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Rosenstock J.,Dallas Diabetes and Endocrine Center at Medical City | Klaff L.J.,Rainier Clinical Research Center | Schwartz S.,Diabetes and Glandular Disease Research Associates | Northrup J.,Eli Lilly and Company | And 3 more authors.
Diabetes Care | Year: 2010

OBJECTIVE - To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). RESEARCH DESIGNANDMETHODS - Obese subjects (n = 152; age 46 ± 12 years, female 82%, weight 108.6 ± 23.0 kg, BMI 39.6 ± 7.0 kg/m2, IGT or IFG 25%) were randomized to receive exenatide (n = 73) or placebo (n = 79), along with lifestyle intervention, for 24 weeks. RESULTS - Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo (exenatide - placebo, P < 0.001). Placebo-subtracted difference in percent weight reduction was -3.3 ± 0.5% (P < 0.001). Both groups reduced their daily calorie intake (exenatide, -449 cal; placebo, -387 cal). IGT or IFG normalized at end point in 77 and 56% of exenatide and placebo subjects, respectively. CONCLUSIONS - Exenatide plus lifestyle modification decreased caloric intake and resulted in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG. © 2010 by the American Diabetes Association.


Bailey T.S.,AMCR Institute Inc. | Ahmann A.,Oregon Health And Science University | Brazg R.,Rainier Clinical Research Center | Christiansen M.,Diablo Clinical Research | And 4 more authors.
Diabetes Technology and Therapeutics | Year: 2014

Objective: This study evaluated the performance and acceptability of the Enlite® glucose sensor (Medtronic MiniMed, Inc., Northridge, CA). Subjects and Methods: Ninety adults with type 1 or type 2 diabetes wore two Enlite sensors on the abdomen and/or buttock for 6 days and calibrated them at different frequencies. On Days 1, 3, and 6, accuracy was evaluated by comparison of sensor glucose values with frequently sampled plasma glucose values collected over a 12-h period. Accuracy was assessed at different reference glucose concentrations and during times when absolute glucose concentration rates of change were <1, 1-2, and >2 mg/dL/min. The sensor's ability to detect hypoglycemia or hyperglycemia was evaluated with simulated alerts. Subject satisfaction was evaluated with a 7-point Likert-type questionnaire, with a score of 7 indicating strong agreement. Results: With abdomen sensors under actual-use calibration (mean, 2.8±0.9 times/day), the overall mean (median) absolute relative difference (ARD) values between sensor and reference values were 13.6% (10.1%); the corresponding buttock sensor ARD values were 15.5% (10.5%). With abdomen sensors under minimal calibration (mean, 1.2±0.9 times/day), the mean (median) ARD values were 14.7% (10.8%). Mean ARD values of abdomen sensors at rates of change of <1, 1-2, and >2 mg/dL/min were 13.6%, 12.9%, and 16.3%, respectively. With abdomen sensors, 79.5% and 94.1% of hypoglycemic and hyperglycemic events, respectively, were correctly detected; 81.9% and 94.9% of hypoglycemic and hyperglycemic alerts, respectively, were confirmed. The failure rates for abdomen and buttock sensors were 19.7% and 13.9%, respectively. Mean responses to survey questions for all subjects related to comfort and ease of use were favorable. Conclusions: The Enlite sensor provided accurate data at different glucose concentrations and rates of change. Subjects found the sensor comfortable and easy to use. © Mary Ann Liebert, Inc.


