A 2-yr national population study of pediatric ketoacidosis in Sweden: predisposing conditions and insulin pump use

Abstract:  The aim was to investigate triggering factors and insulin pump usage (continuous subcutaneous insulin infusion, CSII) at diabetic ketoacidosis (DKA). Data from 1999 and 2000 were collected retrospectively from Sweden. In 1999 and 2000, 7.4 and 11.0%, respectively, of children with diabetes used CSII. One hundred and forty-two episodes of DKA (pH < 7.30) were identified in 115 children (DKA at onset not included). Their hemoglobin A1c (HbA1c) was 10.1 ± 2.0%, age 14.6 ± 3.1 yr (range 1.5–19.9 yr), and diabetes duration 6.6 ± 3.5 yr (range 0.4–17.7 yr). Fourteen persons (seven girls) had more than one episode of DKA. Reported causes of DKA were missed insulin doses (48.6%), gastroenteritis (14.1%), technical pump problems (12.7%), infection (13.4%), social problems (1.4%), unknown (5.6%), and not stated (4.2%). Alcohol was involved in eight episodes and drugs in one. Thirty of 115 patients (19 girls) used insulin pumps. The overall DKA incidence was 1.4/100 patient years in 1999 and 1.7/100 patient years in 2000. For insulin pump users, the DKA incidence was 3.2/100 patient years in 1999 and 3.6/100 patient years in 2000. HbA1c at DKA admission was lower for CSII users than patients who used injections (9.1 ± 1.5 vs. 10.8 ± 2.2%, p < 0.01), but pH and age did not differ. CSII had been used for 6 months (median) before the DKA episode. In conclusion, the DKA frequency in CSII users was approximately twice that of patients who used injections. Seventy-seven percent of the episodes occurred within 1 yr after CSII start. The high number of events reported to be caused by gastroenteritis is alarming because this may reflect a misinterpretation of DKA symptoms.     

胰岛素泵治疗儿童1型糖尿病酮症酸中毒32例临床分析

目的 观察胰岛素泵持续皮下注射胰岛素对儿童1型糖尿病酮症酸中毒(DKA)的疗效.方法 将2005-2008年收治的1型DKA患儿64例分为治疗组32例和对照组32例.治疗组予胰岛素泵治疗,对照组予小剂量胰岛素持续静脉滴注治疗.比较两组患儿血精变化、DKA纠正时间及住院时间.结果 治疗组血糖下降相对稳定,酸中毒纠正时间治疗组[(16.91±4.223)h]短于对照组[(23.31±3.797)h](P<0.001),且无反复.治疗过程中治疗组未出现低血糖,对照组出现1例.住院时间治疗组[(15.63±2.458)d]短于对照组[(20.88±3.348)d](P<0.001).结论 胰岛素泵持续皮下注射胰岛索治疗儿童1型糖尿病酮症酸中毒安全有效.     

Current practice of insulin pump therapy in children and adolescents – the Hannover recipe

Abstract:  Increasing evidence points to the importance of achieving low blood glucose variability and also a low hemoglobin A1c (HbA1c) to prevent diabetic late complications. Continuous subcutaneous insulin infusion (CSII) is associated with lower blood glucose variability in children. Frequent indications for starting CSII in youth are recurrent hypoglycemia, need for increased flexibility, poor glycemic control, dawn phenomenon, or needle phobia. At our center, about one-third of all patients across all age groups are currently on CSII. Although the average glycemic control is not very different from those on multiple daily injections, fewer patients are seen in the segment of very high and very low HbA1c with CSII. Across centers, the 'recipes' tailoring CSII treatment to individual patients and cultures are based more on experience than on evidence. However, several typical pediatric features have been identified. Patterns of the hourly basal rate and prandial insulin requirements vary with age. While many adolescents have increased requirements at dawn and dusk, young children show increasing needs in the second half of the day. Low insulin requirements, particularly in neonates, may need insulin dilution. The selection of catheters and needles has to be appropriate for the age. The opportunity to have an electronic memory read-out of all entries and alarms offers new possibilities of therapeutic monitoring, particularly in those youth not keeping good logbooks. This feature can be helpful, if a trustful relationship between the diabetes team and the family is established.     

