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All-trans retinoic acid (ATRA) is used as standard induction therapy for acute promyelocytic leukemia (APL), but it is contraindicated for patients on hemodialysis. We present a case of a patient with APL on hemodialysis, intubated, and with marked disseminated intravascular coagulation (DIC) who was successfully treated with ATRA. A 49-year-old man was transferred to our hospital and admitted into the intensive care unit due to renal dysfunction, DIC, and pneumonia. Promyelocytes were noted in the peripheral blood, and he was diagnosed with APL after bone-marrow examination. Because of renal dysfunction, only Ara-C was used but with a reduced dose. The patient's condition improved, and he was extubated and withdrawn from dialysis on the 5th day of hospitalization. The patient suffered from APL syndrome during induction therapy, which necessitated ATRA withdrawal and steroid administration. Remission was achieved after induction therapy, and the patient is currently on maintenance therapy. There are few cases of patients with APL on hemodialysis who were treated with ATRA; hence, it is necessary to review the treatment plan for these patients.
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Lesión Renal Aguda , Leucemia Promielocítica Aguda , Masculino , Humanos , Persona de Mediana Edad , Leucemia Promielocítica Aguda/tratamiento farmacológico , Inducción de Remisión , Tretinoina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Diálisis RenalRESUMEN
INTRODUCTION: A new treatment for coronavirus disease (COVID-19), REGN-COV2, a cocktail consisting of two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been approved for patients at a risk of developing more severe disease. METHODS: We retrospectively reviewed patients recently diagnosed with COVID-19 with risk factors for severe infection, who were treated with the REGN-COV2 antibody cocktail between July and September 2021. The REGN-COV2 antibody cocktail was administered to patients within 7 days of disease onset, with an oxygen saturation of >93%, and with at least one comorbidity. We investigated the percentage of patients with COVID-19-related hospitalization or death, the duration of symptoms after treatment, and the adverse effects of treatment. RESULTS: A total of 108 patients were reviewed. Of them, 64% were aged ≥50 years, 31% had obesity, 36% had hypertension, and 18% had diabetes. In addition, 49% had multiple risk factors for severe COVID-19. Overall, 12 patients (11%) needed COVID-19-related hospitalization. No adverse effects of treatment were observed. CONCLUSIONS: This study shows that treatment with the REGN-COV2 antibody cocktail is safe and beneficial in patients at a risk of developing severe COVID-19.
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COVID-19 , SARS-CoV-2 , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes/uso terapéutico , Combinación de Medicamentos , Humanos , Japón , Estudios RetrospectivosRESUMEN
AIMS: To investigate the safety and tolerability of 5 and 10 mg dapagliflozin added to insulin therapy over 52 weeks in Japanese patients with inadequately controlled type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This randomized, open-label, parallel-group, multicentre phase III clinical trial was conducted from October 26, 2015 to June 15, 2017. The primary endpoint was the occurrence of adverse events such as hypoglycaemia and diabetic ketoacidosis. Secondary endpoints included changes in glycaemic parameters, total daily insulin dosage and body weight over time. The efficacy of dapagliflozin in patients stratified by body mass index (BMI) <25.0 and ≥25.0 kg/m2 was evaluated in a subgroup analysis. RESULTS: In total, 151 patients received 5 mg (n = 76) or 10 mg (n = 75) dapagliflozin once daily for 52 weeks. Adverse events were observed in 88.2% and 73.3% of patients in the 5 and 10 mg dapagliflozin groups, respectively. Severe hypoglycaemia was reported in 2.6% (n = 2) and 6.7% (n = 5) of patients, and diabetic ketoacidosis in 2.6% (n = 2) and 1.3% (n = 1) of patients in the 5 and 10 mg dapagliflozin groups, respectively. The adjusted mean (95% confidence interval) changes in glycated haemoglobin at week 52 were -0.33% (-0.50, -0.15) and -0.36% (-0.53, -0.18) in the 5 and 10 mg dapagliflozin groups, respectively. There were no differences in efficacy parameters when stratified by BMI. CONCLUSIONS: This study demonstrated the long-term safety and tolerability of dapagliflozin added to insulin therapy in Japanese patients with inadequately controlled T1DM.