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Background: Sensor-augmented insulin pumps may be programmed to suspend insulin delivery in response to hypoglycemia. The Medtronic Paradigm® Veo™ pump with automatic low glucose suspend (LGS) was released in 2009. Data from 7 months of real-world use of the system were analyzed to assess usage patterns and effectiveness of LGS., Method: Data from 935 patients totaling 49,867 patient days were collected; the LGS feature was on for 82% of these days. A subset of 278 subjects who used the pump for ≥3 months was analyzed separately; these subjects provided 28,401 patient days of data, with LGS used for 92% of the time., Results: The LGS threshold was most commonly set between 50 and 60 mg/dl. A total of 27,216 LGS events occurred, and 60% began in the afternoon or evening. The median duration of LGS events was 9.87 min, 45% lasted for <5 min, and 11% lasted for >115 min (equivalent to the full extent of the LGS event between 115 and 120 min). Among the episodes lasting for >115 min, the mean sensor glucose (SG) was 58.8 ± 12.4 mg/dl at LGS activation (time 0), rose to 102.2 ± 52.8 mg/dl by the end of the LGS episode (when insulin delivery was automatically resumed), and was 150.1 ± 68.6 mg/dl at 240 min. In the 278-subject subgroup, LGS usage significantly reduced the number of SG readings <50 mg/dl (p = 0.001) and >300 mg/dl (p = 0.001)., Conclusions: The LGS feature was on for most of the patient days in the study. Most LGS episodes lasted for <10 min. Use of the LGS feature significantly reduced exposure to hypoglycemia. Profound hyperglycemia resulting from LGS episodes lasting >115 min was not observed., (© 2011 Diabetes Technology Society.)

Background: Type 1 diabetes and dyslipidemia are known risk factors for cardiovascular disease (CVD), but the relationship between lipid levels in youth with type 1 diabetes and future CVD remains unknown., Objective: To characterize lipid levels and CVD risk factors over time in youth with type 1 diabetes., Subjects: The study included adolescents with type 1 diabetes (12-25 yr) with a minimum of 3-yr follow-up., Methods: A longitudinal prospective, observational study of 46 youth with type 1 diabetes was performed. Fasting lipid profiles, A1C, and body mass index (BMI) were measured every 6 months for at least 3 yr (median 4.2 yr). Low-density lipoprotein (LDL)-cholesterol, total cholesterol (TC), and triglycerides (TG) were divided into categorical variables., Results: At baseline, median age was 14.3 yr, mean diabetes duration was 6.4 ± 3.8 yr, mean A1C was 8.1 ± 1.0%, and median BMI z-score was 0.92. Fifty percent of subjects had LDL levels ≤ 100 mg/dL (≤ 2.6 mmol/L) at study onset. After adjusting for confounding factors, increasing BMI z-score [β = 0.2, 95% confidence interval (CI ) = 0.03-0.38, p = 0.03] and increasing A1C (β = 0.18, 95% CI = 0.08-0.29, p = 0.001) were associated with increasing LDL category over time. Non-Hispanic ethnicity (β = 0.45, 95% CI = 0.12-0.79, p = 0.008) and family history of stroke (β = 0.38, 95% CI = 0.04-0.72, p = 0.03) were also associated with increasing LDL category. Age, diabetes duration, and tobacco exposure were not related to change in LDL. Increasing A1C was associated with increases in TG (β = 18.1, 95% CI = 2.3-33.9, p = 0.03), TC (β = 20.3, 95% CI = 9.0-31.5, p < 0.0001), and LDL (β = 13.4, 95% CI = 3.17- 23.6, p = 0.01)., Conclusion: Glycemic control and BMI are modifiable risk factors for dyslipidemia in youth with type 1 diabetes., (© 2011 John Wiley & Sons A/S.)

Context: The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort represents the largest and best-characterized national sample of American youth with recent-onset type 2 diabetes., Objective: The objective of the study was to describe the baseline characteristics of participants in the TODAY randomized clinical trial., Design: Participants were recruited over 4 yr at 15 clinical centers in the United States (n = 704) and enrolled, randomized, treated, and followed up 2-6 yr., Setting: The study was conducted at pediatric diabetes care clinics and practices., Participants: Eligible participants were aged 10-17 yr inclusive, diagnosed with type 2 diabetes for less than 2 yr and had a body mass index at the 85th percentile or greater., Interventions: After baseline data collection, participants were randomized to one of the following groups: 1) metformin alone, 2) metformin plus rosiglitazone, or 3) metformin plus a lifestyle program of weight management., Main Outcome Measures: Baseline data presented include demographics, clinical/medical history, biochemical measurements, and clinical and biochemical abnormalities., Results: At baseline the cohort included the following: 64.9% were female; mean age was 14.0 yr; mean diabetes duration was 7.8 months; mean body mass index Z-score was 2.15; 89.4% had a family history of diabetes; 41.1% were Hispanic, 31.5% were non-Hispanic black; 38.8% were living with both biological parents; 41.5% had a household annual income of less than $25,000; 26.3% had a highest education level of parent/guardian less than a high school degree; 26.3% had a blood pressure at the 90th percentile or greater; 13.6% had a blood pressure at the 95th percentile or greater; 13.0% had microalbuminuria; 79.8% had a low high-density lipoprotein level; and 10.2% had high triglycerides., Conclusions: The TODAY cohort is predominantly from racial/ethnic minority groups, with low socioeconomic status and a family history of diabetes. Clinical and biochemical abnormalities and comorbidities are prevalent within 2 yr of diagnosis. These findings contribute greatly to our understanding of American youth with type 2 diabetes.

