Metformin acts in the gut and induces gut-liver crosstalk.

Metformin is the most prescribed drug for DM2, but its site and mechanism of action are still not well established. Here, we investigated the effects of metformin on basolateral intestinal glucose uptake (BIGU), and its consequences on hepatic glucose production (HGP). In diabetic patients and mice, the primary site of metformin action was the gut, increasing BIGU, evaluated through PET-CT. In mice and CaCo2 cells, this increase in BIGU resulted from an increase in GLUT1 and GLUT2, secondary to ATF4 and AMPK. In hyperglycemia, metformin increased the lactate (reducing pH and bicarbonate in portal vein) and acetate production in the gut, modulating liver pyruvate carboxylase, MPC1/2, and FBP1, establishing a gut-liver crosstalk that reduces HGP. In normoglycemia, metformin-induced increases in BIGU is accompanied by hypoglycemia in the portal vein, generating a counter-regulatory mechanism that avoids reductions or even increases HGP. In summary, metformin increases BIGU and through gut-liver crosstalk influences HGP.

The global diet quality score as an indicator of adequate nutrient intake and dietary quality - a nation-wide representative study.

BACKGROUND: The Global Diet Quality Score (GDQS) was developed to be a simple, timely and cost-effective tool to track, simultaneously, nutritional deficiency and non-communicable disease risks from diet in diverse settings. The objective was to investigate the performance of GDQS as an indicator of adequate nutrient intake and dietary quality in a national-representative sample of the Brazilian population. METHODS: Nationally-representative data from 44,744 men and non-pregnant and non-lactating women aging ≥ 10 years, from the Brazilian National Dietary Survey were used. Dietary data were collected through two 24-h recalls (24HR). The GDQS was calculated and compared to a proxy indicator of nutrient adequate intake (the Minimum Dietary Diversity for Women-MDD-W) and to an indicator of high-risk diet for non-communicable diseases (caloric contribution from ultra-processed foods-UPF). To estimate the odds for overall nutrient inadequacy across MDD-W and GDQS quintiles, a multiple logistic regression was applied, and the two metrics' performances were compared using Wald's post-test. RESULTS: The mean GDQS for Brazilians was 14.5 (0-49 possible range), and only 1% of the population had a low-risk diet (GDQS ≥ 23). The GDQS mean was higher in women, elderly individuals and in higher-income households. An inverse correlation was found between the GDQS and UPF (rho (95% CI) = -0.20(-0.21;-0.19)). The odds for nutrient inadequacy were lower as quintiles of GDQS and MDD-W were higher (p-trend < 0.001), and MDD-W had a slightly better performance than GDQS (p-diff < 0.001). Having a low-risk GDQS (≥ 23) lowered the odds for nutrient inadequacy by 74% (95% CI:63%-81%). CONCLUSION: The GDQS is a good indicator of overall nutrient adequacy, and correlates well with UPF in a nationally representative sample of Brazil. Future studies must investigate the relationship between the GDQS and clinical endpoints, strengthening the recommendation to use this metric to surveillance dietary risks.

Normal bone health in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy.

It is of great importance to investigate any potential detrimental effect on bone health in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy. This study demonstrated normal bone health in well-controlled patients. Additionally, glucocorticoid dose may play an important role in the mineral density of femoral neck region. PURPOSE: To compare regional bone mineral densities (BMDs) and bone statuses of young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency with a control group. The duration and dose of glucocorticoid therapy and relative skeletal muscle index (an indicator of sarcopenia) were also analyzed as parameters to predict bone health. METHODS: This case-control study included 23 patients (7 male and 16 female) and 20 controls (8 male and 12 female) matched by age range (18 to 31 years). Dual energy X-ray absorptiometry and phalangeal quantitative ultrasound (QUS) were used to estimate BMD and bone status, respectively. RESULTS: No difference was observed between patients and controls (of both sexes) in absolute values of BMD and Z-scores for the total body, lumbar spine, and femoral neck; or the bone status (estimated by phalangeal QUS). Multiple linear regression analysis demonstrated that relative skeletal muscle index independently correlated with BMD of the entire body (ß: 0.67, P = 0.007), the lumbar spine (ß: 0.73, P = 0.005), and the femoral neck (ß: 0.67, P = 0.007). However, the dose of glucocorticoids (ß: - 0.38, P = 0.028) independently correlated with BMD in the femoral neck region alone. CONCLUSION: No signs of change in bone health were observed in patients with CAH when compared to the reference group. Additionally, a marker of sarcopenia was demonstrated to have a role in mineral density mechanisms in all analyzed bone sites. Only the femoral neck BMD seemed to be significantly dependent on glucocorticoid dose.

