Publications by authors named "Bruno Geloneze"

104 Publications

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

Osteoporos Int 2021 Aug 18. Epub 2021 Aug 18.

Laboratory of Growth and Development (LabCreD), Center for Investigation in Pediatrics (CIPED), School of Medical Sciences (FCM), State University of Campinas (UNICAMP), 126 Tessália Vieira de Camargo Street, Cidade Universitária Zeferino Vaz, Campinas, SP, 13083-887, Brazil.

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 (β: 0.67, P = 0.007), the lumbar spine (β: 0.73, P = 0.005), and the femoral neck (β: 0.67, P = 0.007). However, the dose of glucocorticoids (β: - 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.
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http://dx.doi.org/10.1007/s00198-021-06097-wDOI Listing
August 2021

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

Int J Clin Pract 2021 Jul 1;75(7):e14233. Epub 2021 May 1.

Laboratory of Growth and Development (LabCreD), Center for Investigation in Pediatrics (CIPED), School of Medical Sciences (FCM), State University of Campinas (UNICAMP), Campinas, Brazil.

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/m , 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.
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http://dx.doi.org/10.1111/ijcp.14233DOI Listing
July 2021

Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses.

Obes Rev 2021 Jun 12;22(6):e13224. Epub 2021 Apr 12.

Department of Cardiology, State University of Campinas, Campinas, Brazil.

Despite being approved for clinical use, evidence of cardiovascular safety (CV) is lacking for treatment with bupropion, naltrexone, or their combination (B-N). The purpose of the study is to determine the relationship between these treatments and the risk of major cardiovascular adverse events (MACE). Phase 3 randomized clinical trials (RCT) evaluating bupropion, naltrexone, or B-N versus control with reported incidence of MACE. The meta-analysis included 12 RCTs, 69% for weight loss and 29% for smoking cessation, with 19,176 patients and 7354 patient-years who were randomized to an active treatment (bupropion [n = 2965] or B-N [n = 6980] or naltrexone [n = 249]) versus control (placebo [n = 6968] or nicotine patch [n = 2014]). The mean age was 54 ± 8 years (55% female), and the baseline BMI was 32 ± 5 kg/m . The additive network meta-analysis model for random effects showed no association between bupropion, B-N, or naltrexone and MACE (odds ratio [OR] = 0.90 [95%CI 0.65-1.25], p = 0.52; OR = 0.97 [95%CI 0.75-1.24], p = 0.79; OR = 1.08 [95%CI 0.71-1.63], p = 0.73, respectively; I = 0%, p = 0.86). Meta-regression analyses showed no significant association between MACE and potential confounders from RCT demographic disparities (p = 0.58). The statistical power (post hoc two-tailed) for non-inferiority was 91%, giving a strong probability of validity. Naltrexone, bupropion, or B-N is not associated with the incidence of MACE as compared with placebo.
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http://dx.doi.org/10.1111/obr.13224DOI Listing
June 2021

Insulin Resistance in Congenital Adrenal Hyperplasia is Compensated for by Reduced Insulin Clearance.

J Clin Endocrinol Metab 2021 03;106(4):e1574-e1585

Laboratory of Investigation in Metabolism and Diabetes (LIMED), Gastrocentro, University of Campinas (UNICAMP), Campinas, Brazil.

Context: Congenital adrenal hyperplasia (CAH) patients have potential normal longevity. However, a greater risk for cardiovascular disease has been reported. Insulin resistance and hyperinsulinemia have been described in CAH patients, whereas the prevalence of overt type 2 diabetes is not higher in CAH than in normal population.

Objective: To examine the contributions of insulin secretion and of hepatic insulin clearance to compensatory hyperinsulinemia in young insulin-resistant adults with classic CAH due to 21-hydroxylase deficiency (21-OHD).

Design: Cross-sectional.

Setting: University outpatient clinics.

Methods: Fifty-one participants: 21 controls, and 30 CAH (15 virilizing and 15 salt-wasting phenotypes), female/male (33/18), age (mean [SD]): 24.0 (3.6) years, body mass index: 24.6 (4.9)kg/m2 with normal glucose tolerance, were submitted to a hyperglycemic clamp study.

Main Outcome Measures: Insulin sensitivity, beta cell function, and hepatic insulin clearance using appropriate modeling.

Results: We found an increased insulin resistance in 21-OHD. The systemic hyperinsulinemia (posthepatic insulin delivery) was elevated in CAH patients. No increases were observed in insulin secretory rate (beta cell function) in the first phase or during the hyperglycemic clamp. The increase in insulin concentrations was totally due to a ~33% reduction in insulin clearance.

Conclusion: 21-OHD nonobese subjects have reduced insulin sensitivity and beta cell response unable to compensate for the insulin resistance, probably due to overexposure to glucocorticoids. Compensatory hyperinsulinemia is most related with reduced hepatic insulin clearance. The exclusive adaptation of the liver acts as a gating mechanism to regulate the access of insulin to insulin-sensitive tissues to maintain glucose homeostasis.
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http://dx.doi.org/10.1210/clinem/dgab010DOI Listing
March 2021

Maternal and paternal obesity are associated with offspring obestatin levels in the Nutritionists' Health Study.

Nutrition 2021 03 19;83:111067. Epub 2020 Nov 19.

