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1.
Endocr J ; 67(6): 655-658, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32101828

RESUMO

Adrenoleukodystrophy (ALD) is an X-linked disorder caused by a hemizygous mutation of the ABCD1 gene. Patients with ALD show progressive central nervous system demyelination and primary adrenal insufficiency. In Japan, most reported ALD cases were childhood-onset, and only one case of an adult patient with Addison's disease form of ALD has ever been reported. Herein, we present a case of a 29-year-old man with Addison's disease form of ALD. The patient had anorexia, weight loss, and skin pigmentation from 18 years of age. At first visit, his weight had decreased by 12 kg from 57 kg when he was 15 years old. Endocrinological examination showed low serum cortisol (1.2 µg/dL) with high plasma ACTH (4,750 pg/mL), and abdominal computed tomography showed normal adrenal glands. Very-long-chain fatty acid (VLCFA) levels were elevated, and the ABCD1 mutation, p.Gly116Arg, was identified in hemizygous state. He had no significant neurological findings on physical examination and no white matter lesions on brain magnetic resonance imaging (MRI). He was diagnosed with ALD presenting as Addison's disease, and glucocorticoid replacement therapy was initiated. Four years after the diagnosis, he still did not show any neurological findings and any white matter lesions on brain MRI. Evaluating VLCFA levels for ALD diagnosis is important in young adult men with idiopathic primary adrenal insufficiency as well as in children. Early diagnosis enables more rational approaches including the early detection of neurological complications and might improve the prognosis of patients.


Assuntos
Doença de Addison/diagnóstico , Adrenoleucodistrofia/diagnóstico , Membro 1 da Subfamília D de Transportadores de Cassetes de Ligação de ATP/genética , Doença de Addison/complicações , Doença de Addison/tratamento farmacológico , Doença de Addison/genética , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/patologia , Adrenoleucodistrofia/complicações , Adrenoleucodistrofia/tratamento farmacológico , Adrenoleucodistrofia/genética , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Diagnóstico Precoce , Glucocorticoides/administração & dosagem , Terapia de Reposição Hormonal , Humanos , Hidrocortisona/administração & dosagem , Masculino
2.
Opt Express ; 27(19): 26807-26820, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674555

RESUMO

This paper details the development of a precise assembly of two supermirrors for neutron-focusing, designed for installation in neutron reflectometer SOFIA at BL16 in J-PARC MLF to intensify the illumination for small samples. The supermirrors are sputtered on two metal substrates, whose surfaces are coated with amorphous Ni-P plating, and are figured by diamond cutting and polished to subnanometer roughness. Special care is taken while polishing the substrates to reduce waviness and surface roughness for achieving a sharp focusing spot and uniform neutron reflectivity. The supermirror could converge the neutrons into a focal spot with a width of 0.13 mm in the full width at half maximum.

3.
Opt Express ; 25(17): 20012-20024, 2017 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-29041686

RESUMO

This paper details methods for the precision design and fabrication of neutron-focusing supermirrors, based on electroless nickel plating. We fabricated an elliptic mirror for neutron reflectometry, which is our second mirror improved from the first. The mirror is a 550-millimeter-long segmented mirror assembled using kinematic couplings, with each segment figured by diamond cutting, polished using colloidal silica, and supermirror coated through ion-beam sputtering. The mirror was evaluated with neutron beams, and the reflectivity was found to be 68-90% at a critical angle. The focusing width was 0.17 mm at the full width at half maximum.

