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1.
Front Endocrinol (Lausanne) ; 12: 719666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777240

RESUMO

Background: Lean body mass (LBM) and fat mass (FM) have been shown to have different associations with several chronic diseases but little is known about the sex-specific association of LBM and FM with diabetic nephropathy (DN) risk among participants with diabetes. Methods: Participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study was used in a post hoc analysis to examine the association of predicted LBM index (LBMI) and FM index (FMI) with incident DN risk (defined as a composite outcome of three types of predefined DN). Because of sex differences in body composition, analyses were conducted separately using sex-specific quartiles of predicted LBMI and FMI. Results: Of the 9,022 participants with type 2 diabetes (5,575 men and 3,447 women) included in this study, 5,374 individuals developed DN (3,396 in men and 1,978 in women). Higher quartiles of LBMI were associated with a reduced risk of DN while higher quartiles of FMI were associated with an increased higher risk of DN among men but not women. Compared with the lowest quartile, the fully adjusted hazard ratios (HRs) and 95% confidence intervals (CIs)for the highest quartile of predicted LBMI and FMI were respectively 0.83 (95% CI 1.71 - 0.96) and 1.23 (95% CI 1.06-1.43) among men; and 0.92 (95% CI 0.63 - 1.33) and 1.14 (95% CI 0.79 - 1.63) among women. Conclusions: Among participants with diabetes, predicted LBMI was inversely associated with risk of DN while predicted FMI was positively associated with an increased risk of incident DN among men but not women. Trial registration: ClinicalTrials.gov., no. NCT00000620.

2.
J Gerontol A Biol Sci Med Sci ; 76(11): 2062-2070, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34331763

RESUMO

BACKGROUND: To investigate the influence of diabetes duration and glycemic control, assessed by glycated hemoglobin (HbA1c) levels, on risk of incident dementia. METHODS: The present study is a prospective study of 461 563 participants from the UK Biobank. The age at diabetes diagnosis was determined by self-report. Diabetes duration was calculated as baseline age minus age at diagnosis. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (CIs). RESULTS: During a median follow-up of 8.1 years, 2 233 dementia cases were recorded. As compared with normoglycemic individuals, individuals with diabetes had higher risk of all-cause dementia, and the risk increased with increasing duration of diabetes; compared with participants with diabetes duration of <5 years, the multivariable-adjusted HRs (95% CIs) were 1.49 (1.12-1.97), 1.71 (1.21-2.41), and 2.15 (1.60-2.90) for those with diabetes durations ≥5 to < 10, ≥10 to <15, and ≥ 15 years, respectively (p for trend < .001). Among participants with diabetes, those with both longer diabetes duration (diabetes duration ≥ 10 years) and poor glycemic control (HbA1c ≥ 8%) had the highest risk of all-cause dementia (multivariable-adjusted HR = 2.07, 95% CI 1.45, 2.94), compared with patients with shorter duration of diabetes and better glycemic control (diabetes duration < 10 years and HbA1c < 8%). CONCLUSIONS: Diabetes duration appeared to be associated with the risk of incident dementia due to factors beyond glycemic control. Clinicians should consider not only glycemic control but also diabetes duration in dementia risk assessments for patients with diabetes.

3.
J Alzheimers Dis ; 80(4): 1591-1601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33720888

RESUMO

BACKGROUND: Wealth and income are potential modifiable risk factors for dementia, but whether wealth status, which is composed of a combination of debt and poverty, and assessed by wealth and income, is associated with cognitive impairment among elderly adults remains unknown. OBJECTIVE: To examine the associations of different combinations of debt and poverty with the incidence of dementia and cognitive impairment without dementia (CIND) and to evaluate the mediating role of depression in these relationships. METHODS: We included 15,565 participants aged 51 years or older from the Health and Retirement Study (1992-2012) who were free of CIND and dementia at baseline. Dementia and CIND were assessed using either the modified Telephone Interview for Cognitive Status (mTICS) or a proxy assessment. Cox models with time-dependent covariates and mediation analysis were used. RESULTS: During a median of 14.4 years of follow-up, 4,484 participants experienced CIND and 1,774 were diagnosed with dementia. Both debt and poverty were independently associated with increased dementia and CIND risks, and the risks were augmented when both debt and poverty were present together (the hazard ratios [95% confidence intervals] were 1.35 [1.08-1.70] and 1.96 [1.48-2.60] for CIND and dementia, respectively). The associations between different wealth statuses and cognition were partially (mediation ratio range: 11.8-29.7%) mediated by depression. CONCLUSION: Debt and poverty were associated with an increased risk of dementia and CIND, and these associations were partially mediated by depression. Alleviating poverty and debt may be effective for improving mental health and therefore curbing the risk of cognitive impairment and dementia.


