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1.
Metabolism ; 124: 154874, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517014

RESUMO

AIMS/HYPOTHESIS: We aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total 'ABCs' metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study. METHODS: We conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. 'ABCs' metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR. RESULTS: The multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05-1.27) for CVD events and 1.33 (95% CI, 1.20-1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21-2.18)] and CKD [1.63 (1.17-2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications. CONCLUSIONS: NAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.

2.
J Diabetes ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427386

RESUMO

BACKGROUND: Gestational hyperglycemia increases the risk of diabetes in later life. However, the risk of future cardiovascular diseases (CVD) related to gestational hyperglycemia remains inconclusive. The purpose of this study was to investigate the impact of gestational hyperglycemia on the subsequent risk of CVD and its modifying factors among elderly Chinese women. METHODS: We conducted a case-control study of elderly women from the baseline survey of Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Women with gestational hyperglycemia (n = 82), and controls matched by age and study site (n = 410) were included. Information on CVD, including reported coronary heart disease, stroke, or myocardial infarction, was collected through an interviewer-assisted questionnaire. RESULTS: Women with gestational hyperglycemia were more likely to develop diabetes (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.18) and CVD (OR, 1.98; 95% CI, 1.05-3.74). Even without progressing to type 2 diabetes, gestational hyperglycemia was associated with an increased risk of CVD (OR, 2.88; 95% CI, 1.18-7.00). However, subgroup analysis indicated that compared with those without gestational hyperglycemia or hypertension, women with both gestational hyperglycemia and hypertension had higher risk of CVD (OR, 3.98; 95% CI, 1.65-9.58), whereas the risk estimate did not significantly change in women with gestational hyperglycemia alone (OR, 2.15; 95% CI, 0.71-6.57). Stratified analysis indicated that among those with overweight/obesity, inactive physical activity, or unhealthy dietary habits, gestational hyperglycemia increased the risk of CVD. CONCLUSIONS: In elderly Chinese women, gestational hyperglycemia was associated with an increased risk of CVD in later life. This association was independent of the progression to diabetes and might be modified by lifestyle factors and hypertension.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34427675

RESUMO

OBJECTIVES: To investigate the associations between individual and combined cardiometabolic morbidities and incident cardiovascular events in Chinese adults. DESIGN: A prospective, nationwide, and population-based cohort study. PARTICIPANTS: 133572 participants aged ≥ 40 years were included in the study. MAIN OUTCOME MEASURES: Cardiovascular disease (CVD) events. RESULTS: Compared with participants without diabetes, hypertension and dyslipidemia, participants with only diabetes (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.32-1.90) or only hypertension (2.04; 1.82-2.28) exhibited significantly higher risk for CVD events, while participants with only dyslipidemia (0.97; 0.84-1.12) exhibited no significantly higher risk for CVD events. When analyzed collectively, participants with diabetes plus hypertension (HR, 2.67; 95%CI, 2.33-3.06), diabetes plus dyslipidemia (1.57; 1.32-1.87), and hypertension plus dyslipidemia (2.12; 1.88-2.39) exhibited significantly higher risk for CVD. Moreover, participants with the combination of diabetes, hypertension and dyslipidemia exhibited the highest risk for CVD events (HR, 3.06; 95%CI, 2.71-3.46). Multivariable-adjusted HRs (95% CIs) for CVD associated with diabetes based on fasting glucose ≥7.0 mmol/L, oral glucose tolerance test-2h glucose ≥11.1 mmol/L, and hemoglobin A1c ≥6.5% were 1.64 (1.51-1.78), 1.57 (1.45-1.69), and 1.54 (1.42-1.66), respectively; associated with hypertension based on systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were 1.89 (1.76-2.03) and 1.74 (1.60-1.88), respectively; associated with dyslipidemia based on total cholesterol ≥6.22 mmol/L, low-density lipoprotein cholesterol ≥4.14 mmol/L, high-density lipoprotein cholesterol <1.04 mmol/L, and triglycerides ≥2.26 mmol/L were 1.18 (1.08-1.30), 1.30 (1.17-1.44), 1.00 (0.92-1.09), and 1.10 (1.01-1.20), respectively. CONCLUSIONS: Diabetes, hypertension and dyslipidemia showed additive associations with the risk of CVD events in middle-aged and elderly Chinese adults.