Department of Epidemiology, School of Public Health, University of São Paulo, Brazil. Electronic address:

Objectives: The aim of this study was to examine whether paternal and maternal body mass indexes (BMIs) were independently associated with obestatin and visfatin levels in adult offspring.

Methods: This cross-sectional analysis included 124 women who participated in the Nutritionists' Health Study (NutriHS) at baseline. Early life events, anthropometry, dual-energy x-ray absorptiometry-determined body composition and blood sample were obtained. Associations of parental BMI with outcomes (obestatin and visfatin) were tested by multiple linear regression, using minimal sufficient adjustments recommended by Directed Acyclic Graph. Participants' mean BMI was 25 ± 5 kg/m and 74% were metabolically healthy. Median obestatin and visfatin levels were 56.4 pg/mL (42-72) and 17.7 ng/mL (14-21.8), respectively. Eleven percent of mothers and 39% of fathers were overweight/obese.

Results: Daughters born from overweight/obese mothers had higher BMI than those born from normal weight women (P = 0.003). In adjusted regression model, offspring obestatin levels were associated with maternal BMI (β = -0.03; P = 0.045) and paternal BMI (β = -0.02; P = 0.048) independently of maternal and paternal education, maternal age, and maternal use of tobacco, alcohol, and/or drugs. No association was detected with visfatin levels.

Conclusion: Inverse associations of maternal and paternal BMIs with offspring obestatin concentrations in women could suggest a utility of this biomarker of energy regulation determined in early adulthood. Whether obestatin could be an indicator of protection against obesity-related disorders in the life course requires investigation in studies designed to test such hypothesis.
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http://dx.doi.org/10.1016/j.nut.2020.111067DOI Listing
March 2021

FODMAP project: Development, validation and reproducibility of a short food frequency questionnaire to estimate consumption of fermentable carbohydrates.

Clin Nutr 2021 05 27;40(5):3409-3420. Epub 2020 Nov 27.

School of Applied Sciences, University of Campinas (UNICAMP), 1300, Pedro Zaccaria Street, University City, 13484-350, Limeira, São Paulo, Brazil; Laboratory of Investigation on Metabolism and Diabetes - LIMED, Gastrocentro, School of Medical Sciences, University of Campinas (UNICAMP), 420, Carlos Chagas Street, University City Zeferino Vaz, 13083-878, Campinas, São Paulo, Brazil. Electronic address:

Background & Aims: Irritable bowel syndrome (IBS) is a functional disorder that is characterized by gastrointestinal symptoms and that has a major impact on quality of life, resulting in direct and indirect health care costs. The majority of patients with IBS suffer from food intolerances, most commonly related to the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs). This study aimed to develop and verify the validity and reproducibility of a short food frequency questionnaire (FFQ) to assess typical FODMAP consumption in adults with IBS.

Methods: The primary FFQ list consisted of source foods of FODMAPs that contributed at least 10% to the frequency of consumption among 855 adults from a population-based study in the municipality of Campinas in 2014/2015. In addition, source foods of FODMAPs (according to the Monash University Low FODMAP Diet application) and foods commonly consumed by the Brazilian population (according to the FFQ for adults validated in the city of São Paulo) were included. One hundred and five (n = 105) healthy subjects were recruited to respond to the FFQ twice and to respond the 24-h dietary recall (24HR) three times during a 3-month period. The relative validity of the proposed instrument was compared with the average of the three 24HRs, and the reproducibility of the instrument was assessed by comparing both FFQ applications. The following statistical analyses were used for validation and reproducibility: Wilcoxon's test, Spearman's correlation analysis, weighted kappa, Bland Altman's plot and index, and interclass correlation coefficient.

Results: The final list of items for the short FFQ included 54 different foods. The foods were organized by FODMAP groups: free fructose, lactose, total oligosaccharides and total polyols, with variations of categories of responses for consumption frequency between 0 and 10 times and the unit of time in days, weeks or months. In the validity analyses, the correlation coefficients ranged from 0.209 (polyols) to 0.652 (lactose) (p < 0.05). There was no correlation between the methods in the fructose and oligosaccharide groups. The lactose group presented good agreement, and the remaining groups had a lack of agreement, with a mean of 15.7%. The Bland-Altman index values were 4.7% (fructose), 3.8% (lactose), 5.7% (oligosaccharides) and 6.6% (polyols). Regarding reproducibility, the interclass and Spearman's correlation coefficients varied from ICC = 0.781 and r = 0.725 (oligosaccharides) to ICC = 0.913 and r = 0.807 (lactose) (p < 0.05), showing strongly reproducible results for lactose and polyols and good results for fructose and oligosaccharides. Accurate agreement between FFQ applications had a mean of 67.3%, and 3.0% showed disagreement between FFQ1 and FFQ2. The weighted kappa coefficient ranged from 0.576 (polyols) to 0.645 (lactose).

Conclusion: The semi-quantitative short FFQ was developed to evaluate the consumption of FODMAPs in adults in São Paulo. The instrument presents good reproducibility for all groups of FODMAPs, good validity for lactose and weaker validity for fructose, polyols and oligosaccharides. As the short FFQ was carefully designed for the study population, its estimates are relatively reliable at the population group level. A future reanalysis of this questionnaire would be useful when the chemical composition data of FODMAPs are available.
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http://dx.doi.org/10.1016/j.clnu.2020.11.021DOI Listing
May 2021

Fat Distribution and Lipid Profile of Young Adults with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Enzyme Deficiency.

