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1.
Metabolism ; 124: 154874, 2021 Nov.
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.
Front Endocrinol (Lausanne) ; 12: 642000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421815

RESUMO

In recent decades, the prevalence of obesity has been rising. One of the major characteristics of obesity is fat accumulation, including hyperplasia (increase in number) and hypertrophy (increase in size). After histological staining, it is critical to accurately measure the number and size of adipocytes for assessing the severity of obesity in a timely fashion. Manual measurement is accurate but time-consuming. Although commercially available adipocyte counting tools, including AdipoCount, Image-Pro Plus, and ImageJ were helpful, limitations still exist in accuracy and time consuming. In the present study, we introduced the protocol of combined usage of these tools and illustrated the process with histological staining slides from adipose tissues of lean and obese mice. We found that the adipocyte sizes quantified by the tool combination were comparable as manual measurement, whereas the combined methods were more efficient. Besides, the recognition effect of monochrome segmentation image is better than that of color segmentation image. Overall, we developed a combination method to measure adipocyte sizes accurately and efficiently, which may be helpful for experimental process in laboratory and also for clinic diagnosis.

5.
Diabetes Obes Metab ; 23(11): 2551-2560, 2021 Nov.
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.

6.
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.

7.
Endocr Connect ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34223825

RESUMO

BACKGROUND: A prolonged heart rate-corrected QT interval (QTc) has been associated with peripheral artery disease (PAD) in the general population. However, no study to date has identified a link between prolonged QTc and the severity of PAD in patients with diabetes mellitus and foot ulcers (DFUs). This study aimed to investigate this relationship. METHODS: This multicenter study enrolled 281 patients with DFUs. The severity of PAD was classified into no severe PAD group (without stenosis or occlusion) and severe PAD group (with stenosis or occlusion) based on duplex ultrasonography. The association of prolonged QTc with severe PAD was evaluated in a multivariable mixed-effect logistic regression model, with the hospital as a random effect. Directed acyclic graphs were used to drive the selection of variables to fit the regression model. RESULTS: Patients with severe PAD had longer QTc than those without. Based on the multivariable mixed-effect logistic regression model, a prolonged QTc was positively associated with severe PAD (Odds ratio [OR] = 2.61; 95% Confidence Interval [CI]: 1.07-6.35) and severe DFUs (Wagner grade score ≥3) (OR = 2.87; 95% CI: 1.42-5.81). CONCLUSIONS: A prolonged QTc was associated with severe PAD in patients with DFUs. Further research is required to ascertain whether the association is causal.

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.
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
11.
Diabetologia ; 64(5): 1066-1078, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33687487

RESUMO

AIMS/HYPOTHESIS: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes. METHODS: In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 µg) for 12 weeks. The primary endpoint was the change in HbA1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA1c < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug. RESULTS: We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 µg, 150 µg and 200 µg groups). At the end of 12 weeks, mean differences in HbA1c in the treatment groups were -7.76 mmol/mol (95% CI -9.23, -4.63, p < 0.001) (-0.72%, 95% CI -1.01, -0.43), -12.89 mmol/mol (95% CI -16.05, -9.72, p < 0.001) (-1.18%, 95% CI -1.47, -0.89) and -11.14 mmol/mol (95% CI -14.19, -7.97, p <0 .001) (-1.02%, 95% CI -1.30, -0.73) in the 75 µg, 150 µg and 200 µg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA1c. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death. CONCLUSIONS/INTERPRETATION: All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03520972 FUNDING: The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

12.
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.

13.
Endocrine ; 71(2): 476-483, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33025562

RESUMO

PURPOSE: To investigate the changes of the serum parathyroid hormone (PTH) and calcium level, as well as bone mineral density (BMD), after percutaneous ultrasound-guided microwave ablation (MWA) for primary hyperparathyroidism (pHPT) caused by single hyperfunctional nodule. METHODS: The study enrolled 20 patients with a total of 20 nodules of MWA treatment to pHPT in one session. The normalization rate of the serum PTH and calcium was evaluated at every 6 months during 2-year follow-up after MWA. The bone mineral density (BMD) at lumbar spine and femoral neck were also compared before and after the procedure. RESULTS: The normalization rate of both PTH and serum calcium at 6-, 12-, 24-month follow-up was 66.6%, 80.0%, and 62.5%, respectively. Though the normalization rate of serum calcium level at 6-, 12-, and 24-month visit after MWA was 100%. The BMD increased 12, 24 months after MWA at lumbar spine (1.022 ± 0.155, 1.057 ± 0.151 vs 0.965 ± 0.145 g/cm2, p < 0.01) and femoral neck at 2-year assessment (0.819 ± 0.094 vs 0.771 ± 0.102 g/cm2, p = 0.015). Seven nodules disappeared in 20 nodules (35.0%), average ablation time was 122.29 ± 107.54 s (34-460 s). Six patients encountered voice change during the procedure, one participant was confirmed recurrent laryngeal injuries but recovered within 2 months. CONCLUSIONS: Percutaneous ultrasound-guided microwave ablation results in improvement of biochemical profiles and bone mineral density in subjects with single hyperfunctional parathyroid nodule. However, the long-term efficacy of the MWA remains to be verified.

