Presence of diabetes risk factors in a large U.S. eighth-grade cohort.

OBJECTIVE: The study was conducted in 12 middle schools to determine the prevalence of diabetes, pre-diabetes, and diabetes risk factors in eighth-grade students who were predominantly minority and evaluate the feasibility of collecting physical and laboratory data in schools. RESEARCH DESIGN AND METHODS: Anthropometric measurements and fasting and 2-h post-glucose load blood draws were obtained from approximately 1,740 eighth-grade students. RESULTS: Mean recruitment rate was 50% per school, 49% had BMI > or = 85th percentile, 40.5% had fasting glucose > or = 100 mg/dl, 0.4% had fasting glucose > or = 126 mg/dl, and 2.0% had 2-h glucose > or = 140 mg/dl and 0.1% > or = 200 mg/dl. Mean fasting insulin value was 30.1 microU/ml, 36.2% had fasting insulin > or = 30 microU/ml, and 2-h mean insulin was 102.1 microU/ml. Fasting and 2-h glucose and insulin values increased across BMI percentiles, and fasting glucose was highest in Hispanic and Native American students. CONCLUSIONS: There was a high prevalence of risk factors for diabetes, including impaired fasting glucose (> or =100 mg/dl), hyperinsulinism suggestive of insulin resistance (fasting insulin > or = 30 microU/ml), and BMI > or = 85th percentile. These data suggest that middle schools are appropriate targets for population-based efforts to decrease overweight and diabetes risk.

Two adult galactosaemia females with normal ovarian function and identical GALT mutations (Q188R/R333G).

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.

A pilot study of the continuous glucose monitoring system: clinical decisions and glycemic control after its use in pediatric type 1 diabetic subjects.

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.

Early identification of children predisposed to low peak bone mass and osteoporosis later in life.

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.

Use of insulin pump therapy at nighttime only for children 7-10 years of age with type 1 diabetes.

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.

Insulin pump therapy in type 1 pediatric patients: now and into the year 2000.

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.

Regular monitoring of bone age is useful in children treated with growth hormone.

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.

The treatment and prevention of diabetic ketoacidosis in children and adolescents with type I diabetes mellitus.

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.

Biochemical markers of bone turnover and the volume and the density of bone in children at different stages of sexual development.

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.

Use of a plastic insulin dosage guide to correct blood glucose levels out of the target range and for carbohydrate counting in subjects with type 1 diabetes.

OBJECTIVE: To improve glycemic control, a hand-held plastic Insulin Dosage Guide was developed to correct blood glucose levels outside of the target range. RESEARCH DESIGN AND METHODS: Protocol 1: Some 40 children (mean age 10.6+/-4.6 years) were randomly assigned for 3 months to use a written-on-paper algorithm or the Insulin Dosage Guide to correct abnormal blood glucose levels. Mean HbA1c and blood glucose levels and time to teach insulin dosage correction were compared. Protocol 2: The Insulin Dosage Guide was used by 83 subjects (mean age 11.4+/-4.3 years) for 1 year, and mean HbA1c levels, blood glucose levels, and number of consecutive high blood glucose values taken before and after the year were compared. Protocol 3: Some 20 patients (mean age 10.1+/-3.7 years) using rapid-acting insulin and 64 patients (mean age 15.9+/-3.6 years) using an insulin pump and rapid-acting insulin used the Insulin Dosage Guide and had mean blood glucose levels, HbA1c, and percentage of blood glucose levels outside of the target range determined. RESULTS: Protocol 1: There was a significant reduction in mean HbA1c (P = 0.04) and blood glucose levels (P = 0.05) and in the time needed to teach how to correct blood glucose values using the Insulin Dosage Guide compared with the paper algorithm. Protocol 2: There was a decrease in mean HbA1c levels (P = 0.0001) and a decrease in the mean number of consecutive blood glucose levels (P = 0.001) over the 1-year time period. Protocol 3: With rapid-acting insulin, there was a significant increase in the percentage of blood glucose levels within the target range (1 month, P = 0.04; at 3 months, P = 0.03). With the insulin pump, there was a high rate (90%) of blood glucose levels in the target range during pump initiation when the Insulin Dosage Guide was used. CONCLUSIONS: This inexpensive hand-held plastic card, which is portable and easy to use, may help patients improve glycemia and successfully manage diabetes.

Neurocognitive functioning in children diagnosed with diabetes before age 10 years.

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.

Association between diabetes control and visits to a multidisciplinary pediatric diabetes clinic.

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.

Diabetes in children and adolescents. Areas of controversy.

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.

Diabetes mellitus.

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.

A longitudinal study of cognitive functioning in patients with classical galactosaemia, including a cohort treated with oral uridine.

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.

Evaluation of a snack bar containing uncooked cornstarch in subjects with diabetes.

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.

Brain infarction in children with diabetic ketoacidosis.

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.