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Neuroimaging databases for neuro-psychiatric disorders enable researchers to implement data-driven research approaches by providing access to rich data that can be used to study disease, build and validate machine learning models, and even redefine disease spectra. The importance of sharing large, multi-center, multi-disorder databases has gradually been recognized in order to truly translate brain imaging knowledge into real-world clinical practice. Here, we review MRI databases that share data globally to serve multiple psychiatric or neurological disorders. We found 42 datasets consisting of 23,293 samples from patients with psychiatry and neurological disorders and healthy controls; 1245 samples from mood disorders (major depressive disorder and bipolar disorder), 2015 samples from developmental disorders (autism spectrum disorder, attention-deficit hyperactivity disorder), 675 samples from schizophrenia, 1194 samples from Parkinson's disease, 5865 samples from dementia (including Alzheimer's disease), We recognize that large, multi-center databases should include governance processes that allow data to be shared across national boundaries. Addressing technical and regulatory issues of existing databases can lead to better design and implementation and improve data access for the research community. The current trend toward the development of shareable MRI databases will contribute to a better understanding of the pathophysiology, diagnosis and assessment, and development of early interventions for neuropsychiatric disorders.
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The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.
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Encefalopatías , Leucoaraiosis , Sustancia Blanca , Persona de Mediana Edad , Humanos , Sustancia Blanca/diagnóstico por imagen , Envejecimiento , Imagen por Resonancia Magnética/métodos , Corteza Cerebral/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagenRESUMEN
Menarche is delayed in patients with type 1 diabetic mellitus (T1DM) compared to non-diabetics. The purpose of this survey study was to define the age of onset of menarche in Japanese patients with T1DM, as well the secular trends in menarcheal age across the period of 1976-2020 and determine the effects of T1DM and disease management on that age. The study subjects (n = 155) were recruited from among Japanese T1DM patients who visited the outpatient clinic of the Department of Pediatrics, Osaka City University Hospital. The study subjects experienced menarche during 1976-2020. They were divided into the menarche-post-T1DM group (n = 117) and the menarche-pre-T1DM group (n = 38), in whom menarche occurred after or before the diagnosis of T1DM, respectively. The time of birth was also stratified into five decade/time bins extending from 1960s to 2000s. The subjects filled a questionnaire on menarche. Other clinical information was obtained from the medical records. The median age at menarche was 12.5 years (11.3-13.4) (25th-75th percentile) for the menarche-post-T1DM group and 11.8 years (10.9-13.0) for the menarche-pre-T1DM group (p = 0.024). Menarche occurred at a significantly younger age in recent years in the menarche-post-T1DM group (r = -0.209, p = 0.023), but no such trend was found in the control group. Analysis of data of subjects born after 1990 still showed significant delay associated with T1DM [post-T1DM group: 12.3 years (11.3-13.2), pre-T1DM group: 11.8 years (11.0-12.2), p = 0.045]. The results suggest that recent advances in insulin therapy seem to improve metabolism under T1DM but might have not enough impact on menarche in Japanese girls.
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Diabetes Mellitus Tipo 1 , Menarquia , Factores de Edad , Niño , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Humanos , Insulina/uso terapéutico , Japón/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: There are few reports pertaining to Asian patients with neonatal diabetes mellitus (NDM) caused by activating mutations in the ATP-sensitive potassium channel genes (KATP-NDM). OBJECTIVES: To elucidate the characteristics of Japanese patients with KATP-NDM. METHODS: By the amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11 and ABCC8 genes, 25 patients with KATP-NDM were identified from a total of 70 patients with NDM. Clinical data were collected from the medical charts. RESULTS: Sixteen patients had mutations in KCNJ11 and nine in ABCC8. Eight novel mutations were identified; two in KCNJ11 (V64M, R201G) and six in ABCC8 (R216C, G832C, F1176L, A1263V, I196N, T229N). Interestingly, V64M caused DEND (developmental delay, epilepsy, neonatal diabetes) syndrome in our patient, while mutation of the same residue (V64G) had been reported to cause congenital hyperinsulinism. Mutations in ABCC8 were associated with TNDM (4/9) or isolated PNDM (5/9), whereas those in KCNJ11 were associated with more severe phenotypes, including DEND (3/16), iDEND (intermediate DEND, 4/16), or isolated PNDM (6/16). Switching from insulin to glibenclamide monotherapy was successful in 87.5% of the patients. Neurological improvement was observed in two patients, one with DEND (T293N) and one with iDEND (R50P) syndrome. Three others with iDEND mutations (R201C, G53D, and V59M) remained neurologically normal at 5, 1, and 4 years of age, respectively, with early introduction of sulfonylurea. CONCLUSION: Overall, clinical presentation of KATP-NDM in Japanese patients was similar to those of other populations. Early introduction of sulfonylurea appeared beneficial in ameliorating neurological symptoms.