Lipids 2021 01 14;56(1):101-110. Epub 2020 Sep 14.

Laboratory of Growth and Development (LabCreD), Center for Investigation in Pediatrics (CIPED), School of Medical Sciences (FCM), State University of Campinas (UNICAMP), Campinas, SP, Brazil.

We aimed to compare detailed fat distribution and lipid profile between young adults with congenital adrenal hyperplasia due to 21-hydroxylase enzyme deficiency and a control group. We also verified independent associations of treatment duration and daily hydrocortisone dose equivalent (HDE) with lipid profile within patients. This case-control study included 23 patients (7 male and 16 female) matched by an age range of young adults (18-31 years) with 20 control subjects (8 male and 12 female). Dual energy X-ray absorptiometry was used to measure the fat distribution. Male patients demonstrated elevated indices of fat mass for total (7.7 ± 2.1 vs. 4.5 ± 1.3 kg/m , p = 0.003), trunk (4.0 ± 1.2 vs. 2.2 ± 0.8 kg/m , p = 0.005), android (0.63 ± 0.24 vs. 0.32 ± 0.15 kg/m , p = 0.008), gynoid (1.34 ± 0.43 vs. 0.74 ± 0.24 kg/m , p = 0.005), arm (0.65 ± 0.16 vs. 0.39 ± 0.10 kg/m , p = 0.009), and leg regions (2.7 ± 0.8 vs. 1.6 ± 0.4 kg/m , p = 0.005) than the control group, but not in females. However, female patients demonstrated elevated ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (1.90 ± 0.46 vs. 1.39 ± 0.47, p = 0.009) than the control group, but not in males. Total fat mass was inversely correlated with total testosterone (r = -0.64, p = 0.014) and positively correlated with leptin in males (r = 0.75, p = 0.002). An elevated daily HDE (β = 0.43, p = 0.038 and β = 0.47, p = 0.033) and trunk to total fat mass ratio (β = 0.46, p = 0.025, and β = 0.45, p = 0.037) were independently correlated with impaired lipid profile markers. Although there is no altered lipid profile, male patients demonstrated an increased fat distribution. However, female patients presented with an impaired lipid profile marker but demonstrated close values of normal fat distribution. Interestingly, the dose of glucocorticoid therapy can have some role in the lipid mechanisms.
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http://dx.doi.org/10.1002/lipd.12280DOI Listing
January 2021

Adipokines in young survivors of childhood acute lymphocytic leukemia revisited: beyond fat mass.

Ann Pediatr Endocrinol Metab 2020 Sep 29;25(3):174-181. Epub 2020 Jul 29.

Division of Pediatric Endocrinology, Faculty of Medical Sciences, UNICAMP, Campinas, Brazil.

Purpose: This cross-sectional study evaluated the relationship between adipokines (leptin, adiponectin, visfatin, and resistin) and adiposity indexes regarding sex and cranial radiotherapy exposure among young acute lymphocytic leukemia survivors.

Methods: A multivariate analysis of covariance (MANCOVA) was used to evaluate the joint effect of sex, cranial radiotherapy, and body mass index (BMI) z-score (model 1) or fat mass index (FMI) (model 2) on adipokines.

Results: This study included 55 survivors of childhood acute lymphocytic leukemia between 15 and 23 years of age from both sexes (56.4% female); 43.6% of the sample had undergone cranial radiotherapy (18-24 Gy). The BMI z-score, the FMI, and sex (P<0.050 for all) influenced at least one adipokine, while cranial radiotherapy exposure was marginal in model 2. Parameter estimates from the MANCOVA's final model showed that the BMI z-score (β=-0.437, P=0.010) and the FMI (β=-0.209, P=0.004) negatively influenced adiponectin, while the FMI positively affected resistin (β=0.142, P=0.020). The relationship between leptin, visfatin, and the adiposity ndexes could not be established. In model 1, females presented with increased adiponectin (β=-1.014, P=0.011) and resistin (β=-1.067, P=0.002) levels; in model 2, female sex positively affected adiponectin (β=-1.515, P=0.001) and marginally influenced resistin (β=-0.707, P=0.054) levels. Cranial radiotherapy negatively determined visfatin levels in both final models (P<0.050).

Conclusion: Changes in body fat may be associated with adipose tissue dysfunction and should be carefully evaluated in survivors of acute lymphocytic leukemia, considering both sex and cranial radiotherapy exposure, to treat disorders that may possibly aggravate their risk for early cardiovascular disease.
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http://dx.doi.org/10.6065/apem.1938174.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538299PMC
September 2020

Practical recommendations for the management of diabetes in patients with COVID-19.

Lancet Diabetes Endocrinol 2020 06 23;8(6):546-550. Epub 2020 Apr 23.

Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital Carl Gustav Carus, Dresden, Germany; Department of Endocrinology and Diabetology, University Hospital Zurich, Zurich, Switzerland; Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Deutsche Forschungsgemeinschaft-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.

Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.
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http://dx.doi.org/10.1016/S2213-8587(20)30152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013PMC
June 2020

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

Am J Physiol Cell Physiol 2020 04 26;318(4):C777-C786. Epub 2020 Feb 26.

Applied Physiology and Nutrition Research Group; School of Physical Education and Sport, Rheumatology Division, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, Brazil.

To test whether high circulating insulin concentrations influence the transport of β-alanine into skeletal muscle at either saturating or subsaturating β-alanine concentrations, we conducted two experiments whereby β-alanine and insulin concentrations were controlled. In , 12 men received supraphysiological amounts of β-alanine intravenously (0.11 g·kg·min for 150 min), with or without insulin infusion. β-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 β-alanine analyses. β-Alanine content in 24-h urine was assessed. In , six men ingested typical doses of β-alanine (10 mg/kg) before insulin infusion or no infusion. β-Alanine was assessed in muscle before and 120 min following ingestion. In , no differences between conditions were shown for plasma β-alanine, muscle β-alanine, muscle carnosine and urinary β-alanine concentrations (all > 0.05). In , no differences between conditions were shown for plasma β-alanine or muscle β-alanine concentrations (all > 0.05). Hyperinsulinemia did not increase β-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the of β-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize β-alanine transport into muscle following β-alanine intake.
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http://dx.doi.org/10.1152/ajpcell.00550.2019DOI Listing
April 2020

Interleukin-17 acts in the hypothalamus reducing food intake.

Brain Behav Immun 2020 07 18;87:272-285. Epub 2019 Dec 18.

Laboratory of Cell Signalling-Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bbi.2019.12.012DOI Listing
July 2020

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

Endocr Pract 2020 Apr 20;26(4):388-398. Epub 2019 Dec 20.

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. This case-control study comprised 29 post-pubertal 21-OH CAH patients regularly followed at the University of Campinas. Elevated serum 17-hydroxyprogesterone and 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. 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; = .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. 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. = 17-hydroxyprogesterone; = classic 21-hydroxylase deficiency congenital adrenal hyperplasia; = body mass index; = resting energy expenditure; = volume of oxygen; = volume of carbon dioxide.
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http://dx.doi.org/10.4158/EP-2019-0390DOI Listing
April 2020

Homeostatic model assessment of adiponectin (HOMA-Adiponectin) as a surrogate measure of insulin resistance in adolescents: Comparison with the hyperglycaemic clamp and homeostatic model assessment of insulin resistance.

PLoS One 2019 25;14(3):e0214081. Epub 2019 Mar 25.

Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil.

Background: Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated.

Objectives: To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance.

Methods: This was a cross-sectional study of 56 adolescents (aged 10-18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis.

Results: In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 (P = 0.02) for HOMA-Adiponectin and 0.859 (P < 0.0001) HOMA-IR.

Conclusions: The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214081PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433366PMC
December 2019

Prevalence of hepatitis B and hepatitis C among diabetes mellitus type 2 individuals.

PLoS One 2019 28;14(2):e0211193. Epub 2019 Feb 28.

Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro State, Brazil.

Diabetes mellitus type 2 (DM2) patients have higher risk to be infected with parenterally transmitted viruses, like hepatitis B or C virus. This study aims to determine HBV and HCV infection prevalence in DM2 patients from Northeast and Southeast Brazil. A total of 537 DM2 patients were included, 194 (36.12%) males and 343 (63.87%) females, with mean age of 57.13±11.49 years. HBV and HCV markers were determined using serological and molecular analysis, and risk factors were evaluated in a subgroup from Southeast (n = 84). Two HBV acute (HBsAg+/anti-HBc -) and one HBV chronic case (HBsAg+/anti-HBc+) were found. Six individuals (1.1%) were isolated anti-HBc, 37 (6.9%) had HBV infection resolved (anti-HBc+/anti-HBs+), 40 (7.4%) were considered HBV vaccinated (anti-HBc-/anti-HBs+). Thirteen patients (2.42%) had anti-HCV and 7 of them were HCV RNA+. In the subgroup, anti-HBc positivity was associated to age and anti-HCV positivity was associated to age, time of diabetes diagnosis, total bilirubin, indirect bilirubin, alkaline phosphatase at bivariate analysis, but none of them was statistically significant at multivariate analysis. As conclusion, low prevalence of HBV and high prevalence HCV was found in DM2 patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211193PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394929PMC
November 2019

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency.

EBioMedicine 2019 Jan 27;39:436-447. Epub 2018 Nov 27.

Laboratory of Cell Signaling, Department of Internal Medicine, University of Campinas, Campinas, São Paulo 13084-970, Brazil; Obesity and Comorbidities Research Center, University of Campinas, Campinas, São Paulo 13084-970, Brazil. Electronic address:

Background: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue.

Methods: The relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice.

Findings: IL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression.

Interpretation: IL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function. FUND: Sao Paulo Research Foundation grant 2013/07607-8.
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http://dx.doi.org/10.1016/j.ebiom.2018.11.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355943PMC
January 2019

Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil.

Diabetol Metab Syndr 2018 21;10:83. Epub 2018 Nov 21.

8Departamento de Medicina da Universidade Federal de São Paulo-UNIFESP, São Paulo, SP Brazil.

