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We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% ± 0.71% to 7.71% ± 0.93%) and voglibose groups (from 8.38% ± 0.73% to 7.68% ± 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 ± 69.38 to 176.80 ± 46.63 mg/dL) compared with the voglibose group (from 224.18 ± 70.07 to 193.01 ± 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528).
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Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inositol/análogos & derivados , Insulina/sangue , Acarbose/efeitos adversos , Glicemia , Diabetes Mellitus Tipo 2/sangue , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Hemoglobinas Glicadas/análise , Inibidores de Glicosídeo Hidrolases , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Inositol/efeitos adversos , Inositol/uso terapêutico , Insulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
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Atorvastatina , LDL-Colesterol , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Dislipidemias , Hemoglobinas Glicadas , Hipoglicemiantes , Metformina , Humanos , Atorvastatina/uso terapêutico , Atorvastatina/administração & dosagem , Metformina/uso terapêutico , Metformina/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Método Duplo-Cego , Pessoa de Meia-Idade , Dislipidemias/tratamento farmacológico , Dislipidemias/sangue , Hemoglobinas Glicadas/análise , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Idoso , LDL-Colesterol/sangue , Resultado do Tratamento , AdultoRESUMO
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.
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Diabetes Mellitus Tipo 2 , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Estudos RetrospectivosRESUMO
Leptin resistance associated with hyperleptinemia in high-fat-diet-induced obese rats and aged obese rats is well established, but it is not clear whether hyperphagia-induced obese rats also develop leptin resistance. We investigated whether Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a strain of hyperphagia-induced obese rats, develop leptin resistance and whether caloric restriction reversed this leptin resistance-induced leptin receptor (ObRb) deficit. Twenty male OLETF rats, 20 male Long-Evans Tokushima Otsuka (LETO) rats, and 10 male Sprague Dawley (SD) rats were used. All rats were initially studied at 10 weeks of age and were freely fed with standard rat chow and water until they were 38 weeks of age. Daily food intake, body weight, and plasma leptin levels of OLETF rats were remarkably increased compared to LETO or SD rats from 10 to 38 weeks of age. When they were 38 weeks of age, all OLETF rats were randomly divided into two groups. One group was freely fed with standard rat chow (FD, or free diet group), and the other group (RD, or restricted diet group) was fed with only 70% of the amount consumed by the FD group. The LETO and SD rats were dismissed from further study. After 4 weeks of caloric restriction, the average body weight (636+/-33 g vs. 752+/-24 g, P<0.05) and abdominal adipose tissue weight (10.6+/-3.2g vs. 15.8+/-1.5 g, P<0.05) of the RD group were decreased compared with those of the FD group. Plasma leptin levels of the RD group were significantly decreased compared with those of the FD group (3.47+/-1.40 ng/mL vs. 11.55+/-1.16 ng/mL, P<0.05). The mRNA expression of ObRb and leptin-related suppressor of cytokine signaling 3 (SOCS3) in the hypothalamus, liver, and skeletal muscles of the RD group were significantly decreased compared with those of the FD group. Caloric restriction did not improve leptin receptor (ObRb) deficit or the downstream signaling of leptin in the liver, skeletal muscles, and hypothalamus. Thus, we demonstrated that OLETF rats, which are a strain of hyperphagia-induced obese rats, did not develop central or peripheral leptin resistance. We suggest that hyperleptinemia in OLETF rats is a compensatory mechanism to overcome obesity induced by hyperphagia.
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Hiperfagia/sangue , Leptina/sangue , Obesidade/sangue , Receptores para Leptina/biossíntese , Gordura Abdominal/metabolismo , Animais , Peso Corporal , Restrição Calórica , Ingestão de Alimentos , Hiperfagia/complicações , Masculino , Obesidade/complicações , Ratos , Ratos Endogâmicos , Ratos Sprague-Dawley , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
BACKGROUND: There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM. METHODS: This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement. RESULTS: Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: -0.81%, P<0.001; glimepiride: -1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001). CONCLUSION: Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Pioglitazona/uso terapêutico , Piperidinas/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Uracila/análogos & derivados , Idoso , Glicemia , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemia/etiologia , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Uracila/uso terapêuticoRESUMO
The American College of Cardiology/American Heart Association (ACC/AHA) recently published a Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. However, the data in other ethnic groups are not well known. We evaluated the prevalence and associated cardiovascular prognosis of Korean subjects with newly reclassified hypertension based on the 2017ACC/AHA guideline. We analyzed data from the Korean Health and Genome Study (n = 10,038). Supine blood pressure (BP) was measured thrice following a standardized protocol and averaged. There was a significant linear relation between BP profiles and cardiovascular disease (CVD)/mortality. Hazard ratio for CVD increased above a systolic BP of 120mm Hg. Systolic BP ≥130mm Hg was significantly associated with increased risk of CVD, coronary heart disease, stroke, CVD death, and total deaths. There was a similar significant linear relation with diastolic BP categories between CVD risk and death. BP is associated with an increased risk of CVD or all-cause mortalities. Moreover, the new BP categories of the 2017ACC/AHA guideline could be applicable for predicting CVD and death in Korean population.
