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1.
Am J Physiol Endocrinol Metab ; 327(2): E194-E202, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38836778

RESUMEN

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with ß-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). ß-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = -0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in ß-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Improvements in BUN after transplantation were associated with improvements in ß-cell function.NEW & NOTEWORTHY In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in ß-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant ß-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus.


Asunto(s)
Glucemia , Intolerancia a la Glucosa , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina , Células Secretoras de Insulina , Trasplante de Riñón , Humanos , Células Secretoras de Insulina/metabolismo , Masculino , Intolerancia a la Glucosa/metabolismo , Femenino , Persona de Mediana Edad , Resistencia a la Insulina/fisiología , Adulto , Glucemia/metabolismo , Anciano
2.
Kidney Int ; 105(6): 1291-1305, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38537677

RESUMEN

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease pathologically characterized by vascular necrosis with inflammation. During AAV development, activated neutrophils produce reactive oxygen species (ROS), leading to the aberrant formation of neutrophil extracellular traps (NETs) via NETosis and subsequent fibrinoid vascular necrosis. Nuclear factor-erythroid 2-related factor 2 (Nrf2) functions as an intracellular defense system to counteract oxidative stress by providing antioxidant properties. Herein, we explored the role of Nrf2 in the pathogenesis of AAV. The role and mechanism of Nrf2 in ANCA-stimulated neutrophils and subsequent endothelial injury were evaluated in vitro using Nrf2 genetic deletion and Nrf2 activator treatment. In corresponding in vivo studies, the role of Nrf2 in ANCA-transfer AAV and spontaneous AAV murine models was examined. Pharmacological activation of Nrf2 in vitro suppressed ANCA-induced NET formation via the inhibition of ROS. In contrast, NET formation was enhanced in Nrf2-deficient neutrophils. Furthermore, Nrf2 activation protected endothelial cells from ANC-induced NETs-mediated injury. In vivo, Nrf2 activation ameliorated glomerulonephritis in two AAV models by upregulating antioxidants and inhibiting ROS-mediated NETs. Furthermore, Nrf2 activation restrained the expansion of splenic immune cells, including T lymphocytes and limited the infiltration of Th17 cells into the kidney. In contrast, Nrf2 genetic deficiency exacerbated vasculitis in a spontaneous AAV model. Thus, the pathophysiological process in AAV may be downregulated by Nrf2 activation, potentially leading to a new therapeutic strategy by regulating NETosis.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Modelos Animales de Enfermedad , Trampas Extracelulares , Ratones Noqueados , Factor 2 Relacionado con NF-E2 , Neutrófilos , Peroxidasa , Especies Reactivas de Oxígeno , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Trampas Extracelulares/inmunología , Trampas Extracelulares/metabolismo , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Neutrófilos/inmunología , Neutrófilos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Peroxidasa/metabolismo , Peroxidasa/genética , Ratones , Humanos , Estrés Oxidativo/inmunología , Ratones Endogámicos C57BL , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Glomerulonefritis/genética , Glomerulonefritis/metabolismo , Glomerulonefritis/etiología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Masculino , Riñón/patología , Riñón/inmunología , Transducción de Señal/inmunología
3.
Clin Immunol ; 264: 110255, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763433

