed and applied to an independent test data set (n=375 subjects). Accuracy was evaluated in the test data set by computing mean absolute deviation (MAD) and mean absolute relative deviation (MARD) of eA1c from reference HbA1c, as well as eA1c-HbA1c correlation. RESULTS: MAD was 0.50, MARD was 6.7%, and correlation between eA1c and reference HbA1c was r=0.76. Using an HbA1c error grid plot, 77.5% of all eA1c fell within 10% from reference HbA1c, and 97.9% fell within 20% from reference. CONCLUSIONS: A dynamical estimation model was developed that achieved accurate tracking of average glycemia over time. The model is capable of working with infrequent SMBG data typical for type 2 diabetes, thereby providing a new tool for HbA1c estimation at the patient level. The computational demands of the procedure are low; thus it is readily implementable into home SMBG meters. Real-time HbA1c estimation could increase patients' motivation to improve diabetes control.

Evaluation of the effects of insufficient blood volume samples on the performance of blood glucose self-test meters.

BACKGROUND: Accuracy of blood glucose readings is (among other things) dependent on the test strip being completely filled with sufficient sample volume. The devices are supposed to display an error message in case of incomplete filling. This laboratory study was performed to test the performance of 31 commercially available devices in case of incomplete strip filling. METHODS: Samples with two different glucose levels (60-90 and 300-350 mg/dl) were used to generate three different sample volumes: 0.20 µl (too low volume for any device), 0.32 µl (borderline volume), and 1.20 µl (low but supposedly sufficient volume for all devices). After a point-of-care capillary reference measurement (StatStrip, NovaBiomedical), the meter strip was filled (6x) with the respective volume, and the response of the meters (two devices) was documented (72 determinations/meter type). Correct response was defined as either an error message indicating incomplete filling or a correct reading (±20% compared with reference reading). RESULTS: Only five meters showed 100% correct responses [BGStar and iBGStar (both Sanofi), ACCU-CHEK Compact+ and ACCU-CHEK Mobile (both Roche Diagnostics), OneTouch Verio (LifeScan)]. The majority of the meters (17) had up to 10% incorrect reactions [predominantly incorrect readings with sufficient volume; Precision Xceed and Xtra, FreeStyle Lite, and Freedom Lite (all Abbott); GlucoCard+ and GlucoMen GM (both Menarini); Contour, Contour USB, and Breeze2 (all Bayer); OneTouch Ultra Easy, Ultra 2, and Ultra Smart (all LifeScan); Wellion Dialog and Premium (both MedTrust); FineTouch (Terumo); ACCU-CHEK Aviva (Roche); and GlucoTalk (Axis-Shield)]. Ten percent to 20% incorrect reactions were seen with OneTouch Vita (LifeScan), ACCU-CHEK Aviva Nano (Roche), OmniTest+ (BBraun), and AlphaChek+ (Berger Med). More than 20% incorrect reactions were obtained with Pura (Ypsomed), GlucoCard Meter and GlucoMen LX (both Menarini), Elite (Bayer), and MediTouch (Medisana). CONCLUSIONS: In summary, partial and incomplete blood filling of glucose meter strips is often associated with inaccurate reading. These findings underline the importance of appropriate patient education on this aspect of blood glucose self-monitoring.

Blood glucose meters employing dynamic electrochemistry are stable against hematocrit interference in a laboratory setting.

BACKGROUND: Hematocrit (HCT) is known to be a confounding factor that interferes with many blood glucose (BG) measurement technologies, resulting in wrong readings. Dynamic electrochemistry has been identified as one possible way to correct for these potential deviations. The purpose of this laboratory investigation was to assess the HCT stability of four BG meters known to employ dynamic electrochemistry (BGStar and iBGStar, Sanofi; Wavesense Jazz, AgaMatrix; Wellion Linus, MedTrust) in comparison with three other devices (GlucoDock, Medisana; OneTouch Verio Pro, LifeScan; FreeStyle Freedom InsuLinx, Abbott-Medisense). METHODS: Venous heparinized blood was immediately aliquoted after draw and manipulated to contain three different BG concentrations (60-90, 130-160, and 280-320 mg/dl) and five different HCT levels (25%, 35%, 45%, 55%, and 60%). After careful oxygenation to normal blood oxygen pressure, each of the resulting 15 different samples was measured six times with three devices and three strip lots of each meter. The YSI Stat 2300 served as laboratory reference method. Stability to HCT influence was assumed when less than 10% difference occurred between the highest and lowest mean glucose deviations in relation to HCT concentrations [hematocrit interference factor (HIF)]. RESULTS: Five of the investigated self-test meters showed a stable performance with the different HCT levels tested in this investigation: BGStar (HIF 4.6%), iBGStar (6.6%), Wavesense Jazz (4.1%), Wellion Linus (8.5%), and OneTouch Verio Pro (6.2%). The two other meters were influenced by HCT (FreeStyle InsuLinx 17.8%; GlucoDock 46.5%). CONCLUSIONS: In this study, meters employing dynamic electrochemistry, as used in the BGStar and iBGStar devices, were shown to correct for potential HCT influence on the meter results. Dynamic electrochemistry appears to be an effective way to handle this interfering condition.

The precision study: examining the inter- and intra-assay variability of replicate measurements of BGStar, iBGStar and 12 other blood glucose monitors.

