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AIMS/INTRODUCTION: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. MATERIALS AND METHODS: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. RESULTS: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician-patient interaction and the impossibility of consultation and examination were cited as sources of concern. CONCLUSIONS: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine.
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COVID-19 , Diabetes Mellitus , Telemedicina , Humanos , Controle Glicêmico , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , Hemoglobinas Glicadas , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapiaRESUMO
An 85-year-old man was being treated with anti-cancer drugs for adenocarcinoma of the lung and was on a tapering dose of prednisolone for interstitial pneumonia. He attended our hospital complaining of fatigue, thirst, and polyuria in September 2020. His postprandial plasma glucose concentration was 976 mg/dL, his glycated hemoglobin was 8.0%, his plasma osmolality was 342 mOsm/kg H2O, his urine ketone body content was 1 +, and his blood pH was 7.356. Therefore, we diagnosed a hyperosmolar-hyperglycemic state and he was admitted to the hospital for treatment. He had had no previous upper respiratory symptoms, and his postprandial plasma glucose and glycated hemoglobin were normal 13 days before he was first assessed (90 mg/dL and 5.9%, respectively). On admission, his serum pancreatic exocrine enzyme activities were high and he was negative for islet-specific autoantibodies. His serum C-peptide concentration was 0.60 ng/mL, suggesting that his endogenous insulin secretion was partially intact at that time. Although he did not meet the diagnostic criteria, we suspected him of having fulminant type 1 diabetes mellitus, because of the abrupt onset of hyperosmolar-hyperglycemic state. His general condition was improved by fluid and insulin administration. His human leukocyte antigen genotype was DRB1*04:05 DQB1*04:01:01, which is a disease susceptibility haplotype for fulminant type 1 diabetes mellitus. In addition, his prednisolone treatment may have caused an autoimmune abnormality, further predisposing toward the development of fulminant type 1 diabetes mellitus.
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AIMS: Most risk calculators that predict future cardiovascular disease (CVD) by baseline profiles are originally developed for primary prevention, but some studies applied the calculators to secondary prevention. We compared the impact of baseline profiles on the future CVD risk between patients with diabetes with and without a CVD history. METHODS: We analyzed a multicenter prospective cohort of 6338 Japanese patients with diabetes aged 40-74 years, including those with (n = 634) and without a CVD history (n = 5704). The future risk of CVD was investigated using the competing risk model, with adjustment for non-cardiovascular mortality. RESULTS: During the median follow-up of 6.9 years, 413 CVD events were observed. The 8-year cumulative incidence rates of CVD were 21.5% and 7.2% in patients with and without a CVD history, respectively. A higher systolic blood pressure and lower high-density lipoprotein cholesterol levels were independently associated with a future CVD risk in patients without a CVD history (both P < 0.05), whereas they were not associated in those with a CVD history. The P values for interaction were 0.040 and 0.005, respectively. The male sex, an older age, a longer duration of diabetes, higher hemoglobin A1c levels, and higher low-density lipoprotein cholesterol levels were common independent risk factors regardless of CVD history (all P < 0.05). CONCLUSIONS: The prognostic impact of metabolic profiles on CVD risk would not be identical between patients with and without a CVD history, suggesting that it might be inappropriate to apply CVD risk calculators developed for primary prevention to patients with a CVD history.
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Doenças Cardiovasculares , Complicações do Diabetes , Diabetes Mellitus , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Metaboloma , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: This study aimed to explore predictive factors of time below target glucose range (TBR) ≥ 1% among patients' characteristics and glycemic variability (GV) indices using continuous glucose monitoring data in elderly patients with type 2 diabetes. METHODS: We conducted a prospective observational study on 179 (71 female) Japanese outpatients with type 2 diabetes aged ≥ 65 years. The characteristics of the participants with TBR ≥ 1% were evaluated by multivariate logistic regression analysis. Receiver-operating characteristic (ROC) curve analyses of GV indices, comprising coefficient of variation (CV), standard deviation, and mean amplitude of glycemic excursions, were performed to identify the optimal index for the identification of patients with TBR ≥ 1%. RESULTS: In the multivariate logistic regression analysis, none of the clinical characteristics, including HbA1c and C-peptide index, were independent markers for TBR ≥ 1%, while all three GV indices showed significant associations with TBR ≥ 1%. Among the three GV indices, CV showed the best performance based on the area under the curve in the ROC curve analyses. CONCLUSIONS: Among elderly patients with type 2 diabetes, CV reflected TBR ≥ 1% most appropriately among the GV indices examined. Trial registration UMIN-CTR: UMIN000029993. Registered 16 November 2017.