4.
Medicine (Baltimore) ; 100(27): e26417, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232173

RESUMO

BACKGROUND: Currently, there are a number of sodium glucose co-transport-2 (SGLT2) inhibitors that are under development or in clinical trials. Prior meta-analyses had established the safety and efficacy of SGLT2 inhibitors in type 1 diabetes mellitus (T1DM), but with low level of evidences and inconsistent conclusions. However, recently many new randomized clinical trials (RCTs) have been published, we hence try to design a study protocol to assess the effect of SGLT2 inhibitors on cardiovascular events via a comprehensive meta-analysis of data from much more RCTs, including sensitivity and subgroup analyses. METHODS: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to conduct this meta-analysis. Two investigators will perform a systematic search of scientific literature in the databases (from conception through June 12, 2021), including PubMed, Embase, and Cochrane Central Register of Controlled Trials. This meta-analysis will be conducted using RevMan statistical software. The risk of bias for each included study will be assessed using the Cochrane Risk of Bias Assessment Tool. RESULTS: Our protocol is conceived to test the hypothesis that SGLT2 inhibitors could lead to better outcomes in patients presenting with T1DM. REGISTRATION NUMBER: 10.17605/OSF.IO/ZD8WX.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Controle Glicêmico , Humanos
5.
J Diabetes ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259386

RESUMO

BACKGROUND: Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. METHODS: We used data from a nationwide multicenter study with 207 961 participants in mainland China. Age, sex, and study site were matched for 31 366 screen-detected type 2 diabetes cases and 31 366 normal controls. Age, sex, study site, and diabetes duration were matched for 7490 self-reported type 2 diabetes cases and 7490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. RESULTS: Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50 to 59, 60 to 69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. CONCLUSIONS: A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.

6.
Diabetes Obes Metab ; 23(11): 2551-2560, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34322974

RESUMO

AIMS: The aims of this study were to evaluate the associations of metabolic abnormalities with incident diabetic kidney disease (DKD) and to explore whether dyslipidaemia, particularly high fasting triglyceride (TG), was associated with the development of DKD. METHODS: In total, 11 142 patients with new-onset type 2 diabetes with baseline estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2 were followed up during 2011-2016. Incident DKD was defined as eGFR <60 mL/min/1.73 m2 at follow-up. Multiple logistic regression analysis was conducted to explore the relationship of metabolic abnormalities at baseline and at follow-up with risks of DKD. High TG was defined by TG ≥1.70 mmol/L. Low high-density lipoprotein cholesterol (HDL-c) was defined by HDL-c <1.0 mmol/L for men or <1.3 mmol/L for women. RESULTS: Participants who developed DKD had higher levels of waist circumference and systolic blood pressure, and lower levels of HDL-c at both baseline and follow-up visits. The DKD group also had higher levels of post-load plasma glucose and TG at follow-up. Multivariate logistic regression analysis revealed that both high TG at baseline [odds ratio (OR) = 1.37, p = .012) and high TG at follow-up (OR = 1.71, p < .001) were significantly associated with increased risks of DKD. Patients with high TG levels at both baseline and follow-up had higher risk of DKD compared with constantly normal TG (OR = 1.65, p < .001) after adjustment for covariates. CONCLUSIONS: In a large population of patients with new-onset type 2 diabetes, a high TG level was an independent risk factor for the development of DKD. Tight TG control might delay the occurrence of DKD.

