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Background: Research has shown that gonadal hormones are involved in metabolic pathways relevant to metabolic syndrome (MetS). Nevertheless, no longitudinal study has been conducted on the association between SHBG and MetS in Chinese. The objective of our study was to determine whether there is any association between middle-aged and elderly males in China. Methods: A total of 531 eligible male subjects, aged above 40 years or older, without MetS at baseline, were recruited. Sex hormone binding globulin (SHBG), total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. A harmonized definition and recommended thresholds for the Chinese population were used to determine metabolic syndrome. Results: During 3.2 years of follow-up, 20.7% of subjects had developed MetS. Compared with the non-MetS group, subjects in the new-onset MetS group had significantly lower SHBG (43.5 nmol/L [28.8, 74.9] vs 53.7nmol/L [33.8, 115.0], P=0.0018), TT (18.1nmol/L [13.6-21.7] vs 19.5nmol/L[15.0-23.6], P=0.0204), and LH (5.13mIU/L [3.63-7.29] vs 5.87mIU/L [4.05-8.36]) at baseline. The incidence of MetS was decreased according to elevated SHBG quartiles (Q1:26.9%, Q2:22.7%, Q3:21.1%, Q4:12.1%, P for trend =0.0035), TT (Q1: 25.2%, Q2:23.7%, Q3: 17.3%, Q4: 16.7%, P for trend=0.0425), and LH (Q1:25.0%, Q2:21.8%, Q3: 21.8%, Q4: 14.3%, P for trend=0.0411). Compared with those in quartile 4, the OR[CI] of incident MetS for participants in Quartile 1 was 2.33[1.13-4.79] after multiple adjustments. But associations between incident MetS and different quartiles of LH, TT, and FSH were not observed after multiple adjustments. In the subgroup analyses, the significant association between SHBG level and Mets was detected in subjects over 60 years or older, with normal BMI, without insulin resistance, and with eGFR ≥90 mL/min per 1.73m2. Conclusion: Compared with TT, LH, and FSH, a lower level of SHBG is significantly related to the incidence of MetS among middle-aged and elderly males in China.
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Hormona Luteinizante , Síndrome Metabólico , Globulina de Unión a Hormona Sexual , Humanos , Masculino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/sangre , Persona de Mediana Edad , China/epidemiología , Estudios Prospectivos , Anciano , Globulina de Unión a Hormona Sexual/metabolismo , Globulina de Unión a Hormona Sexual/análisis , Hormona Luteinizante/sangre , Testosterona/sangre , Hormona Folículo Estimulante/sangre , Hormonas Gonadales/sangre , Adulto , Estudios de Seguimiento , Estudios Longitudinales , Estudios de CohortesRESUMEN
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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Obesidad , Sobrepeso , Humanos , Persona de Mediana Edad , Masculino , Adulto , Femenino , Método Doble Ciego , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Anciano , Adulto Joven , Adolescente , China , Placebos/administración & dosificación , Inyecciones Subcutáneas , Péptido 1 Similar al GlucagónRESUMEN
AIM: Late-onset hypogonadism in men is related to the development of diabetes. The association of gonadal hormones, sex hormone binding globulin with diabetes has been studied in various studies. However, there is no cohort study on the relationship between gonadal hormone, sex hormone binding globulin and diabetes in Chinese. We aimed to provide an insight into the possible association in middle-aged and elderly Chinese males. METHODS: We included a population sample of 673 subjects aged 40 years or older. Total testosterone (TT), sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) were detected. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to estimate insulin sensitivity. Diabetes was diagnosed according to the 2010 American Diabetes Association criteria. RESULTS: With an average follow-up time of 3.2 ± 0.5 years, 9.8% of participants had developed diabetes. The prevalence of diabetes was decreased according to increasing SHBG quartiles (Q1:13.1%, Q2: 12.0%, Q3: 11.2%, Q4: 3.0%, P for trend < .0001) and TT (Q1:16.0%, Q2: 7.9%, Q3: 9.0%, Q4: 6.4%, P for trend < .0001). The ORs of diabetes for increasing SHBG quartiles were 4.52 (95% CI 1.40-14.57), 4.32 (95% CI 1.33-14.06), 3.89 (95% CI 1.21-12.50) and 1.00 (reference) respectively. But the odds of prevalent diabetes were not increased in different quartiles of TT, FSH and LH. In subgroup analyses, the relationship between SHBG and risk of incident diabetes was significantly increased in the population aged over 60, without insulin resistance and with eGFR < 90 mL/min per 1.73 m2 . CONCLUSIONS: Compared with gonadal hormones, a lower level of SHBG is independently associated with the risk of diabetes in middle-aged and elderly Chinese males.