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Diabetes Mellitus/genética , Predisposición Genética a la Enfermedad , Mutación , Canales de Potasio de Rectificación Interna/genética , Receptores de Sulfonilureas/genética , Sustitución de Aminoácidos , Hiperinsulinismo Congénito/sangre , Hiperinsulinismo Congénito/tratamiento farmacológico , Hiperinsulinismo Congénito/genética , Hiperinsulinismo Congénito/fisiopatología , Análisis Mutacional de ADN , Diabetes Mellitus/sangre , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Monitoreo de Drogas , Resistencia a Medicamentos , Epilepsia/sangre , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Epilepsia/fisiopatología , Femenino , Estudios de Asociación Genética , Gliburida/uso terapéutico , Humanos , Hiperglucemia/prevención & control , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Lactante , Enfermedades del Recién Nacido/sangre , Enfermedades del Recién Nacido/tratamiento farmacológico , Enfermedades del Recién Nacido/genética , Enfermedades del Recién Nacido/fisiopatología , Insulina/uso terapéutico , Japón , Masculino , Canales de Potasio de Rectificación Interna/química , Trastornos Psicomotores/sangre , Trastornos Psicomotores/tratamiento farmacológico , Trastornos Psicomotores/genética , Trastornos Psicomotores/fisiopatología , Índice de Severidad de la Enfermedad , Receptores de Sulfonilureas/químicaRESUMEN
Polar auxin movement is a primary regulator of programmed and plastic plant development. Auxin transport is highly regulated at the cellular level and is mediated by coordinated transport activity of plasma membrane-localized PIN, ABCB, and AUX1/LAX transporters. The activity of these transporters has been extensively analyzed using a combination of pharmacological inhibitors, synthetic auxins, and knock-out mutants in Arabidopsis. However, efforts to analyze auxin-dependent growth in other species that are less tractable to genetic manipulation require more selective inhibitors than are currently available. In this report, we characterize the inhibitory activity of 5-alkoxy derivatives of indole 3-acetic acid and 7-alkoxy derivatives of naphthalene 1-acetic acid, finding that the hexyloxy and benzyloxy derivatives act as potent inhibitors of auxin action in plants. These alkoxy-auxin analogs inhibit polar auxin transport and tropic responses associated with asymmetric auxin distribution in Arabidopsis and maize. The alkoxy-auxin analogs inhibit auxin transport mediated by AUX1, PIN, and ABCB proteins expressed in yeast. However, these analogs did not inhibit or activate SCF(TIR1) auxin signaling and had no effect on the subcellular trafficking of PIN proteins. Together these results indicate that alkoxy-auxins are inactive auxin analogs for auxin signaling, but are recognized by PIN, ABCB, and AUX1 auxin transport proteins. Alkoxy-auxins are powerful new tools for analyses of auxin-dependent development.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/antagonistas & inhibidores , Ácidos Indolacéticos/metabolismo , Naftalenos/farmacología , Zea mays/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Ácidos Indolacéticos/farmacología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Saccharomyces cerevisiae/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Zea mays/genéticaRESUMEN
Ensuring quality of life (QOL) while maintaining glycemic control within targets is an important challenge in type 1 and type 2 diabetes treatment. For children with diabetes, QOL includes enjoying meals, feeling safe in school, and perceiving positive, supportive relationships with parents, siblings, and friends. Yet many treatment-related and psychosocial barriers can interfere with a child's QOL and their ability to manage diabetes effectively. Diabetes management also imposes considerable lifestyle demands that are difficult and often frustrating for children to negotiate at a young age. Recent advances in diabetes medications and technologies have improved glycemic control in children with diabetes. Two widely used technologies are the insulin pump and continuous glucose monitoring (CGM) system. These technologies provide patients with more flexibility in their daily life and information about glucose fluctuations. Several studies report improvements in glycemic control in children with type 1 diabetes using the insulin pump or sensor-augmented pump therapy. Importantly, these technologies may impact QOL for children and families with diabetes, although they are rarely used or studied in the treatment of children with type 2 diabetes. Further, emerging closed loop and web- and phone-based technologies have great potential for supporting diabetes self-management and perhaps QOL. A deeper understanding and appreciation of the impact of diabetes technology on children's and parents' QOL is critical for both the medical and psychological care of diabetes. Thus, the purpose of this review is to discuss the impact of new diabetes technologies on QOL in children, adolescents and families with type 1 diabetes.
