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OBJECTIVES: The hemoglobin glycation index (HGI) quantifies interindividual variations in glycated hemoglobin (HbA1c) and is associated with diabetic complications and metabolic diseases. However, information on the association between HGI and non-alcoholic fatty liver disease (NAFLD) in healthy subjects is limited, particularly in Asian populations. This study aimed to investigate the association between HGI and NAFLD in a healthy Korean cohort. DESIGN: Subjects were stratified in quartiles according to their HGI level. NAFLD was diagnosed by hepatic ultrasonography, hepatic steatosis index and fatty liver index. Multiple logistic regression analysis was performed to evaluate the association between HGI quartiles and the risk of NAFLD. PATIENTS: Data from subjects without diabetes who underwent liver ultrasonography during routine health examinations were retrospectively reviewed. RESULTS: Data from 14 465 subjects were included in the analysis. The prevalence of NAFLD increased significantly with each HGI quartile (24.8%, 29.7%, 32.6% and 40.6% in quartiles 1-4, respectively; P < 0.001). In comparison with the lowest HGI quartile group, the highest quartile exhibited worse metabolic parameters, including body weight, waist circumference, body mass index and lipid profiles. Multiple logistic regression analysis adjusted for multiple factors showed that the odds ratio of having NAFLD was 1.564 (95% CI: 1.350-1.813, P < 0.001) in the highest HGI quartile. CONCLUSIONS: Elevated HGI levels are independently associated with NAFLD in a healthy Asian population.
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Hemoglobinas Glicadas/análise , Voluntários Saudáveis/estatística & dados numéricos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Ásia/epidemiologia , Povo Asiático/estatística & dados numéricos , Índice de Massa Corporal , Feminino , Inquéritos Epidemiológicos/métodos , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Lipídeos/sangue , Fígado/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Estudos Retrospectivos , Ultrassonografia/métodos , Circunferência da CinturaRESUMO
BACKGROUND: Previous studies reported mixed results regarding the association between cognition and body weight in late life. We evaluated the relationships between cognitive function and body composition among community-dwelling older adults. METHODS: Three hundred twenty subjects (≥65 years, women 53%) with available data of cognitive function and body composition from 2010 Hallym Aging Study. Cognitive function was assessed using Korean Mini-Mental State Examination (K-MMSE). Dual-energy X-ray absorptiometry (DEXA) was used for measuring body composition including body fat and lean body mass. Anthropometric measurements and laboratory data were collected in clinical examination. Body composition variables were divided into sex-specific tertiles, and examined by multivariable logistic regression. RESULTS: Among female, the highest tertile group of fat mass and second tertile group of total lean body mass were associated with lower risk for cognitive impairment compared to the respective first tertile groups (odds ratios, 0.23 and 0.09, respectively; 95% confidence intervals, 0.04-0.88 and 0.01-0.44, respectively) after adjusting for confounding factors. In male, higher arm bone mineral content was associated with lower risk for cognitive impairment, but significance was lost after adjusting for adiponectin, age, and education. CONCLUSIONS: Higher fat mass and lean body mass were associated with lower risk of cognitive impairment in older women. These observations suggest that body fat and lean mass later in life might be beneficial for cognition.
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Povo Asiático , Composição Corporal/fisiologia , Cognição/fisiologia , Vida Independente , Absorciometria de Fóton , Adiponectina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Testes Neuropsicológicos , Razão de Chances , República da CoreiaRESUMO
Discordance has been proposed as a new predictor of fracture risk that may affect fracture risk via bone mineral density (BMD). With an emphasis on better understanding the relationship between discordance and BMD, the aim of this study was to determine the effect of the number of osteoporotic sites, as an indicator of discordance, on BMD and to explore the clinical significance of BMD modification by this factor. This study was based on data obtained from the Korea National Health and Nutrition Examination Survey 2008-2011, which is a nationwide cross-sectional study. Among postmenopausal women aged 50 years or older, 3,849 women whose BMD was measured at three sites (lumbar spine, femoral neck, and total hip) were included in the study. The diagnosis was consistent across sites in only 39.2-59.0 % of cases. Lumbar spine T-score was reduced by 0.163 for two osteoporotic sites and by 0.462 for three osteoporotic sites, compared with having one osteoporotic site at the lumbar spine only. Femoral neck T-score was reduced by 0.609 for three osteoporotic sites compared with one or two osteoporotic sites. Using BMD adjusted for discordance, we found fracture risk probability changed significantly. Our results confirmed that BMD discordance was considerably high among Korean women in their 50s and older owing to site-dependent differences in the pattern of BMD reduction with age. Mean BMD decreased with increasing number of osteoporotic sites. Using a modified BMD adjusted for the number of osteoporotic sites may offer more accurate fracture risk assessment.