7.
Front Endocrinol (Lausanne) ; 12: 622674, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935965

RESUMO

Background: Osteogenesis imperfecta (OI) type V is a rare form of OI which is often characterized by hyperplastic callus. Misdiagnosis is a possibility due to its rarity and because patients involved are mostly in adolescence, a predisposing age for osteosarcoma. Here, we report this case and aim to improve understanding of patients with OI type V and avoid misdiagnosis. Case Presentation: A male, 14-year-old patient was admitted to Jiangxi Provincial People's Hospital affiliated to Nanchang University in August 2020 due to repeated fractures for more than 11 years and swelling in his right leg for more than 4 years. The patient was diagnosed with OI in 2014 due to repeated fracture and was treated with bisphosphonates. The swelling was accompanied by huge callus formation. Prior to admission to our hospital in 2016 osteosarcoma was suspected by imaging and pathology, and amputation was recommended. OI-V was confirmed after more than four years of follow-up and genetic diagnosis, and the affected limb was preserved. Conclusion: The history of OI and lack of rapid progression suggested OI-V with a hyperplastic callus. Combined with genetic testing, the diagnosis was OI-V. Although the patient was at a predisposing age for osteosarcoma, diagnosis and treatment should be based on the medical history of the patient, imaging,and genetic testing, and sometimes even time-consuming retrospective observation.

8.
Int J Cardiol ; 332: 209-215, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33667580

RESUMO

BACKGROUND: Excessive adiposity in adulthood is positively associated with the risk of cardiovascular disease (CVD). However, it is less studied how the risk is separately explained by early adulthood weight and later weight change, especially in Asian ancestries. METHODS: This study included 121160 participants in a large population-based cohort in China. Body weight at 20 and 40 years of age wase self-reported. Information on CVD history was obtained through standard questionnaires. RESULTS: The odds ratios (ORs) were 1.20 (95% CI, 1.10-1.31) for coronary heart disease (CHD), 1.74 (95% CI, 1.36-2.22) for myocardial infarction (MI), 1.14 (95% CI, 0.99-1.32) for stroke and 1.21 (95% CI, 1.12-1.31) for total CVD among individuals with early overweight, and became more prominent for early obesity. Meanwhile, A moderate weight gain of 2.5 kg between early adulthood and midlife significantly increased the risk of CHD (OR: 1.18, 95% CI: 1.05-1.32), stroke (OR: 1.19, 95% CI: 1.03-1.38) and total CVD (OR: 1.15, 95% CI: 1.04-1.27), and the risk escalated with higher amounts of weight gain. Conversely, a weight loss of 2.5 kg conferred lower risk of CVD compared with a stable weight. In further cross-analysis, participants with early adulthood overweight or obesity and significant weight gain afterwards exhibited the greatest risk of CVD. CONCLUSIONS: High early adulthood BMI and subsequent weight gain had both independent and combined effect on the risk of CVD after midlife. Therefore, weight management should start before early adulthood, and emphasized throughout adulthood for CVD prevention.


Assuntos
Doenças Cardiovasculares , Adulto , Índice de Massa Corporal , Peso Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Humanos , Fatores de Risco
9.
J Diabetes ; 13(11): 857-867, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33710784

RESUMO

BACKGROUND: Parity, pregnancy loss, and breastfeeding duration were found to be associated with diabetes. However, the results are inconsistent. Also, no epidemiological studies have examined the association of these reproductive factors with diabetes in the same large population. We aim to investigate the associations between parity, pregnancy loss, breastfeeding duration, and the risk of maternal diabetes in middle-aged and elderly Chinese females. METHODS: We included 131 174 females aged ≥40 years from the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study). Multivariable linear regression and logistic regression were used to assess the association between parity, pregnancy loss, and breastfeeding duration and type 2 diabetes. RESULTS: The number of parities and breastfeeding duration were positively related to fasting plasma glucose, 2-hour postload glucose, glycosylated hemoglobin, and homeostatic model assessment of insulin resistance. Compared with those with one birth, nulliparous women or women with 2 or ≥3 births had a significantly increased risk of diabetes. The odds ratios (OR) and 95% confidence intervals (CI) were 1.27 (1.10-1.48), 1.17 (1.12-1.22), and 1.28 (1.21-1.35), respectively. Compared with women without pregnancy loss, those who underwent 2 (OR 1.09; 95% CI, 1.04-1.14) or ≥3 pregnancy losses (OR 1.11; 95% CI, 1.04-1.18) had an increased risk of diabetes. Moreover, women with a breastfeeding duration ≥0 to 6 months (OR 0.82; 95% CI, 0.75-0.90) and ≥6 to 12 months (OR 0.94; 95% CI, 0.89-0.99) had a significantly lower risk of diabetes. CONCLUSIONS: Nulliparous women or women with multiparity or more than one pregnancy loss have an increased risk of diabetes in later life, while women who breastfeed more than 0 to 12 months have a lower risk of diabetes.

