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BACKGROUND: TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. METHODS: In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18-75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. RESULTS: A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 µg*h/mL, and AUC0-inf ranged from 159 to 340 µg*h/mL. TG103 had a half-life of 110-116 h, with a median Tmax of 36-48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo. CONCLUSIONS: In this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04855292. Registered on April 22, 2021.
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Obesidade , Sobrepeso , Humanos , Pessoa de Meia-Idade , Masculino , Adulto , Feminino , Método Duplo-Cego , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Idoso , Adulto Jovem , Adolescente , China , Placebos/administração & dosagem , Injeções Subcutâneas , Peptídeo 1 Semelhante ao GlucagonRESUMO
BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.
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Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Glicemia , Hipoglicemiantes/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Método Duplo-Cego , Resultado do TratamentoRESUMO
BACKGROUND: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. METHODS: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). RESULTS: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. CONCLUSION: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03944109.
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Hipercolesterolemia , Inibidores de PCSK9 , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipercolesterolemia/tratamento farmacológico , Inibidores de PCSK9/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Both obesity and subclinical hypothyroidism (SCH) have adverse effects on human body, but the relationship between these two conditions remains inconsistent. The presence of thyroid autoantibodies influences thyroid hormone levels, and may further mediate the interaction between obesity and SCH. This study aimed to explore the association among obesity, SCH and thyroid autoantibodies. METHODS: This study was a cross-sectional survey of 2505 subjects. Obesity was defined as a body mass index ≥28 kg/m2. Serum concentrations of thyroid hormones, thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were examined. Logistic analysis was used to explore the relation among obesity, SCH and thyroid autoantibodies. RESULTS: A proportion of 11.54% (289/2505) subjects were obese, and 165 subjects had SCH. The positive rates of thyroid autoantibodies, TPO-Ab and Tg-Ab were 17.64% (442/2505), 11.02% (276/2505) and 14.13% (354/2505), respectively. The proportion of SCH was significantly higher in obese than nonobese subjects among those with positive thyroid autoantibodies [22.41% (13/58) vs. 11.72% (45/384), p = 0.025, χ2 test]. Moreover, obesity was significantly associated with SCH in the presence of thyroid autoantibodies after adjusting for confounding factors (OR 2.212, 95% CI 1.103 to 4.433, p = 0.025). A higher proportion of subjects with obesity had Tg-Ab positivity [17.99% (52/289) vs. 13.63% (302/2216), p = 0.045, χ2 test], and obesity remained significantly associated with Tg-Ab positivity by multiple logistic analysis (OR 1.504, 95% CI 1.077 to 2.101, p = 0.017). CONCLUSIONS: Obesity was associated with SCH in the presence of thyroid autoantibodies. Examination of SCH is recommended in obese subjects with thyroid autoantibody positivity.
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Hipotireoidismo , Iodeto Peroxidase , Autoanticorpos , Estudos Transversais , Humanos , Hipotireoidismo/complicações , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Obesidade/complicações , Hormônios TireóideosRESUMO
The level of lactate in the blood is associated with obesity, blood pressure, and type 2 diabetes. In addition, lactate is a pro-inflammatory cytokine, which plays an important role in the pathogenesis of cognitive impairment. However, the association between blood lactate, systemic inflammation, and mild cognitive impairment (MCI) has not been investigated. The aim of the study is to explore this association in a Chinese population. This community-based cross-sectional study included 2523 Chinese participants aged 18-88 years. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination. MCI was defined using education-based cutoffs. The concentration of plasma lactate and serum high-sensitivity C-reactive protein (hs-CRP) was measured using the lactate oxidase method and latex enhanced immunoturbidimetric assay, respectively. Compared with participants without a cognitive impairment, participants with a MCI had an increased concentration of plasma lactate and serum hs-CRP (P < 0.001). As blood lactate increased, the concentration of serum hs-CRP and prevalence of MCI also increased (P < 0.001). Logistic regression analysis showed that plasma lactate (odds ratio (OR) 2.76, 95% confidence interval (CI) 2.21-3.45, P < 0.001) and serum hs-CRP (OR 1.15, 95% CI 1.08-1.24, P < 0.001) were significant risk factors for MCI. The adjusted OR for MCI in participants in the fourth lactate quartile was 3.44 (95% CI 2.02-5.88, P < 0.001) compared with the first quartile. Our results showed that plasma lactate is associated with systemic inflammation and MCI.