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Densidade Óssea , Fraturas por Osteoporose/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Prevalência , Probabilidade , Fatores de RiscoRESUMO
BACKGROUND: Since the reference value is the core factor of the T-score calculation, it has a significant impact on the prevalence of osteoporosis. The purpose of this study was to determine the effects of using the Korean reference value on the prevalence of osteoporosis and on the prediction of fracture risk. METHODS: We used femoral neck bone mineral density (BMD) data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011. The Korean reference was identified by the mean and standard deviation of men and women aged 20-29 years. We compared the prevalence and the fracture risk assessment tool (FRAX™) probability obtained from the Korean reference and the NHANES III reference. RESULTS: In men, the prevalence of osteoporosis increased when using the Korean men's reference, and the difference increased up to 9% for those in their 80s. In women, the prevalence increased when using the NHANES III reference, and the difference increased up to 17% for those in their 80s. The reference value also affected the fracture risk probability, and the difference from changing the reference value increased in women and in subjects with more clinical fracture risk factors. In major osteoporotic fractures, the difference of the risk probability was up to 6% in women aged 70-79 years with two clinical risk factors. For femoral neck fractures, the difference was up to 7% in women aged 50-59 years with two clinical risk factors. CONCLUSIONS: We confirmed that the reference value had significant effects on the prevalence of osteoporosis and on the fracture risk probability. The KNHANES 2008-2011 BMD data reflected the characteristics of the Korean BMD status well with regard to data size and study design; therefore, these data can be used as reference values.
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Fraturas Ósseas/etnologia , Fraturas Ósseas/epidemiologia , Inquéritos Nutricionais/normas , Osteoporose/etnologia , Osteoporose/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Valor Preditivo dos Testes , Prevalência , Valores de Referência , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
Obesity and osteoporosis are two important body composition problems with increasing prevalences in aged populations. Traditionally, obesity has been regarded as being beneficial to bone health. However, the protective effect of obesity on osteoporosis has been questioned. In some recent studies, obesity, as defined by percentage body fat, was regarded as a risk factor for osteoporosis. The purpose of this study was to (1) evaluate the effect of waist circumference, a surrogate measure for abdominal obesity, on bone mineral content (BMC) and (2) examine whether the effect of waist circumference increases with advancing age. The study population is made up of women aged over 45 years who completed the body composition and bone mineral density examinations in the fifth Korea National Health and Nutrition Examination Survey in 2010. Subjects who take estrogen or are under medical treatment for osteoporosis were excluded. Stroke patients are also excluded. Femoral neck, total-hip, and whole-body BMC were measured by dual-energy X-ray absorptiometry. A total of 1,434 subjects were included in the analysis. Waist circumference was negatively associated with BMC in all tested regions after correction for weight, menopausal status, smoking, drinking, and exercise. In addition, the negative association between waist circumference and BMC in the femoral neck and total hip increases with age, after correction for confounding factors, showing an interaction effect between waist circumference and age on BMC. In conclusion, this study shows that the negative relationship between waist circumference and BMC in the femoral neck and total hip is greater for older women.
