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1.
Diabetes Obes Metab ; 20(5): 1121-1130, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29272062

RESUMEN

AIM: To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long-term glycaemic control and the preservation of ß-cell function in people with type 2 diabetes mellitus (T2DM). METHODS: Newly diagnosed drug-naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow-up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti-glutamic acid decarboxylase autoantibody-positive. RESULTS: Both intensive treatment methods were effective for short-term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow-up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well-controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow-up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug-free glycaemic remission compared with the COAD method (P = .015). CONCLUSIONS: The findings indicate that outpatient clinic-based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in ß-cell function and glycaemic control over the long term, without serious adverse events.


Asunto(s)
Diabetes Mellitus Tipo 2/diagnóstico , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Metformina/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Adulto , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Resistencia a Múltiples Medicamentos , Quimioterapia Combinada/efectos adversos , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Hospitales Universitarios , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Resistencia a la Insulina , Secreción de Insulina/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Metformina/administración & dosificación , Metformina/efectos adversos , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , República de Corea , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Sulfonilurea/efectos adversos
2.
Artículo en Inglés | MEDLINE | ID: mdl-27901621

RESUMEN

Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells. Incubating MC3T3-E1 cells in different concentrations of PFOA for 48 h resulted in a concentration-dependent decrease in cell viability and significant inductions of ROS and mitochondrial superoxide. Moreover, PFOA induced MMP collapse, cardiolipin peroxidation, cytochrome c release, and decreased ATP levels, which in turn induced apoptosis or necrosis. When osteoblast differentiation markers were assessed, PFOA treatment caused a significant reduction in alkaline phosphatase activity, collagen synthesis, and mineralization in the cells. In summary, we found an ROS- and mitochondria-mediated pathway for the induction of cell damage by PFOA in MC3T3-E1 cells. Together, our results indicate that mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on osteoblast function.


Asunto(s)
Caprilatos/toxicidad , Fluorocarburos/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Apoptosis/efectos de los fármacos , Línea Celular/efectos de los fármacos , Línea Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Humanos , Ratones , Osteoblastos/metabolismo , Especies Reactivas de Oxígeno/metabolismo
3.
J Appl Toxicol ; 35(4): 350-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25042521

RESUMEN

Methylglyoxal (MG), a highly reactive metabolite of hyperglycemia, can enhance protein glycation, oxidative stress or inflammation. The present study investigated the effects of apocynin on the mechanisms associated with MG toxicity in osteoblastic MC3T3-E1 cells. Pretreatment of MC3T3-E1 cells with apocynin prevented the MG-induced protein glycation and formation of intracellular reactive oxygen species and mitochondrial superoxide in MC3T3-E1 cells. In addition, apocynin increased glutathione levels and restored the activity of glyoxalase I inhibited by MG. These findings suggest that apocynin provide a protective action against MG-induced cell damage by reducing oxidative stress and by increasing the MG detoxification system. Apocynin treatment decreased the levels of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 induced by MG. Additionally, the nitric oxide level reduced by MG was significantly increased by apocynin. These findings indicate that apocynin might exert its therapeutic effects via upregulation of glyoxalase system and antioxidant activity. Taken together, apocynin may prove to be an effective treatment for diabetic osteopathy.


Asunto(s)
Acetofenonas/farmacología , Antiinflamatorios no Esteroideos/farmacología , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hipoglucemiantes/farmacología , Osteoblastos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Piruvaldehído/antagonistas & inhibidores , Células 3T3 , Animales , Supervivencia Celular/efectos de los fármacos , Células Clonales , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Glutatión/agonistas , Glutatión/metabolismo , Productos Finales de Glicación Avanzada/agonistas , Productos Finales de Glicación Avanzada/metabolismo , Glicosilación/efectos de los fármacos , Humanos , Lactoilglutatión Liasa/antagonistas & inhibidores , Lactoilglutatión Liasa/química , Lactoilglutatión Liasa/genética , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/inmunología , Mitocondrias/metabolismo , Óxido Nítrico/agonistas , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Osteoblastos/inmunología , Osteoblastos/metabolismo , Piruvaldehído/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismo
4.
J Korean Med Sci ; 29(1): 84-9, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24431910