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Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Previsões , Medição de Risco/métodos , Adulto , Idoso , Doenças Cardiovasculares/fisiopatologia , Causas de Morte/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
Since TNF-related apoptosis inducing ligand (TRAIL) is one of several apoptotic stimuli on articular chondrocytes, the modulation of the mechanism mediated by TRAIL could be considered as a novel strategy for the treatment of osteoarthritis (OA). Previous studies demonstrated that Clematis mandshurica prevents staurosporin-induced apoptosis in articular chondrocytes. This study was undertaken to examine whether Clematis mandshurica could prevent TRAIL-induced apoptosis in articular chondrocytes. Our data show that Clematis mandshurica prevents adenoviral TRAIL (Ad-TRAIL)-induced apoptosis in primary cultured articular chondrocytes. Clematis mandshurica prevents Ad-TRAIL-induced down-regulation of 14-3-3 and phosphorylated Akt. In addition, Clematis mandshurica treatment prevents the Ad-TRAIL-induced reduction of the interactions between 14-3-3 with phospho-ser112-Bad and phospho-ser136-Bad, and BcL-xL with phospho-ser155-Bad. A better understanding of the mechanism underlying inhibition of apoptosis in OA chondrocytes by Clematis mandshurica might lead to the development of a new therapeutic strategy for OA.
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Apoptose/efeitos dos fármacos , Condrócitos/citologia , Clematis , Articulações/citologia , Extratos Vegetais/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidores , Proteínas 14-3-3/metabolismo , Adenoviridae , Animais , Células Cultivadas , Depressão Química , Regulação para Baixo , Proteína Oncogênica v-akt/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/etiologia , Ratos , Ratos Sprague-Dawley , Ligante Indutor de Apoptose Relacionado a TNF/farmacologiaRESUMO
We tested the hypothesis that higher levels of bilirubin, a bile pigment with antioxidant properties, are associated with a decreased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the association between serum total bilirubin (TB) on CVD and CVD death. Serum TB was measured in a total of 8,844 subjects (4,196 males and 4,648 females) and evaluated for the development of new onset CVD from 2001 to 2012 (mean 8.1 years of follow-up). During the follow-up period, 689 cases of incident CVD (7.8%) were identified, and the prevalence of metabolic syndrome (MetS) at baseline was 26.1%. The prevalence of MetS decreased across bilirubin tertile categories. In addition to MetS itself, individual components of MetS significantly decreased with increased bilirubin tertiles. Moreover, the incidence of CVD decreased across bilirubin tertile categories. The hazard ratios (HRs) for developing coronary heart disease (CHD, HR 0.769, 95% CI 0.655-1.000) and CVD death (HR 0.513, 95% CI 0.267-0.985) was significantly lower in the highest tertile group (> 0.63 mg/dL) in comparison to the lowest tertile group (< 0.44 mg/dL) after adjusting for all confounding variables. In the present longitudinal study, a significant negative relationship was demonstrated between baseline bilirubin levels and incident CHD and CVD death.
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Bilirrubina/sangue , Doenças Cardiovasculares/sangue , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Doença das Coronárias/mortalidade , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
AIMS: We examined the association between changes in serum calcium levels with the incidence of type 2 diabetes mellitus (T2DM) in apparently healthy South Korean subjects. METHODS: A retrospective longitudinal analysis was conducted with subjects who had participated in comprehensive health check-ups at least four times over a 7-year period (between 2006 and 2012). In total, 23,121 subjects were categorized into tertiles based on changes in their albumin-adjusted serum calcium levels. Multivariate Cox regression models were fitted to assess the association between changes in serum calcium levels during follow-up and the relative risk of diabetes incidence. RESULTS: After a median follow-up of 57.4months, 1,929 (8.3%) new cases of T2DM occurred. Simple linear regression analysis showed serum calcium level changes correlated positively with changes in HbA1c and fasting plasma glucose (FPG) levels (B=5.72, p<0.001 for FPG; B=0.13, p<0.001 for HbA1c). An increase in albumin-adjusted serum calcium levels during follow-up was related to an increased risk of T2DM. After adjustment for potential confounders, the risk of T2DM was 1.6 times greater for subjects whose albumin-adjusted serum calcium levels were in the highest change tertile during follow-up than for subjects whose levels were in the lowest tertile (HR 1.65, 95% CI 1.44-1.88, P<0.001). CONCLUSIONS: The elevation of albumin-adjusted serum calcium levels was associated with an increased risk of T2DM, independent of baseline glycemic status.
