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1.
Diabetes Obes Metab ; 26(11): 5065-5077, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39223856

RESUMEN

AIM: To evaluate the efficacy and safety of dapagliflozin versus placebo as an add-on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. PATIENTS AND METHODS: In this multicentre, randomized, double-blind, placebo-controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable-dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. RESULTS: In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was -0.70% (-7.7 mmol/mol) (p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol) was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2-h postprandial plasma glucose, fasting insulin, uric acid and gamma-glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. CONCLUSION: Dapagliflozin add-on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients.


Asunto(s)
Compuestos de Bencidrilo , Glucemia , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Glucósidos , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Metformina/uso terapéutico , Glucósidos/uso terapéutico , Glucósidos/efectos adversos , Glucósidos/administración & dosificación , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Método Doble Ciego , Masculino , Femenino , Persona de Mediana Edad , Hemoglobina Glucada/análisis , Hemoglobina Glucada/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Anciano , Glucemia/efectos de los fármacos , Resultado del Tratamiento , Adulto , Control Glucémico/métodos , Piperazinas
2.
Endocrinol Metab (Seoul) ; 39(5): 722-731, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39174014

RESUMEN

BACKGRUOUND: 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.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Ezetimiba , Fenofibrato , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Ezetimiba/uso terapéutico , Ezetimiba/administración & dosificación , Fenofibrato/uso terapéutico , Fenofibrato/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Factores de Riesgo de Enfermedad Cardiaca , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Dislipidemias/tratamiento farmacológico , Anticolesterolemiantes/uso terapéutico , Anticolesterolemiantes/administración & dosificación , Anciano , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Diabetes Obes Metab ; 26(9): 3743-3752, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38978173

RESUMEN

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.


Asunto(s)
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 terapéutico
4.
Drugs R D ; 24(2): 179-186, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38775910

RESUMEN

BACKGROUND AND OBJECTIVE: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. METHODS: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. RESULTS: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. CONCLUSION: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. CLINICAL TRIAL REGISTRATION: This trial (NCT04322266) was retrospectively registered on 9 September 2019.


Asunto(s)
Amlodipino , Estudios Cruzados , Combinación de Medicamentos , Ezetimiba , Voluntarios Sanos , Losartán , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/administración & dosificación , Amlodipino/farmacocinética , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Masculino , Ezetimiba/farmacocinética , Ezetimiba/administración & dosificación , Losartán/farmacocinética , Losartán/administración & dosificación , Adulto , Femenino , Adulto Joven , Persona de Mediana Edad , Antihipertensivos/farmacocinética , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Comprimidos , Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/administración & dosificación , Área Bajo la Curva
5.
Mol Cells ; 47(1): 100005, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38376483

RESUMEN

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease with a complex genetic basis, presenting both in familial and sporadic forms. The hexanucleotide (G4C2) repeat expansion in the C9orf72 gene, which triggers distinct pathogenic mechanisms, has been identified as a major contributor to familial and sporadic Amyotrophic lateral sclerosis cases. Animal models have proven pivotal in understanding these mechanisms; however, discrepancies between models due to variable transgene sequence, expression levels, and toxicity profiles complicate the translation of findings. Herein, we provide a systematic comparison of 7 publicly available Drosophila transgenes modeling the G4C2 expansion under uniform conditions, evaluating variations in their toxicity profiles. Further, we tested 3 previously characterized disease-modifying drugs in selected lines to uncover discrepancies among the tested strains. Our study not only deepens our understanding of the C9orf72 G4C2 mutations but also presents a framework for comparing constructs with minute structural differences. This work may be used to inform experimental designs to better model disease mechanisms and help guide the development of targeted interventions for neurodegenerative diseases, thus bridging the gap between model-based research and therapeutic application.


Asunto(s)
Esclerosis Amiotrófica Lateral , Demencia Frontotemporal , Levamisol/análogos & derivados , Enfermedades Neurodegenerativas , Animales , Drosophila/genética , Esclerosis Amiotrófica Lateral/genética , Proteína C9orf72/genética
6.
Diabetes Obes Metab ; 25(9): 2743-2755, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37337747

RESUMEN

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.


