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1.
Am J Med Sci ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986908

RESUMEN

A 47-year-old woman was diagnosed with myotonic dystrophy when admitted for traumatic subarachnoid hemorrhage. Her glycemic control was poor despite administration of pioglitazone, a PPARɤ agonist, and subcutaneous insulin infusion. However, adding a GLP-1 receptor (GLP-1R) agonist markedly improved blood glucose levels, resulting in eventual insulin withdrawal. Genetic testing revealed a heterozygous variant, p.R131Q, in the GLP1R (rs3765467), a common variant in Asia. This variant is known to be associated with increased endogenous insulin from beta cells in response to exogenous GLP-1 infusion. This is the first report and short review of a Japanese case of myotonic dystrophy accompanied by GLP-1R gene polymorphism.

2.
Expert Opin Pharmacother ; 25(7): 937-944, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38809611

RESUMEN

BACKGROUND: To investigate effects of empagliflozin on plasma amino acids in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized, active-controlled, open-label trial, 58 patients with type 2 diabetes were randomized to 10 mg/day empagliflozin (n = 29) or standard treatment without empagliflozin (control group, n = 29) and treated for 12 weeks. We obtained blood samples at baseline and 12 weeks and assessed the plasma amino acid profile by liquid chromatography-mass spectrometry liquid chromatography. We also calculated the Fischer ratio (the ratio of branched-chain to aromatic amino acids). RESULTS: In the empagliflozin group but not in the control group, plasma levels of citrulline, histidine, and α-aminobutyric acid (AABA), the Fischer ratio, and serum high-molecular weight (HMW) adiponectin increased significantly (p = 0.0099, 0.0277, 0.0318, 0.0135, and 0.0304, respectively) and plasma plasminogen activator inhibitor-1 (PAI-1) decreased significantly (p = 0.0014). In the empagliflozin group, the change in plasma citrulline was positively correlated with the changes in HMW adiponectin (r = 0.488, p = 0.0084) and the Fischer ratio (r = 0.393, p = 0.0353) but negatively correlated with the change in ferritin (r= -0.533,p = 0.0051); the change in plasma histidine was negatively correlated with the change in PAI-1 (r= -0.398, p = 0.0397) and urinary albumin creatinine ratio (r= -0.478, p = 0.0088). CONCLUSION: Empagliflozin significantly increases plasma citrulline, histidine, and AABA in people with type 2 diabetes. CLINICAL TRIAL REGISTRATION: www.umin.ac.jp identifier is UMIN000025418.


Asunto(s)
Compuestos de Bencidrilo , Citrulina , Diabetes Mellitus Tipo 2 , Glucósidos , Histidina , Hipoglucemiantes , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Glucósidos/uso terapéutico , Glucósidos/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Compuestos de Bencidrilo/uso terapéutico , Masculino , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Femenino , Persona de Mediana Edad , Anciano , Citrulina/sangre , Hipoglucemiantes/uso terapéutico , Histidina/sangre , Aminoácidos/sangre
3.
Postgrad Med ; 136(3): 318-324, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38660919