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Cálcio/sangue , Diabetes Mellitus Tipo 2/sangue , Adulto , Idoso , Povo Asiático , Glicemia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , RiscoRESUMO
BACKGROUND: Incretin hormone levels as a predictor of type 2 diabetes mellitus have not been fully investigated. Therefore, we measured incretin hormone levels to examine the relationship between circulating incretin hormones, diabetes, and future diabetes development in this study. METHODS: A nested case-control study was conducted in a Korean cohort. The study included the following two groups: the control group (n=149), the incident diabetes group (n=65). Fasting total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic peptide (GIP) levels were measured and compared between these groups. RESULTS: Fasting total GIP levels were higher in the incident diabetes group than in the control group (32.64±22.68 pmol/L vs. 25.54±18.37 pmol/L, P=0.034). There was no statistically significant difference in fasting total GLP-1 levels between groups (1.14±1.43 pmol/L vs. 1.39±2.13 pmol/L, P=0.199). In multivariate analysis, fasting total GIP levels were associated with an increased risk of diabetes (odds ratio, 1.005; P=0.012) independent of other risk factors. CONCLUSION: Fasting total GIP levels may be a risk factor for the development of type 2 diabetes mellitus. This association persisted even after adjusting for other metabolic parameters such as elevated fasting glucose, hemoglobin A1c, and obesity in the pre-diabetic period.
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Subclinical hypothyroidism (SCH) is a common disorder that is characterized by elevated thyroid-stimulating hormone levels in conjunction with free thyroxine concentrations within the normal reference range. Thyroid hormones are known to affect the heart and vasculature and, as a result, the impact of SCH on the cardiovascular (CV) system has recently become an important topic of research. Strong evidence points to a link between SCH and CV risk factors such as alterations in blood pressure, lipid levels, and atherosclerosis. Additionally, accumulating evidence indicates that SCH is associated with metabolic syndrome and heart failure. The present review proposes that SCH may be a potentially modifiable risk factor of CV disease and mortality. However, large-scale clinical trials with appropriate power investigating the risks and benefits of SCH treatment are required to determine whether these benefits can be achieved with levothyroxine therapy.
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AIMS/INTRODUCTION: To assess the current status of glycemic control in patients with type 2 diabetes treated with a combination of metformin and sulfonylurea for >3 months, as measured by glycosylated hemoglobin (HbA1c). MATERIALS AND METHODS: Data on patient demographics, diabetic complications, HbA1c, fasting plasma glucose (FPG) and type of treatment were collected in this multicenter, cross-sectional, non-interventional study. RESULTS: From April 2008 to February 2009, 5,628 patients were recruited from 299 centers in Korea. Patients characteristics (mean ± SD) were as follows: age 58.4 ± 10.8 years, duration of diabetes 6.1 ± 4.7 years, body mass index 24.7 ± 2.9 kg/m(2), HbA1c 7.77 ± 1.22%, FBG 147.4 ± 46.5 mmol/L and FPG 164.0 ± 54.3 mmol/L. The most common diabetic complication was neuropathy (22.5%), followed by retinopathy (18.3%) and microalbuminuria (16.1%). Just 1,524 (27.1%) patients achieved HbA1c ≤7%. A higher number of patients (32.6%) treated by endocrinologists achieved HbA1c ≤7% than those treated by internists (24.4%) and primary care physicians (23.2%). In multivariate analyses, diabetic retinopathy (odds ratio 0.455, 95% confidence interval 0.341-0.606), nephropathy (odds ratio 0.639, 95% confidence interval 0.43-0.949), diabetes for ≥5 years (odds ratio 0.493, 95% confidence interval 0.4-0.606) and older age added by 1 year (odds ratio 1.019, 95% confidence interval 1.01-1.029) was significantly associated with achieving target HbA1c. In addition, treatment by endocrinologists rather than internists significantly increased chances of achieving target HbA1c (odds ratio 1.417, 95% confidence interval 1.146-1.751). CONCLUSIONS: The majority of patients with type 2 diabetes in Korea had inadequate glycemic control, despite receiving a combination of metformin and sulfonylurea.