RESUMEN

Gestational diabetes mellitus (GDM) is a strong predictor of postpartum prediabetes and transition to overt type 2 diabetes (T2DM). Although many reports indicate that low magnesium is correlated with deteriorated glucose tolerance, the association between postpartum serum magnesium level and the risk for T2DM in women with a history of GDM has not been evaluated. We analyzed postpartum serum magnesium levels and development of prediabetes and T2DM in women with prior GDM according to American Diabetes Association (ADA) criteria using the Korean National Diabetes Program (KNDP) GDM cohort. During a mean follow-up of 15.6 ± 2.0 months after screening, 116 women were divided into three groups according to glucose tolerance status. Ultimately, eight patients (6.9%) were diagnosed with T2DM, 59 patients (50.9%) with prediabetes, and 49 patients (42.2%) with normal glucose tolerance (NGT) after follow-up. The T2DM group had the lowest serum magnesium level (0.65 [0.63-0.68] mM/L) in the postpartum period, but there was no significant difference between the prediabetes group (0.70 [0.65-0.70] mM/L) and the NGT group (0.70 [0.65-0.70] mM/L) (P=0.073) Multiple logistic regression analysis showed that postpartum HOMA-IR was a significant predictor of both prediabetes and T2DM. Moreover, we found that postpartum serum magnesium level was also a possible predictor for T2DM development. Serum magnesium level in the postpartum period may be a possible predictor for T2DM development in women with a history of GDM.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Gestacional/sangre , Intolerancia a la Glucosa/sangre , Magnesio/sangre , Periodo Posparto/sangre , Adulto , Glucemia , Estudios de Cohortes , Diabetes Mellitus Tipo 2/diagnóstico , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Estado Prediabético/diagnóstico , Embarazo , Estudios Prospectivos , República de Corea , Factores de Riesgo
5.
Nutr Res Pract ; 18(1): 78-87, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38352215

RESUMEN

BACKGROUND/OBJECTIVES: The prevalence of obesity, a worldwide pandemic, has been increasing steadily in Korea. Reports have shown that increased intermuscular adipose tissue (IMAT) is associated with an increased risk of cardiovascular disease, independent of body mass index. However, the relationship between dietary intake and IMAT accumulation in the Korean population remains undetermined. The objective of this study was to evaluate regional fat compartments using advanced magnetic resonance imaging (MRI) techniques. We also aimed to investigate the association between IMAT amounts and dietary intake, including carbohydrate intake, among Korean individuals with obesity. SUBJECTS/METHODS: This cross-sectional study, performed at a medical center in South Korea, recruited 35 individuals with obesity (15 men and 20 women) and classified them into 2 groups according to sex. Anthropometry was performed, and body fat distribution was measured using MRI. Blood parameters, including glucose and lipid profiles, were analyzed using commercial kits. Linear regression analysis was used to test whether the IMAT was associated with daily carbohydrate intake. RESULTS: Carbohydrate intake was positively associated with IMAT in all individuals, with adjustments for age, sex, height, and weight. No significant differences in blood indicators were found between the sexes. CONCLUSIONS: Regardless of sex and age, higher carbohydrate intake was strongly correlated with greater IMAT accumulation. This suggests the need to better understand sex differences and high carbohydrate diet patterns in relation to the association between obesity and metabolic risk, which may help reduce obesity prevalence.

