The stability of metabolic syndrome in children and adolescents.

CONTEXT: Some studies suggest the presence of metabolic syndrome before adulthood may identify those at high risk for later cardiovascular morbidity, but there are few data examining the reliability of pediatric metabolic syndrome. OBJECTIVE: To examine the short- and long-term stability of pediatric metabolic syndrome. DESIGN: Metabolic syndrome was defined as having at least three of the following: waist circumference, blood pressure, and fasting serum triglycerides in the 90th or higher percentile for age/sex; high-density lipoprotein-cholesterol 10th or lower percentile for age/sex; and fasting serum glucose of at least 100 mg/dl. Short-term metabolic syndrome stability (repeated measurements within 60 d) was assessed in obese youth ages 6-17 yr. Long-term metabolic syndrome stability (repeated measurements more than 1.5 yr apart) was studied in 146 obese and nonobese children age 6-12 yr at baseline. PATIENTS AND SETTING: Convenience samples of obese and nonobese youth ages 6-17 yr participating in research studies were collected at a clinical research hospital. RESULTS: Short-term metabolic syndrome stability (repeat measurements performed 19.7 +/- 13.1 d apart) was assessed in 220 children. The diagnosis of metabolic syndrome was unstable in 31.6% of cases. At their short-term follow-up visit, incidence of metabolic syndrome among participants who did not have metabolic syndrome at baseline was 24%. In the long term (repeat measurements performed 5.6 +/- 1.9 yr apart), the diagnosis of metabolic syndrome was unstable in 45.5% of cases. CONCLUSIONS: Cutoff-point-based definitions for pediatric metabolic syndrome have substantial instability in the short and long term. The value of making a cutoff-point-based diagnosis of metabolic syndrome during childhood or adolescence remains in question.

Insulin resistance, hyperinsulinemia, and energy intake in overweight children.

OBJECTIVE: To examine the relationship between energy intake during a buffet meal and indexes of insulin dynamics in overweight children. STUDY DESIGN: Ninety-five nondiabetic, overweight (body mass index > or = 95th percentile) children (age 10.3 +/- 1.4 years) selected lunch from a 9835-kcal buffet eaten ad libitum after an overnight fast. The associations between energy intake and measures of insulin dynamics, in the postabsorptive state and during a 2-hour hyperglycemic clamp, were determined. Covariates in the statistical model included race, sex, skeletal age, fat-free mass, fat mass, socioeconomic status, and number of foods in the buffet rated as acceptable. RESULTS: Energy intake was positively associated with the fasting homeostasis model assessment for insulin resistance index (beta = 0.24, P = .042), fasting insulin/glucose ratio (beta = 0.24, P = .044), first-phase insulin (beta = 0.23, P = .032), and first-phase C-peptide (beta = 0.21, P = .046); energy intake was negatively associated with clamp-derived insulin sensitivity (beta = -0.29, P = .042). Each 10% decrease in clamp-derived insulin sensitivity predicted a 27-kcal greater energy intake. CONCLUSIONS: Insulin resistance and hyperinsulinemia are associated with greater energy intake after an overnight fast in overweight children. These associations suggest mechanisms whereby insulin resistance may contribute to excessive weight gain in children.

Oxygen-uptake efficiency slope as a determinant of fitness in overweight adolescents.