Jabuticaba juice improves postprandial glucagon-like peptide-1 and antioxidant status in healthy adults: a randomized crossover trial.

Jabuticaba is a Brazilian berry rich in polyphenols, which may exert beneficial effects on metabolic diseases. This randomized crossover study aimed to determine the effects of jabuticaba juice (250 ml in a portion) on postprandial response. Sixteen healthy subjects (11 women; 5 men; 28.4 ± 3.8 years old; body mass index (BMI) 21.7 ± 2.3 kg m-2) consumed two test products after fasting overnight in a randomized controlled crossover design. Each test product portion had a similar composition of sugar components: 250 mL water with glucose, fructose, colored with artificial non-caloric food colorings (placebo); and 250 mL of jabuticaba juice. Beverages were administered immediately before a carbohydrate meal. Blood samples were collected at 0, 15, 30, 45, 60, 90, and 120 min after each test product to analyze the concentrations of glucose, insulin, C-peptide, antioxidant capacity, plasma glucagon-like peptide-1 (GLP-1), and appetite sensations. Compared to the placebo, the intake of jabuticaba juice resulted in a higher GLP-1 response as the area under the curve (AUC) and peaking at 60 min. Jabuticaba juice also resulted in higher antioxidant capacity. Postprandial glucose, insulin, C-peptide levels, and appetite sensations were not significantly different between tests. In conclusion, 250 mL of jabuticaba juice before a carbohydrate meal was able to improve the antioxidant status and GLP-1 concentrations in healthy subjects.

Cardiovascular dysfunction risk in young adults with congenital adrenal hyperplasia caused by 21-hydroxylase enzyme deficiency.

BACKGROUND: The association of congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase enzyme (21OHase) deficiency, duration of treatment and dosage with cardiovascular dysfunction in young adults remains unclear. We aimed to evaluate myocardial function, vascular structures and epicardial fat thickness in young adults with CAH as a result of 21OHase deficiency. Correlations between the duration and dose of glucocorticoid therapy and cardiovascular parameters were analysed. METHODS: This case-control study of young adults (18-31 years old) included 20 patients (5 men and 15 women) and 16 control subjects (8 men and 8 women). Echocardiographic analysis was performed using high-resolution ultrasound. RESULTS: No ultrasonographic changes in any indices of myocardial function, vascular structures and epicardial fat thickness were found in patients, except for an impaired left ventricular end-diastolic diameter in female patients (28.1 ± 1.6 vs 26.0 ± 2.4 mm/m2 , P = .021), compared with those in individuals in the control group. Nevertheless, the individual patient values were within the normal range. Multiple linear regression analysis in female patients demonstrated that an elevated daily dose of glucocorticoids correlated with increased indices of left ventricular posterior wall thickness (Partial r = 0.68, P = .007), left ventricular end-diastolic diameter (Partial r = 0.62, P = .017), aortic diameter (Partial r = 0.60, P = .022) and left carotid artery intima-media thickness (Partial r = 0.61, P = .021), independently of treatment duration. CONCLUSION: No signs of cardiovascular dysfunction were observed in any patient. The daily dose of glucocorticoids may play a role in the mechanisms of some markers of cardiac hypertrophy, left ventricular and aortic dilation and subclinical atherosclerosis.

Insulin does not stimulate ß-alanine transport into human skeletal muscle.