10.
J Am Soc Nephrol ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33788701

RESUMO

BACKGROUND: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline used eGFR and urinary albumin-creatinine ratio (ACR) to categorize risks for CKD prognosis. The utility of KDIGO's stratification of major CVD risks and predictive ability beyond traditional CVD risk prediction scores are unknown. METHODS: To evaluate CVD risks on the basis of ACR and eGFR (individually, together, and in combination using the KDIGO risk categories) and with the atherosclerotic cardiovascular disease (ASCVD) score, we studied 115,366 participants in the China Cardiometabolic Disease and Cancer Cohort study. Participants (aged ≥40 years and without a history of cardiovascular disease) were examined prospectively for major CVD events, including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. RESULTS: During 415,111 person-years of follow-up, 2866 major CVD events occurred. Incidence rates and multivariable-adjusted hazard ratios of CVD events increased significantly across the KDIGO risk categories in ASCVD risk strata (all P values for log-rank test and most P values for trend in Cox regression analysis <0.01). Increases in c statistic for CVD risk prediction were 0.01 (0.01 to 0.02) in the overall study population and 0.03 (0.01 to 0.04) in participants with diabetes, after adding eGFR and log(ACR) to a model including the ASCVD risk score. In addition, adding eGFR and log(ACR) to a model with the ASCVD score resulted in significantly improved reclassification of CVD risks (net reclassification improvements, 4.78%; 95% confidence interval, 3.03% to 6.41%). CONCLUSIONS: Urinary ACR and eGFR (individually, together, and in combination using KDIGO risk categories) may be important nontraditional risk factors in stratifying and predicting major CVD events in the Chinese population.

11.
BMC Ophthalmol ; 21(1): 122, 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676434

RESUMO

BACKGROUND: Phthirus pubis is an obligate parasite of human beings. Demodex spp. is a much more common parasite of human beings. However, P. pubis infestation accompanied by Demodex mite infestation in eye has not been reported. CASE PRESENTATION: We report the first case of Phthirus pubis and Demodex co-infestation on a 48-years-old woman. She presented to the hospital with itching and burning at her right eye for 2 weeks. Slit lamp examination revealed multiple nits and adults of P. pubis anchored to both upper and lower eyelashes. Eyelashes were trimmed, moxifloxacin eye ointment and fluorometholone eye drops were initiated daily. However, itching didn't improve after 2 weeks of treatment. Light microscopy examination of eyelashes revealed infestation with Demodex. The patient was treated with lid scrubs with 25% tea tree oil daily for 4 weeks and was completely cured. CONCLUSION: Our report shows the importance of an early and comprehensive diagnosis, because both phthiriasis palpebrarum and demodicosis can be confused with blepharitis.


Assuntos
Blefarite , Pestanas , Infestações por Piolhos , Phthirus , Adulto , Animais , Blefarite/diagnóstico , Blefarite/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Pomadas
12.
Biochem Biophys Res Commun ; 544: 8-14, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33516884

