9 research outputs found
A low resting metabolic rate in late childhood is associated with weight gain in adolescence
Background and Objectives. Lower total energy expenditure (TEE) and resting metabolic rate (RMR) are associated with greater weight gain in Native American adults. Whether these effects exist in childhood is unclear. We hypothesized that lower energy expenditure measured in childhood would predict greater relative change in body mass index (BMI) during adolescence. Methods. Measurements of height, weight, body composition, RMR and TEE were completed in 181 Native American children at exams done at age 5 and 10 years, with 126 children having biennial follow-up assessments of weight and height after age 10 years until age 20 years. TEE and RMR were adjusted for age, sex, height, fat mass and fat free mass. BMI-change was assessed using population specific and Center for Disease Control (CDC) BMI z-scores and change in the relative difference to the 95th BMI-centile. Results. Lower adjusted RMR at age 10 years was associated with greater increase in population-specific and CDC BMI z-scores, greater increase in the relative difference to the 95th BMI-centile and greater weight gain (all r ≤ −0.22, p ≤ 0.01). However, no association was found with adjusted RMR at age 5 years and with adjusted TEE and physical activity level assessed at age 5 or 10 years. Conclusions. Lower adjusted RMR at age 10 years predicted greater change in adolescent BMI z-score indicating that the effects of relatively low metabolic rate on future weight gain in this population may begin in late childhood
Use of a High-Density Protein Microarray to Identify Autoantibodies in Subjects with Type 2 Diabetes Mellitus and an HLA Background Associated with Reduced Insulin Secretion
<div><p>New biomarkers for type 2 diabetes mellitus (T2DM) may aid diagnosis, drug development or clinical treatment. Evidence is increasing for the adaptive immune system’s role in T2DM and suggests the presence of unidentified autoantibodies. While high-density protein microarrays have emerged as a useful technology to identify possible novel autoantigens in autoimmune diseases, its application in T2DM has lagged. In Pima Indians, the HLA haplotype (HLA-DRB1*02) is protective against T2DM and, when studied when they have normal glucose tolerance, subjects with this HLA haplotype have higher insulin secretion compared to those without the protective haplotype. Possible autoantibody biomarkers were identified using microarrays containing 9480 proteins in plasma from Pima Indians with T2DM without the protective haplotype (n = 7) compared with those with normal glucose regulation (NGR) with the protective haplotype (n = 11). A subsequent validation phase involving 45 cases and 45 controls, matched by age, sex and specimen storage time, evaluated 77 proteins. Eleven autoantigens had higher antibody signals among T2DM subjects with the lower insulin-secretion HLA background compared with NGR subjects with the higher insulin-secretion HLA background (p<0.05, adjusted for multiple comparisons). PPARG2 and UBE2M had lowest p-values (adjusted p = 0.023) while PPARG2 and RGS17 had highest case-to-control antibody signal ratios (1.7). A multi-protein classifier involving the 11 autoantigens had sensitivity, specificity, and area under the receiver operating characteristics curve of 0.73, 0.80, and 0.83 (95% CI 0.74–0.91, p = 3.4x10<sup>-8</sup>), respectively. This study identified 11 novel autoantigens which were associated with T2DM and an HLA background associated with reduced insulin secretion. While further studies are needed to distinguish whether these antibodies are associated with insulin secretion via the HLA background, T2DM more broadly, or a combination of the two, this study may aid the search for autoantibody biomarkers by narrowing the list of protein targets.</p></div
Volcano plot of 77 proteins.
<p>FDR = False Discovery Rate. Lower p-values are towards the top. The statistically significant p-values are above the line. The proteins which have higher case-to-control signal ratios are further towards the right.</p
Selection of proteins associated with type 2 diabetes mellitus.
<p>T2DM = type 2 diabetes mellitus; NGR = normal glucose regulation; T1DM = type 1 diabetes mellitus; <sup>a</sup> T2DM volunteers were without the higher insulin-secretion HLA-DRB1*02 haplotype and NGR volunteers had the higher insulin-secretion haplotype. <sup>b</sup> IAPP, HSP60, SLC30A8, PTPRN, insulin, CPE, GAD2.</p
Sensitivity and specificity of PPARG2, UBE2M, and 11-protein classifier.
<p>AUC, area under the curve; CI, confidence interval.</p><p>Sensitivity and specificity of PPARG2, UBE2M, and 11-protein classifier.</p
PPARG2, UBE2M, and 11-protein classifier.
<p>(A) Relative signals of PPARG2 and UBE2M. (B) Receiver operating characteristic (ROC) analysis representing the accuracy (AUC) of PPARG2 and UBE2M. (C) ROC analysis of 11 statistically significant proteins.</p