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Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Estilo de Vida , Calidad de Vida , Adolescente , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea/métodos , Automonitorización de la Glucosa Sanguínea/tendencias , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Femenino , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/sangre , Sistemas de Infusión de Insulina/tendencias , Masculino , Monitoreo Ambulatorio/métodos , Monitoreo Ambulatorio/tendencias , Núcleo Familiar , PadresAsunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Educación en Salud , Niño , Humanos , Calidad de VidaRESUMEN
INTRODUCTION: There is no information on the factors that influence the time required to induce resolution of diabetic ketoacidosis (DKA). New methods are currently available for bedside measurement of serum 3-hydroxybutyrate (3HB). The aim of this study was to determine the relationship between serum 3HB and the time to DKA resolution. METHODS: We reviewed the medical records of patients with type 1 diabetes (T1D) and a history of DKA who were admitted to the Department of Pediatrics, Osaka City University Hospital, between November 2008 and October 2018. DKA resolution was defined as 3HB below 1.0 mmol/L as measured by a bedside ketone meter. RESULTS: Data of 52 T1D-DKA episodes were analyzed (median age, 8.0 years; 20 male patients; 32 female patients; new T1D diagnosis, n = 13; established diagnosis, n = 39). In all cases, correction of serum 3HB was an important aspect of T1D management. The median time to DKA resolution (defined as the time from the start of insulin infusion until the fall of 3HB level to below 1.0 mmol/L) was 11 and 10 h in new and established T1D cases, respectively. 3HB on admission and the required insulin infusion dose per body weight, but not blood pH level on admission, correlated with time to DKA resolution. There was no relationship between blood pH level and 3HB on admission. CONCLUSIONS: Our results showed that DKA resolution could be achieved within 10-11 h when DKA treatment is guided by bedside 3HB monitoring without any severe complications. Blood 3HB level is a potentially suitable marker for the severity and resolution of DKA.
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SINEUPs are antisense long noncoding RNAs, in which an embedded SINE B2 element UP-regulates translation of partially overlapping target sense mRNAs. SINEUPs contain two functional domains. First, the binding domain (BD) is located in the region antisense to the target, providing specific targeting to the overlapping mRNA. Second, the inverted SINE B2 represents the effector domain (ED) and enhances translation. To adapt SINEUP technology to a broader number of targets, we took advantage of a high-throughput, semi-automated imaging system to optimize synthetic SINEUP BD and ED design in HEK293T cell lines. Using SINEUP-GFP as a model SINEUP, we extensively screened variants of the BD to map features needed for optimal design. We found that most active SINEUPs overlap an AUG-Kozak sequence. Moreover, we report our screening of the inverted SINE B2 sequence to identify active sub-domains and map the length of the minimal active ED. Our synthetic SINEUP-GFP screening of both BDs and EDs constitutes a broad test with flexible applications to any target gene of interest.