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Compuestos de Bencidrilo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucósidos , Humanos , Hipoglucemiantes/efectos adversos , Japón/epidemiologíaRESUMEN
BACKGROUND: Most existing data regarding effects of uric acid (UA) on diabetic kidney disease have considered patients with preserved kidney function. We examined a hypothesis that there are differences in the effects of serum UA levels on the decline in kidney function depending on baseline kidney function in diabetic patients. METHODS: In this historical cohort study, 7033 type 2 diabetic patients were analyzed and classified into two groups as follows: nonchronic kidney disease (non-CKD), with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 4994), and CKD, with an eGFR <60 mL/min/1.73 m2 (n = 2039). The composite endpoint was a ≥30% decrease in eGFR from baseline or the initiation of renal replacement therapy. The hazard ratio (HR) of serum UA levels at baseline was estimated using multivariate Cox proportional hazards models. RESULTS: There was a significant interaction between UA levels and baseline eGFR with respect to the endpoint (P < 0.001). The HRs of 1 mg/dL increase in UA levels were 1.13 [95% confidence interval (CI) 1.05-1.22, P = 0.002] and 0.93 (95% CI 0.88-0.99, P = 0.02) in the non-CKD and CKD groups, respectively. When patients were classified by quintile of UA levels, the HRs of those in the 5th quintile (versus 1st quintile) were 1.64 (95% CI 1.23-2.18, P < 0.001) and 0.76 (95% CI 0.58-0.99, P = 0.05) in the non-CKD and CKD groups, respectively. CONCLUSIONS: The effects of UA on kidney function decline might differ depending on baseline kidney function in type 2 diabetic patients. High UA levels are the prognostic factor only in patients with preserved kidney function.
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Diabetes Mellitus Tipo 2/sangre , Hiperuricemia/sangre , Insuficiencia Renal Crónica/sangre , Ácido Úrico/sangre , Anciano , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Humanos , Japón , Riñón/fisiología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/terapia , Terapia de Reemplazo Renal/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Clusters of autoimmune diseases (ADs) are present in some people with type 1 diabetes. This clustering suggests the existence of common genetic backgrounds for abnormal autoimmunity in these individuals. However, the genetic differences between type 1 diabetes patients with and without other ADs are not well known. METHODS: To investigate the clinical background and genetic differences between type 1 diabetes patients with and without other ADs, single nucleotide polymorphisms (SNPs) in the CTLA4, SUMO4, PTPN22, IRF5, STAT4, and BLK genes were analysed by using either a TaqMan assay or direct sequencing. The frequencies of alleles, genotypes of each gene, and the human leukocyte antigen (HLA) haplotype were analysed to investigate differences among 3 groups: type 1 diabetes with systemic ADs (group A), type 1 diabetes with other organ-specific ADs (group B), and type 1 diabetes without other ADs (group C). RESULTS: The frequency of the C allele in the -1123G > C SNP in the PTPN22 gene promoter was significantly higher in groups A and B than in group C (P = .0258 and .0207, respectively). The allele frequencies of the other SNPs were comparable. The frequency of HLA DRB1*0405-DQB1*0401 was significantly higher in groups A and B than in group C (P = .021 and .0395, respectively). CONCLUSIONS: The -1123G > C SNP in the PTPN22 gene promoter and HLA DRB1*0405-DQB1*0401 might influence the concurrence of systemic and organ-specific ADs in patients with type 1 diabetes.
