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The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.
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Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.
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PURPOSE: Impaired negative feedback and hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis characterizes type 2 diabetes mellitus (T2DM). The glucocorticoid receptor (GR) is a key mediator of HPA axis negative feedback; however, its role in linking hypercortisolemia and T2DM-associated hyperglycemia, hyperlipidemia and inflammation is not yet known. METHODS: In peripheral mononuclear cells (PBMC) from 31 T2DM patients and 24 healthy controls, we measured various GR-signaling parameters such as phosphorylated GR (pGR-S211), GRα/GRß gene expression and GC-sensitivity [using the basal and dexamethasone (DEX)-induced leucine zipper (GILZ) and FK506 binding-protein (FKBP5) mRNA levels as well as the basal interleukin (IL)-1ß protein levels]. Diurnal salivary cortisol curve parameters such as the cortisol awaking response (CAR) and area under the curve (AUCtotal and AUCi) as well as inflammatory and metabolic indices were also determined. RESULTS: T2DM patients exhibited diminished pGR-S211 protein content, increased GRß, decreased basal GILZ and FKBP5 mRNA levels and increased IL-1ß levels. Flattened DEX-induced GILZ and FKBP5 response curves and a flattened salivary cortisol profile characterized T2DM patients. Significant associations of GR measures and saliva cortisol curve parameters with biochemical and clinical characteristics were found. CONCLUSION: Our novel data implicate an insufficient GR signaling in PBMCs in T2DM patients and HPA axis dysfunction. The significant associations of GR-signaling parameters with inflammatory and metabolic indices implicate that GR may be the critical link between HPA axis dysfunction, hypercortisolemia and diabetes-associated metabolic disturbances. Our findings provide significant insights into the contribution of GR-mediated mechanisms in T2DM aetiopathology and therapy.
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Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/complicações , Hidrocortisona/sangue , Inflamação/patologia , Doenças Metabólicas/patologia , Receptores de Glucocorticoides/metabolismo , Saliva/metabolismo , Glicemia/análise , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Masculino , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , PrognósticoRESUMO
OBJECTIVE: Diabetes mellitus is a disease associated with many complications leading to premature death. The aim of this study was to estimate prevalence of type 2 diabetes (T2D), and the proportion of the population unaware of the condition, in association with modifiable risk factors. STUDY DESIGN: Data from the Hellenic National Nutrition and Health Survey were used (n = 3773 adults, 40.8% men) and were obtained by trained personnel. METHODS: Diabetes mellitus disease status was categorized as per the International Classification of Diseases codes (10th version). A subsample from the two main metropolitan areas was used to assess T2D and impaired fasting glucose (IFG) (n = 990; 38.2% men) from plasma analysis. RESULTS: The prevalence of T2D in the population was 5.2% in total, reaching 13.7% in adults aged >60 years (no sex differences). IFG was observed in 27.3% of adults in the two metropolitan areas, and 40% were unaware of having T2D in this subsample. The likelihood of having T2D significantly increased with age and body weight, whereas it decreased with higher educational level and physical activity (P for all <0.001). CONCLUSION: The high T2D prevalence in adults, especially among the older age-groups, suggests a major public health problem in Greece.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adulto , Idoso , Glicemia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Grécia/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Common autoimmune diseases tend to coexist in the same patients. Few studies have examined the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with inconsistent results. OBJECTIVE: To investigate the prevalence of autoimmune thyroiditis in psoriatic patients with or without PsA, living in an iodine-sufficient area. METHODS: We studied prospectively, 114 psoriatic patients with disease duration of 5-38 years, 30 of them with PsA, and 286 age- and body mass index (BMI)-matched subjects without psoriasis or known thyroid disease or autoimmune disease. A detailed medical history was obtained from all participants and clinical examination and laboratory evaluation was performed. Psoriasis severity was assessed with Psoriasis Area and Severity Index (PASI). Autoimmune thyroiditis was defined by the presence of positive autoantibodies to thyroid peroxidase and/or thyroglobulin. RESULTS: There was no difference in the prevalence of autoimmune thyroiditis between psoriatic patients and controls (20.2% vs. 19.6%). The prevalence of autoimmune thyroiditis in male and female psoriatic patients was similar (9.6% and 10.5% respectively), in contrast to the increased, as expected, prevalence in female vs. male controls (14.7% vs. 4.9%, P < 0.01). Detected cases with hypothyroidism due to autoimmune thyroiditis were similar in psoriatic patients and controls (7.9% and 7.0% respectively). Autoimmune thyroiditis in psoriatic patients was not related with age of psoriasis onset, psoriasis duration, PASI score, PsA and obesity. CONCLUSION: These data support that psoriatic patients with or without PsA do not have an increased risk for autoimmune thyroiditis.