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Biosíntesis de Proteínas/genética , Proteínas/genética , ARN Largo no Codificante/genética , Animales , Línea Celular Tumoral , Células HEK293 , Humanos , Ratones , FosforilaciónRESUMEN
This case report describes involuntary trembling of the tongue accompanied by throat discomfort and affected voice quality in a patient with a history of hypertension and ventricular extrasystole.
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Lengua , Temblor , Humanos , Lengua/diagnóstico por imagen , Temblor/diagnóstico por imagen , UltrasonografíaRESUMEN
The objective of this study was to identify factors affecting on errors in carbohydrate (CHO) content estimation during CHO counting. Thirty-seven type 1 diabetes patients and 22 of their parents and 28 physicians/dieticians were enrolled in this study. CHO counting was counted in "Carb", with 1 Carb defined as 10 g of CHO. To evaluate the accuracy of CHO counting, 80 real-size photographs of cooked meals were presented to the subjects for Carb estimation. Carbs tended to be overestimated for foods containing relatively small amounts of Carbs. On the other hands, Carbs tended to be underestimated for foods with higher than 6 Carbs. Accurate estimation of the Carbs in food containing a large amount of rice was particularly difficult even in the subjects having the CHO counting experience. The Carb contents of high-calorie foods such as meats, fried foods, and desserts tended to be overestimated. This error was smaller in subjects having the CHO counting experience. In conclusion, misunderstanding of high-calorie dishes containing high amounts of CHO was observed in inexperienced subjects, indicating the efficacy of the current methodology of CHO counting. On the other hand it was difficult even for experienced subjects to assess the amount of seasoned rice, suggesting the need for a new methodology for accurate estimation.
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BACKGROUND & AIMS: The utility of transient elastography (FibroScan) is well studied in adults but not in children. We sought to assess the feasibility of performing FibroScans and the characteristics of FibroScan-based liver profiles in Japanese obese and non-obese children. METHODS: FibroScan examinations were performed in pediatric patients (age, 1-18 yr) who visited Osaka City University Hospital. Liver steatosis measured by controlled attenuation parameter (CAP), and hepatic fibrosis evaluated as the liver stiffness measurement (LSM), were compared among obese subjects (BMI percentile ≥ 90%), non-obese healthy controls, and non-obese patients with liver disease. RESULTS: Among 214 children examined, FibroScans were performed successfully in 201 children (93.9%; median, 11.5 yr; range, 1.3-17.6 yr; 115 male). CAP values (mean ± SD) were higher in the obese group (n = 52, 285 ± 60 dB/m) compared with the liver disease (n = 40, 202 ± 62, P < 0.001) and the control (n = 107, 179 ± 41, P < 0.001) group. LSM values were significantly higher in the obese group (5.5 ± 2.3 kPa) than in the control (3.9 ± 0.9, P < 0.001), but there were no significant differences in LSM between the liver disease group (5.4 ± 4.2) and either the obese or control group. LSM was highly correlated with CAP in the obese group (ρ = 0.511) but not in the control (ρ = 0.129) or liver disease (ρ = 0.170) groups. CONCLUSIONS: Childhood obesity carries a high risk of hepatic steatosis associated with increased liver stiffness. FibroScan methodology provides simultaneous determination of CAP and LSM, is feasible in children of any age, and is a non-invasive and effective screening method for hepatic steatosis and liver fibrosis in Japanese obese children.