Asunto(s)
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 Tratamiento
7.
Arch Osteoporos ; 18(1): 61, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37129630

RESUMEN

In this population-based retrospective cohort study, exercising before and after the diagnosis of type 2 diabetes was significantly associated with lower risk of fractures. This result suggested that exercising might be effective in reducing fracture risk. PURPOSE: Patients with diabetes have a significantly higher risk of fractures. We aimed to investigate the association between exercise and fracture risk in new-onset type 2 diabetes. METHODS: This retrospective cohort study using the Korean National Health Insurance Service database included 170,148 patients with new-onset type 2 diabetes who underwent two cycles of health checkup between 2009-2012 and 2011-2014. The patients were classified into four groups (non-exercising, newly exercising, previously exercising, and continuously exercising) and followed up until the date of fracture, death, or December 31, 2018. Hip fractures, vertebral fractures, and any fractures were defined using diagnostic codes. RESULTS: The proportions of non-exercising, newly exercising, previously exercising, and continuously exercising patients were 65.1%, 15.7%, 10.9%, and 8.3%, respectively. Continuously exercising patients showed the lowest risk for fractures, followed by newly exercising patients using the non-exercising group as a reference. The adjusted hazard ratios (95% confidence intervals) for hip fracture, vertebral fracture, and any fracture were 0.69 (0.50-0.94), 0.73 (0.63-0.84), and 0.90 (0.83-0.97), respectively, in the continuously exercising group and 0.76 (0.61-0.95), 0.85 (0.76-0.94), and 0.93 (0.88-0.98) in the newly exercising group. The risk was lower in patients who lost less than 5% of their body weight than in those who lost 5% or more. CONCLUSION: Exercising was associated with lower risk of fractures in newly diagnosed diabetes. However, exercise accompanied by excessive weight loss may not have a significant association with a lower risk of fractures.


Asunto(s)
Diabetes Mellitus Tipo 2 , Fracturas de Cadera , Fracturas de la Columna Vertebral , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios Retrospectivos , Fracturas de Cadera/epidemiología , Fracturas de Cadera/complicaciones , Fracturas de la Columna Vertebral/complicaciones , Riesgo
8.
Diabetes Metab J ; 47(4): 523-534, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37096376

RESUMEN

BACKGRUOUND: Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments. METHODS: The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories. RESULTS: During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFRlowPU- phenotype, followed by eGFRnorPU+ and eGFRnorPU-. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFRnorPU- category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFRnorPU+ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFRlowPU-. Among altered phenotypes, the category converted to eGFRlowPU+ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU- to PU+ showed a higher risk of HHF than those who converted from PU+ to PU-. CONCLUSION: Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Insuficiencia Cardíaca , Humanos , Nefropatías Diabéticas/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Fenotipo , Insuficiencia Cardíaca/epidemiología , República de Corea/epidemiología
9.
Pharmaceuticals (Basel) ; 16(3)2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36986464

RESUMEN

Higher risk of major hemorrhage associated with concomitant use of dabigatran and simvastatin compared to other statins was previously reported with a suggestion of P-glycoprotein-mediated interaction. The aim of this study was to evaluate the effects of simvastatin on pharmacokinetics and anticoagulant effects of dabigatran, a direct oral anticoagulant. A total of 12 healthy subjects were enrolled in an open-label, two-period, single sequence study. Subjects were given 150 mg of dabigatran etexilate followed by 40 mg of once-daily simvastatin for seven days. Dabigatran etexilate was administered with simvastatin on the seventh day of simvastatin administration. Blood samples for pharmacokinetic and pharmacodynamic analyses were obtained until 24 h post-dose of dabigatran etexilate with or without co-administration of simvastatin. Pharmacokinetic parameters were derived from noncompartmental analysis for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide. When simvastatin was co-administered, geometric mean ratios of area under time-concentration curves for dabigatran etexilate, dabigatran, and dabigatran acylglucuronide were 1.47, 1.21, and 1.57, respectively, compared to when dabigatran etexilate was administered alone. Thrombin generation assay and coagulation assay showed similar profiles between before and after co-administration of simvastatin. This study provides evidence that simvastatin treatment plays a minor role in modulating pharmacokinetics and anticoagulant effects of dabigatran etexilate.