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Psoríase/complicações , Tireoidite Autoimune/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due to Candida albicans. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) levels and IL-10/TNF-α ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-α ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation.
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Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidemia/tratamento farmacológico , Janus Quinases/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Sepse/tratamento farmacológico , Animais , Antifúngicos/administração & dosagem , Candida albicans/isolamento & purificação , Candidemia/mortalidade , Citocinas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Camundongos Endogâmicos , Nitrilas , Inibidores de Proteínas Quinases/administração & dosagem , Pirazóis/administração & dosagem , Pirimidinas , Sepse/mortalidadeRESUMO
Women with polycystic ovary syndrome (PCOS) are often characterized by adiposity and insulin resistance (IR). Recent studies in patients with obesity and diabetes mellitus type 2 (DMt2) indicate that adiponectin and resistin may play a role in the pathophysiology of IR. The aim of this study was to identify a possible correlation between the plasma levels of adiponectin and resistin and IR in patients with PCOS. Thirty-one women of reproductive age were enrolled in this prospective study after being diagnosed with PCOS and IR according to Rotterdam and American Diabetes Association (ADA) criteria, respectively. Every patient was treated with a daily dose of 1275 mg metformin for 6 months. Adiponectin, resistin, and the primary hormonal and metabolic parameters of the syndrome were evaluated at entry and endpoint of treatment. Adiponectin plasma levels were reduced after metformin treatment, but resistin levels were not significantly affected. Our study suggests that circulating levels of adiponectin should be evaluated with skepticism in patients with PCOS. The adipokine's role in the manifestation of IR in PCOS remains unclear and needs further investigation.
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Adiponectina/sangue , Metformina/uso terapêutico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Resistina/sangue , Adulto , Índice de Massa Corporal , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Metformina/farmacologia , Síndrome do Ovário Policístico/metabolismo , Adulto JovemRESUMO
Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.
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Adiponectina/farmacologia , Doença da Artéria Coronariana/patologia , Interleucina-10/biossíntese , Interleucina-6/biossíntese , Macrófagos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Depuradores Classe A/genética , Receptores Depuradores Classe A/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
We aimed to determine the prevalence of early ejaculation disorders (EED) and to calculate the prevalence of lifelong premature ejaculation (PE) in Greek urban men. Associations with physiological and psychological conditions, treatment-seeking and treatment efficacy were defined. We surveyed 522 urban men aged 16-62 individually using an open, one-on-one questionnaire. A total of 305 (58.43%) participants reported EED. The prevalence of lifelong PE, according to the International Society for Sexual Medicine criteria, was calculated as 17.7%. Among sufferers of EED, unrelated stress was the most frequent comorbidity (42.6%) and, along with erectile dysfunction and lower urinary tract symptoms, occurred more frequently than in normal participants (P < 0.05). Half (50.3%) of the sufferers believed that their problem was psychological, while 69.5% never sought help. Most (69.2%) of those who did seek help sought it anonymously through the internet. Behavioural treatment was preferred to medical treatment. Few (13.8%) men were satisfied with their treatment. In conclusion, although the observed PE prevalence agrees with the previous findings, more patients suffer negative personal and relationship consequences and may also require treatment. Most men do not seek medical assistance, and from those who do, most are not satisfied with the results of treatment.