Background: Hypoglycemia affects patient safety and glycemic control during insulin treatment of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The Hypoglycemia Assessment Tool study in Brazil aimed to determine the proportion of patients experiencing hypoglycemic events and to characterize patient awareness and fear about hypoglycemia, among insulin-treated T1DM or T2DM patients.

Methods: This was a non-interventional, multicenter study, with a 6-month retrospective and a 4-week prospective evaluation of hypoglycemic events. Patients completed a questionnaire at baseline and at the end of the study, and also a patient diary. The answers 'occasionally' and 'never' to the question 'Do you have symptoms when you have a low sugar level?' denoted impaired hypoglycemia awareness. Fear was reported on a 10-point scale, from 'not afraid at all' to 'absolutely terrified'.

Results: From 679 included patients, 321 with T1DM and 293 T2DM, median age of 33.0 and 62.0 years, 59% and 56% were female, and median diabetes duration was 15.0 and 15.0 years, respectively. Median time of insulin use was 14.0 and 6.0 years. During the prospective period, 91.7% T1DM and 61.8% T2DM patients had at least one hypoglycemic event. In the same period, 54.0% T1DM and 27.4% T2DM patients had nocturnal hypoglycemia, 20.6% T1DM and 10.6% T2DM patients had asymptomatic hypoglycemia, and severe events occurred in 20.0% and 10.3%, respectively. At baseline, 21.4% T1DM and 34.3% T2DM had hypoglycemia unawareness. The mean score of hypoglycemia fear was 5.9 ± 3.1 in T1DM and 5.4 ± 3.9 in T2DM. The most common attitude after hypoglycemic events were to increase calorie intake (60.3%) and blood glucose monitoring (58.0%) and to reduce or skip insulin doses (30.8%).

Conclusions: Referred episodes of hypoglycemia were high, in both T1DM and T2DM insulin users. Patient attitudes after hypoglycemia, such as reduction in insulin and increase in calorie intake, can affect diabetes management. These findings may support clinicians in tailoring diabetes education and insulin treatment for patients with diabetes, in order to improve their glycemic control while reducing the risk of hypoglycemic events.
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http://dx.doi.org/10.1186/s13098-018-0379-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249957PMC
November 2018

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

Pediatr Diabetes 2018 08 6;19(5):882-891. Epub 2018 Apr 6.

Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas - Unicamp, Campinas, São Paulo, Brazil.

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.
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http://dx.doi.org/10.1111/pedi.12664DOI Listing
August 2018

Effect of biliopancreatic diversion on sleep quality and daytime sleepiness in patients with obesity and type 2 diabetes.

Arch Endocrinol Metab 2017 Dec;61(6):623-627

Laboratório de Investigação em Metabolismo e Diabetes (LIMED), Gastrocentro, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brasil.

Objective: The poor quality of sleep and the deprivation thereof have been associated with disruption of metabolic homeostasis, favoring the development of obesity and type 2 diabetes (T2DM). We aimed to evaluate the influence of biliopancreatic diversion (BPD) surgery on sleep quality and excessive daytime sleepiness of obese patients with T2DM, comparing them with two control groups consisting of obese and normal weight individuals, both normal glucose tolerant.

Subjects And Methods: Forty-two women were divided into three groups: LeanControl (n = 11), ObeseControl (n = 13), and ObeseT2DM (n = 18). The LeanC and ObeseC groups underwent all tests and evaluations once. The ObeseT2DM underwent BPD and were reassessed after 12 months. Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were applied before and 12 months after BPD.

Results: Before surgery, there was less daytime sleepiness in LeanC group (p = 0.013) compared with ObeseC and T2DMObese groups. The two obese groups did not differ regarding daytime sleepiness, demonstrating that the presence of T2DM had no influence on daytime sleepiness. After surgery, the daytime sleepiness (p = 0.002) and the sleep quality (p = 0.033) improved. The score for daytime sleepiness of operated T2DMObese group became similar to LeanC and lower than ObeseC (p = 0.047).

Conclusion: BPD surgery has positively influenced daytime sleepiness and sleep quality of obese patients with T2DM, leading to normalization of daytime sleepiness 12 months after surgery. These results reinforce previously identified associations between sleep, obesity and T2DM in view of the importance of sleep in metabolic homeostasis, quality of life and health.
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http://dx.doi.org/10.1590/2359-3997000000314DOI Listing
December 2017

Adiposity and family history of type 2 diabetes in an admixed population of adolescents: Associations with insulin sensitivity, beta-cell function, and hepatic insulin extraction in BRAMS study.

Diabetes Res Clin Pract 2018 Mar 7;137:72-82. Epub 2018 Jan 7.

Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas (Unicamp), Campinas, São Paulo, Brazil; Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil; National Institute of Science and Technology of Obesity and Diabetes, Brazil. Electronic address:

Aims: Insulin resistance and beta-cell dysfunction manifest differently across racial/ethnic groups, and there is a lack of knowledge regarding the pathophysiology of type 2 diabetes mellitus (T2DM) for ethnically admixed adolescents. This study aimed to investigate the influence of adiposity and family history (FH) of T2DM on aspects of insulin sensitivity, beta-cell function, and hepatic insulin extraction in Brazilian adolescents.