RESUMO

Exendin-4 has been found to have hypoglycemic effect and prevent bone loss in diabetic patients, but its mechanism of preventing bone loss is still unclear. In this study, high-fat diet combined with streptozotocin was used to establish type 2 diabetes mellitus (T2DM) mice, and bone marrow mesenchyme stem cells (BMSCs) were isolated for osteogenic induction in vitro. Alizarin red staining and ALP activity detection were used to observe the effect of exendin-4 on osteogenic differentiation of BMSCs. Western blot was used to detect the proteins expression in BMSCs. In vivo, the effects of exendin-4 treatment on body weight, blood glucose, bone density and bone quality of T2DM mice were observed by treatment with exendin-4. The results showed that exendin-4 promoted osteogenic differentiation of T2DM derived BMSCs, down-regulated histone deacetylase 1 (HDAC1) and p-ß-Catenin proteins expression, and up-regulated Wnt3, ß-Catenin and runt-related transcription factor 2 (Runx 2) proteins expression. In vivo, exendin-4 effectively suppressed the blood glucose and increased body weight of T2DM mice, and significantly improved bone density and bone quality of the right tibia. Interestingly, by over-expression of HDAC1 in BMSCs, the effect of exendin-4 on promoting osteogenic differentiation of BMSCs was attenuated, and the regulation of Wnt3a, ß-Catenin, p-ß-Catenin or Runx2 proteins were reversed. By injecting adenovirus containing HDAC1 into the right tibia of mice, the effect of exendin-4 on bone density and bone quality of T2DM mice was significantly attenuated. All above results suggest that the HDAC1-Wnt/ß-Catenin signal axis is involved in the anti-diabetic bone loss effect of exendin-4, and HDAC1 may be the target of exendin-4.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Exenatida/farmacologia , Histona Desacetilase 1/metabolismo , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Hipoglicemiantes/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos ICR
13.
Mediators Inflamm ; 2021: 6679095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33510582

RESUMO

This study is aimed at establishing the prevalence of osteoporosis and osteopenia in kidney transplant recipients (KTRs) and determining the risk factors for bone mass loss. We invited KTRs who were under regular follow-up at Jiangxi Provincial People's Hospital Affiliated with Nanchang University to attend an assessment of osteoporotic risk assessed by questionnaire, biochemical profile, and dual-energy X-ray absorptiometry (DXA) scanning of the lumbar spine, total hip, and femoral neck. Binary logistic regression models were used to investigate the relationship between the different variables and bone mass density (BMD). A total of 216 patients satisfied the inclusion criteria. The group consisted of 156 men (72.22%) and 60 women (27.78%), and the mean age was 41.50 ± 9.98 years. There were 81 patients with normal bone mass (37.50%) and 135 patients with bone mass loss (62.50%). Logistic regression analysis showed that a higher phosphorus value and higher alkaline phosphatase concentration and a longer use of glucocorticoids were risk factors for bone mass loss in KTRs, and maintaining an appropriate weight and exercising an appropriate number of times per week helped to maintain bone mass.


Assuntos
Osso e Ossos/metabolismo , Transplante de Rim , Transplantados , Absorciometria de Fóton , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/complicações , Estudos Transversais , Feminino , Colo do Fêmur/metabolismo , Humanos , Imunossupressores/uso terapêutico , Vértebras Lombares/metabolismo , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Análise de Regressão
14.
J Diabetes ; 13(6): 458-468, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33135296

RESUMO

BACKGROUND: Age at menarche was reported to be associated with the risk of diabetes. However, the impact of ideal cardiovascular health metrics (ICVHMs) on the association between age at menarche and adulthood diabetes risk was unclear. METHODS: We included 121 431 women from the nationwide, population-based cohort of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study). The diagnosis of diabetes was based on the oral glucose tolerance test (OGTT) and glycosylated hemoglobin (HbA1c) measurement. Logistic regression and multiplicative interaction analysis were conducted to investigate the potential interaction effect between age at menarche and ICVHMs on the development of diabetes. RESULTS: The multivariable-adjusted odds ratios of diabetes across categories of age at menarche (<14, 14-17, and > 17 years) were 1.22 (95% confidence interval [CI]: 1.17, 1.28), 1.00 (reference), and 0.89 (95% CI: 0.85, 0.93), respectively. In subgroup analysis, significant interactions were detected between total cholesterol/blood pressure levels and age at menarche regarding the risk of diabetes (P for interaction = .0091 and .0019, respectively). The increased risk associated with age at menarche <14 years was observed in participants with three or fewer ICVHMs, but not in women with four or more ICVHMs (P for interaction = .0001). CONCLUSIONS: Age at menarche was inversely associated with the risk of diabetes in adulthood in Chinese women, and it appeared to be modified by the presence of ICVHMs. Further studies are needed to clarify the precise interrelationship and the generalizability of our results.