The purpose of this study was to document the prevalence of severe obesity and associated risk in the HEALTHY cohort. A total of 6,365 students were assessed at school-based screenings. Results showed that 6.9% of students were severely obese. Severe obesity was associated with elevated cardiometabolic risk and race/ethnicity. Severe obesity is common and requires preventive intervention., (Copyright © 2010 Society for Adolescent Health and Medicine. All rights reserved.)

Objective: The CareLink™ (Medtronic, Inc., Northridge, CA) database houses data from continuous glucose monitoring (CGM), insulin pumps, and blood glucose (BG) meters. This study examined CGM usage and its relationship to insulin delivery and glycemia in CareLink users with type 1 diabetes mellitus (T1DM)., Methods: Users whose CareLink accounts contained =120 days of pump and glucose readings within a 180-day interval were further selected and stratified based on the frequency of CGM use and adequacy of glycemic control; correlations between these variables were sought., Results: The proportion of subjects with pre-specified favorable glycemic parameters rose with increasing sensor use (p<0.001). These subjects administered more and smaller boluses, gave a higher proportion of their total daily dose (TDD) of insulin as boluses, and maintained lower TDDs than those with pre-specified less-favorable glycemic parameters (all p<0.001)., Conclusions: A favorable dose effect of CGM use was evident. CGM data facilitates smaller and more frequent bolus dosing, allowing for improved glycemic control.

Objective: Our objective was to formulate practice guidelines for the treatment and prevention of pediatric obesity., Conclusions: We recommend defining overweight as body mass index (BMI) in at least the 85th percentile but < the 95th percentile and obesity as BMI in at least the 95th percentile against routine endocrine studies unless the height velocity is attenuated or inappropriate for the family background or stage of puberty; referring patients to a geneticist if there is evidence of a genetic syndrome; evaluating for obesity-associated comorbidities in children with BMI in at least the 85th percentile; and prescribing and supporting intensive lifestyle (dietary, physical activity, and behavioral) modification as the prerequisite for any treatment. We suggest that pharmacotherapy (in combination with lifestyle modification) be considered in: 1) obese children only after failure of a formal program of intensive lifestyle modification; and 2) overweight children only if severe comorbidities persist despite intensive lifestyle modification, particularly in children with a strong family history of type 2 diabetes or premature cardiovascular disease. Pharmacotherapy should be provided only by clinicians who are experienced in the use of antiobesity agents and aware of the potential for adverse reactions. We suggest bariatric surgery for adolescents with BMI above 50 kg/m(2), or BMI above 40 kg/m(2) with severe comorbidities in whom lifestyle modifications and/or pharmacotherapy have failed. Candidates for surgery and their families must be psychologically stable and capable of adhering to lifestyle modifications. Access to experienced surgeons and sophisticated multidisciplinary teams who assess the benefits and risks of surgery is obligatory. We emphasize the prevention of obesity by recommending breast-feeding of infants for at least 6 months and advocating that schools provide for 60 min of moderate to vigorous daily exercise in all grades. We suggest that clinicians educate children and parents through anticipatory guidance about healthy dietary and activity habits, and we advocate for restricting the availability of unhealthy food choices in schools, policies to ban advertising unhealthy food choices to children, and community redesign to maximize opportunities for safe walking and bike riding to school, athletic activities, and neighborhood shopping.

Background: The objective of the study was to evaluate the clinical effectiveness and safety of a device that combines an insulin pump with real-time continuous glucose monitoring (CGM), compared to using an insulin pump with standard blood glucose monitoring systems., Methods: This 6-month, randomized, multicenter, treat-to-target study enrolled 146 subjects treated with continuous subcutaneous insulin infusion between the ages of 12 and 72 years with type 1 diabetes and initial A1C levels of >or=7.5%. Subjects were randomized to pump therapy with real-time CGM (sensor group [SG]) or to pump therapy and self-monitoring of blood glucose only (control group [CG]). Clinical effectiveness and safety were evaluated., Results: A1C levels decreased (P<0.001) from baseline (8.44+/-0.70%) in both groups (SG, -0.71+/-0.71%; CG, -0.56+/-0.072%); however, between-group differences did not achieve significance. SG subjects showed no change in mean hypoglycemia area under the curve (AUC), whereas CG subjects showed an increase (P=0.001) in hypoglycemia AUC during the blinded periods of the study. The between-group difference in hypoglycemia AUC was significant (P<0.0002). Greater than 60% sensor utilization was associated with A1C reduction (P=0.0456). Fourteen severe hypoglycemic events occurred (11 in the SG group and three in the CG group, P=0.04)., Conclusions: A1C reduction was no different between the two groups. Subjects in the CG group had increased hypoglycemia AUC and number of events during blinded CGM use; however, there was no increase in hypoglycemia AUC or number of events in the SG group. Subjects with greater sensor utilization showed a greater improvement in A1C levels.

Background: Atherosclerosis appears to begin in youth with type 1 diabetes mellitus (T1DM). Highly sensitive C-reactive protein (hsCRP) is an independent marker of cardiovascular disease (CVD) risk in adults, but its relation to dyslipidemia and other CVD risk factors in adolescents with T1DM is unknown., Objective: To study the association between lipids and hsCRP in youth with T1DM., Design: Cross-sectional cohort., Methods: hsCRP and fasting lipids were measured in 74 patients with T1DM, mean age 16.2 +/- 2.62 yr, mean duration of diabetes 7.3 +/- 4.0 yr, and mean hemoglobin A1c (HbA1c) 8.5 +/- 1.3%. According to the American Heart Association/Centers for Disease Control recommendations, hsCRP values were divided into three groups: group 1: <1.0 mg/L, low CVD risk; group 2: 1.0-3.0 mg/L, average CVD risk; and group 3: >3 mg/L, high CVD risk. Univariate linear regression between hsCRP and lipid and clinical parameters was used, with adjustment for age., Results: hsCRP was significantly associated with triglycerides (Tg), apoB, systolic blood pressure (SBP), and diastolic blood pressure (DBP). Subjects in the high CVD risk group had no further worsening of lipids or BP, except for a higher Tg level. ApoB, SBP, and DBP were elevated in females with hsCRP > or =1 compared with the low-risk group, and high-density lipoprotein was decreased. In males, this difference was only significant for SBP., Conclusions: Elevation of hsCRP to a level > or =1.0 mg/L appears to be associated with elevated lipid levels in adolescents with T1DM, particularly in females. hsCRP is a marker in youth that clusters with dyslipidemia and may indicate an increased CVD risk in youth with T1DM.