Methods: A total of 82 normoglycemic adolescents were assessed. The positive FH of T2DM was defined as the presence of at least one known family member with T2DM. The hyperglycemic clamp test consisted of a 120-min protocol. Insulin secretion and beta-cell function were obtained from C-peptide deconvolution. Analysis of covariance considered pubertal stage as a covariate.

Results: Both lean and overweight/obese adolescents had similar glycemic profiles and disposition indexes. Overweight/obese adolescents had about 1/3 the insulin sensitivity of lean adolescents (1.1 ± 0.2 vs. 3.4 ± 0.3 mg·kg·min·pmol ∗ 1000), which was compensated by an increase around 2.5 times in basal (130 ± 7 vs. 52 ± 10 pmol·l·min) and total insulin secretion (130,091 ± 12,230 vs. 59,010 ± 17,522 pmol·l·min), and in the first and second phases of insulin secretion; respectively (p < 0.001). This increase was accompanied by a mean reduction in hepatic insulin extraction of 35%, and a 2.7-time increase in beta-cell glucose sensitivity (p < 0.05). The positive FH of T2DM was not associated with derangements in insulin sensitivity, beta-cell function, and hepatic insulin extraction.

Conclusions: In an admixed sample of adolescents, the hyperglycemic clamp test demonstrated that adiposity had a strong influence, and FH of T2DM had no direct influence, in different aspects of glucose metabolism.
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http://dx.doi.org/10.1016/j.diabres.2017.12.013DOI Listing
March 2018

Glucose Metabolism Parameters and Post-Prandial GLP-1 and GLP-2 Release Largely Vary in Several Distinct Situations: a Controlled Comparison Among Individuals with Crohn's Disease and Individuals with Obesity Before and After Bariatric Surgery.

Obes Surg 2018 02;28(2):378-388

Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n, 13083-887, Campinas, São Paulo, Brazil.

Background: This study aims to compare the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 among individuals with Crohn's disease (CD), obese individuals before and after bariatric surgery, and healthy controls.

Methods: This an exploratory cross-sectional study that involved five groups of patients (two groups of individuals with CD-active and inactive), bariatric patients (pre- and post-surgery, who were their own controls), and a distinct separated control group of healthy volunteers. C-reactive protein (CRP) levels and the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 curves were assessed and compared.

Results: The pre-RYGB group presented significantly higher levels of CRP than the post-RYGB (p = 0.001) and the control group (p = 0.001). The inactive CD group presented a higher post-prandial GLP-1 area under the curve (AUC) than the pre-RYGB group (p = 0.009). The post-RYGB group presented significantly higher AUCs of GLP-2 than the pre-RYGB group (p < 0.0001), both inactive and active CD groups (p < 0.0001 in both situations), and the control group (p = 0.002). The pre-RYGB group presented a significantly higher AUC of glucose than the post-RYGB (p = 0.02) and both active and inactive CD groups (p = 0.019 and p = 0.046, respectively). The pre-RYGB group presented a significantly higher AUC of insulin than the control (p = 0.005) and both CD groups (p < 0.0001).

Conclusions: Obesity is associated with an inflammatory state comparable to the one observed in CD; inflammation may also be enrolled in the blockade of GLP-2. CD individuals present a more incretin-driven pattern of glucose metabolism, as a way to prevent hypoglycemia and compensate the carbohydrate malabsorption and GLP-2 blockade.
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http://dx.doi.org/10.1007/s11695-017-2851-yDOI Listing
February 2018

Changes in serum levels of lipopolysaccharides and CD26 in patients with Crohn's disease.

Intest Res 2017 Jul 12;15(3):352-357. Epub 2017 Jun 12.

Department of Surgery, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.

Background/aims: Lipopolysaccharide (LPS) is a molecule formed by lipids and polysaccharides and is the major cell wall component of gram-negative bacteria. High LPS levels are known to block CD26 expression by activating Toll-like receptor 4. The aim of this study was to correlate the serum levels of LPS and CD26 in Crohn's disease (CD) patients with serum levels of C-reactive protein (CRP), interleukins, CD activity index, and tumor necrosis factor-α (TNF-α).

Methods: Serum samples were collected from 27 individuals (10 with active CD, 10 with inactive CD, and 7 controls) and the levels of LPS, CD26, TNF-α, interleukin-1β (IL-1β), IL-6, IL-17, and CRP were determined by enzyme-linked immunosorbent assay. The levels of LPS and CD26 were then tested for correlation with TNF-α, IL-1β, IL-6, IL-17, and CRP.

Results: Serum levels of LPS were significantly elevated in the active CD group (=0.003). Levels of IL-1β (=0.002), IL-6 (=0.003), and IL-17 (<0.001) were lower in the CD groups. Serum TNF-α levels were increased in the active CD group. The CRP levels were elevated in the CD groups when compared to controls (<0.001). The CD26 levels were lower in the CD groups than in the control group (<0.001). Among the variables analyzed, there was a correlation between LPS and CRP (r=-0.53, =0.016) in the CD groups.

Conclusions: Individuals with CD exhibited higher serum levels of LPS varying from a 2- to 6-fold increase depending on disease activity, when compared with healthy controls. CD26 levels were lower in the CD groups. Both LPS and CD26 correlated with disease severity and serve as potential CD biomarkers.
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http://dx.doi.org/10.5217/ir.2017.15.3.352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478760PMC
July 2017

Erratum to: Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain-Adipocyte Axis.