RESUMEN

Fibroblast-like synoviocytes (FLS) play critical roles in rheumatoid arthritis (RA). Itaconate (ITA), an endogenous metabolite derived from the tricarboxylic acid (TCA) cycle, has attracted attention because of its anti-inflammatory, antiviral, and antimicrobial effects. This study evaluated the effect of ITA on FLS and its potential to treat RA. ITA significantly decreased FLS proliferation and migration in vitro, as well as mitochondrial oxidative phosphorylation and glycolysis measured by an extracellular flux analyzer. ITA accumulates metabolites including succinate and citrate in the TCA cycle. In rats with type II collagen-induced arthritis (CIA), intra-articular injection of ITA reduced arthritis and bone erosion. Irg1-deficient mice lacking the ability to produce ITA had more severe arthritis than control mice in the collagen antibody-induced arthritis. ITA ameliorated CIA by inhibiting FLS proliferation and migration. Thus, ITA may be a novel therapeutic agent for RA.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Movimiento Celular , Proliferación Celular , Fibroblastos , Succinatos , Sinoviocitos , Animales , Sinoviocitos/efectos de los fármacos , Sinoviocitos/metabolismo , Movimiento Celular/efectos de los fármacos , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Experimental/patología , Proliferación Celular/efectos de los fármacos , Succinatos/farmacología , Ratas , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Masculino , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Ratones , Ratones Noqueados , Células Cultivadas , Ratones Endogámicos DBA , Ciclo del Ácido Cítrico/efectos de los fármacos
4.
Artículo en Inglés | MEDLINE | ID: mdl-39340799

RESUMEN

OBJECTIVE: We aimed to gather real-world clinical evidence of detailed disease activity, treatments, remission rates, and adverse events (AEs) associated with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome in a prospective study. METHODS: Patients in Japan suspected of having VEXAS syndrome were enrolled in a registry study. A novel disease activity measure (VEXASCAF) assessing 11 symptoms associated with VEXAS syndrome was evaluated at enrolment and after 3 months. AEs, survival, CRP levels, and treatments were also recorded at enrolment and 3 months after enrolment. All exons of UBA1 were sequenced using a next-generation sequencer to determine the variant allele frequencies of pathogenic variants in the peripheral blood of all patients. RESULTS: Of the 55 registered patients, 30 patients were confirmed to have pathogenic variants of UBA1. All patients were male, with a median age of 73.5 years. VEXASCAF and CRP levels decreased significantly at 3 months post-enrolment, but the oral prednisolone dose did not change. Only two patients achieved complete remission according to FRENVEX at 3 months after enrolment. During the observation period of 6 months, 28 AEs were observed, including 3 deaths, 4 malignancies from two cases, 2 thromboses, and 13 infections (including 4 mycobacterial infections). Inflammation of the lung and cervical region (i.e. parotid and submandibular gland swelling, tonsillitis, cervical swelling, and pain) were the most common AEs. CONCLUSIONS: Patients with VEXAS syndrome required high-dose glucocorticoids to achieve remission, and complications-such as malignancy, thrombosis, and infection-occurred frequently within a short observation period.

5.
Rheumatology (Oxford) ; 63(3): 772-779, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37307082

RESUMEN

OBJECTIVES: Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in aPL-positive patients with or without a history of thrombosis in an international cohort (the APS ACTION cohort). Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients. METHODS: In this cross-sectional study, we analysed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analysed the demographic, clinical and laboratory characteristics based on two subgroups: (i) thrombotic APS patients with high vs low damage; and (ii) non-thrombotic aPL-positive patients with vs without damage. RESULTS: Of the 826 aPL-positive patients included in the registry as of April 2020, 586 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 174 non-thrombotic). In the thrombotic group, hyperlipidaemia (odds ratio [OR] 1.82; 95% CI 1.05, 3.15; adjusted P = 0.032), obesity (OR 2.14; 95% CI 1.23, 3.71; adjusted P = 0.007), aß2GPI high titres (OR 2.33; 95% CI 1.36, 4.02; adjusted P = 0.002) and corticosteroid use (ever) (OR 3.73; 95% CI 1.80, 7.75; adjusted P < 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55; 95% CI 1.82, 11.35; adjusted P = 0.001) and hyperlipidaemia (OR 4.32; 95% CI 1.37, 13.65; adjusted P = 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95% CI 0.075, 0.77; adjusted P = 0.016). CONCLUSIONS: DIAPS indicates substantial damage in aPL-positive patients in the APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.


