1,721,069 research outputs found
Lower “Awake and Fed Thermogenesis” Predicts Future Weight Gain in Subjects with Abdominal Adiposity
Decline in the Acute Insulin Response in Relationship to Plasma Glucose Concentrations
BACKGROUND:
To investigate (1) whether the decline in acute insulin response (AIR) precedes or coincides with defined glucose regulation categories and whether acute insulin response decline varies by race and adiposity, (2) linearity of the relationship between acute insulin response and increasing plasma glucose concentrations, (3) longitudinal changes in acute insulin response accounting for changes in insulin action across categories of glucose tolerance.
METHODS:
Clinical cross-sectional and longitudinal study of nondiabetic subjects. Inpatient assessment of oral glucose tolerance (2-h PG, fasting PG), and acute insulin response (intravenous glucose tolerance test) in 326 and 84 Native Americans of full and ≤6/8th Southwestern heritage, respectively, and 115 Whites. Linearity of acute insulin response vs plasma glucose concentrations investigated using spline analyses. Follow-up (average = 2.07 years) glucose tolerance, acute insulin response, and insulin action (hyperinsulinemic-euglycemic clamp) assessed in 230 full Native Americans.
RESULTS:
In certain groups, the relationship between acute insulin response and increasing plasma glucose levels was non-linear. In all groups, acute insulin response decline preceded the cut-offs for traditional glucose regulation categories, although the timing with respect to increasing plasma glucose varied by race and adiposity. Longitudinal data indicated that improvement in insulin action is the key factor to preserve insulin secretion, underlying the reversion of glucose tolerance in prediabetic individuals.
CONCLUSIONS:
With worsening insulin action, the decline in insulin secretion occurred prior to current diagnostic guidelines for impaired glucose regulation. However, the relationship between acute insulin response and increasing plasma glucose varies and was not always non-linear. Understanding the dynamics of this relationship may determine when to initiate preventive pharmacotherapy directed at the preservation of β-cell failure
Fasting Hyperglycemia Predicts Lower Rates of Weight Gain by Increased Energy Expenditure and Fat Oxidation Rate
Context:
Body fat-free mass (FFM), energy expenditure (EE), and respiratory quotient (RQ) are known predictors of daily food intake. Because FFM largely determines EE, it is unclear whether body composition per se or the underlying metabolism drives dietary intake.
Objective:
The objective of the study was to test whether 24-hour measures of EE and RQ and their components influence ad libitum food intake independently of FFM.
Design and Participants:
One hundred seven healthy individuals (62 males/45 females, 84 Native Americans/23 whites; age 33 ± 8 y; body mass index 33 ± 8 kg/m2; body fat 31% ± 8%) had 24-hour measures of EE in a whole-room indirect calorimeter during energy balance, followed by 3 days of ad libitum food intake using computerized vending machine systems. Body composition was estimated by dual-energy x-ray absorptiometry.
Main Outcome Measures:
FFM, 24-hour EE, RQ, spontaneous physical activity, sleeping EE (sleeping metabolic rate), awake and fed thermogenesis, and ad libitum food intake (INTAKE) were measured.
Results:
Higher 24-hour RQ (P < .001, partial R2 = 16%) and EE (P = .01, partial R2 = 7%), but not FFM (P = .65), were independent predictors of INTAKE. Mediation analysis demonstrated that 24-hour EE is responsible for 80% of the FFM effect on INTAKE (44.5 ± 16.9 kcal ingested per kilogram of FFM, P= .01), whereas the unique effect due to solely FFM was negligible (10.6 ± 23.2, P = .65). Spontaneous physical activity (r = 0.33, P = .001), but not sleeping metabolic rate (P = .71), positively predicted INTAKE, whereas higher awake and fed thermogenesis determined greater INTAKE only in subjects with a body mass index of 29 kg/m2 or less (r = 0.44, P = .01).
Conclusions:
EE and RQ, rather than FFM, independently determine INTAKE, suggesting that competitive energy-sensing mechanisms driven by the preferential macronutrient oxidation and total energy demands may regulate food intake
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Autoantibodies Against PFDN2 Are Associated With An Increased Risk of Type 2 Diabetes: A Case-Control Study
BackgroundThe adaptive immune system is involved in type 2 diabetes mellitus (T2DM), indicating the presence of unidentified autoantibodies that might be useful biomarkers for emerging immunomodulatory therapy. A prior microarray study with a small number of participants suggested the association of novel autoantibodies with T2DM in Southwest American Indians. We therefore sought to determine whether antibodies against 14 target proteins are associated with T2DM in a large case-control study.
MethodsParticipants were adults (age 20-59y) of Southwest American Indian heritage. Plasma antibodies against 14 possible target proteins were measured in 476 cases with T2DM of less than 5years duration and compared with 424 controls with normal glucose regulation.
