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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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AIM: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. RESULTS: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. CONCLUSIONS: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.
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Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Glucósidos , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Piperidonas , Pirimidinas , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Glucósidos/uso terapéutico , Glucósidos/administración & dosificación , Glucósidos/efectos adversos , Metformina/uso terapéutico , Metformina/administración & dosificación , Compuestos de Bencidrilo/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Anciano , Piperidonas/uso terapéutico , Piperidonas/administración & dosificación , Piperidonas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Glucemia/efectos de los fármacos , Glucemia/análisis , Glucemia/metabolismo , Control Glucémico/métodos , Adulto , Resultado del Tratamiento , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Hipoglucemia/prevención & control , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.
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Adamantano , Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Dipéptidos , Quimioterapia Combinada , Glucósidos , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Metformina/uso terapéutico , Metformina/administración & dosificación , Metformina/efectos adversos , Glucósidos/administración & dosificación , Glucósidos/efectos adversos , Glucósidos/uso terapéutico , Masculino , Femenino , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/efectos adversos , Persona de Mediana Edad , Dipéptidos/efectos adversos , Dipéptidos/administración & dosificación , Dipéptidos/uso terapéutico , Adamantano/análogos & derivados , Adamantano/administración & dosificación , Adamantano/efectos adversos , Adamantano/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Anciano , Resultado del Tratamiento , Hipoglucemia/inducido químicamente , Compuestos de Sulfonilurea/uso terapéutico , Compuestos de Sulfonilurea/administración & dosificación , Compuestos de Sulfonilurea/efectos adversos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Adulto , Aumento de Peso/efectos de los fármacos , Fosfato de Sitagliptina/uso terapéutico , Fosfato de Sitagliptina/administración & dosificación , Fosfato de Sitagliptina/efectos adversosRESUMEN
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.
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Glucemia , Péptido C , Humanos , Péptido C/sangre , República de Corea , Femenino , Masculino , Adulto , Persona de Mediana Edad , Glucemia/análisis , Prueba de Tolerancia a la Glucosa/normas , Estándares de Referencia , Valores de Referencia , Hemoglobina Glucada/análisis , Adulto Joven , Anciano , Biomarcadores/sangreRESUMEN
INTRODUCTION: To investigate the safety and effectiveness of insulin degludec (IDeg) in a real-world population of Korean patients with diabetes requiring insulin therapy. METHODS: This was a multicenter, prospective, single-arm, open-label, non-interventional study. Patients aged ≥ 12 months and treated with previous glucose-lowering medications were eligible to switch to IDeg. The primary endpoint was the incidence of adverse events (AEs), and the secondary endpoints were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial glucose (PPG), and target HbA1c < 7.0%. RESULTS: In total, 3225 and 2450 patients were included in the safety analysis set (SAS) and effectiveness analysis set (EAS), respectively. The mean baseline HbA1c and duration of diabetes were 9.4% and 13.0 years, respectively. Adverse events were reported in 740 patients (22.9%); the majority were mild and resolved. Significant improvements were observed in HbA1c, FPG, and PPG at week 26 (all p < 0.0001). The target of HbA1c < 7% was achieved in 22.2% of patients at week 26. CONCLUSION: In real-world clinical practice, 26 weeks of IDeg treatment resulted in significant reductions in glycemic parameters with a low incidence of AEs in Korean patients with diabetes. No new safety signals were observed. CLINICAL TRIALS REGISTRY AND REGISTRATION NUMBER: This trial is registered under ClinicalTrials.gov (NCT02779413) and the universal trial number is [U1111-1176-2287].