Asunto(s)
Síndrome Antifosfolípido , Hiperlipidemias , Humanos , Síndrome Antifosfolípido/complicaciones , Estudios Transversales , Sistema de Registros , Anticuerpos Antifosfolípidos
6.
Artículo en Inglés | MEDLINE | ID: mdl-39423147

RESUMEN

OBJECTIVES: This study focused on the prevalence and impact of antinuclear antibodies (ANA) in antiphospholipid antibody (aPL)-positive patients without concomitant systemic autoimmune rheumatic diseases (SARDs). METHODS: Data from aPL-positive patients with or without Revised Sapporo APS classification criteria were retrieved from the APS ACTION Registry. Patients with concomitant SARDs were excluded. RESULTS: 430 aPL-positive patients were included in the analysis, 56% ANA-positive and 44% negative. ANA positivity was significantly associated with history of hematologic manifestations (persistent autoimmune hemolytic anaemia, thrombocytopenia, leukopenia and/or lymphopenia) (16% of ANA-positive vs 7% of ANA-negative, p= 0.006). Triple aPL-positivity was more frequent in the ANA-positive subgroup (p= 0.02), along with low baseline C3 and C4 levels (p= 0.05 and p= 0.009, respectively), and higher frequency for extractable nuclear antigens (ENA). Among aPL-positive patients with no APS classification, ANA-positive patients showed a higher rate of arthritis (p= 0.006). Among female patients who have experienced at least one pregnancy, 113 were ANA-positive and 96 were ANA-negative; ANA-negative patients had a higher number of pregnancies (p= 0.018), and number of live births (p= 0.014). A wider proportion of ANA-positive patients were treated with hydroxychloroquine (HCQ) (p< 0.001). CONCLUSION: When we analysed aPL-positive patients with no other SARDs, ANA status was not associated with thrombosis or pregnancy morbidity. Interestingly, ANA-positive patients showed higher rates of systemic autoimmune features, including hematologic manifestations, multiple aPL positivity, lower complement levels, ENA positivity, and joint involvement, and were more often treated with HCQ. Finally, aPL-positive subjects who were ANA-negative had a higher rate of pregnancies and live births.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38460548

RESUMEN

OBJECTIVE: To examine disease and target engagement biomarkers in the RISE-SSc trial of riociguat in early diffuse cutaneous systemic sclerosis and their potential to predict the response to treatment. METHODS: Patients were randomized to riociguat (n = 60) or placebo (n = 61) for 52 weeks. Skin biopsies and plasma/serum samples were obtained at baseline and week 14. Plasma cyclic guanosine monophosphate (cGMP) was assessed using radio-immunoassay. Alpha smooth muscle actin (αSMA) and skin thickness were determined by immunohistochemistry, mRNA markers of fibrosis by qRT-PCR in skin biopsies, and serum CXC motif chemokine ligand 4 (CXCL-4) and soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1) by enzyme-linked immunosorbent assay. RESULTS: By week 14, cGMP increased by 94 ± 78% with riociguat and 10 ± 39% with placebo (p < 0.001, riociguat vs placebo). Serum sPECAM-1 and CXCL-4 decreased with riociguat vs placebo (p = 0.004 and p = 0.008, respectively). There were no differences in skin collagen markers between the 2 groups. Higher baseline serum sPECAM-1 or the detection of αSMA-positive cells in baseline skin biopsies were associated with a larger reduction of modified Rodnan skin score from baseline at week 52 with riociguat vs placebo (interaction P-values 0.004 and 0.02, respectively). CONCLUSION: Plasma cGMP increased with riociguat, suggesting engagement with the nitric oxide-soluble guanylate cyclase-cGMP pathway. Riociguat was associated with a significant reduction in sPECAM-1 (an angiogenic biomarker) vs placebo. Elevated sPECAM-1 and the presence of αSMA-positive skin cells may help to identify patients who could benefit from riociguat in terms of skin fibrosis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02283762.

