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1.
Biol Pharm Bull ; 44(9): 1303-1308, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471058

RESUMO

Peroxisome proliferator-activated receptor gamma (PPARγ) is a master transcription factor in adipocyte differentiation, while distal-less homeobox 5 (Dlx5) is essential for initiating osteoblast differentiation by driving Runt-related transcription factor 2 expression. Considering that adipocytes and osteoblasts share common progenitors, there is a reciprocal correlation between bone and fat formation. However, the mechanism by which Dlx5 controls PPARγ remains unclear. We elucidated that Dlx5 physically binds to PPARγ during immunoprecipitation; in particular, the ligand-binding and DNA-binding domains of PPARγ were involved in the interaction. Transcriptional activity of PPARγ was significantly decreased by Dlx5 overexpression, whereas the opposite results were detected with Dlx5 knockdown. Rosiglitazone, a PPARγ agonist, further enhanced the PPARγ-induced transcriptional activity; however, Dlx5 overexpression effectively repressed the rosiglitazone-mediated increase in activity. Finally, DNA-binding affinity assay revealed that Dlx5 interrupts the interaction of PPARγ with the PPARγ response element promoter. In conclusion, our findings indicate that Dlx5 impedes PPARγ-induced activity, and it may be useful for managing diabetes drug-mediated obesity.

3.
J Diabetes Complications ; 35(4): 107849, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33461925

RESUMO

AIM: To assess the relationship between growth differentiation factor-15 (GDF-15) levels and estimated glomerular filtration rate (eGFR) in type 2 diabetes mellitus (DM) patients with and without albuminuria. METHODS: We examined 324 patients with type 2 DM in a cross-sectional study. eGFR was determined using equations from creatinine (eGFRcr) and the combination of creatinine and cystatin C (eGFRcr-cys). The patients were classified into two groups based on urinary albumin: creatinine ratio (ACR): the normoalbuminuria group (urinary ACR < 30 mg/g) and the albuminuria group (urinary ACR ≥ 30 mg/g). RESULTS: In individuals both with and without albuminuria, higher GDF-15 levels were associated with lower eGFRcr and eGFRcr-cys. Plasma GDF-15 levels were inversely correlated with eGFRcr in individuals both with and without albuminuria (γ = -0.624, p < 0.001 and γ = -0.509, p < 0.001, respectively). A multiple regression analysis showed that GDF-15 levels were significantly associated with eGFRcr after adjusting for age, sex and other confounders, including urinary ACR as a continuous or categorical variable (ß = -0.309, p < 0.001 and ß = -0.318, p < 0.001, respectively). Similarly, these results were replicated when eGFRcr-cys was considered instead of eGFRcr in correlation and regression analyses. CONCLUSION: GDF-15 levels were inversely associated with eGFR in patients with type 2 DM. This relationship was independent of albuminuria status.

4.
Diabetes Metab J ; 45(5): 675-683, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32794385

RESUMO

BACKGROUND: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). METHODS: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. RESULTS: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, -1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. CONCLUSION: This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

5.
Sci Rep ; 10(1): 20568, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239667

RESUMO

The purpose of our study was to investigate the relationship between plasma growth differentiation factor-15 (GDF-15) concentrations and diabetic retinopathy in patients with type 2 diabetes mellitus (DM). We evaluated 235 patients with type 2 DM in a cross-sectional study. Significantly increased levels of the plasma GDF-15 were found in individuals with diabetic retinopathy versus those without. According to the degree of diabetic retinopathy, there was a significant difference in the average plasma GDF-15 levels (no diabetic retinopathy, 1114 ng/L; nonproliferative diabetic retinopathy, 1327 ng/L; proliferative diabetic retinopathy, 1445 ng/L; p for trend = 0.035) after adjustments for confounders. Logistic regression analyses indicated that plasma GDF-15 concentrations were significantly associated with diabetic retinopathy (odds ratio per 1 standard deviation increment in the log-transformed value, 1.78; 95% confidence interval, 1.05-3.03, p = 0.032). Our study showed a significant positive relationship between plasma GDF-15 concentrations and diabetic retinopathy in type 2 DM patients.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Retinopatia Diabética/metabolismo , Fator 15 de Diferenciação de Crescimento/metabolismo , Adulto , Idoso , Estudos Transversais , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Fatores de Diferenciação de Crescimento/sangue , Fatores de Diferenciação de Crescimento/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Índice de Gravidade de Doença
6.
Sci Rep ; 10(1): 12768, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728147