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Ejaculação , Disfunções Sexuais Fisiológicas/epidemiologia , Inquéritos e Questionários , População Urbana , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Although insulin resistance in obesity is established, information on insulin action on lipid fluxes, in morbid obesity, is limited. This study was undertaken in morbidly obese women to investigate insulin action on triacylglycerol fluxes and lipolysis across adipose tissue. SUBJECTS AND DESIGN: A meal was given to 26 obese (age 35+/-1 years, body mass index 46+/-1 kg m(-2)) and 11 non-obese women (age 38+/-2 years, body mass index 24+/-1 kg m(-2)). Plasma samples for glucose, insulin, triglycerides and non-esterified fatty acids (NEFAs) were taken for 360 min from a vein draining the abdominal subcutaneous adipose tissue and from the radial artery. Adipose tissue blood flow was measured with (133)Xe. RESULTS: In obese vs non-obese: (1) Arterial glucose was similar, but insulin was increased (P=0.0001). (2) Adipose tissue blood flow was decreased (P=0.0001). (3) Arterial triglycerides (P=0.0001) and NEFAs (P=0.01) were increased. (4) Lipoprotein lipase was decreased (P=0.0009), although the arteriovenous triglyceride differences were similar. (5) Veno-arterial NEFA differences across the adipose tissue were similar. (6) NEFA fluxes and hormone-sensitive lipase-derived glycerol output from 100 g adipose tissue were not different. (7) Total adipose tissue NEFA release was increased (P=0.02). CONCLUSIONS: In morbid obesity: (a) hypertriglycerinemia could be attributed to a defect in the postprandial dynamic adjustment of triglyceride clearance across the adipose tissue, partly caused by blunted BF; and (b) postprandially, there is an impairment of adipose tissue to buffer NEFA excess, despite hyperinsulinemia.
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Tecido Adiposo/metabolismo , Glicemia/metabolismo , Insulina/fisiologia , Lipólise , Lipase Lipoproteica/metabolismo , Obesidade Mórbida/metabolismo , Período Pós-Prandial , Adulto , Índice de Massa Corporal , Feminino , Humanos , Hipertrigliceridemia/etiologia , Triglicerídeos/metabolismoRESUMO
BACKGROUND/OBJECTIVES: The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140-199mg/dL at 120min (IGT-A) or PG levels 140-199mg/dL at 120min and >200mg/dL at 30/60/90min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D). SUBJECTS/METHODS: In this randomized crossover study, subjects with IGT-A (n=15, BMI: 32.4±5.2kg/m2), IGT-B (n=20, BMI: 32.5±5kg/m2) or T2D (n=12, BMI: 32.2±5.2kg/m2) followed a weight-maintenance diet (45% carbohydrates, 20% proteins, 35% fats) in 3 or 6 meals/day (each intervention lasting 12 weeks). Anthropometrics, diet compliance and subjective appetite were assessed every 2 weeks. OGTT and measurements of HbA1c and plasma lipids were performed at the beginning and end of each intervention period. RESULTS: Body weight and physical activity levels remained stable throughout the study. In T2D, HbA1c and PG at 120min post-OGTT decreased with 6 vs 3 meals (P<0.001 vs P=0.02, respectively). The 6-meal intervention also improved post-OGTT hyperinsulinaemia in IGT-A subjects and hyperglycaemia in IGT-B subjects. In all three groups, subjective hunger and desire to eat were reduced with 6 vs 3 meals/day (P<0.05). There were no differences in HOMA-IR or plasma lipids between interventions. CONCLUSION: Although weight loss remains the key strategy in hyperglycaemia management, dietary measures such as more frequent and smaller meals may be helpful for those not sufficiently motivated to adhere to calorie-restricted diets. Our study shows that 6 vs 3 meals a day can increase glycaemic control in obese patients with early-stage T2D, and may perhaps improve and/or stabilize postprandial glucose regulation in prediabetes subjects.