8.
Diabetes Obes Metab ; 26(3): 961-970, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38073422

RESUMEN

AIM: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) continuation, in people with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-label, prospective, randomized, parallel-group comparison study, participants receiving DPP-4is were either switched to oral semaglutide (3-14 mg/day) or continued on DPP-4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored. RESULTS: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP-4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP-4i continuation [-0.65 (95% confidence interval: -0.79, -0.51) vs. +0.05 (95% confidence interval: -0.07, 0.16) (p < .001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP-4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2-R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms. CONCLUSIONS: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP-4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Hemoglobina Glucada , Control Glucémico , Estudios Prospectivos , Hipoglucemiantes/efectos adversos , Péptidos Similares al Glucagón/efectos adversos , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/uso terapéutico
9.
Circ J ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39261026

RESUMEN

BACKGROUND: This study aimed to clarify recent clinical features and treatment outcomes in Japanese patients with newly diagnosed Takayasu arteritis (TAK) during the first 2 years of treatment. METHODS AND RESULTS: A nationwide multicenter retrospective cohort study for TAK was implemented to collect data between 2007 and 2014. The primary outcome of the study was clinical remission at Week 24. Of the 184 participants registered, 129 patients with newly diagnosed TAK were analyzed: 84% were female and the mean age at onset was 35 years. Clinical symptoms at diagnosis were mostly associated with large-vessel lesions. Frequent sites of vascular involvement included the carotid artery, subclavian artery, aortic arch, and descending aorta. The mean initial dose of prednisolone administered was 0.68 mg/kg/day, and 59% and 17% of patients received immunosuppressive drugs and biologics, respectively, by Week 104. Clinical remission at Week 24 and sustained clinical remission with daily prednisolone at ≤10 mg at Week 52 were achieved in 107 (82.9%) and 51 (39.5%) patients, respectively. The presence of signs and symptoms linked to large-vessel lesions was associated with failure to achieve sustained clinical remission at Week 52. CONCLUSIONS: We elucidated the clinical characteristics, treatment outcomes, and factors associated with failure to achieve sustained clinical remission in patients with newly diagnosed TAK in Japan during the first 2 years of treatment.

10.
BMC Endocr Disord ; 24(1): 124, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049060

RESUMEN

BACKGROUND: Oral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world. METHODS: We retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65-74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity. RESULTS: We studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (- 13.1 ± 7.5 mmol/mol and - 3.0 ± 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = -0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = -0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4). CONCLUSIONS: Oral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of ≥ 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence.


Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Anciano , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada/análisis , Anciano de 80 o más Años , Administración Oral , Glucemia/análisis , Glucemia/efectos de los fármacos , Resultado del Tratamiento , Hipoglucemia/inducido químicamente , Estudios de Seguimiento , Cognición/efectos de los fármacos
11.
Cereb Cortex ; 33(13): 8342-8351, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37005068

RESUMEN

Aberrant functional connectivity (FC) of the brain regions, evaluated by functional magnetic resonance imaging (fMRI), affects clinical courses in inflammatory arthritis (IA). The static analysis methods would be simplistic to estimate the whole picture of resting-state brain function because blood oxygen level-dependent (BOLD) signals fluctuate over time. The effects of FC dynamics on clinical course are unknown in IA. Therefore, we aimed to evaluate dynamic FC for therapeutic responsiveness to biologics in IA patients. We analyzed resting-state fMRI data of 64 IA patients in 2 cohorts. Dynamic FC was derived as a correlation coefficient of the windowed BOLD signal time series. We determined representative whole-brain dynamic FC patterns by k-means++ cluster analysis, leading to 4 distinct clusters. In the first cohort, occurrence probability of the distinct cluster was associated with favorable therapeutic response in disease activity and patients' global assessment, which was validated by the second cohort. The whole-brain FC of the distinct cluster indicated significantly increased corticocortical connectivity, and probabilistically decreased after therapy in treatment-effective patients compared with -ineffective patients. Taken together, frequent emergence of corticocortical connections was associated with clinical outcomes in IA. The coherence of corticocortical interactions might affect pain modulation, possibly relevant to therapeutic satisfaction.