The growing number of obese children and adolescents across the world creates a diagnostic challenge to caregivers. The early clinical manifestations of abnormalities related to childhood obesity, attributed to obesity-driven insulin resistance, are impaired glucose metabolism and nonalcoholic fatty liver disease. Both have no symptoms and demand a high index of suspicion and the proper choice of tests for establishing the diagnosis. The clinician should gather information derived from thoroughly taken history and a focused physical examination to stratify patients by their risk. Focused lifestyle modification-aimed interventions are showing promising results in improving the metabolic profile of obese children. Early diagnosis may help allocate resources for intensive interventions that may benefit individuals at greatest risk for early obesity-related morbidity.

Transition to adulthood for young people with diabetes is a critical milestone in their lives. It is a time when many facets of life are changing simultaneously. It is most important to recognize the special needs of adolescents with diabetes during this period. A successful and smooth transition of diabetes care should be based on a well-organized plan that includes the young person and the family. The process should be facilitated by collaboration between the pediatric and adult clinics. It should be guided by structured policies and guidelines, including posttransition evaluation. Finally, it should be a process, not an event. The school nurse can play a critical role in its success.

The SEARCH, TODAY, and HEALTHY studies, and NASN's SCOPE intervention, illustrate that collaboration between schools, school nurses, clinicians, students, and families can help treat and prevent diabetes and obesity in youth. Findings will help identify the prevalence of diabetes in young people, the best ways to treat youth with new-onset type 2 diabetes, and healthful practices that can reduce risk factors for cardiovascular disease. Findings about diabetes prevention in the school setting can guide school nurses and school leadership to incorporate effective changes into food and physical activity offerings to students. Finally, school nurses can communicate with primary care providers and provide culturally sensitive letters to parents and guardians regarding the BMI results for the child.

Real-time continuous glucose monitoring and the insulin pump have been combined into the Sensor-Augmented Pump system (Medtronic MiniMed, Northridge, CA). This short-term pilot trial demonstrated that pediatric subjects with type I diabetes improved mean hemoglobin A1c (A1c) and glucose levels and reduced hypoglycemia and hyperglycemia using the Sensor-Augmented Pump system.

Objective: To evaluate the prevalence of risk factors that are associated with the metabolic syndrome and insulin resistance in overweight youth and to determine the effect of a short-term, family-centered, lifestyle intervention on various associated anthropometric and metabolic measures., Methods: Overweight youth who were between 8 and 16 years of age participated in a 12-week, family-centered, lifestyle intervention program. Anthropometric and metabolic measures were assessed before the program in all participants (n = 109) and after the program in a subset of the participants (n = 43)., Results: At baseline, 49.5% of youth had multiple risk factors associated with the metabolic syndrome, based on a modified definition of the National Cholesterol Education Program, and 10% had impaired fasting glucose and/or impaired glucose tolerance. Measures of insulin resistance correlated significantly with the risk factors of the metabolic syndrome. Forty-three youth had pre- and postintervention evaluations that showed statistically significant improvements in body mass index, systolic blood pressure, lipids (total, low-density lipoprotein cholesterol, and triglycerides), postprandial glucose, and leptin levels., Conclusion: Overweight youth have multiple risk factors associated with the metabolic syndrome. A 12-week lifestyle program may have a positive effect on reducing risk factors for the metabolic syndrome and insulin resistance in overweight youth.

The number of children and youth diagnosed with type 2 diabetes has increased dramatically over the last decade. Much still needs to be learned about why this epidemic is occurring presently with regard to other environmental factors that might promote insulin resistance and beta-cell failure. The TODAY trial will help to determine the best treatment strategies to improve glycemia, reduce complications, and ameliorate insulin resistance and beta-cell failure. As type 2 diabetes emerges as a worldwide public health problem, improved care for affected youth must be coupled with a focus on prevention.

Objective: To evaluate the degree of atherosclerosis and its risk factors in adolescents and young adults with type 1 diabetes., Study Design: We measured carotid artery intima-media thickness (IMT) in 142 subjects with type 1 diabetes (mean [SD] age = 16.0 [2.6] years) and 87 control subjects (18.8 [3.1] years). Fasting lipid and homocysteine levels, degree of glycemic control, blood pressure, and body mass index were measured in persons with diabetes., Results: The mean carotid IMT was greater in persons with diabetes ( P = .002). Among subjects with type 1 diabetes, lipid levels were significantly higher in female subjects compared with male subjects. The mean carotid IMT was significantly higher in persons with a diabetic complication (including hypertension, retinopathy, or microalbuminuria). In male subjects but not female subjects, HDL cholesterol and the LDL/HDL ratio were correlated with carotid IMT., Conclusions: Adolescents with type 1 diabetes have increased atherosclerosis compared with control subjects. Risk factors for increased carotid IMT in these younger patients include diabetic complications and HDL cholesterol and the LDL/HDL ratio, which may be sex-specific.

We report two unrelated cases of adult galactosaemia females with normal ovarian function and Q188R/R333G mutations. Clinical history has been followed for 40 years. Biochemical finding in one patient are consistent with the presence of small amounts of galactose-1-phosphate uridyltransferase (GALT) activity, which differs from classical galactosaemia.