ResultsHigher levels of antibodies against prefoldin subunit 2 (PFDN2) were associated with T2DM (P=.0001; Bonferroni-corrected threshold for multiple tests=0.0036 [=0.05]). The association between anti-PFDN2 antibodies and T2DM remained in multivariable logistic regression (odds ratio 1.27; 95% confidence interval, 1.09-1.49; per one SD difference in anti-PFDN2 antibody). The odds of T2DM were increased in the highest anti-PFDN2 antibody quintile by 66% compared with the lowest quintile. Differences in anti-PFDN2 antibodies were most prominent among cases with earlier onset of disease (ie, age 20-39y) compared with controls.
ConclusionsAnti-PFDN2 antibodies are associated with T2DM and might be a useful biomarker. These findings indicate that autoimmunity may play a role in T2DM in Southwest American Indians, especially among adults presenting with young onset of disease
Identification of individuals with insulin resistance using routine clinical measurements
Insulin resistance is a treatable precursor of diabetes and potentially of cardiovascular disease as well. To identify insulin-resistant patients, we developed decision rules from measurements of obesity, fasting glucose, insulin, lipids, and blood pressure and family history in 2,321 (2,138 nondiabetic) individuals studied with the euglycemic insulin clamp technique at 17 European sites; San Antonio, Texas; and the Pima Indian reservation. The distribution of whole-body glucose disposal appeared to be bimodal, with an optimal insulin resistance cutoff of 28.9 kg/m(2), homeostasis model assessment of insulin resistance (HOMA-IR) >4.65, or BMI > 27.5 kg/m(2) and HOMA-IR > 3.60. The fasting serum insulin concentrations corresponding to these HOMA-IR cut points were 20.7 and 16.3 muU/ml, respectively. This rule had a sensitivity and specificity of 84.9 and 78.7%, respectively. The second model, which included clinical measurements but no laboratory determinations, had an aROC of 85.0% and generated a decision rule that had a sensitivity and specificity of 78.7 and 79.6%, respectively. The third model, which included clinical measurements and lipid measurements but not insulin (and thus excluded HOMA-IR as well), had a similar aROC (85.1%), sensitivity (81.3%), and specificity (76.3%). Thus, insulin-resistant individuals can be identified using simple decision rules that can be tailored to specific needs
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Differential methylation of genes in individuals exposed to maternal diabetes in utero
Aims/hypothesis
Individuals exposed to maternal diabetes in utero are more likely to develop metabolic and cardiovascular diseases later in life. This may be partially attributable to epigenetic regulation of gene expression. We performed an epigenome-wide association study to examine whether differential DNA methylation, a major source of epigenetic regulation, can be observed in offspring of mothers with type 2 diabetes during the pregnancy (OMD) compared with offspring of mothers with no diabetes during the pregnancy (OMND).
Methods
DNA methylation was measured in peripheral blood using the Illumina HumanMethylation450K BeadChip. A total of 423,311 CpG sites were analysed in 388 Pima Indian individuals, mean age at examination was 13.0 years, 187 of whom were OMD and 201 were OMND. Differences in methylation between OMD and OMND were assessed.
Results
Forty-eight differentially methylated CpG sites (with an empirical false discovery rate ≤0.05), mapping to 29 genes and ten intergenic regions, were identified. The gene with the strongest evidence was LHX3, in which six CpG sites were hypermethylated in OMD compared with OMND (p ≤ 1.1 × 10−5). Similarly, a CpG near PRDM16 was hypermethylated in OMD (1.1% higher, p = 5.6 × 10−7), where hypermethylation also predicted future diabetes risk (HR 2.12 per SD methylation increase, p = 9.7 × 10−5). Hypermethylation near AK3 and hypomethylation at PCDHGA4 and STC1 were associated with exposure to diabetes in utero (AK3: 2.5% higher, p = 7.8 × 10−6; PCDHGA4: 2.8% lower, p = 3.0 × 10−5; STC1: 2.9% lower, p = 1.6 × 10−5) and decreased insulin secretory function among offspring with normal glucose tolerance (AK3: 0.088 SD lower per SD of methylation increase, p = 0.02; PCDHGA4: 0.08 lower SD per SD of methylation decrease, p = 0.03; STC1: 0.072 SD lower per SD of methylation decrease, p = 0.05). Seventeen CpG sites were also associated with BMI (p ≤ 0.05). Pathway analysis of the genes with at least one differentially methylated CpG (p < 0.005) showed enrichment for three relevant biological pathways.
Conclusions/interpretation
Intrauterine exposure to diabetes can affect methylation at multiple genomic sites. Methylation status at some of these sites can impair insulin secretion, increase body weight and increase risk of type 2 diabetes
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