10.
Diabetol Metab Syndr ; 15(1): 32, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36855144

RESUMEN

BACKGROUND: Diabetes mellitus is a major risk factor for heart failure. A recent consensus statement recommended annual cardiac biomarker testing (e.g. natriuretic peptide or high-sensitivity cardiac troponin) for all patients with diabetes. We aimed to identify patients at a higher risk of hospitalization for heart failure among patients with type 2 diabetes to prioritize those who would require screening. METHODS: Overall, 1,189,113 patients who underwent two medical health checkup cycles (2009-2012 and 2011-2014) and had stable diabetic kidney disease (DKD) phenotype in the Korean National Health Insurance Service database were included in this study. After excluding those with concurrent proteinuria (PU) and reduced estimated glomerular filtration rate, three groups (no-DKD, PU+DKD, and PU-DKD) were identified. A fatty liver index of ≥ 60 was defined as metabolic dysfunction-associated fatty liver disease (MAFLD). Patients were followed up until December 2018 or until outcomes developed. The Cox proportional hazard model was used to compare the risk of hospitalization for heart failure across groups. RESULTS: During an average of 6.6 years of follow-up, 5781 patients developed hospitalization for heart failure. After adjusting for covariates, the risk of hospitalization for heart failure was highest in the PU+DKD group [HR 3.12, 95% CI (2.75-3.55)], followed by the PU-DKD group [HR 1.85, 95% CI (1.73-1.99)] using the no-DKD group as the reference category. The risk of hospitalization for heart failure was comparable regardless of MAFLD status in patients who already had DKD. However, in the no-DKD group, the risk of hospitalization for heart failure was 1.4 times higher in patients with MAFLD than in those without [HR 1.41, 95% CI (1.31-1.52)]. CONCLUSIONS: In lines with the international consensus statement, we suggest that annual cardiac biomarker testing should be conducted at least in patients with DKD and/or MAFLD.

11.
J Obstet Gynaecol Res ; 49(1): 280-288, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36251735

RESUMEN

AIM: To evaluate the safety and effectiveness of uterine fibroid embolization (UFE) in patients with a scarred uterus caused by a previous myomectomy or cesarean section. METHODS: A total of 140 patients who underwent embolization for symptomatic fibroids were included in this retrospective study. The patients were divided into two groups, those with a history of myomectomy and/or cesarean section (scarred uterus group, n = 56), and those without surgical history involving the uterus (no-scar group, n = 84). Demographics, embolization details, outcomes, and complications were analyzed. RESULTS: The overall clinical success rate was 89.28% in the scarred uterus group and 95.24% in the no-scar group. There was no statistical difference in infarction rate or change in fibroid volume in follow-up magnetic resonance imaging between the groups. There was one major complication in the no-scar group, but there was no statistical difference in complications between the groups. The mean follow-up period was 25.9 months. The mean symptom-free time was 27.2 months in the scarred uterus group and 21.9 months in the no-scar group without a significant difference. There were no statistically significant differences in symptom changes, recurrence, and complication rates between the groups. Recurrence seen on imaging or regrowth was more common in the group with myomectomy history. However, there was no significant difference in symptom recurrence rates. CONCLUSION: No statistically significant difference in technical and clinical outcomes was observed between the two groups. There was no significant increase in complication rates of UFE in scarred uterus group.


Asunto(s)
Embolización Terapéutica , Leiomioma , Miomectomía Uterina , Neoplasias Uterinas , Humanos , Femenino , Embarazo , Neoplasias Uterinas/cirugía , Estudios Retrospectivos , Cesárea , Útero/patología , Leiomioma/cirugía , Miomectomía Uterina/efectos adversos , Miomectomía Uterina/métodos , Resultado del Tratamiento
12.
Metabolites ; 12(12)2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36557230