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.     

Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population‐based study

Blasetti A, Di Giulio C, Tocco AM, Verrotti A, Tumini S, Chiarelli F, Altobelli E. Variables associated with severe hypoglycemia in children and adolescents with type 1 diabetes: a population‐based study. Objective: Hypoglycemia remains a central problem in the management of type 1 diabetes mellitus (T1DM) and limits the achievement of good or normal glycemic control. The Diabetes Control and Complication Trial showed that intensive treatment of T1DM increased the risk of severe hypoglycemia (SH) when compared to conventional therapy. The aim of our study was to determine the incidence of SH and associated variables in a population of children and adolescents with T1DM. Research design and methods: We performed a 7.5‐yr prospective study enrolling 195 patients aged 13.9 ± 6.6 yr. The study was carried out by referring to the T1DM population‐based register in the Abruzzo region of Italy. The incidence of SH, defined as blood glucose levels <50 mg/dL (<2.77 mmol/L) associated with altered states of consciousness (including confusional state, seizures, and coma) was recorded. Glycated hemoglobin (HbA1c) percentage, insulin dose, insulin regimen, time since diagnosis, and age at onset were also recorded. Results: One hundred and thirty‐three severe hypoglycemic events occurred during the study period; the overall incidence was 9.4 episodes per 100 patient‐years. Significant predictors of hypoglycemia were diabetes duration >10 yr (p = 0.01), basal/bolus insulin ratio (ratio of daily basal insulin units to daily bolus insulin units) >0.8 (p = 0.01). No relationship was found between hypoglycemic episodes and HbA1c levels, daily insulin requirements, or insulin regimen. Conclusions: In these patients, a relatively low incidence of SH was recorded, without pronounced association with lower HbA1c or multiple daily injection insulin therapy. SH seems to be mainly related to management of diabetes. We believe that the main path to SH prevention is through patient and family education in the management of T1DM.     

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.     

Pancreatic enzyme elevations in children with diabetic ketoacidosis

The incidence of pancreatic enzyme elevations in children with diabetic ketoacidosis (DKA) compared with children with newly diagnosed diabetes without DKA was assessed in a prospective study. Pancreatic enzyme elevations, particularly hyperlipasemia, are common but not associated with significant symptomatology. Acute pancreatitis was diagnosed in 2% of children with DKA.     

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.     

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.     

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.     

A randomized, controlled study of insulin pump therapy in diabetic preschoolers

OBJECTIVE: To compare glycemic control, safety, and parental satisfaction in preschool-aged diabetic children randomized to treatment either with continuous subcutaneous insulin infusion (CSII) or intensive insulin injection therapy. STUDY DESIGN: This clinical trial enrolled 42 patients <5 years of age who had been diagnosed with diabetes for at least 12 months. Children were randomly assigned to CSII (n = 21) or intensive insulin injection therapy (n = 21). Hemoglobin A1c (HbA1c) level was measured at baseline, 3, and 6 months. Secondary outcomes included severe hypoglycemic events, meter-detected hypoglycemia, blood sugar variability, body mass index (BMI), and satisfaction with therapy. RESULTS: Thirty-seven patients completed 6 months of therapy. There was a significant decrease in HbA1c during the study period for both groups (from 8.9% +/- 0.6% to 8.6% +/- 0.6% at 3- and 6-month visits). At 3 months, children using pumps had a significantly lower HbA1c than the injection group (8.4% vs 8.8%); however, by 6 months the two groups were similar (8.5% vs 8.7%). No differences in pre-meal blood sugar variabilities were seen between groups. Children on pumps had increases in the number of meter-detected episodes of hypoglycemia. Pump therapy was safe and well tolerated. No episodes of ketoacidosis occurred in either group, whereas one hypoglycemic seizure occurred in each group. Parents reported satisfaction with CSII, with 95% of families continuing on CSII beyond the 6-month study period. CONCLUSION: Pump therapy in preschool-aged children was not associated with clinically significant differences in glycemic control as compared with intensive injection therapy. The rationale for initiating CSII in this age group should be based on patient selection and lifestyle preference.     