RESUMO

The aim of this study was to test the hypothesis that plasma sphingosine 1-phosphate (S1P) levels are associated with the risk of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes patients. This cross-sectional study included 287 individuals with type 2 diabetes. CAN was evaluated using cardiovascular reflex tests. Logistic regression analyses were conducted to assess the relationship between plasma S1P levels and CAN. Plasma S1P concentrations were significantly lower in individuals with CAN than in those without CAN. There was a significant interaction between plasma S1P levels and sex with respect to CAN (p for interaction = 0.003). When stratified by sex, the association between plasma S1P levels and CAN exhibited a sex difference; in multivariable analysis, plasma S1P levels were significantly associated with CAN in women (odds ratio per standard deviation increase in the log-transformed value, 0.40; 95% confidence interval, 0.23-0.70, p = 0.001). However, there was no significant association between plasma S1P and CAN in men. Plasma S1P concentrations were inversely associated with CAN only in women with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Lisofosfolipídeos/sangue , Doenças do Sistema Nervoso/sangue , Esfingosina/análogos & derivados , Adulto , Idoso , Sistema Nervoso Autônomo , Sistema Cardiovascular/inervação , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Análise de Regressão , Fatores de Risco , Esfingosina/sangue
7.
J Diabetes Complications ; 34(7): 107592, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32354624

RESUMO

AIM: To examine the relationship between serum myostatin levels and diabetic retinopathy in individuals with type 2 diabetes mellitus (DM). METHODS: This cross-sectional study evaluated 246 individuals with type 2 DM. Analysis of covariance was performed after adjusting for confounders. A logistic regression model was used to evaluate the relationship between serum myostatin levels and diabetic retinopathy. RESULTS: Serum myostatin levels were significantly higher in individuals with diabetic retinopathy than in those without. After adjusting for other covariates, the mean serum myostatin levels were significantly different according to the severity of retinopathy (without diabetic retinopathy, 2234 pg/mL; non-proliferative diabetic retinopathy, 2698 pg/mL; and proliferative diabetic retinopathy, 3076 pg/mL; p for trend = 0.004). The multivariate analysis showed that serum myostatin levels were significantly associated with diabetic retinopathy (odds ratio for every 1 standard deviation-increase in logarithmic value, 1.77; 95% confidence interval: 1.21-2.59; p = 0.003). CONCLUSION: Serum myostatin levels were positively associated with diabetic retinopathy in individuals with type 2 DM.