RESUMEN

This study aimed to evaluate whether the single nucleotide polymorphisms of ATP-binding cassette subfamily G member 2 (ABCG2) and solute carrier family 2 member 9 (SLC2A9) affect individual blood uric acid levels using pyrosequencing. ABCG2 (rs2231142, rs72552713, rs2231137), SLC2A9 (rs3734553, rs3733591, rs16890979), and individual uric acid levels were prospectively analyzed in 250 healthy young Korean male participants. Prominent differences in uric acid levels of the alleles were observed in the SLC2A9 rs3733591 polymorphism: wild-type (AA) vs. heterozygote (AG), 0.7 mg/dL (p < 0.0001); AA vs. mutant type (GG), 1.32 mg/dL (p < 0.0001); and AG vs. GG, 0.62 mg/dL (p < 0.01). In ABCG2 single nucleotide polymorphisms (SNPs), the statistically significant differences in uric acid levels were only found in rs2231142 between CC vs. AA (1.06 mg/dL; p < 0.001), and CC vs. CA (0.59 mg/dL; p < 0.01). Serum uric acid levels based on the ABCG2 and SLC2A9 diplotype groups were also compared. The uric acid levels were the lowest in the CC/AA diplotype and highest in the AA/AG diplotype. In addition, the SNP SLC2A9 rs3733591 tended to increase the uric acid levels when the ABCG2 rs2231142 haplotypes were fixed. In conclusion, both the ABCG2 rs2231142 and SLC2A9 rs3733591 polymorphisms may additively elevate blood uric acid levels.

13.
Cancer Epidemiol ; 81: 102265, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36183558

RESUMEN

BACKGROUND: The survival rate of patients with cancer has been increasing because of the sustained anticancer effect of new drugs, such as immune checkpoints inhibitors (ICI). Unlike the existing cytotoxic chemotherapies, immunotherapy causes immune system disturbance, such as hypothyroidism. Comparative studies on hypothyroidism following administration of ICI alone and in combination with other drugs are scarce. Therefore, we investigated the incidence of hypothyroidism after ICI in patients with cancer using a national population-based database. METHODS: Using the claims data from the Health Insurance Review and Assessment service in Korea, we retrospectively investigated patients with cancer who received chemotherapy between January 1, 2014 and February 28, 2021. RESULTS: Of all patients with cancer (n = 665,445) who received all kinds of chemotherapy, those who have received ICI accounted for 1.91 %. Compare with cytotoxic chemotherapy and angiogenesis inhibitors (AIs), ICI was associated with earlier (236.1 ± 248.4 vs. 811.1 ± 661.7, P < 0.01) and more frequent (7.7 % vs. 4.4 %, P < 0.01) occurrence of hypothyroidism, as well as an increased risk of developing hypothyroidism (odds ratio [OR] 1.69, 95 % confidence interval [CI] 1.58-1.80). However, the incidence of grade 2 or higher hypothyroidism was similar in both groups of patients who received ICI (3.3 %) and AI (3.1 %). The incidence of hypothyroidism was 4.4 times higher in patients who received both AI and ICI than in those who were treated with ICI alone (OR 4.41, 95 % CI 3.40-5.71). CONCLUSIONS: This study showed a synergistic effect in patients who received multiple administrations of a drug that might be associated with thyroid dysfunction. Therefore, special attention should be paid to the treatment-related side effects when using drugs, such as AIs, concomitant with ICI treatment.

14.
Pharmaceutics ; 14(7)2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-35890386

RESUMEN

There is a large variability in individual responses to atorvastatin administration. This study assessed the pharmacogenetic effects of solute carrier organic anion transporter family member 1B1 (SLCO1B1, c.388A>G and c.521T>C) and cytochrome P450 3A5 (CYP3A5, CYP3A5*3) genetic polymorphisms on the pharmacokinetics of atorvastatin and its active metabolite, 2-hydroxy (2-OH) atorvastatin, in 46 individuals who were administered a clinically used single oral dosage of 80 mg. The Cmax and AUC of atorvastatin in CYP3A5*3/*3 carriers were 2.6- and 2.8-fold higher, respectively, than those in CYP3A5*1/*1 carriers, and similar results were observed for 2-OH atorvastatin pharmacokinetics. SLCO1B1 c.521T>C also increased the AUC of atorvastatin and 2-OH atorvastatin. The AUC ratio of atorvastatin and 2-OH atorvastatin were not affected by SLCO1B1 c.388A>G or c.521T>C, whereas CYP3A5*3 reduced the AUC ratio. In an analysis evaluating the simultaneous effect of the SLCO1B1 c.521T>C and CYP3A5*3 polymorphisms, SLCO1B1 c.521TT/CYP3A5*1/*1 carriers showed lower Cmax and AUC values for atorvastatin and 2-OH atorvastatin than in individuals with the SLCO1B1 c.521T>C and/or CYP3A5*3 genotypes. Among the participants with the SLCO1B1 c.521TT genotype, the CYP3A5*3 carriers had a higher systemic exposure to atorvastatin and 2-OH atorvastatin than the CYP3A5*1/*1 carriers. Thus, SLCO1B1 c.521T>C and CYP3A5*3 polymorphisms affect the pharmacokinetics of atorvastatin and 2-OH atorvastatin.

