Sustained metabolic control and low rates of severe hypoglycaemic episodes in preschool diabetic children treated with continuous subcutaneous insulin infusion

AIM: To evaluate the safety and efficacy of continuous subcutaneous insulin infusion (CSII) in children under 7 years of age. METHODS: One hundred and ten children, aged 0.9-7 years, who had received CSII therapy for at least 6 months, were studied for 237 patient-years by a retrospective chart review. Charts were reviewed for glycosylated hemoglobin (HbA1c), severe hypoglycaemia (SH), ketoacidosis (DKA), height, weight and insulin requirement. In 69 cases (children aged 1.6-7 years) CSII was administered after at least 3 months of insulin therapy with pens. In this group, data from the year from before CSII administration were compared with values recorded during 1 year of CSII treatment. RESULTS: Mean HbA1c decreased from 7.8 +/- 0.9 before CSII to 7.5 +/- 1.0 after 6 and 12 months of pump therapy (p = 0.04). In the whole group, the mean HbA1c after 6 months of CSII was 7.5 +/- 1.0 and remained unchanged for up to 4 years of follow-up. Some episodes of SH--4.2 per 100 patient-years, and DKA--5.7 per 100 patient-years were recorded. No increase in BMI z-score occurred. CONCLUSIONS: In the youngest children, CSII therapy lowers HbA1c values and provides sustained metabolic control without increases in hypoglycaemia or ketoacidosis episodes.     

Parental fear of hypoglycemia: young children treated with continuous subcutaneous insulin infusion

BACKGROUND: The objective of this study was to examine the association between parental fear of hypoglycemia and average daily blood glucose control of young children with type 1 diabetes receiving continuous subcutaneous insulin infusion (CSII). We hypothesized that parental fear of hypoglycemia would correlate positively with children's average daily blood glucose control. METHODS: Twenty-four families of children with type 1 diabetes who were receiving CSII were recruited from a pediatric hospital. Children had a mean age of 5.7 +/- 1.8 yr (range 2-8 yr) and were evenly split on gender. Parents completed a modified version of the Hypoglycemia Fear Survey - Parents of Young Children (HFS-PYC), a measure designed to assess fear and avoidance behaviors associated with hypoglycemia. Blood glucose was assessed for the 2 wk following completion of the HFS-PYC using a standard home blood glucose meter. RESULTS: Parents of young children obtained a mean total HFS-PYC score of 81 +/- 14.1 (possible range 26-130), suggesting a moderate level of fear. The HFS-PYC was found to be internally consistent and had good test-retest reliability. For parents of young children receiving CSII, fear of hypoglycemia correlated positively with children's mean daily blood glucose levels (r = 0.41, p = 0.05). CONCLUSIONS: Parents of young children with type 1 diabetes who are receiving CSII report significant fear of hypoglycemia. Parental fear of hypoglycemia may be a barrier to prevent optimal glycemic control.     

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.     

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.     

Insulin allergy desensitization with simultaneous intravenous insulin and continuous subcutaneous insulin infusion

Abstract:  Persistent 'IgE-mediated' insulin allergy (type 1 allergy) (1) , unresponsive to changes in insulin type or the use of antihistamines, necessitates desensitization. A number of case reports (2–7) and recent reviews (8, 9) have demonstrated that desensitization can be achieved with continuous subcutaneous insulin infusion (CSII), but in type 1 diabetes mellitus, the need to slowly increase insulin dose from sub-therapeutic levels competes with the need for glycaemic control and suppression of ketogenesis. Tolerance to intravenous (IV) insulin despite persistent life-threatening allergic reactions to subcutaneous human insulin (bolus or CSII) has been recently described (10) . We present the cases of two unrelated 9-yr-old boys with persistent generalized urticarial reactions to subcutaneous injections of all available insulin types, despite treatment with oral antihistamines. After failed rapid desensitization to insulin delivered by either subcutaneous injection or CSII, the concurrent use of IV insulin allowed desensitization to CSII over 5–6 d.     

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.     

Endotoxin stimulated nitroblue-tetrazolium (NBT)-test in patients with hypoparathyroidism,pseudohypoparathyroidism and other forms of hypocalcemia

Endotoxin-stimulated NBT-tests were carried out in 15 patients with hypocalcemia of varying etiology and in 14 normocalcemic children free of infection. In the control group the formazan cell percentage (FCP) was 73.8±1.6% (range 63% to 83%). In 5 patients with hypoparathyroidism or pseudohypoparathyroidism the FCP before treatment was lower than normal. Vitamin D₃ therapy produced a rapid increase of serum calcium but normalisation of NBT-test was only achieved after a latent period of one or more months. Patients with hypocalcemic rickets and children with an acute relapse of the nephrotic syndrome also showed abnormal results. The clinical significance of the NBT-test in hypocalcemic conditions is discussed.     

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.     

Survival and long-term outcomes in children with hepatoblastoma treated with continuous infusion of cisplatin and doxorubicin

Despite high survival rates, many survivors of hepatoblastoma develop late effects including ototoxicity and cardiomyopathy. With the goal of minimizing long-term toxicities, our institution treated hepatoblastoma with continuous infusion of doxorubicin and cisplatinum (PLADO), rather than short infusion or bolus dosing as used in other treatment protocols. This retrospective cohort study includes consecutive patients diagnosed between 1985 and 2007. Patients were scheduled for treatment with 6 cycles of continuous infusion of PLADO with resection after the third or fourth cycle. Audiograms and echocardiograms were obtained at baseline, after every 2 chemotherapy cycles and yearly after the completion of therapy. Fifty-five patients were treated (34 localized; 21 metastatic). Fifty-one patients received at least 1 cycle of PLADO. Median follow-up was 7.0 years (range, 0.11 to 17.8 y). Event-free and overall survival for these 51 patients were 72.2% (standard error 6.3%) and 75.6% (standard error 6.2%) respectively. Of the 38 survivors treated with cisplatin who had an audiogram during follow-up, 4 (11%) demonstrated severe (Brock grade 3/4) and 13 (34%) mild (Brock grade 1/2) hearing loss. At a median of 10.0 years (range, 5.0 to 13.0 y) after therapy, 2 of 41 (5%) patients who were still alive had evidence of cardiac dysfunction. Overall, continuous infusion of PLADO therapy resulted in survival rates consistent with those observed in intergroup studies, but rates of chronic cardiac and ototoxicity did not differ sufficiently from those observed after shorter infusion of PLADO therapy to warrant the use of continuous infusions.     