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Densidade Óssea/fisiologia , Obesidade/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Análise dos Mínimos Quadrados , Pessoa de Meia-Idade , Circunferência da CinturaRESUMO
BACKGROUND: Ultraviolet irradiation by sun exposure has been associated with both harms and benefits to metabolic health. OBJECTIVE: The objective of this study was to determine whether unprotected daily sun exposure is associated with the prevalence of diabetes and explore the underlying mechanism. METHODS: We analyzed the Korean National Health and Nutrition Survey V from 2010 to 2011. Participants 19-60 years of age were asked about the average amount of time they had been exposed to direct sunlight per day since the age of 19. We categorized participants into three groups with different levels of lifetime daily sun exposure and explored the association of sun exposure with the prevalence of diabetes. RESULTS: The risk of diabetes was higher in subjects with more than 5h of unprotected sun exposure per day, with an odds ratio of 2.39 (95% CI 1.75-3.25), compared to those with less than 2h of sun exposure, and the association remained significant after adjusting for diabetes risk factors. Long-term sun exposure was associated with increased central obesity and the possibility of an increase in visceral adiposity, especially among women, and with decrease in beta cell function and peripheral adiposity or percent body fat in men. CONCLUSIONS: Our study provides a cutoff for upper limit of sun exposure and suggests unprotected daily sun exposure for more than 5h should be avoided to prevent diabetes. Increased central adiposity and decreased beta cell function were observed in women and men, respectively, who had long-term unprotected daily sun exposure.
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Adiposidade , Diabetes Mellitus/epidemiologia , Inquéritos Nutricionais , Obesidade/epidemiologia , Luz Solar/efeitos adversos , Adulto , Diabetes Mellitus/etiologia , Diabetes Mellitus/patologia , Feminino , Humanos , Resistência à Insulina/efeitos da radiação , Células Secretoras de Insulina/patologia , Células Secretoras de Insulina/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Obesidade/etiologia , Obesidade/patologia , Prevalência , República da Coreia/epidemiologia , Caracteres Sexuais , Adulto JovemRESUMO
BACKGROUND AND AIMS: Seasonal variations in lifestyle, such as food intake and physical activity, have been reported. Glycemic control in type 2 diabetes mellitus (T2DM) may be affected by such changes. We investigated seasonal variations in glycemic control, food intake, and physical activity in type 2 diabetic patients. METHODS: This prospective observational study included 37 Korean female patients who had <8.0 % hemoglobin A1c (HbA1c) and managed diabetes by oral anti-diabetic drugs or lifestyle modification only. Participants underwent four or five assessments, including total physical activity (household, leisure-time, and occupational activity) (metabolic equivalent of test-h/day), food intake (kcal/day), HbA1c, and anthropometry every 3 months (August, November, February, May, and August in the Northern Hemisphere) over 1 year. When anti-diabetic drugs were changed, we analyzed the data just before the changes. RESULTS: The mean HbA1c levels (%) of August and November in 2008, and February, May, and August in 2009 were 7.0 ± 0.1, 6.9 ± 0.1, 7.2 ± 0.2, 7.4 ± 0.2, and 7.2 ± 0.2, respectively (P = 0.018). The change of HbA1c was nearly 0.5 % for the 1-year period. From August to May of the following year, there were also seasonal variations in food intake (1,872 ± 143, 1,739 ± 97, 1,673 ± 86, 1,561 ± 132, respectively; P = 0.013), and total physical activity [7.7 (3.7-14.6), 6.3 (2.8-10.4), 5.1 (2.7-12.6), and 11.2 (4.7-20.5), respectively; P = 0.048]. However, the seasonal variations of HbA1c and total physical activity became non-significant when farmers were excluded. CONCLUSIONS: These data suggested that glycemic control, total physical activity, and food intake varied seasonally in Korean T2DM patients. These seasonal variations should be considered in education for glycemic control.