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Disfunção Cognitiva/sangue , Disfunção Cognitiva/imunologia , Inflamação/imunologia , Ácido Láctico/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Disfunção Cognitiva/epidemiologia , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
BACKGROUND: Diabetic foot ulceration is receiving more attention because of its high amputation and mortality rate. It is essential to establish the frequency of amputations in people with diabetes after any change to the management of diabetic foot care. The present study aim to compare the frequency of lower-extremity amputations in patients with diabetes foot ulcer over a ten-year period. METHODS: Six hundred forty eight patients with diabetes foot ulcer were retrospectively studied from 2004 to 2013. The clinical features, laboratory results and the lower-extremity amputations were recorded. Major amputation was defined as amputations above the ankle while minor amputation was amputations below the ankle in the present study. RESULTS: Patients with diabetic foot ulcer were old (age 66.96 ± 11.96 years), with a long duration of diabetes (10.30 ± 6.94 years), high HbA1c (9.19 ± 2.62 %), SBP (144.05 ± 24.18 mmHg), DBP (79.53 ± 11.88 mmHg), LDL-C (2.71 ± 0.93 mmol/L) and had great frequency of neuropathy (62.7 %), retinopathy (45.0 %), nephropathy (39.5 %) and PAD (33.2 %). From 2004 to 2013, the frequency of all lower-extremity amputations is 12.0 % (5.2 % major amputation, 6.8 % minor amputation). The frequency of major amputations decreased from 9.5 % in 2004 and 14.5 % in 2005 to less than 5.0 % after 2006. In particular, there was a significant decline in major amputations of diabetic foot patient with Wagner 3 to 4 wounds. The frequency rate of major amputations in diabetic foot patient with Wagner 3 to 4 wounds fell from 35.7 % in 2004 to 4.4 % after 2007. The change in frequency of minor amputations was fluctuation. CONCLUSION: This study demonstrates that the introduction of a multidisciplinary team, coordinated by an endocrinologist and a podiatrist, for managing diabetic foot disease is associated with a reduction in the frequency of major amputations in patients with diabetes.
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Amputação Cirúrgica/estatística & dados numéricos , Pé Diabético/terapia , Equipe de Assistência ao Paciente , Idoso , Humanos , Relações Interprofissionais , Prognóstico , Avaliação de Programas e Projetos de Saúde , Qualidade da Assistência à Saúde , Estudos RetrospectivosRESUMO
BACKGROUND: China has the highest absolute disease burden of diabetes worldwide. For diabetic patients, diabetes-related vascular complications are major causes of morbidity and mortality. The roles of lipoprotein-associated phospholipase A2 (Lp-PLA2) and secretory phospholipase A2 (sPLA2) as inflammatory markers have been recently evaluated in the pathogenesis of both diabetes and atherosclerosis. We aimed to determine the mechanism through which patients with newly diagnosed type 2 diabetes gain long-term vascular benefit from intensive insulin therapy by evaluating the change in Lp-PLA2 and sPLA2 levels after early intensive insulin treatment and its relevance with insulin resistance and pancreatic ß-cell function. METHODS: In total, 90 patients with newly diagnosed type 2 diabetes mellitus were enrolled. All patients received continuous subcutaneous insulin infusion (CSII) for approximately 2 weeks. Intravenous glucose-tolerance test (IVGTT) and oral glucose-tolerance test (OGTT) were performed, and plasma concentrations of Lp-PLA2 and sPLA2 were measured before and after CSII. RESULTS: Levels of Lp-PLA2 and sPLA2 were significantly higher in diabetic patients with macroangiopathy than in those without (P < 0.05). After CSII, the sPLA2 level decreased significantly in all diabetic patients (P < 0.05), while the Lp-PLA2 level changed only in those with macroangiopathy (P < 0.05). The area under the curve of insulin in IVGTT and OGTT, the acute insulin response (AIR3-5), early phase of insulin secretion (ΔIns30/ΔG30), modified ß-cell function index, and homeostatic model assessment for ß-cell function (HOMA-ß) increased after treatment even when adjusted for the influence of insulin resistance (IR; P < 0.001). The HOMA-IR was lower after treatment, and the three other indicators adopted to estimate insulin sensitivity (ISIced, IAI, and QUICKI) were higher after treatment (P < 0.05). Correlation analysis showed that the decrease in the Lp-PLA2 and sPLA2 levels was positively correlated with a reduction in HOMA-IR after CSII (P < 0.05). Additionally, multiple linear regression analysis showed that Lp-PLA2 and sPLA2 independently correlated with HOMA-IR (P < 0.05). CONCLUSIONS: Lp-PLA2 and sPLA2 are closely related to insulin resistance and macroangiopathy in diabetic patients. Intensive insulin therapy might help improve IR and protect against diabetic macroangiopathy by influencing the Lp-PLA2 and sPLA2 levels. TRIAL REGISTRATION: ChiCTR-TRC-10001618 2010 September 16.