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AIMS: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. MATERIALS AND METHODS: This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans. RESULTS: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm2 VAT area, -18.39 cm2 SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m2 body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. CONCLUSION: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/uso terapéutico , Hemoglobina Glucada , Glucemia , Hipoglucemiantes/efectos adversos , Compuestos de Bencidrilo/efectos adversos , Composición Corporal , Quimioterapia Combinada , Método Doble Ciego , Resultado del TratamientoRESUMEN
AIMS/INTRODUCTION: We investigated the classification of diabetic peripheral neuropathy (DPN) patients by subjective symptoms, and identification of the relationship between the patterns and intensities of symptoms and the clustered groups of DPN patients. MATERIALS AND METHODS: This multicenter study analyzed epidemiological data and sensory symptoms of 649 patients with DPN. Cluster analysis was carried out to identify subgroups of patients with characteristic symptom profiles. Factor analysis was carried out to investigate the symptom patterns of the clustered groups of DPN patients. RESULTS: Three clusters of patients with DPN were identified: severe symptoms with decreased quality of life (cluster 1, n = 119, 18.3%), predominantly insensate symptoms with relatively good quality of life (cluster 2, n = 318, 49.0%), and moderate pain intensity and decreased quality of life (cluster 3, n = 204, 31.4%). The frequency of symptoms on each item of the Michigan Neuropathy Screening Instrument questionnaire showed a similar distribution according to pain intensities along with the three clusters. CONCLUSIONS: Our study supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach. Based on a multicenter study, we identified three clusters of patients with DPN. Our research supports the hypothesis that diversity in sensory symptoms exists in patients with DPN. Heterogeneity in DPN patients should be taken into account for a more stratified or individualized treatment approach.
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Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/epidemiología , Dolor , Fenotipo , Calidad de VidaRESUMEN
INTRODUCTION: Various kidney diseases reportedly show different urinary extracellular vesicle (EV) RNA profiles. Although obesity is one of the main causes of chronic kidney disease, the expression pattern of urinary EV RNA in obesity is uncertain. Our aim was to sequence the small RNA profiles of urinary EVs in obese patients before and after weight reduction and compare them to those of healthy volunteers (HVs). METHODS: We recruited age-sex-matched obese patients and HVs. The small RNA profiles of urinary EVs were analyzed using RNA sequencing. To evaluate the effect of weight reduction, small RNA profiles of urinary EVs 6 months after bariatric surgery were also analyzed. RESULTS: The proportion of urinary EVs transfer RNA and microRNA of obese patients differed from that of HVs. Obese patients showed differential expression of 1,343 small RNAs in urinary EVs compared to HVs (fold change ≥2 and p value <0.05). Among those, 61 small RNAs were upregulated in obese patients and downregulated after weight reduction, whereas 167 small RNAs were downregulated in obese patients and upregulated after weight reduction. RNA sequencing revealed the correlation between the specific urinary EV small RNAs and clinical parameters including body weight, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol, serum glucose, estimated glomerular filtration rate, and albuminuria. CONCLUSION: Obese patients showed distinct urinary EV small RNA profiles compared to HVs. Weight reduction altered urinary EV small-RNA profiles in obese patients.
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Vesículas Extracelulares , MicroARNs , Colesterol/metabolismo , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Humanos , MicroARNs/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Pérdida de PesoRESUMEN
BACKGROUND: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. METHODS: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing's syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. RESULTS: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6ß-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. CONCLUSION: The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.
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Neoplasias de las Glándulas Suprarrenales , Síndrome de Cushing , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Cromatografía Liquida , Síndrome de Cushing/diagnóstico , Humanos , Estudios Prospectivos , EsteroidesAsunto(s)
Diabetes Mellitus Tipo 2 , Estado Prediabético , Glucemia , Proteínas Sanguíneas , HumanosRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease. Early detection of prediabetes is important to reduce the risk of T2DM. Some cytokines are known to be associated with T2DM. Therefore, we aimed to identify cytokines as novel biomarkers of glucose dysmetabolism. METHODS: The first stage of the study included 43 subjects (13 subjects with newly diagnosed T2DM, 13 with prediabetes, and 16 with normoglycemia) for cytokine microarray analysis. Blood samples of the subjects were assessed for 310 cytokines to identify potential indicators of prediabetes. The second stage included 142 subjects (36 subjects with T2DM, 35 with prediabetes, and 71 with normoglycemia) to validate the potential cytokines associated with prediabetes. RESULTS: We identified 41 cytokines that differed by 1.5-fold or more in at least one out of the three comparisons (normoglycemia vs. prediabetes, normoglycemia vs. T2DM, and prediabetes vs. T2DM) among 310 cytokines. Finally, we selected protein Z (PROZ) and validated this finding to determine its association with prediabetes. Plasma PROZ levels were found to be decreased in patients with prediabetes (1,490.32±367.19 pg/mL) and T2DM (1,583.34±465.43 pg/mL) compared to those in subjects with normoglycemia (1,864.07±450.83 pg/mL) (P<0.001). There were significantly negative correlations between PROZ and fasting plasma glucose (P=0.001) and hemoglobin A1c (P=0.010). CONCLUSION: PROZ levels were associated with prediabetes and T2DM. We suggest that PROZ may be a promising biomarker for the early detection of prediabetes. Further large-scale studies are needed to evaluate the relationship and mechanism between PROZ and prediabetes and T2DM.
