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Immune cell function is impaired in hyperglycemic patients with diabetes but thought to improve with normalization of blood glucose levels. In this study, we hypothesized that this improvement might involve changes in T cell function. We compared the peripheral T cell markers between the people with and without type 2 diabetes (T2D) admitted to our hospital for glycemic control, and then in patients with T2D before and after the improvement of hyperglycemia by inpatient treatment. Expression of programmed death 1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (TIM-3), co-suppressive molecules, CD26 and CD28 on CD4-positive and/or CD8-positive T cells, the Th1/Th2 ratio, and the number of regulatory T cells (Tregs) were not significantly different between the people with and without T2D. Although an average of 10.6 days of inpatient treatment with improved hyperglycemia did not affect expression of PD-1 and TIM-3 in T cells, the Th1/Th2 ratio, or Tregs, it significantly reduced expression of CD26 and CD28 on CD4-positive T cells. CD26 and CD28 on CD4-positive T cells may be associated with the altered immune function after rapid improvement of hyperglycemia but that the other T-cell markers investigated here may not be. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00697-7.
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Aims/introduction: In patients with diabetes, obesity is an aggravating factor for glycemic control and its vascular complications. However, the psychological and behavioral characteristics of those patients with obesity have not been fully clarified. This study investigated eating and coping behavior, personality traits, quality of life (QOL), and depression status in patients with diabetes with or without obesity. Materials and methods: Questionnaires obtained from 567 patients with diabetes at Dokkyo Medical University were analyzed. Eating behavior, coping behavior, personality traits, QOL, and depression status were evaluated by the Eating Behavior Questionnaire, Brief COPE, Japanese Ten-Item Personality Inventory, EuroQol 5 Dimensions-5 Level, and Patient Health Questionnaire-9, respectively. Participants were divided according to body mass index (BMI) into a non-obese group (BMI < 25), obese group (BMI 25-35), and high-degree obese group (BMI ≥ 35), and results were compared between groups. Results: On all items of the Eating Behavior Questionnaire, scores were higher in the obese and high-degree obese groups than non-obese group, indicating worse eating behavior. In coping behavior, significant intergroup differences were found in self-distraction, substance use, using emotional support, using instrumental support, and venting. As for personality traits, the obese group had significantly lower conscientiousness and higher emotional instability than the non-obese group. There was no significant difference in QOL or depression status. Conclusions: These results suggest that there are some characteristics in eating and coping behaviors and some personality traits between obese and non-obese patients with diabetes. Treatment based on such characteristics may be useful for patients with diabetes and obesity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00721-w.
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OBJECTIVE: Imeglimin is a novel anti-diabetic drug with insulinotropic and insulin-sensitizing effects that targets mitochondrial bioenergetics. We investigated acute effects of add-on therapy with imeglimin to preceding metformin on the 24-hour glucose profile and glycemic variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes. METHODS: We studied 30 outpatients with type 2 diabetes inadequately controlled with metformin. CGM was used for 14 days straight during the research period. Imeglimin 2000 mg/day was started on day 7 after initiating CGM. Several CGM parameters were compared between days 4-6 (prior to imeglimin treatment) and 11-13 (following the initiation of imeglimin treatment). RESULTS: After treatment with imeglimin, mean 24-hour glucose acutely decreased from 161.6ï±48.0 mg/dl to 138.9ï±32.2 mg/dl (p < 0.0001), while Time in range (i.e., at a glucose level of 70-180 mg/dL) was significantly increased from 69.9ï± 23.9% to 80.6ï± 21.0% (p < 0.0001). Addition of imegliimin to metformin significantly decreased the standard deviation (SD) of 24-hour glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability. Baseline serum HDL cholesterol was negatively correlated with changes in mean 24-hour glucose (r = 0.3859, p = 0.0352) and those in SD (r = 0.4015, p = 0.0309). CONCLUSIONS: Imeglimin add-on therapy to metformin acutely lowered 24-hour glucose levels and improved glycemic variability in patients with type 2 diabetes on metformin. A higher serum HDL cholesterol at baseline was associated with a better response to acute effects of imeglimin on 24-hour glucose levels and glycemic variability.
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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.
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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.
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Compostos Benzidrílicos , Citrulina , Diabetes Mellitus Tipo 2 , Glucosídeos , Histidina , Hipoglicemiantes , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Compostos Benzidrílicos/uso terapêutico , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Feminino , Pessoa de Meia-Idade , Idoso , Citrulina/sangue , Hipoglicemiantes/uso terapêutico , Histidina/sangue , Aminoácidos/sangueRESUMO
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).
