Alternative diagnostic criteria for idiopathic hypersomnia: A 32-hour protocol.

OBJECTIVE: To assess the diagnostic value of extended sleep duration on a controlled 32-hour bed rest protocol in idiopathic hypersomnia (IH). METHODS: One hundred sixteen patients with high suspicion of IH (37 clear-cut IH according to multiple sleep latency test criteria and 79 probable IH), 32 with hypersomnolence associated with a comorbid disorder (non-IH), and 21 controls underwent polysomnography, modified sleep latency tests, and a 32-hour bed rest protocol. Receiver operating characteristic curves were used to find optimal total sleep time (TST) cutoff values on various periods that discriminate patients from controls. RESULTS: TST was longer in patients with clear-cut IH than other groups (probable IH, non-IH, and controls) and in patients with probable IH than non-IH and controls. The TST cutoff best discriminating clear-cut IH and controls was 19 hours for the 32-hour recording (sensitivity = 91.9%, specificity = 85.7%) and 12 hours (100%, 85.7%) for the first 24 hours. The 19-hour cutoff displayed a specificity and sensitivity of 91.9% and 81.2% between IH and non-IH patients. Patients with IH above the 19-hour cutoff were overweight, had more sleep inertia, and had higher TST on all periods compared to patients below 19 hours, whereas no differences were found for the 12-hour cutoff. An inverse correlation was found between the mean sleep latency and TST during 32-hour recording in IH patients. INTERPRETATION: In standardized and controlled stringent conditions, the optimal cutoff best discriminating patients from controls was 19 hours over 32 hours, allowing a clear-cut phenotypical characterization of major interest for research purposes. Sleepier patients on the multiple sleep latency test were also the more severe in terms of extended sleep. Ann Neurol 2018;83:235-247.

Lower Vitamin D Levels, but Not VDR Polymorphisms, Influence Type 2 Diabetes Mellitus in Brazilian Population Independently of Obesity.

Background and Objectives: Vitamin D levels have been associated with a diversity of diseases, including obesity. Vitamin D presents a pleiotropic action, and can regulate insulin secretion and inflammatory responses. Vitamin D receptor (VDR) gene polymorphisms are involved in the gene expression regulation and have been associated with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the polymorphisms ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810), and TaqI (rs731236) in the VDR gene in people diagnosed with T2DM, and plasma 25-hydroxivitamin D levels [25(OH)D]. Materials and Methods: A total of 101 T2DM patients and 62 gender, age, and body mass index (BMI) matched non-diabetic controls were included in this study. Molecular analyzes were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma 25(OH)D levels were measured by high performance liquid chromatography. Results: The plasma 25(OH)D levels were lower in T2DM patients (17.2 (16.6) ng/mL) when compared with the control subjects (30.8 (16.2) ng/mL, p < 0.0001), independently of obesity status. We found no difference between genotypic and allelic frequencies of the VDR polymorphisms when comparing the T2DM group and control group (p > 0.05 for all), and did not show any association with plasma 25(OH)D levels. Conclusions: These results suggest that T2DM is associated with lower plasma 25(OH)D levels, which are not related to BMI and VDR gene polymorphisms.

Development of hypothalamic serotoninergic neurons requires Fgf signalling via the ETS-domain transcription factor Etv5b.

Serotonin is a monoamine neurotransmitter that is involved in numerous physiological functions and its dysregulation is implicated in various psychiatric diseases. In all non-placental vertebrates, serotoninergic (5-HT) neurons are present in several regions of the brain, including the hypothalamus. In placental mammals, however, 5-HT neurons are located in the raphe nuclei only. In all species, though, 5-HT neurons constitute a functionally and molecularly heterogeneous population. How the non-raphe 5-HT populations are developmentally encoded is unknown. Using the zebrafish model we show that, in contrast to the raphe populations, hypothalamic 5-HT neurons are generated independently of the ETS-domain transcription factor Pet1 (Fev). By applying a combination of pharmacological tools and gene knockdown and/or overexpression experiments, we demonstrate that Fgf signalling acts via another ETS-domain transcription factor, Etv5b (Erm), to induce hypothalamic 5-HT neurons. We provide evidence that Etv5b exerts its effects by regulating cell cycle parameters in 5-HT progenitors. Our results highlight a novel role for Etv5b in neuronal development and provide support for the existence of a developmental heterogeneity among 5-HT neurons in their requirement for ETS-domain transcription factors.

Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium.

Maintaining the homeostasis of germinal zones in adult organs is a fundamental but mechanistically poorly understood process. In particular, what controls stem cell activation remains unclear. We have previously shown that Notch signaling limits neural stem cell (NSC) proliferation in the adult zebrafish pallium. Combining pharmacological and genetic manipulations, we demonstrate here that long-term Notch invalidation primarily induces NSC amplification through their activation from quiescence and increased occurrence of symmetric divisions. Expression analyses, morpholino-mediated invalidation and the generation of a notch3-null mutant directly implicate Notch3 in these effects. By contrast, abrogation of notch1b function results in the generation of neurons at the expense of the activated NSC state. Together, our results support a differential involvement of Notch receptors along the successive steps of NSC recruitment. They implicate Notch3 at the top of this hierarchy to gate NSC activation and amplification, protecting the homeostasis of adult NSC reservoirs under physiological conditions.

Diabetes related phenotypes and their influence on outcomes of patients with corona virus disease 2019 (COVID-19).

INTRODUCTION: Diabetes mellitus (DM) is associated with severe forms of COVID-19 but little is known about the diabetes-related phenotype considering pre-admission, on-admission and data covering the entire hospitalization period. METHODS: We analyzed COVID-19 inpatients (n = 3327) aged 61.2(48.2-71.4) years attended from March to September 2020 in a public hospital. RESULTS: DM group (n = 1218) differed from Non-DM group (n = 2109) by higher age, body mass index (BMI), systolic blood pressure and lower O2 saturation on admission. Gender, ethnicity and COVID-19-related symptoms were similar. Glucose and several markers of inflammation, tissue injury and organ dysfunction were higher among patients with diabetes: troponin, lactate dehydrogenase, creatine phosphokinase (CPK), C-reactive protein (CRP), lactate, brain natriuretic peptide, urea, creatinine, sodium, potassium but lower albumin levels. Hospital (12 × 11 days) and intensive care unit permanence (10 × 9 days) were similar but DM group needed more vasoactive, anticoagulant and anti-platelet drugs, oxygen therapy, endotracheal intubation and dialysis. Lethality was higher in patients with diabetes (39.3% × 30.7%) and increased with glucose levels and age, in male sex and with BMI < 30 kg/m2 in both groups (obesity paradox). It was lower with previous treatment with ACEi/BRA in both groups. Ethnicity and education level did not result in different outcomes between groups. Higher frequency of comorbidities (hypertension, cardiovascular/renal disease, stroke), of inflammatory (higher leucocyte number, RCP, LDH, troponin) and renal markers (urea, creatinine, potassium levels and lower sodium, magnesium) differentiated lethality risk between patients with and without diabetes. CONCLUSIONS: Comorbidities, inflammatory markers and renal disfunction but not Covid-19-related symptoms, obesity, ethnicity and education level differentiated lethality risk between patients with and without diabetes.

Proteomics of high-density lipoprotein subfractions and subclinical atherosclerosis in type 1 diabetes mellitus: a case-control study.

BACKGROUND: Subclinical atherosclerosis is frequently observed in type 1 diabetes (T1D) although the mechanisms and markers involved in the evolution to established cardiovascular disease are not well known. High-density lipoprotein cholesterol in T1D is normal or even high, and changes in its functionality and proteomics are considered. Our aim was to evaluate the proteomics of HDL subfractions in T1D and control subjects and its association with clinical variables, subclinical atherosclerosis markers and HDL functionality. METHODS: A total of 50 individuals with T1D and 30 matched controls were included. Carotid-femoral pulse wave velocity (PWV), flow-mediated vasodilation (FMD), cardiovascular autonomic neuropathy (CAN), and ten-year cardiovascular risk (ASCVDR) were determined. Proteomics (parallel reaction monitoring) was determined in isolated HDL2 and HDL3 that were also utilized to measure cholesterol efflux from macrophages. RESULTS: Among 45 quantified proteins, 13 in HDL2 and 33 in HDL3 were differentially expressed in T1D and control subjects. Six proteins related to lipid metabolism, one to inflammatory acute phase, one to complement system and one to antioxidant response were more abundant in HDL2, while 14 lipid metabolism, three acute-phase, three antioxidants and one transport in HDL3 of T1D subjects. Three proteins (lipid metabolism, transport, and unknown function) were more abundant in HDL2; and ten (lipid metabolism, transport, protease inhibition), more abundant in HDL3 of controls. Individuals with T1D had higher PWV and ten-year ASCVDR, and lower FMD, Cholesterol efflux from macrophages was similar between T1D and controls. Proteins in HDL2 and HDL3, especially related to lipid metabolism, correlated with PWV, CAN, cholesterol efflux, HDLc, hypertension, glycemic control, ten-year ASCVDR, and statins use. CONCLUSION: HDL proteomics can be predictive of subclinical atherosclerosis in type 1 diabetes. Proteins that are not involved in reverse cholesterol transport may be associated with the protective role of HDL.