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1-Alquil-2-acetilglicerofosfocolina Esterase/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Adulto , China , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas , Feminino , Humanos , Infusões Subcutâneas , Insulina/administração & dosagem , Insulina/farmacologia , Resistência à Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
Short-term intensive insulin therapy is effective for type 2 diabetes because it offers the potential to achieve excellent glycemic control and improve ß-cell function. We observed that the time to glycemic goal (TGG) was adjustable. Original data of 138 newly diagnosed type 2 diabetic patients received intensive insulin therapy by continuous subcutaneous insulin infusion for 2-3 weeks were retrospectively collected. Subjects underwent an intravenous glucose tolerance test (IVGTT) and an oral glucose tolerance test (OGTT) pre and post treatment. The glycemic goal was achieved within 6 (4-8) days. Patients were divided into two groups by TGG above (TGG-slow) and below (TGG-fast) the median value. Patients in both groups had significantly better glycemic control. Compared with TGG-fast, TGG-slow required a few more total insulin and performed more improvement of HOMA-ß and IVGTT-AUCIns, but less improvement of HOMA-IR and QUICKI. Multiple linear regression analysis revealed that TGG was always an explanatory variable for the changes (HOMA-ß, IVGTT-AUCIns, HOMA-IR and QUICKI). The hypoglycemia prevalence was lower in TGG-slow (1.48% vs. 3.40%, P<0.01). Multivariate logistic regression analysis indicated that individuals in TGG-slow had a lower risk of hypoglycemia (adjusted OR, 0.700; 95% CI, 0.567-0.864; P<0.05). Multiple linear regression analysis confirmed that the ratio of the incremental insulin to glucose responses over the first 30 min during OGTT (ΔIns30/ΔG30), average insulin dose before achieving targets, initial insulin dose and LDL-c were independent predictors for TGG. It is intriguing to hypothesize that patients with fast time to glycemic goal benefit more in improving insulin sensitivity, but patients with slow time benefit more in improving ß-cell function and reducing the risk of hypoglycemia.
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Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Objetivos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Incidência , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de TempoRESUMO
The primary objective of this study is to understand the regulatory role of epigenetics in thyroid-associated ophthalmopathy (TAO) using multi-omics sequencing data. We utilized tRFs sequencing data, DNA methylation sequencing data, and lncRNA/circRNA/mRNA sequencing data, as well as several RNA methylation target prediction websites, to analyze the regulatory effect of DNA methylation, non-coding RNA, and RNA methylation on TAO-associated genes. Through differential expression analysis, we identified 1019 differentially expressed genes, 985 differentially methylated genes, and 2601 non-coding RNA. Functional analysis showed that differentially expressed genes were mostly associated with the PI3K signaling pathway and the IL17 signaling pathway. Genes regulated by DNA epigenetic regulatory networks were mainly related to the Cytokine-cytokine receptor interaction pathway, whereas genes regulated by RNA epigenetic regulatory networks were primarily related to the T cell receptor signaling pathway. Finally, our integrated regulatory network analysis revealed that epigenetics mainly impacts the occurrence of TAO through its effects on key pathways such as cell killing, cytokine production, and immune response. In summary, this study is the first to reveal a new mechanism underlying the development of TAO and provides new directions for future TAO research.