To test whether high circulating insulin concentrations influence the transport of ß-alanine into skeletal muscle at either saturating or subsaturating ß-alanine concentrations, we conducted two experiments whereby ß-alanine and insulin concentrations were controlled. In experiment 1, 12 men received supraphysiological amounts of ß-alanine intravenously (0.11 g·kg-1·min-1 for 150 min), with or without insulin infusion. ß-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and ß-alanine analyses. ß-Alanine content in 24-h urine was assessed. In experiment 2, six men ingested typical doses of ß-alanine (10 mg/kg) before insulin infusion or no infusion. ß-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1, no differences between conditions were shown for plasma ß-alanine, muscle ß-alanine, muscle carnosine and urinary ß-alanine concentrations (all P > 0.05). In experiment 2, no differences between conditions were shown for plasma ß-alanine or muscle ß-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase ß-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the Vmax of ß-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize ß-alanine transport into muscle following ß-alanine intake.

Interleukin-17 acts in the hypothalamus reducing food intake.

Interleukin-17 (IL-17) is expressed in the intestine in response to changes in the gut microbiome landscape and plays an important role in intestinal and systemic inflammatory diseases. There is evidence that dietary factors can also modify the expression of intestinal IL-17. Here, we hypothesized that, similar to several other gut-produced factors, IL-17 may act in the hypothalamus to modulate food intake. We confirm that food intake increases IL-17 expression in the mouse ileum and human blood. There is no expression of IL-17 in the hypothalamus; however, IL-17 receptor A is expressed in both pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons. Upon systemic injection, IL-17 promoted a rapid increase in hypothalamic POMC expression, which was followed by a late increase in the expression of AgRP. Both systemic and intracerebroventricular injections of IL-17 reduced calorie intake without affecting whole-body energy expenditure. Systemic but not intracerebroventricular injection of IL-17 increase brown adipose tissue temperature. Thus, IL-17 is a gut-produced factor that is controlled by diet and modulates food intake by acting in the hypothalamus. Our findings provide the first evidence of a cytokine that is acutely regulated by food intake and plays a role in the regulation of eating.

ENERGY EXPENDITURE IN 21-HYDROXYLASE CONGENITAL ADRENAL HYPERPLASIA PATIENTS AND COMPARISON WITH PREDICTIVE EQUATIONS.

Objective: To characterize resting energy expenditure (REE) in patients with classic 21-hydroxylase congenital adrenal hyperplasia (21-OH CAH) using indirect calorimetry and compare it to the most commonly used REE predictive equations. Methods: This case-control study comprised 29 post-pubertal 21-OH CAH patients regularly followed at the University of Campinas. Elevated serum 17-hydroxyprogesterone and CYP21 gene molecular analysis confirmed the diagnosis. A healthy control group paired by age, gender, and body mass index was examined. Dual-energy X-ray absorptiometry (DEXA) measured body compositions. A bioimpedance analyzer determined fat-free mass, and indirect calorimetry using a metabolic cart measured REE. Results: Unlike our initial hypothesis, REE was similar between the groups (18.7 ± 3.1 kcal/kg/day in CAH vs. 20.3 ± 3.5 kcal/kg/day in controls; P = .728). No predictive equations reached the stipulated accuracy criteria, thus lacking validity in REE assessment in adults with the characteristics of the group studied. DEXA analysis revealed higher body fat and diminished nonbone lean mass in 21-OH CAH. Anthropometric and bioelectrical impedance parameters were not significantly different. Conclusion: Classic 21-OH CAH is generally followed in reference centers, which may facilitate indirect calorimetry use for REE measurement. Alternatively, considering our REE findings in adult 21-OH CAH patients, nutrition management based on 25 kcal/body weight/day (measured REE × activity factor 1.2 to 1.3) may be reasonable for current body weight maintenance in these patients. Abbreviations: 17-OHP = 17-hydroxyprogesterone; 21-OH CAH = classic 21-hydroxylase deficiency congenital adrenal hyperplasia; BMI = body mass index; REE = resting energy expenditure; VO2 = volume of oxygen; VCO2 = volume of carbon dioxide.

Sagittal abdominal diameter resembles waist circumference as a surrogate marker of insulin resistance in adolescents-Brazilian Metabolic Syndrome Study.

