Utility of Hemoglobin A1c for Diagnosing Prediabetes and Diabetes in Obese Children and Adolescents

OBJECTIVE-Hemoglobin A(1c) (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking. RESEARCH DESIGN AND METHODS-We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of similar to 2 years in 218 subjects. RESULTS-At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C 6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% Cl 0.70-0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time. CONCLUSIONS-The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents

A1C Level and Future Risk of Diabetes: A Systematic Review

The use of A1C for the identification of persons with undiagnosed diabetes has been investigated for a number of years (1–3). A1C better reflects long-term glycemic exposure than current diagnostic tests based on point-in-time measures of fasting and postload blood glucose (4,5) and has improved test-retest reliability (6). In addition, A1C includes no requirement for fasting or for the oral glucose tolerance test's 2-h wait. These advantages should lead to increased identification and more timely treatment of persons with diabetes. Recently, an American Diabetes Association (ADA)-organized international expert committee recommended the adoption of the A1C assay for the diagnosis of diabetes at a cut point of 6.5% (7). This cut point was primarily derived from a review of studies that examined the association of A1C values with incident retinopathy, and some of the most influential data were obtained from recently published prospective studies. Retinopathy was chosen as the ultimate criterion because it is among the main complications of diabetes. Identification of the point on the A1C distribution most closely related to future retinopathy will identify persons in the greatest need of interventions for the prevention of diabetes complications. In addition to utility and convenience, A1C could help identify persons at increased risk of developing diabetes. This is an important public health priority since a structured lifestyle program or the drug metformin can reduce the incidence of diabetes by at least 50 and 30%, respectively (8). Ideally, selection of diagnostic cut points for pre-diabetes would be based on evidence that intervention, when applied to the high-risk group of interest, results not only in the prevention of diabetes but also later complications. However, currently there are no trials that can provide data to determine the ideal method for defining cut points. In the absence of such data, expert committees had to rely on information about the shape of risk curves for complications such as retinopathy. Previous expert committees assembled to address this issue have noted that there is no clear difference in retinopathy risk between different levels of impaired glucose tolerance (7). We are unaware of published prospective studies of adequate sample size or duration that have followed people in various pre-diabetic categories across the full span of time until complications developed. In the absence of informative trials (as well as prospective studies), the studies that measure A1C at baseline and incident diabetes may provide the definitions of high-risk states. To better define A1C ranges that might identify persons who would benefit from interventions to prevent or delay type 2 diabetes, we carried out a systematic review of published prospective studies that have examined the relationship of A1C to future diabetes incidence

In situ conjugation of dithiophenol maleimide polymers and oxytocin for stable and reversible polymer–peptide conjugates

The in situ one-pot synthesis of peptide–polymer bioconjugates is reported. Conjugation occurs efficiently without the need for purification of dithiophenol maleimide functionalized polymer as a disulfide bridging agent for the therapeutic oxytocin. Conjugation of polymers was demonstrated to be reversible and to significantly improve the solution stability of oxytocin

Bayesian Inference for Structural Vector Autoregressions Identified by Markov-Switching Heteroskedasticity

In this study, Bayesian inference is developed for structural vector autoregressive models in which the structural parameters are identified via Markov-switching heteroskedasticity. In such a model, restrictions that are just-identifying in the homoskedastic case, become over-identifying and can be tested. A set of parametric restrictions is derived under which the structural matrix is globally or partially identified and a Savage-Dickey density ratio is used to assess the validity of the identification conditions. The latter is facilitated by analytical derivations that make the computations fast and numerical standard errors small. As an empirical example, monetary models are compared using heteroskedasticity as an additional device for identification. The empirical results support models with money in the interest rate reaction function.Comment: Keywords: Identification Through Heteroskedasticity, Bayesian Hypotheses Assessment, Markov-switching Models, Mixture Models, Regime Chang

PEG−peptide conjugates

The remarkable diversity of the self-assembly behavior of PEG−peptides is reviewed, including self-assemblies formed by PEG−peptides with β-sheet and α-helical (coiled-coil) peptide sequences. The modes of self-assembly in solution and in the solid state are discussed. Additionally, applications in bionanotechnology and synthetic materials science are summarized

Formation of giant amphiphiles by post-functionalization of hydrophilic protein-polymer conjugates

A novel, generic method for the synthesis of families of tri-block protein-polymer giant amphiphiles was designed and developed. We have synthesized a hydrophilic alpha-maleimido poly-1-alkyne with M-n = 9.5 kDa (H-1-NMR) and narrow PDi (1.15 as measured by SEC) via ATRP (Atom Transfer Radical Polymerization). This polymer was successfully coupled to BSA to afford a hydrophilic multifunctional bioconjugate which was isolated using protein purification techniques and fully characterized. Following the post-functionalization approach, we introduced hydrophobicity to the resulting hydrophilic biohybrid by a straightforward, high yield "click'"-chemistry cycloaddition step. The resulting tri-block protein-polymer amphiphiles were isolated and showed interesting aggregation patterns (TEM, confocal microscopy)

Branching of Substituted Push-Pull Polyenes for Enhanced Two-Photon Absorption

The paper will focus on the branching of substituted push-pull polyenes in the weak to medium interaction limit. Branching of dipolar units of increasing length is achieved through connection via a central triphenylamine core, leading to three-branched structures. Linear and nonlinear optical properties of these octupolar chromophores are compared to those of their dipolar analogues. In particular, photophysical properties, solvatochromism and two-photon absorption (TPA) cross sections are investigated. Results confirm that the branching strategy leads to TPA activation in spectral regions were the dipolar units are almost transparent and that large TPA enhancement can be achieved on a very large spectral range. Localization of the emitting excited state on a single dipolar branch is also evidenced

Branching of substituted push-pull polyenes for enhanced two-photon absorption.

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