Drugs 2017 07;77(10):1141

Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas-UNICAMP, Campinas, Brazil.

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http://dx.doi.org/10.1007/s40265-017-0766-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828282PMC
July 2017

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) in the Brain-Adipocyte Axis.

Drugs 2017 Apr;77(5):493-503

Laboratory of Cell Signaling, Obesity and Comorbidities Research Center, University of Campinas-UNICAMP, Campinas, Brazil.

The complexity of neural circuits that control food intake and energy balance in the hypothalamic nuclei explains some of the constraints involved in the prevention and treatment of obesity. Two major neuronal populations present in the arcuate nucleus control caloric intake and energy expenditure: one population co-expresses orexigenic agouti-related peptide (AgRP) and neuropeptide Y and the other expresses the anorexigenic anorectic neuropeptides proopiomelanocortin and cocaine- and amphetamine-regulated transcript (POMC/CART). In addition to integrating signals from neurotransmitters and hormones, the hypothalamic systems that regulate energy homeostasis are affected by nutrients. Fat-rich diets, for instance, elicit hypothalamic inflammation (reactive activation and proliferation of microglia, a condition named gliosis). This process generates resistance to the anorexigenic hormones leptin and insulin, contributing to the genesis of obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have increasingly been used to treat type 2 diabetes mellitus. One compound (liraglutide) was recently approved for the treatment of obesity. Although most studies suggest that GLP-1RAs promote weight loss mainly due to their inhibitory effect on food intake, other central effects that have been described for native GLP-1 and some GLP-1RAs in rodents and humans encourage future clinical trials to explore additional mechanisms that potentially underlie the beneficial effects observed with this drug class. In this article we review the most relevant data exploring the mechanisms involved in the effects of GLP-1RAs in the brain-adipocyte axis.
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http://dx.doi.org/10.1007/s40265-017-0706-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357258PMC
April 2017

Postprandial GLP-2 Levels Are Increased After Biliopancreatic Diversion in Diabetic Individuals with Class I Obesity: a Prospective Study.

Obes Surg 2017 07;27(7):1809-1814

Department of Surgery; Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil.

Background: Biliopancreatic diversion (BPD) is a predominantly malabsorptive procedure. Glucagon-like peptide 2 (GLP-2) plays predominantly trophic effects on the gut. A significant increase in GLP-2 after BPD in rats was previously observed, but there are no studies investigating the effect of BPD in GLP-2 levels in humans.

Objective: The aim of this study is to evaluate the influence of BPD on the release of GLP-2.

Methods: This is a prospective cohort study that evaluated diabetic individuals with class I obesity which underwent BPD (Scopinaro operation) and were followed up for 12 months. Of 12 individuals, four did not comply with the proposed follow-up and were excluded from the analysis. GLP-2 levels were determined by means of an enzyme-linked immunosorbent assay (ELISA), and we collected serial lab samples through a standard meal tolerance test (MTT) in the immediate preoperative period and 12 months after surgery.

Results: During standard MTT, we observed significant increases of GLP-2 levels from 15 to 60 min (respectively, at 15 min, 5.7 ± 3.4 versus 12.4 ± 4.3, p = 0.029; 30 min, 6 ± 3.5 versus 14.6 ± 3.9; p = 0.004; 45 min, 5.6 ± 4.1 versus 12.6 ± 5.2, p = 0.013; 60 min, 5.8 ± 2.9 versus 10.6 ± 5.6, p = 0.022); then it began to gradually decrease to levels close to the basal.

Discussion: Our findings have confirmed that there is a significant increase in GLP-2 levels after BPD in humans. GLP-2 plays a number of roles which may be adaptive, compensatory, and beneficial in the context of BPD. The clinical implications of this finding remain to be completely understood.
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http://dx.doi.org/10.1007/s11695-017-2554-4DOI Listing
July 2017

GLP-2: A POORLY UNDERSTOOD MEDIATOR ENROLLED IN VARIOUS BARIATRIC/METABOLIC SURGERY-RELATED PATHOPHYSIOLOGIC MECHANISMS.

Arq Bras Cir Dig 2016 Nov-Dec;29(4):272-275

Department of Surgery.

Introduction: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone whose effects are predominantly trophic on the intestinal mucosa.

Aim: Critically evaluate the current literature on the influence of bariatric/metabolic surgery on the levels of GLP-2 and its potential clinical implications.

Methods: Narrative review through online research on the databases Medline and Lilacs. There were six prospective human studies, two cross-sectional human studies, and three experimental animal studies selected.

Results: There is evidence demonstrating significant increase in the levels of GLP-2 following gastric bypass, Scopinaro operation, and sleeve gastrectomy. There are no differences between gastric bypass and sleeve gastrectomy in regards to the increase in the GLP-2 levels. There is no correlation between the postoperative levels of GLP-2 and the occurrence of adequate or insufficient postoperative weight loss.