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Hígado Graso/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Hígado/diagnóstico por imagen , Obesidad Infantil/diagnóstico por imagen , Adiposidad , Adolescente , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Niño , Preescolar , Diagnóstico por Imagen de Elasticidad , Hígado Graso/sangre , Femenino , Humanos , Lactante , Japón , Hígado/patología , Cirrosis Hepática/sangre , Masculino , Obesidad Infantil/sangre , Obesidad Infantil/patología , Triglicéridos/sangreRESUMEN
UNLABELLED: Aims/Introduction: The daily basal insulin doses/body weight and the daily basal insulin doses/total daily insulin doses of Japanese type 1 diabetes mellitus patients are less than those of Western type 1 diabetes mellitus patients. It is known that Western meals are richer in fat than Japanese meals. We speculated that fat intake might be associated with basal insulin dose in type 1 diabetes mellitus patients. MATERIALS AND METHODS: Forty-one outpatients with type 1 diabetes mellitus (20 males, 21 females, mean age 15.9) were enrolled. Variables investigated included: gender, SDS-BMI, HbA1c, duration of diabetes, therapy (MDI or CSII), insulin doses and meal contents. Meal contents were recorded for 3 days using a digital camera. Correlation and multiple regression analyses were performed for all subjects and each age group. RESULTS: The mean daily basal insulin doses/total daily insulin doses was 0.35. In the multiple regression analysis among all subjects, when daily basal insulin doses/body weight was used as a dependent variable, fat energy ratio of the meal was obtained as an entered variable (P = 0.001). This tendency was particularly strong among the patients aged 14 or above (P < 0.001, standardized coefficient ß = 0.683). CONCLUSIONS: In the type 1 diabetes patients who are aged 14 or above, an association between daily basal insulin doses/body weight and fat energy ratio of meal was suggested. This may explain the aforementioned expectation of increased fat intakes making higher basal insulin doses. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00171.x, 2011).
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The plant hormone auxin is a master regulator of plant growth and development. By regulating rates of cell division and elongation and triggering specific patterning events, indole 3-acetic acid (IAA) regulates almost every aspect of plant development. The perception of auxin involves the formation of a ternary complex consisting of an F-box protein of the TIR1/AFB family of auxin receptors, the auxin molecule, and a member the Aux/IAA family of co-repressor proteins. In this study, we identified a potent auxin antagonist, α-(phenylethyl-2-oxo)-IAA, as a lead compound for TIR1/AFB receptors by in silico virtual screening. This molecule was used as the basis for the development of a more potent TIR1 antagonist, auxinole (α-[2,4-dimethylphenylethyl-2-oxo]-IAA), using a structure-based drug design approach. Auxinole binds TIR1 to block the formation of the TIR1-IAA-Aux/IAA complex and so inhibits auxin-responsive gene expression. Molecular docking analysis indicates that the phenyl ring in auxinole would strongly interact with Phe82 of TIR1, a residue that is crucial for Aux/IAA recognition. Consistent with this predicted mode of action, auxinole competitively inhibits various auxin responses in planta. Additionally, auxinole blocks auxin responses of the moss Physcomitrella patens, suggesting activity over a broad range of species. Our works not only substantiates the utility of chemical tools for plant biology but also demonstrates a new class of small molecule inhibitor of protein-protein interactions common to mechanisms of perception of other plant hormones, such as jasmonate, gibberellin, and abscisic acid.
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Proteínas de Arabidopsis/antagonistas & inhibidores , Diseño de Fármacos , Proteínas F-Box/antagonistas & inhibidores , Ácidos Indolacéticos/antagonistas & inhibidores , Receptores de Superficie Celular/antagonistas & inhibidores , Arabidopsis/química , Arabidopsis/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Ácidos Indolacéticos/síntesis química , Ácidos Indolacéticos/química , Ácidos Indolacéticos/aislamiento & purificación , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacología , Modelos Moleculares , Estructura Molecular , Relación Estructura-ActividadRESUMEN
OBJECTIVE: Nearly one-half of diabetic patients have glycated hemoglobin A(1c) (HbA(1c)) levels above recommended targets. Effective physician-patient communication improves glycemia and diabetes self-care; however, communication gaps may exist that prevent patients from discussing self-care problems with treatment providers. RESEARCH DESIGN AND METHODS: We assessed diabetic patients' (n = 316, 85% white, 51% female, 71% type 2 diabetes, 59 ± 11 years old, 16 ± 3 years education, 19 ± 13 years diabetes duration, and HbA(1c) = 7.9 ± 1.4%) HbA(1c), frequency of self-care, diabetes-related distress, depressive and anxiety symptoms, coping styles, diabetes quality of life, and self-care communication in the treatment relationship. Multivariate logistic regression models examined the main and interaction effects of health and psychosocial factors associated with patients' reluctance to discuss self-care. RESULTS: Patients reported positive relationships with their doctors and valued honest communication; however, 30% of patients were reluctant to discuss self-care. Reluctant patients reported less frequent self-care (P = 0.05), lower diabetes quality of life (P = 0.002), and more diabetes-related distress (P = 0.001), depressive symptoms (P < 0.001), and anxiety symptoms (P = 0.001). Patients who reported elevated depressive symptoms, although not necessarily major depression, were more likely to be reluctant to discuss self-care (odds ratio [OR] 1.66 for 10-point change in t score; P < 0.001), whereas patients who were older (OR 0.78 for 10-year change; P = 0.05) and those who used more self-controlled coping styles (OR 0.78 for 10-point change; P = 0.007) were less likely to be reluctant. CONCLUSIONS: Awareness of elevated depressive symptoms is important in clinical practice given that these patients may be more reluctant to discuss self-care. Interventions and evidence-based approaches are needed to improve both depressive symptoms and physician-patient communication about self-care.