RESUMEN

AIMS: To investigate whether higher serum CCL11/Eotaxin-1, a biomarker for aging and neurodegenerative and neuroinflammatory disorders, is associated with diabetic sensorimotor polyneuropathy (DSPN), peripheral nerve dysfunction, and cardiac autonomic neuropathy in people with type 2 diabetes. METHODS: This cross-sectional study included 106 patients with type 2 diabetes and 40 healthy controls, matched for the age and sex distribution of the diabetes group as a whole. The CC chemokines CCL11/Eotaxin-1 and CCL22/MDC were measured in fasting serum samples. DSPN and peripheral nerve function were assessed by neurological examination and nerve conduction studies, and cardiac autonomic function, by heart rate variability (HRV) and corrected QT (QTc) time. The cardio-ankle vascular index (CAVI) was measured as a marker for arterial stiffness. RESULTS: Serum CCL11/Eotaxin-1 levels were significantly higher in diabetic patients than in healthy controls (183 ± 63.5 vs. 113.1 ± 38.5 pg/ml, p < 0.001), but serum CCL22/MDC levels were not significantly different between the two groups. In the diabetes group, the serum CCL11/Eotaxin-1 level was positively correlated with ulnar and sural nerve conduction velocities (p = 0.0009, p = 0.0208, respectively) and sensory nerve action potential (p = 0.0083), and CAVI (p = 0.0005), but not with HRV indices or QTc time, and serum CCL22/MDC was not significantly correlated with any indices of nerve conduction. In a model adjusted for age and duration of diabetes, serum CCL11/Eotaxin-1 was still associated with ulnar nerve conduction velocity (p = 0.02124). Serum CCL11/Eotaxin-1, but not CCL22/MDC, was significantly higher in patients with than in those without DSPN (208.2 ± 71.6 vs. 159.1 ± 45.1 pg/ml, respectively; p < 0.0001). CONCLUSIONS: Serum CCL11/Eotaxin-1 is elevated in patients with DSPN and is associated with peripheral nerve dysfunction, in particular sensory nerve conduction velocity, suggesting that serum CCL11/Eotaxin-1 may be a potential biomarker for DSPN. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000040631).


Asunto(s)
Biomarcadores , Quimiocina CCL11 , Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Humanos , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/diagnóstico , Estudios Transversales , Persona de Mediana Edad , Biomarcadores/sangre , Quimiocina CCL11/sangre , Anciano , Conducción Nerviosa/fisiología , Enfermedades del Sistema Nervioso Autónomo/sangre , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Frecuencia Cardíaca/fisiología , Estudios de Casos y Controles , Adulto
4.
J Diabetes Complications ; 38(1): 108650, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38035640

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is increasing globally, and seeking therapeutic molecule targets is urgent. Several studies have demonstrated that IL-33 plays an important role in the progression of Non-alcoholic steatohepatitis (NASH) with fibrosis and the proliferation of hepatocellular carcinoma (HCC). However, whether the inhibition of IL-33 signaling prevents NAFLD from progressing to NASH and HCC has not been clarified. We investigated the effects of a novel antibody, IL-33RAb, and luseogliflozin, a SGLT2 inhibitor, when administered to a model mouse for NASH and HCC, and their effects were compared to investigate the mechanisms of how IL-33 is involved in the pathogenesis of NASH progression. Compared with the positive control of luseogliflozin, inhibition of IL-33 signaling ameliorated decreasing hepatic fibrosis via decreasingαSMA and MCP-1, and also partially suppressed the progression of the HCC cell line in in vitro experiments. These findings suggest that inhibition of IL-33 possibly prevents progression from NASH to HCC, and their effect may be a newly arrived therapeutic agent.


Asunto(s)
Carcinoma Hepatocelular , Diabetes Mellitus , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Sorbitol , Animales , Ratones , Carcinoma Hepatocelular/prevención & control , Diabetes Mellitus/tratamiento farmacológico , Modelos Animales de Enfermedad , Interleucina-33/metabolismo , Interleucina-33/uso terapéutico , Hígado/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Cirrosis Hepática/prevención & control , Neoplasias Hepáticas/prevención & control , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Sorbitol/análogos & derivados
5.
Diabetol Int ; 14(1): 94-102, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36636156