Asunto(s)
Productos Biológicos , Mapeo Encefálico , Humanos , Mapeo Encefálico/métodos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Encéfalo/fisiología , Imagen por Resonancia Magnética/métodos
12.
Endocr J ; 71(4): 403-408, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38403638

RESUMEN

The proinsulin-to-C-peptide (PI:C) ratio is an index applied during the early stage of pancreatic ß-cell dysfunction. The aim of this study was to identify the characteristics associated with the PI:C ratio to discuss pancreatic ß-cell dysfunction progression during the natural course of type 2 diabetes and its relationship with glycemic management. This multicenter, prospective observational study included 272 outpatients with type 2 diabetes. Continuous glucose monitoring was performed and fasting blood samples were collected and analyzed. We identified the clinical factors associated with the PI:C ratio by multiple regression analysis. The mean age of the cohort was 68.0 years, mean hemoglobin A1c 7.1% (54 mmol/mol), and mean body mass index 24.9 kg/m2. Multiple regression analysis showed that a prolonged time above the target glucose range (>180 mg/dL) and high body mass index contributed to a high PI:C ratio. However, no associations were found between the PI:C ratio and glucose variability indices. These findings suggested that the PI:C ratio is positively associated with a prolonged hyperglycemic time in type 2 diabetes, whereas its relationship with glucose variability remains unclear.


Asunto(s)
Glucemia , Péptido C , Diabetes Mellitus Tipo 2 , Hiperglucemia , Proinsulina , Humanos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Proinsulina/sangre , Anciano , Péptido C/sangre , Persona de Mediana Edad , Hiperglucemia/sangre , Estudios Prospectivos , Glucemia/metabolismo , Glucemia/análisis , Índice de Masa Corporal , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Células Secretoras de Insulina/metabolismo , Automonitorización de la Glucosa Sanguínea
13.
Endocr J ; 71(2): 193-197, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38123335

RESUMEN

The post-hoc study, derived from our previous prospective observational study, investigated the association between fasting serum proinsulin levels and hepatic steatosis in people with type 2 diabetes. The severity of hepatic steatosis was assessed using the fatty liver index. A total of 268 participants were divided into three groups: low (n = 110), moderate (n = 75), and high fatty liver index (n = 83). In both the crude and age/sex-adjusted analysis, logarithm-transformed proinsulin was significantly higher in the high fatty liver index group than in the low or moderate groups (all p < 0.01). The moderate fatty liver index group showed higher logarithm-transformed proinsulin than the low group (both p < 0.01). Positive associations between proinsulin and fatty liver index shown in this study would support an involvement of hepato-pancreatic crosstalk in the pathophysiology of type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hígado Graso , Enfermedad del Hígado Graso no Alcohólico , Humanos , Proinsulina , Estudios Prospectivos , Enfermedad del Hígado Graso no Alcohólico/complicaciones
14.
Endocr J ; 71(6): 603-616, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38658349

RESUMEN

Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 ± 12.6 years; body mass index 29.6 ± 6.0 kg/m2) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 ± 1.11% to 6.88 ± 0.91% (p < 0.001) and 80.2 ± 19.2 kg to 77.6 ± 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting.


Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Anciano , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Adulto , Administración Oral , Japón , Resultado del Tratamiento , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Glucemia/análisis , Peso Corporal/efectos de los fármacos
15.
Mod Rheumatol ; 34(6): 1202-1212, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38581672

RESUMEN

OBJECTIVES: To investigate the diagnostic and therapeutic landscape for patients with connective tissue disease (CTD) and CTD-associated pulmonary arterial hypertension (CTD-PAH) in acute-care general hospitals in Japan. METHODS: We conducted a retrospective cohort study by analysing the Medical Data Vision (MDV) database from April 2008 to September 2020. CTD patients who prescribed immunosuppressants were included in cohort 1, and CTD-PAH patients extracted from cohort 1 were included in cohort 2. Patient characteristics, diagnostic screening frequencies for PAH, and initial PAH-specific treatment patterns were assessed. RESULTS: Overall, 16,648 patients with CTD and 81 patients with CTD-PAH were included in cohorts 1 and 2, respectively. The frequencies of screening tests for PAH, including brain natriuretic peptide (BNP), transthoracic echocardiogram (TTE), and 'diffusing capacity' of the 'lungs for carbon monoxide' (DLCO), among CTD patients were 0.7, 0.3, and 0.1 tests/person-year, respectively. The most common initial PAH-specific treatment therapy was monotherapy (87.7%), followed by dual therapy (7.4%) and triple therapy (2.5%). CONCLUSION: This is the first study to describe the patient flow from PAH diagnosis to initial PAH-specific treatment for real-world patients who were followed regularly due to CTD in Japanese clinical practice.