OBJECTIVE: To evaluate the association of the sagittal abdominal diameter (SAD) with insulin resistance (IR) and metabolic syndrome (MetS) components, and to compare SAD with waist circumference (WC). SUBJECTS/METHODS: This was a multicenter, cross-sectional study of 520 adolescents (10- to 18-years old). IR was assessed using the homeostasis model assessment of IR (HOMA-IR) and the hyperglycaemic clamp (n = 76). RESULTS: SAD and WC were positively correlated with HOMA-IR (r = 0.637 and r = 0.653) and inversely correlated with the clamp-derived insulin sensitivity index (ISI) (r = -0.734 and r = -0.731); P < .001. In the multivariable linear regression analysis, SAD was positively associated with HOMA-IR (B = 0.046 ± 0.003) and inversely associated with the clamp-derived ISI (B = -0.084 ± 0.009) after adjusting for sex, age, and Tanner's stages (P < .001). When WC replaced the SAD, it was positively associated with HOMA-IR (B = 0.011 ± 0.001) and inversely associated with the clamp-derived ISI (B = -0.018 ± 0.002); P < .001. The values of the areas under the curves (AUC) were 0.823 and 0.813 for SAD and WC, respectively. In Bland-Altman analysis, there were agreement between both, SAD and WC, with the clamp-derived ISI (mean = 0.00; P > .05). The SAD and WC were positively associated with blood pressure, triglycerides, and uric acid, and inversely associated with high-density lipoprotein (HDL)-cholesterol after adjusting for sex, age, and Tanner's stages. CONCLUSION: The SAD was associated with IR and MetS components, with a good discriminatory power for detecting IR. When compared to WC, SAD showed equivalent results.

Visfatin is a positive predictor of bone mineral density in young survivors of acute lymphocytic leukemia.

Bone mass acquisition may be compromised in survivors of childhood acute lymphocytic leukemia due to various factors, including adiposity. Fat accumulation can affect bone through the direct effect of adipokines or indirectly through the state of chronic inflammation. The aim of this study was to evaluate the effect of body composition and adipokines on bone mass in survivors of acute lymphocytic leukemia. This was a cross-sectional study of 56 survivors aged between 15 and 24 years, 44.6 % of whom received cranial radiotherapy (18-24 Gy), assessed according to body fat, lean mass, and bone mineral density (dual energy X-ray absorptiometry), computed tomography scan-derived abdominal adipose tissue, and adipokines by a multiple regression analysis. Both lumbar spine L1-L4 (trabecular bone) and total body (cortical bone) bone mineral density were positively correlated with visfatin (p < 0.050). Lean mass index was positively correlated, while waist-to-height ratio was negatively correlated with cortical bone (p < 0.010). Low bone mineral density for chronological age was detected in 5.4 % of patients in total body, and 8.9 % at the lumbar spine. In survivors of acute lymphocytic leukemia, visfatin may play an important role in the complex relationship between body composition and bone. At present, visfatin may represent a model for further study of bone metabolism, and could possibly explain the unknown mechanisms linking bone metabolism and cancer.

The Obese Brain--Effects of Bariatric Surgery on Energy Balance Neurocircuitry.

Obesity is a highly prevalent disease in the world and with a major impact on global health. While genetic components are also involved in its pathogenesis, in recent years, it has shown a critical role of the innate and adaptive immune cell response in many tissues triggered by excess of nutrients such as lipids and glucose. Free fatty acids and other nutrient-related signals induce damage such as insulin resistance in the peripheral tissues but also in the brain. Specifically in the hypothalamus, these metabolic signals can trigger significant changes in the control of energy balance. Recent studies have shown that saturated fat disrupts melanocortin signaling of hypothalamic neuronal subgroups pivotal to energy control. Bariatric surgery is a treatment option for obesity when other tools have failed, because it is more effective than pharmacotherapy concerning of weight loss itself and in improvement of obesity-related comorbidities. Here, we review the mechanisms by which Roux-en Y gastric bypass (RYGB) can change peripheral signals that modulate melanocortin circuits involved in the regulation of energy balance.

Jaboticaba peel improves postprandial glucose and inflammation: A randomized controlled trial in adults with metabolic syndrome.