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The aim of this study was to evaluate the efficacy and safety of pemafibrate in people with type 2 diabetes and hypertriglyceridaemia over a 52-week period. Participants were randomly assigned to receive treatment with placebo or pemafibrate at a dose of 0.2 or 0.4 mg/d for 24 weeks (treatment period 1). The main results from treatment period 1 have been reported previously. The assigned treatment was continued up to week 52, except that the placebo was changed to pemafibrate 0.2 mg/d after week 24 (treatment period 2). The percentage changes in fasting serum triglyceride (TG) levels at week 52 (last observation carried forward) were -48.2%, -42.3%, and -46.4% in the placebo/pemafibrate 0.2 mg/d (n = 57), pemafibrate 0.2 mg/d (n = 54), and pemafibrate 0.4 mg/d (n = 55) groups, respectively. Levels of TG, non-HDL cholesterol and total cholesterol stably decreased, whereas levels of HDL cholesterol increased with pemafibrate treatments over 52 weeks. Pemafibrate was well tolerated throughout the study period. The present study is the first to show that pemafibrate treatment substantially ameliorated lipid abnormalities and was well tolerated for 52 weeks in people with type 2 diabetes and hypertriglyceridaemia.
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Benzoxazóis , Butiratos , Diabetes Mellitus Tipo 2/complicações , Hipertrigliceridemia , Hipolipemiantes , Benzoxazóis/efeitos adversos , Benzoxazóis/uso terapêutico , Butiratos/efeitos adversos , Butiratos/uso terapêutico , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/tratamento farmacológico , Hipolipemiantes/efeitos adversos , Hipolipemiantes/uso terapêutico , Triglicerídeos/sangueRESUMO
OBJECTIVE: Type 2 diabetes is frequently complicated with atherogenic dyslipidemia. This study aimed to evaluate the efficacy and safety of pemafibrate (K-877) in patients with type 2 diabetes comorbid with hypertriglyceridemia. RESEARCH DESIGN AND METHODS: Patients were randomly assigned to three groups and received placebo (n = 57), 0.2 mg/day pemafibrate (n = 54), or 0.4 mg/day pemafibrate (n = 55) for 24 weeks (treatment period 1). Subsequently, the patients received follow-up treatment for another 28 weeks (treatment period 2), in which the placebo was switched to 0.2 mg/day pemafibrate. This article presents the results of treatment period 1, which were the primary objectives. RESULTS: The pemafibrate groups showed significantly reduced fasting serum triglyceride levels by â¼45% compared with the placebo group (P < 0.001). Additionally, the pemafibrate groups displayed significant decreases in non-HDL and remnant lipoprotein cholesterol, apolipoprotein (Apo) B100, ApoB48, and ApoCIII levels and significant increases in HDL cholesterol and ApoA-I levels. LDL cholesterol levels were not considerably altered in the pemafibrate groups. Furthermore, the 0.2 mg/day pemafibrate group showed a significantly reduced HOMA-insulin resistance score compared with the placebo group; however, no significant changes compared with placebo were found in fasting plasma glucose, fasting insulin, glycoalbumin, or HbA1c levels. The pemafibrate groups also showed significantly increased fibroblast growth factor 21 levels compared with the placebo group. All groups displayed comparable rates of adverse events and drug reactions. CONCLUSIONS: Pemafibrate significantly ameliorated lipid abnormalities and was well tolerated in patients with type 2 diabetes comorbid with hypertriglyceridemia.