6.
Cardiovasc Diabetol ; 12: 9, 2013 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-23302150

RESUMEN

BACKGROUND: Although an association between low-level environmental heavy metal exposure and the incidence of metabolic syndrome (MS) has been hypothesized, little research on this topic has been conducted on a population-wide level. METHODS: We analyzed MS status and whole blood lead, mercury, cadmium, manganese, and creatinine-adjusted urine arsenic concentrations in 1,405 subjects, ≥ 20 years of age, who were registered for the Korea National Health and Nutrition Examination Survey, 2008. RESULTS: Various demographic and biochemical parameters were associated with MS and blood heavy metal status. After adjusting for these variables, lead was the only heavy metal that was significantly associated with MS. Lead concentrations in subjects with MS were significantly higher than those in subjects without MS (p = 0.015). The prevalence of MS and a moderate/high risk for cardiovascular disease, as determined by Framingham risk score, also increased significantly according to the logarithmic transformation of the lead quartile (p < 0.001). The odds ratios and 95% confidence intervals for MS were 1.56 (0.90-2.71), 1.63 (0.94-2.83), and 2.57 (1.46-4.51) for the second, third, and fourth quartiles of the log-transformed lead quartile, respectively, as compared with those of the lowest quartile after multiple adjustments for confounding factors. Serum triglyceride level was the only MS diagnostic component significantly associated with lead level in a multiple linear regression analysis (p = 0.006). CONCLUSIONS: These findings suggest that a higher prevalence of MS is associated with higher blood lead levels in the Korean population.


Asunto(s)
Contaminantes Ambientales/sangre , Plomo/sangre , Síndrome Metabólico/sangre , Adulto , Factores de Edad , Anciano , Pueblo Asiatico , Biomarcadores/sangre , Carga Corporal (Radioterapia) , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Síndrome Metabólico/etnología , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Prevalencia , República de Corea/epidemiología , Factores de Riesgo , Factores de Tiempo , Adulto Joven
7.
J Korean Med Sci ; 28(6): 861-8, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23772150

RESUMEN

It has been suggested that there is an association between environmental, low-level arsenic exposure and the risk of diabetes mellitus (DM), but little research has been conducted. Here, the glucose tolerance status and urinary creatinine adjusted total arsenic concentrations were analyzed in 3,602 subjects ≥ 20 yr of age who were registered for the Korea National Health and Nutrition Examination Survey, 2008-2009. Various demographic parameters were associated with urinary arsenic concentrations. After adjusting for these variables, urinary arsenic concentrations in subjects with DM were significantly higher than those in subjects with normal glucose tolerance and those with impaired fasting glucose (P < 0.001). Compared with the lowest quartile ( < 70.7 µg/g creatinine), the odds ratios and 95% confidence intervals for DM were 1.11 (0.73-1.68), 1.42 (0.94-2.13), and 1.56 (1.03-2.36) for urinary arsenic concentrations of 70.7 to < 117.7, 117.7 to < 193.4, and ≥ 193.4 µg/g creatinine, respectively, following multivariate adjustment. Furthermore, the urinary total arsenic concentration was inversely associated with the insulin secretion index, HOMA2 %B (ß = -0.033, P = 0.032). These findings suggest that arsenic exposure, possibly involving beta cell dysfunction, is associated with an increased risk of DM in the Korean population.


Asunto(s)
Arsénico/orina , Diabetes Mellitus/epidemiología , Adulto , Consumo de Bebidas Alcohólicas , Pueblo Asiatico , Glucemia/análisis , Diabetes Mellitus/etiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Oportunidad Relativa , Prevalencia , República de Corea/epidemiología , Factores de Riesgo , Fumar
8.
Biol Pharm Bull ; 35(1): 121-6, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22223348