Sussman A.,Rainier Clinical Research Center | Taylor E.J.,MassResearch | Patel M.,Abbott Laboratories | Ward J.,Abbott Laboratories | And 3 more authors.
Journal of Diabetes Science and Technology | Year: 2012

Background: Patients consider multiple parameters in adjusting prandial insulin doses for optimal glycemic control. Dificulties in calculations can lead to incorrect doses or induce patients to administer fixed doses, rely on empirical estimates, or skip boluses. Method: A multicenter study was conducted with 205 diabetes subjects who were on multiple daily injections of rapid/short-acting insulin. Using the formula provided, the subjects manually calculated two prandial insulin doses based on one high and one normal glucose test result, respectively. They also determined the two doses using the FreeStyle InsuLinx Blood Glucose Monitoring System, which has a built-in, automated bolus calculator. After dose determinations, the subjects completed opinion surveys. Results: Of the 409 insulin doses manually calculated by the subjects, 256 (63%) were incorrect. Only 23 (6%) of the same 409 dose determinations were incorrect using the meter, and these errors were due to either confirmed or potential deviations from the study instructions by the subjects when determining dose with meter. In the survey, 83% of the subjects expressed more confidence in the meter-calculated doses than the manually calculated doses. Furthermore, 87% of the subjects preferred to use the meter than manual calculation to determine prandial insulin doses. Conclusions: Insulin-using patients made errors in more than half of the manually calculated insulin doses. Use of the automated bolus calculator in the FreeStyle InsuLinx meter minimized errors in dose determination. The patients also expressed confidence and preference for using the meter. This may increase adherence and help optimize the use of mealtime insulin. © Diabetes Technology Society.


Garg S.,University of Colorado at Denver | Brazg R.L.,Rainier Clinical Research Center | Bailey T.S.,AMCR Institute Inc. | Buckingham B.A.,Stanford University | And 5 more authors.
Diabetes Technology and Therapeutics | Year: 2012

Background: The efficacy of automatic suspension of insulin delivery in induced hypoglycemia among subjects with type 1 diabetes was evaluated. Subjects and Methods: In this randomized crossover study, subjects used a sensor-augmented insulin pump system with a low glucose suspend (LGS) feature that automatically stops insulin delivery for 2 h following a sensor glucose (SG) value ≤70 mg/dL. Subjects fasted overnight and exercised until their plasma glucose (measured with the YSI 2300 STAT Plus™ glucose and lactate analyzer [YSI Life Sciences, Yellow Springs, OH]) value reached ≤85 mg/dL on different occasions separated by washout periods lasting 3-10 days. Exercise sessions were done with the LGS feature turned on (LGS-On) or with continued insulin delivery regardless of SG value (LGS-Off). The order of LGS-On and LGS-Off sessions was randomly assigned. YSI glucose data were used to compare the duration and severity of hypoglycemia from successful LGS-On and LGS-Off sessions and to estimate the risk of rebound hyperglycemia after pump suspension. Results: Fifty subjects attempted 134 sessions, 98 of which were successful. The mean±SD hypoglycemia duration was less during LGS-On than during LGS-Off sessions (138.5±76.68 vs. 170.7±75.91 min, P=0.006). During LGS-On compared with LGS-Off sessions, mean nadir YSI glucose was higher (59.5±5.72 vs. 57.6±5.69 mg/dL, P=0.015), as was mean end-observation YSI glucose (91.4±41.84 vs. 66.2±13.48 mg/dL, P<0.001). Most (53.2%) end-observation YSI glucose values in LGS-On sessions were in the 70-180 mg/dL range, and none was >250 mg/dL. Conclusions: Automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia without causing rebound hyperglycemia. © 2012, Mary Ann Liebert, Inc.


Hirsch L.J.,Becton Dickinson | Gibney M.A.,Becton Dickinson | Albanese J.,Becton Dickinson | Qu S.,Becton Dickinson | And 3 more authors.
Current Medical Research and Opinion | Year: 2010