Assuntos
Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Depressão/complicações , Depressão/etiologia , Pobreza/psicologia , Idoso , China/epidemiologia , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Análise de Mediação , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Aposentadoria/psicologia , Fatores de Risco
4.
Diabetes Obes Metab ; 23(6): 1361-1370, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33620747

RESUMO

AIMS: To assess the associations of diabetes duration and glycaemic control (defined by plasma glycated haemoglobin [HbA1c] level) with the risks of cardiovascular disease (CVD) and all-cause mortality and to determine whether the addition of either or both to the established CVD risk factors can improve predictions. MATERIALS AND METHODS: A total of 435 679 participants from the UK Biobank without CVD at baseline were included. Cox models adjusting for classic risk factors (sociodemographic and anthropometric characteristics, lipid profiles and medication use) were used, and predictive utility was determined by the C-index and net reclassification improvement (NRI). RESULTS: Compared with participants without diabetes, participants with longer diabetes durations and poorer glycaemic control had a higher risk of fatal/nonfatal CVD. Among participants with diabetes, the fully-adjusted hazard ratios (HRs) for diabetes durations of 5 to <10 years, 10 to <15 years and ≥15 years were 1.15 (95% confidence interval [CI] 0.99, 1.34), 1.50 (95% CI 1.26, 1.79) and 2.22 (95% CI 1.90, 2.58; P-trend <0.01), respectively, compared with participants with diabetes durations <5 years. In addition, those with the longest disease duration (≥15 years) and poorer glycaemic control (HbA1c ≥64 mmol/mol [8%]) had the highest risk of fatal/nonfatal CVD (HR 3.12, 95% CI 2.52, 3.86). Among participants with diabetes, the addition of both diabetes duration and glycaemic control levels significantly improved both the C-index (change in C-index +0.0254; 95% CI 0.0111, 0.0398) and the overall NRI for fatal/nonfatal CVD (0.0992; 95% CI 0.0085, 0.1755) beyond the use of the classic risk factors. CONCLUSIONS: Both longer diabetes duration and poorer glycaemic control were associated with elevated risks of CVD and mortality. Clinicians should consider not only glycaemic control but also diabetes duration in CVD risk assessments for participants with diabetes.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/análise , Controle Glicêmico , Humanos , Fatores de Risco
5.
J Hypertens ; 39(8): 1594-1601, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33560057

RESUMO

OBJECTIVE: The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines lowered the hypertension threshold from a SBP/DBP level of at least 140/90 mmHg to at least 130/80 mmHg. The cardiovascular impact of isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) under the new definition remains unclear. METHODS: We used data from the UK Biobank study, which is a prospective population-based cohort study. Participants were categorized into five groups: normal BP, normal high BP, ISH, IDH and systolic and diastolic hypertension. The primary endpoint for this study was the composite of nonfatal myocardial infarction (MI), nonfatal ischaemic stroke, nonfatal haemorrhagic stroke and cardiovascular disease (CVD) death. We also explored the results for the above-mentioned CVD outcomes separately. Baseline BP measurements were obtained twice after the participant had been at rest for at least 5 min in a seated position. RESULTS: We included 385 955 participants who were not taking antihypertensive medications, were free of CVD at baseline and had available data on BP measurements. During a median follow-up of 8.1 years, 8959 CVD events were recorded, including 4729 nonfatal MIs, 2287 nonfatal ischaemic strokes, 813 nonfatal haemorrhagic strokes, and 1826 CVD deaths. According to the hypertension threshold of at least 130/80 mmHg by the American College of Cardiology/American Heart Association guidelines, both ISH (hazard ratio 1.39; 95% confidence interval 1.27, 1.15) and IDH (hazard ratio 1.28; 95% confidence interval 1.15, 1.43) were significantly associated with a higher overall CVD risk than normal BP. ISH was associated with most CVD risk, except for ischaemic stroke, while the excess CVD risk associated with IDH appeared to be driven mainly by MI and CVD death. We found heterogeneity by sex and age regarding the effects of IDH on overall CVD risk, with significant associations in younger adults (age <60 years) and women and null associations in men and older adults (age ≥60 years). CONCLUSION: ISH was associated with the risk of most CVD events, while the association between IDH and CVD risk was mainly driven by MI incidence and CVD death. Further research is needed to identify participants with IDH who have a particular risk for developing CVD.