The modulation of glucose metabolism through dietary sources has been recognized as 1 of the most sustainable approaches for preventing of cardiometabolic diseases. Although fibers and phenolic compounds derived from jaboticaba (Plinia jaboticaba) peel have demonstrated improvements in metabolic pathways in preclinical models, their beneficial effects in clinical trials remain to be fully determined. This study aimed to assess the impact of jaboticaba peel (JP) powder supplementation on glucose metabolism compared with a placebo in individuals with metabolic syndrome (MetS). A single-blind, parallel, randomized, placebo-controlled trial involving 49 individuals with MetS was conducted. Participants were assigned to receive either a JP supplement (15 g/day) or a matched placebo. Anthropometry measurements, body composition, blood pressure, metabolic and inflammatory parameters, and a mixed-meal tolerance test were assessed at weeks 0 and 5. Daily intake of JP improved the area under the curve of glucose (P = .025) and the interleukin-6 (IL-6) (P = .045). No significant time × treatment effects were observed for blood pressure, body weight, body composition, lipid metabolism, glucagon-like peptide-1, inflammatory cytokines (tumor necrosis factor-α, IL-1ß), C-reactive protein, and insulin sensitivity and resistance indexes. JP supplementation may be a promising approach for managing MetS disorders, potentially by reducing the area under the curve for glucose and the proinflammatory cytokine IL-6. This research is registered at the Brazilian Registry of Clinical Trials (RBR-8wwq9t).

Gut bacterial markers involved in association of dietary inflammatory index with visceral adiposity.

OBJECTIVE: To deepen the understanding of the influence of diet on weight gain and metabolic disturbances, we examined associations between diet-related inflammation and body composition and fecal bacteria abundances in participants of the Nutritionists' Health Study. METHODS: Early-life, dietary and clinical data were obtained from 114 women aged ≤45 years. A validated food frequency questionnaire was used to calculate the energy-adjusted dietary inflammatory index (E-DII). Participants' data were compared by E-DII quartiles using ANOVA or Kruskal-Wallis. Associations of DXA-determined body composition with the E-DII were tested by multiple linear regression using DAG-oriented adjustments. Fecal microbiota was analyzed targeting the V4 region of the 16S rRNA gene. Spearman correlation coefficients were used to test linear associations; differential abundance of genera across the E-DII quartiles was assessed by pair-wise comparisons. RESULTS: E-DII score was associated with total fat (b=1.80, p<0.001), FMI (b=0.08, p<0.001) and visceral fat (b=1.19, p=0.02), independently of maternal BMI, birth type and breastfeeding. E-DII score was directly correlated to HOMA-IR (r=0.30; p=0.004), C-reactive protein (r=0.29; p=0.003) and to the abundance of Actinomyces, and inversely correlated to the abundance of Eubacterium.xylanophilum.group. Actinomyces were significantly more abundant in the highest (most proinflammatory) E-DII quartile. CONCLUSIONS: Association of E-DII with markers of insulin resistance, inflammation, body adiposity and certain gut bacteria are consistent with beneficial effects of anti-inflammatory diet on body composition and metabolic profile. Bacterial markers, such as Actinomyces, could be involved in the association between the dietary inflammation with visceral adiposity. Studies designed to explore how a pro-inflammatory diet affects both central fat deposition and gut microbiota are needed.

Appetite-regulating hormones from the upper gut: disrupted control of xenin and ghrelin in night workers.

OBJECTIVE: Shift work is associated with circadian rhythm disorder, impaired sleep and behavioural changes, including eating habits, predisposing to obesity and metabolic dysfunctions. It involves a neuro-hormonal dysregulation of appetite towards positive energy balance, including increased ghrelin and decreased leptin, but little is known about other hormones, such as xenin, derived from the upper gut (like ghrelin), and lower gut hormones. Our objective was to compare night workers with day workers in relation to appetite-regulating hormones and other metabolic parameters. DESIGN: Cross-sectional, observational study. PARTICIPANTS: Twenty-four overweight women, divided into night shift workers (n = 12) and day shift workers (n = 12). MEASUREMENTS: BMI, waist circumference, fat mass percentage; diet composition; Pittsburgh Sleep Quality Index; lipids; adipokines; meal tolerance test curves of glucose, insulin, ghrelin, PYY3-36, oxyntomodulin, xenin, GLP-1; insulin sensitivity (Stumvoll index). RESULTS: Night workers, as compared with day workers, had greater body fat mass percentage and tendency to greater waist circumference despite similar BMI; greater energy intake; impaired sleep; lower insulin sensitivity; increased triglycerides and tendency to increased C-reactive protein; similar levels of leptin and other adipokines. Night workers had a blunted post-meal suppression of ghrelin (AUCi(0-60 min) 19·4 ± 139·9 vs -141·9 ± 9·0 ng/ml·60 min, P < 0·01); blunted rise of xenin (AUC(0-180 min) 8690·9 ± 2988·2 vs 28 504·4 ± 20 308·3 pg/ml·180 min, P < 0·01) and similar curves of PYY3-36, oxyntomodulin and GPL-1. CONCLUSION: Compared with day workers within the same BMI range, night workers presented a disrupted control of ghrelin and xenin, associated with behavioural changes in diet and sleep and increased adiposity and related metabolic alterations.