4.
Endocr J ; 64(2): 163-170, 2017 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-27760891

RESUMO

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM), believed to be caused by ß-cell destruction through islet-cell autoimmunity, gradually progresses to an insulin-dependent state over time. Although the presence of anti-glutamic acid decarboxylase antibody (GADA) is required for the diagnosis of SPIDDM, a recent change in the GADA assay kit from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA) yields mismatched GADA test results between the two kits, leading to confusion in understanding the pathological conditions of SPIDDM in Japan. Thus, this study aimed to clarify the difference in the clinical characteristics of GADA-ELISA-positive and GADA-ELISA-negative patients originally diagnosed as SPIDDM by GADA-RIA test. As a result, 42 of 63 original GADA-RIA-positive SPIDDM patients (66.7%) were found to be GADA-ELISA-positive, whereas the remaining 21 patients (33.3%) were found to be GADA-ELISA-negative. In patients with shorter disease duration, GADA-ELISA-positive patients showed significantly lower serum C-peptide levels than GADA-ELISA-negative patients. Meanwhile, in patients with longer disease duration, serum C-peptide levels were comparably decreased in GADA-ELISA-positive and GADA-ELISA-negative patients. A significant inverse correlation between serum C-peptide level and disease duration was observed in GADA-ELISA-negative patients, but not in GADA-ELISA-positive patients, suggesting that insulin secretory capacity may be gradually impaired over time also in GADA-ELISA-negative SPIDDM patients. In conclusion, physicians should be aware that GADA-ELISA-positive SPIDDM may be strongly associated with a future insulin-dependent state. Meanwhile, physicians should be careful in treating GADA-ELISA-negative SPIDDM patients diagnosed as type 2 DM, and cautiously follow the clinical course, in accordance with SPIDDM.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glutamato Descarboxilase/imunologia , Insulina/uso terapêutico , Idoso , Autoimunidade , Estudos Transversais , Diabetes Mellitus Tipo 1/patologia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
5.
Neuro Endocrinol Lett ; 37(8): 540-542, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28326749

RESUMO

A 26-year-old Japanese woman presented with adrenal insufficiency, and treatment was started with cortisone and fludrocortisone in 1975. A few years later, she presented with hypoparathyroidism and was diagnosed with autoimmune polyendocrine syndrome type I (APS I), and treatment with calcium and alfacalcidol was started. She was found to have subacute thyroiditis and relative adrenal failure in 2006. Her condition remained stable under treatment with cortisone, fludrocortisone, levothyroxine, calcium lactate, precipitated calcium carbonate and alfacalcidol. While antibodies against pancreatic glutamic acid decarboxylase (GAD) were strongly positive (7,690 U/ml), fasting glucose level was 4.9 mmol/L and HbA1c was 6.3% on admission. As GAD antibody showed a high-titer of >10,000 U/ml and fasting plasma glucose level showed a rising trend, we performed 75-g oral glucose tolerance test (OGTT) 6 years after discharge. Whereas OGTT in 2012 showed impaired glucose tolerance, glucose tolerance had reverted to normal in 2014. A patient with a high-titer GAD antibody does not always have progressive glucose intolerance. GAD antibody positivity is common in not only type 1 diabetes, but also APS I and stiff-person syndrome (SPS). There are differences in recognized epitopes among the three disorders. Epitopes for GAD65 antibody associated with type 1 diabetes are located in the middle region and the COOH-terminal of the GAD65 protein, whereas epitopes associated with SPS reside in the NH2-terminal in addition to the middle region and COOH-terminal. The present case suggests that these differences in epitopes may be related to various pathogenic mechanisms including glucose intolerance.


Assuntos
Autoanticorpos/sangue , Glutamato Descarboxilase/sangue , Poliendocrinopatias Autoimunes/imunologia , Adulto , Glicemia/análise , Epitopos/imunologia , Feminino , Teste de Tolerância a Glucose , Humanos , Poliendocrinopatias Autoimunes/sangue , Poliendocrinopatias Autoimunes/diagnóstico , Rigidez Muscular Espasmódica/sangue , Rigidez Muscular Espasmódica/diagnóstico
6.
Proc Jpn Acad Ser B Phys Biol Sci ; 93(9): 746-754, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29129852

RESUMO

It is difficult to distinguish the onset of renal function decline from the typical variation in estimated glomerular filtration rate (eGFR) measurements in clinical practice. In this study, we used data analysis incorporating smoothing techniques to identify significant trends despite large amounts of noise. We identified the starting points of meaningful eGFR decline based on eGFR trajectories. This was a retrospective observational study of 2533 type 2 diabetes patients. We calculated 1-year eGFR decline rates from the difference between each eGFR value and that of the previous year. We examined the prediction capacity of 1-year eGFR decline rate for renal prognosis. When we performed receiver operating characteristic analysis, the area under the curve of 1-year eGFR decline rate was 0.963 (95% confidence interval: 0.953-0.973). With a cut-off value of more than 7.5% eGFR decline during a 1-year period, the sensitivity was 98.8% and specificity was 82.3%. The predictive accuracy of 1-year eGFR decline rate for renal prognosis was high.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Taxa de Filtração Glomerular , Insuficiência Renal/diagnóstico , Insuficiência Renal/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal/complicações , Estudos Retrospectivos , Fatores de Tempo
7.
Endocr Res ; 41(1): 8-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26167855