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Glicemia , Diabetes Mellitus Tipo 2/sangue , Ingestão de Alimentos/fisiologia , Exercício Físico/fisiologia , Hemoglobinas Glicadas/análise , Estilo de Vida , Estações do Ano , Adulto , Idoso , Povo Asiático , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , República da CoreiaRESUMO
Epidemiologic studies have shown that low vitamin D levels are associated with reduced insulin sensitivity and increased risk of developing type 2 diabetes mellitus (T2DM). However, there is little evidence that vitamin D supplementation improves glucose intolerance. We evaluated the glucose-lowering effect of vitamin D in Korean T2DM subjects. We enrolled 158 T2DM patients who had stable glycemic control [hemoglobin A1c (HbA1c) <8.5%] and vitamin D levels less than 20 ng/mL. The participants were randomized into two groups: Placebo (100 mg daily of elemental calcium administered twice a day) or Vitamin D (1000 IU daily of cholecalciferol combined with 100 mg of elemental calcium administered twice a day). We compared outdoor physical activity, glycemic control, homeostasis model of assessment - insulin resistance (HOMA-IR), and parathyroid hormone (PTH), during the 24-week intervention. We analyzed the data of 129 participants (placebo =65, vitamin D =64) who completely followed the protocol. Outdoor physical activity and oral anti-diabetic drugs did not differ between the groups. While there were significant differences in the vitamin D levels (15.6 ± 7.1 ng/mL vs 30.2 ± 10.8 ng/mL, P<0.001) and change in PTH levels (1.4 ± 15.3 pg/mL vs -5.5 ± 9.8 pg/mL, P=0.003) between the placebo and vitamin D groups, there were no differences in HbA1c (7.27 ± 0.87% vs 7.40 ± 0.90%) (P=0.415) and HOMA-IR. Serum calcium and kidney function results showed that the vitamin D supplementation was safe. While vitamin D supplementation is safe and effective in the attainment of vitamin D sufficiency, it had no effect on long-term glycemic control for T2DM in our study.
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Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Deficiência de Vitamina D/tratamento farmacológico , Adulto , Idoso , Glicemia , Cálcio , Cálcio da Dieta/uso terapêutico , Diabetes Mellitus Tipo 2/etiologia , Método Duplo-Cego , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo , República da Coreia , Deficiência de Vitamina D/complicaçõesRESUMO
BACKGROUND: Body composition changes with ageing can influence the adiponectin concentration. However, the component of body composition that is associated with adiponectin concentrations in older adults remains unclear. METHODS: There were 152 males and 168 females aged 65 years or older that participated in the 2010 Hallym Aging Study (HAS). Body composition (assessed by dual energy X-ray absorptiometry; DXA), anthropometric parameters and adiponectin were obtained from all participants. Multivariate linear regression models assessed the association of body fat percentage, regional muscle and bone mineral contents of body composition and waist/height ratio with adiponectin concentration. Age, albumin, testosterone concentration and metabolic parameters were considered as confounding factors. RESULTS: In correlation analysis, age was positively associated with adiponectin in males (P < 0.01), but not in females. Fasting glucose, albumin, arm skeletal muscle mass and bone mineral content were negatively associated with adiponectin in males (P < 0.05). Testosterone and leg bone mineral content were negatively associated with adiponectin in females (P < 0.05). In multivariate linear regression models, body fat percentage and albumin (P < 0.05) were negatively associated with adiponectin, and high-density lipoprotein cholesterol (HDL-C) (P < 0.001) and age (P < 0.01) were positively associated with adiponectin in older males. In older females, the only factors that correlated significantly with adiponectin concentration were the homeostasis model assessment of insulin resistance (P < 0.001) and HDL-C (P < 0.05). The waist/height ratio and bone mineral content were not associated with adiponectin in either gender. CONCLUSION: Plasma adiponectin levels correlated negatively with body fat percentage in older males but not in older females. The differential results between older males and females suggest that certain gender-specific mechanisms may affect the association between adiponectin and age-related body composition changes.