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Metilação de DNA , Epigênese Genética , Redes Reguladoras de Genes , Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/genética , Transdução de Sinais/genética , Inflamação/genética , RNA Longo não Codificante/genética , Perfilação da Expressão Gênica , Regulação da Expressão GênicaRESUMO
INTRODUCTION: China now has the highest number of diabetes in the world. Angiotensin II (Ang II) causes insulin resistance by acting on the insulin signaling pathway of peripheral target tissues. However, its effect on islet ß-cells remains unclear. The possible role of Angiotensin-( 1-7) [Ang-(1-7)] as an antagonist to the effects of Ang II and in treating diabetes needs to be elucidated. OBJECTIVES: To assess the effects of Ang II and Ang-(1-7) on the function and growth of islet ß cell line NIT-1, which is derived from the islets of non-obese diabetic/large T-antigen (NOD/LT) mice with insulinoma. METHODS: NIT-1 cells were treated with Ang II, Ang-(1-7) and their respective receptor antagonists. The impact on cell function and growth was then evaluated. RESULTS: Ang II significantly reduced insulin-stimulated IR-ß-Tyr and Akt-Ser; while Ang-(1-7), saralasin (an Ang II receptor antagonist), and diphenyleneiodonium [DPI, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) antagonist] reversed the inhibiting effect. Conversely, Ang II significantly increased insulin-stimulated intracellular H2O2 and P47 phox, while saralasin and DPI reverted the effect. Furthermore, Ang-(1-7) reduced the elevated concentrations of ROS and MDA while increasing the proliferation rate that was reduced by high glucose, all of which were reversed by A-779, an antagonist of the Mas receptor (MasR). CONCLUSION: Angiotensin II poses a negative regulatory effect on insulin signal transduction, increases oxidative stress, and may inhibit the transcription of insulin genes stimulated by insulin in NIT-1 cells. Meanwhile, angiotensin-(1-7) blocked these effects via MasR. These results corroborate the rising potential of the renin-angiotensin system (RAS) in treating diabetes.
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Angiotensina II , Angiotensina I , Células Secretoras de Insulina , Fragmentos de Peptídeos , Angiotensina II/farmacologia , Angiotensina I/farmacologia , Animais , Fragmentos de Peptídeos/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Insulina/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular , Estresse Oxidativo/efeitos dos fármacos , Secreção de Insulina/efeitos dos fármacosRESUMO
INTRODUCTION: This study aims to analyze risk factors for ocular surface irritation symptoms in patients with non-corneal-damage inactive mild and moderate-to-severe Graves' orbitopathy (GO). METHODS: This retrospective study enrolled 307 patients with non-corneal-damage inactive GO admitted to Sun Yat-sen Memorial Hospital from April 2017 to September 2023. The activity and severity of GO were evaluated using the Clinical Activity Score (CAS) and the European Group on Graves' Orbitopathy (EUGOGO) classification, respectively. Multivariate logistic regression analysis was performed to analyze risk factors for ocular surface irritation symptoms. RESULTS: Among patients with inactive GO, for mild cases, CAS (P < 0.001), upper eyelid lag (P = 0.049), and extraocular muscle involvement (P = 0.019) in the symptomatic group were greater than those in the asymptomatic group, and multivariate logistic regression analysis demonstrated that upper eyelid lag (P = 0.048), CAS 1 (P < 0.001), CAS 2 (P = 0.005), and extraocular muscle involvement (P = 0.029) were risk factors for ocular surface irritation symptoms; for moderate-to-severe cases, CAS (P = 0.004), extraocular muscle involvement (P < 0.001), marginal reflex distance 1 (MRD1) (P = 0.030), and thyroid-stimulating hormone (TSH) (P = 0.034) in the symptomatic group were greater than those in the asymptomatic group, while multivariate logistic regression analysis indicated that extraocular muscle involvement (P = 0.018) and MRD1 (P = 0.012) were risk factors for ocular surface irritation symptoms. CONCLUSION: In non-corneal-damage inactive mild and moderate-to-severe GO, eyelid malposition and periocular muscle inflammation are risk factors for ocular surface irritation symptoms.
Graves' orbitopathy is the most common outward sign of Graves' disease. Patients with inactive Graves' orbitopathy often complain of ocular surface irritation symptoms. This study retrospectively collected clinical data from 307 patients with inactive Graves' orbitopathy and no concurrent corneal damage. The aim was to analyze risk factors for ocular surface irritation symptoms. Upper lid lag, eye movement disorder, and the Clinical Activity Score were found to be risk factors for mild cases. Eye movement disorder and the distance between the upper eyelid margin and corneal reflection point were risk factors for moderate-to-severe cases. To reduce symptoms, it may be helpful to treat inflammation around the eyes and address any eyelid abnormalities.