RESUMO

The objective was to clarify whether dietary palmitic acid supplementation affects glucose-stimulated insulin secretion (GSIS) and the endoplasmic reticulum (ER) stress pathway in pancreatic islets in mice. Eight-week-old male C57BL/6J mice were randomly divided into three treatment diet groups: control diet, palmitic acid-supplemented diet (PAL) and oleic acid-supplemented diet (OLE). After 2 weeks of treatment, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were performed. GSIS was assessed by pancreatic perfusion in situ with basal (100 mg/dL) glucose followed by a high (300 mg/dL) glucose concentration. We measured mRNA levels of ER stress markers such as C/EBP homologous protein (CHOP), immunoglobulin heavy-chain binding protein (BIP) and X-box binding protein (XBP)-1 using real-time polymerase chain reaction (PCR) analyses in isolated islets. Immunohistochemical staining was also performed. Mice fed PAL showed significantly decreased glucose tolerance (p < 0.05). In the perfusion study, GSIS was significantly suppressed in the PAL group (p < 0.05). Semi-quantitative RT-PCR revealed that islet CHOP, BIP, and XBP-1 mRNA expression were significantly increased in the PAL group (p < 0.05). TUNEL-positive ß-cells were not detected in all groups. Dietary palmitic acid-supplementation for 2 weeks might suppress GSIS and induce ER stress in pancreatic islets in mice, in the early stage of lipotoxicity.


Assuntos
Gorduras na Dieta/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glucose/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ácido Palmítico/farmacologia , Animais , Dieta , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Endocr J ; 62(5): 399-409, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25739726

RESUMO

There is little information on direct comparison between metformin and glucagon-like peptide-1 (GLP-1) receptor agonists in the Asian population. This study examined the efficacy and safety of liraglutide monotherapy compared with metformin monotherapy in overweight/obese Japanese patients with type 2 diabetes (T2DM). The study was a 24-week, open-labeled, randomized controlled study. Overweight or obese patients with T2DM aged 20-75 years with suboptimal glycemic control were randomized to liraglutide or metformin monotherapy. The primary endpoint was change in HbA1c at week 24. Secondary endpoints included changes in daily glycemic profile, body weight, incidence of hypoglycemia and other adverse events. The study, which was originally planned to enroll 50 subjects in each group, was ended with insufficient recruitment. A total of 46 subjects completed the study, and analysis was conducted in this cohort. Reduction in HbA1c at week 24 was comparable between the metformin (n = 24) and liraglutide (n = 22) groups (-0.95 ± 0.80% vs. -0.80 ± 0.88%, p = 0.77), while the liraglutide group reached maximal reduction more rapidly than did the metformin group. There was no significant difference in weight gain or incidence of hypoglycemia between the groups. Diarrhea was more frequent in the metformin group, while constipation was more frequent in the liraglutide group. There was no significant difference in treatment satisfaction between the groups. In conclusion, liraglutide and metformin monotherapy showed similar reduction in HbA1c during 24 weeks, with no difference in weight gain or incidence of hypoglycemia in overweight or obese Japanese patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes , Liraglutida/uso terapêutico , Metformina/uso terapêutico , Obesidade/complicações , Sobrepeso/complicações , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Japão , Liraglutida/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Aumento de Peso
9.
Endocr J ; 61(2): 149-57, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24212881