RESUMEN

Glucose toxicity contributes to progressive ß-cell failure and the development of overt diabetes. Oxidative stress is an important aspect of glucose toxicity in pancreatic ß-cells. We investigated whether the flavonoid apigenin protects pancreatic ß-cells from 2-deoxy-D-ribose (dRib)-induced oxidative cell damage. HIT-T15 pancreatic ß-cells were cultured with or without apigenin in the presence of dRib. Time- and dose-dependent cell viability was monitored using a cell counting kit (CCK-8), while the induction of apoptosis was analyzed using a cell death enzyme-linked immunosorbent assay (ELISA) kit. Mitochondrial membrane potential (ΔΨ(m)) was determined using the JC-1 kit. Intracellular oxidative stress was measured by fluorometric analysis of DCFH oxidation using 2',7'-dichlorofluorescin diacetate (DCFH-DA) as the probe. In addition, the DNA binding activity of the oxidative stress-related transcriptional factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were analyzed. dRib reduced cell survival and ΔΨ(m), while it markedly increased intracellular levels of reactive oxygen species (ROS), apoptosis, and the activity of the oxidative stress-related transcription factors NF-κB and AP-1. However, pretreatment of cells with apigenin attenuated all the dRib-induced effects. The anti-oxidants, N-acetyl-L-cysteine (NAC) and alpha lipoic acid (ALA), also prevented both dRib-induced oxidative damage and activation of NF-κB and AP-1. Taken together, these results suggest that apigenin attenuates dRib-induced cell damage in pancreatic ß-cells via oxidative stress-related signaling.


Asunto(s)
Antioxidantes/farmacología , Apigenina/farmacología , Desoxirribosa/efectos adversos , Glucosa/toxicidad , Células Secretoras de Insulina/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , ADN/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , FN-kappa B/metabolismo , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/metabolismo
9.
Endocr J ; 59(8): 709-16, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22673600

RESUMEN

Sarpogrelate, a selective 5-HT(2) receptor antagonist, is known to have a significant effect on antiplatelet action. This study was a double-blinded, randomized, paralleled multicenter trial to compare the effects of sarpogrelate and aspirin on preventing macrovascular complications in patients with type 2 diabetes. The subjects were randomly assigned to either the sarpogrelateor the aspirin group. The baseline parameters for macrovascular complications, such as intima media thickness (IMT), ankle-brachial index (ABI), IL-6, serotonin, adiponectin, and hsCRP, were measured before drug administration. Changes were compared at 6 and 12 months after the administration of each drug. A total of 127 subjects (63 in the sarpogrelate group and 64 in the aspirin group) were pooled during the study period. No significant differences were found in baseline IMT or in other predictors of macrovascular complications. The mean IMT increased in both groups after 12 months, but there was no significant difference between the two groups. No significant change was found in the other predictors of macrovascular complications nor in the incidence of drug-related adverse events between the two groups. During the study period, no significant differences were found between the sarpogrelate group and aspirin group in the clinical indices or in the safety of the subjects related to macrovascular complications. This suggests that sarpogrelate may be clinically useful for the primary prevention of macrovascular complications in patients with type 2 diabetes.


Asunto(s)
Angiopatías Diabéticas/prevención & control , Succinatos/uso terapéutico , Adiponectina/sangre , Adulto , Anciano , Índice Tobillo Braquial , Aspirina/uso terapéutico , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad
10.
J Korean Med Sci ; 27(8): 876-82, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22876053

RESUMEN

We analyzed the direct medical costs for Korean patients with type 2 diabetes according to the type of complications and the number of microvascular complications. We analyzed costs for type 2 diabetes and associated complications in 3,125 patients. These data were obtained from the Korean National Diabetes Program (KNDP), a large, ongoing, prospective cohort study that began in 2005. The cost data were prospectively collected, using an electronic database, for the KNDP cohort at six hospitals. The costs were analyzed according to complications for 1 yr from enrollment in the study. Among 3,125 patients, 918 patients had no vascular complications; 1,883 had microvascular complications only; 51 had macrovascular complications only; and 273 had both complications. The annual direct medical costs for a patient with only macrovascular, only microvascular, or both macrovascular and microvascular complications were 2.7, 1.5, and 2.0 times higher than the medical costs of patients without complications. Annual direct medical costs per patient increased with the number of microvascular complications in patients without macrovascular complications. The economic costs for type 2 diabetes are attributable largely to the management of microvascular and macrovascular complications. Proper management of diabetes and prevention of related complications are important for reducing medical costs.