RESUMEN

Objective: Cardiac autonomic neuropathy (CAN) is an independent risk factor for cardiovascular mortality and also is associated with a high risk of lethal arrhythmias and sudden death in people with type 1 or 2 diabetes. Heart rate variability (HRV) is an index of cardiac autonomic function. To investigate the relationship between HRV and arterial stiffness evaluated by the cardio-ankle vascular index (CAVI), a relatively new marker for arterial stiffness and a predictor of cardiovascular disease, in patients with type 2 diabetes. Materials and methods: We studied consecutive 313 patients with type 2 diabetes in a cross-sectional design. HRV was estimated by the coefficient of variation of 100 R-R intervals (CVR-R) at rest and during deep breathing (DB). The difference in CVR-R was defined as CVR-R during DB minus CVR-R at rest. Arterial stiffness was evaluated by CAVI, which is independent of blood pressure (BP). A CAVI greater than or equal to 9.0 was defined as significant arterial stiffening. Results: Linear regression analysis showed that CAVI correlated positively with age, duration of diabetes, urinary albumin creatinine ratio (UACR), CVR-R during DB, and the difference in CVR-R and negatively with body mass index (BMI), estimated glomerular filtration rate, and sensory nerve conduction velocity and action potential of the sural nerve. Multivariate analysis found that age, BMI, systolic blood pressure, UACR, and CVR-R during DB were independently associated with arterial stiffness determined by CAVI. The CVR-R at rest and during deep breathing was significantly lower in the patients with arterial stiffness than in those without it. Conclusion: Low HRV estimated by CVR-R during DB is closely associated with arterial stiffness measured by CAVI in people with type 2 diabetes, suggesting that arterial stiffness associated with CAN may be an independent risk factor for cardiovascular disease in people with type 2 diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00604-y.

6.
Int J Mol Sci ; 23(23)2022 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-36499635

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide health concern. The disease may involve immune cells including T cells, but little is known about the role(s) of the innate-like T cells in the liver. Furthermore, the most abundant innate-like T cells in the human liver are mucosal-associated invariant T (MAIT) cells, but the involvement of MAIT cells in NAFLD remains largely unexplored because of their paucity in mice. In this study, we used a novel mouse line, Vα19, in which the number of MAIT cells is equivalent to or greater than that in humans. Compared with the control mice, Vα19 mice fed a high-fat diet (HFD) exhibited a reduction in lipid accumulation, NAFLD activity score, and transcripts relevant to lipogenesis. In addition, serum triglyceride and non-esterified fatty acids were lower in Vα19 mice fed normal chow or HFD. In contrast, the Vα19 mice showed little or no change in glucose tolerance, insulin sensitivity, inflammation in adipose tissues, or intestinal permeability compared with the controls, irrespective of diet. These results suggest that the presence of MAIT cells is associated with reduced lipogenesis and lipid accumulation in the liver; however, further studies are needed to clarify the role of MAIT cells in hepatic lipid metabolism.


Asunto(s)
Células T Invariantes Asociadas a Mucosa , Enfermedad del Hígado Graso no Alcohólico , Ratones , Humanos , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Hígado/metabolismo , Ácidos Grasos no Esterificados/metabolismo
7.
Clin Endocrinol (Oxf) ; 97(6): 841-848, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35692119

RESUMEN

OBJECTIVE: We investigated longitudinal changes in circulating CD4+ and CD8+ T cells positive for programed cell death protein-1 (PD-1) and in other subsets of CD4+ T cells in untreated hyperthyroid patients with Graves' disease after treatment with methimazole (MMI). DESIGN AND PATIENTS: The study included 18 untreated hyperthyroid patients with Graves' disease and 18 age-matched controls. Before and after 12-week treatment with MMI, we used flow cytometry to measure circulating PD-1+  D4+ and PD-1+ CD8+ T cells and subsets of CD4+ T cells in peripheral blood, as well as serum levels of chemokines related to T-helper type 1 (Th-1) and Th-2 cells. RESULTS: At baseline, the percentage of CD4+ and CD8+ T cells expressing PD-1 was significantly higher in patients than in age-matched controls. Serum levels of chemokines related to Th-1 and Th-2 also were higher in patients. Twelve weeks after initiation of MMI, the percentage of CD4+ T cells expressing PD-1 was significantly lower than at baseline, but no such change was seen in CD8+ T cells. Furthermore, the percentage of Th-1 cells among CD4+ T cells and the serum levels of soluble CD26/dipeptidyl peptidase-4, a surface marker of Th-1 cells, also were significantly lower than at baseline. CONCLUSIONS: The expression of PD-1 on circulating CD4+ and CD8+ T cells is increased in hyperthyroid patients with active Graves' disease. MMI significantly decreases levels of circulating PD-1+  CD4+ T cells, suggesting that PD-1+ T lymphocytes may be associated with the pathogenesis of Graves' disease.