15.
Parkinsonism Relat Disord ; 100: 13-18, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35667188

RESUMEN

INTRODUCTION: Type 2 diabetes is a risk factor for Parkinson's disease (PD). Recently, it has been reported that proteinuria without reduced estimated glomerular filtration rate (eGFR) can increase the risk of PD development. The objective of this study was to evaluate the risk of PD among Korean adults with type 2 diabetes stratified by proteinuria (PU) and eGFR levels. METHODS: Using the Korean National Health Insurance Service database, a total of 2,217,326 patients with type 2 diabetes who underwent regular health check-ups from 2009 to 2012 were included. These patients were classified into four groups (no-diabetic kidney disease (DKD) (PU-GFR-), proteinuric DKD with normal eGFR (PU+GFR-), nonproteinuric DKD (PU-GFR+), and proteinuric DKD with reduced eGFR (PU+GFR+) and followed up until 2018. PD was defined using International Classification of Diseases, 10th revision. RESULTS: The prevalence of PU-GFR-, PU+GFR-, PU-GFR+, or PU+GFR+ phenotype was 83.3%, 5.0%, 10.1%, or 1.6%, respectively. During a median follow-up of 7.2 years, 16,079 participants developed PD. Hazard ratios for PD were 1.10 (95% confidence interval [CI]: 1.01-1.21, p = 0.0091), 1.15 (95% CI: 1.09-1.21, p < 0.0001), and 1.23 (95% CI: 1.09-1.39, p < 0.0001) for participants in PU+GFR-, PU-GFR+, and PU+GFR+ groups relative to those in the PU-GFR- group, respectively. Effects of DKD on PD were more pronounced in those aged less than 65 years. CONCLUSION: Reduced eGFR and/or proteinuria might be independent risk factors for boosting PD development among patients with type 2 diabetes. More attention should be paid to PD in patients with DKD, even in a younger aged population.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Enfermedad de Parkinson , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/etiología , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Proteinuria/complicaciones , Proteinuria/epidemiología , República de Corea/epidemiología , Factores de Riesgo
16.
Endocrinol Metab (Seoul) ; 37(1): 148-158, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35255607

RESUMEN

BACKGROUND: Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype. METHODS: In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU-GFR-), proteinuric DKD with normal eGFR (PU+GFR-), non-proteinuric DKD with reduced eGFR (PU-GFR+), and proteinuric DKD with reduced eGFR (PU+GFR+). RESULTS: The cumulative incidence of hip fractures was highest in the PU+GFR+ group, followed by the PU-GFR+ group and the PU+GFR- group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU+GFR+ group. However, the PU+GFR- group had a higher HR for hip fracture than the PU-GFR+ group (PU+GFR+ : HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU+GFR- : HR, 1.37; 95% CI, 1.30 to 1.46; PU-GFR+ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PU-GFR- group as the reference category). CONCLUSION: The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Fracturas de Cadera , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Nefropatías Diabéticas/epidemiología , Fracturas de Cadera/epidemiología , Fracturas de Cadera/etiología , Humanos , Fenotipo , República de Corea/epidemiología , Estudios Retrospectivos
17.
Pharmaceutics ; 14(3)2022 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35335967