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Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/genética , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/genética , Adulto , Anciano , Antígeno CTLA-4/genética , Diabetes Mellitus Tipo 1/inmunología , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Humanos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genética , Adulto JovenRESUMEN
BACKGROUND/AIMS: Glyceraldehyde-derived advanced glycation end products (glycer-AGE; also called Toxic-AGE [TAGE]) play a crucial role in the pathogenesis of diabetic angiopathy. However, the relationships between vitreous glycer-AGE levels and diabetic retinopathy (DR) severity, and between glycer-AGE levels and the levels of other angiogenic factors remain unknown. We investigated the correlation between levels of vitreous biomarkers, including glycer-AGE and angiogenic factors (vascular endothelial growth factor [VEGF], interleukin [IL]-8, leptin, placental growth factor [PlGF], endoglin, and fibroblast growth factor [FGF]-2) in patients with DR, using three DR staging groups. METHODS: In this cross-sectional study, we examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (non-proliferative DR [NPDR, n = 8]; PDR with simple vitreous haemorrhage [VH, n = 17]; or PDR with a fibrovascular proliferative membrane [FVM, n = 8]). Vitreous levels of glycer-AGE and VEGF were evaluated using enzyme-linked immunosorbent assays. Vitreous levels of IL-8, leptin, PlGF, endoglin, and FGF-2 were evaluated using beaded assay methods. RESULTS: Vitreous levels of glycer-AGE in the FVM group were significantly higher than those in the NPDR and VH groups (all p < 0.05). Vitreous levels of VEGF (r = 0.85, p = 1.7 × 10-6) and leptin (r = 0.60, p = 5.0 × 10-3) were significantly correlated with levels of PlGF. CONCLUSION: The two systems (VEGF-PlGF-leptin and glycer-AGE) were represented in these measured biomarkers. High vitreous levels of both VEGF and glycer-AGE may be linked to more severe DR, suggesting that anti-VEGF and anti-TAGE therapy may be an important part of the therapeutic strategy for DR.
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Inductores de la Angiogénesis/metabolismo , Retinopatía Diabética/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Cuerpo Vítreo/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Estudios Transversales , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: There are no reports of very long follow-up studies of pregnant women with type 2 diabetes after delivery. Here we describe cases of Japanese women whom we treated for 20 to 50 years after deliveries to investigate the relationship between blood glucose control and diabetic complications. METHODS: In Japan, the prevalence of type 1 diabetes is very low, and we have very few long-term follow-up cases with type 1 diabetes. Therefore, we chose to describe subjects with type 2 diabetes only. We present data on a total of 80 deliveries, 68 cases, treated by one of us (Y.O.) for more than a 50-year period. They are divided into 4 groups based on duration of treatment after delivery: more than 50 years (1 delivery, 1 patient), 40 to 49 years (13 deliveries, 11 patients), 30 to 39 years (19 deliveries, 16 patients), and 20 to 29 years (47 deliveries, 40 patients). Their present average ages in these 4 groups are 77, 72.4, 65.9, and 55.5 years, respectively. Their average HbA1c levels at last visit, in May 2014, are 8.2%, 7.6%.,7.2%, and 8.3%, respectively. RESULTS: Despite elevated HbA1c levels, they had relatively few complications: 40% (no retinopathy), 43.8% (simple retinopathy), and 12.5% (treated with photocoagulation); 67.5% (no albuminuria), 26.3% (albuminuria), and 6.3% (treated with renal transplantation or hemodialysis). Therefore, even if glycemic control is not ideal, nonstop treatment of Japanese women for type 2 diabetes after deliveries is effective to prevent diabetic complications. CONCLUSIONS: Long-term attention to care of diabetes after pregnancy may be preventive of diabetic complications in other populations as well.