Asunto(s)
Enfermedad de Graves , Metimazol , Humanos , Metimazol/uso terapéutico , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/patología , Receptor de Muerte Celular Programada 1 , Linfocitos T CD4-Positivos/patología , Muerte Celular
8.
Int J Cardiol Heart Vasc ; 41: 101071, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35757147

RESUMEN

Aims: To investigate synergistic effects of liver fibrosis evaluated by FibroScan and sarcopenia on endothelial function and arterial stiffness in patients with type 2 diabetes. Methods: This cross-sectional study evaluated liver fibrosis (LF) and sarcopenia in 115 patients with type 2 diabetes. LF was assessed as the liver stiffness measurement (LSM) in transient elastography (FibroScan) and was defined as an LSM greater than or equal to 8.0 kPa. Sarcopenia was defined as a ratio of appendicula skeletal muscle mass to body mass index of<0.789 in men and<0.512 in women. Endothelial function was measured by reactive hyperemia index (RHI) with tonometry, and arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Endothelial dysfunction was defined an RHI value below 1.67, while arterial stiffness was defined a CAVI value above 9.0. Patients were divided into four groups: no LF and no sarcopenia; LF but no sarcopenia; no LF but sarcopenia; and LF and sarcopenia. The composite of endothelial dysfunction of arterial stiffness was defined as an outcome. Results: In patients with LF, RHI was significantly lower and CAVI was significantly higher than in patients without LF. Furthermore, RHI was significantly lower in patients with sarcopenia than in those without it. Patients with both LF and sarcopenia had the lowest RHI and the highest CAVI and urinary albumin levels. Sarcopenia and HDL cholesterol were independent factor the composite of endothelial dysfunction and arterial stiffness. Conclusion: LF and sarcopenia are independently associated with endothelial dysfunction and arterial stiffness in patients with type 2 diabetes. Coexistence of LF and sarcopenia may synergistically lead to vascular damage and thus contribute to the high risk of cardiovascular disease in people with type 2 diabetes.

9.
Endocr J ; 69(8): 941-945, 2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-35249899

RESUMEN

We describe a case of a 38-year-old woman who, after radioactive iodine therapy for Graves' disease, developed severe hypothyroidism despite receiving a high dose of levothyroxine (L-T4) tablet as replacement therapy. Her thyroid stimulating hormone (TSH) remained to be high despite the dose of L-T4 tablets to 400 µg/day after treatment for hypothyroidism, and the patient complained of general malaise and edema of the legs. Reduced intestinal absorption of L-T4 is the most common cause of failure to achieve the therapeutic target in hypothyroid patients receiving replacement therapy. She was admitted to our hospital for severe hypothyroidism due to resistance to treatment with L-T4 tablet. Our patient was found to have lactose intolerance (LI) by a detailed examination during hospitalization. Therefore, we assumed that LI was impairing intestinal absorption of L-T4 tablet in our patient, leading to severe hypothyroidism. The patient was switched to the powder formulation of L-T4 at the same daily dose, and serum levels of thyroid-stimulating hormone and thyroid hormones normalized. This is the case in which hypothyroidism due to reduced absorption of L-T4 tablet in a patient with LI was resolved by switching to L-T4 powder formulation.


Asunto(s)
Hipotiroidismo , Intolerancia a la Lactosa , Neoplasias de la Tiroides , Adulto , Femenino , Humanos , Radioisótopos de Yodo , Polvos , Comprimidos , Tirotropina , Tiroxina
10.
Intern Med ; 61(17): 2631-2635, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35135915

RESUMEN

Pancytopenia due to malnutrition sometimes occurs after gastric bypass but is rare after sleeve gastrectomy. A 35-year-old patient underwent sleeve gastrectomy for severe obesity. Twelve months after the operation, rapid progression of macrocytic anemia with leukopenia and thrombocytopenia occurred, and a decrease in some vitamins and trace elements due to an insufficient food intake was also detected. Haptoglobin decreased, suggesting the presence of hemolysis. In addition, IgM antibody against parvovirus B19 was detected, followed by IgG antibody. Parvovirus B19 infection was suggested to be involved in the rapid progression of anemia in this malnourished patient after bariatric surgery.