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Diabetes Mellitus , Globulina de Unión a Hormona Sexual , Adulto , Anciano , China/epidemiología , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , TestosteronaRESUMEN
AIM: Male obesity-associated secondary hypogonadism (MOSH) is becoming a public health issue. We aimed to know MOSH among young and middle-aged men in our hospital, to analyse their sex hormones and other index, and to determine leptin as a risk factor for MOSH. METHODS: In total, 258 men (ages ranging from 20 to 60, mean 38 ± 15) were enrolled in this study, and 242 of these men had their complete data, body mass index (BMI), waist circumference and sex hormones retrospectively investigated. The leptin and lipid levels were also evaluated, and comparisons were made between young (20-39 years old) and middle-aged (40-60 years old) men. RESULTS: Among all the participants, 7 were thin, with a BMI < 18.5 kg/m2 , 95 had a normal BMI (18.5 ≤ BMI < 23.9 kg/m2 ), 87 (35.9%) were overweight (24 ≤ BMI ≤ 27.9 kg/m2 ) and 53 (21.9%) were obese (BMI ≥ 28 kg/m2 ), 173 (71.5%) had a waist sized ≥ 85 cm. Among the 242 men, 104 (43%) had hypogonadism (TT ≤ 331.412 ng/dL). Compared with the men of normal weight, the level of testosterone of the obese men decreased (P = .006), while the level of serum lipids (including total cholesterol, TG and low-density lipoprotein cholesterol, P < .05) was elevated, higher UA, FSH and leptin were also present in the obese men. There were 83 (34.2%) men with MOSH. Compared with middle-aged men with MOSH, the FSH in young men was significantly reduced (P < .05); no significant increase in estradiol was observed in the MOSH group. The leptin levels in the MOSH group were significantly higher than those in the hypogonadism only group (P < .001). CONCLUSION: Obesity increases the prevalence of hypogonadism. The decrease in testosterone levels in young men maybe due to inhibition of the hypothalamic pituitary gonadal axis. Leptin is an independent risk factor for MOSH.
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Índice de Masa Corporal , Hipogonadismo/metabolismo , Obesidad/metabolismo , Adulto , Anciano , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Estudios Retrospectivos , Testosterona/sangre , Circunferencia de la Cintura , Adulto JovenRESUMEN
OBJECTIVES: Hypogonadism in men is related to the deterioration of general health. However, the association between lipid overaccumulation and ageing-related hypogonadism remains an undetermined concept. We aimed to provide an insight into the possible links between the lipid accumulation product (LAP) and late-onset hypogonadism (LOH). SETTING: Sun Yat-sen Memorial Hospital of Sun Yat-sen University. PARTICIPANTS: We included a population sample of 997 subjects aged 40 years or older. PRIMARY AND SECONDARY OUTCOME MEASURES: The LAP was calculated by gender-specific equations using waist circumference (WC) and triglyceride (TG). LOH was defined by the presence of androgen deficiency symptoms and low serum total testosterone levels. RESULTS: The prevalence of LOH was 9.4% in this population and gradually increased according to increasing LAP quartiles. Compared with subjects without LOH, ageing men with LOH had higher body mass index, WC, systolic blood pressure, percentage of subjects currently smoking, TG and follicle stimulating hormone and lower low-density lipoprotein cholesterol and sex hormone binding globulin. In multivariate logistic regression analysis, the adjusted ORs of LOH for increasing LAP quartiles 1-4 were 1.00 (reference), 1.10 (95% CI 0.45-2.69), 2.15 (95% CI 0.93-4.94) and 3.83 (95% CI 1.73-8.45), respectively. CONCLUSION: Body lipid accumulation evaluated by the LAP is independently associated with the prevalence of LOH in middle-aged and elderly Chinese men.