Asunto(s)
Diabetes Mellitus Tipo 2/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Estudios de Cohortes , Costos y Análisis de Costo , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea , Enfermedades Vasculares/complicaciones , Adulto Joven
11.
J Korean Med Sci ; 27(10): 1188-95, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23091316

RESUMEN

The aim of the study was to assess the association between usual dietary nutrient intake and obesity in Korean type 2 diabetic patients. We examined 2,832 type 2 diabetic patients from the Korean National Diabetes Program cohort who completed dietary assessment and clinical evaluation in this cross-sectional study. In men, higher dietary fiber intake was associated with a lower odds of being obese (P(trend) = 0.003) and in women, higher protein intake was associated with a lower odds of being obese (P(trend) = 0.03) after adjustment for age, diabetes duration, HbA1c, alcohol drinking, income, education level, and calorie intake. In men, higher fiber intake was associated with lower odds of obesity after further adjustment for diastolic blood pressure, physical activity, and possible confounding nutritional intake and medication. The multivariable adjusted odds ratio for the highest quintile of fiber intake was 0.37 (P(trend) < 0.001). In women, protein intake was not associated with obesity after further adjustment. In conclusion, higher intake of dietary fiber is associated with lower odds of being obese in type 2 diabetic men, suggesting a role for dietary fiber in the management and prevention of obesity in type 2 diabetes (ClinicalTrials.gov: NCT 01212198).


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Ingestión de Energía , Obesidad/etiología , Pueblo Asiatico , Estudios de Cohortes , Estudios Transversales , Demografía , Diabetes Mellitus Tipo 2/diagnóstico , Fibras de la Dieta , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , República de Corea , Factores de Riesgo
12.
Heliyon ; 8(6): e09571, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35711980

RESUMEN

Background: The formation of advanced glycation end products (AGEs) takes place during normal aging; however, their production is faster in people having diabetes. The accumulated AGEs reportedly play a role in the occurrence of various age-related disorders. Furthermore, the skin autofluorescence (SAF) technique can be used to detect accumulated AGEs levels. There are few reports on the association between skin accumulation of AGEs and risk of complications in type 2 diabetes mellitus. Methods: In this study, we aimed to describe the association between the skin accumulation of AGEs and cardiovascular risk factors in Korean patients with type 2 diabetes. A total of 310 Korean patients with diabetes were enrolled, and the levels of AGEs were measured using SAP. Levels of fasting blood glucose (FBS), triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol, proteinuria, arterial pulse wave velocity (PWV), and blood vessel age were measured using an automatic waveform analyzer. General linear models were used to identify the independent effect of AGEs after adjusting for covariates (age, weight, and duration of diabetes). Results: The skin levels of AGEs were strongly correlated with the diabetes duration. Significant independent associations were observed for AGEs with FBS (P < 0.01), proteinuria (P < 0.001), and PWV (P < 0.001). The advanced glycated product was independently associated to the arterial pulse wave conduction velocity that is used as a representative method for measuring arteriosclerosis by analysis early cardiovascular risk factors. Conclusion: Our results show that an increase in SAF levels in Korean patients with type 2 diabetes is associated with PWV and vein age, and thereby with arterial stiffness. Therefore, our results suggest that AGEs are associated with cardiovascular risk factors. The level of AGEs can thus be used as an indicator of cardiovascular diseases in the clinical diagnosis of patients with type 2 diabetes.