Asunto(s)
Anemia , Eritema Infeccioso , Leucopenia , Obesidad Mórbida , Infecciones por Parvoviridae , Parvovirus B19 Humano , Trombocitopenia , Adulto , Anemia/etiología , Gastrectomía/efectos adversos , Humanos , Obesidad Mórbida/complicaciones , Obesidad Mórbida/cirugía , Infecciones por Parvoviridae/complicaciones
11.
Int J Clin Pract ; 75(11): e14732, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34388297

RESUMEN

AIM: To investigate acute effects of add-on therapy with the sodium glucose co-transporter 2 inhibitor tofogliflozin to dipeptidyl peptidase (DPP)-4 inhibitors on 24-hours glucose profile and glycaemic variability evaluated by continuous glucose monitoring (CGM) in patients with type 2 diabetes. PATIENTS AND METHODS: We studied 17 patients with type 2 diabetes who were hospitalised for glycaemic control. CGM was performed for 7 consecutive days in the last week of hospitalization. Tofogliflozin 20 mg/d was started on day 4 after initiating CGM and was administered to 10 patients receiving DPP-4 inhibitors and 7 patients not receiving DPP-4 inhibitors. We compared several CGM parameters between day 2-3 (ie, before treatment with tofogliflozin) and day 5-6 (ie, after starting treatment with tofogliflozin). RESULTS: After starting treatment with tofogliflozin, mean 24-hours glucose and postprandial glucose after each meal were significantly decreased in both groups of patients. Time in range (ie, at a glucose level of 70-180 mg/dL) was significantly increased in both groups. The standard deviation of 24-hours glucose and mean amplitude of glycaemic excursions (MAGE), 2 indexes of glycaemic variability, were significantly decreased in patients receiving DPP-4 inhibitors but were unchanged in those not receiving these drugs. CONCLUSIONS: Add-on therapy with tofogliflozin to DPP-4 inhibitors acutely reduces 24-hours glucose levels and improves glycaemic variability in patients with type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Preparaciones Farmacéuticas , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Simportadores , Compuestos de Bencidrilo , Glucemia , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas , Glucosa , Glucósidos , Humanos , Hipoglucemiantes/uso terapéutico , Sodio , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
12.
Biochem Biophys Res Commun ; 562: 139-145, 2021 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-34052659

RESUMEN

We recently isolated a novel co-activator of peroxisome proliferator-activated receptor γ, helicase with zinc finger 2 (HELZ2). HELZ2 null mice were resistant to diet-induced obesity and NAFFL/NASH, and HELZ2 was phosphorylated at tyrosine residues. In order to find a factor related to HELZ2, we analyzed products co-immunoprecipitated with phosphorylated HELZ2 by mass spectrometry analyses. We identified proline- and glutamine-rich (SFPQ) as a protein associating with tyrosine-phosphorylated HELZ2. The knockdown of SFPQ in 3T3-L1 cells downregulated mRNA levels of transcription factors including Krox20, Cebpß, and Cebpδ: key factors for early-stage adipocyte differentiation. In addition, knockdown of SFPQ inhibited 3T3-L1 cell differentiation to mature adipocytes. These findings demonstrated that SFPQ associating with HELZ2 is an important novel transcriptional regulator of adipocyte differentiation.


Asunto(s)
Adipocitos/citología , Adipocitos/metabolismo , Diferenciación Celular , Núcleo Celular/metabolismo , PPAR gamma/metabolismo , Factor de Empalme Asociado a PTB/metabolismo , Transactivadores/metabolismo , Factores de Transcripción/metabolismo , Células 3T3-L1 , Animales , Regulación de la Expresión Génica , Células HeLa , Humanos , Gotas Lipídicas/metabolismo , Ratones , Fosforilación , Fosfotirosina/metabolismo , Unión Proteica , ARN Interferente Pequeño/metabolismo
13.
Endocr J ; 68(10): 1187-1195, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-33980771