Background: The Diabetes Control and Complications Trial (DCCT) demonstrated that the rate-limiting step to the intensification of diabetes management in adolescents and adults was hypoglycemia. Young children were presumed to be at even greater risk for hypoglycemia with severe consequences, particularly if they had HbA1c levels < 8%., Subjects: A retrospective chart review was performed on 148 patients with type 1 diabetes on insulin injection therapy who were < 8 yr of age (mean age 5.7 +/- 1.5, mean diabetes duration 3.0 +/- 1.4 yr) followed quarterly from July 1999 to June 2001., Methods: The subjects were divided into two groups based on their mean HbA1c values (< 8 vs. > or = 8%) averaged over the 2-yr time period. The following variables were analyzed comparing the two groups: age, duration of diabetes, insulin dose, severe hypoglycemic episodes, episodes of diabetic ketoacidosis (DKA), percentage of glucose levels above, within, and below the target range, and number of diabetes home-management competencies obtained., Results: Patients with HbA1c < 8% spent more time within target range (40.0 vs. 29.5%, p = 0.0001) and less time above their target range (36.9 vs. 51.2%, p = 0.0003). There was no difference in the percentage of glucose levels below target (23.2 vs. 19.4%, p = NS), percentage of severe hypoglycemic episodes (3 vs. 7 episodes per 100 patient-yr, p = NS), or episodes of DKA (1 vs. 3 episodes per 100 patient-yr, p = NS) between the two groups. SUBJECTS with lower HbA1c levels had acquired more home-management competencies (4.0 vs. 3.5, p = 0.01)., Conclusions: If families are competent in fundamental diabetes management, young children can achieve HbA1c levels < 8.0% without increasing the risk of hypoglycemia.

Objective: To use the Continuous Glucose Monitoring System (CGMS, MiniMed, Sylmar, Calif) to determine if bedtime blood glucose levels were associated with the occurrence of nocturnal hypoglycemia., Study Design: Patients (n = 47, 18 boys, mean age 11.8 +/- 4.6 years) with type 1 diabetes used CGMS for 167 nights. Data were analyzed for glucose 100 mg/dL and 150 mg/dL., Results: A glucose value of 100 mg/dL, P = NS), and no bedtime glucose value between 110 and 300 mg/dL decreased the incidence of nocturnal hypoglycemia to

Type 2 diabetes mellitus (DM) has been described as a new epidemic affecting the American pediatric population. This is coincident with an overall 33% increase in DM prevalence documented during the last decade. In 1992, type 2 DM was a rare occurrence in most pediatric centers. By 1994, it represented up to 16% of new cases in urban areas, and by 1999, the incidence of new type 2 DM diagnoses ranged between 8% and 45%, depending on geographic location. These patients have been observed primarily in African American, Mexican American, Native American, and Asian American children and youth. As in the adult population, type 2 DM in children and youth occurs as a result of insulin resistance coupled with relative beta-cell failure. While there appears to be a host of potential genetic and environmental risk factors for these aberrations, perhaps the most significant risk factor is obesity. Other risk factors include a family history of type 2 DM, puberty, intrauterine exposure to DM, sedentary lifestyle, female gender, and certain ethnicities. To date, few studies have addressed the role of physical activity and nutrition counseling in improving glycemic outcome, the most effective ways to reduce cardiovascular risk, or the most effective treatment regimens for this population. Once type 2 DM is established, the persistence of obesity often interferes with the response to treatment and exacerbates the comorbidities of hypertension, dyslipidemia, atherosclerosis, and polycystic ovarian syndrome (PCOS). Since fewer than 10% of youth with type 2 DM can be treated with diet and exercise alone, pharmacological intervention is generally required to achieve normoglycemic targets. In most surveys, practitioners prescribe insulin or an oral agent, most often metformin. Specific treatment algorithms for pediatric patients with type 2 DM need to be rigorously investigated.

A 16-5/12 year-old male was diagnosed with classical growth hormone (GH) deficiency at the age of 8-6/12 years and was treated with recombinant methionyl human growth hormone (m-hGH). Height increased from 104.0 cm to 107.4 cm over the first 6 months. After that, for 1 year, he demonstrated poor growth velocity which was found to be secondary to a high titer of GH antibodies with GH binding capacity >2 mg/l. After a 7-month washout period during which no GH was given, at age 11 years he was placed on recombinant methionyl-free human growth hormone (met-free hGH). His height increased 14.9 cm in 11 months (annualized growth rate of 16.2 cm/year). This report illustrates that evaluation of growth failure during GH therapy should include measurement of anti-GH antibodies so that an appropriate alteration of GH therapy can be made if indicated.

To better understand factors contributing to behavioral development, we studied patients with Turner syndrome (TS), a disorder typically marked by prenatal onset of ovarian dysfunction. We compared girls and women (ages 12 and up) with TS (n = 21) to matched controls (n = 21) in cognitive and motor skills, as well as sex-typed personality characteristics and activity preferences. Measures were categorized (based on prior studies) as showing an average male advantage (male-superior measures), female advantage (female-superior measures), or no sex difference (sex-neutral measures). It was hypothesized that, if gonadal function contributes to behavioral development, effects of this deficiency would be more prominent on sexually differentiated than sex-neutral measures and thus that patient-control differences would be most marked for measures that show sex differences. Our findings indicated that TS patients and controls differed more on cognitive and motor domains that show sex differences than on sex-neutral domains. Patients also had more "undifferentiated" personalities and showed reduced sex-typed interests and activities. Differing experiences, as indexed by interests and activities, did not explain the observed cognitive and motor differences. These results are consistent with a role for ovarian hormones acting on the brain to influence cognitive and behavioral development, although they do not rule out other possible interpretations., (Copyright 2002 Elsevier Science (USA).)