Subcellular TSC22D4 localization in cerebellum granule neurons of the mouse depends on development and differentiation.

We previously demonstrated that TSC22D4, a protein encoded by the TGF-ß1-activated gene Tsc22d4 (Thg-1pit) and highly expressed in postnatal and adult mouse cerebellum with multiple post-translationally modified protein forms, moves to nucleus when in vitro differentiated cerebellum granule neurons (CGNs) are committed to apoptosis by hyperpolarizing KCl concentrations in the culture medium. We have now studied TSC22D4 cytoplasmic/nuclear localization in CGNs and Purkinje cells: (1) during CGN differentiation/maturation in vivo, (2) during CGN differentiation in vitro, and (3) by in vitro culturing ex vivo cerebellum slices under conditions favoring/inhibiting CGN/Purkinje cell differentiation. We show that TSC22D4 displays both nuclear and cytoplasmic localizations in undifferentiated, early postnatal cerebellum CGNs, irrespectively of CGN proliferation/migration from external to internal granule cell layer, and that it specifically accumulates in the somatodendritic and synaptic compartments when CGNs mature, as indicated by TSC22D4 abundance at the level of adult cerebellum glomeruli and apparent lack in CGN nuclei. These features were also observed in cerebellum slices cultured in vitro under conditions favoring/inhibiting CGN/Purkinje cell differentiation. In vitro TSC22D4 silencing with siRNAs blocked CGN differentiation and inhibited neurite elongation in N1E-115 neuroblastoma cells, pinpointing the relevance of this protein to CGN differentiation.

-1131T>C and SW19 polymorphisms in APOA5 gene and lipid levels in type 2 diabetic patients.

Type 2 diabetes mellitus is a metabolic, vascular, and neuropathic disease with a high risk of atherosclerotic events due to dyslipidemic states. Polymorphisms in Apolipoprotein A5 gene (APOA5) have been associated with increased triglyceride levels in many different populations. This study aimed to identify the frequencies of the APOA5 -1131T>C and SW19 polymorphisms and evaluate their effects on lipid levels in patients with type 2 diabetes. Genotyping of APOA5 -1131T>C and SW19 polymorphisms was performed by PCR-RFLP in 146 diabetic patients and in controls (n = 173), from 30 to 80 years of age. Diabetic patients were divided into two groups: patients not treated with lipid lowering drugs (group G1; n = 62) and those treated with lipid lowering drugs (group G2, n = 84). Lipids and lipoproteins were determined enzymatically. Among participants not treated with lipid-lowering drugs (diabetics G1 and controls; n = 235), the -1131C was associated with lower LDLc levels (p = 0.015). In the diabetic patients, the 19W allele was associated with higher triglyceride levels (p = 0.004). In G1 diabetic patients, the combined analysis of APOA5 -1131T>C and SW19 polymorphisms showed that [TC or CC] + SS carriers presented lower total cholesterol levels than did other genotype combinations (p = 0.049). It could therefore be concluded that APOA5 -1131T>C and SW19 polymorphisms influence lipid levels in type 2 diabetic patients.

Increased tissue kallikrein amidase activity in urine of patients with type 1 diabetes under insulin therapy, and in those with gestational diabetes mellitus not under insulin therapy.

