Plasma branched-chain amino acid concentrations in the study associated with the infusion of insulin at 40 mU/m²/min.

<p>Values are means ± SE and median (1^st quartile—3^rd quartile); Time 0, prior to the initiation of any infusions; Basal Period, infusion of saline (Control, N = 5) or branched-chain amino acids (BCAA, N = 5); Hyperinsulinemic-euglycemic Clamp, infusion of 40 mU/m²/min insulin together with variable rate of 20% dextrose to maintain the plasma glucose concentrations at those measured at the end of the Basal Period.</p><p>*Statistically different compared to Time 0 (<i>P</i> ≤0.05)</p><p>^#Statistically different compared to Time 0 and Basal Period (<i>P</i> ≤0.05)</p><p>†Statistically different between Control and BCAA groups (<i>P</i> ≤0.05)</p><p>Plasma branched-chain amino acid concentrations in the study associated with the infusion of insulin at 40 mU/m²/min.</p

Experimental design.

<p>Infusion protocol depicting the “basal” and “hyperinsulinemic-euglycemic clamp” study periods described in the text. [6,6–²H₂]glucose, branched-chain amino acids (BCAA; i.e., BranchAmin), saline, insulin and glucose were infused as indicated; [BCAA], total branched-chain amino acids concentration.</p

Insulin-stimulated changes in plasma glucose turnover.

<p>Changes from the basal period in the rates of endogenous glucose production (EGP) and whole-body glucose disposal (GDR) as a result of the insulin infusion at either 40 mU/m²/min (A) or 80 mU/m²/min (B) in the control group (Control) and the group with the increased plasma branched-chain amino acid (BCAA) concentrations. Boxes describe interquartile range (IQR; 1^st quartile—3^rd quartile) with the horizontal line in the box representing the median value.</p

Plasma glucose and insulin concentrations in the study associated with the infusion of insulin at 80 mU/m²/min.

<p>Values are means ± SE and median (1^st quartile—3^rd quartile); Time 0, prior to the initiation of any infusions; Basal Period, infusion of saline (Control, N = 3) or branched-chain amino acids (BCAA, N = 4); Hyperinsulinemic-euglycemic Clamp, infusion of 80 mU/m²/min insulin together with variable rate of 20% dextrose to maintain the plasma glucose concentrations at those measured at the end of the Basal Period;</p><p>*<i>P</i> ≤0.05 when compared to Time 0 and Basal Period</p><p>^&<i>P</i> = 0.09 when compared to Time 0 and Basal Period</p><p>Plasma glucose and insulin concentrations in the study associated with the infusion of insulin at 80 mU/m²/min.</p

Plasma branched-chain amino acid concentrations in the study associated with the infusion of insulin at 80 mU/m²/min.

<p>Values are means ± SE and median (1^st quartile—3^rd quartile); Time 0, prior to the initiation of any infusions; Basal Period, infusion of saline (Control, N = 3) or branched-chain amino acids (BCAA, N = 4); Hyperinsulinemic-euglycemic Clamp, infusion of 80 mU/m²/min insulin together with variable rate of 20% dextrose to maintain the plasma glucose concentrations at those measured at the end of the Basal Period.</p><p>*Statistically different compared to Time 0 (<i>P</i> ≤0.05)</p><p>†Statistically different between Control and BCAA groups (<i>P</i> ≤0.05).</p><p>Plasma branched-chain amino acid concentrations in the study associated with the infusion of insulin at 80 mU/m²/min.</p

Plasma glucose turnover.

<p>Rates of endogenous glucose production (EGP) and whole-body glucose disposal (GDR) in the basal period (i.e., Basal) and following insulin infusion (i.e., Insulin). Insulin was infused at either 40 mU/m²/min in a control group (A) and a group with increased plasma branched-chain amino acid concentrations (B) or 80 mU/m²/min in a control group (C) and a group with increased plasma branched-chain amino acid concentrations (D). Boxes describe interquartile range (IQR; 1^st quartile—3^rd quartile) with the horizontal line in the box representing the median value. <i>P</i> values are for the comparison of the corresponding medians.</p

Physical and clinical characteristics of the subjects.

