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Background: Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Objective: Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG. Methods: To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry. Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO. Results: The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P=0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P =0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P=0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P =0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P =0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P =3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P =0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P =1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P =0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P =0.796). Conclusion: AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.
Assuntos
Doença de Hashimoto , Hipotireoidismo , Miastenia Gravis , Tireoidite Autoimune , Humanos , Análise da Randomização Mendeliana , Miastenia Gravis/complicações , Miastenia Gravis/epidemiologia , Miastenia Gravis/genética , Hipotireoidismo/complicações , Hipotireoidismo/epidemiologia , Hipotireoidismo/genética , TireotropinaRESUMO
Background: Previous studies have suggested a potential association between Autoimmune thyroid disease Thyroid nodules and Sleep Traits, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Objective: Therefore, we employed a MR analysis to investigate the causal relationship between Autoimmune thyroid disease, Thyroid nodules and Sleep Traits. Methods: To explore the interplay between Autoimmune thyroid disease Thyroid nodules and Sleep Traits, we employed MR studies utilizing summary statistics derived from GWAS in individuals of European ancestry. To ensure robustness, multiple techniques were employed to assess the stability of the causal effect, including random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated using Cochran's Q value. Additionally, we investigated the presence of horizontal pleiotropy through MR-Egger regression and MR-PRESSO. Results: The IVW method indicates a significant causal relationship between "Getting up" and autoimmune hypothyroidism, as revealed by the IVW method (OR: 0.59, 95% CI: 0.45 to 0.78, P-value = 1.99e-4). Additionally, there might be a potential correlation between sleep duration and autoimmune hypothyroidism (OR: 0.76, 95% CI: 0.60 to 0.79, P-value = 0.024). Moreover, the observed potential positive link between daytime nap and thyroid nodules (OR: 1.66, 95% CI: 1.07 to 2.58, P-value = 0.023) is subject to caution, as subsequent MR PRESSO testing reveals the presence of horizontal pleiotropy, raising concerns about the reliability of the findings. The findings suggested a potential inverse association between Autoimmune hypothyroidism and Getting up (OR: 0.99, 95% CI: 0.98 to 1.00, P-value = 6.66e-3).As the results of MR-Egger method(OR: 1.00, 95% CI: 0.98 to 1.02, P-value = 0.742) exhibited an opposing trend to that observed with the IVW method and the results did not reach significance after P-value correction. Conclusion: The results of our study reveal a notable cause-and-effect relationship between Getting up and Autoimmune hypothyroidism, indicating its potential role as a protective factor against this condition. However, no causal connection was observed between sleep traits and Graves' disease or Thyroid nodules.
Assuntos
Doença de Graves , Doença de Hashimoto , Hipotireoidismo , Nódulo da Glândula Tireoide , Tireoidite Autoimune , Humanos , Nódulo da Glândula Tireoide/complicações , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/genética , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , SonoRESUMO
OBJECTIVES: We found that activation of the nicotinic acid receptor GPR109A, expressed by the MIN6 murine pancreatic ß cell line, inhibits nitric oxide accumulation induced by IFN-γ and TNF-α, implicating an anti-inflammatory effect of GPR109A in MIN6 cells. Nevertheless, the mechanism of its anti-inflammatory effect is still unknown. In this study, we used palmitic acid to stimulate MIN6 cells to induce inflammatory cytokine production and explored the mechanism by which GPR109A exerts anti-inflammatory effects. MATERIALS AND METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of GPR109A in MIN6 cells. Western blotting was used to detect the activation of the Akt/mTOR signaling pathway and expression of the inflammatory cytokine INF-γ, in MIN6 cells, following treatments with palmitic acid and palmitic acid+nicotinic acid, or with different concentrations of nicotinic acid and 3-hydroxybutyrate. RESULTS: In MIN6 cells, GPR109A transcripts and protein are expressed and GPR109A protein is mainly located in the cell membrane and cytoplasm. Palmitic acid enhanced the phosphorylation of Akt and p70S6K and elevated the expression of IFN-γ. Co-treatment with nicotinic acid, which is an agonist of GPR109A, inhibited the palmitic acid-induced phosphorylation of Akt, mTOR, and p70S6K, as well as the expression of IFN-γ. CONCLUSIONS: GPR109A may inhibit inflammatory cytokine production, induced by palmitic acid, by MIN6 cells possibly via inhibiting the Akt/mTOR signaling pathway.