RESUMO

The aim of this study was to clarify the relationship between baseline beta cell function and future glycated albumin (GA) to glycated hemoglobin ratio (GA/HbA1c) in patients with type 2 diabetes. In our retrospective cohort, 210 type 2 diabetic patients who had been admitted to our hospital and in whom HbA1c and GA had been measured at baseline and 2 years after admission were included in this study. Baseline beta cell function was assessed by postprandial C-peptide immunoreactivity index (PCPRI) during admission. With intensification of treatment during admission, HbA1c and GA were significantly decreased 1 year and 2 years after admission. While baseline HbA1c was not significantly correlated with HbA1c after 2 years, baseline GA/HbA1c was strongly correlated with GA/HbA1c after 2 years (r = 0.575, P <0.001). When the patients were divided into two groups according to median PCPRI, patients with low PCPRI showed higher GA/HbA1c both at baseline and after 2 years compared to those with high PCPRI. There was a significant negative correlation between PCPRI and GA/HbA1c after 2 years (r = -0.379, P <0.001). Multiple regression analysis revealed that PCPRI was an independent predictor of GA/HbA1c after 2 years. In conclusion, our findings suggest that lower beta cell function is associated with sustained higher GA/HbA1c ratio in patients with type 2 diabetes.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Hemoglobinas Glicadas/metabolismo , Células Secretoras de Insulina/fisiologia , Albumina Sérica/metabolismo , Idoso , Povo Asiático , Feminino , Produtos Finais de Glicação Avançada , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Albumina Sérica Glicada
10.
Biochem Biophys Res Commun ; 433(2): 181-7, 2013 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-23454127

RESUMO

Excessive nitric oxide (NO) plays a pivotal role in the progression of ß-cell apoptosis in type 1 diabetes mellitus. We used mouse insulinoma Min6 cells as a model of ß cells in this research. We found that (-)-DHMEQ, an NF-κB inhibitor, rescued ß cells from NO-induced apoptosis, and then studied the mechanism of apoptosis inhibition. (-)-DHMEQ activated Nrf2 and induced transcription of Nrf2-target genes following the increase of antioxidant response element (ARE) reporter activity. Similarly, tert-butyl hydroquinone (tBHQ), a known activator of Nrf2, inhibited NO-induced cell death along with the transcriptional activation of ARE. RNAi-mediated knockdown of Nrf2 lowered the cytoprotective effect of (-)-DHMEQ against NO, suggesting that (-)-DHMEQ inhibited NO-induced cell death via Nrf2 activation. Furthermore, overexpression of Nrf2 rendered cells to be more resistant to NO, indicating that Nrf2 activation provides critical defense function against NO in Min6 cells. Taken together, we conclude that (-)-DHMEQ may be a useful therapeutic agent for type 1 diabetes mellitus in the onset of disease by protecting ß cells from apoptosis.


Assuntos
Elementos de Resposta Antioxidante/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Benzamidas/farmacologia , Cicloexanonas/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/farmacologia , Animais , Técnicas de Silenciamento de Genes , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Insulinoma/tratamento farmacológico , Insulinoma/metabolismo , Insulinoma/patologia , Camundongos , Fator 2 Relacionado a NF-E2/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Células Tumorais Cultivadas
11.
Endocr J ; 60(4): 517-23, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23268927

RESUMO

The aim of this study was to clarify the association between C-peptide immunoreactivity (CPR), a marker of beta cell function, and future glycemic control in patients with type 2 diabetes. We conducted a retrospective analysis of 513 consecutive patients with type 2 diabetes who were admitted to our hospital between 2000 and 2007 and followed up for 2 years. Serum and urinary CPR levels were measured during admission, and CPR index was calculated as the ratio of CPR to plasma glucose. The associations between these markers at baseline and glycemic control after 2 years were assessed by means of logistic regression models. After 2 years, 167 patients (32.6%) showed good glycemic control (HbA1c <6.9%). Baseline serum and urinary CPR indices were significantly associated with good glycemic control after 2 years, and the postprandial CPR to plasma glucose ratio (postprandial CPR index) showed the strongest association (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.12-1.50, P = 0.001) among CPR indices. Multivariate analyses showed consistent results (OR 1.23, 95%CI 1.03-1.48, P = 0.021). In conclusion, preserved beta cell function at baseline was associated with better glycemic control thereafter in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Células Secretoras de Insulina/metabolismo , Idoso , Algoritmos , Biomarcadores/sangue , Glicemia/análise , Peptídeo C/sangue , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Modelos Logísticos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Período Pós-Prandial , Estudos Retrospectivos
12.
Neuro Endocrinol Lett ; 44(5): 336-339, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37524323