Objective: To determine whether the continuous glucose monitoring system (CGMS) (MiniMed, Sylmar, CA) could be used to make clinical decisions and whether it has an impact on glycemia in pediatric type 1 diabetic subjects., Research Design and Methods: Pediatric subjects were recruited if they had HbA(1c) >8.0% with management problems (n = 35) or episodes of severe or nocturnal hypoglycemia or hypoglycemia unawareness associated with HbA(1c) < or =8.0% (n = 12). A total of 47 patients with a mean HbA(1c) value of 8.6 +/- 1.6% (mean age 11.8 +/- 4.6 years, youngest 2.7 years, and diabetes duration 5.5 +/- 3.5 years) on three to four insulin injections/day (n = 24) or insulin pump therapy (n = 23) were followed with the CGMS for a mean of 69.5 +/- 28 h. Comparisons were made between the number of high (>150 mg/dl) and low (<70 mg/dl) glucose patterns discerned with the sensor or the logbook, and HbA(1c) levels were evaluated., Results: In patients on injection therapy, 30 high or low glucose patterns were discerned with the logbook records and 120 patterns with the CGMS. Specific alterations of the diabetes regimen were made. An overall significant change in HbA(1c), from 3 months before wearing the sensor to 6 months after (analysis of variance 0.04), was found in the subjects. Post hoc analysis showed a significant change in HbA(1c) from 8.6 +/- 1.5% at baseline to 8.4 +/- 1.3% at 3 months (paired Student's t test 0.03)., Conclusions: The CGMS can be used by pediatric patients to detect abnormal patterns of glycemia. The information that was obtained could be used to alter the diabetes regimen and impact glycemic outcome.

The amount of bone that is gained during adolescence is the main contributor to peak bone mass, which, in turn, is a major determinant of osteoporosis and fracture risk in the elderly. We examined whether computed tomography measurements for the density and the volume of bone in the axial and the appendicular skeletons could be tracked through puberty in 40 healthy white children (20 girls and 20 boys). Longitudinal measurements of the cross-sectional area and cancellous bone density of the vertebral bodies and the cross-sectional and cortical bone areas of the femurs at the beginning of puberty accounted for 62-92% of the variations seen at sexual maturity; on average, 3 yr later. When baseline values for these bone traits were divided into quartiles, a linear relation across Tanner stages of sexual development was observed for each quartile in both girls and boys. The regression lines differed among quartiles for each trait, paralleled each other, and did not overlap. Thus, we are now in a position to identify those children who are genetically prone to develop low values for peak bone mass and toward whom osteoporosis prevention trials should be geared.

Objective: Because of age-related developmental and cognitive issues, children <10 years of age may not be able to wear an insulin pump safely when they are not under direct parental supervision. The purpose of this study was to determine if insulin pump therapy at nighttime only, when children are at home, could improve fasting and nighttime blood glucose levels without adverse effects., Research Design and Methods: The study cohort consisted of 10 children aged 7-10 years. A randomized crossover design was used to compare nighttime-only pump usage from dinner and throughout the night, combined with a prebreakfast injection of intermediate-acting NPH and rapid-acting lispro insulin, with 3 insulin injections per day. Comparisons were made among mean blood glucose values and percentage of blood glucose levels within the target range (70-150 mg/dl) before meals, at bedtime, and at 3:00 A.M.; serum fructosamine levels; and scores on measures of adherence and fear of hypoglycemia., Results: Compared with baseline levels, the use of the pump resulted in a significant decrease in the mean average (P < 0.001), breakfast (P < 0.0001), and 3:00 A.M. (P < 0.003) blood glucose levels. There was a decrease in the percentage of blood glucose values less than the target range (P < 0.01) and in fructosamine (P < 0.01) values and an increase in the percentage of blood glucose levels within the target range (P < 0.03)., Conclusions: Nighttime-only insulin pump therapy may be a viable alternative that young children can use to improve glycemia when they are not capable of independently managing an insulin pump.

Bone mass and biochemical markers of bone turnover increase significantly during puberty. We studied the possible relationships between markers of bone formation and bone resorption and increases in skeletal size, bone volume, and bone density in healthy children at different stages of sexual development. Serum concentrations of bone specific alkaline phosphatase (BALP) and osteocalcin (bone Gla protein, BGP), urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) and computed tomography (CT) measurements of the cross-sectional areas of the vertebrae and the femurs, the apparent density of cancellous bone in the vertebrae, and the volume and the material density of cortical bone in the femurs were determined in 126 boys and 143 girls, ages 7-18 years. Serum levels of BALP and BGP and urinary concentrations of Pyr and Dpyr peaked in early puberty and were lowest in the later stages of puberty. CT measurements for the cross-sectional areas of the vertebrae and the femurs, the femoral cortical bone areas, and the apparent density of cancellous bone increased in all children during puberty, while values for material bone density did not change significantly with the stage of sexual development. BALP and BGP showed significant inverse correlations with the material density of bone (r = -0.23 and -0.24, respectively), but no association with bone volume in the appendicular or axial skeleton. In contrast, Pyr and Dpyr correlated with femoral cross-sectional area (r = -0.24 and -0.33, respectively) and cortical bone area (r = -0.29 and -0.33, respectively), and with the apparent density of vertebral cancellous bone (r = -0.26 and -0.19, respectively), but not with the material density of bone. We conclude that, during puberty, there is a differential association between the two components of bone mass and the markers of bone formation and bone resorption; while markers of bone formation are related to the material density of bone, markers of bone resorption are related to the volume of bone.