Assuntos
Adiponectina/sangue , Envelhecimento/sangue , Composição Corporal/fisiologia , Caracteres Sexuais , Absorciometria de Fóton/métodos , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Biomarcadores/sangue , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologiaRESUMO
We investigated the frequency of sleep disturbances and the association between sleep disturbances and glucoregulation in type 2 diabetic patients. The frequency of sleep disturbances in 614 type 2 diabetic patients was investigated using validated sleep questionnaires. There were 381 male and 233 female patients. The mean age was 59.7 ± 11.1 yr; the mean body mass index was 24.9 ± 4.4 kg/m(2); the mean HbA1c was 7.8% ± 1.5%; and the mean duration of diabetes was 10.3 ± 8.4 yr. The questionnaires revealed insomnia in 48.2% of the patients while 8.5% reported excessive daytime sleepiness. A total of 49% of the patients was poor sleepers, while 28.5% had depression. Multivariate logistic regression analysis showed that there was no significant association between HbA1c and other sleep disturbances, such as poor sleep, insomnia, and short duration of sleep. Sleep disturbances were very common in patients with type 2 diabetes mellitus, whereas there was no association between poor or short sleep and glucoregulation. Awareness and identifying sleep complaints in such patients are necessary to improve their quality of daily life.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Transtornos do Sono-Vigília/complicações , Adulto , Idoso , Índice de Massa Corporal , Depressão/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Inquéritos e QuestionáriosRESUMO
The possible roles of spinal histamine receptors in the regulation of the blood glucose level were studied in ICR mice. Mice were intrathecally (i.t.) treated with histamine 1 (H1) receptor agonist (2-pyridylethylamine) or antagonist (cetirizine), histamine 2 (H2) receptor agonist (dimaprit) or antagonist (ranitidine), histamine 3 (H3) receptor agonist (α-methylhistamine) or antagonist (carcinine) and histamine 4 (H4) receptor agonist (VUF 8430) or antagonist (JNJ 7777120), and the blood glucose level was measured at 30, 60 and 120 min after i.t. administration. The i.t. injection with α-methylhistamine, but not carcinine slightly caused an elevation of the blood glucose level. In addition, histamine H1, H2, and H4 receptor agonists and antagonists did not affect the blood glucose level. In D-glucose-fed model, i.t. pretreatment with cetirizine enhanced the blood glucose level, whereas 2-pyridylethylamine did not affect. The i.t. pretreatment with dimaprit, but not ranitidine, enhanced the blood glucose level in D-glucose-fed model. In addition, α-methylhistamine, but not carcinine, slightly but significantly enhanced the blood glucose level D-glucose-fed model. Finally, i.t. pretreatment with JNJ 7777120, but not VUF 8430, slightly but significantly increased the blood glucose level. Although histamine receptors themselves located at the spinal cord do not exert any effect on the regulation of the blood glucose level, our results suggest that the activation of spinal histamine H2 receptors and the blockade of spinal histamine H1 or H3 receptors may play modulatory roles for up-regulation and down-regulation, respectively, of the blood glucose level in D-glucose fed model.
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BACKGRUOUND: The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population. METHODS: Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (≥100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs. RESULTS: A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34-3.18, 4.74±3.57 and 1.14-8.33, and 4.85±3.58 and 1.25-8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels. CONCLUSION: The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields.
Assuntos
Glicemia , Peptídeo C , Humanos , Peptídeo C/sangue , República da Coreia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Glicemia/análise , Teste de Tolerância a Glucose/normas , Padrões de Referência , Valores de Referência , Hemoglobinas Glicadas/análise , Adulto Jovem , Idoso , Biomarcadores/sangueRESUMO
In patients with mild cognitive impairment (MCI), a lower level of cognitive function is associated with a higher likelihood of progression to dementia. In addition, gait disturbances and structural changes on brain MRI scans reflect cognitive levels. Therefore, we aimed to classify MCI based on cognitive level using gait parameters and brain MRI data. Eighty patients diagnosed with MCI from three dementia centres in Gangwon-do, Korea, were recruited for this study. We defined MCI as a Clinical Dementia Rating global score of ≥0.5, with a memory domain score of ≥0.5. Patients were classified as early-stage or late-stage MCI based on their mini-mental status examination (MMSE) z-scores. We trained a machine learning model using gait and MRI data parameters. The convolutional neural network (CNN) resulted in the best classifier performance in separating late-stage MCI from early-stage MCI; its performance was maximised when feature patterns that included multimodal features (GAIT + white matter dataset) were used. The single support time was the strongest predictor. Machine learning that incorporated gait and white matter parameters achieved the highest accuracy in distinguishing between late-stage MCI and early-stage MCI.