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Benzoxazóis/uso terapêutico , Glicemia/efeitos dos fármacos , Butiratos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertrigliceridemia/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , PPAR alfa/metabolismo , PlacebosRESUMO
AIMS/INTRODUCTION: To explore the relationships between periodontitis and microvascular complications as well as glycemic control in type 2 diabetes patients. MATERIALS AND METHODS: This multicenter, hospital-based, cross-sectional study included 620 patients with type 2 diabetes. We compared the prevalence and severity of periodontitis between patients with ≥1 microvascular complication and those without microvascular complications. We also compared the prevalence and severity of periodontitis among patients with different degrees of glycemic control. RESULTS: After adjusting for confounding factors, multiple logistic regression analysis showed that the severity of periodontitis was significantly associated with the number of microvascular complications (odds ratio 1.3, 95% confidence interval 1.1-1.6), glycated hemoglobin ≥8.0% (64 mmol/mol; odds ratio 1.6; 95% confidence interval 1.1-2.3), and older age (≥50 years; odds ratio 1.7; 95% confidence interval 1.1-2.6). However, the prevalence of periodontitis was not significantly associated with the number of microvascular complications, but was associated with male sex, high glycated hemoglobin (≥8.0% [64 mmol/mol]), older age (≥40 years), longer duration of diabetes (≥15 years) and fewer teeth (≤25). Furthermore, propensity score matching for age, sex, diabetes duration and glycated hemoglobin showed that the incidence of severe periodontitis was significantly higher among patients with microvascular complications than among those without microvascular complications (P < 0.05). CONCLUSIONS: The number of microvascular complications is a risk factor for more severe periodontitis in patients with type 2 diabetes, whereas poor glycemic control is a risk factor for increased prevalence and severity of periodontitis.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Periodontite/complicações , Periodontite/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Microvasos/fisiopatologia , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
AIMS/INTRODUCTION: 'The Standard Diabetes Manual' has been developed by clinical researchers from multiple major institutions in Japan, such as the National Center for Global Health and Medicine, as a comprehensive disease management program, including collaboration between primary care physicians (PCPs) and specialist services. The present study evaluated the efficacy of the manual as a quality improvement strategy in diabetes care by PCPs. MATERIALS AND METHODS: A total of 42 PCPs in eight domestic districts of the Japan Medical Association were allocated to either the intervention group or the control group in a cluster-randomized design. The PCPs in both groups were provided with a copy of the Diabetes Treatment Guide published by the Japan Diabetes Society, and the PCPs in the intervention group additionally received a copy of the manual and a 30-min relevant seminar at the inception of the intervention. The primary end-point was the adherence to the following performances as quality indicators: evaluation of retinopathy, and urinary albumin excretion measurements and serum creatinine measurements, as recommended by the Japan Medical Association. RESULTS: A total of 416 patients were enrolled by 36 PCPs. During the 1-year follow-up period, the proportion of PCPs who adhered to recommendation-concordant measurements of urinary albumin excretion was significantly higher in the intervention group than in the control group (adherence: 17.9% vs 5.3%, P = 0.016). The other parameters were not statistically different between the two groups. CONCLUSIONS: Implementation of 'The Standard Diabetes Manual' potentially leads to an improved quality of diabetes management by PCPs.
