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Background: Completing phase 3 trials of new drugs for youth with type 2 diabetes is challenging. The Pediatric Diabetes Consortium (PDC) of U.S. pediatric treatment centers developed a Consortium model to improve the efficiency of successfully completing these trials. Aims and Innovations: An aim of the PDC model is to utilize the resources of the PDC Coordinating Center and Executive Committee to improve study protocols, centralize interactions with sponsors, and oversee the performance of PDC Clinical Centers. Key features include a Consulting Group to improve protocol design; Master Service Agreements between the Coordinating Center and Clinical Centers covering confidentiality agreements and contract language; negotiation of a standard Site Budget with Contract Research Organizations (CROs)/Sponsors that reflect actual Clinical Center costs; Weekly Conference Calls with CROs/sponsors to track progress of Clinical Center launches, Monthly Oversight Calls with investigators and study Coordinators to track Clinical Center performance, discuss enrollment strategies, and identify emerging problems. Successes and Challenges: The Consortium model played a key role in the completion of the pivotal trial of liraglutide for treatment of youth with type 2 diabetes. PDC centers also played a pivotal role in exceeding the projected number of randomized subjects needed by two ongoing studies that are nearing completion. Conclusions: While the Consortium model is still a work in progress, PDC has assisted in the successful launch of new type 2 diabetes studies, and negotiations are in underway for PDC participation in pediatric type 1 diabetes and other diabetes-related studies.

Background: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated. Methods: Adolescents (n = 30, ages 14–21 years) and adults (n = 94, ages 22–75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase. Results: Adolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%–88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%–92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P

This study was undertaken to investigate the effect of an insulin infusion site warming device, the InsuPatch(40)(™) (IP(40)) (InsuLine Medical Ltd., Petach-Tikvah, Israel), on insulin aspart pharmacodynamics (PD) and pharmacokinetics (PK) in adolescents with type 1 diabetes.Seventeen subjects with type 1 diabetes (age, 15±1 years; hemoglobin A1c, 7.5±0.2% [58±2.2 mmol/mol]) underwent two euglycemic clamps performed on separate mornings with and without IP(40) activation with warming temperature at 40°C. On both days, the basal infusion was suspended, and glucose levels were maintained between 90 and 100 mg/dL by a variable rate dextrose infusion for up to 5 h after a 0.2 U/kg bolus of insulin aspart.Time to peak insulin action and time to half-maximal action occurred earlier with a greater early glucodynamic effect (area under the curve [AUC] for glucose infusion rate from 0 to 30 min) with IP(40) than without the IP(40), whereas the AUC for the time-action profile and the peak action did not differ with and without infusion site warming. PK parameters were in agreement with PD parameters, namely, a significantly earlier time to reach the maximum increment in insulin concentrations and greater early bioavailability (AUC for the change in insulin concentration from 0 to 30 min) with the IP(40). The tail of the plasma insulin response curve was also shortened with infusion site warming, with the time to reach baseline insulin concentration occurring significantly earlier (P=0.04).Our data demonstrate that skin warming around the infusion site to 40°C with the IP(40) is an effective means to accelerate absorption and action of rapid-acting insulin. These improvements in time-action responses have the potential to enhance the performance of open- and closed-loop insulin delivery systems.

The use of continuous glucose monitoring (CGM) in the pediatric population is not well characterized. We have evaluated the use of CGM over a 12-month interval in youth with type 1 diabetes (TID) and have provided a description of CGM use.Eighty subjects 8-17 years old with T1D and baseline hemoglobin A1c (HbA1c)or=7.0% used CGM as part of a 6-month randomized trial and subsequent 6-month extension study. Outcomes included frequency of CGM use, HbA1c levels, rate of severe hypoglycemia, and a CGM satisfaction scale.Seventy-six (95%) of 80 subjects were using CGM after 6 months (median use = 5.5 days/week) compared with 67 (84%) after 12 months (median use = 4.0 days/week). The 17 subjects using CGMor=6 days/week in month 12 had substantially greater improvement from baseline in HbA1c than did the 63 subjects using CGM6 days/week in month 12 (mean change - 0.8 +/- 0.6% vs. +0.1 +/- 0.7%, P0.001). They also reported greater satisfaction with use of CGM (P = 0.001). The incidence of severe hypoglycemic events was low during the 12 months of the study irrespective of the amount of CGM use.In youth with T1D, frequency of use decreases over time. Individuals who use CGM on a near-daily basis can have substantial improvement in glycemic control.

Objectives: It has been proposed that the first step towards a closed-loop artificial pancreas might be to use a continuous glucose sensor to automatically suspend the basal insulin delivery based on projected low sensor glucose values. Methods: We reviewed our recent experience with an artificial pancreas system, utilizing a proportional-integrative-derivative (PID) algorithm, in 17 adolescents with type 1 diabetes (T1D) to assess the safety and efficacy of this maneuver. Results: During 34 h of closed-loop automated insulin delivery, 18 pump suspensions ≥60 min (90 ± 18 min) occurred in eight subjects. Sensor glucose levels fell from 159 ± 42 mg/dL to a nadir of 72 ± 13 mg/dL. Corresponding plasma glucose levels fell from 168 ± 51 to 72 ± 16 mg/dL, with values