Prevalence of intentional under- and overdosing of insulin in children and adolescents with type 1 diabetes

Schober E, Wagner G, Berger G, Gerber D, Mengl M, Sonnenstatter S, Barrientos I, Rami B, Karwautz A, Fritsch M, on behalf of the Austrian Diabetic Incidence Study Group. Prevalence of intentional under‐ and overdosing of insulin in children and adolescents with type 1 diabetes. Objective: The aim of this study was to evaluate the prevalence of insulin under‐ and overdosing in paediatric patients. Research design and methods: Cross‐sectional study including 241 patients (age 14.0 + 2.7 yr, 42.5% males) with type 1 diabetes from 21 diabetic outpatient clinics. Haemoglobin A1c (HbA1c), height, and weight were available from clinical records. Patients were interviewed with the Diabetes Self‐Management Profile (DSMP) interview. T test, U test, and chi‐squared test were used for comparison. Results: On the basis of the DSMP, 103 (42.7%) patients (group A) showed adherence to the therapeutic insulin regimen, while 71 (29.5%) patients (group B) confessed intentional over and/or under‐dosing of insulin. Sixty‐seven (27.8%) adolescents (group C) reported management problems leading to unintended inappropriate insulin dosages. In group B, 55 (22.8%) injected higher insulin doses and 58 (24.1%) omitted insulin. Patients of group B compared to group A were older 15.0 (±2.5) vs. 14.0 (±2.5) yr (p < 0.01), older at onset 9.5 (±3.6) vs. 8.3 (±3.8) yr (p = 0.05), were more often girls (69 vs. 45.6%), had a higher actual HbA1c (8.7 ± 1.7 vs. 7.8 ± 1.2%), and a higher average HbA1c in the previous year (8.3 ± 1.6 vs. 7.9 ± 1.2%) (p < 0.01). No significant differences could be found between group A and group C. Conclusion: Intentional overdosing of insulin is almost as prevalent in children and adolescents as insulin omission. Females are more at risk.     

Fulfilling the promise of insulin pump therapy in childhood diabetes

Abstract:  Although insulin pump or continuous subcutaneous insulin infusion (CSII) treatment was first introduced more than 25 yr ago, very few children and adolescents with type 1 diabetes mellitus (T1DM) utilized this therapy until recently. In this paper, we review many of the early triumphs, as well as a number of unexpected obstacles that were encountered in applying CSII in the treatment of T1DM. Nevertheless, the greater urgency to obtain optimal control of diabetes following the Diabetes Control and Complications Trial (DCCT), the introduction of rapid-acting insulin analogs and improvements in pump technology have led to a sharp increase in the use of this therapy in youth with T1DM and, generally, favorable outcomes. Moreover, the recent introduction of continuous glucose monitoring systems (CGMSs) offers the prospect of finally realizing the full potential of insulin pump therapy to normalize hemoglobin A1c (HbAlc) levels with minimal risk of hypoglycemia.     

Emerging evidence for the use of insulin pump therapy in infants, toddlers, and preschool-aged children with type 1 diabetes

Abstract:  Insulin pump therapy has, within the last 10 years, emerged as an increasingly popular modality of treatment to achieve intensive glycemic targets in type 1 diabetes (T1D). The evidence for the benefits of pump therapy has been demonstrated in adults and adolescents; however, until recently there has been a paucity of studies examining the efficacy and safety in pump therapy in very young children. The purpose of this article is to discuss the rationale for insulin pump therapy in infants and toddlers, review the available studies of pump therapy in this population, and show that the data support the use of insulin pumps in our very youngest of patients.