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BACKGROUND: Sleep plays a critical role in maintaining human health. This study aimed to explore the association between sleep status and thyroid nodules. METHODS: A total of 2414 individuals aged 18 or older with euthyroidism were enrolled in this community-based survey. Sleep status was self-reported. Thyroid ultrasonography was performed to measure nodules. Multiple logistic analyses were applied to adjust for confounding factors. RESULTS: The percentages of thyroid nodules among individuals who slept <5 hours, 5-8 hours, and >8 hours per night were 57.79% (115/199), 44.19% (833/1885) and 42.73% (141/330), respectively (p = 0.001). Individuals who slept <5 hours per night had a significantly higher percentage of thyroid nodules than those who slept 5-8 hours per night (57.79% vs. 44.19%, p = 0.001) or >8 hours per night (57.79% vs. 42.73%, P < 0.001). However, no similar result was shown between individuals who slept >8 hours and 5-8 hours per night (42.73% vs. 44.19%, p = 0.621). Multiple logistic analysis showed that a sleep duration of <5 hours per night was significantly associated with thyroid nodules (odds ratio (OR) 1.643, 95% confidence interval (CI) 1.084-2.490, p = 0.019) when compared to a sleep duration of >8 hours per night. However, a sleep duration of <5 hours per night was not associated with thyroid nodules compared to a sleep duration of 5-8 hours (OR 1.294, 95% CI 0.918-1.824, p = 0.141). Similarly, no significant differences were seen among sleep duration per day, time of falling asleep, habit of daytime napping or thyroid nodules in multiple logistic analyses (all p > 0.05). CONCLUSIONS: Short nighttime sleep duration was associated with thyroid nodules in our community-based population. Screening for thyroid nodules among these individuals is recommended.
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Duração do Sono , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/epidemiologia , Sono , Inquéritos e Questionários , China/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: The RAS system is involved in the regulation of islet function, but its regulation remains unclear. OBJECTIVE: This study investigates the role of an islet-specific miR-375 in the effect of RAS system on islet ß-cells. METHODS: miR-375 mimics and inhibitors were transfected into insulin-secreting MIN6 cells in the presence or absence of RAS component. RESULTS: Compared to control, in Ang II-treated MIN6 cells, miR-375 mimic transfection results in a decrement in cell viability and Akt-Ser levels (0.739±0.05 vs. 0.883±0.06 and 0.40±0.04 vs. 0.79±0.04, respectively), while the opposite occurred in miR-375 inhibitor-transfected cells (1.032±0.11 vs. 0.883±0.06 and 0.98±0.05 vs. 0.79±0.04, respectively, P<0.05). Mechanistically, transfection of miR- 375 mimics into Ang II-treated MIN6 cells significantly reduced the expression of Mapkap1 protein (0.97±0.15 vs. 0.63±0.06, P<0.05); while miR-375 inhibitor-transfected cells elevated Mapkap1 expression level (0.35±0.11 vs. 0.90±0.05, P<0.05), without changes in mRNA expression. Transfection of miR-375 specific inhibitors TSB-Mapkap1 could elevate Mapkap1 (1.62±0.02 vs. 0.68±0.01, P<0.05), while inhibition of Mapkap1 could significantly reduce the level of Akt-Ser473 phosphorylation (0.60±0.14 vs. 1.80±0.27, P<0.05). CONCLUSION: The effects of Ang II on mouse islet ß cells were mediated by miR-375 through miR- 375/Mapkap 1 axis. This targeted regulation may occur by affecting Akt phosphorylation of ß cells. These results may provide new ideas and a scientific basis for further development of miRNA-targeted islet protection measures.