Asunto(s)
Enfermedades del Tejido Conjuntivo , Hipertensión Arterial Pulmonar , Humanos , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Japón/epidemiología , Estudios Retrospectivos , Anciano , Adulto , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Hipertensión Arterial Pulmonar/diagnóstico , Bases de Datos Factuales , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Pueblos del Este de Asia
16.
Mod Rheumatol ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39187460

RESUMEN

OBJECTIVES: Primary antiphospholipid syndrome (PAPS) is an autoimmune disorder characterized by thrombosis and pregnancy morbidity. Although PAPS is distinct from systemic lupus erythematosus (SLE), the two conditions share clinical features and susceptibility genes. Progression from PAPS to SLE is well-recognized. However, risk factors for this transition are poorly understood. We aimed to identify predictors of progression to SLE in patients with PAPS. METHODS: A longitudinal single-center study was conducted at Hokkaido University Hospital from 1990 to 2021. Baseline characteristics including clinical features, laboratory data, aPL profiles were compared between patients who progressed to SLE (SLE group) and those who did not (non-SLE group). RESULTS: Among 64 patients diagnosed with PAPS at baseline, nine (13.8%) progressed to SLE over a mean follow-up of 9 years (incidence rate, 1.61 per 100 person-years). At the diagnosis of PAPS, the SLE group had a higher prevalence of anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and anti-dsDNA antibodies compared to the non-SLE group. Other clinical findings, autoantibody profiles, and serum complement levels were similar between the two groups. Multivariate Cox analysis showed that IgG aPS/PT was significantly associated with SLE development (Hazard ratio: 10.3, 95% CI: 1.13-92.6, p=0.04). CONCLUSION: IgG aPS/PT may be a predictive factor for new-onset SLE in patients with PAPS, suggesting its utility in guiding risk stratification and monitoring strategies for these patients.

17.
Mod Rheumatol ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753311

RESUMEN

OBJECTIVES: We investigated whether our in-house software equipped with partial image phase-only correlation (PIPOC) can detect subtle radiographic joint space narrowing (JSN) progression at six months and predict JSN progression in rheumatoid arthritis (RA) patients receiving Tocilizumab. METHODS: The study included 39 RA patients who were treated with Tocilizumab. Radiological progression of the metacarpophalangeal and the proximal interphalangeal joints was evaluated according to the Genant-modified Sharp score (GSS) at 0, 6, and 12 months. Automatic measurements were performed with the software. We validated the software in terms of accuracy in detecting the JSN progression. RESULTS: The success rate of the software for joint space width (JSW) measurement was 96.8% (449/464). The 0-12-month JSW change by the software was significantly greater in joints with the 0-6-month PIPOC (+) group than the 0-6-month PIPOC (-) group (p < 0.001). The 0-12-month JSW change by the software was 0-12-month GSS (+) than with 0-12-month GSS (-) (p = 0.02). Here, "(+)" indicates the JSN progression during the follow-up period. Meanwhile, "(-)" indicates no JSN progression during the follow-up period. Linear regression tests showed significant correlations between the 0-6-month and the 0-12-month PIPOC in the left 2nd and 3rd MCP joints (R2 = 0.554 and 0.420, respectively). CONCLUSIONS: Our in-house software equipped with PIPOC could predict subsequent JSN progression with only short-term observations.