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Albuminuria/prevención & control , Parto Obstétrico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Retinopatía Diabética/prevención & control , Hipoglucemiantes/uso terapéutico , Adulto , Biomarcadores/análisis , Glucemia/análisis , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Japón , Embarazo , PronósticoRESUMEN
Poorly controlled diabetes mellitus (DM) patients sometimes show serum transaminase elevations due to steatohepatitis. However, we experienced four cases with type 1 DM with sharp elevations in serum transaminases that could not be explained by steatohepatitis alone and showed bright liver. They were diagnosed with glycogenic hepatopathy (GH) clinicopathologically. The four patients had a median age of 22.5 years (range, 19-29 years) and 12.5 (4-15)-year histories of type 1 DM and showed marked increases in serum transaminases (aspartate aminotransferase, 698 U/L [469-2763 U/L]; alanine transaminase, 255 U/L [216-956 U/L]). Diabetes mellitus control was poor and hemoglobin A1c was 12.7% (11-16.5%). Three cases had a past history of diabetic ketoacidosis. Hepatomegaly and hyperdense liver were seen on computed tomography scans. Magnetic resonance imaging showed low intensity in T2-weighted images. The pathological findings revealed pale and swollen hepatocytes and glycogenated nuclei. The architecture of the liver was preserved, and steatosis and fibrosis were mild. The cytoplasm of hepatocytes stained densely positive with periodic acid-Schiff, and the positive staining disappeared after diastase digestion, suggesting glycogen deposition. No other cause of hepatitis was evident, and the diagnosis was GH. Elevated transaminases improved within 1 month with good glycemic control. Transaminase elevations were observed several times in three cases with poor glycemic control. Glycogenic hepatopathy is rare, but extremely high serum elevations of transaminases are important to identify clinically. Despite showing a good clinical course in general, GH sometimes recurs and requires strict glycemic control. Clinicians should be aware of and recognize GH when dealing with uncontrolled DM patients.
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BACKGROUND: Effects of statins on kidneys in diabetic patients remain unclear. METHODS: This was an observational, historical cohort study of type 2 diabetic patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. We studied 412 patients newly prescribed statins, and 946 controls without a prescription history of statins (including the follow-up period). Outcomes were annual change in eGFR, ≥30 % decrease in eGFR from baseline, and progression of albuminuria, analyzed using a propensity score matching. RESULTS: A total of 168 pairs were matched for propensity score. Annual eGFR change (mL/min/1.73 m2/year) in the statin group was greater than in controls (-2.24 vs. -1.56, p = 0.024). The hazard ratio of the statin group (vs. controls) for ≥30 % decrease in eGFR and progression of albuminuria was 1.74 (p = 0.082) and 0.85 (p = 0.624), respectively. When the statin group was classified by differences in statin solubility, eGFR change and hazard ratio for ≥30 % decrease in eGFR in the lipophilic statin group were greater than in controls (-2.64 vs. -1.71, p = 0.031 and 2.15, p = 0.049); however, the outcomes in the hydrophilic statin group were not different (-2.35 vs. -1.71, p = 0.106 and 1.08, p = 0.827). The hazard ratio of lipophilic and hydrophilic statin group (vs. controls) for progression of albuminuria was 1.31 (p = 0.552) and 0.69 (p = 0.367). In the analyses using the unmatched cohort, similar results were obtained. CONCLUSIONS: Statins have no beneficial effects on kidneys in diabetic patients. In fact, lipophilic statins might have potential harmful effects on kidney function.
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Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Dislipidemias/tratamiento farmacológico , Tasa de Filtración Glomerular/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Riñón/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Albuminuria/etiología , Albuminuria/fisiopatología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Dislipidemias/sangre , Dislipidemias/complicaciones , Dislipidemias/diagnóstico , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Riñón/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: We investigated the relationship between vitreous levels of soluble receptor for advanced glycation end products (sRAGE) and vascular endothelial growth factor (VEGF) and renal function, and correlations between vitreous sRAGE levels and proliferative diabetic retinopathy (PDR) activity. METHODS: We examined 33 eyes from 33 patients with diabetes mellitus who underwent a vitrectomy (eight patients in the non-PDR [NPDR] group and 25 in the PDR group). Serum creatinine levels and estimated glomerular filtration rate (eGFR) were measured and classified according to the chronic kidney disease (CKD)-staging method. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify vitreous sRAGE and VEGF levels. RESULTS: Vitreous sRAGE levels were significantly higher in PDR group compared to NPDR group (p = 0.00003). Vitreous sRAGE levels were significantly higher in patients with CKD stage 5 (end-stage renal failure or hemodialysis) than in patients with CKD stage 1 or 2 (p < 0.01) and 3 or 4 (p < 0.05), and were significantly correlated with eGFR (r = - 0.490, p = 0.007) and creatinine levels (r = 0.484, p = 0.006). Within the PDR group, patients with low (<27 pg/mL) sRAGE levels required repeat vitreous surgeries for early postoperative vitreous hemorrhage significantly more frequently than those with high (≥27 pg/mL) sRAGE levels (p = 0.0067). CONCLUSIONS: Vitreous sRAGE levels were significantly correlated with renal function, and low vitreous sRAGE levels in patients with PDR were associated with postoperative vitreous hemorrhage. Vitreous sRAGE may be a useful biomarker for renal dysfunction associated with diabetic retinopathy.