RESUMO

An 80-year-old Japanese woman had shown no indication of diabetes but regularly saw a primary-care physician for health management. Six months before her referral to our hospital, her HbA1c was 6.0%. She was referred to us for diabetic ketosis because she was urine ketone body-positive with a blood glucose level of 397 mg/dL and HbA1c of 14.6%. She was diagnosed with type 1 diabetes mellitus (T1DM) with glutamic acid decarboxylase (GAD) antibodies >2,000 U/mL (by ELISA) and IA-2 antibodies >30 U/mL. Insulin injections were introduced, and she was discharged. Laboratory tests during her hospitalization were negative for thyroid antibodies (TgAb, TPOAb). Elderly individuals with first-onset T1DM who are positive for IA-2 antibody are rare, and multiple-positive cases of pancreatic islet-associated autoantibodies are particularly rare. IA-2 antibodies have an approx. 60% positive rate in acute-onset T1DM, but they are more likely to be positive in children and adolescents and are known to turn negative earlier than anti-GAD antibodies. Although a large amount of insulin is needed in general in such cases, our patient was successfully treated with a small amount of insulin. IA-2 antibody has been reported to be positive even in GAD antibody-negative individuals. In some cases, IA-2 antibody and other antibodies are positive even in elderly-onset diabetes, and this contributes to the diagnosis of T1DM.


Assuntos
Diabetes Mellitus Tipo 1 , Ilhotas Pancreáticas , Humanos , Criança , Feminino , Adolescente , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas , Autoanticorpos , Insulina/uso terapêutico , Glutamato Descarboxilase
13.
Diabetol Int ; 14(1): 103-108, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36636158

RESUMO

Aims: Self-monitoring of blood glucose is a useful method for monitoring blood glucose. It is often a key role of a management plan to reduce glycemic variability and diabetic complications. Wireless monitoring systems to connect blood glucose and insulin pumps can facilitate glycemic control. In this study, we evaluated the accuracy of Contour® Next Link 2.4, a blood glucose monitoring system that cooperates wirelessly with most insulin pumps, in Japanese individuals. Methods: In this study, finger-stick samples from 59 individuals were collected at the Tokyo Saiseikai Central Hospital. Blood glucose concentrations were measured with the monitoring systems against an available reference. We evaluated the accuracy of the system based on the ISO 15197:2013 Section 6.3 accuracy criteria. Results: In the present study, 100% of the results fulfilled the ISO 15197:2013 Section 6.3 accuracy criteria (95% within ± 15 mg/dL or ± 15% of reference for glucose < 100 and ≥ 100 mg/dL, respectively). The Parkes-Consensus Error Grid analysis showed that 100% of the results fulfilled within Zone A. Conclusions: The Contour® Next Link 2.4 blood glucose monitoring system fulfilled the ISO 15197:2013 accuracy criteria limit and the consensus error grid criterion. Therefore, this monitoring system for observing blood glucose levels is accurate for Japanese individuals.

14.
Endocr J ; 59(3): 187-95, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22156325

RESUMO

It has been reported that beta cell function progressively declines in patients with type 2 diabetes. The objective of this study was to assess the effect of obesity on declining beta cell function after diagnosis of type 2 diabetes. We conducted a cross-sectional study of 689 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007. Fasting and postprandial serum C-peptide immunoreactivity (CPR) and urinary CPR levels had been measured during admission. The subjects were stratified according to BMI and time since diagnosis. CPR index was calculated as CPR (ng/mL) / plasma glucose (mg/dL) x 100. All CPR measurements were significantly higher in the 263 obese (BMI ≥25) subjects compared to the 426 lean subjects (BMI <25). There was a significant negative correlation between CPR indices and duration of diabetes, suggesting a progressive decline in beta cell function after diagnosis of type 2 diabetes. However, this decline was more apparent in obese subjects (postprandial CPR index 0.059/year) compared to lean subjects (0.025/year). The significant difference in serum CPR indices between the lean and obese subjects was lost in subjects more than 10 years after diagnosis. In conclusion, our observations suggest that beta cell function shows a greater progressive decline in obese subjects than in lean subjects with type 2 diabetes. Treatment of obesity may be an important strategy to preserve beta cell function in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Células Secretoras de Insulina/fisiologia , Obesidade/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Peptídeo C/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Jejum/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Período Pós-Prandial/fisiologia , Estudos Retrospectivos
15.
Endocr Res ; 37(4): 175-81, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22621443