Human tissue kallikrein (hK1) is reduced in hypertension, cardiovascular and renal diseases. There is little information on the participation of hK1 in type 1 diabetes mellitus (DM), type 2 DM, and gestational diabetes mellitus (GDM), respectively. The aim of this study was to evaluate the roles of insulin and hyperglycemia on urinary hK1 activity in type 1 DM and in GDM. Forty-three type 1 DM patients (5-35 years, disease duration ≤ 5years, receiving insulin, HbA(1c)>7.6%) were selected. Forty-three healthy individuals, paired according to gender and age, were used as controls. Thirty GDM patients (18-42 years, between the 24th and 37th week of pregnancy, recently diagnosed, not under insulin therapy) were also selected. Thirty healthy pregnant (18-42years, between the 24th and 37th week of pregnancy) and 30 healthy non-pregnant women (18-42years) were selected as controls. Random midstream urine was used. hK1 amidase activity was estimated with D-Val-Leu-Arg-Nan substrate. Creatinine was determined by Jaffe's method. hK1 specific amidase activity was expressed as µM/(minmg creatinine) to correct for differences in urine flow rate. hK1 specific amidase activity was significantly higher in the urine of type 1 DM than in controls, and in the urine of GDM patients than in healthy pregnant women and healthy non-pregnant women, respectively. The data suggest that hyperglycemia, rather than insulin, is involved in the mechanism of increased hK1 specific amidase activity in both type 1 DM and GDM patients, respectively.

THG-1pit moves to nucleus at the onset of cerebellar granule neurons apoptosis.

Thg-1pit (Tsc22d4), a murine gene belonging to the TGF-beta1-stimulated clone 22 domain (TSC22D) family, is expressed in developing and adult cerebellar granule neurons and mature Purkinje cells. We have studied THG-1pit function in primary cultures of mouse cerebellar granule neurons maintained in vitro in the presence of a medium containing 25 mM K+ (differentiating condition) or 5 mM K+ (pro-apoptotic condition), and determined the effect of culture medium, TGF-beta1 and IGF-1 on THG-1pit expression and intracellular localization. Thg-1pit encoded a 42 kDa MW protein and other, higher MW and developmentally-regulated forms. Cell exposure to 5 mM K+ elicited early and/or late waves of Thg-1pit transcription, depending on the presence/absence of TGF-beta1, and caused THG-1pit to massively and transiently move from cytoplasm and neurites to the nucleus. THG-1pit nuclear entrance was concomitant to that of AIF, suggesting that THG-1pit is involved in the induction of granule neuron apoptosis.

Improvement in Food Intolerance Resulting from Roux-En-Y Gastric Bypass after Speech Therapy Intervention in Chewing.

INTRODUCTION: Food intolerance is expected during the postoperative period following gastric bypass and may be associated with inadequate chewing. OBJECTIVE: To evaluate chewing before and after speech therapy intervention in subjects undergoing Roux-en-Y gastric bypass who present with food intolerance. MATERIALS AND METHODS: This was a randomized controlled trial, approved by the Brazilian Ethics and Research Committee under n. 438,600. The study population was allocated into two groups: the study group (SG), who received speech therapy intervention, and the control group (CG), who did not receive any intervention, in six visits at 7, 15, 30, 60, and 90 days (v7, v15, v30, v60, and v90) after the initial visit (v0). During v0 and v90, a chewing evaluation was performed according to the MBGR protocol adapted. The significance level adopted was 5%. RESULTS: A total of 30 females (88%) and 4 males (12%) were analyzed. The SG had 18 subjects, and the CG had 16, with mean ages of 50.17 ± 12.28 years and 45.69 ± 9.78 years, respectively. The postoperative time ranged from 4 to19 months. In the SG, a marked improvement in the number of episodes of food intolerance was observed (p < 0.001), an improvement in the intake of cereals and meats (p = 0.004 and p < 0.001, respectively), and an improvement in chewing capacity and swallowing (p = 0.002 and p = 0.011, respectively). CONCLUSION: Speech therapy intervention in chewing led to a marked improvement of food acceptance and food intolerance resulting from Roux-en-Y gastric bypass.

French Language Online Cognitive Behavioral Therapy for Insomnia Disorder: A Randomized Controlled Trial.