Primary infantile hypomagnesaemia: outcome after 21 years and treatment with continuous nocturnal nasogastric magnesium infusion

Primary infantile hypomagnesaemia is an infrequent cause of neonatal hypocalcaemic seizures but one that responds well to magnesium supplementation. We describe a 22-year-old male, first reported at 4 months of age, who is currently free of neurological deficit but has suffered from intermittent hypomagnesaemic tetany and chronic diarrhoea due to large oral magnesium supplements. Hypothesizing that modest hypercalcaemia might prevent the tetany, we conducted a trial of 5 μg/day 1,25(OH)₂D₃ over 5 days. Despite the resultant increase in calcium, he developed tetany with the reduction of magnesium intake and decline of serum magnesium from 0.63 to 0.39 mmol/l (normal >0.65 mmol/l). After 1,25(OH)₂D₃ was stopped and the parenteral magnesium injections suspended, 33% of his usual oral supplement was given instead by continuous nasogastric infusion and serum magnesium rose to 0.60 mmol/l. This regimen was better tolerated because of decreased gastrointestinal side-effects and freedom from parenteral injections. We observed that 1,25(OH)₂D₃ supplements do not promote magnesium retention nor does the resultant hypercalcaemia prevent hypomagnesaemic tetany. Conclusion Continuous nocturnal nasogastric infusion may be considered in lieu of parenteral therapy in primary infantile hypomagnesaemia. Received: 22 February 1999 and in revised forms: 15 April 1999 and 21 June 1999 / Accepted: 21 June 1999     

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.     

The impact of continuous subcutaneous insulin infusion on health-related quality of life in children and adolescents with type 1 diabetes

AIM: To study the impact of continuous subcutaneous insulin infusion (CSII) therapy on health-related quality of life in children and adolescents with type 1 diabetes. METHODS: 31 children and adolescents with poorly regulated type 1 diabetes (mean HbA1c 10.4%, SD 1.8), mean age 14.4 (1.5) y (range 9.7-17.1) and mean diabetes duration of 6.8 (3.2) y (range 1.3-14.6) were consecutively assigned to CSII therapy. Data for generic (CHQ-CF87) and diabetes-specific quality of life (DQOL) were obtained before initiating pump therapy and twice during 15 mo of treatment. HbA1c, BMI and episodes of severe hypoglycaemia and ketoacidosis were recorded over 15 mo prior to and 15 mo during pump therapy. RESULTS: Analysis showed improvements on the family activity scale (p=0.041) and change in health score (p=0.042) (CHQ-CF87). Mean HbA1c decreased from 10.4% (1.8) to 9.0% (0.9) after 3 mo, increasing to 9.6% (1.2) after 15 mo. The number of overweight and obese children increased from 4 and 2 before CSII, to 6 and 3 after 15 mo (IOTF criteria). There was a reduction in severe hypoglycaemia episodes from 43.8 to 5.2 per 100 patient years, but no change in ketoacidosis episodes. CONCLUSION: The degree of limitation experienced by families due to adolescents' general health and well-being was significantly reduced. Expected improvement in metabolic control and frequency of severe hypoglycaemia was observed.     

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。     

Basal rates and circadian profiles in continuous subcutaneous insulin infusion (CSII) differ for preschool children, prepubertal children, adolescents and young adults

Bachran R, Beyer P, Klinkert C, Heidtmann B, Rosenbauer J, Holl RW; for the German/Austrian DPV Initiative, the German Pediatric CSII Working Group and the BMBF Competence Network Diabetes. Basal rates and circadian profiles in continuous subcutaneous insulin infusion (CSII) differ for preschool children, prepubertal children, adolescents and young adults. Objective: Initiation of continuous subcutaneous insulin therapy (CSII) requires an appropriate basal rate profile. Different approaches exist; however, there is a lack of evidence‐based recommendations, especially in young children. Study design: In this large multicenter survey, 5941 CSII patients from the German/Austrian prospective documentation system (DPV) were analyzed. Patients were divided into four age groups: <6 yr (n = 837), 6 to <12 yr (n = 1739), 12 to <18 yr (n = 2985) and 18 to <25 yr (n = 380). Basal insulin requirement and diurnal distribution were evaluated based on the most recent documentation for each patient. Results: Basal insulin requirement differed significantly between the four age groups (<6: 0.25 ± 0.12; 6 to <12: 0.33 ± 0.12; 12 to <18: 0.43 ± 0.15; 18 to <25: 0.35 ± 0.13 U/kg; p < 0.001). Circadian insulin profiles were markedly different between the younger and older age groups. In addition to age, longer diabetes duration, female gender, higher HbA1c and lower body mass index standard deviation score (BMI‐SDS) were related to higher basal insulin requirement per kilogram of body weight. Conclusions: Age of the patient is the primary factor that influences both total daily requirement and circadian distribution of basal insulin in CSII. Experience from a large database may therefore facilitate the initiation of pump therapy in pediatric patients.     

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.