RESUMEN

Chromosome 22q11.2 deletion syndrome is a multisystem genetic disorder that presents with hypocalcemia due to congenital hypoparathyroidism; cardiovascular, renal, and facial anomalies; and skeletal defects. This syndrome is also associated with an increased risk of autoimmune disease. We report here on a 33-year-old Japanese woman with 22q11.2 deletion syndrome complicated by Graves' disease. The patient had facial abnormalities and a history of a surgical procedure for a submucous cleft palate at age 3 years. At age 33, the patient was diagnosed with Graves' disease because both hyperthyroidism and thyroid stimulating hormone receptor antibody were present. The patient's serum calcium level was within the normal range, but symptomatic hypocalcemia developed 1 month after treatment with methimazole was started for thyrotoxicosis. Methimazole was discontinued because it caused liver dysfunction, so the patient underwent total thyroidectomy to treat her Graves' disease. We examined longitudinal changes in the number of subsets of CD4 and CD8 lymphocytes, including regulatory T (T reg) cells and PD-1+CD4+ and PD-1+CD8+ T cells, after treatment by total thyroidectomy. A flowcytometry analysis demonstrated that circulating PD-1+CD4+ and PD-1+CD8+ T cells gradually decreased over time, as did circulating T reg cells and circulating CD19+ B cells. These findings suggest that PD-1-positive CD4+ and CD8+ T cells and T reg cells may have been associated with the autoimmunity in our patient with chromosome 22q11.2 deletion syndrome complicated by Graves' disease.


Asunto(s)
Antitiroideos/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Síndrome de DiGeorge/inmunología , Enfermedad de Graves/inmunología , Hipocalcemia/sangre , Metimazol/uso terapéutico , Adulto , Linfocitos B/inmunología , Femenino , Citometría de Flujo , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/cirugía , Humanos , Hipocalcemia/fisiopatología , Estudios Longitudinales , Receptor de Muerte Celular Programada 1/inmunología , Linfocitos T Reguladores/inmunología , Tiroidectomía
14.
J Investig Med ; 69(7): 1324-1329, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34016738

RESUMEN

A better baseline renal function is associated with a better response to sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes. Low serum adiponectin is associated with visceral fat accumulation and hepatic steatosis. We investigated the relationship between baseline serum adiponectin and glycemic response to dapagliflozin in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to either the dapagliflozin (5 mg/d) group or the control group. Both groups were treated for 24 weeks. Serum high-molecular-weight (HMW) adiponectin was measured with an ELISA kit. Visceral fat area (VFA) was measured by dual bioelectrical impedance analysis. Hepatic steatosis was assessed by the controlled attenuation parameter (CAP) measured by a transient elastography (FibroScan). Treatment with dapagliflozin significantly decreased HbA1c from 8.4%±1.5% at baseline to 7.4%±1.2% at 24 weeks. Both VFA and CAP decreased in the dapagliflozin group. Baseline serum HMW adiponectin was negatively correlated with changes in HbA1c from baseline to 24 weeks with dapagliflozin therapy. In the multivariate analysis, baseline HbA1c (ß=-0.559, p=0.002) and serum HMW adiponectin (ß=0.471, p=0.010) were independent determinants for the change (reduction) in HbA1c. In the dapagliflozin group, the change in HbA1c was positively correlated with the changes of CAP, but negatively correlated with the change in serum HMW adiponectin. In conclusion, a lower serum level of HMW adiponectin was associated with a better response to dapagliflozin in patients with type 2 diabetes and NAFLD.Trial registration numberUMIN000022155.


