The use of continuous subcutaneous insulin infusion (CSII) as the treatment of choice in children and adolescents with type 1 diabetes

Continuous subcutaneous insulin infusion (CSII) by external pumps is shown in several clinical trials to be a safe and effective treatment modality for patients with T1D. The present prospective observational study evaluated the efficacy and safety of CSII in children and adolescents treated in a routine clinical setting. 186 patients using CSII from 3 to 30 months were included in the analysis. A significant decrease of GlyHbA1c was observed after 3 months (p < 0.005) and was sustained throughout the study with a mean all over reduction of 0.7%. Events of ketoacidosis and severe hypoglycemia amounted to 0.027 and 0.014 per patient-year, respectively. Routine use of CSII in children and adolescents with T1D is effective in improving metabolic control and associated with a very low incidence of ketoacidosis or severe hypoglycemia.     

应用胰岛素泵治疗儿童及青少年1型糖尿病对糖代谢的影响

为观察应用胰岛素泵治疗儿童及青少年1型糖尿病(T1DM)对糖代谢的影响 ,随访10例胰岛素泵治疗的T1DM患儿 ,分别观察胰岛素泵治疗前、后6个月的糖化血红蛋白值(HbA1c)、胰岛素用量、严重低血糖及酮症酸中毒发生次数的变化情况。结果显示 ,胰岛素泵治疗6个月后HbA1c 显著下降 ,治疗前为8.97 %±1.69 %,治疗后为7.51 %±1.17 % (t=2.52 ,P<0.05) ;胰岛素用量无显著下降 ;未发生严重低血糖和酮症酸中毒。表明胰岛素泵治疗可有效控制血糖 ,明显降低HbA1c,减少低血糖及酮症酸中毒的发生 ,是儿童及青少年T1DM常规治疗的较好选择。     

The selection of children and adolescents for treatment with continuous subcutaneous insulin infusion (CSII)

Abstract:  Continuous subcutaneous insulin infusion (CSII) was first introduced as a mode of treatment for persons with type 1 diabetes mellitus (T1DM) in the late 1970s. Since that time, there have been many reports and reviews of this modality of treatment in adults and adolescents with diabetes and several reports of the use of this technology in the treatment of children with T1DM. Conflicting data have accumulated on the consistency of improvement in hemoglobin A1c (HbA1c) and in the frequency of complications, most significantly that of hypoglycemia. Some studies report the findings of controlled randomized studies, but many of these studies were conducted on small numbers of highly selected patients. Some studies are prospective but not randomized, where subjects pre-CSII serve as their own controls. Yet other studies are retrospective reviews of children and adolescents who have been treated with CSII. This paper reviews what has been learned about patient selection and outcomes of CSII treatment, with the goal of outlining steps in the selection and preparation of patients for CSII that will facilitate optimum outcome.     

Sociodemographic and psychosocial factors associated with continuous subcutaneous insulin infusion in adolescents with type 1 diabetes

Cortina S, Repaske DR, Hood KK. Sociodemographic and psychosocial factors associated with continuous subcutaneous insulin infusion in adolescents with type 1 diabetes. Objective: To examine the role of sociodemographic factors and psychosocial adjustment in continuous subcutaneous insulin infusion (CSII) use among adolescents with type 1 diabetes. Methods: A total of 150 adolescents with type 1 diabetes and their caregivers completed measures of general psychological functioning, diabetes functioning, and stressful life events. Blood glucose monitoring (BGM) frequency and glycemic control were also assessed. Logistic regression was used to determine associations between CSII use and sociodemograpic and psychosocial factors. Results: All logistic regression models were significant, indicating a large proportion of the variance in CSII use was associated with sociodemographic, diabetes‐specific and psychosocial variables. Final models showed higher frequency of BGM and having private insurance as significant correlates of CSII use. CSII use was also associated with adolescent and caregiver reports of sharing of responsibilities around diabetes management and negative affect regarding BGM. Conclusions: Adolescents currently prescribed CSII therapy evidenced key differences from their counterparts using multiple daily injections (MDI) in insurance status, diabetes management behavior, and family functioning related to diabetes. Efforts to understand the role of family factors in the maintenance of CSII therapy with clinical indicators of CSII use may inform treatment effectiveness.     