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Hipogonadismo , Producto de la Acumulación de Lípidos , Anciano , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Humanos , Hipogonadismo/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Testosterona/sangre , Circunferencia de la CinturaRESUMEN
A 71-year-old woman had presented to our clinic with the history of trigeminal neuralgia involving the second and third divisions on the right side. The magnetic resonance tomography angiography examination before operation revealed that the root of the right trigeminal nerve was compressed by the superior cerebellar artery (SCA) artery. During the operation, a fusiform aneurysm was visualized at the distal portion of the SCA. The symptoms of pain disappeared after the surgery of microvascular decompression and the wrapping of the SCA aneurysm. Trigeminal neuralgia coexisting with the aneurysm of the ipsilateral SCA is extremely rare, and it has not been reported before.
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Arterias Cerebrales/cirugía , Aneurisma Intracraneal/cirugía , Cirugía para Descompresión Microvascular/métodos , Nervio Trigémino/cirugía , Neuralgia del Trigémino/cirugía , Anciano , Arteria Basilar/cirugía , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/diagnóstico , Angiografía por Resonancia Magnética , Tomografía Computarizada por Rayos X , Neuralgia del Trigémino/complicaciones , Neuralgia del Trigémino/diagnósticoRESUMEN
To investigate dynamic changes in plantar pressure in Chinese diabetes mellitus patients and to provide a basis for further preventing diabetic foot. This is a cross-sectional investigation including 649 Chinese diabetes mellitus patients (diabetes group) and 808 "normal" Chinese persons (nondiabetes group) with normal blood glucose levels. All the subjects provided a complete medical history and underwent a physical examination and a 75-g oral glucose tolerance test. All subjects walked barefoot with their usual gait, and their dynamic plantar forces were measured using the one-step method with a plantar pressure measurement instrument; 5 measurements were performed for each foot. No significant differences were found in age, height, body weight, or body mass index between the two groups. The fasting blood glucose levels, plantar contact time, maximum force, pressure-time integrals and force-time integrals in the diabetes group were significantly higher than those in the nondiabetes group (p < 0.05). However, the maximum pressure was significantly higher in the nondiabetes group than in the diabetes group (p < 0.05). No difference was found in the contact areas between the two groups (p > 0.05). The maximum plantar force distributions were essentially the same, with the highest force found for the medial heel, followed by the medial forefoot and the first toe. The peak plantar pressure was located at the medial forefoot for the nondiabetes group and at the hallucis for the diabetes group. In the diabetes group, the momentum in each plantar region was higher than that in the nondiabetes group; this difference was especially apparent in the heel, the lateral forefoot and the hallucis. The dynamic plantar pressures in diabetic patients differ from those in nondiabetic people with increased maximum force and pressure, a different distribution pattern and significantly increased momentum, which may lead to the formation of foot ulcers.
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Pueblo Asiatico , Pie Diabético/prevención & control , Antepié Humano/irrigación sanguínea , Cicatrización de Heridas , China/epidemiología , Estudios Transversales , Pie Diabético/epidemiología , Pie Diabético/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Presión , Caminata , Soporte de PesoRESUMEN
Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.