18.
Mod Rheumatol ; 34(3): 515-522, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37340865

RESUMEN

OBJECTIVES: The objective of the study was to compare the efficacy of intravenous immunoglobulin (IVIG) therapy for obstetric antiphospholipid syndrome (APS) refractory to conventional treatment. METHODS: We conducted a single-arm, open-label multicentre clinical intervention trial. The enrolled criteria were patients with refractory APS who had a history of still or premature birth before 30 weeks of gestational age, even though they had been treated with conventional treatment, i.e. heparin and low-dose aspirin. After confirming the foetal heartbeats, a single course of IVIG (0.4 g/kg body weight daily for 5 days) was added to conventional treatment. The primary outcome was a live birth ratio of >30 weeks of gestational period, and the secondary outcome included improving pregnancy outcomes compared to previous pregnancy. RESULTS: Twenty-five per cent of patients (2 of 8 cases) achieved a live birth after the 30th week of pregnancy by IVIG-only add-on treatment, which is the same prevalence as the historical control. However, by adding other second-line therapy to IVIG and conventional treatment, further three patients (37.5%) achieved improvements in pregnancy outcome compared to previous treatments. In total, five patients (62.5%) were able to achieve preferable pregnancy outcomes through combination treatment including IVIG. CONCLUSIONS: This clinical trial could not demonstrate the efficacy of IVIG-only add-on therapy at improving the pregnancy outcomes of patients with obstetric APS refractory to conventional treatment. However, the combination of IVIG with rituximab or statins adding to conventional treatment improved pregnancy outcomes and resulted in more live births. Further studies are needed to investigate the efficacy of multi-targeted therapy to treat obstetric refractory APS.


Asunto(s)
Síndrome Antifosfolípido , Complicaciones del Embarazo , Femenino , Embarazo , Humanos , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Resultado del Embarazo , Aspirina/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológico
19.
Mod Rheumatol ; 34(2): 382-390, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-36988333

RESUMEN

OBJECTIVES: This study elucidated the prognosis and risk factors associated with damage accrual during long-term remission maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We obtained data from 120 patients registered in a nationwide prospective cohort study on remission induction therapy in Japanese patients with AAV and rapidly progressive glomerulonephritis (RemIT-JAV-RPGN), who achieved remission at 24 months after treatment initiation and were followed up for additional 24 months. The primary outcome was the vasculitis damage index (VDI) score at Month 48, and the secondary outcome included risk factors associated with increased total VDI at Month 48. RESULTS: The understudied patients comprised 52 men and 68 women aged 68 ± 13 years. Between Months 25 and 48, the patients' survival rate was 95% (114/120). End-stage renal disease developed in seven patients by Month 48, and 64 cases had increased VDI. The multivariable analysis results revealed that oral prednisolone (PSL) doses at Month 24 were associated with damage accrual between Months 24 and 48. CONCLUSIONS: VDI accrual was observed in more than half of patients with AAV during maintenance therapy, and increased VDI scores were associated with oral PSL doses 24 months after initiating remission induction therapy in Japan.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Masculino , Humanos , Femenino , Estudios Prospectivos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Prednisolona/uso terapéutico , Pronóstico , Inducción de Remisión
20.
Mod Rheumatol ; 34(6): 1170-1177, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38590037

RESUMEN

OBJECTIVES: A quality indicator (QI) for the treatment of systemic lupus erythematosus (SLE) during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a QI for SLE associated with pregnancy and childbirth. METHODS: To identify candidate QIs, we conducted a systematic literature review on the development of QIs for SLE related to pregnancy and childbirth and on clinical practice guidelines. Candidate QI items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as QIs. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related SLE QIs. RESULTS: Four articles on SLE QI development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate QIs were extracted that were limited to items related to pregnancy and childbirth and 41 items were selected on which all panel members agreed. CONCLUSION: We developed pregnancy-related SLE QIs using the RAND/UCLA method and selected 41 items, which could be used clinically.


Asunto(s)
Lupus Eritematoso Sistémico , Complicaciones del Embarazo , Indicadores de Calidad de la Atención de Salud , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Embarazo , Femenino , Parto
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