Objective: Pen needles (PN) for subcutaneous insulin therapy have become smaller; 5mm PNs are now the shortest in use. We evaluated the safety, efficacy and patient ratings of a new 4mm×32 gauge (G) PN. Research design and methods: Subjects with type 1 and type 2 diabetes and HbA1c 5.5 to 9.5 participated in a randomized non-inferiority cross-over trial, at four U.S. centers. Subjects used 4mm×32G PNs and either 5mm×31G PNs (4/5mm) or 8mm×31G PNs (4/8mm) in two, 3-week treatment periods; order of needle use was controlled. Subjects were either low dose or regular dose users (highest single insulin dose≤20 units and 2140 units, respectively). Percent absolute change in serum fructosamine (|Δ Fru|) was the primary endpoint; unexplained, severe hypo-or hyperglycemia was a secondary measure. Leakage at injection sites and pain measured by visual analog scale were tertiary measures. Equivalent glycemic control was defined priori as |Δ Fru| (including 95 CI) within 20; 40 subjects per subgroup provides 90 power at 0.05. Clinical trial registration: The study was registered on clinicaltrials.gov (identifier: NCT00928057). Results: Of 173 subjects randomized, 168 completed the study, and 163 were included in the fructosamine analyses 83 and 80 in the 4/5mm and 4/8mm groups, respectively. Subjects were 56 male, mean 52.6 yrs, 63 type 2. Baseline HbA1c7.51.0 and fructosamine 30155.1μmol/L. Mean |Δ Fru| was 4.9 (95 CI 3.8, 6.0) and 5.5 (4.5, 6.4), respectively, for the 4/5mm and 4/8mm groups, meeting glycemic equivalence criteria; results were similar in both dose groups. The median |Δ Fru| was 11.0μmol/L (8.0, 13.0) and 13.5μmol/L (9.8, 18.0) for the 4/5mm and 4/8mm groups, respectively. Unexplained, severe hypo-and hyperglycemic episodes were infrequent and not different between PNs. The 4mm PN was rated significantly less painful and preferred by approximately 2/3 of subjects (p<0.01). All three PNs had similar reported injection site leakage. Limitations: The study was of relatively short duration, in adults in the U.S. Further trials in other patients (e.g., GLP-1 users, pediatrics, obese) should be performed. Conclusions: The 4mm×32G PN provided equivalent glycemic control compared to 31G, 5mm and 8mm PNs with reduced pain, no difference in insulin leakage and was preferred by patients. © 2010 Informa UK Ltd All rights reserved.


Garg S.K.,Aurora University | Moser E.G.,Aurora University | Bode B.W.,Atlanta Diabetes Associates | Klaff L.J.,Rainier Clinical Research Center | And 3 more authors.
Endocrine Practice | Year: 2013

Objective: Peripheral insulin resistance in type 1 diabetes may be related to a paradoxical postprandial glucagon increase. This study evaluated the effects of sitagliptin (dipeptidyl peptidase-IV [DPP-IV] inhibitor, approved for patients with type 2 diabetes), in adults with type 1 diabetes to improve glycemic control through decreasing postprandial glucagon. Methods: This investigator-initiated, double-blind, randomized-parallel 20-week study enrolled 141 subjects. Subjects received sitagliptin 100 mg/day or placebo for 16 weeks. A subset of 85 patients wore blinded continuous glucose monitors (CGM) for 5 separate 7-day periods. The primary outcome was post-meal (Boost™) reduction in 4-hour glucagon area under the curve (AUC). Secondary endpoints included changes in glycated hemoglobin (A1c), CGM data, insulin dose, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and C-peptide levels. Results: There were no differences at screening between groups; however, after a 4-week run-in phase, A1c was significantly lower in the sitagliptin vs. placebo group. Post-meal GLP-1 levels were higher (P<.001) and GIP levels lower (P = .03), with glucagon suppression at 30 minutes (LS means 23.2 ± 1.9 versus 16.0 ± 1.8; P = .006) in the sitagliptin group at 16 weeks. There were no differences between the groups in change in A1c, insulin dose, weight, or C-peptide after 16 weeks of treatment. However, C-peptide positive patients randomized to sitagliplin had a non-significant trend toward decrease in A1c, mean glucose, and time spent in hyperglycemia. Conclusion: Sitagliptin use in type 1 diabetes did not change glucagon AUC, A1c, insulin dose, or weight despite post-meal rise in GLP-1 levels. C-peptide positive subjects treated with sitagliptin had a nonsignificant trend in decreasing hyperglycemia, which needs further evaluation. Copyright © 2013 AACE.