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Retinopatía Diabética/metabolismo , Fallo Renal Crónico/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Cuerpo Vítreo/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Creatinina/análisis , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
PURPOSE: Total pancreatectomy (TP) for pancreatic neoplasms is associated with high morbidity and mortality rates. However, with recent advances in surgical techniques and improved postoperative management, the number of cases with clinical indications for TP is increasing. Here, we evaluated the clinical outcomes post-TP. MATERIALS AND METHODS: Patients (n = 41) who underwent TP between 2004 and 2011 at Tokyo Women's Medical University were retrospectively examined. Pre- and postoperative clinicophysiological data were collected up to 12 months post-TP and then analyzed. RESULTS: Only glycated hemoglobin (HbA1c), percentage of lymphocytes and hepatic Hounsfield unit level on computed tomography (CT) were significantly different between the preoperative state and at 12 months post-TP, while other clinicophysiological parameters remained unchanged. The quantity of the pancreatic enzyme administered significantly influenced glycemic control at 12 months post-TP (p < 0.05). CONCLUSIONS: All clinicophysiological parameters except for HbA1c were temporarily decreased after TP but normalized by 12 months. Thus, TP is a feasible surgical approach to treating pancreatic neoplasms with the potential to spread across the entire pancreas when adequately supplemented by synthetic insulin and pancreatic enzymes.
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Hígado/diagnóstico por imagen , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Anciano , Glucemia , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina/administración & dosificación , Japón , Masculino , Persona de Mediana Edad , Morbilidad , Pancreatectomía/efectos adversos , Neoplasias Pancreáticas/terapia , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Análisis de Regresión , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Post-transplant hyperglycaemia of diabetic patients may cause recurrent diabetic kidney disease (DKD) in kidney allografts. We report a patient with slowly progressive DKD with calcineurin inhibitor toxicity (CNI) toxicity after the kidney transplantation. A 28-year-old female with type 1 diabetes mellitus underwent successful kidney transplantation from her mother in April 2003, and the kidney graft survived for more than 10 years. She was treated with combined immunosuppressive therapy consisting of cyclosporine and mycophenolate mofetil. After transplantation, she continued to take insulin injection four times per day, but her glycosylated haemoglobin (HbA1c) was above 10%. Protocol allograft kidney biopsies performed 5 and 10 years after transplantation revealed the recurrence of slowly progressive diabetic kidney disease. In addition, arteriolar hyalinosis partly associated with calcineurin inhibitor toxicity (CNI) was detected with progression. Post-transplant hyperglycaemia causes recurrent diabetic kidney disease (DKD) in kidney allografts, but its progression is usually slow. For long-term management, it is important to prevent the progression of the calcineurin inhibitor arteriolopathy, as well as maintain favourable glycaemic control.