15.
Diabetes Care ; 44(2): 499-510, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33355246

RESUMO

OBJECTIVE: Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS: We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS: In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS: These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adulto , Ácidos e Sais Biliares , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Jejum , Humanos , Pessoa de Meia-Idade
16.
Sheng Wu Gong Cheng Xue Bao ; 36(11): 2367-2376, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33244931

RESUMO

p-coumaric acid is an important natural phenolic compound with a variety of pharmacological activities, and also a precursor for the biosynthesis of many natural compounds. It is widely used in foods, cosmetics and medicines. Compared with the chemical synthesis and plant extraction, microbial production of p-coumaric acid has many advantages, such as energy saving and emission reduction. However, the yield of p-coumaric acid by microbial synthesis is too low to meet the requirements of large-scale industrial production. Here, to further improve p-coumaric acid production, the directed evolution of tyrosine ammonia lyase (TAL) encoded by Rhodotorula glutinis tal gene was conducted, and a high-throughput screening method was established to screen the mutant library for improve the property of TAL. A mutant with a doubled TAL catalytic activity was screened from about 10,000 colonies of the mutant library. There were three mutational amino acid sites in this TAL, namely S9Y, A11N, and E518A. It was further verified by a single point saturation mutation. When S9 was mutated to Y, I or N, or A11 was mutated to N, T or Y, the catalytic activity of TAL increased by more than 1-fold. Through combinatorial mutation of three types of mutations at the S9 and A11, the TAL catalytic activity of S9Y/A11N or S9N/A11Y mutants were significantly higher than that of other mutants. Then, the plasmid containing S9N/A11Y mutant was transformed into CP032, a tyrosine-producing E. coli strain. The engineered strain produced 394.2 mg/L p-coumaric acid, which is 2.2-fold higher than that of the control strain, via shake flask fermentation at 48 h. This work provides a new insight for the biosynthesis study of p-coumaric acid.


Assuntos
Amônia-Liases , Escherichia coli , Amônia-Liases/genética , Escherichia coli/genética , Propionatos , Rhodotorula , Tirosina/genética
17.
Sheng Wu Gong Cheng Xue Bao ; 36(11): 2387-2397, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33244933

RESUMO

Recently, fast-growing Vibrio natriegens, as the great potential chassis, has shown a wide application in synthetic biology. Genome editing is an indispensable tool for genetic modification in synthetic biology. However, genome editing tools with high efficiency and fidelity are still to be developed for V. natriegens synthetic biology. To deal with this problem, the physiological characteristics of 6 V. natriegens strains were evaluated, and CICC 10908 strain with fast and stable growth was selected as the host strain for genome editing study. Then, the natural transformation system of V. natriegens was established and optimized. The efficiencies of optimized natural transformation that integrates antibiotic resistance marker cat-sacB or Kan(R) onto the chromosome of V. natriegens could reach 4×10⁻5 and 4×10⁻4, respectively. Based on the optimized natural transformation, a double-selection cassette was used to achieve seamless genome editing with high efficiency and fidelity. The positive rates of four different types of genetic manipulation, including gene deletion, complementation, insertion and substitution, were 93.8%, 100%, 95.7% and 100%, respectively. Finally, transformation and elimination of the recombinant plasmid could be easily achieved in V. natriegens. This work provides a seamless genome editing system with high efficiency and fidelity for V. natriegens synthetic biology.


Assuntos
Edição de Genes , Vibrio , Plasmídeos/genética , Biologia Sintética , Vibrio/genética
18.
Exp Ther Med ; 20(2): 1514-1520, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32765674

