Is an automatic pump suspension feature safe for children with type 1 diabetes? An exploratory analysis with a closed-loop system.

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 > or =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 <60 mg/dL recorded in only four of the 18 events. CONCLUSIONS: These data suggest that automatic pump suspension using the PID algorithm may be an effective means to prevent hypoglycemia in youth with T1D.

Continuous subcutaneous insulin infusion (CSII) in children with type 1 diabetes.

Recent studies have shown that continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, provides a treatment option that can assist in the attainment of current goals of treatment in children and adolescents with type 1 diabetes (T1DM). In pediatric patients, CSII has been demonstrated to reduce both glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or excessive weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children are reviewed.

Case study: contrasting challenges of insulin pump therapy in a toddler and adolescent with type 1 diabetes.

PURPOSE: To describe the challenges and outcomes of continuous subcutaneous insulin infusion (CSII) pump therapy in a toddler and adolescent with type 1 diabetes. Insight into patient-family aspects motivating pump use is provided. METHODS: Two cases treated at the Pediatric Diabetes Clinic at Yale University. RESULTS: Upon parental request, CSII was initiated to improve glycemic control in a 4-year-old boy (case 1) with unpredictable food intake. During 68 months of CSII therapy, hemoglobin A1C levels averaged 6.3% +/- 0.6%. Severe hypoglycemic episodes ceased 36 months ago, and occasional postprandial hyperglycemia during early school years was corrected with school nurses' reminders about premeal insulin bolus doses. Currently 9.5 years old, he independently manages all his insulin injections with parental assistance only to change the catheter site. Case 2 is a girl who was nearly 12 years of age when diagnosed with type 1 diabetes. Initially managed with daily injections, hypoglycemic episodes were interfering with her physically active lifestyle. At age 13 years, she elected CSII therapy, and glycemic control improved. Temporarily erratic in the immediate period pre- and postmenarche, metabolic control has since stabilized. At 15 years old, she successfully manages her diabetes independently. CONCLUSIONS: To optimize glycemic control, CSII can be initiated and used effectively, both in children of all ages and in adolescents with type 1 diabetes. CSII may be ideal therapy for toddlers, with no apparent lower age boundary for initiating CSII; however, the parenting challenges and requirements for supportive education differ between toddlers and adolescents. When disease and pump management are appropriately individualized, CSII therapy can help children with diabetes achieve and sustain glycemic control. Lifestyle flexibility, quality-of-life improvement, and independence can thus begin early in childhood and be maintained throughout young adulthood.

Insulin pump treatment of childhood type 1 diabetes.

Current goals for the treatment of children and adolescents with type 1 diabetes mellitus include achieving near-normal blood sugar levels, minimizing the risk of hypoglycemia, optimizing quality of life, and preventing or delaying long-term microvascular complications. Continuous subcutaneous insulin infusion (CSII) provides a treatment option that can assist in the attainment of all of these goals in all ages of children. Usage of CSII has been demonstrated to reduce glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children are reviewed.

A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine.

OBJECTIVE: The efficacy of the insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes has not yet been established in pediatric patients. Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA(1c) levels in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Thirty-two youth with type 1 diabetes (age 8-21 years) were randomly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart. Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA(1c). HbA(1c), total daily insulin dose (TDD), self-monitored blood glucose readings, and adverse events were compared after 16 weeks of therapy. RESULTS: While there was no significant change in the glargine group (HbA(1c) 8.2% at baseline vs. 8.1% at 16 weeks), youth randomized to CSII had a sharp reduction in HbA(1c) levels, from 8.1 to 7.2% after 16 weeks of therapy (P < 0.02 vs. baseline and <0.05 vs. glargine group). TDD was unchanged in the glargine group, but significantly dropped with CSII (1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks, P < 0.01). Both groups had similar basal doses and insulin-to-carbohydrate ratios. Fasting self-monitored blood glucose was similar in both groups, but lunch, dinner, and bedtime readings were significantly lower in the CSII group (P < 0.01). CONCLUSIONS: Lower HbA(1c) and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment. CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes.

Safety of nighttime 2-hour suspension of Basal insulin in pump-treated type 1 diabetes even in the absence of low glucose.

OBJECTIVE: An integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2 h if patients fail to respond to low-glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low glucose levels detected by sensor could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2 h in the overnight period would not lead to clinically important increases in blood ß-hydroxybutyrate levels despite widely varying glucose values prior to the suspension. RESEARCH DESIGN AND METHODS: Subjects measured blood glucose and blood ß-hydroxybutyrate levels using a meter each night at 9:00 p.m., then fasted until the next morning. On control nights, the usual basal rates were continued; on experimental nights, the basal insulin infusion was reprogrammed for a 2-h zero basal rate at random times after 11:30 p.m. RESULTS: In 17 type 1 diabetic subjects (mean age 24 ± 9 years, diabetes duration 14 ± 11 years, A1C level 7.3 ± 0.5% [56 mmol/mol]), blood glucose and blood ß-hydroxybutyrate levels were similar at 9:00 p.m. on suspend nights (144 ± 63 mg/dL and 0.09 ± 0.07 mmol/L) and nonsuspend nights (151 ± 65 mg/dL and 0.08 ± 0.06 mmol/L) (P = 0.39 and P = 0.47, respectively). Fasting morning blood glucose levels increased after suspend nights compared with nonsuspend nights (191 ± 68 vs. 141 ± 75 mg/dL, P < 0.0001), and the frequency of fasting hypoglycemia decreased the morning following suspend nights (P < 0.0001). Morning blood ß-hydroxybutyrate levels were slightly higher after suspension (0.13 ± 0.14 vs. 0.09 ± 0.11 mmol/L, P = 0.053), but the difference was not clinically important. CONCLUSIONS: Systems that suspend basal insulin for 2 h are safe and do not lead to clinically significant ketonemia even if the blood glucose level is elevated at the time of the suspension.