The BD Logic((R)) (Becton, Dickinson and Co., Franklin Lakes, NJ) and FreeStyle((R)) (Abbott Diabetes Care, Alameda, CA) meters are used to transmit data directly to insulin pumps for calculation of insulin doses and to calibrate continuous glucose sensors as well as to monitor blood glucose levels.The accuracy of the two meters was evaluated in two inpatient studies conducted by the Diabetes Research in Children Network (DirecNet). In both studies, meter glucose measurements made with either venous or capillary blood were compared with reference glucose measurements made by the DirecNet Central Laboratory at the University of Minnesota using a hexokinase enzymatic method.The BD Logic tended to read lower than the laboratory reference regardless of whether venous (median difference = -9 mg/dL) or capillary blood (median difference = -7 mg/dL) was used. This resulted in lower accuracy of the BD Logic compared with the FreeStyle meter based on the median relative absolute difference (RAD) for both venous blood (median RAD, 9% vs. 5%, P0.001) and capillary blood (median RAD, 11% vs. 6%, P = 0.008). The greatest discrepancy in the performance of the two meters was at higher reference glucose values. Accuracy was not significantly different when the reference wasor = 70 mg/dL.The BD Logic meter is less accurate than the FreeStyle meter.

BACKGROUND The objective of this study was to assess how the accuracy of the FreeStyle Flash (Abbott Diabetes Care, Alameda, CA) meter compares with that of the One Touch Ultra (Lifescan, Milpitas, CA) home glucose meter (HGM). RESEARCH DESIGN AND METHODS Fifty children with type 1 diabetes (T1D), 10-17 years old, were admitted for two separate 24-h periods to assess the effect of exercise on subsequent nocturnal hypoglycemia. Resulting data were used in a preplanned analysis of the accuracy of the Ultra and FreeStyle HGMs. Glucose levels were measured throughout the day and night and every 15-20 min during a standardized exercise protocol. Reference samples were assayed in a central laboratory using a hexokinase enzymatic method. These reference glucose measurements were paired with HGM values from venous blood obtained within +/- 5 min. RESULTS The median relative absolute difference was 5% for both the Ultra and FreeStyle HGMs, and the percentages of pairs meeting the International Organisation for Standardization criteria were 99% and 98%, respectively. The FreeStyle tended to read slightly higher than the reference method (median difference = +3 mg/dL; P < 0.001), and there was trend in this direction for the Ultra (median difference = +2 mg/dL, P = 0.15). Sensitivities for detection of hypoglycemia (reference < or = 60 and HGM < or = 70 mg/dL) were 96% and 100% for the Ultra and FreeStyle, respectively, and corresponding false-positive rates were both 5%. CONCLUSIONS In a controlled clinical setting using venous blood samples, both the Ultra and FreeStyle meters demonstrated a high degree of accuracy compared with the laboratory reference over a broad range of glucose concentrations in children with T1D.

S-53 IMMUNE-MEDIATED TYPE 1 DIABETES MELLITUS has traditionally been the only form of diabetes considered prevalent among children, while type 2 diabetes mellitus is commonly thought of as a disease of adulthood. Recently, however, there has been an alarming rise in the incidence of type 2 diabetes in children and adolescents, particularly among American children of non-European ancestry.1 At a consensus conference convened by the American Diabetes Association (ADA), it was reported that, depending on race/ethnicity and sampling strategy, 8–45% of newly diagnosed children have non-immune-mediated diabetes (Table 1).2,3 The majority of these children have type 2 diabetes, although an increase in idiopathic or non-immune-mediated type 1 diabetes also has been reported. In the past, only 1% to 2% of children were considered to have type 2 diabetes or other rare forms of non-immune-mediated diabetes. The importance of this phenomenon is underscored by a study of glucose abnormalities conducted among inner-city Mexican American middle school children (aged 11–14 years) in San Antonio, Texas. A report of preliminary data from this survey indicated that 8% of these children had impaired fasting glucose as defined by the ADA (i.e., fasting glucose levels of 110–125 mg/dL).4 Significant numbers had marked cardiovascular and metabolic risks, including family history of diabetes (54%), obesity (27% females, 40% males), acanthosis nigricans (19%), hypertension (15% males), and elevated insulin concentrations (26%). The rise in type 2 diabetes in children is not confined to North America. The incidence of type 2 diabetes among school children in Japan increased from 0.2/100,000 in 1976 to 7.3/ 100,000 in 1995.5,6 The incidence was greatest among children between the ages of 13 and 15, who had an incidence of 13.9/100,000. As in the United States, the problem has been attributed, at least in part, to changes in diet and an increased prevalence of obesity.

A vacuum-lancet device was applied to the forearm for the purpose of obtaining capillary blood samples for glucose monitoring with minimal pain. In four clinical trials, a total of 215 individuals aged 12-77 years were tested four times using standard conditions and four times with either a different depth of lancing, different brand of lancet or a larger-sized device. The volume of blood collected using one-half atmosphere of vacuum in 40 sec was measured. The sensation and visual appearance of each lancet puncture on the forearm was recorded. Glucose was measured in forearm and in conventional fingerstick blood samples. The distribution of volumes was skewed to higher values with median values for each trial in the range of 3-10 microL. Ninety-five percent of the lancet sticks were judged as less painful than a fingerstick. Redness and bruising around the lanced sites were noted in some patients but disappeared within a few days. Overall correlation of the forearm versus fingerstick glucose values was 0.96. The vacuum-lancet device was very successful in obtaining capillary blood samples for glucose testing in a relatively painless manner. Incorporation of a glucose measuring system into the device might improve testing compliance among those who fear pain or the sight of blood.