RESUMO

There has been concern as to whether dipeptidyl peptidase-4 (DPP-4) inhibitors can be used safely in patients with relatively good glycemic control. This study, approved by the institutional review board of Hanzoumon Diabetes City Atlas Clinic, examined whether DPP-4 inhibitor sitagliptin could safely achieve good glycemic control without severe hypoglycemia by employing the "added food" concept. The subjects were 60 patients (46 men and 14 women) with type 2 diabetes who started sitagliptin therapy during a 1-month period from December 15, 2009 to January 15, 2010. They were recommended to have added food between meals to prevent hypoglycemia, while maintaining the same daily calorie intake. HbA(1c) decreased from 7.1 ± 1.2% to 6.5 ± 0.6% after 6 months of sitagliptin treatment (p < 0.001). In patients with a baseline HbA(1c) <7%, it decreased from 6.5 ± 0.3% to 6.1 ± 0.4% (p < 0.001). Systolic blood pressure was significantly reduced from 127.7 ± 17.0 to 122.7 ± 17.9 mmHg in the patients with a baseline HbA(1c) < 7% (p = 0.018). However, body weight increased by approximately 900 g and high-density lipoprotein cholesterol decreased significantly from 1.57 ± 0.46 to 1.43 ± 0.35 mmol/L (p < 0.01) in the patients concomitantly receiving sulfonylureas with sitagliptin. Excellent glycemic control was achieved by sitagliptin treatment together with the added food concept. However, combined use of sitagliptin with sulfonylureas requires attention to weight gain and the lipid profile. Further clinical studies will elucidate whether sitagliptin can decrease cardiovascular events as well as normalizing blood glucose and lowering the blood pressure.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Ingestão de Alimentos , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Pirazinas/uso terapêutico , Triazóis/uso terapêutico , Idoso , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/análise , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fosfato de Sitagliptina , Compostos de Sulfonilureia/uso terapêutico , Resultado do Tratamento , Aumento de Peso/efeitos dos fármacos
16.
Endocr J ; 58(7): 607-11, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21519152

RESUMO

Insulin overdose results in prolonged hypoglycemia. We hypothesized that if a huge amount of insulin is subcutaneously injected, the duration of hypoglycemia depends on the dose of insulin rather than the type of insulin. We conducted a literature review of insulin overdose and 33 cases were included in this study. We assessed the correlation between recovery time from hypoglycemia and insulin dose. As a result, there was a significant correlation between recovery time from hypoglycemia and insulin dose (r=0.88, p<0.0001) and this correlation was expressed as y=0.045x; where y is time (h) and x is insulin dose (U), corresponding to that if 1000 U insulin is injected, hypoglycemia will persist for ~45 h. This equation may be useful to predict the duration of glucose supplementation for treatment of insulin overdose.


Assuntos
Hipoglicemia/induzido quimicamente , Insulina/intoxicação , Adulto , Idoso , Overdose de Drogas , Feminino , Humanos , Insulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Análise de Regressão , Adulto Jovem
17.
Endocr J ; 58(4): 315-22, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21415555

RESUMO

Type 2 diabetes is a progressive disease and most patients with type 2 diabetes eventually need insulin therapy. The objective of this study was to clarify C-peptide immunoreactivity (CPR), a marker of beta cell function, as a predictor of requirement for insulin therapy. We conducted a retrospective study of 579 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007 and were able to be followed up for at least 6 months after discharge. Fasting and postprandial serum CPR and urinary CPR levels had been measured during admission. Information about insulin therapy at the last visit was obtained from medical records. At the last visit, 364 subjects (62.9%) were treated with insulin. Mean interval between discharge and the last visit was 4.5 ± 2.3 years. Serum and urine CPR levels at baseline were significantly associated with insulin treatment at the last visit (P<0.001 for all). Among CPR values, postprandial serum CPR to plasma glucose ratio (CPR index) showed the greatest area under the receiver operating characteristic (ROC) curve for insulin therapy. Multivariate logistic regression analysis evaluating the effect of postprandial CPR index adjusted for other confounders showed consistent results with unadjusted results. In conclusion, beta cell dysfunction is significantly correlated with future insulin therapy in patients with type 2 diabetes. Our study indicates that among CPR measurements, postprandial CPR index is the best predictive marker for future insulin therapy.