Assuntos
Anti-Inflamatórios/metabolismo , Células Secretoras de Insulina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Nicotínicos/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Ácido 3-Hidroxibutírico/farmacologia , Animais , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/patologia , Interferon gama/metabolismo , Camundongos , Niacina/farmacologia , Ácidos Fosfatídicos/farmacologia , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Nicotínicos/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismoRESUMO
BACKGROUND: Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM. METHODS: This cross-sectional analysis included 827 participants who were 18 years of age or older and had been living with T1DM for at least 1 year. Participants with HbA1c levels <7% were compared against those with HbA1c levels ≥ 7%. A multivariate logistic regression model was used to examine factors associated with glycaemic control. RESULTS: Among the 827 participants, the mean age was 34.2 ± 12.1 years and the median (interquartile range) duration of diabetes was 6.1 (3.4, 10.4) years. The median HbA1c level was 8.5% (7.5%, 10.2%). Only one-fifth of participants had HbA1c levels <7%. Insufficient glycaemic control (HbA1c ≥ 7%) was strongly associated with infrequent self-monitoring of blood glucose (OR = 1.21, 95% CI 1.14 ~ 1.29, p = 0.000), high insulin dose (OR = 1.27, 95% CI 1.07 ~ 1.52, p = 0.006), smoking (OR = 3.11, 95% CI 1.44 ~ 6.72, p = 0.004), low-frequency clinical visits (OR = 2.74, 95% CI 1.47 ~ 5.10, p = 0.001), the presence of diabetic autoantibodies (OR = 1.63, 95% CI 1.07 ~ 2.48, p = 0.022) and low fasting C-peptide (FCP) levels (OR = 1.21, 95% CI 1.01 ~ 1.46, p = 0.049) after adjustment for age at disease onset, education level, household income and diet control. CONCLUSIONS: Most adult patients with T1DM did not achieve the HbA1c target. Identifying determinants for glycaemic control provides us valuable information to improve glycaemic control in these patients. Copyright © 2015 John Wiley & Sons, Ltd.
Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Adolescente , Adulto , China , Estudos Transversais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To explore the glycemic control status and related risk factors of overweight or obesity patients with type 2 diabetes mellitus (T2DM) in Guangdong province. METHODS: The medical records of overweight or obesity patients with T2DM from 60 tertiary and secondary hospitals in Guangdong Province were collected by questionnaire and physical examination. And the clinical data were analyzed to explore the influencing factors of glycemic control. The HbA1c level was used to assess glycemic control. HbA1c < 7.0% indicated that glycemic control was up to standard. RESULTS: From August 2011 to March 2012, 5241 T2DM patients were recruited. The scope of current analysis was restricted to 4768 subjects with true data and deficiency no more than 5%. There were 2252 males and 2516 females. The age range was from 16 to 90 years, a median age 59.0 (50.0 - 69.0) years, onset age of diabetes 52.0 (44.0 - 60.0) years; a range of disease duration from 1 day to 42 years and a median of 5.0 (2.0 - 11.0) years. The median body mass index was 26.33(24.88 - 28.34) kg/m(2) and median waist circumference 93.0 (88.0 - 100.0) cm. Median HbA1c was 8.1% (6.9% - 10.1%) and only 26.2% patients reached the target level of HbA1c < 7.0%. Influencing factors of poor glycemic control were central obesity, high levels of resting heart rate, concurrent fatty liver and high intensity of treatment. And influencing factors of good glycemic control were regular exercises, smoking cessation, regular glycemic monitoring and good control of total cholesterol/triglyceride. CONCLUSION: A majority of Guangdong type 2 diabetics fail to achieve target values for glycemic control. There is an urgent need for comprehensive management for improving glycemic control.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Prevalência , Fatores de Risco , Adulto JovemRESUMO
Sirtuin 1 (SIRT1) is one member of the silent information regulator 2 (Sir2)-like family of proteins involved in glucose homeostasis in mammals. It has been reported that SIRT1 modulates endocrine signaling of glucose and fat homeostasis by regulating transcription factors such as forkhead transcription factor 3a (FOXO3a), glucose transporter 4 (GLUT4), peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator (PGC-1α). However, it is still not clear how SIRT1 is involved in the development of insulin resistance. To determine the location and expression of SIRT1 and its target proteins in rats and analyze the interactions and functions of these proteins in insulin resistance. Forty-eight male Sprague-Dawley rats were randomly divided into four regimen groups: normal control (NC), calorie restriction (CR), high-fat (HFa), and high-fructose (HFr). Animals were fed for 12 weeks and blood samples collected from tail veins at weeks 2, 4, 6, 8 and 12 after fasting for 16 h. Baseline metabolic parameters such as fasting blood sugar, insulin, cholesterol and triglycerides were analyzed. A glucose tolerance test was carried out at the end of the study. Visceral fat, consisting of epididymis and perirenal fat, was isolated and weighed. The pancreas from each animal was also immediately removed. Immunohistochemical staining was performed to detect the locations of SIRT1, FOXO3a, GLUT4, PPARγ and PGC-1α in the ß-cell of the rat pancreas. Expression in the pancreas was analyzed by western blotting. Blood biochemical analysis indicated that the HFa and HFr groups were insulin-resistant. Immunohistochemical staining showed that GLUT4 was a nuclear protein. SIRT1, FOXO3a, PPARγ and PGC-1α were present in both the nucleus and the cytoplasm of ß-cells of pancreatic islets. The expression of SIRT1, GLUT4 and PGC-1α increased significantly in response to CR, but decreased in the HFr and HFa groups. FOXO3a was similar in the CR and the NC groups, whereas it declined in the HFa and HFr groups. PPARγ was elevated in the HFa group, but dropped in the CR and HFr groups. These data suggest that SIRT1 and its regulators are involved in the development of insulin resistance.