Objective. This study was undertaken to determine whether serial bone age (BA) radiographs were obtained in patients with growth hormone deficiency and to assess whether there were differences in outcome between subjects with and without monitoring of BA radiographs. Research Design and Methods. Data were collected from the National Cooperative Growth Study database on growth hormone-deficient subjects who were treated for at least 3 years. Comparisons were made among three groups of subjects: 1) those with BAs at entry versus those without; 2) those with BA values in the first year of follow-up if an entry radiograph had not been done versus those with no first-year examination; and 3) those with a BA at entry and yearly for 3 years versus those with no radiographs during the same period. Differences in the change in height standard deviation score (SDS); change in height age, age, pubertal progression, number of visits, growth hormone dosage; and number of growth hormone injections per week were compared. Results. Of the 6191 subjects assessed, 93% had at least one BA radiograph obtained; there was a mean of 3.6 +/- 2.6 total number of BA radiographs per patient during the 5.2 +/- 1.9 years of follow-up. Subjects with BA values at entry were older and had slightly higher cumulative height SDS and height age change compared with those without BA values at entry. Subjects with BA assessment during the first year were older and had shorter growth hormone treatment time and slightly better cumulative change in height SDS and height age than did those without BA in the first year. Comparing those with serial BA determination for the first 3 years of treatment versus those with no BA values, those with BA were older, more pubertal, seen more often, had more growth hormone injections per week of a comparable growth hormone dosage, and had slightly larger cumulative change in height SDS and height age than those without x-rays. Conclusions. These data suggest that National Cooperative Growth Study investigators find it of benefit to obtain baseline and follow-up measurements of BA in most subjects treated with growth hormone. Subjects with BA monitoring do slightly better than do those whose skeletal maturation is not measured. BA assessment should be considered part of the follow-up of patients treated with growth hormone therapy.

There are a number of medical conditions such as growth failure in children, pregnancy, lipid abnormalities, and early complications that are improved by the meticulous glycemic control that can be achieved with insulin pump therapy (CSII). By using an insulin pump, many patients with severe hypoglycemia, the dawn phenomenon, extremes of glycemic excursion, recurrent diabetic ketoacidosis (DKA) and hypoglycemia unawareness have amelioration of these problems. However, pump therapy involves problems such as weight gain, recurrent ketosis due to pump failure, infections, and risk of hypoglycemia. Owing to many developmental issues, young children may not be able to wear the pump without parental supervision. We have used the pump at night time only in these patients. This has allowed children of 7-10 years of age to benefit from improved nocturnal glycemia without the risk of pump therapy when they are without an adult to help. We have also used the pump in subjects with recurrent DKA and in our general patient population (mean age 13.6+/-3.9 years). In our pump cohort, CSII led to improvement in quality of life, knowledge, adherence, and responsibility. A reduction in hypoglycemia, DKA rate and mean HbA(1c) was associated with pump usage. For this to occur, however, pump education must be geared to the pediatric subject and his/her family. Education materials and tools help in learning how to use the pump and how to deal with the intricacies of basal and bolus dosing, and the effect of exercise, food and illness on diabetes management. The pump has improved since it was first introduced and these modifications have made it easier, more painless and less hazardous. With the development of continuous glucose sensors and implantable pumps, the next century will see pump therapy lead to the artificial pancreas., (Copyright 1999 John Wiley & Sons, Ltd.)

There remain a number of important controversies in the management of pediatric DKA. From the sodium content of the hydrational fluid to the rate of fluid administration that is best able to reverse the hyperosmolar dehydration attendant with DKA with minimal morbidity and mortality, there is no universal agreement on how patients with this devastating metabolic disturbance should be treated. It is still unclear what promotes or protects patients from neurologic insult during DKA reversal. It is appropriate to begin to develop a national approach to eradicating DKA. This would require widespread public and professional education programs aimed at detecting new-onset type I patients prior to the onset of DKA. It would involve promoting diabetes screening programs aimed at detecting patients before the onset of symptomatic disease, and these would most appropriately be centered in the pediatrician's office. In the known patient, DKA still occurs as the result of intercurrent illness and nonadherence to the diabetes regimen due to patient or family chaos and dysfunction. Clearly, more strategies are needed to address these psychological and family patterns and the fact that many tenuous families have insufficient access to appropriate medical care. Those caring for children and adolescents must do all they can to prevent DKA and to treat it optimally to avert the toll this metabolic aberration takes on the pediatric diabetes population.

Objective: To determine if there is a relationship between diabetes outcome as measured by HbA1C and the number of multidisciplinary clinic visits per year in children and youth with diabetes., Research Design and Methods: The number of clinic visits per year, the mean HbA1C (by DCA 2000, Miles, Tarrytown, NY), type of insurance, parental marital status, parental age, maximal parental grade level achieved, family income, self-identified race, and scores on adherence and knowledge tests were compared for 1995 in 360 patients with a mean age of 11.6 +/- 4.8 years (1-2 visits, 85 patients; 3-4 visits, 275 patients), for 1996 in 412 patients with a mean age of 11.6 +/- 4.7 years (1-2 visits, 115 patients; 3-4 visits, 297 patients), and for 1997 in 442 patients with a mean age of 11.8 +/- 4.9 years (1-2 visits, 126 patients; 3-4 visits, 332 patients)., Results: There was a significant difference in the mean HbA1C levels between subjects with 1 to 2 visits versus 3 to 4 visits during the 3 years of this study. In 1995, the mean HbA1C was 9.0 +/- 2.0% for subjects with 1 to 2 visits and 8.3 +/- 1.6% for subjects with 3 to 4 visits. In 1996, the mean HbA1C was 9.3 +/- 2.0% for subjects with 1 to 2 visits and 8.4 +/- 1.6% in those with 3 to 4 visits, whereas in 1997, the mean HbA1C was 9.1 +/- 1.9% with 1 to 2 visits and 8.3 +/- 1.5% with 3 to 4 visits. There was a significant difference in the number of visits by the age of the subject. The mean age of patients with 1 to 2 visits was 13.6 +/- 4.5 years; it was 10.8 +/- 4.6 years with 3 to 4 visits. However, for age groups <13 years versus >/=13 years, there was still a difference between HbA1C levels for subjects with 1 to 2 visits compared with 3 to 4 visits (8.9 +/- 1.7% versus 8.1 +/- 1.3%, respectively). The only patient/family characteristic that had an association with number of visits was the marital status of the parents. Children from single-parent households had fewer visits. There was no association between health insurance status and number of visits and there was no difference between the number of visits and the mean scores on tests of adherence or knowledge. Multivariate analysis showed that the number of visits was a significant predictor of HbA1C even after controlling for age, duration of diabetes, and scores on adherence and knowledge tests., Conclusions: The finding that subjects with more frequent visits to a multidisciplinary diabetes clinic had lower HbA1C levels during the 3 years of this study suggests that strategies should be developed to promote adherence with quarterly visits, particularly targeted to children from single-parent households and to teens.