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Modelos Animales de Enfermedad , Genes erbB-1 , Glioblastoma/genética , Glioblastoma/patología , Ratones Transgénicos , Animales , Línea Celular Tumoral , Femenino , Expresión Génica , Glioblastoma/irrigación sanguínea , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Ratones , Ratones Desnudos , Invasividad Neoplásica , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
OBJECTIVE: To investigate the relationship of erectile dysfunction (ED) with blood vessel-, nerve- and androgen-related factors in young and middle-aged men with type 2 diabetes mellitus (T2DM) in order to provide some clinical evidence for early prevention and treatment of ED. METHODS: We divided 53 male T2DM patients under 50 years into an ED group (IIEF-5 score < or = 21, n = 28) and a non-ED (NED) group (IIEF-5 score > or = 22, n = 25). We detected the levels of blood lipid, glucose, total testosterone (TT), sex hormone-binding globulin (SHBG), sulfate dehydroepiandrosterone (DHEA-S), calculated free testosterone (cFT), and examined the complications of macroangiopathy (MA), diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and compared the above indicators between the two groups. RESULTS: There were no significant differences between the two groups in age, diabetes duration, body mass index, blood pressure, and blood lipid and glucose levels (P > 0.05). The incidence rate of DR was significantly higher in the ED than in the NED group (39.3% vs 4.0%, P < 0.05), but no statistically significant differences were found in the levels of TT, cFT, SHBG and DHEA-S and the incidence rates of MA and DPN between the two groups (P > 0.05). CONCLUSION: The incidence of ED is closely related to DR in young and middle-aged men with T2DM. Therefore particular attention should be paid to the erectile function of T2DM patients with DR as early as possible.
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Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/complicaciones , Disfunción Eréctil/etiología , Adulto , Neuropatías Diabéticas/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Lipoapoptosis of pancreatic beta cells caused by elevated circulating free fatty acids (FFAs) has now been recognized to be a pivotal factor contributing to beta cellular dysfunction and beta-mass lose in type 2 diabetes. Although recent studies suggested an important role for the ceramide pathway in the late destructive phase of lipid overload in the pancreatic beta cells, the overall underlying mechanisms leading to lipoapoptosis, however, remained poorly understood. mir-375 was recently characterized to be a pancreatic islet-specific miRNA implicated in the regulation of insulin secretion and beta-mass turnover. In the present study we further examined its effect on palmitate-induced lipoapoptosis in NIT-1 cells, a NOD-derived beta-cell line. It was found that NIT-1 cells with ectopic mir-375 expression were much more susceptible to palmitate-induced lipoapoptosis. In contrast, knockdown of endogenous pri-mir-375 expression by a modified antisense oligo, 2'-O-me-375, almost completely protected NIT-1 cells from palmitate-induced lipoapoptosis. We further demonstrated that mir-375 could target V1 mRNA and repress its translation. Consistent with this assumption, NIT-1 cells transfected with 2'-O-me-375 showed significant higher levels of V1 protein after palmitate induction. Together, our data suggest that mir-375 could be a potential therapeutic target for prevention and intervention of beta-cell dysfunction and beta-mass lose in type 2 diabetes.
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Apoptosis/fisiología , Diabetes Mellitus Tipo 1/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , MicroARNs/metabolismo , Palmitatos/efectos adversos , Animales , Línea Celular , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Células Secretoras de Insulina/patología , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Ratones Endogámicos NOD , MicroARNs/genética , Oligonucleótidos Antisentido/farmacologíaRESUMEN
OBJECTIVE: To investigate the difference and distribution of plantar pressure in normal Chinese population and diabetic patients and their influencing factors. METHODS: 1035 diabetic patients and 1022 normal subjects were evaluated by the "first step approach". Each trial included five acceptable separate barefoot walks across the EMED-AT system for each foot. The whole foot was divided into ten "masks", including the heel, midfoot, the first, second, third, fourth, fifth metatarsals, hallux, second toe and the third-to-fifth toes. The mean of maximum peak pressure (MPP) of each mask as calculated. RESULTS: The MPP were 410 +/- 122 and 427 +/- 128 kPa in left and right foot of diabetics while 415 +/- 113 and 428 +/- 116 kPa in left and right foot of normal subjects with P > 0.05. The top three places with the hight MPP value in the in diabetics and normal subjects were hallux > the second metatarsal > the third metatarsals in both left and right foot. The disease course, sex, age, BMI, WHR and history of foot ulcer had few influence on the plantar pressure in diabetics. The MPP in the diabetics with peripheral neuropathy (DPN) was higher than that of normal subjects, with no significant difference compared to that of non-DPN diabetics. CONCLUSION: The plantar pressure in the diabetics is almost the same as that of the normal subjects, but with different distribution is different. Complication with DPN may lead to the increase of plantar pressure in the diabetic. But factors such as disease course, sex, age, BMI and WHR have few influence on MPP.