8.
J Bone Metab ; 27(1): 43-52, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32190608

RESUMO

Background: Adequate suppression of bone turnover rate is important to decrease fracture risk without mineralization defect due to oversuppression. This study was performed to determine reference intervals (RIs) for 2 bone turnover markers, serum C-terminal telopeptide of type I collagen (CTX) and osteocalcin, in Korean women. Methods: A total of 461 Korean women (287 premenopausal and 174 postmenopausal) without any disease or drug history affecting bone metabolism was included. Serum CTX and osteocalcin were measured after overnight fasting. Bone mineral density (BMD) was measured at the 1st to 4th lumbar vertebra using dual energy X-ray absorptiometry. Subjects with normal spinal BMD (T-score ≥-1.0) were included in this study. Results: After stable concentrations were maintained, both CTX and osteocalcin were abruptly increased in 50 to 59 years, and then decreased with increasing age. Median levels and interquartile range of serum CTX and osteocalcin in all subjects were 0.322 (0.212-0.461) ng/mL and 15.68 (11.38-19.91) ng/mL. RIs for serum CTX and osteocalcin in all subjects were 0.115 to 0.861 ng/mL and 6.46 to 36.76 ng/mL. Those were higher in postmenopausal women (CTX, 0.124-1.020 ng/mL, osteocalcin, 5.42-41.57 ng/mL) than in premenopausal women (CTX, 0.101-0.632 ng/mL, osteocalcin, 6.73-24.27 ng/mL). If we use target reference levels as lower half of premenopausal 30 to 45 years in patients with antiresorptive drugs, those were 0.101 to 0.251 ng/mL and 6.40 to 13.36 ng/mL. Conclusions: We established RIs for serum CTX and osteocalcin in healthy Korean women with normal lumbar spine BMD. Premenopausal RIs for serum CTX and osteocalcin would be useful to monitor patients with low bone mass using osteoporosis drugs.

9.
Exp Clin Endocrinol Diabetes ; 128(9): 607-614, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31610588

RESUMO

OBJECTIVE: To investigate the association between serum C-peptide level and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (DM) according to estimated glomerular filtration rate (eGFR) METHODS: In a cross-sectional study, we examined 939 individuals with type 2 DM. We measured fasting C-peptide, 2-hour postprandial C-peptide, and ΔC-peptide (postprandial C-peptide minus fasting C-peptide) levels. The individuals were classified into 2 groups based on eGFR: individuals without impaired renal function (eGFR ≥60 ml∙min-1 1.73m-2) and those with impaired renal function (eGFR <60 ml∙min-1 1.73m-2). RESULTS: Individuals with CAN had lower fasting C-peptide, postprandial C-peptide, and ΔC-peptide levels in patients both with and without impaired renal function. Multivariate logistic regression analyses adjusted for gender, age, and other confounders, including eGFR, showed that serum C-peptide level was significantly associated with CAN (odds ratio [OR] per standard deviation increase in the log-transformed value, 0.67; 95% confidence interval [CI], 0.52-0.87 for fasting C-peptide, P < 0.01; OR, 0.62; 95% CI, 0.47-0.83 for postprandial C-peptide, P < 0.01; OR, 0.71; 95% CI, 0.54-0.93 for ΔC-peptide, P < 0.05). CONCLUSIONS: Serum C-peptide level was negatively associated with CAN in individuals with type 2 DM independent of eGFR.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/sangue , Adulto , Idoso , Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/sangue , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
10.
Medicine (Baltimore) ; 98(43): e17693, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651899

RESUMO

This study sought to assess the hypothesis that anemia is associated with diabetic retinopathy in type 2 diabetes mellitus (DM) and investigate the factors mediating the relationship between anemia and diabetic retinopathy.In total, 1637 individuals with type 2 DM were examined in a cross-sectional study. Anemia was defined as hemoglobin level <120 g/L in women and <130 g/L in men. A logistic regression model was used to determine the association between anemia and diabetic retinopathy.Anemia was more prevalent in individuals with diabetic retinopathy. Logistic regression analysis found a statistically significant association between anemia and diabetic retinopathy after adjustment for traditional risk factors (odds ratio, 1.44; 95% confidence interval, 1.10-1.89, P = .009). Further adjustment for serum bilirubin levels removed the statistically significant association.In individuals with type 2 DM, anemia is related to diabetic retinopathy, and its association may be mediated by a correlated change in serum bilirubin levels.