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Glicemia/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Intolerância à Glucose/dietoterapia , Resistência à Insulina/fisiologia , Refeições , Resposta de Saciedade/fisiologia , Adulto , Índice de Massa Corporal , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Feminino , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial/fisiologia , Resultado do TratamentoRESUMO
Biosorption of Cd(II) and Cr(VI) ions in single solutions using Staphylococcus xylosus and Pseudomonas sp., and their selectivity in binary mixtures was investigated. Langmuir and Freundlich models were applied to describe metal biosorption and the influence of pH, biomass concentration and contact time was determined. Maximum uptake capacity of cadmium was estimated to 250 and 278 mg g(-1), whereas that of chromium to 143 and 95 mg g(-1) for S. xylosus and Pseudomonas sp., respectively. In binary mixtures with Cd(II) ions as the dominant species, there is a profound selectivity for cadmium biosorption, reaching 96% and 89% for Pseudomonas sp. and S. xylosus, respectively, at 10 mg l(-1) Cd(II) and 5 mg l(-1) Cr(VI). Interesting, when chromium (VI) ions are the dominant species, there is selectivity towards chromium around 92% with S. xylosus only.
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Cádmio/metabolismo , Cromo/metabolismo , Pseudomonas/metabolismo , Staphylococcus/metabolismo , Concentração de Íons de Hidrogênio , Modelos MolecularesRESUMO
BACKGROUND: Functional dyspepsia (FD) susceptibility might be influenced by polymorphisms of genes related to inflammation (CD14, macrophage migration inhibitory factor [MIF]), motor (GNB3), and sensory dysfunction (GNB3, TRPV1). We examined the association between CD14 rs2569190, GNB3 rs5443, MIF rs222747, and TRPV1 rs755622 gene polymorphisms with FD (Rome III criteria) in the Greek population. METHODS: We genotyped 174 dyspeptics (115 with epigastric pain syndrome; 41% Helicobacter pylori positive) and 181 controls using polymerase chain reaction-based methods and we measured disease symptoms' burden with a modified Gastrointestinal Symptoms Related Scale. KEY RESULTS: Homozygous for the TT genotype and the T allele of the CD14 gene were significantly associated (OR [95% CI]) with FD (2.65 [1.42-4.94] and 1.67 [1.23-2.26], respectively). The CT, TT genotypes, and T allele frequencies of GNB3 showed also significant association with FD (2.18 [1.35-3.54], 3.46 [1.30-9.23], and 2.18 [1.48-3.19]). While heterozygous GC MIF genotype was more common in dyspeptics (1.67 [1.07-2.60]), homozygous CC genotype and the C allele of TRPV1 gene were more prevalent in controls (0.47 [0.25-0.87] and 0.69 [0.51-0.92], respectively). None of the gene polymorphism was related either to dyspepsia clinical syndrome type or to the H. pylori infection. Among dyspeptics, CD14 TT genotype was related to lower epigastric pain burden score (p<.011); CD14 CT genotype was related to higher epigastric burning and nausea burden scores (p<.04) while belching score was lower (p=.027) in MIF CG dyspeptics. CONCLUSION & INFERENCES: Functional dyspepsia susceptibility is related to CD14, GNB3, MIF, and TRPV1 gene polymorphisms, while CD14 and MIF gene variants are also associated with dyspepsia symptoms burden.