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Células Secretoras de Insulina , Ilhotas Pancreáticas , MicroRNAs , Animais , Camundongos , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , TransfecçãoRESUMO
Purpose: To assess the outcomes of balanced orbital decompression for chorioretinal folds (CRFs) with and without optic disc edema (ODE) in dysthyroid optic neuropathy (DON). Method: A retrospective, interventional study was performed at Sun Yat-sen Memorial Hospital from April 2018 to November 2021. We collected the medical records of 13 patients (24 eyes) with DON and CRFs. Then, we divided them into the ODE group (15 eyes, 62.5%) and the non-ODE group (NODE group, 9 eyes, 37.5%). The valid ophthalmic examination parameters of 8 eyes in each group after balanced orbital decompression were compared at the 6-month follow-up. Results: The mean best corrected visual acuity (BCVA, 0.29 ± 0.27) and visual field-mean deviation (VF-MD, -6.55 ± 3.71 dB) in the ODE group were significantly worse than those in the NODE group (0.06 ± 0.15 and -3.49 ± 1.56 dB; all p < 0.01). Six months after orbital decompression, all parameters were found to have significantly improved in both groups, including BCVA and VF-MD (all p < 0.05). Moreover, the improvement amplitude of BCVA (p = 0.020) in the ODE group was significantly greater than that in the NODE group. There was no difference in BCVA between the ODE group (0.13 ± 0.19) and the NODE group (0.10 ± 0.13). The disc edema of all eyes (8/8 eyes, 100%) in the ODE group was completely mitigated after orbital decompression. The CRF resolution of 2 eyes (2/8 eyes, 25%) in the ODE group and no eyes in the NODE group was mitigated. Conclusions: Balanced orbital decompression can significantly improve visual functions and eliminate optic disc edema in DON patients, whether CRF relieves or not.
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Descompressão , Papiledema , Humanos , Papiledema/etiologia , Papiledema/cirurgia , Estudos RetrospectivosRESUMO
Objective: Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD. Methods: We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß and the development of CKD. Results: With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31). Conclusion: HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.
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A tool was constructed to assess need of an oral glucose tolerance test (OGTT) in patients whose fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are normal. Data was collected from the longitudinal REACTION study conducted from June to November 2011 (14,686 subjects, aged ≥ 40 y). In people without a prior history of diabetes, isolated high 2-hour plasma glucose was defined as 2-hour plasma glucose ≥ 11.1 mmol/L, FPG < 7.0 mmol/L, and HbA1c < 6.5%. A predictive nomogram for high 2-hour plasma glucose was developed via stepwise logistic regression. Discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test; performance was externally validated in Northeast China. Parameters in the model included gender, age, drinking status, marriage status, history of hypertension and hyperlipidemia, waist-to-hip ratio, FPG, and HbA1c. All variables were noninvasive, except FPG and HbA1c. The AUC of the nomogram for isolated high 2-hour plasma glucose was 0.759 (0.727-0.791) in the development dataset. The AUCs of the internal and externally validation datasets were 0.781 (0.712-0.833) and 0.803 (0.778-0.829), respectively. Application of the nomogram during the validation study showed good calibration, and the decision curve analysis indicated that the nomogram was clinically useful. This practical nomogram model may be a reliable screening tool to detect isolated high 2-hour plasma glucose for individualized assessment in patients with normal FPG and HbA1c. It should simplify clinical practice, and help clinicians in decision-making.
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Glicemia , Nomogramas , Jejum , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , HumanosRESUMO
Background: Diabetic kidney disease (DKD) is a kind of common microvascular complication of diabetes. This study aims to explore the possible links between blood sugar level and albuminuria, providing the exact cut point of the "risk threshold" for blood glucose with DKD. Methods: The relationship between blood glucose and albuminuria was modeled using linear and logistic regression in the REACTION study cohorts (N= 8932). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. Two-slope linear regression was used to simulate associations between blood glucose and ACR. Results: We found that the increase in ACR was accompanied by increased HbA1c, with a turning point at 5.5%. The positive correlation remained highly significant (P<0.001) when adjusted for age, sex, marital status, education, smoking status, drinking status, BMI, waistline, SBP and DBP. In subgroup analyses including gender, obesity, hypertension, and smoking habits, the relationship was significant and stable. Conclusions: We determined a risk threshold for HbA1c associated with albuminuria in a Chinese population over the age of 40. HbA1c ≥ 5.5% was positively and independently associated with ACR. These results suggest the necessity of early blood glucose control and renal function screening for DKD in at-risk populations.