Continuous subcutaneous insulin infusion in the treatment of children and adolescents with type 1 diabetes mellitus

Continuous subcutaneous insulin infusion (CSII) with a portable insulin pump has been used for several years in the treatment of adult patients with diabetes mellitus (DM). This treatment, however, has rarely been utilised in children and adolescents. We studied the use of CSII in 16 children and adolescents with type 1 DM at Tampere and Kuopio University Hospitals between 1992 and 1997. The longest treatment periods are more than 4 years. The reasons for switching to CSII treatment and the goals achieved were evaluated. Glycaemic control before and during CSII treatment and the occurrence of hypoglycaemia and ketoacidosis were analysed. Compared with conventional insulin treatment, improved glycaemic control and a reduced frequency of hypoglycaemic events were achieved with CSII in those with particularly poor initial metabolic control (HbA1c >10.0%). The overall satisfaction with pump therapy was high in both patients and their families. According to our experience, CSII may be of benefit, especially in young infants with type 1 DM, but also in affected adolescents with unacceptable glycaemic control.     

Risk and benefits of continuous subcutaneous insulin infusion (CSII) treatment in school children and adolescents

Abstract:  Continuous subcutaneous insulin infusion (CSII) therapy with technically advanced modern insulin pumps is a treatment option enabling patients and multidisciplinary diabetes teams to achieve all current goals for the treatment of children and adolescents with type 1 diabetes mellitus (T1DM): near-normoglycemia, low rate of hypoglycemia, preventing or delaying long-term complications and increasing quality of life. Clinical studies demonstrate that CSII therapy reduces glycosylated hemoglobin A1c (HbA1c) with a concomitant decrease in the rate of hypoglycemic events, without excessive weight gain and with an increase of patients' treatment satisfaction in all pediatric age groups. With the development of continuous glucose sensing coupled with an insulin pump, patients can hope for an ever-increasing technological support for the management of insulin therapy in the foreseeable future.     

Benefits of continuous subcutaneous insulin infusion in children with type 1 diabetes

OBJECTIVE: To examine the effect of continuous subcutaneous insulin infusion (CSII) therapy on parameters affecting long-term outcome in type 1 diabetes.Study design Height, weight, body mass index, insulin dose, glycosylated hemoglobin (HbA(1C)), and blood glucose data from home meter downloads were collected prospectively for analysis in 51 children (age, 10.7+/-3.1 years, mean+/-SD) throughout the 12 months before and after introducing CSII. RESULTS: Before pump initiation, HbA(1C) was relatively stable, but it fell to 7.7+/-0.2% (P<.001) within 3 months of CSII and remained decreased (7.9+/-0.1%) at 12 months (P<.01). In contrast, weight standard deviation score increased before CSII (from 0.50+/-0.13 to 0.60+/-0.13, P<.05), but remained unchanged (0.61+/-0.11) in the year thereafter. Although severe hypoglycemia (<50 mg/dL) was reduced in the entire cohort, HbA(1C) improved primarily in young children and teenagers. Comparison of glycemic responders (HbA(1C) <7.5, or a decrease >1% on CSII, n=23) with nonresponders demonstrated no differences with respect to gender, socioeconomic status, weight standard deviation score, body mass index, initial HbA(1C), frequency of hypoglycemia, or number of education visits before CSII. CONCLUSION: Continuous subcutaneous insulin infusion is effective in lowering HbA(1C) and the occurrence of severe nocturnal hypoglycemia without excessive weight gain in most children with type 1 diabetes. HbA(1C) response to CSII is poorer in preadolescents than in young children or teenagers.     

Transition from multiple daily injections to continuous subcutaneous insulin infusion in type 1 diabetes mellitus

