bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Sphingolipids, Insulin, HOMA-IR, and HOMA-B—The Strong Heart Family Study
Authors: LEMAITRE ROZENN N. , YU CHAOYU , HOOFNAGLE ANDREW , NAIR HARI , JENSEN PAUL N. , FRETTS AMANDA M. , UMANS JASON G. , SITLANI COLLEEN , SISCOVICK DAVID , KING IRENA , SOTOODEHNIA NONA , MCKNIGHT BARBARA 
Published: June 2018

High levels of fasting plasma insulin, reflecting insulin resistance, are an early event in the progression to type 2 diabetes. Experimental studies implicate ceramides in insulin resistance; however, whether circulating ceramides and related sphingolipids are associated with plasma insulin in humans is uncertain. We measured 15 ceramide and sphingomyelin species with different saturated fatty acids in baseline fasting plasma samples from the Strong Heart Family Study, a prospective cohort of American Indians. We examined associations of sphingolipids with plasma insulin, HOMA-IR and HOMA-B at baseline and follow-up (median 5 years later) using linear mixed models adjusted for family structure. Among 2086 participants without diabetes, higher levels of plasma ceramides carrying the fatty acids 16:0, 18:0, 20:0 or 22:0 were associated with higher plasma insulin and higher HOMA-IR at baseline and follow-up (Table). BMI modified associations of sphingomyelin species carrying 18:0, 20:0, 22:0 or 24:0 with insulin (p&lt;0.003); higher sphingomyelin levels were associated with lower fasting insulin and HOMA indices only among those with normal BMI. Our study suggests lowering circulating ceramides might be a target in prediabetes, and targeting sphingomyelins should take into account BMI.
Table. Plasma Ceramides, Insulin and HOMAIR.SpeciesFold change in geometric mean with 2 fold higher ceramide (95% CI), p-valueBaseline insulinFollow-up insulinBaseline HOMAIRFollow-up HOMAIRCer-16:01.13 (1.07-1.20) 1.9x10-51.10 (1.01-1.21) 0.031.15 (1.08-1.22) 4.7x10-61.11 (1.01-1.22) 0.03Cer-18:01.11 (1.06-1.15) 1.0x10-61.12 (1.06-1.19) 1.0x10-51.12 (1.08-1.17) 6.3x10-81.13 (1.06-1.20) 2.0x10-4Cer-20:01.12 (1.07-1.17) 1.5x10-71.10 (1.03-1.18) 0.0031.13 (1.08-1.18) 1.3x10-71.11 (1.04-1.19) 0.002Cer-22:01.13 (1.08-1.19) 3.9x10-71.12 (1.04-1.20) 0.0041.15 (1.09-1.21) 1.0x10-71.13 (1.04-1.22) 0.004Cer-24:01.(0.99-1.11) 0.081.09 (1.01-1.19) 0.041.(1.00-1.13) 0.041.11 (1.01-1.21) 0.03Covariates: age, sex, site, education, smoking, log(BMI), waist, physical activity.

Disclosure
R.N. Lemaitre: None. C. Yu: None. A. Hoofnagle: Research Support; Self; Waters Corporation. H. Nair: None. P.N. Jensen: None. A.M. Fretts: None. J.G. Umans: None. C. Sitlani: None. D. Siscovick: None. I. King: None. N. Sotoodehnia: None. B. McKnight: None.
Metformin Regresses Left Ventricular Hypertrophy in Normotensive Patients with Coronary Artery Disease without Type 2 Diabetes Mellitus—The MET-REMODEL Trial
Authors: MOHAN MOHAPRADEEP , AL-TALABANY SHAWEEN , MCKINNIE ANGELA M. , MORDI IFY , SINGH JAGDEEP S. , GANDY STEPHEN J. , CHOY ANNAMARIA , HOUSTON JOHN G. , GEORGE JACOB , STRUTHERS ALLAN D. , LANG CHIM C. ,   MET-REMODEL INVESTIGATORS
Published: June 2018