RESUMO

Expression levels of miR-223-3p and NLRP3 in high glucose and high fat (HGHF)-induced diabetic mice, and the mechanism on the injury of mouse cardiac microvascular endothelial cells (MCMECs) were investigated. Four-week C57BL/6J laboratory mice were selected and randomized into a control group and a model group (n=10 each). Mice in the model group were fed with HGHF diet to establish a mouse model of diabetes. Further MCMECs were purchased to construct carriers through transient transfection, and were separated into a normal group (cultured in the normal environment), a model group (not transfected), a blank carrier group (transfected with miR-NC), a miR-223-3p-mimics group, and a miR-223-3p-inhibitor group. RT-qPCR was used to detect the expression levels of miR-223-3p and NLRP3, and western blot analysis to detect the expression levels of NLRP3, apoptosis-related proteins Bax and caspase-3, and anti-apoptotic protein Bcl-2. Flow cytometry was used to observe apoptosis and TargetScan to predict the target relationship between miR-223-3p and NLRP3. Dual-luciferase reporter gene assay was used to detect the relationship between miR-223-3p and NLRP3. Compared with those in the control group, the mice in the model group had significantly lower expression of miR-223-3p. However, significantly higher mRNA and protein expression levels of NLRP3 were observed (P<0.05). After modeling, miR-223-3p overexpression downregulated the expression levels of NLRP3 mRNA, Bax and NLRP3 protein, as well as inhibited endothelial cell apoptosis (P<0.05), while the inhibition of miR-223-3p expression upregulated the expression levels and promoted apoptosis. In conclusion, miR-223-3p expression is low, however, NLRP3 is highly expressed in the heart tissue of HGHF-induced diabetic mice. miR-223-3p reduces the injury of MCMECs and inhibits endothelial cell apoptosis in mice by regulating the expression of NLRP3.

19.
Diabetes Care ; 43(8): 1902-1909, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32499384

RESUMO

OBJECTIVE: We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk. RESEARCH DESIGN AND METHODS: This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963-1974), fetal exposed (1959-1962), and childhood exposed (1949-1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes. RESULTS: During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05-1.31) and 1.12 (0.96-1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m2, or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata (P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes (P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24-2.04]), but not in those with two or more ICVHMs. CONCLUSIONS: The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Diabetes Mellitus , Fome Epidêmica/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde , Inanição/epidemiologia , Adulto , Experiências Adversas da Infância/estatística & dados numéricos , Idade de Início , Sistema Cardiovascular/fisiopatologia , Criança , China/epidemiologia , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Seguimentos , Humanos , Incidência , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Indicadores de Qualidade em Assistência à Saúde/normas , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Fatores de Risco , Inanição/complicações , Inanição/fisiopatologia
20.
Diabetes Care ; 43(8): 1929-1936, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32540923

RESUMO

OBJECTIVE: We aimed to determine the individual and combined associations of lifestyle and metabolic factors with new-onset diabetes and major cardiovascular events among a Chinese population aged ≥40 years. RESEARCH DESIGN AND METHODS: Baseline lifestyle information, waist circumference, blood pressure, lipid profiles, and glycemic status were obtained in a nationwide, multicenter, prospective study of 170,240 participants. During the up to 5 years of follow-up, we detected 7,847 individuals with new-onset diabetes according to the American Diabetes Association 2010 criteria and 3,520 cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. RESULTS: On the basis of 36.13% (population-attributable fraction [PAF]) risk attributed to metabolic risk components collectively, physical inactivity (8.59%), sedentary behavior (6.35%), and unhealthy diet (4.47%) moderately contributed to incident diabetes. Physical inactivity (13.34%), unhealthy diet (8.70%), and current smoking (3.38%) significantly contributed to the risk of major cardiovascular events, on the basis of 37.42% PAF attributed to a cluster of metabolic risk factors. Significant associations of lifestyle health status with diabetes and cardiovascular events were found across all metabolic health categories. Risks of new-onset diabetes and major cardiovascular events increased simultaneously according to the worsening of lifestyle and metabolic health status. CONCLUSIONS: We showed robust effects of lifestyle status on new-onset diabetes and major cardiovascular events regardless of metabolic status and a graded increment of risk according to the combination of lifestyle and metabolic health, highlighting the importance of lifestyle modification regardless of the present metabolic status.


Assuntos
Doenças Cardiovasculares/epidemiologia , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Estilo de Vida , Doenças Metabólicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , China/epidemiologia , Estudos de Coortes , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Dieta , Modificador do Efeito Epidemiológico , Feminino , Nível de Saúde , Humanos , Incidência , Masculino , Doenças Metabólicas/complicações , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/epidemiologia , Estudos Prospectivos , Fatores de Risco , Comportamento Sedentário , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
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