OBJECTIVE: To review our experience with insulin dosing during the conversion from multiple daily injections to continuous subcutaneous insulin infusion (CSII) for children and adolescents with type 1 diabetes mellitus. STUDY DESIGN: The charts of 65 children who started CSII from January 1998 to April 2000 were reviewed. Data regarding insulin dose and hemoglobin A1c levels were collected from the prepump visit and first (at 1 to 2 months) and second (at 3 to 6 months) visits after being placed on pump therapy. RESULTS: Pubertal patients had a decrease in total insulin dose taking CSII; prepubertal patients had little change (-18 +/- 3.5% vs -1.7 +/- 5%, P =.01). On CSII, the basal insulin dose comprised 40% to 45% of total insulin in both prepubertal and pubertal patients. Maximal basal rate in prepubertal patients occurred from 9 PM to 12 AM and in pubertal patients from 3 AM to 9 AM and from 9 PM to 12 AM. CONCLUSION: Guidelines established for CSII dosing in adults do not necessarily apply to children. The total daily insulin dose needs to be decreased in pubertal patients but may remain unchanged in prepubertal patients. The basal rate comprises 40% to 45% of the total daily insulin dose, and the timing of maximum basal rates is likely to occur in the late evening hours in prepubertal children.     

1型糖尿病患儿皮下连续输注胰岛素疗效观察

目的　观察胰岛素泵连续皮下输注胰岛素 (CSII)与皮下多次注射胰岛素 (MSII)治疗 1型糖尿病(T1DM)疗效。方法　利用CSII控制血糖为一组。MSII控制血糖分为两组 ,A组予MSII合用二甲双胍 ;B组单用MSII;并测定 3餐前后及凌晨 2∶0 0时血糖。结果　 3组血糖均可控制达标。CSII平均达标天数、胰岛素用量明显短于MSII组 ,A组达标天数也短于B组。结论　CSII控制血糖 ,达标时间短 ,血糖平稳下降 ,能够抑制黎明现象 ,低血糖及高血糖发生率低 ,适合T1DM治疗。     

Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion

OBJECTIVE: To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS). DESIGN: Open randomized crossover comparing 3(1/2) months of multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII). SETTING: Tertiary care, university-affiliated medical center.Patients Twenty-three children and adolescents with type 1 diabetes mellitus. INTERVENTIONS: The CGMS was applied for 72 hours after 1 month and at the end of each study arm. MAIN OUTCOME MEASURES: Hemoglobin A(1c) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm. RESULTS: The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0% [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01 and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03 and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03), but 24-hour duration and area under the curve for hyperglycemia were similar. Compared with the first CGMS reading in each arm, the second had a longer mean duration of postprandial within-target glucose levels (P =.04), tendency for lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia (P =.04). CONCLUSIONS: Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as a smaller area under the curve for hypoglycemia. Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia.     

Continuous subcutaneous insulin infusion pump treatment in children with type 1 diabetes mellitus

Data were reviewed from 73 consecutive medical charts of children and adolescents with type 1 diabetes mellitus using insulin pumps for more than 6 months at The Hospital for Sick Children, Toronto, Canada. Statistically significant differences in HbA1c (-0.8%), body mass index (+1.45 kg/m2) and total daily dose of insulin (-0.23 U/kg/day) were found between the start of pump use and evaluation 6-30 months later. There was a close correlation between the HbA1c before and after 6-30 months of pump therapy.     

A cross-sectional international survey of continuous subcutaneous insulin infusion in 377 children and adolescents with type 1 diabetes mellitus from 10 countries

OBJECTIVE: To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90-d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel. METHODS: Data of patients (1-18 yr) treated with CSII in 23 centers from nine European countries and Israel were recorded with the encapture software (PEC International, Frankfurt, Germany). The number of patients who participated was 377 (48% female; mean diabetes duration +/- SD: 6.8 +/- 3.7 yr; age: 12.9 +/- 3.8 yr, preschool n = 33; prepubertal n = 95; adolescent n = 249; CSII duration: 1.6 +/- 1.2 yr; local HbA1c: 8.1 +/- 1.2%). RESULTS: The total insulin dose was lower than previously reported for injection therapy (0.79 +/- 0.20 U/kg/d). Covariance coefficient of daily total insulin was high in all age groups (adolescents 19 +/- 9%, prepubertal 18 +/- 8 and preschool 17 +/- 8). The distribution of basal insulin infusion rates over 24 hr (48 +/- 12% of total dose) varied significantly between centers and age groups. The number of boluses per day (7 +/- 3) was not significantly different between the age groups (average daily bolus amount: 0.42 +/- 0.16 U/kg). The rate of severe hypoglycemia (coma/convulsions) was 12.4 episodes per 100 patient-years and the number of diabetes-related hospital days was 124 per 100 patient-years. DISCUSSION: Pediatric CSII patients show a high variability in their insulin therapy. This relates both to age-dependent differences in the distribution of basal insulin as to the age-independent day-to-day variation in prandial insulin.     