Background: Left ventricular hypertrophy (LVH) is highly prevalent in patients with coronary artery disease (CAD) and is an independent predictor of cardiovascular mortality. Metformin has been shown to regress LV mass (LVM) in animal models of LVH. We hypothesize that metformin may regress LVH in nondiabetic and normotensive CAD patients with prediabetes and/or insulin resistance.
Methods: In this randomized double-blind placebo controlled trial, 68 patients with prediabetes (HbA1c ?39 mmol/mol and less than 48 mmol/mol) and/or insulin resistance (fasting insulin resistance index ? 2.7) were assigned to receive either metformin (2g daily dose) or placebo for 12 months. An intention-to-treat (ITT) and per-protocol analysis was designed to determine the effect of metformin on the following study endpoints: Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging; other endpoints were changes in LVM, changes in body weight, office blood pressure (BP) and biomarkers.
Results: In the ITT analysis (n=61), metformin treatment significantly reduced: LVMI (metformin -2.7 ± 2.3 g/m1.7 vs. placebo -1.4 ± 2.7 g/m1.7; P=0.05), body weight (lowered by 3.6 kgs, p=0.002), office systolic BP (metformin -4.8 ± 15.6 mmHg vs. placebo 4.6 ± 15.7 mmHg; P=0.02) and reduced concentration of thiobarbituric acid reactive substances (TBARs), a biomarker for oxidative stress (p=0.04). In the on-per protocol analysis (n=56), metformin resulted in a greater reduction of LVMI (metformin -3.1 ± 1.9 g/m1.7 vs. placebo -1.2 ± 2.7 g/m1.7; P=0.005), and greater weight reduction of 4.2kgs (p=0.001).
Conclusions: Metformin treatment significantly reduced LVMI, office SBP, body weight and oxidative stress. These results reveal a novel mechanism for the cardioprotective effect of metformin and raise the possibility of using metformin in nondiabetic patients with CAD.

Disclosure
M. Mohan: None. S. Al-Talabany: None. A.M. McKinnie: None. I. Mordi: None. J.S. Singh: None. S.J. Gandy: None. A. Choy: None. J.G. Houston: None. J. George: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca. C.C. Lang: None.
Nationwide Analysis of Excess Deaths Attributable to Diabetes in Brazil
Authors: BRACCO PAULA , GREGG EDWARD W. , ROLKA DEBORAH B. , SCHMIDT MARIA I. , BARRETO SANDHI MARIA , LOTUFO PAULO A. , MELO ENIRTES C. , DUNCAN BRUCE B. 
Published: June 2018

Background: Little is known about the magnitude of excess mortality due to diabetes in low and middle income countries. Brazilian data to that end have been limited by reliance on death certificates and their subjective assignment of diabetes as a cause of death. We provide estimates of excess mortality due to diabetes by combining mortality risks from the ELSA-Brasil cohort with nationally representative surveys and databases.
Methods: We calculated the standardized mortality rate ratio for those with (vs. without) self-reported diabetes in ELSA-Brasil by Poisson regression adjusting for age, sex, race and education. We obtained similarly adjusted, self-reported diabetes prevalence from the 2013 National Health Survey. Mortality and population projections were from national statistics. We combined these data to model the excess deaths due to diabetes.
Results: In 2013, among adults with diabetes aged 35 to 74 (table), 73,092 deaths (13% of total) could have been avoided if the mortality rate in people with diabetes were the same as in those without diabetes. The percent ranged from 5.9% in persons aged 35-49 to more than 16% in those 60 or older. In the national mortality system, only 31,117 deaths had diabetes as a main cause.
Age GroupStandardized Mortality Rate Ratio Population NTotal Deaths NDeaths among People with Diabetes NExcess Deaths Associated with Self-Reported Diabetes With diabetesWithout diabetes Assuming diabetes mortality rateAssuming non-diabetes mortality rateExcess deaths among people with diabetes N% of total deaths35-492.40 (1.13 - 5.08)746,790 (3.7 %)19,538,124 (96.3%)120,20011,7224,6777,0455.950-591.94 (1.24 - 3.04)992,878 (10.2%)8,781,526 (79.8%)140,57730,86012,91417,94612.860-691.93 (1.35 - 2.74)941,815 (16.3%)4,853,378 (83.7%)182,45055,78725,15930,62816.870-741.58 (0.94 - 2.66)338,769 (20.3%)1,333,776 (79.7%)106,63735,53518,06217,47316.4Total1.91 (1.51 - 2.41)3,020,252 (8.1%)34,506,804 (92.9%)549,864133,90460,81273,09213.3
Conclusion: This calculation of excess deaths related to known diabetes in Brazil suggests a major diabetes mortality burden, which is considerably underestimated by calculations based only on death certificates.