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Diabetes Mellitus Tipo 2 , Estado Prediabético , Proteínas Sanguíneas , Diabetes Mellitus Tipo 2/diagnóstico , Ayuno , Hemoglobina Glucada/metabolismo , Humanos , Estado Prediabético/diagnósticoRESUMEN
BACKGROUND: We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines. METHODS: This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe. RESULTS: Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy. CONCLUSION: According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.
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Aterosclerosis , Diabetes Mellitus Tipo 2 , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Aterosclerosis/epidemiología , LDL-Colesterol , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Estudios RetrospectivosRESUMEN
This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.
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Diabetes Mellitus , Neuropatías Diabéticas , Estudios de Cohortes , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/epidemiología , Humanos , Programas Nacionales de Salud , Prevalencia , República de Corea/epidemiologíaRESUMEN
PURPOSE: Dyslipidemia is an important risk factor for cardiovascular disease (CVD). Statins are known to effectively reduce not only low-density lipoprotein cholesterol (LDL-C) level but also death and nonfatal myocardial infarction due to coronary heart disease. The risk for CVD from atherogenic dyslipidemia persists when elevated triglyceride (TG) and reduced high-density lipoprotein cholesterol (HDL-C) levels are not controlled with statin therapy. Therefore, statin/fenofibrate combination therapy is more effective in reducing CVD risk. Here, we assessed the efficacy and tolerability of pitavastatin/fenofibrate combination therapy in patients with mixed dyslipidemia and a high risk for CVD. METHODS: This multicenter, randomized, double-blind, parallel-group, therapeutic-confirmatory clinical trial evaluated the efficacy and tolerability of fixed-dose combination therapy with pitavastatin/fenofibrate 2/160 mg in Korean patients with a high risk for CVD and a controlled LDL-C level (<100 mg/dL) and a TG level of 150-500 mg/dL after a run-in period with pitavastatin 2 mg alone. In the 8-week main study, 347 eligible patients were randomly assigned to receive pitavastatin 2 mg with or without fenofibrate 160 mg after a run-in period. In the extension study, patients with controlled LDL-C and non-HDL-C (<130 mg/dL) levels were included after the completion of the main study. All participants in the extension study received the pitavastatin/fenofibrate combination therapy for 16 weeks for the assessment of the tolerability of long-term treatment. FINDINGS: The difference in the mean percentage change in non-HDL-C from baseline to week 8 between the combination therapy and monotherapy groups was -12.45% (95% CI, -17.18 to -7.72), and the combination therapy was associated with a greater reduction in non-HDL-C. The changes in lipid profile, including apolipoproteins, fibrinogen, and high-sensitivity C-reactive protein from baseline to weeks 4 and 8 were statistically significant with combination therapy compared to monotherapy at all time points. Furthermore, the rates of achievement of non-HDL-C and apolipoprotein B targets at week 8 in the combination therapy and monotherapy groups were 88.30% versus 77.98% (P = 0.0110) and 78.94% versus 68.45% (P = 0.0021), respectively. The combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. IMPLICATIONS: In these Korean patients with mixed dyslipidemia and a high risk for CVD, combination therapy with pitavastatin/fenofibrate was associated with a greater reduction in non-HDL-C compared with that with pitavastatin monotherapy, and a significantly improvement in other lipid levels. Moreover, the combination therapy was well tolerated, with a safety profile similar to that of statin monotherapy. Therefore, pitavastatin/fenofibrate combination therapy could be effective and well tolerated in patients with mixed dyslipidemia. ClinicalTrials.gov identifier: NCT03618797.