Age-dependent basal insulin patterns in children with type 1 diabetes treated with continuous subcutaneous insulin infusion

Aims: Identifying age-dependent basal rates in type 1 diabetic children treated with continuous subcutaneous insulin infusion (CSII).
Methods: CSII-treated children with type 1 diabetes exhibiting insulin requirement > 0.5U/kg and glycated haemoglobin (HbA1c) < 8%. The study population was composed of 198 Caucasian children (111 girls) with mean age of 9.8 ± 3.8 years, mean duration of diabetes of 4.3 ± 3.1 years and mean HbA1c value of 6.7 ± 0.7%. Data were evaluated for four age groups (0–6; 6–9; 9–12, 12–18 years). Basal rates records were downloaded from pump memory. HbA1c, weight, height were measured at scheduled visits.
Results: Significant differences in the average hourly basal rate between groups were observed: I gr. 0.14 versus II gr. 0.24 versus III gr. 0.39 versus IV gr. 0.72 units/h; p < 0.0001. The average hourly basal rate correlated with age, body weight, BMI, diabetes duration and total insulin daily dose. Insulin peaks were observed for: I gr. – before midnight, II gr. – before midnight and in the early morning, gr. III and IV – in the early morning.
Conclusion: Basal insulin infusion rate profiles in well-controlled paediatric patients on CSII reflect the age-dependent amount of basal insulin (20–40%) and affect circadian distribution of insulin needs.     

Insulin glulisine for continuous subcutaneous insulin infusion in pediatric type 1 diabetes

We evaluated the efficacy and safety of insulin glulisine (GLU) used for continuous s.c. insulin infusion (CSII) in 20 children with type 1 diabetes after 1 year of GLU treatment. There were no significant differences in mean plasma glucose before breakfast and before dinner between before and after using GLU, but the levels after breakfast and after dinner significantly improved, from 192.5 ± 31.7 to 162.0 ± 27.3 mg/dL for breakfast, and from 191.1 ± 33.3 to 161.1 ± 24.5 mg/dL for dinner (P < 0.01). Mean hemoglobin A1c significantly decreased (from 8.0 ± 0.8 to 7.7 ± 0.8%, P < 0.05), and the mean frequency of hypoglycemia significantly reduced after using GLU (from 8.3 ± 4.9 to 6.0 ± 3.4/month, P < 0.05). In conclusion, the use of GLU rather than other rapid‐acting analogues for CSII might be an effective treatment option in children with type 1 diabetes.     

Initial insulin therapy in children and adolescents with type 1 diabetes mellitus

Weitzel D, Pfeffer U, Dost A, Herbst A, Knerr I, Holl R. Initial insulin therapy in children and adolescents with type 1 diabetes mellitus. Objective: The aim of the study was to define parameters that influence the initial insulin dosage in young subjects with type 1 diabetes regarding the amount of daily insulin, the ratios of basal and prandial insulin, and the insulin/carbohydrate ratios. Study design: We used a computer‐based registry (with prospectively collected data) in Germany and Austria, a software for the management and data documentation of diabetic patients (DPV), to analyze the initial insulin therapy in 2247 children with newly diagnosed type 1 diabetes to identify factors that influence diabetes therapy within the first 10 d. Results: For both genders, glucosylated hemoglobin A1c (HbA1c), blood pH at diabetes onset, and pubertal status are the major factors determining the initial insulin dosage calculated as the amount of daily insulin per kilogram body weight (kg), the basal and prandial insulin dose per kilogram, and day and the insulin/carbohydrate ratios for meals. The frequency of hypoglycemia correlated with increasing quotient of applied to calculated insulin dosage. Conclusion: The predictive factors of insulin requirement may exert beneficial effects on the assessment and adjustment of insulin therapy in young diabetic subjects at disease onset. On the basis of a multiple, linear regression, we suggest a formula to calculate the initial insulin therapy.     