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Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Relaciones Médico-Paciente , Autocuidado/psicología , Adaptación Psicológica , Adulto , Anciano , Ansiedad/psicología , Glucemia/metabolismo , Comunicación , Estudios Transversales , Depresión/psicología , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 2/psicología , Escolaridad , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y CuestionariosRESUMEN
INTRODUCTION: The in-hospital sliding scale (Sc) to determine the insulin dose was changed to a carbohydrate counting sliding scale (CSc). Blood glucose levels before and after the change were compared. METHODS: The Sc was used in 32 patients in July and August 2009 (Sc group) and the CSc was used in 32 patients in September and October 2009 (CSc group). The blood glucose levels recorded before breakfast, lunch, and supper for 14 days were analyzed. The overall and daily mean of all blood glucose data were compared between the 2 groups. RESULTS: The overall blood glucose level was significantly lower in the CSc group than in the Sc group (p<0.001). The percentage of blood glucose level below 199mg/dL was 47% in the Sc group and 59% in the CSc group. The daily blood glucose level in the Sc group was 203-229mg/dL until day 14, while the daily mean blood glucose level decreased significantly to 186mg/dL on day 4 in the CSc group and remained in the 176-200mg/dL range on subsequent days (p=0.049). CONCLUSIONS: The CSc is easy to use, safe and useful in controlling the blood glucose level.
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Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Insulina/administración & dosificación , Insulina/uso terapéutico , Anciano , Anciano de 80 o más Años , Glucemia/efectos de los fármacos , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease. Insulin seems to be a critical antigen recognized by autoreactive T cells. In this study, we performed T cell epitope mapping of insulin using serial overlapping peptides in Japanese patients with T1D. Serial overlapping insulin peptides comprising 23 peptides, which were each 15-amino acid long, were prepared based on insulin sequence. Cytokine secretion from peripheral T cells against these peptides was studied by enzyme-linked immunospot (ELISPOT) assay in 18 patients with recent-onset T1D and 12 patients with established T1D, and compared with 17 healthy control subjects. In ELISPOT assay, IFN-gamma-secreting T cells, but not IL-4, against several insulin peptides were observed in 77.8% of patients with recent-onset T1D, 50.0% of patients with established T1D, and 0% of healthy control subjects. All epitopes recognized by T cells were identified in the B-chain of insulin. The most frequent epitope existed at the B10-24 region (9/18), followed by B1-15 and B11-25 regions (6/18, each), with B4-18, B9-23, and B12-26 identified in some patients. These data did not correlate with insulin autoantibodies or HLA-DRB1 of the patients. This is the first report of T cell epitope mapping using one amino acid serial overlapping peptides of insulin in T1D. ELISPOT assay revealed the frequent existence of insulin peptide-specific T cells in patients with recent-onset and established T1D. The T cell epitopes of insulin were similar but not identical in our cohort, which probably explains the difficulty encountered in prevention of human T1D by using insulin.