Disclosure
P. Bracco: None. E.W. Gregg: None. D.B. Rolka: None. M.I. Schmidt: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company. S. Barreto: None. P.A. Lotufo: Consultant; Self; AbbVie Inc.. E.C. Melo: None. B.B. Duncan: Research Support; Self; Eli Lilly and Company. Research Support; Spouse/Partner; Eli Lilly and Company.
Maternal Exposure to Perfluorooctane Sulfonate (PFOS) Is Associated with Maternal Hyperglycaemia and Adverse Neonatal and Childhood Outcomes
Authors: MA RONALD C.W. , TAM CLAUDIA H.T. , YIU CHEUNG GRACE PUI , LOWE WILLIAM , METZGER BOYD E. , TAM WING H. , WONG CHRIS K. 
Published: June 2018

Perfluorooctane sulfonate (PFOS) belongs to a class of endocrine-disrupting chemicals, perfluoroalkyl chemicals (PFCs), implicated in adiposity. Although supposedly phased out since 2002, its use remains widespread in Asia. We aim to examine the relationship between exposure to PFOS and maternal hyperglycaemia and metabolic outcomes in the offspring. We measured blood PFOS and other PFCs in archived samples taken at 24-32weeks gestation from mothers in the Hong Kong centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study between 2002-2004. All mothers underwent 75g OGTT and GDM was diagnosed according to the IADPSG/WHO 2013 criteria. Pregnancy outcomes, neonatal anthropometrics and childhood outcomes at 7 years were documented. PFCs were measured using high performance LC-MS-MS. We completed analysis of PFCs in 1,601 maternal samples, a subset of 99 cord blood samples, and 970 offspring at 7 years follow-up. There is strong correlation among PFOS and other PFCs in cord blood (ρ=0.51-0.74, p&lt;0.001), as well as correlation with maternal levels (ρ=0.60, p&lt;0.001). Ratio of cord blood to maternal PFOS was 0.60. Using regression analysis with adjustment for maternal age, BMI, and offspring gender, maternal PFOS showed association with maternal 1 hour glucose, 2 hour glucose, HbA1c, AUC during OGTT and GDM, though only the association with HbA1c remained significant using log-transformed PFOS (beta 0.0746 ± 0.0132, p=1.7x10-8). Log-transformed maternal PFOS was associated with higher birthweight, lower birth length, higher ponderal index and lower neonatal sum of skin fold thickness (beta -0.337 ± 0.085, p=7.1x 10-5), after adjustment for all covariates. Maternal PFOS during pregnancy was associated with lower height in offspring at age 7, but not offspring glycaemic parameters. Exposure to PFOS may be an important contributing factor to the epidemic of hyperglycaemia in pregnancy and childhood metabolic disorders in Asia.

Disclosure
R.C.W. Ma: Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Pfizer Inc.. Advisory Panel; Self; Boehringer Ingelheim GmbH, Nippon Boehringer Ingelheim Co. Ltd.. C.H.T. Tam: None. G. Cheung: None. W. Lowe: None. B.E. Metzger: None. W.H. Tam: None. C.K. Wong: None.
Prognostic Cut Points for Prediabetes Glucose Levels and HbA1c Values in Predicting All-Cause Mortality—A Systematic Review and Meta-analysis
Authors: HUANG MINXUAN , GUJRAL UNJALI , HE SIRAN , JAGANNATHAN RAM , WEI JINGKAI , STAIMEZ LISA R. , VENKAT NARAYAN K.M. 
Published: June 2018