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Dislipidemias/tratamiento farmacológico , Fenofibrato/administración & dosificación , Quinolinas/administración & dosificación , Anciano , Apolipoproteínas B/sangre , Colesterol/sangre , LDL-Colesterol/sangre , Método Doble Ciego , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lípidos/sangre , Masculino , Persona de Mediana Edad , República de Corea , Triglicéridos/sangreRESUMEN
Type 2 diabetes is a metabolic disease with a group of metabolic derangements and inflammatory reactants in the serum. Despite the substantial public health implications, markers of diabetes progression with abdominal obesity are still needed to facilitate early detection and treatment. In this study, we performed a proteomic approach to identify differential target proteins underlying diabetes progression in patients with abdominal obesity. Proteomic differences were investigated in the serum of controls and patients with prediabetes or diabetes with or without abdominal obesity by 2-DE combined with MALDI-TOF-MS. Proteomics data were validated by western blot analyses and major protein-protein interactions were assessed using a network analysis with String database. Among 245 matched protein spots, 36 exhibited marked differences in normal patients with abdominal obesity, prediabetes, and diabetes compared to levels in normal patients without abdominal obesity. Seven (Alpha-1-antichymotrypsin, Alpha-1-antitrypsin, Apolipoprotein A-I, haptoglobin, retinol-binding protein 4, transthyretin, and zinc-alpha2-glycoprotein) of these spots exhibited significant differences between normal and prediabetes/diabetes patients. After a network analysis, functional annotation using Gene Ontology indicated that most of the identified proteins were involved in lipid transport, lipid localization, and the regulation of serum lipoprotein particle levels. Our results indicated that variation in the levels of these identified protein biomarkers has been reported in normal, prediabetes and diabetic Assessment of the levels of these biomarkers may contribute to the development of biomarkers for not only early diagnosis but also in prognosis of diabetes mellitus type 2.
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Diabetes Mellitus/sangre , Obesidad Abdominal/complicaciones , Proteoma/química , Adipoquinas , Adulto , Apolipoproteínas/sangre , Biomarcadores/sangre , Proteínas Portadoras/sangre , Diabetes Mellitus/diagnóstico , Femenino , Glicoproteínas/sangre , Haptoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Prealbúmina/análisis , República de Corea , Proteínas de Unión al Retinol/análisis , alfa 1-Antitripsina/sangreRESUMEN
Abdominal or visceral obesity is a well-known risk factor for metabolic diseases. However, whether abdominal obesity significantly affects plasma lipid profile during the development of type 2 diabetes has not been fully elucidated. We investigated the differences in plasma lipid concentrations in 63 participants categorized into six groups (middle-aged Korean men); Normal, Pre-diabetes (pre-DM), and Diabetes mellitus (DM) with or without abdominal obesity (AO or lean). The lipidomic profiles were determined by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sphingomyelin (SM) levels in plasma were significantly higher in the pre-DM with AO than in pre-DM with lean (p = 0.021). SM concentrations correlated positively with waist-to-hip ratio (WHR) (r = 0.256, p = 0.044), cholesteryl ester (CE) (r = 0.483, p < 0.0001), ceramide (r = 0.489, p < 0.0001) and plasmanyl phosphatidylcholine (PC) (r = 0.446, p < 0.0001). The present study found that pre-diabetic patients with AO were characterized by increased plasma concentrations of SM. Plasma SM levels in individuals with AO may be an early prognostic biomarker to better predict the progression toward type 2 diabetes and metabolic syndrome.