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.
Cell Death Dis ; 11(12): 1040, 2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-33288747

RESUMO

Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.


Assuntos
Chalconas/uso terapêutico , Hiperglicemia/tratamento farmacológico , Inflamação/complicações , Rim/lesões , Estresse Oxidativo , Sirtuína 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Chalconas/química , Chalconas/farmacologia , Fibrose , Rim/efeitos dos fármacos , Rim/patologia , Camundongos Endogâmicos C57BL , Modelos Moleculares , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos
17.
Int J Obes (Lond) ; 44(8): 1784-1789, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32572128

RESUMO

BACKGROUND/OBJECTIVES: During the 2019 coronavirus disease (COVID-19) outbreak, obesity may contribute to COVID-19 transmission and deterioration. In addition, many patients with COVID-19 infection have suffered liver damage which might contribute to a worse prognosis. We conducted a clinical epidemiological analysis to investigate the association of overweight/obesity and abnormal liver function (ALF) with hospitalized duration in patients infected with COVID-19. SUBJECTS/METHODS: Fifty-eight patients with diagnosed COVID-19 (22 women & 36 men; average age: 49.2 ± 13.1 yr) were included, and their clinical data were collected at The Second Affiliated and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang. Overweight/obesity was determined as body mass index (BMI) ≥24 kg/m2, ALF was determined as alanine aminotransferase >40 U/L, and prolonged hospitalization was lasting more than the median value of the hospitalized days (19 days) in this population. RESULTS: The proportions of prolonged hospitalization were elevated in patients with overweight/obesity and ALF compared with those without overweight/obesity (62.1% versus 26.1%, P = 0.010) and those without ALF (70.6% versus 41.5%, P = 0.043). Kaplan-Meier analysis showed that the hospitalized duration was increased from the patients with neither overweight/obesity nor ALF to those with either overweight/obesity or ALF, and to those with both of overweight/obesity and ALF (mean with 95% confidence interval: 16.4 [14.5-18.3] versus 25.3 [21.6-29.1] versus 28.3 [24.6-32.0], P for trend = 0.001). Being discharged from hospital in time was inversely and independently associated with BMI (hazard ratio [HR] = 0.75, 95% CI: 0.63-0.90, P for trend = 0.002) and ALT (HR = 0.95, 95% CI: 0.92-0.99, P for trend = 0.007). CONCLUSIONS: Present findings suggested that overweight/obesity and/or ALF contributed to predicting a probability of prolonged hospitalization in patients with COVID-19 infection, to whom extra attentions and precautions should be paid during clinical treatments.


Assuntos
Alanina Transaminase/sangue , Infecções por Coronavirus/epidemiologia , Tempo de Internação/estatística & dados numéricos , Fígado/fisiopatologia , Pneumonia Viral/epidemiologia , Adulto , COVID-19 , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Fígado/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Sobrepeso/fisiopatologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Estudos Retrospectivos
18.
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
19.
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
20.
Diabetes ; 69(8): 1779-1792, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32404351

RESUMO

Diabetes-induced oxidative stress is one of the major contributors to dysfunction of endothelial progenitor cells (EPCs) and impaired endothelial regeneration. Thus, we tested whether increasing antioxidant protein metallothionein (MT) in EPCs promotes angiogenesis in a hind limb ischemia (HLI) model in endothelial MT transgenic (JTMT) mice with high-fat diet- and streptozocin-induced diabetes. Compared with littermate wild-type (WT) diabetic mice, JTMT diabetic mice had improved blood flow recovery and angiogenesis after HLI. Similarly, transplantation of JTMT bone marrow-derived mononuclear cells (BM-MNCs) stimulated greater blood flow recovery in db/db mice with HLI than did WT BM-MNCs. The improved recovery was associated with augmented EPC mobilization and angiogenic function. Further, cultured EPCs from patients with diabetes exhibited decreased MT expression, increased cell apoptosis, and impaired tube formation, while cultured JTMT EPCs had enhanced cell survival, migration, and tube formation in hypoxic/hyperglycemic conditions compared with WT EPCs. Mechanistically, MT overexpression enhanced hypoxia-inducible factor 1α (HIF-1α), stromal cell-derived factor (SDF-1), and vascular endothelial growth factor (VEGF) expression and reduced oxidative stress in ischemic tissues. MT's pro-EPC effects were abrogated by siRNA knockdown of HIF-1α without affecting its antioxidant action. These results indicate that endothelial MT overexpression is sufficient to protect against diabetes-induced impairment of angiogenesis by promoting EPC function, most likely through upregulation of HIF-1α/SDF-1/VEGF signaling and reducing oxidative stress.


Assuntos
Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/prevenção & controle , Células Progenitoras Endoteliais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metalotioneína/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/prevenção & controle , Animais , Western Blotting , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Quimiocina CXCL12/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Membro Posterior/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia/genética , Isquemia/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Metalotioneína/genética , Camundongos , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
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