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Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/cirugía , Trasplante de Riñón/efectos adversos , Riñón/patología , Adulto , Arterioloesclerosis/inducido químicamente , Biomarcadores/sangre , Biopsia , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Inhibidores de la Calcineurina/efectos adversos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/etiología , Progresión de la Enfermedad , Esquema de Medicación , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Inmunosupresores/efectos adversos , Insulina/administración & dosificación , Riñón/efectos de los fármacos , Riñón/metabolismo , Donadores Vivos , Microscopía Electrónica , Recurrencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: The first clinical manifestation of diabetic kidney disease is usually the development of microalbuminuria. However, recent studies have focused on diabetic patients with reduced glomerular filtration rate (GFR) without albuminuria. To evaluate the association of albuminuria and GFR with renal outcomes, we performed an observational study. METHODS: A total of 3231 type 2 diabetic patients were included in this study between 2003 and 2005. There were 1249 women and the mean age was 59 ± 12 years. The renal endpoints were defined as the initiation of renal replacement therapy (RRT) or 50% reduction from the baseline of estimated GFR (eGFR). RESULTS: At baseline, 669 (20.7%) patients had eGFR <60 mL/min per 1.73 m(2) and 1134 (35.1%) had albuminuria. During the mean follow-up period of 5.9 ± 1.6 years, 107 patients initiated RRT. A 50% reduction of eGFR from the baseline value was found in 279 patients. None of the normoalbuminuric subjects with or without reduced eGFR required RRT during the observational period (P < 0.01). Compared to normoalbuminuria patients with eGFR ≥60 mL/min per 1.73 m(2) at baseline, the group of normoalbuminuria patients with reduced eGFR had a 2.5-fold risk of developing the renal endpoints, (95% confidence interval (CI): 1.0-6.3, P = 0.053). Patients with microalbuminuria with eGFR ≥60 mL/min per 1.73 m(2) at baseline had a 5.0-fold risk of developing the evaluated renal endpoints (95% CI: 2.8-8.8, P < 0.001). CONCLUSION: Albuminuria was a significant predictor for the evaluated renal endpoints, but the impact of eGFR is likely to be less than that of albuminuria.
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Albuminuria/etiología , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Tasa de Filtración Glomerular , Riñón/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Albuminuria/diagnóstico , Albuminuria/fisiopatología , Albuminuria/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/terapia , Progresión de la Enfermedad , Femenino , Hospitales Universitarios , Humanos , Japón , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Diálisis Renal , Factores de Riesgo , Adulto JovenRESUMEN
Glucagon-like peptide (GLP)-1 analog based therapies are used not only for their insulinotropic effects, but also for their pleiotropic effects that improve pancreatic ß cell function. Liraglutide is a long acting derivative of human GLP-1(7-37), which is a cleavage product encompassing amino acids 7-37 of GLP-1. In this study, we examined whether Liraglutide treatment restore the glucose-stimulated mitochondrial response of ß cells with chemically induced mitochondrial damage. We tested three GLP-1-related proteins: human GLP-1(1-37), GLP-1(7-37) and Liraglutide. To measure changes of the mitochondrial pH quantitatively in real-time, we have developed a bioengineered ß cell line. We generated a mitochondrial damaged model by treating ß cells with ethidium bromide (EtBr; 0.5 or 1 µg/mL for 48 h). EtBr treatment reduced the response to 25 mM glucose in mitochondrial pH in a dose- and time-dependent manner. GLP-1(7-37) (100 nM) enhanced the response of mitochondria to glucose stimulation in undamaged ß cells. Preincubation with Liraglutide (1 nM) or GLP-1 (100 nM) for 3h recovered the mitochondrial response to glucose in damaged ß cells, however, GLP-1(7-37) (100 nM) did not. When GLP-1(7-37) was administered in stepwise increments (i.e., starting with 20 nM to reach 100 nM in 3h), similar recovery of the mitochondrial function was observed. The results suggest that Liraglutide is effective to recover glucose-stimulated mitochondrial response in damaged ß cells.