Assuntos
Anemia/sangue , Bilirrubina/sangue , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco
11.
J Neurogastroenterol Motil ; 25(3): 387-393, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31177651

RESUMO

Background/Aims: Delayed gastric emptying (GE) is associated with high morbidity and mortality in subjects with diabetes. The aim of this study is to investigate associations between GE time and the major cardiovascular events (coronary heart diseases and ischemic stroke) in diabetic subjects with upper gastrointestinal (UGI) symptoms. Methods: Among 259 subjects with chronic UGI symptoms who underwent gastric emptying study (GES) over 13 years, 122 diabetic subjects without gastric surgery and/or rapid GE were enrolled in this study. We also gathered data about baseline demographics, clinical characteristics, estimated GE half-time (GE T½) and incidence of cardiovascular events following GES. Results: The mean age of subjects was 64.0 ± 17.4 years. There were 86 women and 104 subjects with type 2 diabetes. There were 52 (42.6%) subjects with normal GE, 50 (41.0.%) subjects with mild delayed GE, and 20 (16.4%) subjects with marked delayed GE. During follow-up (median, 207 weeks), cardiovascular events occurred in 7 (13.5%) subjects with normal GE, 4 (8.0%) subjects with mild delayed GE and 7 (35.0%) subjects with marked GE ( P = 0.015). Univariate analysis showed that GE T½ was significantly associated with incidence of cardiovascular events (crude OR, 1.74; 95% CI, 1.12-2.69; P = 0.014). In a multivariate model, association between GE T½ and incidence of cardiovascular events remained statistically significant after adjustment for baseline characteristics and comorbidities (adjusted OR, 1.94; 95% CI, 1.21-3.12; P = 0.006). Conclusion: A delay of GE was associated with an increased incidence of cardiovascular events in diabetic subjects with chronic UGI symptoms.

12.
Medicine (Baltimore) ; 98(20): e15703, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096517

RESUMO

The published data regarding the role of serum apolipoprotein (apo) A-I, apoB, and the apoB/A-I ratio in the risk of diabetic retinopathy remain inconsistent, and there is limited information about the effect of renal status on their associations in individuals with type 2 diabetes. The aim of this study was to investigate whether serum apoA-I, apoB, and the apoB/A-I ratio are associated with the presence of diabetic retinopathy in type 2 diabetes and to explore whether the relationships between these apolipoproteins and diabetic retinopathy are modified by urinary albumin excretion rate (UACR) and estimated glomerular filtration rate (eGFR).In total, 1215 individuals with type 2 diabetes were included in this cross-sectional study. Serum levels of apoA-I and apoB and the apoB/apoA-I ratio were measured. A logistic regression model was performed to explore associations of apolipoproteins with retinopathy.Individuals with diabetic retinopathy had significantly lower levels of serum apoA-I and higher apoB/apoA-I ratio than those without diabetic retinopathy. In the multivariable analyses, the associations between apoA-I and diabetic retinopathy and between the apoB/apoA-I ratio and diabetic retinopathy were statistically significant after adjustment for the traditional risk factors (odds ratio [OR] per standard deviation [SD] increase in the log-transformed value; 0.55, 95% confidence interval (CI); 0.32 to 0.97, P = .038; OR per SD increase in the log-transformed value; 2.83, 95% CI; 1.18 to 6.76, P = .019; respectively). Additional adjustments for UACR or eGFR removed the significant associations.In individuals with type 2 diabetes, serum apoA-I and the apoB/apoA-I ratio are associated with presence of diabetic retinopathy, which might be attributable to the correlated changes in UACR and eGFR.


Assuntos
Albuminúria/urina , Apolipoproteínas/sangue , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Taxa de Filtração Glomerular/fisiologia , Adulto , Idoso , Apolipoproteína A-I , Apolipoproteína B-100 , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença
13.
J Bone Miner Metab ; 37(3): 563-572, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30238428

RESUMO

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.