Conclusion: GLP-2 plays significant roles on the regulation of nutrient absorption, permeability of gut mucosa, control of bone resorption, and regulation of satiety. The overall impact of these effects potentially exerts a significant adaptive or compensatory effect within the context of varied bariatric surgical techniques.
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http://dx.doi.org/10.1590/0102-6720201600040014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225870PMC
March 2017

CORRELATION BETWEEN PRE AND POSTOPERATIVE LEVELS OF GLP-1/GLP-2 AND WEIGHT LOSS AFTER ROUX-EN-Y GASTRIC BYPASS: A PROSPECTIVE STUDY.

Arq Bras Cir Dig 2016 Nov-Dec;29(4):257-259

Department of Surgery.

Background: The role of gut hormones in glucose homeostasis and weight loss achievement and maintenance after bariatric surgery appears to be a key point in the understanding of the beneficial effects observed following these procedures.

Aim: To determine whether there is a correlation between the pre and postoperative levels of both GLP-1 and GLP-2 and the excess weight loss after Roux-en-Y gastric bypass (RYGB).

Methods: An exploratory prospective study which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 after standard meal tolerance test (MTT) were determined before and after surgery and then correlated with the percentage of excess loss (%EWL).

Results: GLP-2 AUC presented a significant postoperative increase (945.3±449.1 vs.1787.9±602.7; p=0.0037); GLP-1 AUC presented a non-significant trend towards increase after RYGB (709.6±320.4 vs. 1026.5±714.3; p=0.3808). Mean %EWL was 66.7±12.2%. There was not any significant correlation between both the pre and postoperative GLP-1 AUCs and GLP-2 AUCs and the %EWL achieved after one year.

Conclusion: There was no significant correlation between the pre and postoperative levels of the areas under the GLP-1 and GLP-2 curves with the percentage of weight loss reached after one year.
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http://dx.doi.org/10.1590/0102-6720201600040010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225866PMC
March 2017

Long-Term Outcomes of Biliopancreatic Diversion on Glycemic Control, Insulin Sensitivity and Beta Cell Function.

Obes Surg 2016 11;26(11):2572-2580

Laboratory of Investigation on Metabolism and Diabetes, Gastrocentro, University of Campinas, Campinas, SP, Brazil.

Background: We aimed to assess the long-term outcomes of biliopancreatic diversion (BPD) surgery on glycemic control, insulin sensitivity (IS), and beta cell function using complementary oral and intravenous dynamic tests.

Methods: A total of 57 women were divided into three groups: 19 lean, 18 obese (both groups with normal glucose tolerance (NGT)), and 20 obese with type 2 diabetes who underwent BPD and were reassessed 12 months after the procedure. OGTTs and hyperglycemic clamps (HG) were performed. Mathematical modeling was used to analyze IS, beta cell function, and delayed time of beta cell response. The basal, dynamic (first phase/steps of insulin secretion), and static (second phase/steps of insulin secretion) disposition indexes were calculated.

Results: After surgery, the patients exhibited improvements in glycemic control and 15 patients achieved diabetes remission. The surgical patients demonstrated normalized IS in OGGT and HG tests compared to the control groups. The basal beta cell function was improved but remained impaired compared to the Lean NGT group. The stimulated beta cell function parameters showed marked improvements regarding the intravenous stimulus and the second phase/distal steps of insulin secretion. The delay time markedly decreased and became normalized in both dynamic tests.

Conclusions: The common physiopathology features of type 2 diabetes, i.e., impaired IS and beta cell dysfunction, were demonstrated to be primarily functional and were likely to be reversible to some degree after the BPD. The marked long-term improvement in glycemic control after BPD was closely related to IS improvement and mainly by the recovery of several beta cell physiological features.
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http://dx.doi.org/10.1007/s11695-016-2159-3DOI Listing
November 2016

Biliopancreatic Diversion Decreases Postprandial Apolipoprotein A-IV Levels in Mildly Obese Individuals with Type 2 Diabetes Mellitus: a Prospective Study.

Obes Surg 2017 04;27(4):1008-1012

Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz; CEP 13085-000, Campinas, SP, Brazil.

Background: Bariatric surgery usually leads to improvement on the general lipid profile, but its role in the levels of apolipoprotein A-IV (Apo-AIV) is not completely understood. Apo-AIV is a gut-released lipoprotein which is enrolled in satiety regulation and presents anti-inflammatory, anti-atherogenic, and anti-oxidative properties. The objective of this study was to determine the influence of biliopancreatic diversion (BPD) in the levels of Apo-AIV.

Methods: This is a prospective exploratory study which evaluated eight obese individuals with type 2 diabetes mellitus (T2DM) who underwent BPD (Scopinaro operation) and were followed-up for 12 months. Apo-AIV levels were determined by means of serial dosages through a standard meal tolerance test (MTT) in the immediate preoperative period and then 12 months later.

Results: There was a significant change in the Apo-AIV curve following MTT before and after surgery. At 0 and 45 min, the Apo-AIV levels did not significantly differ before and after surgery; at 120 and 180 min, Apo-AIV levels were significantly lower following BPD.

Conclusions: We observed a decrease of postprandial levels of Apo-AIV following MTT in mildly obese individuals with T2DM. This finding appears to be related to the suppression in the Apo-AIV response that obese individuals tend to present. Weight reduction itself, endotoxemia, and the large segments of bypassed intestine may be enrolled in this impaired response.
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http://dx.doi.org/10.1007/s11695-016-2414-7DOI Listing
April 2017
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