RESUMEN

Dapagliflozin, a selective sodium-glucose co-transporter-2 inhibitor, and linagliptin, a competitive, reversible dipeptidyl peptidase-4 inhibitor, are commonly prescribed antidiabetic medications in general clinics. Since there are several merits to combining them in a fixed-dose combination product, this study investigated the pharmacokinetic equivalence between the individual component (IC) and fixed-combination drug product (FCDP) forms of dapagliflozin and linagliptin. A randomized, open-label, single-dose crossover study was conducted. All participants (n = 48) were randomly allocated to group A (period 1: ICs, period 2: FCDP) or group B (period 1: FCDP, period 2: ICs), and each group received either a single dose of IN-C009 (FCDP) or single doses of both dapagliflozin and linagliptin. There was no statistically significant difference found between the pharmacokinetic variables of FCDP and IC. The values of estimated geometric mean ratios and the 90% confidence interval for both maximum concentration and area under the plasma drug concentration-time curve were within the range of 0.8-1.25 for both dapagliflozin and linagliptin. The results of the clinical study demonstrated comparable pharmacokinetic characteristics between IC and FCDP forms of dapagliflozin and linagliptin. The combined use of dapagliflozin and linagliptin was safe and tolerable in both formulations.

18.
Diabetes Metab J ; 46(4): 567-577, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35130688

RESUMEN

BACKGROUND: Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients. METHODS: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF). RESULTS: After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease. CONCLUSION: In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Accidente Cerebrovascular , Tiazolidinedionas , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa , Insuficiencia Cardíaca/epidemiología , Humanos , Hipoglucemiantes/uso terapéutico , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Tiazolidinedionas/uso terapéutico
19.
Pharmaceutics ; 14(2)2022 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-35213990

RESUMEN

Dabigatran (DAB) is an orally administered thrombin inhibitor. Both DAB and its main metabolite dabigatran acylglucuronide (DABG) have established anticoagulant effects. Here, we aimed to compare the relative anticoagulant effects of DABG and DAB in humans. Anticoagulant effects of DAB and DABG were measured in vitro using a thrombin generation assay. Additionally, their effects on other coagulation assays including PT, aPTT, TT, and fibrinogen were compared. Both DAB and DABG showed inhibitory effects on thrombin generation in a dose-dependent manner, but DABG exhibited a weaker inhibitory effect than that of DAB. The IC50 values of DAB and DABG on thrombin generation AUC were 134.1 ng/mL and 281.9 ng/mL, respectively. DABG also exhibited weaker anticoagulant effects than DAB on PT, aPTT, and TT. The results of the present study indicate that the anticoagulant effect of DABG, a main active DAB metabolite, is weaker than that of DAB.

20.
Yonsei Med J ; 63(2): 133-140, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35083898

RESUMEN

PURPOSE: Bone mineral density (BMD) determined by dual-energy X-ray absorptiometry is considered a gold standard for diagnosing osteoporosis. Some people show discordance in BMD values measured at the femur and that at the lumbar spine (LS). The aim of the present study was to investigate whether differences in BMD T-scores between the LS and femur neck (FN) are associated with renal dysfunction in the general population of Korea. MATERIALS AND METHODS: We analyzed national data for 17306 adults from the Korean National Health and Nutrition Examination Survey conducted between 2008 and 2011. BMD T-score differences between LS and FN (termed BMD offset) were calculated by subtracting FN T-scores from LS T-scores. Diminished renal function was defined as estimated glomerular filtration rates (eGFR) less than 60 mL/min/1.73 m². RESULTS: Among those aged ≥50 years, BMD offset was negatively associated with eGFR levels. Additionally, eGFR levels decreased linearly across increasing BMD offset quartiles. Men and women with an offset of >1.5 showed a 4.79-times and 2.51-times higher risk of renal dysfunction, respectively, compared to individuals with an offset of ≤0, after adjusting for age, body mass index, educational level, current smoking, and physical activity. In contrast, there was little evidence of an association between renal dysfunction and BMD offset in subjects aged <50 years. CONCLUSION: Discordance between LS and FN BMDs was significantly associated with renal dysfunction in subjects aged ≥50 years. When assessing bone health in older chronic kidney disease patients, physicians should consider the possibility of BMD discordance between LS and FN.


Asunto(s)
Densidad Ósea , Enfermedades Renales , Absorciometría de Fotón , Adulto , Anciano , Femenino , Cuello Femoral/diagnóstico por imagen , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Encuestas Nutricionales
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