Assuntos
Adesão à Medicação , Osteoporose Pós-Menopausa/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Conservadores da Densidade Óssea/uso terapêutico , Estudos Transversais , Difosfonatos/uso terapêutico , Feminino , Humanos , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , República da Coreia , Inquéritos e Questionários , Resultado do Tratamento
14.
Diabetes Metab J ; 42(5): 425-432, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30113148

RESUMO

BACKGROUND: Whether pancreatic steatosis has a local or systemic effect, like ectopic fat of other major organs, remains unknown. Data on the influence of pancreatic steatosis on microvascular complication are rare. Therefore, we investigated the relationship between pancreatic steatosis and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: The attenuation of three pancreatic regions (head, body, and tail) and the spleen (S) in 186 patients with T2DM was measured using non-enhanced computed tomography imaging. We used three parameters for the assessment of pancreatic steatosis ('P' mean: mean attenuation of three pancreatic regions; P-S: difference between 'P' mean and 'S'; P/S: the 'P' mean to 'S' ratio). The presence of DR was assessed by an expert ophthalmologist using dilated fundoscopy. RESULTS: The average P mean was 29.02 Hounsfield units (HU), P-S was -18.20 HU, and P/S was 0.61. The three pancreatic steatosis parameters were significantly associated with the prevalence of DR in non-obese T2DM patients. In the non-obese group, the odds ratios of P mean, P-S, and P/S for the prevalence of DR, after adjustment for age, sex, and glycosylated hemoglobin level, were 2.449 (P=0.07), 2.639 (P=0.04), and 2.043 (P=0.02), respectively. CONCLUSION: In this study, pancreatic steatosis was significantly associated with DR in non-obese patients with T2DM. Further studies are necessary to clarify the causal relationship between pancreatic steatosis and the development of DR.

15.
Medicine (Baltimore) ; 97(32): e11783, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30095635

RESUMO

The purpose of the study was to test the hypothesis that anemia is related with serum C-peptide concentrations in individuals with type 2 diabetes mellitus (DM).This cross-sectional study was carried out in 1300 individuals with type 2 DM. We measured fasting C-peptide, 2-hour postprandial C-peptide, and postprandial C-peptide minus fasting C-peptide (ΔC-peptide) concentrations. Anemia was defined as hemoglobin (Hb) concentrations <130 g/L in men and <120 g/L in women. Anemia was graded into 2 groups: grade I anemia of Hb concentrations ≥110 g/L and grade II anemia of Hb concentrations <110 g/L.Fasting C-peptide, postprandial C-peptide, and ΔC-peptide concentrations were lower in individuals with anemia. According to the grade of anemia, the average C-peptide concentrations differed significantly after adjusting for other covariates. In the multivariable model, the statistically significant relation between anemia and serum C-peptide concentrations remained after adjusting for confounders, including age, gender, family history of diabetes, body mass index, duration of diabetes, glycated Hb, free fatty acids, hypertension, and hyperlipidemia (fasting C-peptide concentration: ß = -0.057, P = .032; postprandial C-peptide concentration: ß = -0.098, P < .001; ΔC-peptide concentration: ß = -0.095, P < .001).Anemia was inversely associated with serum C-peptide concentrations in individuals with type 2 DM.


Assuntos
Anemia/sangue , Anemia/epidemiologia , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Peptídeo C/metabolismo , Estudos Transversais , Jejum/metabolismo , Feminino , Hemoglobina A Glicada , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial/fisiologia
16.
J Diabetes Complications ; 32(4): 357-361, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29453140

RESUMO

OBJECTIVE: To evaluate the relationship between levels of serum apolipoproteins and the prevalence of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. METHODS: In total, 3199 individuals with type 2 diabetes were investigated in a cross-sectional study. The diagnosis of CAN was made based on the results of a cardiovascular reflex test. Serum apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) levels were measured. RESULTS: Serum apoA-1 levels were significantly low in individuals with CAN, but there was no significant association between serum apoB levels and CAN. According to the degree of cardiovascular autonomic dysfunction, the average apoA-I levels were significantly different after adjusting for other covariates (normal, 1.32 g/l, 95% confidence interval [CI] 1.30-1.35; early, 1.29 g/l, 95% CI 1.27-1.31; definite, 1.27 g/l, 95% CI 1.25-1.30; P for trend = 0.010). In the multivariable analysis, the statistically significant association between apoA-I and CAN remained after adjusting for the risk factors (odds ratio per standard deviation increase in the log-transformed value, 0.65; 95% CI, 0.43-0.97, P = 0.036). Additional adjustments for serum high-sensitivity C-reactive protein (or fibrinogen) concentrations eliminated this relationship. CONCLUSIONS: Serum apoA-I levels are inversely associated with the prevalence of CAN in individuals with type 2 diabetes. Our data also suggest that a putatively increased risk of CAN associated with decreased apoA-I levels might be mediated by correlated increases in the levels of inflammatory markers.