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Albuminúria/epidemiologia , Biomarcadores/sangue , Glicemia/análise , Creatinina/sangue , Diabetes Mellitus/fisiopatologia , Nefropatias Diabéticas/etiologia , Hemoglobinas Glicadas/análise , Albuminúria/patologia , China/epidemiologia , Estudos Transversais , Nefropatias Diabéticas/patologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: Adiponectin is an adipocyte-derived hormone with an important role in glucose metabolism. The present study explored the effect of adiponectin in diverse population groups on pre-diabetes and newly diagnosed diabetes. METHODS: A total of 3300 individuals were enrolled and their data were collected in the analyses dataset from December 2018 to October 2019. Cluster analysis was conducted based on age, BMI, waistline, body fat, systolic blood pressure, triglycerides, and glycosylated hemoglobin 1c. Cluster analysis divided the participants into four groups: a young-healthy group, an elderly-hypertension group, a high glucose-lipid group, and an obese group. Odds ratio (OR) and 95% CIs were calculated using multivariate logistic regression analysis. RESULTS: Compared with the first quartile of adiponectin, the risk of pre-diabetes of fourth quartile was decreased 61% (aOR = 0.39, 95% CI (0.20-0.73)) in the young-healthy group; and the risk of diabetes of fourth quartile was decreased 85% (aOR = 0.15, 95% CI (0.02-0.67)) in the obese group. There were no significant correlations between the adiponectin level and diabetes/pre-diabetes in the other two groups. Additionally, receiver operating characteristic curve analysis indicated that adiponectin could significantly improve the diagnosis based on models in the young-healthy group (from 0.640 to 0.675) and the obese group (from 0.714 to 0.761). CONCLUSIONS: Increased adiponectin levels were associated with decreased risk of pre-diabetes in the young-healthy population, and with a decreased the risk of diabetes in the obese population. An increased adiponectin level is an independent protective factor for pre-diabetes and diabetes in a specific population in south China.
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OBJECTIVES: A variety of factors differed between rural and urban areas may further influence iodine status and thyroid structure. Hence, this study compared iodine nutrition, the prevalence of thyroid goiter, and nodules between rural and urban residents in Guangzhou, a southern coastal city of China. METHODS: A total of 1211 rural residents and 1305 urban residents were enrolled in this cross-sectional study. A questionnaire regarding personal characteristics was administered. Urinary iodine concentration (UIC) was examined. Ultrasonography of the thyroid was performed to evaluate thyroid goiter and nodules. Multiple logistic analysis was used to identify the potential associated factors. RESULTS: The median UIC was significantly lower in rural residents than in urban residents (120.80 µg/L vs 136.00 µg/L, P < 0.001). Although the coverage rate of iodized salt was much higher in rural residents than in urban residents (99.59% vs 97.29%, P < 0.001), the percentages of seafood intake (8.60% vs 29.29%, P < 0.001), iodine-containing drug consumption (0.33% vs 1.24%, P = 0.011), and iodine contrast medium injection (0.58% vs 1.87%, P = 0.004) were lower in rural residents than in urban residents. Both the prevalence of thyroid goiters and nodules was significantly higher in rural residents than in urban residents (goiter: 8.06% vs 1.20%, P < 0.001; nodules: 61.89% vs 55.04%, P = 0.023). Living in rural areas was associated with thyroid goiter (OR 5.114, 95% CI 2.893-9.040, P < 0.001). CONCLUSIONS: There were differences in iodine nutrition and the prevalence of thyroid goiter and nodules in rural and urban residents in Guangzhou. Differentiated and specialized monitoring is recommended in our area.
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BACKGROUND: To investigate the clinical characteristics of Graves' orbitopathy (GO) with elevated intraocular pressure (IOP) using the European Group of Graves' Orbitopathy (EUGOGO) system. METHODS: In this retrospective study, the clinical data of GO patients with elevated IOP (≥21 mmHg) were collected in Sun Yat-sen Memorial Hospital from January 2010 to June 2016. The demographic characteristics, clinical history of thyroid disease and GO, and ocular examination data were evaluated, and the activity and severity of GO were classified. RESULTS: Data were collected from 58 eyes of 39 patients. The durations of thyroid disease and GO were 15.9 ± 18.9 months and 7.5 ± 6.2 months, respectively. The average IOP was 24.8 ± 5.3 mmHg (range: 21-55 mmHg). No significant difference in IOP was observed between active and inactive eyes. Eight eyes (13.8%), 29 eyes (50.0%), and 21 eyes (36.2%) were graded as mild, moderate-severe, and sight-threatening disease, respectively, according to the EUGOGO classification. The IOP was not significantly different among the three EUGOGO grades. No glaucomatous optic nerve damage or visual field defects were found. CONCLUSION: Increased IOP was evident for every grade of GO severity and activity of the EUGOGO system. IOP, glaucomatous optic nerve damage, and visual fields must be evaluated regularly during follow-up evaluations, regardless of the degree of activity and severity of GO.