Effect of age of infusion site and type of rapid-acting analog on pharmacodynamic parameters of insulin boluses in youth with type 1 diabetes receiving insulin pump therapy.

OBJECTIVE: The purpose of this study was to examine the effect of type of insulin analog and age of insertion site on the pharmacodynamic characteristics of a standard insulin bolus in youth with type 1 diabetes receiving insulin pump therapy. RESEARCH DESIGN AND METHODS: Seventeen insulin pump-treated adolescents with type 1 diabetes underwent two euglycemic clamp procedures after a 0.2 unit/kg bolus of either insulin aspart or lispro on day 1 and day 4 of insulin pump site insertion. The glucose infusion rate (GIR) required to maintain euglycemia was the primary pharmacodynamic measure. RESULTS: There were no statistically significant differences in any of the pharmacodynamic parameters between aspart and lispro during day 1 and day 4. However, when the two groups were combined, time to discontinuation of exogenous glucose infusion, and time to half-maximal onset and offset of insulin action were observed significantly earlier during day 4 compared with day 1 (P = 0.03-0.0004), but the overall area under the GIR curve was similar on day 1 and day 4. CONCLUSIONS: With both insulin aspart and lispro, there is an earlier peak and shorter duration of action with increasing duration of infusion site use, but overall insulin action is not affected.

The renaissance of insulin pump treatment in childhood type 1 diabetes.

Current goals for the treatment of children and adolescents with type 1 diabetes mellitus include achieving near-normal blood sugar levels, minimizing the risk of hypoglycemia, optimizing quality of life, and preventing or delaying long-term microvascular and macrovascular complications. Continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, provides a treatment option that can assist in the attainment of all of these goals in all ages of children. In pediatric patients, CSII has been demonstrated to reduce both glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children are reviewed, as well as criteria for patient selection and practical considerations using pump therapy in youth with T1DM.

Optimal control of type 1 diabetes mellitus in youth receiving intensive treatment.

OBJECTIVE: To investigate the impact of factors that might interfere with optimal glycemic control in youth with type 1 diabetes mellitus (T1DM) in the current era of intensive management, including the interplay of race/ethnicity and socioeconomic status (SES) on HbA1c levels. STUDY DESIGN: This study comprised a database review of all patients under age 18 years with T1DM for at least 6 months duration. Sex, age, race/ethnicity, duration of diabetes, mode of insulin administration (pump vs injection), body mass index, SES, and HbA1c level were recorded at each patient's most recent visit between January and September 2003. RESULTS: Mean HbA1c level for the 455 patients was 7.6% +/- 1.4%; only 31% of patients failed to meet the therapeutic goal of < 8.0%. Multiple linear regression analysis identified female sex (P = .02), older age (P = .001), longer duration of diabetes (P < .001), injection therapy (P < .001), and lower SES (P = .001) as significantly associated with higher HbA1c level. After adjustment for SES, race/ethnicity was not a determinant of HbA1c level. CONCLUSIONS: Low SES had a greater association with poor metabolic control than did race/ethnicity, which was not associated with differences in HbA1c level after controlling for SES. Most children were able to attain glycemic targets at least as good as the Diabetes Control and Complications Trial recommendations in a large clinical practice.

Persistence of benefits of continuous subcutaneous insulin infusion in very young children with type 1 diabetes: a follow-up report.

OBJECTIVE: Use of continuous subcutaneous insulin infusion (CSII) has increased dramatically in recent years, and pump therapy has been shown to be a safe and effective alternative to multiple daily injections in adults and older pediatric patients with type 1 diabetes. Its use in very young children, however, has been limited, although this group might be expected to benefit the most from CSII. The objective of this study was to analyze the CSII efficacy and safety data in very young children with type 1 diabetes from our Diabetes Clinic database. METHODS: Glycosylated hemoglobin (HbA1c), severe hypoglycemia (SH), and ketoacidosis (DKA) in the year before CSII were compared with corresponding values during pump treatment in all children who started CSII before age 7. RESULTS: Sixty-five children (mean age: 4.5 y at CSII initiation; range: 1.4-6.9 years; 28 girls; 3 black, 1 Hispanic) were analyzed for >162 patient-years of follow-up. Mean HbA(1c) (7.4 +/- 1.0 prepump) decreased to 7.0 +/- 0.9 after 12 months of CSII and continued to improve even after 4 years on CSII. The rate of SH was reduced by 53% (from 78 to 37/100 patient-years). Children who received daytime care from paid caregivers (n = 26) experienced significant reductions in HbA1c and hypoglycemia frequency. There were no episodes of DKA requiring emergency treatment in the year before CSII and 4 episodes (4 per 100 patient-years) after transition to pump. CONCLUSIONS: CSII is a durable and effective means of optimizing glycemic control in very young patients with type 1 diabetes and may be superior to multiple daily injections in minimizing the risk of severe hypoglycemia in this age group. Employment of paid caregivers does not preclude safe and effective use of CSII.