Background: Despite cognitive-behavioral therapy for insomnia (CBT-I) being the recommended treatment for insomnia disorder, its access remains very limited. Automated Internet-delivered CBT-I (eCBT-I) is an emerging cost-effective strategy for adults with insomnia, however no such program is currently available in French Language. We evaluated a French-speaking, eCBT-I intervention to improve insomnia disorder in comparison to minimal psychoeducation therapy (mPT). Methods: Forty-six adults with insomnia disorder were randomly allocated to eCBT-I or mPT. The eCBT-I program consisted of seven sessions that delivered the typical components of CBT-I during 12 weeks. The mPT provided structured and non-tailored information about sleep and insomnia during a 1 h session. Insomnia severity Index (ISI, primary outcome), measures of fatigue, sleepiness, anxiety, depressive symptoms and quality of life were collected at baseline and endpoint. Electronic sleep diaries were completed over 2 week periods pre- and post-intervention. Results: Compared to mPT, eCBT-I resulted in greater decrease in ISI scores between baseline and endpoint. Sleep diaries parameters improved in both groups, with a greater improvement in the eCBT-I group. Patients allocated to eCBT-I group also improved depressive, fatigue, anxiety symptoms, and quality of life. Among patients with CNS-active drug at baseline, 91.7% reduced or stopped their hypnotic medication, and 16.7% in the mPT group. Conclusions: The present eCBT-I program seems feasible, acceptable and effective in reducing insomnia severity and insomnia-related functional outcomes in this small clinically-derived population. Given the high prevalence of insomnia, our data are supportive of the use of such program as an effective alternative to treat insomnia in daily clinical practice in French speaking countries.

Haptoglobin levels are influenced by Hp1-Hp2 polymorphism, obesity, inflammation, and hypertension in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an inflammatory condition associated to obesity and increased oxidative stress. Haptoglobin (Hp) is an acute phase reactant that scavenges extracorpuscular hemoglobin from circulation and prevents heme-iron oxidative damage. OBJECTIVE: To assess the association between Hp levels and Hp1-Hp2 gene polymorphism and clinical and laboratory parameters in patients with T2DM. METHODS: The study sample consisted of 102 T2DM patients and 62 controls. Hp plasma levels were measured using an ELISA assay, and Hp genotyping was performed using a specific two-step allelic polymerase chain reaction. RESULTS: Hp levels were higher in T2DM patients as compared to controls (p=0.005). T2DM patients with high blood pressure had higher Hp levels than patients without this comorbidity (p=0.021). Obese T2DM patients had higher Hp levels as compared to obese controls (p=0.009) and to non-obese T2DM patients (p=0.003). The Hp1-Hp1 genotype was showed to be associated to T2DM according to additive (OR=3.038, 95% CI 1.127-8.192; p=0.036) and dominant model (OR=0.320, 95% CI 0.118-0.839; p=0.010), but Hp2 allele carriers contributed with higher Hp levels in T2DM as compared to controls. Waist circumference (p=0.002), BMI (p=0.001), and IL-6 (p=0.012), and hs-CRP (p=0.001) levels positively correlated with Hp levels in the T2DM group. CONCLUSION: These results suggest that Hp levels are influenced by Hp1-Hp2 polymorphism, obesity, inflammatory status, and high blood pressure in T2DM.

Effect of psychostimulants on blood pressure profile and endothelial function in narcolepsy.

OBJECTIVE: To assess the effect of psychostimulant treatments on the 24-hour blood pressure (BP) profile of patients with narcolepsy type 1 (NT1). METHODS: Heart rate (HR) and BP were monitored for 24 hours and morning endothelial function was evaluated in 160 consecutive patients with NT1: 68 untreated (41 male, median age 34.9 years), 54 treated (32 male, median age 40.9 years), and 38 evaluated twice (21 male, median age 32 years), before and during treatment. RESULTS: Patients treated for NT1 showed higher 24-hour, daytime, and nighttime diastolic BP and HR values compared with the untreated group. Similarly, HR as well as 24-hour and daytime systolic BP were increased during treatment in the group evaluated twice. The combination of stimulant and anticataplectic drugs showed a synergistic effect on BP, without differences among stimulant categories. Based on 24-hour BP monitoring, hypertension was diagnosed in 58% of treated patients and in 40.6% of untreated patients. After adjustments for age, sex, and body mass index, the percentage of REM sleep remained associated with 24-hour hypertension in untreated and treated patients. Endothelial function was comparable in treated and untreated patients. CONCLUSIONS: The finding that patients with NT1 treated with psychostimulants have higher diastolic BP and HR than untreated patients suggests an increased long-term risk of cardiovascular diseases that requires careful follow-up and specific management.