13.
Metab Syndr Relat Disord ; 20(10): 551-557, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36269325

RESUMEN

Background: Obesity is commonly associated with a high risk of metabolic disorders, and obesity-related metabolic abnormalities are affected by some specific obesity phenotypes, regional fat distribution, and body mass index. However, few studies have investigated the relationship between obesity phenotypes and regional fat distribution in Korean subjects. This study aimed to assess regional fat distribution by gender using magnetic resonance imaging (MRI), and to identify a link between fat distribution and metabolic disorders in Korean subjects. Methods: This study included 35 Korean subjects (20 women, 15 men) who were classified into two groups by gender, and further divided into two groups based on their obesity phenotype: a metabolically abnormal obesity (MAO) and metabolically healthy obesity (MHO) group. Fat distribution was measured using MRI. The blood parameters were measured using a commercially available kit. Results: Women in the MAO group had more risk factors for metabolic abnormalities than those in the MHO group. Serum glucose, triglyceride, and high-density lipoprotein cholesterol (HDL-C) levels were also significantly higher in women with MAO than in those with MHO. The intermuscular adipose tissue (IMAT) of women with MAO was significantly higher than that of women with MHO. Serum HDL-C level was negatively correlated with IMAT, whereas leptin showed a positive correlation with IMAT in all subjects. Conclusions: Metabolic abnormalities according to obesity phenotype posed a higher risk in women than that in men. These findings suggest that an understanding of gender differences in relation to the association between obesity and metabolic risk would be helpful to reduce the prevalence of obesity.


Asunto(s)
Enfermedades Metabólicas , Obesidad Metabólica Benigna , Humanos , Femenino , Pueblos del Este de Asia , Obesidad/diagnóstico por imagen , Obesidad/epidemiología , Obesidad/complicaciones , Tejido Adiposo/metabolismo , Obesidad Metabólica Benigna/complicaciones , Fenotipo , Enfermedades Metabólicas/metabolismo , Imagen por Resonancia Magnética , Monoaminooxidasa/metabolismo
14.
Circulation ; 121(23): 2584-91, 2010 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-20516379

RESUMEN

BACKGROUND: Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetic patients. However, the efficacy and usefulness of 2 different antiplatelet drugs, aspirin and cilostazol, in the progression of carotid intima-media thickening are unknown. METHODS AND RESULTS: To compare prevention by cilostazol and aspirin of progression of atherosclerosis, we conducted a prospective, randomized, open, blinded end point study in 4 East Asian countries. A total of 329 type 2 diabetic patients suspected of peripheral artery disease were allocated to either an aspirin-treated (81 to 100 mg/d) group or a cilostazol-treated (100 to 200 mg/d) group. The changes in intima-media thickness of the common carotid artery during a 2-year observation period were examined as the primary end point. The regression in maximum left, maximum right, mean left, and mean right common carotid artery intima-media thickness was significantly greater with cilostazol compared with aspirin (-0.088 + or - 0.260 versus 0.059 + or - 0.275 mm, P<0.001; -0.042 + or - 0.274 versus 0.045 + or - 0.216 mm, P=0.003; -0.043 + or - 0.182 versus 0.028 + or - 0.202 mm, P=0.004; and -0.024 + or - 0.182 versus 0.048 + or - 0.169 mm, P<0.001). In a regression analysis adjusted for possible confounding factors such as lipid levels and hemoglobin A(1c), the improvements in common carotid artery intima-media thickness with cilostazol treatment over aspirin treatment remained significant. CONCLUSIONS: Compared with aspirin, cilostazol potently inhibited progression of carotid intima-media thickness, an established surrogate marker of cardiovascular events, in patients with type 2 diabetes mellitus. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: C000000215.


Asunto(s)
Enfermedades de las Arterias Carótidas/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Fosfodiesterasa/uso terapéutico , Tetrazoles/uso terapéutico , Anciano , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/enzimología , Aterosclerosis/etiología , Enfermedades de las Arterias Carótidas/enzimología , Enfermedades de las Arterias Carótidas/etiología , Cilostazol , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
15.
Cell Physiol Biochem ; 28(5): 873-86, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22178940