<p>Values are means ± SE; BMI, body mass index, ALT, alanine aminotransferase; AST, aspartate aminotransferase; BCAA, branched-chain amino acids; HDL-C, High Density Lipoprotein-Cholesterol; HOMA-IR, Homeostatic model assessment of insulin resistance; Body fat was determined using bioimpedance; There were no significant differences between groups (<i>P</i> >0.05).</p><p>Physical and clinical characteristics of the subjects.</p

DataSheet1_A performance review of novel adiposity indices for assessing insulin resistance in a pediatric Latino population.docx

IntroductionBody mass index (BMI) percentile or BMI adjusted for age and sex is the most common anthropometric index to monitor and assess obesity in children. However, the ability of BMI to accurately predict insulin resistance (IR) in youth is debated. Determining the best method to noninvasively measure IR in the pediatric population is especially important due to the growing prevalence of type 2 diabetes mellitus (T2DM), which is more likely to develop in people with IR. Therefore, this study analyzed the performance of BMI against newer anthropometric indices in assessing IR in a pediatric Latino identifying sample.MethodsWe studied 127 pediatric Latino participants from the Arizona Insulin Resistance (AIR) registry and performed linear regression analyses between various measures of IR and adiposity indices, including body mass index (BMI), triponderal mass index (TMI), body adiposity index (BAI), pediatric body adiposity index (pBAI), a body shape index (ABSI), abdominal volume index (AVI), waist to height ratio (WtHR) and waist to hip ratio (WHR). Log transformations of each index adjusted for age and sex and IR were used for the linear regressions. Additionally, we generated receiver operating characteristics (ROC) from logistic regressions between HOMA-IR and HOMA2IR against the same indices.ResultsUsing the homeostatic assessment of insulin resistance (HOMA-IR), HOMA2IR, the quantitative insulin-sensitivity check index (QUICKI), fasting serum insulin, and FPG/FSI to measure IR, we showed that BMI adjusted for age and sex performs similarly to many of the newer indices in our sample. The correlation coefficients for pBAI [R2: 0.27, 95% confidence interval: 0.88–1.81, p 2 value for all measures of IR. Area under the curve (AUC) values for the receiver operating characteristics (ROC) for HOMA-IR and HOMA2IR support these conclusions.ConclusionsBMI adjusted for age and sex, despite its usage and simplicity, still stacks up well against newer indices in our Latino sample. Testing these indices across larger samples is necessary to generalize these findings and translate performance to adults.</p

Whole Blood Gene Expression Profiles in Insulin Resistant Latinos with the Metabolic Syndrome

<div><p>Although insulin resistance in skeletal muscle is well-characterized, the role of circulating whole blood in the metabolic syndrome phenotype is not well understood. We set out to test the hypothesis that genes involved in inflammation, insulin signaling and mitochondrial function would be altered in expression in the whole blood of individuals with metabolic syndrome. We further wanted to examine whether similar relationships that we have found previously in skeletal muscle exist in peripheral whole blood cells. All subjects (n=184) were Latino descent from the Arizona Insulin Resistance registry. Subjects were classified based on the metabolic syndrome phenotype according to the National Cholesterol Education Program’s Adult Treatment Panel III. Of the 184 Latino subjects in the study, 74 were classified with the metabolic syndrome and 110 were without. Whole blood gene expression profiling was performed using the Agilent 4x44K Whole Human Genome Microarray. Whole blood microarray analysis identified 1,432 probes that were altered in expression ≥1.2 fold and P<0.05 after Benjamini-Hochberg in the metabolic syndrome subjects. KEGG pathway analysis revealed significant enrichment for pathways including ribosome, oxidative phosphorylation and MAPK signaling (all Benjamini-Hochberg P<0.05). Whole blood mRNA expression changes observed in the microarray data were confirmed by quantitative RT-PCR. Transcription factor binding motif enrichment analysis revealed E2F1, ELK1, NF-kappaB, STAT1 and STAT3 significantly enriched after Bonferroni correction (all P<0.05). The results of the present study demonstrate that whole blood is a useful tissue for studying the metabolic syndrome and its underlying insulin resistance although the relationship between blood and skeletal muscle differs.</p> </div

Flow diagram of the steps used in the analysis of the microarray data.

<p>Flow diagram of the steps used in the analysis of the microarray data.</p