Neck circumference as a simple tool for identifying the metabolic syndrome and insulin resistance: results from the Brazilian Metabolic Syndrome Study.

OBJECTIVE: To investigate the relationship of the neck circumference (NC) with the metabolic syndrome (MetS) and insulin resistance (IR) in a large Brazilian population-based sample, within a wide range of adiposity and glucose tolerance, and to establish cut-off values of the NC for MetS and IR. CONTEXT: The NC correlates with cardiovascular risk factors, IR and components of MetS. Upper-body subcutaneous (sc) fat, as estimated by the NC, is associated with cardiovascular risk factors as much as abdominal fat, which is usually estimated by the waist circumference (WC). There are few epidemiological population-based studies on the clinical significance of the NC to MetS and IR. DESIGN: This is a cross-sectional study. PATIENTS: About 1053 Brazilian adults (18-60 years). MEASUREMENTS: Patients with BMI 18.5-40.0 kg/m(2), with normal glucose tolerance or type 2 diabetes (T2DM), were submitted to anthropometric measurements including waist circumference (WC), NC and BMI. Abdominal visceral fat (VF) was assessed by ultrasound. Insulin sensitivity (IS) was assessed by euglycaemic-hyperinsulinaemic clamp (10% of total sample) and HOMA-IR. Spearman correlations were used to evaluate the association between NC and IR and MetS risk factors. Receiver operating characteristic (ROC) curves were used for gender-specific cut-off values for the prediction of IR and MetS. Binary logistic regression analysis was used to assess the chance of developing IR or MetS according to the enlargement of NC and WC. RESULTS: The sample consisted of 28.6% men, with a mean age of 39.4 (12 years). T2DM diagnosis was present in 306 individuals, of whom 34% were men. NC correlated with WC and BMI in both men and women (P < 0.001). In both genders, NC showed a positive correlation with triglycerides, fasting glucose, fasting insulin and HOMA-IR, and NC had a negative association with high-density lipoprotein (HDL). NC and IS showed a moderate negative correlation. A significant correlation was demonstrated between VF and NC. In the ROC curves, NC presented the largest AUC for IR in women (P < 0.001), while NC presented a large AUC for MetS in both genders. CONCLUSIONS: Neck circumference measurements are an alternative and innovative approach for determining body fat distribution. The NC is positively associated with MetS risk factors, IR and VF, with established cut-off values for the prediction of MetS and IR.

The threshold value for identifying insulin resistance (HOMA-IR) in an admixed adolescent population: A hyperglycemic clamp validated study.