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Biomarcadores/sangre , Lípidos/sangre , Obesidad Abdominal/sangre , Estado Prediabético/sangre , Esfingomielinas/sangre , Adulto , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad Abdominal/fisiopatología , Estado Prediabético/epidemiología , República de Corea/epidemiología , Factores de RiesgoRESUMEN
INTRODUCTION: Patients with type 2 diabetes are at risk of microvascular and macrovascular complications. Intensive glycaemic control, especially in patients with short duration of diabetes, is the mainstay of management of type 2 diabetes to lower the risk of complications. However, despite the improvement in the understanding of the pathophysiology of type 2 diabetes and development of novel glucose-lowering agents, long-term durable glycaemic control remains a difficult goal to achieve. Several challenging clinical trials proved that an early combination therapy with a variety of glucose-lowering agents had a more favourable effect than conventional stepwise therapy in terms of glycaemic control. We aim to evaluate the efficacy and tolerability of a novel, initial triple combination therapy with metformin, sodium glucose cotransporter 2 inhibitor (dapagliflozin) and dipeptidyl peptidase-4 inhibitor (saxagliptin) compared with conventional stepwise add-on therapy in drug-naïve patients with recent-onset type 2 diabetes. METHODS AND ANALYSIS: This study is a multicentre, prospective, randomised, open-label, parallel group, comparator-controlled trial. A total of 104 eligible participants will be randomised to either the initial combination therapy group or the conventional stepwise add-on therapy group for 104 weeks. The primary endpoint is the proportion of patients who achieved haemoglobin A1c level<6.5% without hypoglycaemia, weight gain or discontinuation due to adverse events at 104 weeks. This trial will determine whether a novel triple combination therapy with metformin, dapagliflozin and saxagliptin has a beneficial effect on durable glycaemic control compared with conventional therapy in drug-naïve patients with type 2 diabetes. ETHICS AND DISSEMINATION: This study protocol was approved by the local institutional review boards and independent ethics committees over the recruitment sites. Results of this study will be disseminated in scientific journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT02946632; Pre-results.
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Adamantano/análogos & derivados , Compuestos de Bencidrilo , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus Tipo 2 , Dipéptidos , Quimioterapia Combinada/métodos , Glucósidos , Metformina , Adamantano/administración & dosificación , Adamantano/efectos adversos , Adulto , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/efectos adversos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Dipéptidos/administración & dosificación , Dipéptidos/efectos adversos , Monitoreo de Drogas/métodos , Monitoreo de Drogas/normas , Glucósidos/administración & dosificación , Glucósidos/efectos adversos , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Masculino , Metformina/administración & dosificación , Metformina/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: A relationship between renin-angiotensin system (RAS) components and metabolic syndrome (MetS) has been suggested, but not elucidated clearly. We examined the levels of RAS components in patients with and without MetS and their association with MetS in Korean population. METHODS: This study was approved by the review boards of the participating institutions and endorsed by the Korean Society of Lipid and Atherosclerosis. We screened 892 Koreans aged ≥20 years who underwent evaluation of hypertension, diabetes, or dyslipidemia at 6 tertiary hospitals in 2015-2016. After excluding patients who were taking diuretics, ß-blockers, or RAS blockers, or suspected of primary aldosteronism, 829 individuals were enrolled. Anthropometric and biochemical parameters including aldosterone, plasma renin activity (PRA), and aldosterone-to-PRA ratio were evaluated. The homeostasis model assessment for insulin resistance (HOMA-IR) were used for evaluating insulin resistance. RESULTS: The mean age of the participants was 52.8±12.8 years, 56.3% were male, and their mean systolic and diastolic blood pressures were 133.9±20.0 and 81.2±14.6 mmHg, respectively. The levels of serum aldosterone, but not PRA, were significantly higher in subjects with MetS than in those without (20.6±33.6 vs. 15.3±12.2 ng/dL, p<0.05), and positively correlated with waist circumference, blood pressure, triglycerides, and glycated hemoglobin. The levels of aldosterone were independently associated with the number of MetS components and HOMA-IR after adjusting for conventional risk factors. CONCLUSIONS: Serum aldosterone levels were higher in Korean adults with MetS than in those without. This finding suggests that increased aldosterone level might be closely associated with insulin resistance.
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BACKGROUND: Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass density and destruction of microstructure, which can lead to an increased risk of fracture. Although many studies have been published about the relationship between end-stage renal disease and osteoporosis, research on the relationship between proteinuria and the prevalence of osteoporosis is still lacking. METHODS: We assessed 91 postmenopausal women with type 2 diabetes who visited our hospital from January 2009 to January 2012. RESULTS: Among 91 patients, the prevalence of osteoporosis and osteopenia was 35.2% (32 cases) and 32.9% (30 cases) according to bone mineral density. The patients with microalbuminuria and macroalbuminuria (urine albumin-to-creatinine ratio [UACR] ≥ 30) had a significantly higher incidence of osteoporosis compared to subjects with normoalbuminuria (P<0.05). CONCLUSIONS: This study indicates that UACR may be a useful biomarker for increased risk of osteoporosis in postmenopausal women with type 2 diabetes who have been linked to higher UACR levels.