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Biomarcadores , Quimiocina CCL11 , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/diagnóstico , Estudos Transversais , Pessoa de Meia-Idade , Biomarcadores/sangue , Quimiocina CCL11/sangue , Idoso , Condução Nervosa/fisiologia , Doenças do Sistema Nervoso Autônomo/sangue , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Frequência Cardíaca/fisiologia , Estudos de Casos e Controles , AdultoRESUMO
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.
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Carcinoma Hepatocelular , Diabetes Mellitus , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Inibidores do Transportador 2 de Sódio-Glicose , Sorbitol , Animais , Camundongos , Carcinoma Hepatocelular/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Modelos Animais de Doenças , Interleucina-33/metabolismo , Interleucina-33/uso terapêutico , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sorbitol/análogos & derivadosRESUMO
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.
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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.
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Células T Invariantes Associadas à Mucosa , Hepatopatia Gordurosa não Alcoólica , Camundongos , Humanos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Ácidos Graxos não Esterificados/metabolismoRESUMO
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.
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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.
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Doença de Graves , Metimazol , Humanos , Metimazol/uso terapêutico , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Receptor de Morte Celular Programada 1 , Linfócitos T CD4-Positivos/patologia , Morte CelularRESUMO
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.
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Hipotireoidismo , Intolerância à Lactose , Neoplasias da Glândula Tireoide , Adulto , Feminino , Humanos , Radioisótopos do Iodo , Pós , Comprimidos , Tireotropina , TiroxinaRESUMO
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.
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Anemia , Eritema Infeccioso , Leucopenia , Obesidade Mórbida , Infecções por Parvoviridae , Parvovirus B19 Humano , Trombocitopenia , Adulto , Anemia/etiologia , Gastrectomia/efeitos adversos , Humanos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Infecções por Parvoviridae/complicaçõesRESUMO
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.
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Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Preparações Farmacêuticas , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Compostos Benzidrílicos , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dipeptidil Peptidases e Tripeptidil Peptidases , Glucose , Glucosídeos , Humanos , Hipoglicemiantes/uso terapêutico , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
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.
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Adiponectina/sangue , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2 , Glucosídeos/uso terapêutico , Hepatopatia Gordurosa não Alcoólica , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
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.
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Antitireóideos/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Síndrome de DiGeorge/imunologia , Doença de Graves/imunologia , Hipocalcemia/sangue , Metimazol/uso terapêutico , Adulto , Linfócitos B/imunologia , Feminino , Citometria de Fluxo , Doença de Graves/tratamento farmacológico , Doença de Graves/cirurgia , Humanos , Hipocalcemia/fisiopatologia , Estudos Longitudinais , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T Reguladores/imunologia , TireoidectomiaRESUMO
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.
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Adipócitos/citologia , Adipócitos/metabolismo , Diferenciação Celular , Núcleo Celular/metabolismo , PPAR gama/metabolismo , Fator de Processamento Associado a PTB/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Células 3T3-L1 , Animais , Regulação da Expressão Gênica , Células HeLa , Humanos , Gotículas Lipídicas/metabolismo , Camundongos , Fosforilação , Fosfotirosina/metabolismo , Ligação Proteica , RNA Interferente Pequeno/metabolismoAssuntos
COVID-19 , Controle de Doenças Transmissíveis/estatística & dados numéricos , Diabetes Mellitus Tipo 2 , Serviços Médicos de Emergência/estatística & dados numéricos , Hemoglobinas Glicadas/análise , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/psicologia , Exercício Físico , Comportamento Alimentar/fisiologia , Humanos , Japão/epidemiologia , Distanciamento Físico , População Rural/estatística & dados numéricosRESUMO
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 ≥280â¯dB/m; and significant liver fibrosis, as LSMâ¯≥â¯8.0â¯kPa. LSM was divided into 3 severity levels: significant fibrosis (8.0 to <9.7â¯kPa); advanced fibrosis, (9.7 to <13.0â¯kPa); and liver cirrhosis (≥ 13.0â¯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 LSMâ¯≥â¯8.0â¯kPa than in those with LSM <8.0â¯kPa and was significantly elevated in patients who are at risk for non-alcoholic steatohepatitis (NASH) with fibrosis (FAST scoreâ¯≥â¯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 LSMâ¯≥â¯13.0â¯kPa indicating probable cirrhosis.
Assuntos
Diabetes Mellitus Tipo 2 , Dipeptidil Peptidase 4/sangue , Técnicas de Imagem por Elasticidade , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
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 10â¯mg/day (nâ¯=â¯32) or standard therapy (nâ¯=â¯19) for 12â¯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 12â¯weeks after treatment. In the empagliflozin group, serum HDL-c, but not LDL-c, significantly increased between baseline and 12â¯weeks (54.4⯱â¯16.3 vs. 58.8⯱â¯19.6â¯mg/dl; pâ¯=â¯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⯵g/ml, pâ¯=â¯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⯵g/ml, pâ¯<â¯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.