Our objective was to determine scores on tests of neurocognitive functioning in children diagnosed with diabetes before age 10 years and to determine the association of age of diagnosis, duration of diabetes, subtle hypoglycemia, severe hypoglycemia, and history of hypoglycemic seizures with these neurocognitive test scores. Fifty-five of 62 eligible patients with a mean age of 7.9 +/- 1.6 years followed in our center were given the Woodcock-Johnson Psychoeducational Battery, Beery Developmental Test of Visual-Motor Integration, Finger Tapping, Grooved Pegboard, and Verbal Selective Reminding tests to evaluate the following domains: memory/attention, visual-perceptual, broad cognitive function, academic achievement, and fine motor speed/coordination. Fifteen age-matched siblings served as controls. Twenty-seven subjects were less than 5 years of age when diagnosed with diabetes, the mean age at diagnosis was 4.5 +/- 2.1 years of age, and mean diabetes duration was 2.6 +/- 2.0 years. Eighteen patients had a history of severe hypoglycemia, eight of whom had hypoglycemic seizures. The mean HbA1c was 7.8 +/- 1.1% for the year prior to testing. Our results showed that the overall mean scores for the extensive neurocognitive battery were within the normal range and were comparable to the scores of the age-matched sibling controls. Age of diagnosis and duration of diabetes did not relate to neurocognitive test results. Mean HbA1c had a negative association with some tests of memory/attention (p < 0.03-0.04) and academic achievement (p < 0.005-0.03), while number of blood glucose levels less than mg/dL had a positive association with memory/attention (p < 0.004-0.04), verbal comprehension (p < 0.03) and academic achievement (p < 0.018-0.05). There was no association of neurocognitive test scores with severe hypoglycemia, but subjects with history of hypoglycemic seizures had a decrease in scores on tests assessing memory skills (p < 0.03) including short term memory and memory for words. These data suggest that overall neurocognitive test scores were within the normal range and comparable to controls. However, specific aspects of neurocognitive functioning may be adversely affected by having had a hypoglycemic seizure, but not by episodes of severe hypoglycemia without seizure. Lower HbA1c and an increase in the number of blood glucose levels less than 70 mg/ dL (subtle hypoglycemia) which were associated with higher scores in some domains of academic achievement and memory suggests that stable glycemia may influence cognitive abilities and/or that successful diabetes management requires cognitive skills. Strategies to diminish the risk of seizures with hypoglycemia should be investigated.

A number of important areas of controversy remain in the management of diabetes in the pediatric population. From the fluid regimen used to reverse the dehydration associated with DKA to the glycemic targets and insulin schedules suggested for young children, to the evaluation of and treatment algorithms for older children and teens suspected of having type 2 diabetes, specific data need to be derived in the pediatric population to optimize outcome and reduce risk. While further studies continue to attempt to resolve many of these important issues, those caring for children and adolescents must remain cautious.

The effective management of diabetes in children and teens requires a daily balancing of insulin administration, food intake, and exercise. To optimize outcome and avoid the neuropathic and microcirculatory effects of hyperglycemia, blood glucose levels should be maintained within a targeted range, which can be accomplished with frequent evaluation and adjustment of the overall treatment regimen. This requires meticulous attention to the disease not only by the patient and family, but by school personnel, baby sisters, coaches, and other individuals responsible for the child's welfare. Diabetes must be diagnosed as early as possible once the signs and symptoms of insulin deficiency have developed to avoid DKA and the associated risks of this acute metabolic disturbance. In addition, careful monitoring of patient progress and assurance that osmolality is reduced gradually without a rapid decrease in the serum sodium level may be required to help prevent cerebral edema associated with DKA. Individuals at risk for autoimmune diabetes should be offered the option of diabetes screening, and if appropriate, entered into diabetes prevention trials. With these aggressive measures, it is possible to decrease the acute complications and the long-term morbidity of this chronic disease and the tremendous negative impact that it has on the health-care system.

Existing longitudinal data on patients with classical galactosaemia suggests that neurocognitive functioning is impaired and, in isolated case reports, may show a decline in performance over time. The present study explored whether there are long-term changes in cognitive abilities in patients with galactosaemia and whether oral uridine can improve neurocognitive performance. Thirty-five patients (18 males, 17 females), 29 of whom received oral uridine powder at 150 mg/kg per day (divided dose, three times daily), were evaluated over a 2-5-year period with the Woodcock-Johnson Revised Cognitive Abilities Test, three academic achievement tests, and the Beery Test of Visual Motor Integration. Results showed that the uridine cohort and a comparison group that received only dietary restriction made small gains in cognitive performance over the treatment period and the size of the gains did not differ significantly. Seven subjects who started uridine prior to the age of 14 months did not differ significantly in their cognitive test scores at an average age of 3.5 years from a group of older children who had begun treatment at 4.5 years of age. These results provide no support for any developmental or uridine-treatment-related change in cognitive functioning for this sample of galactosaemic subjects.