OBJECTIVE: Self-monitoring of blood glucose is a key element in diabetes management. Accurate and precise performance of blood glucose monitors (BGMs) ensures that valid values are obtained to guide treatment decisions by patients and physicians. BGStar and iBGStar are hand-held BGMs that use dynamic electrochemistry to correct for potential interferences and thereby minimize system errors. RESEARCH DESIGN AND METHODS: A single-center, in vitro diagnostic device performance evaluation with heparinized oxygenated venous blood samples (intra-assay precision) and control solutions (interassay precision) was performed in a laboratory setting, comparing BGStar and iBGStar with 12 competitors. MAIN OUTCOME MEASURES: The primary outcome was the coefficient of variation percent (CV%) of the BGMs investigated. RESULTS: In inter-assay precision analyses, all but GlucoMen LX had a CV <5%, and in intra-assay precision analyses, 10 of the 14 devices tested had CV <5%. BGStar and iBGStar had a CV <5% in both the inter- and intra-assay precision analyses. The smallest variation was found in the near-normoglycemic glucose range (5.3 - 8.0 mmol/l) for both BGStar and iBGStar in the inter-assay precision analysis. CONCLUSIONS: BGStar and iBGStar were proven to have very good inter-assay and high intra-assay precision, demonstrating low scattering of replicate measurements with both clinical samples and control solutions.

Determining factors of patient compliance to treatment in allergic rhinitis.

BACKGROUND: Compliance with prescribed treatment is essential for reducing costs of health care and improving efficacy of treatment in patients with allergic rhinitis. OBJECTIVE: To evaluate the extent of compliance and identify predictive factors and risk profiles for patient noncompliance with the therapeutic regiments of sublingual immunotherapy and H1-antihistamines. METHODS: In this retrospective study we analysed data from two non-interventional studies: one study with a total of 42,111 patients taking H1-antihistamines and one study with 354 patients receiving sublingual immunotherapy. Both studies were approved by the local ethics committees and competent authorities. By performing univariate and multivariate logistic regression analysis we calculated odds ratios with a 95% confidence interval for given characteristics. RESULTS: There was a compliance rate of 79.6% with the administration of sublingual immunotherapy. Factors associated with compliance were severe nasal, eye and airways symptoms, and strong impairment in social and work life. Compliance with the intake of H1-antihistamines was 98%. Patients with a concomitant disease, especially with a bronchialasthma or a psychiatric disorder had higher odds for being non-compliant. CONCLUSION: Compliance with intake of sublingual immunotherapy and H1-antihistamines is high. However, our findings point out that patients with characteristics such as a comorbid bronchial asthma or mild symptoms have higher odds for noncompliance and require attentive monitoring to reduce healthcare costs and morbidity.

Common standards of basal insulin titration in type 2 diabetes.

Type 2 diabetes mellitus has become a worldwide major health problem, and the number of people affected is steadily increasing. Thus, not all patients suffering from the disease can be treated by specialized diabetes centers or outpatient clinics, but by primary care physicians. The latter, however, might have time constraints and have to deal with many kinds of diseases or with multimorbid patients, so their focus is not so much on lowering high blood glucose values. Thus, the physicians, as well as the patients themselves, are often reluctant to initiate and adjust insulin therapy, although basal insulin therapy is considered the appropriate strategy after oral antidiabetic drug failure, according to the latest international guidelines. A substantial number of clinical studies have shown that insulin initiation and optimization can be managed successfully by using titration algorithms-even in cases where patients themselves are the drivers of insulin titration. Nevertheless, tools and strategies are needed to facilitate this process in the daily life of both primary health care professionals and patients with diabetes.

Determination of hematocrit interference in blood samples derived from patients with different blood glucose concentrations.

BACKGROUND: We performed a blood glucose meter hematocrit (HCT) interference test with lower sample manipulation requirements by using blood samples from patients with different blood glucose (BG) levels. METHODS: Blood from five patients with different BG levels (2.8, 5.6, 8.3, 13.9, 19.4 mmol/liter) was manipulated to contain five different HCT concentrations (35/40/45/50/55%). Each sample was measured three times in parallel with 14 BG testing devices (reference method: YSI 2300 STAT Plus™ Glucose Analyzer). The largest mean deviations in both directions from the reference method (normalized to 100% at 45% HCT) were added as a measure for hematocrit interference factor (HIF). A HIF >10% was considered to represent clinically relevant HCT interference. RESULTS: Few devices showed no clinically relevant HCT interference at high/low BG levels: BGStar® (7.2%, 7.3%), iBGStar® (9.0%, 8.6%), Contour® (10.0%, 4.6%), OneTouch® Verio™ 2 (10.0%, 5.2%), and GlucoMen® LX (7.2%, 5.1%). Other devices showed interference at one or both glucose ranges: ACCU-CHEK® Aviva (12.6%, 10.7%), Aviva Nano (7.2%, 10.5%), Breeze2 (3.6%, 30.2%), GlucoCard G+ (12.6%, 7.0%), OneTouch® Ultra®2 (12.6%, 25.6%), FreeStyle Freedom Lite® (9.0%, 11.0%), Precision Xceed (16.2%, 15.3%), and MediTouch® (19.8%, 28.0%). The deviations in all devices were less pronounced in the HCT range of 35-50%. CONCLUSIONS: The results of this trial with less sample manipulation (HCT only) confirmed previous examinations with HCT and glucose manipulation. The same devices showed HCT stability as previously observed. Artificial sample manipulation may be less crucial than expected when evaluating HCT interference.