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Hepatocyte growth factor (HGF) is a potent mitogen and promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF, an adenoviral vector carrying the human HGF (Ad.hHGF) gene was transfected into the streptozotocin-induced diabetic mice and evaluated the effect on the blood glucose metabolism and the insulin-secreting beta cells of pancreatic islets. Ad.hHGF gene transfection resulted in amelioration of hyperglycemia and prolongation of survival period in the diabetic mice. Concomitantly adenoviral- mediated hHGF gene therapy slightly increased serum insulin concentration and the expression of insulin in the pancreatic islet. Although the proliferation of beta-cell mass was not noticeable, the beneficial effect of HGF is significant to an almost deteriorated pancreatic islets. Taken together, these data suggest that the Ad.hHGF gene therapy into diabetic mice may prevent the further destruction and present as a beneficial remedy for type 1 diabetic patients.
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Adenoviridae/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Terapia Genética , Fator de Crescimento de Hepatócito/metabolismo , Hiperglicemia/terapia , Ilhotas Pancreáticas/patologia , Adenoviridae/fisiologia , Animais , Glicemia/análise , Peso Corporal , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Fator de Crescimento de Hepatócito/genética , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/genética , Insulina/sangue , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Taxa de SobrevidaRESUMO
This study examined a 55 kDa protein in the rat cerebellar postsynaptic density (PSD) fraction. The amino acid sequence of an HPLC-purified peptide derived from tryptic digestion of the protein was contained in eukaryotic translation elongation factor-1A (eEF1A, formerly known as eEF-1alpha). Immunoblot analysis showed that eEF1A is enriched in the PSD fraction and is tightly associated with the PSD 'core'. The association of eEF1A with the PSD was further evidenced by colocalization of the protein with PSD95, a PSD marker, in dissociated cerebellar cultures and immunoelectron microscopy of the adult rat cerebellum. Combined, our results indicate that eEF1A is associated with the PSD.
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Cerebelo/química , Fator 1 de Elongação de Peptídeos/análise , Sinapses/química , Animais , Contagem de Células/métodos , Cerebelo/ultraestrutura , Ratos , Sinapses/ultraestruturaRESUMO
BACKGROUND: Metabolic syndrome (MetS) is a condition characterized by a cluster of metabolic disorders and is associated with increased risk of cardiovascular disease (CVD). This study analyzed data from the Korean Health and Genome Study to examine the impact of MetS on CVD. METHODS: A total of 8,898 subjects (4,241 males and 4,657 females), 40 to 69 years of age, were enrolled and evaluated for the development of new onset CVD from 2001 to 2012 (median 8.1 years of follow-up). RESULTS: The prevalence of MetS at baseline was 22.0% (932/4,241) and 29.7% (1,383/4,657) in males and females, respectively. MetS was associated with increased risk of coronary heart disease (CHD; hazard ratio [HR], 1.818; 95% confidence interval [CI], 1.312 to 2.520 in males; HR, 1.789; 95% CI, 1.332 to 2.404 in females) and CVD (HR, 1.689; 95% CI, 1.295 to 2.204 in males; HR, 1.686; 95% CI, 1.007 to 2.192 in females). Specifically, MetS was associated with risk of future stroke in females only (HR, 1.486; 95% CI, 1.007 to 2.192). Among MetS components, abdominal obesity and hypertension were independent predictors of both CHD and CVD. In addition, a higher number of MetS components correlated with higher CVD risk. CONCLUSION: MetS is a significant risk factor for the development of CVD although its impact varies between sexes.
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AIMS/INTRODUCTION: Small dense low-density lipoprotein (sdLDL) has been suggested to be a potential risk factor for cardiovascular diseases (CVD). MATERIALS AND METHODS: We carried out a prospective nested case-control study in the Korean Health and Genome Study. Participants were men and women aged 40-69 years who developed CVD (n = 313), and were matched by age and sex to controls who remained free of CVD (n = 313) during the 8-years follow-up period (from 2001 to 2009). LDL subfractions were analyzed in frozen samples collected from the 626 participants using polyacrylamide tube gel electrophoresis. RESULTS: Patients with CVD had a significantly higher glycated hemoglobin level compared with the controls (5.72 vs 5.56). The proportion of patients with diabetes mellitus (DM) was higher in those who developed CVD during follow up (8.0% vs 1.9%). The frequency of CVD according to each tertile of LDL particle size and the number of metabolic syndrome components did not differ significantly. In the multivariate analysis, DM (odds ratio 4.244, 95% confidence interval 1.693-10.640, P = 0.002) was the only independent predictive factor of CVD. LDL particle size was not associated with the risk for future CVD. CONCLUSIONS: Small dense LDL might not be a significant predictor of CVD in this Korean community-based prospective cohort study.