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Dispepsia/genética , Proteínas Heterotriméricas de Ligação ao GTP/genética , Oxirredutases Intramoleculares/genética , Receptores de Lipopolissacarídeos/genética , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo de Nucleotídeo Único/genética , Canais de Cátion TRPV/genética , Idoso , Estudos de Casos e Controles , Dispepsia/diagnóstico , Dispepsia/epidemiologia , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População/métodosRESUMO
OBJECTIVE: The metabolic syndrome (MetS) is a cluster of risk factors related to cardiovascular disease. Prediabetes, identified by impaired fasting glucose and/or impaired glucose tolerance, may predict future development of diabetes mellitus. However, it is not clear whether MetS and prediabetes represent the same or different clinical entities. This study compares MetS and prediabetes in terms of cardiovascular risk factors and target organ damage. RESEARCH DESIGN AND METHODS: A total of 524 overweight and obese (body mass index, BMI >or= 27 kg/m (2)) adults, mean age 53.6 +/- 10.3 years, 264 men and 260 women, were studied. All participants underwent a thorough clinical and laboratory evaluation, including an oral glucose tolerance test and insulin measurements. Echocardiography, carotid ultrasonography, and pulse wave analysis were also performed for the detection of target organ damage. NCEP-ATP III and ADA criteria were used for the diagnosis of MetS and prediabetes. RESULTS: The prevalence of MetS and prediabetes was 38.7 and 25.4 %, respectively. Overall, 129 individuals (24.6 %) had MetS without prediabetes (group M) and another 59 (11.3 %) prediabetes without MetS (group P). Group P had decreased albumin excretion (p = 0.033) and more thickened common carotid intima-media in comparison to group M (p = 0.032). Furthermore, group M was associated with higher C-reactive protein levels. Multiple logistic regression analysis revealed that advanced age (p < 0.0001, OR 1.11, 95 % CI 1.06 - 1.16), low insulin secretion (p < 0.0001, OR 0.05, 95 % CI 0.02 - 0.18 for insulinogenic index), and increased insulin resistance (p = 0.0003, OR 3.22, 95 % CI 1.71 - 6.07 for HOMA-IR) were associated with group P. CONCLUSIONS: Our data demonstrate that MetS and prediabetes have an overlapping pattern. MetS appears to have a more pronounced effect on early renal dysfunction and increased inflammatory activation, while prediabetes tends to be associated with early carotid structural changes. These findings may be due to a different pathophysiologic substrate of these clinical phenotypes in terms of insulin resistance and secretion, as well as to the varying prevalence of cardiovascular risk factors.
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Síndrome Metabólica/classificação , Sobrepeso , Estado Pré-Diabético/classificação , Adulto , Idoso , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Anamnese , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estado Pré-Diabético/diagnósticoRESUMO
BACKGROUND/OBJECTIVES: The aim of the study was to compare the effect of two-meal patterns (three vs six meals per day) on glucose and insulin levels in women with polycystic ovary syndrome (PCOS). SUBJECTS/METHODS: In a randomised, crossover, 24-week study, 40 women with PCOS, aged 27±6 years, body mass index 27±6 kg/m(2), followed a weight maintenance diet (% carbohydrates:protein:fat, 40:25:35), consumed either as a three- or a six-meal pattern, with each intervention lasting for 12 weeks. Anthropometric measurements, diet compliance and subjective hunger, satiety and desire to eat were assessed biweekly. All women underwent an oral glucose tolerance test (OGTT) with 75 g glucose for measurement of plasma glucose and insulin at the beginning and end of each intervention. HaemoglobinA1c (HbA1c), blood lipids and hepatic enzymes were measured at the beginning and end of each intervention. RESULTS: Body weight remained stable throughout the study. Six meals decreased significantly fasting insulin (P=0.014) and post-OGTT insulin sensitivity (Matsuda index, P=0.039) vs three meals. After incorporation of individual changes over time, with adjustment for potential confounders, the only variable that remained significant was the Matsuda index, which was then used in multivariate analysis and general linear models. Six meals improved post-OGTT insulin sensitivity independently of age and body weight vs three meals (P=0.012). No significant differences were found between six and three meals for glucose, HbA1c, blood lipids, hepatic enzymes, subjective desire to eat and satiety. CONCLUSIONS: Six meals had a more favourable effect on post-OGTT insulin sensitivity in women with PCOS compared with isocaloric three meals.