Elevated but nondiabetic glucose levels, including impaired fasting glucose (IFG), 2-hour impaired glucose tolerance (IGT), and glycosylated hemoglobin A1c (HbA1c), are associated with increased risk for all-cause mortality. However, the glucose measures may differ in their abilities to predict adverse outcomes. The World Health Organization (WHO) and the American Diabetes Association (ADA) also differ in their definitions of IFG, and it remains unclear which definition best predicts future adverse outcomes. The objective of this study was to evaluate the prognostic value of different cut-points of prediabetic glucose measures for predicting all-cause mortality in individuals without diabetes. In databases including MEDLINE, PubMed, Embase, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform, and Cochrane, we searched prospective cohort studies with minimum 3 years of follow-up, in adults without diabetes at enrollment. Data from eligible studies were pooled to synthesize results for each glucose measure. Random effect regression model was used to calculate pooled hazard ratio or relative risk for all-cause mortality. We screened over 4,000 abstracts and identified 170 eligible studies with mean follow-up of 10.2 years. Compared with individuals with normal glycemia, those with IFG defined by the WHO criteria had 1.14 times increased risk for all-cause mortality. There was no significant increase in mortality risk among those with IFG diagnosed by the ADA criteria. Individuals with IGT had 1.17 times higher risk for all-cause mortality compared with individuals with normal glycemia. HbA1c as low as 5.5% was associated with an increased risk for mortality. The WHO criteria for IFG seems to have better predictive value for all-cause mortality than the ADA criteria. Furthermore, individuals with HbA1c levels at 5.5% may have higher risk for mortality.

Disclosure
M. Huang: None. U. Gujral: None. S. He: None. R. Jagannathan: None. J. Wei: None. L.R. Staimez: None. K. Narayan: None.
The Maternal Impact of AdGHRKO Mice on Glucose Metabolism
Authors: WANG XIAOSHUANG , MI AI , LIU YANSHUANG , WANG DAN , RAN LIYUAN , WU YINGJIE 
Published: June 2018

Genetically modified mouse models provide effective tools to explore the occurrence development and therapy of various diseases, especially the metabolic diseases such as diabetes. In line with the reported maternal inheritance of glucose homeostasis via maternally expressed gene activity, we found that a tissue-specific knockout exhibited maternal influence on insulin sensitivity, resulting in a lower liability for diabetes in the offsprings. Using the Cre/LoxP system, we constructed a mouse model of adipose tissue-specific growth hormone receptor (GHR) knockout (AdGHRKO). Unlike other tissue-specific GHR knockouts, AdGHRKO was found to be maternally inheritable. Compared with female AdGHRKO mice born from Flox mothers, female KO mice born from KO mothers displayed resistance to diet-induced obesity from a high-fat diet for 8 weeks. and the difference in body weight was exclusively due to a significant reduction in white fat tissue, especially from decreased subcutaneous deposition. Moreover, KO mice from KO mothers had better insulin sensitivity and glucose tolerance after high-fat treatment for 8 weeks. Our data suggests that the phenotype of metabolic stability in progeny is strongly affected by the maternal genotype. To support this, we also found that Flox mice born from KO mothers presented similar phenotypic traits (improved glucose tolerance and insulin resistance) of protection from high fat induced diabetes, which was comparable to the KO mice born from KO mothers. Our ongoing studies are to determine if this phenomenon is caused by alterations in maternal hormone levels or some unknown mitochondrial activities. Nonetheless, how adipose tissue specific ablation of GHR exerts its effects on metabolic syndromes through maternal cues is of high interest not only to pure genetic studies but also to medical practice.

Disclosure
X. Wang: None. A. Mi: None. Y. Liu: None. D. Wang: None. L. Ran: None. Y. Wu: None.
Characterization of a Type 2 Diabetes–Associated Islet-Specific Enhancer Cluster in STARD10 by Genome Editing of EndoC-ßH1 Cells
Authors: HU MING , GADUE PAUL , RUTTER GUY A. 
Published: June 2018