Assuntos
Apolipoproteína A-I/sangue , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Neuropatias Diabéticas/sangue , Idoso , Apolipoproteínas B/sangue , Doenças Cardiovasculares/etiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Feminino , Coração/inervação , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição Aleatória
17.
J Bone Metab ; 24(4): 249-255, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29259965

RESUMO

Background: The aim of this study is to determine the proportion of cancers presenting with parathyroid hormone (PTH) related protein (PTHrP)-mediated hypercalcemia, examine the clinical and biochemical characteristics, identify predictive factors for survival. And we also compared those characteristics between solid organ and hematologic malignancy groups. Methods: Cancer patients with PTHrP-mediated hypercalcemia who were treated at Chonnam National University Hospital in Korea from January 2005 to January 2015 were retrospectively reviewed. Results: Of all 115 patients, solid organ malignancies were the most common etiology (98 cases, 85.2%), with squamous cell carcinoma (50 cases, 43.4%), adenocarcinoma (27 cases, 23.4%). Interestingly, hepatocellular carcinoma (HCC; 18 cases, 15.7%) and cholangiocarcinoma (11 cases, 9.6%) were much more common causes than other previous reports. Hematologic malignancy was less common (17 cases, 14.8%), with multiple myeloma (9 cases, 7.8%) and non-Hodgkin's lymphoma (5 cases, 4.3%). Overall median survival was only 37 days. There was significant difference in median survival between two groups (35 days for solid organ malignancy and 72 days for hematologic malignancy; P=0.015). Cox regression analysis identified age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis as independent predictive factors for survival time. Conclusions: PTHrP-mediated hypercalcemia was most frequently caused by solid organ malignancy. However, HCC and cholangiocarcinoma were important causes of PTHrP-mediated hypercalcemia may be due to geographic differences in cancer incidence in Korean population. Age, the type of malignancy and the time interval of developing hypercalcemia after cancer diagnosis were independent poor predictive factors for survival time.

18.
Medicine (Baltimore) ; 96(15): e6586, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28403090

RESUMO

To investigate the relationship among anemia, physiological serum bilirubin levels, and cardiovascular autonomic neuropathy (CAN) in subjects with type 2 diabetes. In total, 2230 subjects with type 2 diabetes were evaluated in this cross-sectional study. CAN was diagnosed with a cardiovascular reflex test. The prevalence of anemia was greater in subjects with CAN. In multivariable analysis, the relationship between anemia and CAN remained statistically significant after adjusting for the risk factors (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.07-1.80, P = .015). Additional adjustment for serum bilirubin concentrations abolished this relationship (OR 1.20, 95% CI 0.91-1.58, P = .189). Anemia is positively associated with the prevalence of CAN in subjects with type 2 diabetes. In addition, our results suggest that the putative increased CAN risk associated with anemia might be mediated by a correlated decrease in serum bilirubin levels.