Asunto(s)
Adiponectina/sangre , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2 , Glucósidos/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina Glucada , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico
16.
J Diabetes Complications ; 35(5): 107885, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33602617

RESUMEN

AIM: To investigate the relationship in people with type 2 diabetes between serum soluble dipeptidyl peptidase-4 (sDDP-4) and degree of liver fibrosis assessed as the liver stiffness measurement (LSM) and FAST (FibroScan-AST) score, both of which were measured by transient elastography (FibroScan). SUBJECTS AND METHODS: In this cross-sectional study, we examined 115 patients with type 2 diabetes. With transient elastography (FibroScan), we assessed the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) as measures of hepatic steatosis and liver fibrosis, respectively. We calculated the FAST score, which identifies progressive non-alcoholic steatohepatitis (NASH), from CAP, LSM, and the serum aspartate aminotransferase level. Significant hepatic steatosis was defined as CAP ≥280 dB/m; and significant liver fibrosis, as LSM ≥ 8.0 kPa. LSM was divided into 3 severity levels: significant fibrosis (8.0 to <9.7 kPa); advanced fibrosis, (9.7 to <13.0 kPa); and liver cirrhosis (≥ 13.0 kPa). RESULTS: Serum sDPP-4 correlated positively with liver enzymes, CAP, LSM, and FAST score. Multivariate analysis showed that LSM remained to be an independent factor for serum sDDP-4. Serum sDPP-4 was significantly higher in patients with LSM ≥ 8.0 kPa than in those with LSM <8.0 kPa and was significantly elevated in patients who are at risk for non-alcoholic steatohepatitis (NASH) with fibrosis (FAST score ≥ 035 or 0.67). Patients with both hepatic steatosis and liver fibrosis had the highest serum sDPP-4. CONCLUSION: Serum sDPP-4 was strongly associated with severity of liver fibrosis evaluated by LSM and the FAST score and was markedly elevated in diabetic patients with LSM ≥ 13.0 kPa indicating probable cirrhosis.


Asunto(s)
Diabetes Mellitus Tipo 2 , Dipeptidil Peptidasa 4/sangre , Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/patología
17.
Int J Cardiol ; 331: 243-248, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33556413

RESUMEN

BACKGROUND AND AIMS: Sodium/glucose cotransporter 2 (SGLT2) inhibitors decrease plasma triglyceride levels and slightly increase low-density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c). However, the mechanisms underlying such changes in the blood lipid profile remain to be determined. We investigated how empagliflozin affects plasma markers of cholesterol absorption and synthesis, and evaluated the relationship between changes in these markers and blood lipids in patients with type 2 diabetes. METHODS AND RESULTS: In a randomized, active-controlled, open-label trial, 51 patients were randomly allocated in 2:1 ratio to receive empagliflozin 10 mg/day (n = 32) or standard therapy (n = 19) for 12 weeks. We measured plasma levels of lathosterol as a marker of cholesterol synthesis, and campesterol and sitosterol as markers of cholesterol absorption, at baseline and 12 weeks after treatment. In the empagliflozin group, serum HDL-c, but not LDL-c, significantly increased between baseline and 12 weeks (54.4 ±â€¯16.3 vs. 58.8 ±â€¯19.6 mg/dl; p = 0.0006), whereas in the standard therapy group, HDL-c and LDL-c remained unchanged. In the empagliflozin group, plasma campesterol also increased significantly (4.14 ±â€¯1.88 vs. 4.90 ±â€¯2.26 µg/ml, p = 0.0008), whereas no change in plasma campesterol or sitosterol was found in the control group. Although plasma lathosterol showed no change in the whole empagliflozin group, it decreased significantly in patients who were not taking statins. In statin non-users, plasma lathosterol decreased significantly after treatment with empagliflozin (2.71 ±â€¯0.99 vs. 1.91 ±â€¯0.99 µg/ml, p < 0.05). In the empagliflozin group, changes in plasma campesterol correlated positively with changes in HDL-c. CONCLUSION: Empagliflozin increases serum campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes. This increase may be associated with SGLT2 inhibitor-induced increases in HDL cholesterol.


Asunto(s)
Diabetes Mellitus Tipo 2 , Fitosteroles , Compuestos de Bencidrilo , Colesterol/análogos & derivados , HDL-Colesterol , LDL-Colesterol , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Glucósidos , Humanos
18.
Clin Case Rep ; 8(12): 2619-2624, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33363791

RESUMEN

Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis.