Circulating microparticles levels are increased in patients with diabetic kidney disease: A case-control research.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with chronic lowgrade inflammation. Microparticles (MPs) are extracellular microvesicles released during apoptosis and cellular activation. The MP's pro-coagulant and pro-inflammatory activities are involved in endothelial dysfunction observed in T2DM patients. This study aimed to evaluate the circulating MPs profile in T2DM patients with diabetic kidney disease (DKD) and correlate it with clinical and laboratorial parameters. METHODS: MPs derived from platelets (PMPs), leukocytes (LMPs), endothelial cells (EMPs), and expressing tissue factor (TFMPs) were measured by flow cytometry, in plasma of 39 DKD patients and 30 non-diabetic controls. RESULTS: We observed higher PMPs, LMPs, EMPs, and TFMPs (all p<0.0001) levels in case group as compared to controls. For patients with DKD, circulating MPs levels were influenced by gender, but not by obesity status nor by T2DM onset. Fasting glucose and 25-hydroxyvitamin D levels showed correlation with circulating MPs levels in both groups. CONCLUSIONS: These results suggest that type 2 diabetes mellitus patients with DKD presented higher circulating MPs levels - PMPs, LMPs, EMPs, and TFMPs - which correlated with metabolic alterations.

Proresolving protein Annexin A1: The role in type 2 diabetes mellitus and obesity.

BACKGROUND: Annexin A1 (AnxA1) is a protein involved in inflammation resolution that might be altered in obesity-associated type 2 diabetes mellitus (DM), which is a chronic inflammatory disease. The aim of this study was to evaluate AnxA1 serum levels in individuals with and without DM stratified according to the body mass index (BMI), and the dynamic of AnxA1 expression in adipose tissue from humans with obesity and non-obesity. METHODS: Serum samples were obtained from 41 patients with DM (lean, overweight and obese) and 40 controls, and adipose tissue samples were obtained from 16 individuals with obesity (with or without DM), and 15 controls. RESULTS: DM patients showed similar AnxA1 serum levels when compared to controls. However, when the individuals were stratified according to BMI, AnxA1 levels were higher in individuals with obesity than lean or overweight, and in overweight compared to lean individuals. Moreover, AnxA1 was correlated positively with IL-6 levels. AnxA1 levels were also positively correlated with BMI, waist circumference and waist-to-hip ratio. Furthermore, higher levels of cleaved AnxA1 were observed in adipose tissue from individuals with obesity, independently of DM status. CONCLUSIONS: Enhanced levels of AnxA1 in serum of individuals with obesity suggest an attempt to counter-regulate the systemic inflammation process in this disease. However, the higher levels of cleaved AnxA1 in the adipose tissue of individuals with obesity could compromise its anti-inflammatory and proresolving actions, locally. Considering our data, AnxA1 cleavage in the adipose tissue, despite increased serum levels of this protein, and consequently the failure in inflammation resolution, suggests an important pathophysiological mechanism involved in inflammatory status observed in obesity.

MMP-9 Levels and IMT of Carotid Arteries are Elevated in Obese Children and Adolescents Compared to Non-Obese.

BACKGROUND: Childhood obesity is associated with increased risk of atherosclerosis and cardiovascular disease in adulthood. Increased intima-media thickness (IMT) of the carotid artery is linked to the initiation and progression of the chronic inflammatory processes implicated in cardiovascular disease. Matrix metalloproteinase-9 (MMP-9) plays an important role in the degradation of the extracellular matrix and, consequently, in the development, morphogenesis, repair and remodeling of connective tissues. OBJECTIVES: (i) to determine and compare the concentrations of MMP-9, tissue inhibitor of metalloproteinase -1 (TIMP-1), and MMP-9/TIMP-1 ratio in obese and non-obese children and adolescents; (ii) to investigate the association of these markers with common and internal IMT of carotid arteries. METHODS: Cross-sectional study involving 32 obese and 32 non-obese (control) individuals between 8 - 18 years of age. RESULTS: Significantly (p < 0.05) higher values of MMP-9 concentration, as well as a higher MMP-9/TIMP-1 ratio were detected in the obese group compared to control counterparts. Common and internal carotid IMT values were significantly higher (p < 0.001) in the obese group compared to the control group. Positive correlations were observed between the common carotid IMT values and MMP-9 concentrations as well as MMP-9/TIMP-1 ratio. CONCLUSIONS: Our data demonstrate that obese children and adolescents present higher mean IMT values, plasma MMP-9 and MMP-9/TIMP-1 ratio compared to the non-obese. Thus, these findings indicate that this group presents a risk profile for early atherosclerosis.

IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals.

OBJECTIVE: This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. SUBJECTS AND METHODS: One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. RESULTS: IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. CONCLUSIONS: These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.