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Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Avaliação de Programas e Projetos de Saúde , Garantia da Qualidade dos Cuidados de Saúde , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Médicos de Atenção Primária , Resultado do TratamentoRESUMO
OBJECTIVE: To better understand patient resistance to initiation of insulin therapy, this study examined the perception gap concerning initiation of insulin therapy between individuals with type 2 diabetes and their physicians by using data from the DAWN Japan study. METHODS: The DAWN Japan study is a multi-center, questionnaire-based survey, conducted between 2004-2005. Patients recommended to start insulin therapy (n = 148) answered a questionnaire by rating degree of agreement with 16 statements concerning insulin therapy on a 5-point scale (1: strongly disagree to 5: strongly agree). Ratings of 1 and 2 were categorized as 'disagree' with a statement, and 3, 4, and 5 as 'agree'. Their attending physicians (n = 68) selected statements which could be associated with patient's concerns about insulin therapy. RESULTS: Nearly all the patients agreed with the statements 'I don't want to inject myself for the rest of my life' (95%), and 'I don't want to be bothered with doing injections' (90%); fewer than half agreed with 'My friendships may suffer' (46%), and 'I don't understand why insulin is necessary for me' (45%). Estimation by the physicians and the actual perceptions patients reported differed significantly for 13 statements. Physicians seemed to particularly under-estimate the impact associated with social aspects of insulin use (e.g., 'I don't want to be different from others', 55% patients vs 7% physicians). On the contrary, the statement 'Injections are painful' was the only concern over-estimated by the physicians. CONCLUSIONS: It was demonstrated that differences in perceptions regarding insulin therapy exist between physicians and patients, particularly in terms of social impacts. The data, obtained in 2004, may not precisely reflect the present situation, but still represents a barrier to insulin therapy widely held by patients and physicians. These results suggest that appropriate understanding of patients' concerns about insulin therapy is important to encourage timely insulin initiation.
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Atitude do Pessoal de Saúde , Diabetes Mellitus Tipo 2/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Insulina/uso terapêutico , Conhecimento do Paciente sobre a Medicação , Adulto , Gerenciamento Clínico , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Pacientes/psicologia , Percepção , Médicos/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Perilipin A (PeriA) exclusively locates on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Previously, we reported that adipocyte specific overexpression of PeriA caused resistance to diet-induced obesity and resulted in improved insulin sensitivity. In order to better understand the biological basis for this observed phenotype, we performed additional studies in this transgenic mouse model. METHODOLOGY AND PRINCIPAL FINDINGS: When compared to control animals, whole body energy expenditure was increased in the transgenic mice. Subsequently, we performed DNA microarray analysis and real-time PCR on white adipose tissue. Consistent with the metabolic chamber data, we observed increased expression of genes associated with fatty acid ß-oxidation and heat production, and a decrease in the genes associated with lipid synthesis. Gene expression of Pgc1a, a regulator of fatty acid oxidation and Ucp1, a brown adipocyte specific protein, was increased in the white adipose tissue of the transgenic mice. This observation was subsequently verified by both Western blotting and histological examination. Expression of RIP140, a regulator of white adipocyte differentiation, and the lipid droplet protein FSP27 was decreased in the transgenic mice. Importantly, FSP27 has been shown to control gene expression of these crucial metabolic regulators. Overexpression of PeriA in 3T3-L1 adipocytes also reduced FSP27 expression and diminished lipid droplet size. CONCLUSIONS: These findings demonstrate that overexpression of PeriA in white adipocytes reduces lipid droplet size by decreasing FSP27 expression and thereby inducing a brown adipose tissue-like phenotype. Our data suggest that modulation of lipid droplet proteins in white adipocytes is a potential therapeutic strategy for the treatment of obesity and its related disorders.
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Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Perfilação da Expressão Gênica , Fosfoproteínas/genética , Células 3T3-L1 , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Proteínas de Transporte , Metabolismo Energético , Ácidos Graxos/metabolismo , Humanos , Immunoblotting , Imuno-Histoquímica , Canais Iônicos/genética , Canais Iônicos/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína 1 de Interação com Receptor Nuclear , Análise de Sequência com Séries de Oligonucleotídeos , Consumo de Oxigênio , Perilipina-1 , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fosfoproteínas/metabolismo , Proteínas/genética , Proteínas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição , Transfecção , Proteína Desacopladora 1RESUMO
Familial hypocalciuric hypercalcemia (FHH) is a benign disorder with heterozygous inactivating mutations in the calcium-sensing receptor (CASR) gene. The present study describes the identification and functional analysis of a novel CASR gene mutation leading to FHH. The proband is a 33-yr-old woman (Ca 11.0 mg/dL, intact-PTH 68 pg/mL, FECa 0.17 %). Leukocyte DNA was isolated in four family members and a novel heterozygous mutation (D190G, GAT>GGT) in exon 4 of CASR gene was identified by direct sequence analysis. The mutant CASR expression vector was constructed by mutagenesis procedure and its response to Ca(2+) was characterized by transient transfection into human embryonic kidney (HEK) 293 cells and treatment with increasing extracellular Ca(2+) concentrations. HEK cells didn't activate intracellular signaling (MAPK activation) in response to increases of extracellular Ca(2+) concentrations when the mutant receptor was expressed normally at the cell surface. The novel heterozygous mutation (D190G) identified in the present study showed that the reduction of activity of CASR to extracellular Ca(2+) caused FHH in patients and our study demonstrated the importance of Asp-190 participated in response to Ca(2+) in CASR.
