Single Islet Autoantibody at Diagnosis of Clinical Type 1 Diabetes is Associated With Older Age and Insulin Resistance.

CONTEXT: Multiple islet autoantibody positivity usually precedes clinical (stage 3) type 1 diabetes (T1D). OBJECTIVE: To test the hypothesis that individuals who develop stage 3 T1D with only a single autoantibody have unique metabolic differences. DESIGN: Cross-sectional analysis of participants in the T1D TrialNet study. SETTING: Autoantibody-positive relatives of individuals with stage 3 T1D. PARTICIPANTS: Autoantibody-positive relatives who developed stage 3 T1D (at median age 12.4 years, range = 1.4-58.6) and had autoantibody data close to clinical diagnosis (n = 786, 47.4% male, 79.9% non-Hispanic white). MAIN OUTCOME MEASURES: Logistic regression modeling was used to assess relationships between autoantibody status and demographic, clinical, and metabolic characteristics, adjusting for potential confounders and correcting for multiple comparisons. RESULTS: At diagnosis of stage 3 T1D, single autoantibody positivity, observed in 119 (15.1%) participants (72% GAD65, 13% microinsulin antibody assay, 11% insulinoma-associated antigen 2, 1% islet cell antibody, 3% autoantibodies to zinc transporter 8 [ZnT8]), was significantly associated with older age, higher C-peptide measures (fasting, area under the curve, 2-hour, and early response in oral glucose tolerance test), higher homeostatic model assessment of insulin resistance, and lower T1D Index60 (all P < 0.03). While with adjustment for age, 2-hour C-peptide remained statistically different, controlling for body mass index (BMI) attenuated the differences. Sex, race, ethnicity, human leukocyte antigen DR3-DQ2, and/or DR4-DQ8, BMI category, and glucose measures were not significantly associated with single autoantibody positivity. CONCLUSIONS: Compared with multiple autoantibody positivity, single autoantibody at diagnosis of stage 3 T1D was associated with older age and insulin resistance possibly mediated by elevated BMI, suggesting heterogeneous disease pathogenesis. These differences are potentially relevant for T1D prevention and treatment.

Effect of conjugated linoleic acid on body fat accretion in overweight or obese children.

BACKGROUND: Conjugated linoleic acid (CLA) is a supplemental dietary fatty acid that decreases fat mass accretion in young animals. OBJECTIVE: The aim of this study was to determine CLA's efficacy with regard to change in fat and body mass index (BMI; in kg/m(2)) in children. DESIGN: We conducted a 7 +/- 0.5-mo randomized, double-blind, placebo-controlled trial of CLA in 62 prepubertal children aged 6-10 y who were overweight or obese but otherwise healthy. The subjects were randomly assigned to receive 3 g/d of 80% CLA (50:50 cis-9,trans-11 and trans-10,cis-12 isomers) or placebo in chocolate milk. RESULTS: Fifty-three subjects completed the trial (n = 28 in the CLA group, n = 25 in the placebo group). CLA attenuated the increase in BMI (0.5 +/- 0.8) compared with placebo (1.1 +/- 1.1) (P = 0.05). The percentage change in body fat measured by dual-energy X-ray absorptiometry was smaller (P = 0.001) in the CLA group (-0.5 +/- 2.1%) than in the placebo group (1.3 +/- 1.8%). The change in abdominal body fat as a percentage of total body weight was smaller (P = 0.02) in the CLA group (-0.09 +/- 0.9%) than in the placebo group (0.43 +/- 0.6%). There were no significant changes in plasma glucose, insulin, or LDL cholesterol between groups. Plasma HDL cholesterol decreased significantly more (P = 0.05) in the CLA group (-5.1 +/- 7.3 mg/dL) than in the placebo group (-0.7 +/- 8 mg/dL). Bone mineral accretion was lower (P = 0.04) in the CLA group (0.05 +/- 0.03 kg) than in the placebo group (0.07 +/- 0.03 kg). Reported gastrointestinal symptoms did not differ significantly between groups. CONCLUSIONS: CLA supplementation for 7 +/- 0.5 mo decreased body fatness in 6-10-y-old children who were overweight or obese but did not improve plasma lipids or glucose and decreased HDL more than in the placebo group. Long-term investigation of the safety and efficacy of CLA supplementation in children is recommended.

School-based exercise improves fitness, body composition, insulin sensitivity, and markers of inflammation in non-obese children.

BACKGROUND: Poor cardiovascular fitness (CVF) is a risk factor for obesity, as well as insulin resistance (IR), inflammation, and cardiovascular disease. We have previously shown that a school-based fitness curriculum can improve CVF, as well as IR and body composition in obese children. Whether such a program improves CVF, IR, and other health indicators in non-obese children is unresolved. AIM: To determine whether a school-based fitness program improves body composition, CVF, markers of inflammation (e.g. CRP, TNF-alpha, adiponectin), and insulin sensitivity in nonobese children. STUDY DESIGN: 35 non-obese middle school children with body mass index below the 95th percentile for age were enrolled in a 'fitness-oriented' gym class. Children underwent fasting evaluation of insulin, glucose, adiponectin, CRP, TNF-alpha, body composition by dual X-ray absorptiometry (DXA), and maximal VO2 treadmill testing at baseline (prior to the school year) and again at end of the school year. MAIN OUTCOME MEASURES: Testing for CVF (maximal VO2 treadmill testing), DXA, and fasting evaluation of insulin, glucose, adiponectin, CRP and TNF-alpha. RESULTS: Children demonstrated a decrease in BMI z-score (-0.14 +/- 0.33, p = 0.02), HOMA-IR (-0.15 +/- 0.35, p = 0.016), and TNF-alpha (-2.55 +/- 1.79 pg/ml, p < 0.001), and an increase in VO2(max) (+1.58 +/- 2.34 ml/kg/min, p < 0.001), adiponectin (+7,553 +/- 11,100 ng/ml, p < 0.001), and muscle mass (+2,282 +/- 1,882.73 g, p < 0.001) after nine months of study. CONCLUSIONS: The school-based fitness oriented curriculum resulted in improved body composition and insulin sensitivity, increased CVF, and decreased inflammation in non-obese children. Combined with prior studies, these data demonstrate that school-based fitness curricula can benefit both obese and non-obese children. Partnerships with schools to promote fitness should be part of a public health approach to improving children's health.

Fitness level and body composition are associated with inflammation in non-obese children.

Childhood obesity and poor fitness are associated with insulin resistance (IR), risk for coronary heart disease (CHD), and type 2 diabetes mellitus. Elevated markers of inflammation (e.g., C-reactive protein [CRP]) are independent predictors of CHD. Whether higher percent body fat and poor fitness in non-obese children are associated with evidence of inflammation and IR is unclear. We evaluated 75 children with non-obese body mass index (BMI) for age (<95th percentile), ages 11-14 years for fasting insulin, glucose, adiponectin, CRP, body composition, and maximum oxygen-consumption (VO2max). CRP correlated positively with body composition (BMI z-score, p = 0.00062; percent body fat, p = 0.00007; and total body fat in grams, p = 0.00006) and negatively with VO2max, p = 0.036. Using multivariate analysis, VO2max and percent body fat were both independent predictors of CRP. Fasting insulin and insulin resistance as assessed by QUICKI did not correlate with CRP, fitness, or fatness in these non-obese children. Adiponectin showed no significant correlations, and gender did not influence correlation analyses. We conclude that in non-obese children, low fitness and higher body fat are both associated with inflammation (i.e., higher levels of CRP). This observation strengthens the importance of promoting both fitness and healthy body composition in all children.