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Social Network Analysis (SNA) provides a dynamic framework for examining interactions and connections within networks, elucidating how these relationships impact behaviors and outcomes. This study targeted small residential communities in Gangwon State, South Korea, to explore network formation theories and derive strategies for enhancing health promotion services in rural communities. Conducted in 12 small residential areas, the survey led to a network categorization model distinguishing networks as formal, informal, or non-existent. Key findings demonstrated that demographic and socio-economic factors, specifically age, income, living environment, leisure activities, and education level, significantly influence network formation. Importantly, age, environmental conditions, satisfaction with public transportation, and walking frequency were closely associated with the evolution of formal networks. These results highlight the importance of early community network assessments, which must consider distinct network traits to develop effective health promotion models. Utilizing SNA early in the assessment process can improve understanding of network dynamics and optimize the effectiveness of health interventions.
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Análise de Rede Social , República da Coreia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Fatores Socioeconômicos , Rede Social , População Rural , Idoso , Características de Residência , Promoção da Saúde , Apoio Social , Adulto JovemRESUMO
Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
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The possible involvement of glucocorticoid system in interleukin-1ß (IL-1ß)-induced nociception and the blood glucose level was studied in ICR mice. In the first experiment, mice were treated intrathecally (i.t.) with IL-1ß (100 pg). Corticotrophin releasing hormone (CRH) mRNA (hypothalamus) and c-Fos mRNA (pituitary gland, spinal cord, and the adrenal gland) levels were measured at 30, 60 and 120 min after IL-1ß administration. We found that i.t. injection with IL-1ß increased CRH mRNA level in the hypothalamus. The IL-1ß administered i.t. elevated c-Fos mRNA levels in the spinal cord, pituitary and adrenal glands. Furthermore, i.t. administration of IL-1ß significantly increased the plasma corticosterone level up to 60 min. In addition, the adrenalectomy caused the reductions of the blood glucose level and pain behavior induced by IL-1ß injected i.t. in normal and D-glucose-fed groups. Furthermore, intraperitoneal (i.p.) pretreatment with RU486 (100mg/kg) attenuated the blood glucose level and pain behavior induced by IL-1ß administered i.t. in normal and D-glucose-fed groups. Our results suggest that IL-1ß administered i.t. increases the blood glucose level and pain behavior via an activation of the glucocorticoid system.
Assuntos
Glicemia/efeitos dos fármacos , Interleucina-1beta/metabolismo , Nociceptividade/efeitos dos fármacos , Dor/tratamento farmacológico , Receptores de Glucocorticoides/metabolismo , Glândulas Suprarrenais/metabolismo , Adrenalectomia , Animais , Corticosterona/sangue , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Glucose/administração & dosagem , Antagonistas de Hormônios/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Mifepristona/farmacologia , Dor/metabolismo , Hipófise/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismo , Receptores de Glucocorticoides/antagonistas & inibidores , Medula Espinal/metabolismoRESUMO
The possible roles of gamma-amino butyric acid (GABA) receptors located in the spinal cord for the regulation of the blood glucose level were studied in ICR mice. We found in the present study that intrathecal (i.t.) injection with baclofen (a GABAB receptor agonist; 1-10 µg/5 µl) or bicuculline (a GABAA receptor antagonist; 1-10 µg/5 µl) caused an elevation of the blood glucose level in a dose-dependent manner. The hyperglycemic effect induced by baclofen was more pronounced than that induced by bicuculline. However, muscimol (a GABAA receptor agonist; 1-5 µg/5 µl) or phaclofen (a GABAB receptor antagonist; 5-10 µg/5 µl) administered i.t. did not affect the blood glucose level. Baclofen-induced elevation of the blood glucose was dose-dependently attenuated by phaclofen. Furthermore, i.t. pretreatment with pertussis toxin (PTX; 0.05 or 0.1 µg/5 µl) for 6 days dose-dependently reduced the hyperglycemic effect induced by baclofen. Our results suggest that GABAB receptors located in the spinal cord play important roles for the elevation of the blood glucose level. Spinally located PTX-sensitive G-proteins appear to be involved in hyperglycemic effect induced by baclofen. Furthermore, inactivation of GABAA receptors located in the spinal cord appears to be responsible for tonic up-regulation of the blood glucose level.