Genome-wide association studies have identified &gt;100 genetic loci associated with type 2 diabetes. We recently analysed one locus on chromosome 11q and mapped 5 causal variants in an islet-specific enhancer cluster within the STARD10 gene (Carrat, et al., Am J Hum Gen, 2017). Here, we aimed to understand the function of this cluster in beta cells and how causal variants influence enhancer activity. Using published ATAC-seq data (Varshney A, et al., PNAS, 2017) we analysed the transcriptional activity of 10 open chromatin regions (0.2-2 kb) using promoter-luciferase assay in EndoC-βH1 cells. Of these regions, HS1b displayed a 6.25-fold increase compared with empty vector [luciferase/renilla ratio: 6.25 ± 0.14; Student’s t-test, p&lt;0.001; n=3]. Deletion of HS1b using CRISPR/Cas9 technology led to a significant reduction of glucose-stimulated insulin secretion (GSIS) (15/0.5 mM glucose, fold change: Control, 4.23 ± 0.41 vs. HS1b-del 2.21 ± 0.06; p&lt;0.05; n=3) and ∼50% reduction of STARD10 gene expression (Fold: control 1 vs. HS1b-del, 0.486 ± 0.04; p&lt;0.001, n=3). Chromosome conformation capture (4C and 3C) identified two enhancer regions, termed HS1 and HS5, as interacting with the causal variants including rs140130268. Both regions contain multiple defined CTCF binding sites. To test whether these CTCF binding sites create a chromatin loop defining an enhancer complex, we mutated four of the CTCF binding sites one by one. This resulted in a significant (p&lt;0.05; n=3) impairment in GSIS assays [Control, 4.± 0.46, vs. HS5-1-Mu, 2.75 ± 0.07; HS5-2-Mu, 2.66 ± 0.13; HS1-1-Mu, 3.49 ± 0.02 and HS1-2-Mu, 3.47 ± 0.57]. Taken together, we show that the modification of enhancer elements at the STARD10 locus affects beta cell function. The causal variants, which are physically associated with both HS5 and HS1, are likely to exert their effects through the formation and activity of an enhancer-cluster complex which affects the expression of STARD10 and possibly other genes.

Disclosure
M. Hu: None. P. Gadue: None. G.A. Rutter: Research Support; Self; Servier.
Ancestral Differences in Hemoglobin A1C (A1C) Associations of Erythrocyte Genes Using NHLBI Trans-Omics for Precision Medicine (TOPMed) Whole Genome Sequence (WGS) Data
Authors: SARNOWSKI CHLOÉ , LEONG AARON , RAFFIELD LAURA ,   TOPMED DIABETES WORKING GROUP
Published: June 2018

The latest transethnic genome wide association study on A1C identified 22 loci that modify A1C independently of glycemia. These loci overlap genes implicated in erythrocyte phenotypes that vary in prevalence across populations. We used TOPMed WGS data to estimate ancestral differences in associations with A1C at these loci and 23 additional erythrocyte genes not previously known to be related to A1C.
We conducted WGS association analyses of A1C in 5224 nondiabetic individuals [2662 European ancestry (EA): Framingham Heart Study and Amish; 2562 African ancestry (AA): Jackson Heart Study] using age and sex-adjusted linear mixed-effect regression, and meta-analyzed cohort-specific results. We used Cochran heterogeneity and Fisher’s exact tests to assess ancestral differences in effect and Minor Allele Frequency (MAF).
We detected single variant associations in 11 genes/loci (P &lt; 0.001; α = 0.05/45; ≥ 1 cohort; Table). Variants had ancestral differences in MAF (P &lt; 1%) and ancestry-specific signals (AA: G6PD, HBB, HBA1; EA: ANK1, PIEZO1, SPTA1, SPTB, HBA2).
Genetic variation at erythrocyte genes exhibit ancestral differences in A1C effect and MAF. These variants may differ in their contributions to inter-individual A1C variation, which may impact glucose estimation and diabetes diagnosis by A1C, particularly in minority populations.

Disclosure
C. Sarnowski: None. A. Leong: None. L. Raffield: None.
Genome-Wide Association Study of Inflammatory Cytokines in Southwestern Native Americans Identifies Novel Association between WWOX and Serum TNF-? Levels
Authors: WEDEKIND LAUREN E. , WALTER MARY , KOBES SAYUKO , CHEN PENG , HSUEH WEN-CHI , NELSON ROBERT , BAIER LESLIE , KNOWLER WILLIAM C. , HANSON ROBERT L. 
Published: June 2018