PURPOSE: Peak oxygen uptake (VO2peak) is frequently difficult to assess in overweight individuals; therefore, submaximal measures that predict VO2peak are proposed as substitutes. Oxygen uptake efficiency slope (OUES) has been suggested as a submaximal measurement of cardiorespiratory fitness that is independent of exercise intensity. There are few data examining its value as a predictor of V O2peak in severely overweight adolescents. METHODS: One hundred seven severely overweight (BMI Z 2.50 +/- 0.34) and 43 nonoverweight (BMI Z 0.13 +/- 0.84) adolescents, performed a maximal cycle ergometer test with respiratory gas-exchange measurements. OUES was calculated through three exercise intensities: lactate inflection point (OUES LI), 150% of lactate inflection point (OUES 150), and VO2peak (OUES PEAK). RESULTS: When adjusted for lean body mass, VO2peak and OUES at all exercise intensities were lower in overweight subjects (VO2peak: 35.3 +/- 6.4 vs 46.8 +/- 7.9 mL.kg(-1) LBM.min(-1), P < 0.001; OUES LI: 37.9 +/- 10.0 vs 43.7 +/- 9.2 mL.kg(-1) LBM.min(-1).logL(-1) P < 0.001; OUES 150: 41.6 +/- 9.0 vs 49.8 +/- 11.1 mL.kg(-1) LBM.min(-1).logL(-1) P < 0.001; and OUES PEAK: 45.1 +/- 8.7 vs 52.8 +/- 9.6 mL.kg(-1) LBM.min(-1).logL(-1) P < 0.001). There was a significant increase in OUES with increasing exercise intensity in both groups (P < 0.001). OUES at all exercise intensities was a significant predictor of VO2peak for both groups (r2 = 0.35-0.83, P < 0.0001). However, limits of agreement for predicted VO2peak relative to actual VO2peak were wide (+/- 478 to +/- 670 mL.min(-1)). CONCLUSIONS: OUES differs significantly in overweight and nonoverweight adolescents. The wide interindividual variation and the exercise intensity dependence of OUES preclude its use in clinical practice as a predictor of VO2peak.

Influence of serum leptin on weight and body fat growth in children at high risk for adult obesity.

OBJECTIVE: Our objective was to examine serum leptin prospectively as a predictor of weight and body fat growth in children at high risk for adult obesity. We hypothesized that leptin measurements would be positively associated with increased growth of adipose tissue because children with high baseline leptin for their body fat mass have greater leptin resistance and thus would have greater susceptibility to weight gain. METHODS: Children ages 6-12 yr at high risk for adult obesity because of early-onset childhood overweight and/or parental overweight were recruited from 1996-2004. Growth in body mass index (BMI) was studied in 197 children, and growth in total body fat mass was examined in 149 children over an average follow-up interval of 4.4 yr (range, 1-8 yr). Longitudinal analyses accounted for sex, race, socioeconomic status, initial body composition, age, skeletal age, and physical activity and included all available interim visits for each individual so that a total of 982 subject visits were included in the analysis. RESULTS: At baseline, 43% of children studied were overweight (BMI > or = 95th percentile); during follow-up, an additional 14% became overweight. Independent of initial body composition, baseline leptin was a statistically significant positive predictor of increased BMI (P = 0.0147) and increased total body fat mass (P < 0.007). CONCLUSIONS: High serum leptin, independent of body fat, may be an indicator of increased leptin resistance, which predisposes children at high risk for adult obesity to somewhat greater growth in weight and body fat during childhood.

Differences between the perceived and actual age of overweight onset in children and adolescents.

OBJECTIVE: Little is known about whether children or their parents can accurately recall the age at which they became overweight. DESIGN, SUBJECTS AND MAIN OUTCOME MEASURES: We interviewed 64 overweight children (7-18 years old) about their weight history and compared reported age of overweight onset with actual onset, as determined by the age at which the child's measured BMI first exceeded the 95th percentile. RESULTS: Only 28% of children reported overweight onset within 1 year of actual overweight onset. Reported overweight onset age (7.6 +/- 2.5 y) and actual onset age (5.3 +/- 2.5 y; P < .001) were not significantly correlated (r2 = .03, P = .22). Children who became overweight before 8 years of age tended to report becoming overweight at a later age than actual onset, whereas children who became overweight after 8 years of age tended to report becoming overweight at an earlier age than actual onset (P < .001), with 27% of children either underreporting or overreporting their overweight onset by at least 5 years. Similar results were found when analyzing parent reports of their children's overweight onset. CONCLUSIONS: Reported and actual overweight onset ages were uncorrelated in our sample, suggesting that families may not be cognizant of children's growth trajectories. Greater efforts should be made to help parents and children understand and track growth patterns with the aim of preventing excessive weight gain.