Long-acting insulin analogues (insulin glargine or determir) and continuous subcutaneous insulin infusion in the treatment of type 1 diabetes mellitus in the paediatric population

Despite many improvements in the treatment of type 1 diabetes mellitus (DM1), the non-physiological time-action profiles of conventional insulins remain a significant obstacle. In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular and NPH insulin. The rapid insulin analogs used as prandial and the long-acting insulin analogs used as basal simulate physiological insulin profiles more closely than the older conventional insulins. The efficacy of insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in DM1 has been established in pediatric patients. Insulin pumps have improved since they were first introduced. CSII therapy may provide an effective alternative for selected pediatric patients with DM1. In most studies at pediatric age, CSII therapy resulted in a improvement in HbA1c, a decreased rate of hypoglycemia without an abnormal increase in BMI, and without adversely affecting psychosocial outcomes in children and adolescents with DM1.     

Life with continuous subcutaneous insulin infusion (CSII) therapy: child and parental perspectives and predictors of metabolic control

Abstract: Objective: The purpose of this study was twofold (i): to evaluate metabolic control in patients receiving CSII therapy in a routine pediatric diabetes clinic by describing reasons for initiating therapy and daily management issues, including needle fear; and (ii) to assess the change in parental involvement and anxiety once their child initiated CSII therapy. Research design and methods: The study included 52 subjects (aged 7.6–23.6 yr) from a general pediatric diabetes clinic. Management issues were defined as diet, exercise, home blood glucose monitoring (HBGM) frequency, and self/staff assessment of needle fear. Characteristics were analyzed both according to a 0.5% change in HbA1c status (decreased vs. stable vs. increased) compared with pre‐CSII therapy, and final HbA1c achieved (≤ 8.1 vs. > 8.1%). Results: The primary recommendation source for CSII use was most often the physician/diabetes team (48.1%), followed by a combination of the former with a personal referral source (32.7%). The most common reason (71.2%) for CSII initiation was a combination of wanting to achieve better metabolic control, dislike of insulin injections, and/or increased flexibility in daily living. Over one‐quarter (26.9%) of subjects were identified as being needle‐fearful, and this characteristic was predictive of final metabolic control (3/25 subjects ≤ 8.1% vs. 11/27 subjects > 8.1%, p = 0.03). On CSII therapy, dietary carbohydrate consistency was highly variable, and most subjects (65.3%) exclusively used an insulin to carbohydrate ratio for insulin bolus dosage calculation. The most common adjustment strategy (63.5%) for exercise was a combination of decreasing the insulin basal rate, disconnecting the pump, and/or eating extra carbohydrates. For the total cohort, the frequency of HBGM significantly increased on CSII therapy (4.31–4.85 tests/day, p = 0.02). Females did not have a significant change in HBGM frequency, while the youngest subjects had the highest HBGM frequency. Parental involvement and anxiety primarily stayed the same or decreased, regardless of the child's age (≤ 18 vs. > 18 yr) or metabolic control. Conclusions: Analyses of the various characteristics identified only needle fearfulness as being predictive of poor metabolic control. Interestingly, poor control with CSII therapy did not result in a significant increase in parental involvement and/or anxiety.     

Cost-effectiveness of continuous subcutaneous insulin infusion (CSII) in children: illusion or delusion?

Abstract:  Cost-effectiveness of continuous subcutaneous insulin infusion (CSII) in children is reviewed in the context of possible improvement of percentage of hemoglobin A1c (HbA1c) and of other clinical benefits over multiple daily injections (MDI). Cost-effectiveness depends on clinical efficacy but reported clinical efficacy parameters may overlook definite benefits perceived by children and parents using CSII. There are few detailed reports on cost comparisons between CSII and MDI in adults, even less in children or adolescents. Review of direct extra costs for CSII over conventional treatment, including MDI, suggest that these may double, 5000–6000 EUR vs. 3000 EUR per patient year. An example is given of how to calculate direct cost differences, showing local differences. Randomized comparisons between CSII and MDI in childhood and adolescence show few marked clinical effects, but non-randomized comparisons favor CSII. Quality of life parameters fall short in any such comparison in children and adolescents alike. The reasons for the apparent discrepancy between non-randomized childhood studies and the randomized prospective ones are given. There is a dire need for better parameters to assess the well-being of diabetic children treated by CSII or MDI. Only then is it warranted to estimate the cost-effectiveness of CSII vs. MDI in childhood and adolescence.