RESUMEN

Mitochondrial oxidative damage is thought to play a key role in pancreatic ß-cell failure in the pathogenesis of type 2 diabetes. Despite this, the potential of mitochondria-targeted antioxidants to protect pancreatic ß-cells against oxidative stress has not yet been studied. Therefore, we investigated if mitochondria-targeted antioxidants protect pancreatic ß-cells such as RINm5F and HIT-T15 cells against oxidative stress under glucotoxic and glucolipotoxic conditions. When ß-cells were incubated under these conditions, the expression levels of mitochondrial electron transport chain complex subunits, mitochondrial antioxidant enzymes (such as MnSOD and Prx3), ß-cell apoptosis, lipogenic enzymes (such as ACC, FAS and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, mitochondrial membrane depolarization, nuclear NF- κB and sterol regulatory element binding protein 1c (SREBP1c) were all increased, in parallel with decreases in intracellular ATP content, citrate synthase enzymatic activity and glucose-stimulated insulin secretion. These changes were consistent with elevated mitochondrial oxidative stress, and incubation with the mitochondria-targeted antioxidants, MitoTempol or Mitoquinone (MitoQ), prevented these effects. In conclusion, mitochondria-targeted antioxidants protect pancreatic ß-cells against oxidative stress, promote their survival, and increase insulin secretion in cell models of the glucotoxicity and glucolipotoxicity associated with Type 2 diabetes.


Asunto(s)
Antioxidantes/farmacología , Glucosa/toxicidad , Células Secretoras de Insulina/efectos de los fármacos , Insulina/metabolismo , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Línea Celular , Cricetinae , Proteínas de Homeodominio/metabolismo , Secreción de Insulina , Mitocondrias/metabolismo , Membranas Mitocondriales/efectos de los fármacos , FN-kappa B/metabolismo , Compuestos Organofosforados/farmacología , Ratas , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Superóxido Dismutasa/metabolismo , Ubiquinona/farmacología
16.
Cell Biol Toxicol ; 26(3): 189-99, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19757103

RESUMEN

Epigallocatechin-3-gallate (EGCG) is the main polyphenolic constituent in green tea and is believed to function as an antioxidant. However, increasing evidence indicates that EGCG produces reactive oxygen species (ROS) and subsequent cell death. In this study, we investigated the prooxidative effects of EGCG on the HIT-T15 pancreatic beta cell line. Dose-dependent cell viability was monitored with the cell counting kit-8 assay, while the induction of apoptosis was analyzed by a cell death ELISA kit and comet assay. Extracellular H(2)O(2) was determined using the Amplex Red Hydrogen Peroxide Assay Kit. Intracellular oxidative stress was measured by fluorometric analysis of 2',7'-dichlorofluorescin (DCFH) oxidation using DCFH diacetate (DA) as the probe. Treatment with EGCG (5-100 microM) decreased the viability of pancreatic beta cells, caused concomitant increases in apoptotic cell death, and increased the production of H(2)O(2) and ROS. Catalase, the iron-chelating agent diethylenetriaminepentaacetic acid, and the Fe(II)-specific chelator o-phenanthroline all suppressed the effects of EGCG, indicating the involvement of both H(2)O(2) and Fe(II) in the mechanism of action of EGCG. The antioxidant N-acetyl-cysteine and alpha-lipoic acid also suppressed the effects of EGCG. Furthermore, EGCG did not scavenge exogenous H(2)O(2), but rather, it synergistically increased H(2)O(2)-induced oxidative cell damage in pancreatic beta cells. Together, these findings suggest that in the HIT-T15 pancreatic beta cell line, EGCG mediated the generation of H(2)O(2), triggering Fe(II)-dependent formation of a highly toxic radical that in turn induced oxidative cell damage.