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Péptido 1 Similar al Glucagón/análogos & derivados , Células Secretoras de Insulina/efectos de los fármacos , Membranas Mitocondriales/efectos de los fármacos , Animales , Etidio/toxicidad , Péptido 1 Similar al Glucagón/farmacología , Glucosa/farmacología , Humanos , Liraglutida , Fragmentos de Péptidos/farmacología , RatasRESUMEN
BACKGROUND: A recent genome-wide association study for diabetic nephropathy in European type 1 diabetes identified 3 candidate loci for diabetic nephropathy. In this study, we examined the association of the 3 single nucleotide polymorphism (SNP) loci with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes. METHODS: We genotyped 3 SNPs, rs7583877 in AFF3, rs12437854 in the RGMA-MCTP2 locus and rs7588550 in ERBB4, for 2,300 Japanese patients with type 2 diabetes [initial study, 1,055 nephropathy cases with overt proteinuria or with end-stage renal disease (ESRD) and 1,245 control patients with normoalbuminuria]. The association of these SNPs with diabetic nephropathy was examined by using a logistic regression analysis. RESULTS: We observed a significant association of rs7588550 in ERBB4 with diabetic nephropathy in the Japanese patients with type 2 diabetes, although the effect direction was not consistent with that in the European study [p = 0.0126, odds ratio (OR) = 0.79, 95 % confidence interval (CI): 0.65-0.95]. We further examined the association of rs7588550 with diabetic nephropathy in an independent Japanese cohort (596 nephropathy cases and 311 controls) and observed the same trend of the association with the initial study. We did not observe any association of the remaining 2 SNP loci with diabetic nephropathy in the present Japanese sample. CONCLUSION: The association of SNP loci derived from GWAS in European type 1 diabetes with diabetic nephropathy was not replicated in the Japanese patients with type 2 diabetes, although the ERBB4 locus may have some effect also in Japanese type 2 diabetes.
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Pueblo Asiatico/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/genética , Población Blanca/genética , Anciano , Receptores ErbB/genética , Femenino , Proteínas Ligadas a GPI/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Fallo Renal Crónico/genética , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Receptor ErbB-4RESUMEN
This study aimed to elucidate the prognostic influence of statins in relation to the degree of inflammation at the time of endovascular therapy (EVT) for patients with peripheral artery disease (PAD). This observational study included patients with PAD who underwent EVT, including 285 statin users and 275 statin non-users. They were assigned into four groups depending on C-reactive protein (CRP) level at the time of EVT: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1-0.3 mg/dL), intermediate-high CRP (0.3-1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category. Overall, statin users showed a lower event rate than non-users (log-rank, p=0.02). However, the event rates did not differ significantly between statin users and non-users in the low, intermediate-low, and intermediate-high CRP categories. In the high CRP category, statin users showed a lower event rate than non-users (p=0.002). In this population, multivariate Cox regression analysis revealed that statin use was independently associated with the primary endpoint (hazard ratio: 0.28 [95% confidence interval: 0.14-0.55]). Statins may exert favorable prognostic effects in PAD patients with highly elevated CRP levels, but not in those with low-to-moderate CRP levels.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedad Arterial Periférica , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pronóstico , Proteína C-Reactiva/metabolismo , Enfermedad Arterial Periférica/tratamiento farmacológico , Amputación Quirúrgica , Factores de RiesgoRESUMEN
Aims: To find an index of glycemic exposure that predicts retinopathy by a simple regression setting regardless of duration in type 1 diabetes which might be useful for the care of diabetes. Materials and methods: To exclude the possible disturbing effect of metabolic memory, we examined a subgroup of patients with glycohemoglobin A1c (A1C) data for the total period of type 1 diabetes selected from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications data. Three indices-(1) mean value of yearly A1C (mA1C), (2) sum of yearly A1C values (Æ©A1C), and (3) sum of yearly A1C values above 6.5% (Æ©excessA1C)-were assessed as potential candidates. Development of retinopathy was defined by ≥ 3-steps' progression of retinopathy from baseline. Results: The areas under the receiver operating characteristics curves of the indices for development of retinopathy at years 5, 9, and 13 after the onset of diabetes were the same: 0.8481, 0.8762, and 0.8213, respectively, indicating that each index was substantially capable of predicting development of retinopathy at each timepoint. Linear regression analyses showed that each index had significant and substantial linear relations to retinopathy at each timepoint: all P < 0.0001 for slopes; contribution rate R2 = 0.21 (year 5), 0.46 (year 9), and 0.48 (year 13) for each index. But only Æ©excessA1C index appeared to have similar linear relations to retinopathy at all three timepoints (interactions by timepoint: for slopes: P = 0.1393; for intercepts: P = 0.9366). Conclusion: Æ©excessA1C may have the potential to predict retinopathy by just one linear regression setting regardless of duration in type 1 diabetes.