Assuntos
Isquemia Encefálica , Cardiologia , Doenças Cardiovasculares , Hipertensão , Acidente Vascular Cerebral , Idoso , American Heart Association , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Estados Unidos/epidemiologia
6.
J Clin Endocrinol Metab ; 104(8): 3370-3378, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30869791

RESUMO

CONTEXT: The patterns of the association between high-density lipoprotein cholesterol (HDL-C) concentrations and mortality among the elderly are still unclear. OBJECTIVE: To examine the association of HDL-C concentrations with mortality and to identify the optimal HDL-C concentration range that predicts the lowest risk of all-cause mortality among the elderly. DESIGN: This was a nationwide, community-based, prospective cohort study. PARTICIPANTS: This study included 7766 elderly individuals (aged ≥65 years; mean age: 74.4 years) from the Health and Retirement Study. Cox proportional hazards models and Cox models with penalized smoothing splines were used to estimate hazard ratios (HRs) with 95% CI for all-cause and cause-specific mortality. RESULTS: During a median follow-up of 5.9 years, 1921 deaths occurred. After a full adjustment for covariates, a nonlinear (P < 0.001 for nonlinearity) association was found between HDL-C and all-cause mortality [minimum mortality risk at 71 mg/dL (1.84 mM)]; the risk for all-cause mortality was significantly higher in the groups with HDL-C concentration <61 mg/dL (1.58 mM; HR: 1.18; 95% CI: 1.05 to 1.33) and with HDL-C concentration >87 mg/dL (2.25 mM; HR: 1.56; 95% CI: 1.17 to 2.07) than in the group with HDL-C concentrations ranging from 61 to 87 mg/dL (1.58 to 2.25 mM). Nonlinear associations of HDL-C concentrations with both cardiovascular and noncardiovascular mortality were also observed (both P < 0.001 for nonlinearity). CONCLUSIONS: Among the elderly, nonlinear associations were found between HDL-C and all-cause and cardiovascular mortality. The single optimal HDL-C concentration and range were 71 mg/dL and 61 to 87 mg/dL, respectively.


Assuntos
Doenças Cardiovasculares/mortalidade , Causas de Morte , HDL-Colesterol/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
7.
J Clin Endocrinol Metab ; 104(8): 3345-3354, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30896760

RESUMO

CONTEXT: The patterns of associations between glycated Hb (HbA1c) and mortality are still unclear. OBJECTIVE: To explore the extent to which ranges of HbA1c levels are associated with the risk of mortality among participants with and without diabetes. DESIGN, SETTING, AND PATIENTS: This was a nationwide, community-based prospective cohort study. Included were 15,869 participants (median age 64 years) of the Health and Retirement Study, with available HbA1c data and without a history of cancer. Cox proportional hazards regression models were used to estimate hazard ratios with 95% CIs for mortality. RESULTS: A total of 2133 participants died during a median follow-up of 5.8 years. In participants with diabetes, those with an HbA1c level of 6.5% were at the lowest risk of all-cause mortality. When HbA1c level was <5.6% or >7.4%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 6.5%. As for participants without diabetes, those with an HbA1c level of 5.4% were at the lowest risk of all-cause mortality. When the HbA1c level was <5.0%, the increased all-cause mortality risk became statistically significant as compared with an HbA1c level of 5.4%. However, we did not observe a statistically significant elevated risk of all-cause mortality above an HbA1c level of 5.4%. CONCLUSIONS: A U-shaped and reverse J-shaped association for all-cause mortality was found among participants with and without diabetes. The corresponding optimal ranges for overall survival are predicted to be 5.6% and 7.4% and 5.0% and 6.5%, respectively.


Assuntos
Diabetes Mellitus/mortalidade , Hemoglobina A Glicada/análise , Idoso , Causas de Morte , Diabetes Mellitus/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taxa de Sobrevida
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(11): 1448-1455, 2017 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-29180323