Asunto(s)
Catequina/análogos & derivados , Células Secretoras de Insulina/efectos de los fármacos , Oxidantes/toxicidad , Apoptosis/efectos de los fármacos , Catequina/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Flavonoides/toxicidad , Peróxido de Hidrógeno/metabolismo , Células Secretoras de Insulina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fenoles/toxicidad , Polifenoles , Especies Reactivas de Oxígeno/metabolismo , Té/química
17.
Phytother Res ; 24(3): 419-23, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19827031

RESUMEN

During the progression of Type 2 diabetes, glucose toxicity is likely to contribute importantly to progressive beta cell failure. Oxidative stress is an important aspect of glucose toxicity in pancreatic beta cells, and reducing sugars, such as 2-deoxy-D-ribose (dRib), produce reactive oxygen species. Furthermore, many of the biological properties of flavonoids are likely to be related to their antioxidant and free-radical scavenging abilities. Accordingly, in the present study, we investigated whether kaempferol (a flavonol) protects beta cells from dRib-induced oxidative damage. HIT-T15 cells were cultured with various concentrations of dRib for 24h. Cell survivals, amounts of reactive oxygen species (ROS) generated, apoptosis, and lipid peroxidation were measured. dRib was found to dose-dependently reduce cell survival and to markedly increase intracellular ROS levels, apoptosis, and lipid peroxidation. However, kaempferol (10 microM) suppressed dRib (20 mM) induced intracellular ROS, apoptosis, and lipid peroxidation. So, we demonstrate that kaempferol reduces dRib-mediated beta cell damage interfering with ROS metabolism and protective effects against lipid peroxidation. Our findings indicate that kaempferol protects HIT-T15 cells from dRib-induced associated oxidative damage.


Asunto(s)
Desoxirribosa , Células Secretoras de Insulina/efectos de los fármacos , Quempferoles/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Apoptosis , Línea Celular , Supervivencia Celular , Humanos , Peroxidación de Lípido , Especies Reactivas de Oxígeno/metabolismo
18.
Clin Nutr Res ; 9(3): 205-212, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32789150

RESUMEN

The relationship between phase angle (PhA) of bioelectrical impedance analysis (BIA) and glycemic parameters in diabetes mellitus (DM) patients has not been well studied. To evaluate the prognostic value of the PhA from BIA as a glycemic marker, we investigated the relationship of PhA with various variables such as age, body mass index (BMI), and glycemic parameters in Korean patients with type 2 DM (T2DM). We evaluated the anthropometric data, body composition, glycemic parameters, and PhA of 321 T2DM patients aged 30-83 years. The patients were classified by sex into men (n = 133) and women (n = 188). General linear models identified the independent effects of PhA after covarying for age, sex and BMI. The PhA, body cell mass (BCM), extracellular mass (ECM), lean body mass, intracellular water (ICW), extracellular water (ECW), total body water (TBW), fasting blood glucose, and hemoglobin A1c (HbA1c) of T2DM Korean patients were significantly higher in men than in women. However, fat mass, ECM/BCM, ECW/ICW, ECW/TBW, and serum insulin were significantly higher in women than in men. Statistically significant independent associations were observed between PhA and age, BCM, ECM, ECM/BCM, ICW, ECW, ECW/ICW, and ECW/TBW for both sexes. There was no significant association between PhA and BMI the patients. Glycemic parameters, such as HbA1c and fasting blood glucose were independently associated with PhA. These results suggest that PhA could be an indicator for assessing ability to control fasting blood glucose in T2DM patients in Korea.

19.
Diabetes Metab J ; 43(6): 840-853, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-30877715

RESUMEN

BACKGROUND: Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function. METHODS: In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year. RESULTS: Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P<0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; P<0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, P=0.016). CONCLUSION: Close monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.


Asunto(s)
Estenosis Carotídea/etiología , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Placa Aterosclerótica/etiología , Adulto , Anciano , Biomarcadores , Grosor Intima-Media Carotídeo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo
20.
Diabetes Metab J ; 2018 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-30112876

RESUMEN

In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are actively produced and accumulated in the circulating blood and various tissues. AGEs also accelerate the expression of receptors for AGEs, and they play an important role in the development of diabetic vascular complications through various mechanisms. Active interventions for glucose and related risk factors may help improve the clinical course of patients by reducing AGEs. This review summarizes recent updates on AGEs that have a significant impact on diabetic vascular complications.

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