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[This corrects the article DOI: 10.1007/s13340-023-00654-w.].
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AIMS/INTRODUCTION: In Japan, the increasing frequency of underweight among women of reproductive age and the accompanying increase in the rate of low birth weight (LBW) are social issues. The study aimed to establish a prospective registry system for gestational diabetes mellitus (GDM) in Japan and to clarify the actual status of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. MATERIALS AND METHODS: Pregnant women with gestational diabetes mellitus and those in the normal glucose tolerance (NGT) group were enrolled in the Diabetes and Pregnancy Outcome for Mother and Baby study from October 2015. Pregnant women with positive glucose screening in early and mid-to-late pregnancy underwent a 75 g oral glucose tolerance test by gestational week 32. Gestational diabetes mellitus was diagnosed according to IADPSG criteria. Women with a positive glucose screening test at mid-to-late pregnancy but NGT were enrolled as references (NGT group). Treatment for gestational diabetes mellitus and maternal and neonatal pregnancy data were prospectively collected on outcomes. RESULTS: In total 1,795 singleton pregnancies (878 women with GDM and 824 NGT women) were analyzed. The risk of LBW and small-for-gestational age in the GDM group was significantly higher than in the NGT group. A similar relationship was found for LBW risk in the non-overweight/obese group but not in the overweight/obese group. CONCLUSIONS: We established a prospective GDM registry system in Japan. In the management of GDM in Japan, suppression of maternal weight gain may be associated with reduced fetal growth, especially in non-overweight/obese women with GDM; however, further investigation is required.
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Diabetes Gestacional , Enfermedades del Recién Nacido , Recién Nacido , Embarazo , Femenino , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Japón/epidemiología , Resultado del Embarazo/epidemiología , Obesidad/complicaciones , GlucosaRESUMEN
Inappropriately high activated clotting time (ACT) during percutaneous coronary intervention (PCI) is associated with an increased risk of bleeding events. However, whether the prescription of direct oral anticoagulants (DOACs) affects ACT kinetics during heparin use and adverse clinical events in patients who underwent PCI remains unclear. We aimed to evaluate the relations between ACT changes during and adverse clinical events after PCI in patients who were prescribed DOAC. This observational study included 246 patients who underwent PCI at the 2 cardiovascular centers who were not receiving warfarin and whose ACT was recorded immediately before and 30 minutes after injection of unfractionated heparin. Patients were divided into 2 groups according to DOAC prescription at the time of the index PCI: DOAC users (n = 31) and nonusers (n = 215). Any bleeding and systemic thromboembolic events were investigated until 30 days after PCI. The average age of this population was 70.5 years, and 66.3% were male. Average ACT was significantly higher in DOAC users than nonusers both before and 30 minutes after unfractionated heparin induction (157.2 ± 30.1 vs 131.8 ± 25.1 seconds, p <0.001; 371.1 ± 122.2 vs 308.3 ± 82.2 seconds, p <0.001; respectively). The incidence of systemic thromboembolism after PCI was low and comparable between the 2 groups (0% vs 3.7%, p = 0.60). However, the rate of any bleeding event was significantly higher in DOAC users than in nonusers (16.1% vs 4.7%, p = 0.028). Patients receiving DOAC have higher ACT during PCI and higher incidence of bleeding events than those not receiving DOAC.