The objective of this study was to determine the effect of a snack bar containing uncooked cornstarch, equivalent to 1 1/2 starch/bread exchanges (bar 1), compared to a control bar (bar 2), on the incidence of nocturnal and morning hypoglycemia in subjects with diabetes. Adolescent campers and counselors with diabetes (n = 79) were randomly assigned to Group A (5 nights of snack bar 1 as the evening snack, followed by 5 nights of snack bar 2) or Group B (5 nights of snack bar 2 as the evening snack, followed by 5 nights of snack bar 1). Midnight and morning finger stick blood glucose levels were compared to determine the incidence of hypoglycemia (< 60 mg/dl) and hyperglycemia (> 250 mg/dl), and events were analyzed for the total cohort, Group A, and Group B and by glycated hemoglobin quartile to determine the effect of each bar on glycemia. For subjects with diabetes there was a significant decrease in the number of hypoglycemic episodes with bar 1 compared to bar 2 at midnight (total cohort and Groups A and B) and in the morning (total cohort and Group A). There was a significant decrease in the number of subjects to ever experience hypoglycemia with snack bar 1 compared to snack bar 2, a significantly lower incidence of hyperglycemic episodes at midnight with snack bar 1, and no difference in the incidence of hypoglycemia by glycated hemoglobin quartile. These data suggest that the snack bar containing uncooked cornstarch can diminish night time and morning hypoglycemia in subjects with diabetes, without causing hyperglycemia.

Intensive management of type I diabetes mellitus may lead to a significant increase in hypoglycemia. This study evaluated the use of uncooked cornstarch to avert hypoglycemia in 13 patients, ages 3.0-17.5 years, with diabetes and a history of nighttime hypoglycemia. The usual bedtime snack (Standard Snack Period) was given for 14 days followed by 14 days in which 25%-50% of the carbohydrate content was given as uncooked cornstarch in milk (Test Snack Period). Blood glucose levels were obtained at 0200 and before breakfast during the 28-day study. No difference was found between the mean (+/- SD) before breakfast blood glucose levels during the two periods; however, the mean (+/- SD) number of hypoglycemic episodes (blood glucose < 60 mg/dL or 3.3 mmol/L) was reduced significantly during the Test Snack Period at both 0200 (p < 0.025) and before breakfast (p < 0.01) compared to Standard Snack Period (Standard Snack 2.00 +/- 2.12 versus Test Snack 0.61 +/- 0.87 at 0200, Standard Snack 2.61 +/- 2.25 versus Test Snack 0.69 +/- 1.03 before breakfast). In addition, in four children who were evaluated with every-2-h glucose levels through the night, stable glycemia was achieved after cornstarch ingestion. Our results suggest that uncooked cornstarch may be useful to decrease the frequency of nocturnal hypoglycemia in type I diabetes patients. This low-cost, simple intervention might be considered as an adjunctive therapy to diminish the risk of intensive diabetes management.

During the last 10 years, five children were treated at Childrens Hospital Los Angeles for acute, persistent neurologic loss during diabetic ketoacidosis (DKA). Four were transferred from local hospitals after the neurologic crisis. Computed tomography (CT) studies showed one or more areas of brain infarction in each patient, and none had evidence of diffuse cerebral edema. As three of the five patients had been treated for cerebral edema before their CT, brain edema may have been present initially. Our findings emphasize the importance of brain infarction as a cause of persistent neurologic loss in children with DKA.

Our objective was to retrospectively evaluate glycemic excursion and insulin dosage in the perioperative period in children and adolescents with type I diabetes mellitus receiving prolonged intravenous insulin infusion for 2-3 days compared to conventional subcutaneous insulin treatment. A retrospective review of surgical admissions at the Children's Hospital of Los Angeles in patients with type I diabetes mellitus was conducted for the 3-year period from July 1989 to June 1992, to evaluate two treatment protocols used during that period. For the nine admissions in group 1, patients received 0.06-0.1 units regular insulin/kg/h beginning 2 h prior to surgery and lasting for 2-3 days postoperatively; while, for the ten admissions in group 2 subjects were given subcutaneous regular and intermediate-acting insulin as 2-4 injections daily, with the regular insulin dose prior to surgery decreased to 66-75% of usual. Blood glucose levels were determined at the bedside at hourly intervals and insulin dose adjustment done with the aim of achieving blood glucose levels between 5.5 and 8.3 mmol/L (100-150 mg/dL). The mean bedside blood glucose levels for group 2 were significantly higher 1 h prior to surgery and during the intraoperative period (p < 0.05). In the postoperative period, group 2 blood glucose levels were significantly higher at multiple times for up to 3 days with multiple levels greater than 11.1 mmol/L (200 mg/dL), which was not seen in group 1. The mean insulin dosage (units/kg) prior to admission was not different for the two groups. On the day of surgery and during postoperative days 1 and 2, patients in group 1 received a greater insulin dosage than group 2 subjects (p < 0.025). In group 1, insulin dosage was increased 23% and 15% over baseline for postoperative days 1 and 2, respectively, then, by day 3, was decreased back toward the baseline. In group 2 subjects, a 13.8% increase occurred on the day of surgery due to extra insulin given immediately following the procedures, followed by a 5.4, 44.2, and 66.6% increase over baseline for postoperative days 1 through 3, respectively. In conclusion, meticulous glycemic control was readily achieved in the perioperative period with a constant intravenous insulin infusion for up to 3 days in children and adolescents with type I diabetes. To achieve glycemic control, insulin dosage needs to be increased on the day of surgery and for approximately 2 postoperative days.