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Hipercalcemia/genética , Receptores de Detecção de Cálcio/genética , Adulto , Cálcio/farmacologia , Cálcio/urina , Feminino , Células HEK293 , Humanos , Hiperparatireoidismo/genética , Masculino , Pessoa de Meia-Idade , Linhagem , Receptores de Detecção de Cálcio/fisiologia , TransfecçãoRESUMO
Perilipin A is the most abundant phosphoprotein on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced catecholamine-stimulated lipolysis, and increased insulin resistance. To understand the physiological consequences of increased perilipin expression in vivo, we generated transgenic mice that overexpressed either human or mouse perilipin using the adipocyte-specific aP2 promoter/enhancer. Phenotypes of female transgenic and wild-type mice were characterized on chow and high-fat diets (HFDs). When challenged with an HFD, transgenic mice exhibited lower body weight, fat mass, and adipocyte size than wild-type mice. Expression of oxidative genes was increased and lipogenic genes decreased in brown adipose tissue of transgenic mice. Basal and catecholamine-stimulated lipolysis was decreased and glucose tolerance significantly improved in transgenic mice fed a HFD. Perilipin overexpression in adipose tissue protects against HFD-induced adipocyte hypertrophy, obesity, and glucose intolerance. Alterations in brown adipose tissue metabolism may mediate the effects of perilipin overexpression on body fat, although the mechanisms by which perilipin overexpression alters brown adipose tissue metabolism remain to be determined. Our findings demonstrate a novel role for perilipin expression in adipose tissue metabolism and regulation of obesity and its metabolic complications.
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Dieta/efeitos adversos , Obesidade/genética , Obesidade/prevenção & controle , Fosfoproteínas/genética , Adipócitos/metabolismo , Adipócitos/patologia , Animais , Proteínas de Transporte , Catecolaminas/farmacologia , Tamanho Celular , Gorduras na Dieta/efeitos adversos , Feminino , Expressão Gênica , Glucose/metabolismo , Homeostase/genética , Humanos , Insulina/metabolismo , Lipólise/efeitos dos fármacos , Lipólise/genética , Masculino , Camundongos , Camundongos Transgênicos , Obesidade/etiologia , Obesidade/metabolismo , Especificidade de Órgãos , Oxirredução , Perilipina-1 , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/genéticaRESUMO
OBJECTIVE: Gitelman's syndrome, recognized as a variant of Bartter's syndrome, is characterized by hypokalaemic metabolic alkalosis in combination with hypomagnesaemia and hypocalciuria. Overlapping biochemical features in Gitelman's syndrome and Bartter's syndrome has been observed. Here, we investigated the clinical, biochemical, and genetic characteristics of five, chronic, nonhypertensive and hypokalaemic Japanese patients. METHODS: Serum and urinary electrolytes, plasma renin activity and plasma aldosterone concentration were measured in five patients (four males and one female) with hypokalaemia. Renal clearance tests were performed and distal fractional chloride reabsorption calculated. Finally, mutational analysis of the thiazide-sensitive Na-Cl co-transporter gene was performed. RESULTS: Symptoms in patients varied from mild (muscle weakness and numbness) to severe (tetany and foot paralysis). All patients were normotensive or hypotensive, and all had hypokalaemia, hypocalciuria, and hyperreninaemic hyperaldosteronism. However, two male patients had normomagnesaemia, while the remainder was hypomagnesaemic. Renal clearance tests showed that the administration of furosemide decreased distal fractional chloride reabsorption, while thiazide ingestion failed to decrease it. Genetic analysis identified six thiazide-sensitive Na-Cl co-transporter gene mutations, including two novel ones. Therefore, on the basis of the confirmatory renal clearance tests and mutational analysis, a diagnosis of Gitelman's syndrome was made in these patients. CONCLUSIONS: Two of the five patients diagnosed with Gitelman's syndrome were normomagnesaemic, which is uncommon in this syndrome. Our study indicates that renal clearance tests and mutation analysis can play an important role in diagnosing Gitelman's syndrome more precisely.