Assuntos
Anemia/epidemiologia , Doenças do Sistema Nervoso Autônomo/epidemiologia , Bilirrubina/sangue , Diabetes Mellitus Tipo 2/sangue , Neuropatias Diabéticas/epidemiologia , Anemia/sangue , Anemia/etiologia , Doenças do Sistema Nervoso Autônomo/sangue , Doenças do Sistema Nervoso Autônomo/etiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/etiologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Fatores de Risco
19.
AJR Am J Roentgenol ; 208(5): 1141-1146, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28177652

RESUMO

OBJECTIVE: The purpose of this study is to evaluate the MRI appearance of the irreversible electroporation zone in porcine liver, with histopathologic correlation. MATERIALS AND METHODS: Nine irreversible electroporation ablations were percutaneously created in two Yorkshire pigs. Irreversible electroporation was performed with a bipolar 16-gauge electrode with 3-cm exposure tip and fixed 8-mm interpolar distance. Gadoxetate disodium-enhanced 3-T MRI was performed 50 hours after irreversible electroporation. Livers were harvested immediately after MRI for histopathologic analysis. Ablation zone size was measured on each pulse sequence and correlated with pathologic ablation zone size. Qualitative MRI features of the ablation zone were assessed, and contrast-to-noise ratios (CNRs) were calculated. Statistical analysis included Pearson correlation and t tests. RESULTS: Histopathologically, three distinct layers were present in the irreversible electroporation ablation zone: an inner layer of coagulative necrosis (hyperintense at T1- and T2-weighted imaging and nonenhancing), a middle layer of congestion and hemorrhage (hypointense at T1-weighted imaging, hyperintense at T2-weighted imaging and DWI, and progressively enhancing but hypointense at the hepatobiliary phase), and a peripheral layer of inflammation (hyperintense at the arterial phase but isointense at all other sequences). The hepatobiliary phase ablation zone size showed the highest correlation with the pathologic ablation zone size (r = 0.973). This correlation was significant (p < 0.001). T2-weighted imaging had the highest lesion-to-normal tissue CNR. CONCLUSION: The irreversible electroporation ablation zone contains three distinct histopathologic zones, each with unique MRI features. T2-weighted imaging had the highest CNR, and the hepatobiliary phase had the strongest correlation with ablation zone size.


Assuntos
Eletroporação/métodos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Imageamento por Ressonância Magnética/métodos , Animais , Meios de Contraste , Gadolínio DTPA , Marcação In Situ das Extremidades Cortadas , Masculino , Modelos Animais , Necrose , Suínos
20.
Biochem Biophys Res Commun ; 478(2): 683-8, 2016 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-27498006

RESUMO

Osterix is an essential transcription factor for osteogenesis and is expressed in osteoblasts. Although Osterix has been shown to be induced by bone morphogenetic protein 4, the molecular mechanism underlying Osterix function during osteoblast differentiation remains unclear. Connexin43 (Cx43) is the most abundant gap junction protein in bone cells and plays a critical role in osteoblast differentiation. However, little is known about the functional interactions between Osterix and the Cx43 promoter. In the present study, we investigated the relationship between Osterix and Cx43 in HEK293 and C2C12 cells. Cx43 expression was significantly repressed by the addition of shRNA against Osterix, whereas overexpression of Osterix resulted in enhanced Cx43 expression. Furthermore, Osterix directly occupied the promoter region of Cx43 and subsequently increased Cx43 promoter activity in a dose-dependent manner. In addition, phosphorylation of the Ser76 and Ser80 residues in Osterix were found to be critical for its activity on the Cx43 promoter. Our results suggest that Osterix plays an important role in increasing bone morphogenetic protein 4-induced Cx43 activity.


Assuntos
Proteína Morfogenética Óssea 4/genética , Conexina 43/genética , Osteoblastos/metabolismo , Fatores de Transcrição/genética , Animais , Proteína Morfogenética Óssea 4/metabolismo , Linhagem Celular , Conexina 43/metabolismo , Regulação da Expressão Gênica , Genes Reporter , Células HEK293 , Humanos , Luciferases/genética , Luciferases/metabolismo , Camundongos , Modelos Biológicos , Mioblastos/citologia , Mioblastos/metabolismo , Osteoblastos/citologia , Plasmídeos/química , Plasmídeos/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fator de Transcrição Sp7 , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Transfecção
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