Jarrahian C.,PATH | Zehrung D.,PATH | Saxon E.,PATH | Griswold E.,PATH | Klaff L.,Rainier Clinical Research Center
Procedia in Vaccinology | Year: 2012

Several vaccines, diagnostic tests, and medications are currently delivered intradermally, and it is likely that this route of administration will grow in importance. A phase I clinical study was conducted to evaluate the intradermal (ID) adapter, a prototype intradermal delivery aid, for safety and precision of injection. Healthy adult volunteers received two injections each of 0.1. mL of sterile saline solution in the upper deltoid region of the arm using the ID adapter. Injection performance was determined by the proportion of injections delivered to the dermal layer by measuring wheals and fluid leakage, and through ultrasound imaging. Of the 40 study injections, 100% were determined to be successful intradermal injections. Leakage of liquid at the injection site was negligible. Performance was similar with the bevel orientation both upward and downward. Minor bleeding and skin abrasions were the only reported adverse events. Injections were well tolerated based on self-reporting of pain of injection. Based on these results, the ID adapter appears to be safe and effective as an alternative to the Mantoux method of ID delivery for future use in clinical evaluations of ID delivery of vaccines, skin tests, and other drugs. © 2012.


Klaff L.J.,Rainier Clinical Research Center | Brazg R.,Rainier Clinical Research Center | Hughes K.,Rainier Clinical Research Center | Tideman A.M.,Bayer AG | And 5 more authors.
Diabetes Technology and Therapeutics | Year: 2015

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 (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; One Touch ® Ultra® 2 (LifeScan, Inc., Milpitas, CA), 10.20 mg/dL; One Touch® 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. © 2015 Mary Ann Liebert, Inc.


Brazg R.L.,Rainier Clinical Research Center | Klaff L.J.,Rainier Clinical Research Center | Parkin C.G.,CGParkin Communications Inc.
Journal of Diabetes Science and Technology | Year: 2013

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. © Diabetes Technology Society.


Bailey T.,AMCR Institute Inc. | Bode B.W.,Atlanta Diabetes Associates | Christiansen M.P.,Diablo Clinical Research | Klaff L.J.,Rainier Clinical Research Center | Alva S.,Abbott Laboratories
Diabetes Technology and Therapeutics | Year: 2015

Introduction: The purpose of the study was to evaluate the performance and usability of the FreeStyle® Libre™ Flash glucose monitoring system (Abbott Diabetes Care, Alameda, CA) for interstitial glucose results compared with capillary blood glucose results. Materials and Methods: Seventy-two study participants with type 1 or type 2 diabetes were enrolled by four U.S. clinical sites. A sensor was inserted on the back of each upper arm for up to 14 days. Three factory-only calibrated sensor lots were used in the study. Sensor glucose measurements were compared with capillary blood glucose (BG) results (approximately eight per day) obtained using the BG meter built into the reader (BG reference) and with the YSI analyzer (Yellow Springs Instrument, Yellow Springs, OH) reference tests at three clinic visits (32 samples per visit). Sensor readings were masked to the participants. Results: The accuracy of the results was demonstrated against capillary BG reference values, with 86.7% of sensor results within Consensus Error Grid Zone A. The percentage of readings within Consensus Error Grid Zone A on Days 2, 7, and 14 was 88.4%, 89.2%, and 85.2%, respectively. The overall mean absolute relative difference was 11.4%. The mean lag time between sensor and YSI reference values was 4.5±4.8min. Sensor accuracy was not affected by factors such as body mass index, age, type of diabetes, clinical site, insulin administration, or hemoglobin A1c. Conclusions: Interstitial glucose measurements with the FreeStyle Libre system were found to be accurate compared with capillary BG reference values, with accuracy remaining stable over 14 days of wear and unaffected by patient characteristics. © Copyright 2015, Mary Ann Liebert, Inc.

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