Assuntos
Glicemia/metabolismo , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Células Secretoras de Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Prognóstico , Estudos Retrospectivos
18.
Clin Drug Investig ; 31(4): 237-45, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21184621

RESUMO

BACKGROUND AND OBJECTIVE: Angiotensin II type 1 (AT1) receptor antagonists (angiotensin receptor blockers [ARBs]) are widely used for the treatment of not only hypertension but also cardiac dysfunction. B-type natriuretic peptide (BNP) is secreted mainly by the cardiac ventricle and plays an important role in the regulation of blood pressure (BP) and body fluid. It has been established that the plasma level of BNP is increased in patients with chronic heart failure in proportion to the severity of cardiac dysfunction. Because cardiac dysfunction is closely associated with a high risk of mortality in patients with diabetes mellitus, early identification and prevention of cardiac dysfunction are important. The objective of this study was to determine the effects of olmesartan medoxomil, a novel ARB, on the plasma level of BNP in hypertensive patients with type 2 diabetes. METHODS: This was a preliminary, prospective, observational, open-label study. Sixty-eight type 2 diabetic patients with hypertension (systolic BP [SBP]≥140 mmHg or diastolic BP [DBP]≥90 mmHg) received olmesartan medoxomil 10­20 mg/day for 24 weeks. Plasma levels of BNP, as well as several clinical parameters of glycaemic control and lipid metabolism, were compared before and after 24 weeks of treatment. Another group consisting of 22 age- and body mass index-matched subjects not treated with olmesartan medoxomil was observed for reference purposes. RESULTS: In the olmesartan medoxomil group, mean±SD SBP decreased from 152.8±16.4 at baseline to 146.8±14.4 mmHg after 24 weeks' treatment (p<0.05); similarly, mean±SD DBP decreased from 85.6±10.5 to 81.3±11.6 mmHg (p<0.05). In 53 subjects in whom plasma levels of BNP could be measured both before and after treatment, mean±SD BNP decreased from 41.3±49.9 to 32.5±36.3 pg/mL (p<0.05). Change in plasma BNP level over the 24-week treatment period in the olmesartan medoxomil group was not correlated with change in SBP or DBP. Multiple regression analysis revealed that change in plasma BNP level was not correlated with baseline value of or change in any other parameters. No other parameters in the olmesartan medoxomil group, and no parameters in the non-olmesartan medoxomil reference group, showed significant changes. CONCLUSION: The current preliminary study showed that olmesartan medoxomil treatment might decrease plasma BNP levels, independent of its BP-lowering effect, in hypertensive patients with type 2 diabetes.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Peptídeo Natriurético Encefálico/sangue , Tetrazóis/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Olmesartana Medoxomila , Estudos Prospectivos
19.
Rev Sci Instrum ; 79(1): 014101, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18248051

RESUMO

The design and performance of a new high-pressure and high-temperature cell for measurement of x-ray absorption fine structure (XAFS) spectra of solid catalysts working in a flowing liquid are presented. The cell has flat, high-purity sintered cubic boron nitride (c-BN) windows which can tolerate high temperature (900 K) and high pressure (10 MPa). The c-BN is a new material which has the highest tensile strength, second only to diamond, and is also chemically and thermally stable. The use of the cell is demonstrated for measurements of PtPdAl(2)O(3) and Ni(2)PSiO(2) hydrodesulfurization catalysts at reaction conditions. A technique called delta chi (Deltachi), involving determining the difference between XAFS spectra of the sample at reaction conditions and the bare sample, is introduced.

20.
Anal Sci ; 34(11): 1265-1270, 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29984782

RESUMO

The characterization of radionuclides in Fukushima is important to determine their origins and current state in the environment. Radionuclides exist as fine particles and are mixed with other constituents. A measurement method with both micro-imaging capability and highly selective element detection is necessary to analyze these particles. We developed such an imaging technique using a time-of-flight secondary ion mass spectrometry and wavelength-tunable Ti:Sapphire lasers for the resonance ionization of target elements without mass interference. This is called resonant laser ionization sputtered neutral mass spectrometry. The instrument has a high lateral resolution and a higher ionization selectivity using two-step resonance excitation of Cs with two lasers at different wavelengths. Optimization of the wavelength for resonance ionization using a Cs compound was performed, and a real environmental particle containing radioactive Cs was analyzed. Isotope images of three kinds of Cs were successfully obtained without interfere from Ba isotopes for the first time.

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