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BACKGROUND: The aim of this study is to investigate the cardio-metabolic parameters and surrogate markers of insulin resistance in a discordant group of type 2 diabetes (T2DM) subjects who satisfy the Adults Treatment Panel (ATP) III criteria, but not the International Diabetes Federation (IDF) criteria, for metabolic syndrome (MetS). METHODS: We assessed the prevalence of MetS in T2DM subjects (n=167) who were selected from subjects registered at the diabetes center of Dong-A University Medical Center. We used the ATP III criteria and the IDF criteria for the diagnosis of MetS and sorted the subjects into 2 MetS groups: one group diagnosed per ATP III criteria (MetSa) and one diagnosed per IDF criteria (MetSi). We then compared the clinical characteristics, metabolic parameters (homeostasis model assessment of insulin resistance, aspartate aminotransferase, alanine aminotransferase, and uric acid values) and co-morbidities (prevalence of microalbuminuria, fatty liver, and cardiovascular disease) between the MetSa, MetSi, and discordant MetS groups. RESULTS: The prevalence of MetS in the MetSa group (73.6%) was higher than in the MetSi group (62.2%). The MetS prevalence in the discordant group was 11.4%. The discordant group showed no significant differences in clinical characteristics (except waist circumference and body mass index), metabolic parameters, or prevalence of co-morbidities, as compared with subjects with MetS by both criteria. CONCLUSION: In this study, cardio-metabolic features of the subjects diagnosed with MetS using ATP III criteria, but not IDF criteria, are not significantly different from those of subjects diagnosed with MetS using both criteria.
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Fenofibrate is a selective peroxisome proliferator-activated receptor α (PPARα) activator and is prescribed to treat hyperlipidemia. The mechanism through which PPARα agonists reduce food intake, body weight, and adiposity remains unclear. One explanation for the reduction of food intake is that fenofibrate promotes fatty acid oxidation and increases the production of ketone bodies upon a standard experimental dose of the drug (100~300 mg/kg/day). We observed that low-dose treatment of fenofibrate (30 mg/kg/day), which does not cause significant changes in ketone body synthesis, reduced food intake in Long-Evans Tokushima (LETO) rats. LETO rats are the physiologically normal controls for Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are obese and cholecystokinin (CCK)-A receptor deficient. We hypothesized that the reduced food intake by fenofibrate-treated LETO rats may be associated with CCK production. To investigate the anorexic effects of fenofibrate in vivo and to determine whether CCK production may be involved, we examined the amount of food intake and CCK production. Fenofibrate-treated OLETF rats did not significantly change their food intake while LETO rats decreased their food intake. Treatment of fenofibrate increased CCK synthesis in the duodenal epithelial cells of both LETO and OLETF rats. The absence of a change in the food intake of OLETF rats, despite the increase in CCK production, may be explained by the absence of CCK-A receptors. Contrary to the OLETF rats, LETO rats, which have normal CCK receptors, presented a decrease in food intake and an increase in CCK production. These results suggest that reduced food intake by fenofibrate treatment may be associated with CCK production.
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BACKGROUND: Our study group established "3H care" in 2002. The meaning of "3H care" attain and maintain adequate controls over hypertension, hyperlipidemia, and hyperglycemia in type 2 diabetic patients. This study evaluated the achievement of target goals after one year or more of "3H care" by specialists in our diabetic clinic. METHODS: This was a retrospective study of 200 type 2 diabetic patients who received "3H care" for one year or more in our diabetic clinic. We evaluated achievement of target goals for metabolic controls as suggested by the American Diabetes Association. RESULTS: Overall, 200 type 2 diabetes patients were enrolled, of whom 106 were males (53%) and 94 were females (47%). After one year of "3H care," the mean HbA1c was 7.2±1.5% and the percentage of patients achieving glycemic control (HbA1c <7%) was 51.8%. However only 32.2% of hypertensive patients achieved the recommended target. After one year of "3H care," the percentages of those who achieved the target value for dyslipidemia were 80.0% for total cholesterol, 66.3% for low density lipoprotein cholesterol, 57.9% for triglyceride, and 51.8% for high density lipoprotein cholesterol. The percentage that achieved all three targets level was only 4.4% after one year and 14.8% after two years. CONCLUSION: The results of this study demonstrate that only a minor proportion of patients with type 2 diabetes achieved the recommended goals despite the implementation of "3H care." It is our suggestion that better treatment strategies and methods should be used to control hypertension, hyperlipidemia and hyperglycemia.
RESUMO
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.