RESUMO

OBJECTIVE: To analyze the characteristics of pathogenic microorganisms in the infected bone tissues in patients with diabetic foot osteomyelitis (DFO) using 16S rRNA high-throughput sequencing to facilitate rapid and accurate detection of pathogens and effective infection control. METHODS: Between September, 2016 and April, 2017, 16 patients with DFO were admitted in our department and infected bone specimens were obtained during debridement. The pathogenic microorganisms in the specimens were identified using both 16S rRNA high-throughput sequencing and automatic blood culture analyzer, and the characteristics of the microflora were analyzed based on 16S rRNA sequencing data in comparison with the results of blood culture. RESULTS: The results of 16S rRNA sequencing showed that bone tissues of DFO contained diverse and uniformly distributed pathogenic organisms, among which 20 (87%) dominant genera were identified with Prevotella as the most abundant pathogen. Both 16S rRNA sequencing and routine culture results suggested the domination of gram-negative bacteria among the pathogens in DFO bone tissues. 16S rRNA sequencing, compared with routine culture, yielded a higher positivity rate (100% vs 88.24%) and detected a greater average number of pathogens (12.56 vs 1.50) and a higher proportion of gram-negative bacteria (67.16% vs 50.00%) in the samples. 16S rRNA sequencing detected nearly all the pathogens identified by routine culture except for Escherichia coli, Serratia marcescens and Enterobacter cloaca, and identified 13 genera that failed to be detected by routine culture, including the obligate or strict anaerobes Anaerococcus, Veillonella, Bacteroides, Fusobacterium, Porphyromonas, Finegoldia, Prevotella, Peptostreptococcus, Parvimonas, Peptoniphilus and Bulleidia. Routine culture did not detect any anaerobes in the samples but identified multidrug-resistant strains in as many as 58.33% of the pathogens. CONCLUSIONS: 16S rRNA high-throughput sequencing is capable of demonstrating the diversity and abundance of microflora in DFO bone tissues, where diverse and uniformly distributed pathogens can be detected with a discrete distribution of the dominant genera, most of which are gram-negative. Compared with routine culture method, 16S rRNA sequencing allows more convenient and accurate identification of the pathogens (especially gram-negative bacteria and anaerobes), and can be useful in clinical decision on appropriate treatment of DFO.


Assuntos
Bactérias/classificação , Pé Diabético/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Osteomielite/microbiologia , Bactérias/isolamento & purificação , DNA Bacteriano/genética , Humanos , RNA Ribossômico 16S/genética
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(10): 1410-1416, 2016 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-27777208

RESUMO

OBJECTIVE: To investigate foot biomechanics characteristic of patients with type 2 diabetes mellitus. METHODS: This study was conducted among 303 patients with type 2 diabetes. The whole foot was divided into 10 regions, namely the first toe (T1); the second to fifth toes (T2-5); the first, second, third, fourth, and fifth metatarsals (M1, M2, M3, M4, and M5, respectively); midfoot (MF), and the heel medial (HM). Foot arch index, foot angle and maximum peak pressure (MPP) of the 10 regions were measured using a Footscan gait system. RESULTS: The maximum peak pressure of 10 regions decreased in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the left foot, and in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the right foot. The MPP in M1 region was higher in the right than in the left foot (P<0.05). The MPP in M3, M4, M5, and MF was higher in the left than in the right foot (P<0.05). The percentage of high-risk foot (defined by a total plantar pressure ≥70 N/cm2) was 34% on the left and 17.7% on the right. An increased BMI was associated with a significant increase in high-risk foot, but not for the right foot in underweight patients. Foot flat phase was extended and forefoot push-off phase shortened in stance phase in the patients. Compared with the right foot, the left foot showed a significantly increased foot arch index and increased low and high arch rates with a decreased normal arch rate. Total plantar pressure was higher in of the left high arch foot than in normal arch foot. The foot angle was significantly larger on the right than on the left. The bilateral total plantar pressures were significantly greater in male patients (P<0.05) and increased with age but were not associated with the duration of DM, foot angle, or glycosylated hemoglobin level. CONCLUSION: Diabetic patients have obvious alterations in foot biomechanics with abnormalities of the plantar pressure, and the percentage of high-risk foot increases in overweight and obese patients, suggesting the need of body weight control in these patients when administering offloading treatment for prevention of diabetic foot ulcer.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Pé/fisiopatologia , Marcha , Fenômenos Biomecânicos , Pé Diabético/prevenção & controle , Feminino , Calcanhar/fisiopatologia , Humanos , Masculino , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Pressão
10.
Biomed Environ Sci ; 27(3): 197-203, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24709100

RESUMO

OBJECTIVE: To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells. METHODS: After the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy. RESULTS: The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the U0126-blocked export of SphK2. CONCLUSION: ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Butírico/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Apoptose/fisiologia , Células HCT116/efeitos dos fármacos , Humanos , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , RNA Interferente Pequeno , Transdução de Sinais/efeitos dos fármacos
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