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Glicemia/análise , Comportamento Alimentar , Insulina/sangue , Refeições/fisiologia , Síndrome do Ovário Policístico/dietoterapia , Adulto , Estudos Cross-Over , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Arterial stiffness is associated with increased risk for cardiovascular disease. The purpose of this study is to investigate the arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 before and after glycemic control by optimal medication. METHODS: In 50 patients with uncontrolled type 2 diabetes(age:52±10years)and 25 controls of similar age and sex and no atherosclerotic risk factors we measured at baseline and 6 months after glycemic control a) carotid-femoral pulse wave velocity(PWVc m/sec-Complior SP ALAM),central systolic blood pressure(cSBP -mmHg),augmentation index(AI%), of the aortic pulse wave(ArteriographTensioMed) b)S',E'(m/sec)andE'/A'of mitral annulus by Tissue Doppler c)LV longitudinal strain(GLS-%),systolic(LongSr-l/sec)and diastolic(LongSrE-l/sec)strain rate, twisting(Tw-deg),peak twisting(Tw)and untwisting(unTw-deg/sec)velocity using speckle tracking echocardiography.The degree of LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO(%dp PeakTw-UntwMVO)and between peak twisting and untwisting at peak and end of the mitral inflow E wave d)perfusion boundary region(PBR- micrometers)of the sublingual arterial microvessels(ranged from 5-25 micrometers)using Sideview,Darkfield imaging(Microscan,Glycocheck).Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness because of a deeper RBC penetration in the glucocalyx e) Flow mediated dilatation(FMD) of the brachial artery and percentage difference of FMD (FMD%). RESULTS: Compared to controls,diabetics had higher PWVa(10.3±2.2 vs. 8.1±1.9), AI(27.9±15 vs. 19.4±14.7), PWVc(11.8±3.2 vs. 8.8±1.3),cSBP(136±20 vs. 119±18),PBR (2.1±0.2 vs 1.89±0.1)and lower GLS(-15±3 vs. -18±3),LongSr(-0.78±0.1 vs. -0.96±0.2),LongSrE(0.77±0.29 vs. 1.2±0.3),S',E' and E/A(p<0.05 for all comparisons). Baseline FMD was related with Untw at peak E%(r=0,65, p<0.05). Six months after the modification of antidiabetic medication all patients achieved glycaemic control and there was a reduction of PWVc(12.3±2.9 vs. 11.3±3.2,p<0.05) in parallel with a increase of Untw velocity (-73±27 vs. -98±43,p<0.05),Untw MVO%(20±9 vs. 30±2),Untw peak E% (40±14 vs. 50±16)and FMD%(7.8±3 vs. 13.6±11,p<0.01).Reduced PWVc was related with reduced SBP(r=0.62),cSBP(r=0.55)and increased LongsrE(r=-0.50), Untw at end E(r=-0.56)respectively(p<0.05 for all associations). CONCLUSION: Glycaemic control after optimizing medical treatment improves arterial stiffness, LV myocardial strain, twisting and untwisting velocity in diabetics.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Rigidez Vascular/efeitos dos fármacos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Glicemia/análise , Determinação da Pressão Arterial , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Monitorização Hemodinâmica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
To assess the normality of islet A- and B-cell responses to a nonglucose secretogogue as well as the modulating effect of glucose in NIDDM, we examined plasma C-peptide and glucagon responses to arginine in eight patients with NIDDM and in six age- and weight-matched nondiabetic volunteers under conditions of identical hypoglycemia (approximately 70 mg/dl), euglycemia (94 mg/dl), and hyperglycemia (approximately 190 mg/dl). Plasma C-peptide responses to glucose and to arginine in the diabetic subjects were both significantly reduced at all glucose concentrations studied (P less than 0.01-0.005). The modulating effect of glucose on both islet A- and B-cell responses (slope of relation between plasma C-peptide or glucagon response versus plasma glucose concentration) was reduced greater than 80% in the diabetic subjects (P less than 0.01). We conclude that islet A- and B-cell responses to nonglucose secretogogues are abnormal in patients with NIDDM and that this may result from a functional defect in the modulating effect of glucose on insulin and glucagon secretion, which in some patients may be compensated for by hyperglycemia.