Objective: To validate the homeostasis model assessment (HOMA) of insulin resistance (IR) as a surrogate to the hyperglycemic clamp to measure IR in both pubertal and postpubertal adolescents, and determine the HOMA-IR cutoff values for detecting IR in both pubertal stages. Subjects and methods: The study sample comprised 80 adolescents of both sexes (aged 10-18 years; 37 pubertal), in which IR was assessed with the HOMA-IR and the hyperglycemic clamp. Results: In the multivariable linear regression analysis, adjusted for sex, age, and waist circumference, the HOMA-IR was independently and negatively associated with the clamp-derived insulin sensitivity index in both pubertal (unstandardized coefficient - B = -0.087, 95% confidence interval [CI] = -0.135 to -0.040) and postpubertal (B = -0.101, 95% CI, -0.145 to -0.058) adolescents. Bland-Altman plots showed agreement between the predicted insulin sensitivity index and measured clamp-derived insulin sensitivity index in both pubertal stages (mean =-0.00 for pubertal and postpubertal); all P > 0.05. The HOMA-IR showed a good discriminatory power for detecting IR with an area under the receiver operator characteristic curve of 0.870 (95% CI, 0.718-0.957) in pubertal and 0.861 (95% CI, 0.721-0.947) in postpubertal adolescents; all P < 0.001. The optimal cutoff values of the HOMA-IR for detecting IR were > 3.22 (sensitivity, 85.7; 95% CI, 57.2-98.2; specificity, 82.6; 95% CI, 61.2-95.0) for pubertal and > 2.91 (sensitivity, 63.6; 95% CI, 30.8-89.1, specificity, 93.7; 95%CI, 79.2-99.2) for postpubertal adolescents. Conclusion: The threshold value of the HOMA-IR for identifying insulin resistance was > 3.22 for pubertal and > 2.91 for postpubertal adolescents.

Association of physical activity and sitting with metabolic syndrome and hyperglycemic clamp parameters in adolescents - BRAMS pediatric study.

Introduction: Obesity and metabolic syndrome (MetS) have immediate and long-term consequences on adolescent health and well-being. Among the available treatments for MetS in adolescents, behavioral interventions such as increasing physical activity (PA) are preferred. This study aimed to investigate the association of PA and sitting time with MetS and a complete set of metabolic health parameters. Methods: Data from the Pediatric Brazilian Metabolic Syndrome Study (BRAMS-P), a cross-sectional multicenter study conducted using a convenience sample of 448 Brazilian adolescents (10y-19y), were used. Sociodemographic and lifestyle information were collected using a standardized questionnaire. Daily PA and sitting time were estimated from the International PA Questionnaire. Anthropometric parameters, body composition, and blood pressure were measured by trained researchers. Blood lipids, uric acid, hepatic enzymes, creatinine, glycated hemoglobin, glucose, and insulin were measured in fasting blood samples, and the Homeostasis Model Assessment for Insulin Resistance was calculated. A subsample of 57 adolescents underwent the hyperglycemic clamp protocol. Results: The odds for metabolic syndrome were higher among adolescents who spent >8h sitting (OR (95%CI)=2.11 (1.02 - 4.38)), but not in those classified as active (OR (95%CI)=0.98 (0.42 - 2.26)). Adolescents who spent more time sitting had higher BMI, waist circumference, sagittal abdominal diameter, neck circumference, percentage of body fat, and worse blood lipid profile. The insulin sensitivity index was moderately and positively correlated with moderate-to-high PA in minutes per day (rho=0.29; p=0.047). Conclusion: Time spent sitting was associated with worse metabolic parameters and must be restricted in favor of adolescent health. Regular PA is associated with improved insulin sensitivity and may be encouraged not only in adolescents with obesity or metabolic disorders but also to prevent adverse metabolic outcomes in normal-weight adolescents.

Normal ambulatory blood pressure in young adults with 21-hydroxylase enzyme deficiency undergoing glucocorticoid replacement therapy.

Objective: Herein, we compared ambulatory blood pressure (ABP) between young adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase enzyme (21OHase) deficiency and a control group. Additionally, we analyzed correlations between the glucocorticoid dose and androgen levels and ABP parameters. Subjects and methods: This case-control study included 18 patients (6 males and 12 females) and 19 controls (8 males and 11 females) matched by age (18-31 years). ABP monitoring was used to estimate blood pressure (BP) over a 24-h period. Results: No difference was noted between patients and controls in terms of systolic BP (males, 115.5 ± 5.6 vs. 117.0 ± 9.3, P = 0.733; and females, 106.4 ± 7.9 vs. 108.4 ± 7.6, P = 0.556, respectively) and diastolic BP during 24 h (males, 62.8 ± 7.5 vs. 66.2 ± 5.6, P = 0.349; and females, 62.7 ± 4.9 vs. 62.3 ± 4.9, P = 0.818, respectively). Systolic and diastolic BP and pulse pressure during daytime and nocturnal periods were similar between patients and controls. Furthermore, no differences were detected in the percentage of load and impaired nocturnal dipping of systolic and diastolic BP between patients and controls during the 24-h period. Additionally, the glucocorticoid dose (varying between r = -0.24 to 0.13, P > 0.05) and androgens levels (varying between r = 0.01 to 0.14, P > 0.05) were not associated with ABP parameters. Conclusion: No signs of an elevated risk for hypertension were observed based on ABP monitoring in young adults with CAH attributed to 21OHase deficiency undergoing glucocorticoid replacement therapy.