19.
J Diabetes Complications ; 34(11): 107703, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32883567

RESUMEN

AIMS: Elevation of the plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a rapid-acting inhibitor of fibrinolysis, is associated with development of vascular thrombotic diseases, including coronary artery disease and stroke. We investigated the effects of empagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on the plasma concentration of PAI-1 and fibrinolytic activity in patients with type 2 diabetes. METHODS: In a randomized, active-controlled, open-label trial, 51 patients with type 2 diabetes were randomly allocated at a 2:1 ratio to receive empagliflozin (10 mg/day, n = 31) or standard therapy (n = 18) for 12 weeks. We measured the plasma concentrations of PAI-1 and plasmin-α2-antiplasmin complex (PAP) as indicators of fibrinolytic activity. Serum leptin and high-molecular weight (HMW) adiponectin were also measured. RESULTS: In 49 patients who completed the trial, baseline plasma PAI-1 showed a positive correlation with body weight, visceral fat area (VFA), γ-glutamyltranspeptidase (GGT), leptin, and the platelet count, while it showed a negative correlation with HDL cholesterol and PAP. Body weight and VFA decreased significantly in the empagliflozin group, but not in the control group. The serum level of GGT showed a significant decrease at 12 weeks in the empagliflozin group, while it was unchanged in the control group. Serum HMW adiponectin increased significantly in the empagliflozin group. Plasma PAI-1 decreased significantly by 25% in the empagliflozin group, but not in the control group. In the empagliflozin group, the change of plasma PAI-1 was positively correlated with the changes of body weight and leptin, but was negatively correlated with the change of PAP. CONCLUSIONS: Empagliflozin reduced the plasma PAI-1 concentration through its synergistic actions of a glucose-lowering effect, VFA loss, and restoring the adipokine balance. (Clinical trial registry: UMIN000025418).


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2 , Fibrinólisis , Glucósidos/uso terapéutico , Inhibidor 1 de Activador Plasminogénico , Adiponectina/sangre , Peso Corporal , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Leptina/sangre , Inhibidor 1 de Activador Plasminogénico/sangre
20.
Sci Rep ; 10(1): 9999, 2020 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-32561878

RESUMEN

Brief refeeding times (~60 min) enhanced hepatic Angptl8 expression in fasted mice. We cloned the mouse Angptl8 promoter region to characterise this rapid refeeding-induced increase in hepatic Angptl8 expression. Deletion of the -309/-60 promoter region significantly attenuated basal promoter activity in hepatocytes. A computational motif search revealed a potential binding motif for hepatocyte nuclear factor 1α/1ß (HNF-1α/ß) at -84/-68 bp of the promoter. Mutation of the HNF-1 binding site significantly decreased the promoter activity in hepatocytes, and the promoter carrying the mutated HNF-1 site was not transactivated by co-transfection of HNF-1 in a non-hepatic cell line. Silencing Hnf-1 in hepatoma cells and mouse primary hepatocytes reduced Angptl8 protein levels. Electrophoretic mobility-shift assays confirmed direct binding of Hnf-1 to its Angptl8 promoter binding motif. Hnf-1α expression levels increased after short-term refeeding, paralleling the enhanced in vivo expression of the Angptl8 protein. Chromatin immunoprecipitation (ChIP) confirmed the recruitment of endogenous Hnf-1 to the Angptl8 promoter region. Insulin-treated primary hepatocytes showed increased expression of Angptl8 protein, but knockdown of Hnf-1 completely abolished this enhancement. HNF-1 appears to play essential roles in the rapid refeeding-induced increases in Angptl8 expression. HNF-1α may therefore represent a primary medical target for ANGPTL8-related metabolic abnormalities. The study revealed the transcriptional regulation of the mouse hepatic Angptl8 gene by HNF-1.


Asunto(s)
Proteínas Similares a la Angiopoyetina/genética , Regulación de la Expresión Génica , Factor Nuclear 1 del Hepatocito/genética , Hígado/metabolismo , Transcripción Genética/genética , Proteína 8 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina/metabolismo , Animales , Línea Celular , Inmunoprecipitación de Cromatina , Factor Nuclear 1 del Hepatocito/metabolismo , Hepatocitos/metabolismo , Ratones , Regiones Promotoras Genéticas
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