The ASPIRE study: design and methods of an in-clinic crossover trial on the efficacy of automatic insulin pump suspension in exercise-induced hypoglycemia.

Rainier Clinical Research Institute, Renton, Washington, USA.
Journal of diabetes science and technology 11/2011; 5(6):1466-71. DOI: 10.1177/193229681100500621
Source: PubMed

ABSTRACT The Paradigm®Veo™ System includes a low glucose suspend (LGS) feature which suspends insulin delivery when a prespecified glucose threshold setting is reached by the associated continuous glucose monitoring (CGM) sensor. The ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) study is a multicenter, in-clinic, randomized, crossover study to examine the efficacy of LGS in exercise-induced hypoglycemia.
Insulin-pump users underwent two separate exercise sessions, one with the LGS feature set to suspend insulin (LGS-on) when the CGM-detected glucose concentration was ≤ 70 mg/dl and one with the LGS feature off. Exercise sessions were conducted after an overnight fast and with initial plasma glucose level as measured by the YSI 2300 STAT Plus glucose analyzer (YSI) of 100-140 mg/dl. Subjects exercised until their YSI value fell to ≤ 85 mg/dl; subsequent YSI values <70 mg/dl were recorded for up to 4 h to measure the duration and nadir of hypoglycemia. The protocol required that subjects with YSI values <50 or >300 mg/dl were rescued with carbohydrates or insulin, respectively, based on the provider's recommendation. The primary end point was comparison of duration and severity of hypoglycemia between LGS-on and LGS-off sessions. Secondary end points included areas under the glucose concentration curve, CGM sensor accuracy, and last YSI glucose. Device- and procedure-related adverse events and serious adverse events were recorded.
Fifty adults and teenagers (17-58 years) with type 1 diabetes were randomized. Study completion is expected in November 2011.

Download full-text


Available from: Xuan Nguyen, Jun 21, 2015
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Background: The ASPIRE in-clinic study established that automatic suspension of insulin with the threshold suspend (TS) feature reduces the duration of induced hypoglycemia. The study's crossover design allowed the effects of antecedent hypoglycemia to be studied. Subjects and Methods: The study enrolled 50 subjects who exercised until plasma glucose (YSI glucose and lactate analyzer; YSI, Inc., Yellow Springs, OH) reached ≤85 mg/dL. Hypoglycemia was evaluated after the YSI value reached <70 mg/dL. In TS experiments, insulin was stopped for 2 h once a sensor glucose (SG) value of ≤70 mg/dL was detected; in control experiments, basal insulin delivery continued. Subjects were randomly assigned to Group A (TS in Period 1; control in Period 2) or Group B (control in Period 1; TS in Period 2). Experiments were separated by 3-10 days. Results: Hypoglycemia was 63.7 min shorter in Period 1 TS experiments (no preceding control experiment) than in Period 2 TS experiments (one or more preceding control experiment(s)) (P<0.01). The number of experiments prior to a successful TS experiment was lower for Period 1 than for Period 2 (0.36±0.64 vs. 1.57±0.84; P<0.001), as was the cumulative duration of antecedent hypoglycemia (16.6 min vs. 204.6 min; P<0.001). The between-groups difference in hypoglycemia duration was not attributable to differences in SG rates of change, the duration of exercise, or area under the curve of <70 mg/dL×min in the 2 days before the successful experiment (all P>0.3). Conclusions: The TS feature's ability to mitigate hypoglycemia was decreased by an episode or episodes of prolonged antecedent hypoglycemia, suggesting hypoglycemia begets hypoglycemia. The effect of antecedent hypoglycemia should be taken into consideration in the design of future experiments assessing strategies to reduce hypoglycemia.
    Diabetes Technology &amp Therapeutics 01/2014; DOI:10.1089/dia.2013.0219 · 2.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Continuous subcutaneous insulin infusion (CSII) by insulin pump seems to improve glycemia and quality of life as compared to conventional insulin therapy in type 1 diabetes (T1DM). However, while many T1DM subjects achieve excellent glycemic control, some others cannot reach recommended goals. In a retrospective analysis, we searched for factors associated with glycemic control in T1DM patients treated with insulin pump therapy. Data from 192 patients (133 women and 59 men) treated with personal insulin pumps at the Department of Metabolic Diseases, University Hospital, Krakow, Poland were analyzed. Sources of information included medical records, memory read-outs from insulin pumps and data from glucose meters. Univariate, multivariate linear and logistic regression analysis for the association with hemoglobin A1c (HbA1c) level were performed. The mean age of the subjects was 28.9 (±11.2) years, the mean duration of T1DM—14.6 (±7.6) years, mean body mass index—23.5 (±3.1) kg/m2. The mean HbA1c level in the entire study group was 7.4 % (57 mmol/mol). In the multivariate linear regression analysis, HbA1c correlated with the mean number of daily blood glucose measurements, number of hypoglycemic episodes per 100 blood glucose measurements, age at the examination, and continuous glucose monitoring system use. Multivariate logistic regression analysis for reaching the therapeutic target of HbA1c < 7.0 % (53 mmol/mol) showed that the independent predictors of achieving this goal included the same four variables. In a large clinical observation, we identified that patient-related and technological factors associated with glycemic control in adult pump-treated T1DM subjects.
    Endocrine 02/2015; 48(1):164-169. DOI:10.1007/s12020-014-0274-2. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In type 1 diabetes severe hypoglycemia is a barrier to optimal metabolic control. The combination of a continuous glucose sensor and an insulin pump with a mechanism of automatic shut-off in the presence of low glucose values (low glucose suspend, LGS) can be used to reduce the risk of hypoglycemia. In a prospective study, we investigated the effect of the LGS algorithm on the frequency of hypoglycemic episoses in children and adolescents with type 1 diabetes under real-life conditions. We found that 2 hr insulin shut-off increased glucose levels by approximately 35 mg/dL/hour and decreased significantly the number of hypoglycemic episodes. Reactive ketoacidosis was not detected, even in the presence of serious patient errors (e.g., calibration-associated errors). The ASPIRE study showed that these conclusions can be extended to adult patients. As children are at greatest risk for hypoglycemia it is important to study in this population safety and efficacy of predictive low glucose suspend.
    Technological Advances in the Treatment of Type 1 Diabetes, Frontiers in Diabetes Vol. 24 edited by D. Bruttomesso, G.Grassi, 01/2015: chapter Insulin Delivery System: pages 151-165; KARGER Publishing House., ISBN: 978-3-312-02336-7