Parental body mass index and maternal gestational weight gain associations with offspring body composition in young women from the Nutritionists' Health Study.

Objective: Intrauterine environment can induce fetal metabolic programming that predisposes to adiposity-related chronic diseases in its lifespan. We examined the associations of parental nutritional status and gestational weight gain with offspring body composition in early adulthood. Methods: This is cross-sectional analysis of female participants of the NutriHS who were submitted to questionnaires, clinical examinations and body composition assessed by DXA. Association of preconception parental BMI and maternal gestational weight gain (exposures) with body composition measurements (outcomes) were analyzed using multiple linear models adjusted for Directed Acyclic Graphs-based covariables (maternal and paternal educational level, maternal age, and tobacco, alcohol and/or drugs use). The sample included 124 women (median 28 (24-31) years) with a mean BMI of 25.4 ± 4.7 kg/m2. Results: No association between previous paternal BMI and offspring's body composition was detected. In the fully adjusted linear regression model, maternal BMI was associated with offspring's total lean mass (ß = 0.66, p = 0.001), appendicular skeletal muscle mass index (ASMI) (ß = 0.11, p = 0.003) and fat mass index (FMI) (ß = 0.03, p = 0.039). Gestational weight gain was associated with increased offspring's BMI (OR 1.12 [95% CI 1.02-1.20], p = 0.01). The linear regression model adjusted for maternal age and maternal and paternal education levels showed associations of gestational weight gain with offspring's ASMI (ß = 0.42, p = 0.046), FMI (ß = 0.22, p = 0.005) and android-to-gynoid fat ratio (ß = 0.09, p = 0.035). Conclusion: Our findings suggest that preconception maternal BMI could influence lean mass and general adiposity of young adult female offspring and that gestational weight gain could be useful for predicting centrally distributed adiposity.

Short-chain fatty acids are associated with adiposity, energy and glucose homeostasis among different metabolic phenotypes in the Nutritionists' Health Study.

BACKGROUND AND AIMS: The gut microbiome is associated with obesity, mainly mediated by bacteria-produced short-chain fatty acids (SCFAs). It is unknown how SCFA concentrations are associated with the phenotypes metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy obese/overweight (MHO), and metabolically unhealthy obese/overweight (MUO). We compared plasma and fecal SCFA concentrations among adult women categorized according to the metabolic phenotypes mentioned above and examined associations between SCFA and adiposity and components of energy and glucose homeostasis. METHODS: This was a cross-sectional study involving 111 participants. Body composition was assessed by DEXA. Energy and glycemic homeostasis were assessed by the standard mixed-meal tolerance test coupled with indirect calorimetry. SCFAs were quantified by gas chromatography and mass spectrometry. RESULTS: Only plasma propionate was increased in the MHNW phenotype compared to the MHO and MUO phenotypes [p < 0.05]. Fecal propionate and butyrate concentrations and plasma propionate concentrations were inversely associated with total and visceral adiposity [p < 0.05]. Fecal and plasma SCFA concentrations were associated with reduced glucose, insulin and HbA1c levels, increased fasting and postprandial GLP-1 levels; and more preserved beta-cell function [p < 0.05]. Fecal and plasma SCFA concentrations were positively correlated with resting energy expenditure and lipid oxidation rate and inversely correlated with the oxidation rate of carbohydrates [p < 0.05]. CONCLUSION: These findings reinforce the concept that fecal and plasma SCFA concentrations are linked to specific components of energy and glucose homeostasis; and body adiposity. However, it was not possible to discriminate the different metabolic phenotypes of adiposity based on the determination of fecal SCFA concentrations.