Assuntos
Glicemia/análise , Receptores de GABA/efeitos dos fármacos , Animais , Baclofeno/administração & dosagem , Baclofeno/análogos & derivados , Baclofeno/farmacologia , Injeções Espinhais , Masculino , Camundongos , Camundongos Endogâmicos ICRRESUMO
We have recently demonstrated that some anti-diabetic drugs such as biguanide and thizolidinediones administered centrally modulate the blood glucose level, suggesting that orally administered anti-diabetic drugs may modulate the blood glucose level by acting on central nervous system. The present study was designed to explore the possible action of another class of anti-diabetic drugs, glinidies, administered centrally on the blood glucose level in ICR mice. Mice were administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) with 5 to 30 µg of repaglinide or nateglinide in D-glucose-fed and streptozotocin (STZ)-treated models. We found that i.c.v. or i.t. injection with repaglinide dose-dependently attenuated the blood glucose level in D-glucose-fed model, whereas i.c.v. or i.t. injection with nateglinide showed no modulatory action on the blood glucose level in D-glucose-fed model. Furthermore, the effect of repaglinide administered i.c.v. or i.t. on the blood glucose level in STZ-treated model was studied. We found that repaglinide administered i.c.v. slightly enhanced the blood glucose level in STZ-treated model. On the other hand, i.t. injection with repaglinide attenuated the blood glucose level in STZ-treated model. The plasma insulin level was enhanced by repaglinide in D-glucose-fed model, but repaglinide did not affect the plasma insulin level in STZ-treated model. In addition, nateglinide did not alter the plasma insulin level in both D-glucose-fed and STZ-treated models. These results suggest that the anti-diabetic action of repaglinide appears to be, at least, mediated via the brain and the spinal cord as revealed in both D-glucose fed and STZ-treated models.
RESUMO
In the present study, the effect of intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration with cholera toxin (CTX) on the blood glucose level was examined in ICR mice. The i.t. treatment with CTX alone for 24 h dose-dependently increased the blood glucose level. However, i.c.v. treatment with CTX for 24 h did not affect the blood glucose level. When mice were orally fed with D-glucose (2 g/kg), the blood glucose level reached to a maximum level at 30 min and almost returned to the control level at 120 min after D-glucose feeding. I.c.v. pretreatment with CTX increased the blood glucose level in a potentiative manner, whereas i.t. pretreatment with CTX increased the blood glucose level in an additive manner in a D-glucose fed group. In addition, the blood glucose level was increased in formalin-induced pain animal model. I.c.v. pretreatment with CTX enhanced the blood glucose level in a potentiative manner in formalin-induced pain animal model. On the other hand, i.t. pretreatment with CTX increased the blood glucose level in an additive manner in formalin-induced pain animal model. Our results suggest that CTX administered supraspinally or spinally differentially modulates the regulation of the blood glucose level in D-glucose fed model as well as in formalin-induced pain model.
RESUMO
As the association between obesity and bone health remains controversial in children and adolescents, we investigate the effects of obesity parameters on bone mineral density (BMD) in 2060 Korean adolescents who participated in the 2008-2011 Korea National Health and Nutrition Examination Survey (KNHANES). Multiple regression analysis and analysis of covariance (ANCOVA) were conducted to examine both the linear and non-linear associations between total-body-less-head (TBLH) BMD and four obesity parameters: body mass index, waist circumference, waist-to-height ratio, and total-body fat mass (FM). In a multiple linear regression analysis adjusted for age, menarcheal status (in females only), and total-body lean mass, there was no significant linear association between obesity parameters and TBLH BMD, except for total-body FM in males. However, upon adding a second-order polynomial term for each obesity parameter, a significant quadratic relationship between all obesity parameters and TBLH BMD was observed, with the corresponding quadratic term being negative. The results of ANCOVA also revealed an inverted U-shaped relationship between each obesity parameter and TBLH BMD. Our findings suggest the existence of an optimal range of obesity parameters for developing or maintaining optimal bone health in Korean Adolescents. Deviation from this range, in either direction (being underweight or having obesity), may compromise bone health.