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Síndrome de Gitelman/sangue , Síndrome de Gitelman/diagnóstico , Magnésio/sangue , Adolescente , Adulto , Aldosterona/sangue , Análise Mutacional de DNA , Feminino , Síndrome de Gitelman/genética , Síndrome de Gitelman/urina , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Receptores de Droga/genética , Renina/sangue , Simportadores de Cloreto de Sódio/genética , Adulto JovemAssuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Administração Oral , Diabetes Mellitus Tipo 2/fisiopatologia , Esquema de Medicação , Quimioterapia Combinada , Humanos , Insulina/análogos & derivados , Células Secretoras de Insulina/fisiologiaRESUMO
We investigated the effect of glucokinase activator (GKA) on glucose metabolism and beta-cell mass. We analyzed four mouse groups: wild-type mice and beta-cell-specific haploinsufficiency of glucokinase gene (Gck(+/-)) mice on a high-fat (HF) diet. Each genotype was also treated with GKA mixed in the HF diet. Rodent insulinoma cells and isolated islets were used to evaluate beta-cell proliferation by GKA. After 20 wk on the above diets, there were no differences in body weight, lipid profiles, and liver triglyceride content among the four groups. Glucose tolerance was improved shortly after the GKA treatment in both genotypes of mice. beta-Cell mass increased in wild-type mice compared with Gck(+/-) mice, but a further increase was not observed after the administration of GKA in both genotypes. Interestingly, GKA was able to up-regulate insulin receptor substrate-2 (Irs-2) expression in insulinoma cells and isolated islets. The administration of GKA increased 5-bromo-2-deoxyuridine (BrdU) incorporation in insulinoma cells, and 3 d administration of GKA markedly increased BrdU incorporation in mice treated with GKA in both genotypes, compared with those without GKA. In conclusion, GKA was able to chronically improve glucose metabolism for mice on the HF diet. Although chronic GKA administration failed to cause a further increase in beta-cell mass in vivo, GKA was able to increase beta cell proliferation in vitro and with a 3-d administration in vivo. This apparent discrepancy can be explained by a chronic reduction in ambient blood glucose levels by GKA treatment.
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Glucoquinase/metabolismo , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/citologia , Animais , Peso Corporal/efeitos dos fármacos , Bromodesoxiuridina/farmacocinética , Células Cultivadas , Dieta Aterogênica , Gorduras na Dieta/farmacologia , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Glucoquinase/genética , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Camundongos , Camundongos Transgênicos , Tamanho do Órgão/efeitos dos fármacosRESUMO
We report an elderly patient with maternally inherited diabetes with deafness (MIDD). A 69-year-old woman was found to be diabetic for the first time when she visited her local medical doctor for the symptoms of a common cold. Her casual plasma glucose level was 311 mg/dl and HbA1c was 8.3%. She had been aware of muscle atrophy of the lower extremities and hearing disturbance since age 66. As for her family history, her mother, older sister and younger brother were diabetic with hearing difficulty and all of them had died suddenly in their middle age. Her 45-year-old daughter was also diabetic with some difficulty in hearing. Therefore, we suspected both the patient and her daughter had MIDD, and found alterations in mitochondrial DNA3243A-G. MIDD is a condition that needs to be diagnosed accurately and treated at an early stage, since diabetic complications can progress rapidly and could cause myocardial complications and mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). According to a report of 115 cases of MIDD in Japan, MIDD had been diagnosed at the age of 32.8 on average and our case was strikingly old for the age of onset of the disease.