The genome and proteome of coliphage T1.

The genome of enterobacterial phage T1 has been sequenced, revealing that its 50.7-kb terminally redundant, circularly permuted sequence contains 48,836 bp of nonredundant nucleotides. Seventy-seven open reading frames (ORFs) were identified, with a high percentage of small genes located at the termini of the genomes displaying no homology to existing phage or prophage proteins. Of the genes showing homologs (47%), we identified those involved in host DNA degradation (three endonucleases) and T1 replication (DNA helicase, primase, and single-stranded DNA-binding proteins) and recombination (RecE and Erf homologs). While the tail genes showed homology to those from temperate coliphage N15, the capsid biosynthetic genes were unique. Phage proteins were resolved by 2D gel electrophoresis, and mass spectrometry was used to identify several of the spots including the major head, portal, and tail proteins, thus verifying the annotation.

Modem transmission of glucose values reduces the costs and need for clinic visits.

OBJECTIVE: To determine whether modem technology allows for effective management of type 1 diabetes when used in lieu of a clinic visit. RESEARCH DESIGN AND METHODS: A total of 70 adolescent patients with diabetes were prospectively randomized to either a control group or a modem group. Control group patients continued the standard of care of quarterly clinic visits, and modem group patients were instructed to transmit blood glucose data every 2 weeks for 6 months instead of a usual quarterly clinic visit. Health care providers analyzed the data received by modem and contacted patients to discuss diabetes treatment changes. GHbA(1c) levels were determined at 0 and 6 months, and the number of high and low blood glucose levels and adverse events were tracked. Clinic visit costs, patient expenses, and health care provider times were tracked for cost analysis for both groups. RESULTS: A total of 63 patients (33 control, 30 modem) completed the 6-month study. The GHbA(1c) values significantly decreased in both groups, with no statistically significant difference between groups (P = 0.96). The occurrence of mild-to-moderate hypoglycemic events were similar in the two groups, and there were no severe hypoglycemic events. The average cost of care for a clinic visit was $305.00, whereas the cost for 6 months of modem transmission was $163.00. CONCLUSIONS: This study shows that electronic transmission of blood glucose levels and other diabetes data every 2 weeks-in lieu of a clinic visit-results in a similar level of glucose control and incidence of acute diabetes complications when compared with current standard care.

Use of the GlucoWatch biographer in children with type 1 diabetes.

OBJECTIVE: To determine whether use of the GlucoWatch biographer improves glucose control in children and adolescents with type 1 diabetes. METHODS: Forty children in poor glucose control (glycohemoglobin [HbA1c] >8%) were randomized to diabetes management with or without glucose monitoring using the biographer. Conventional glucose monitoring was performed 4 times daily in both groups. Those randomized to the biographer group were asked to wear the device 4 times per week for 3 months (intervention phase) and to perform blood glucose monitoring if the biographer alerted them that glucose was < or =70 mg/dL (3.9 mmol/L) or > or =300 mg/dL (16.7 mmol/L). After 3 months, all patients received biographers and were followed for 6 months (observation phase). HbA1c values were determined at baseline and after 1, 3, 6, and 9 months. RESULTS: The median HbA1c was 8.6% and 8.9% (control versus biographer) at baseline and was significantly lower in the biographer group after 3 months (8.4% vs 9%). More hypoglycemia was detected when subjects were wearing the biographer, especially at night. No severe hypoglycemia occurred. During the observation phase, HbA1c values at 6 months were 8.5% and 8.3% and at 9 months were 8.6% and 8.4% in the control and biographer groups, respectively. Two children dropped out of the study, 1 because of skin irritation from using the device. CONCLUSIONS: The GlucoWatch biographer was well tolerated by children and adolescents and significantly improved glucose control compared with standard therapy. The use of the biographer with an alarm to detect nocturnal hypoglycemia has the potential to increase the safety of diabetes management in children.