Inflammatory processes may contribute to type 2 diabetes (T2D), but there is limited information about genetic associations with circulating levels of inflammatory cytokines. We performed a genome-wide association study (GWAS) of cytokines in 1061 nondiabetic Southwestern Native Americans (500 women; 561 men).
Fasting serum concentrations of interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor-α (TNF-α) were measured using EMD Millipore assays. Genotypic data on 496,190 single-nucleotide polymorphisms (SNPs) with minor allele frequency &gt;1% were derived from an Affymetrix Axiom array designed to capture common variation in Pima Indians. Data were normalized and analyzed for associations using a mixed model accounting for familial relationships, adjusted for age, sex and genetic principal components 1-5.
The strongest associations were on chromosome 3 near A4GNT with IL-6 levels (rs2724711 p=4.2×10-6), and on chromosome 7 with PAI-1 levels (rs1608488 (p=8.3×10-7). An association of genome-wide statistical significance (rs1862840; p=1.2×10-8) was observed on chromosome 16 near WWOX with TNF-α levels. Each copy of the G allele (frequency=0.12) confers a 0.41-SD increase in TNF-α levels. In a larger cohort of Southwestern Native Americans, rs1862840 was not associated with T2D (N=7,659; p=0.17). Among 3,983 nondiabetic subjects it did associate with 2 hour corrected insulin response (β=0.06-SD decrease per G allele copy, p=0.011). Among 300 normal glucose tolerant subjects it associated with the acute insulin response to intravenous glucose (β=20% decrease per G allele copy, p=0.045).
This study identified a novel association for TNF-α levels at WWOX (a gene previously implicated in T2D and insulin secretion in Han Chinese study populations) and suggests potential genetic links between inflammation and insulin secretion.

Disclosure
L.E. Wedekind: None. M. Walter: None. S. Kobes: None. P. Chen: None. W. Hsueh: None. R. Nelson: None. L. Baier: None. W.C. Knowler: None. R.L. Hanson: None.
Sleep Disturbances and Daytime Sleepiness in Pregnant Women with Diabetes
Authors: FACANHA CRISTINA , SOUSA FILIPE L. , FACANHA ARTHUR S. , FORTI ADRIANA C. , ROCHA HELLEN CRISTINA L. , PINHEIRO DE ARAUJO MARIANA SILTON , BRUIN VERALICE M.S. 
Published: June 2018

Sleep disturbances in pregnancy are associated with depression, preterm delivery, hypertension, hyperglycemic disorders, and higher rate of cesarean as well as adverse perinatal outcomes. Diabetes is other prevalent condition in pregnancy related to these adverse outcomes, and insulin resistance is a common disruptor. As such, it is important to evaluate the quality of sleep and daytime somnolence in diabetic pregnancy.
Aim: Evaluate sleep quality and excessive daytime sleepiness in pregnancy complicated by diabetes mellitus. This is a cross-sectional study involving 115 pregnant women with diabetes (PWD), gestational age from 10 to 39 weeks. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI-BR) and daytime sleepiness by the Epworth Sleepiness Scale (ESS). The study was approved by IPADE ethic board (1.801.860). Statistical analysis was performed using the software IBM SPSS.
Results: Poor sleep quality (PSQI&gt;5) was observed in60,4% of PWD, which is higher them most reported rates for normal pregnancy (60,4% vs. 45% p: 0.01, CI99%. SEDOV, 2017) but similar to reported data on Brazilian overweight pregnant women (65,9%; RIBEIRO 2015). The mean PSQI score was 6.91. Short sleep duration was present in 35,8% (mean sleep duration: 7,2 hours/night). Sleep was disturbed by frequent urination in 66,1% of PWD. Daytime somnolence reported in 20.8% of PWD, and was not related with the quality of sleep. The higher number of parity was independently associated with poor sleep quality [p=0.03; 0R=1.74; CI=1.03-2.97]. The presence of obesity, hypertension, educational level, type of diabetes or treatment were non-influential to sleep quality or daytime sleepiness.
Conclusion: Poor sleep quality and excessive daytime sleepiness are frequent in PWD and a higher number of parity is independently associated with poor sleep quality. Given that sleep disturbances are related to adverse outcomes in PWD, we suggest that this group of patients should be the focus of therapeutic measures to improve sleep.

Disclosure
C. Facanha: None. F.L. Sousa: None. A.S. Facanha: None. A.C. Forti: None. H.L. Rocha: None. M. de Araujo: None. V.M.S. Bruin: None.