RESUMO
Bone marrow derived cells (BMDCs) migrate into the hypothalamus, where those cells give rise to microglia to regulate food intake. Given the fact that diabetes functionally impairs BMDCs, we hypothesized that diabetic microglia would fail to exhibit physiological function, accounting for hyperphagia in diabetes. To examine the role of BMDCs, total bone marrow cells from GFP transgenic mice were transplanted into wild type mice in which diabetes was induced by streptozotocin. We first confirmed that bone marrow transplantation could be utilized to examine BMDCs in the brain parenchyma as GFP positive cells could engraft the brain parenchyma and give rise to microglia even when the BBB was intact in the recipient mice. While diabetic mice manifested hyperphagia, BMDCs were in smaller number in the hypothalamus with less response to fasting in the brain parenchyma compared to nondiabetic mice. This finding was also confirmed by examining nondiabetic chimera mice in which BMDCs were diabetic. Those mice also exhibited less response of BMDCs in response to fasting. In conclusion, diabetic BMDCs had less response of microglia to fasting, perhaps accounting for diabetic hyperphagia.
Assuntos
Medula Óssea , Diabetes Mellitus Experimental , Camundongos , Animais , Medula Óssea/metabolismo , Microglia/metabolismo , Apetite , Camundongos Transgênicos , Transplante de Medula Óssea , Células da Medula Óssea/metabolismo , Hiperfagia , Hipotálamo/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Fluorescência Verde/metabolismoRESUMO
BACKGROUND: The association of proteinuria and reduced estimated glomerular filtration rate (eGFR) with cognition needs more clarification. We cross-sectionally examined whether proteinuria and reduced eGFR, even in moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. METHODS: Our cohort initially comprised 1,094 men aged 40-79 years from a random sample from Shiga, Japan in 2006-2008. Of 853 men who returned for the follow-up examination (2009-2014), we analyzed 561 who were ≥65 years, free of stroke, and completed the Cognitive Abilities Screening Instrument (CASI) at follow-up (higher CASI scores [range 0 to 100] indicate better cognition). Proteinuria was assessed via dipstick. eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration Equation. Participants were divided into three groups either by eGFR (≥60, 59-40, and <40 mL/min/1.73 m2) or by proteinuria (no, trace, and positive), considered normal, moderate, and advanced, respectively. Using linear regression, we computed mean CASI score, with simultaneous adjustment for proteinuria and eGFR in addition to other potential confounders. RESULTS: Significant trends of lower cognition were observed across the groups of worse proteinuria and lower eGFR independently: multivariable-adjusted mean CASI scores were 90.1, 89.3, and 88.4 for proteinuria (Ptrend = 0.029), and 90.0, 88.5, and 88.5 for eGFR (Ptrend = 0.015) in mutual-adjustment model. CONCLUSIONS: Proteinuria and reduced eGFR, even in their moderate stages, were independently associated with lower cognition in a community-based sample of elderly men. The results suggest the importance of proteinuria and low eGFR for early detection and prevention of cognitive decline.
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Cognição/fisiologia , Disfunção Cognitiva/epidemiologia , Taxa de Filtração Glomerular/fisiologia , Proteinúria/epidemiologia , Idoso , Estudos de Coortes , Estudos Transversais , Humanos , Vida Independente , Japão/epidemiologia , Masculino , Fatores de RiscoRESUMO
Laparoscopic sleeve gastrectomy has been proven effective in treating obesity-associated type 2 diabetes mellitus (T2DM). However, reports of the effect of laparoscopic sleeve gastrectomy on glucose metabolism in Japanese obese patients with T2DM are rare. The aim of this study was to evaluate the effects of laparoscopic sleeve gastrectomy on glucose tolerance in Japanese obese patients with T2DM, and to analyze factors influencing diabetes remission after surgery. This was a retrospective analysis of data for 24 consecutive patients with T2DM who underwent laparoscopic sleeve gastrectomy. We investigated weight loss and its impact on T2DM 1 year postoperatively. We also compared baseline characteristics and postoperative factors between patients who achieved diabetes remission and patients without remission. Mean body weight loss and percent total weight loss were 23.9 kg and 23.3%, respectively. Mean hemoglobin A1c levels dropped from 7.3 ± 0.3% to 6.1 ± 0.2%, and 18 patients (75%) achieved diabetes remission 1 year postoperatively. Patients achieving remission had significantly lower hemoglobin A1c levels (p = 0.026), higher fasting C-peptide values (p < 0.001), shorter diabetes duration (p < 0.001), lower insulin requirement (p = 0.002), and higher area under the insulin response curve (p < 0.001) and insulinogenic index (p < 0.001) during oral glucose tolerance testing. In conclusion, laparoscopic sleeve gastrectomy is an effective treatment for Japanese obese patients with T2DM. Preserving insulin secretion is the major determinant of diabetes remission.
Assuntos
Citoproteção , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Células Secretoras de Insulina/fisiologia , Obesidade/cirurgia , Adulto , Glicemia/metabolismo , Citoproteção/fisiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Gastrectomia/métodos , Teste de Tolerância a Glucose , Humanos , Japão , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/fisiopatologia , Período Pós-Operatório , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Pericardial fat volume (PFV), defined as the volume of ectopic fat in and around the heart, is associated with the atherosclerotic process in coronary arteries. The magnitude of change in PFV over time and the factors affecting this change in a general population, however, have not been investigated. MethodsâandâResults: Cardiac computed tomography (CT) was carried out at baseline and at follow-up in 623 Japanese men aged 40-79 years without a history of cardiovascular disease who were selected randomly in Kusatsu (Shiga, Japan). PFV was measured on cardiac CT in a qualified laboratory. Age, heart rate, triglycerides, and obesity measurements (weight, body mass index, and waist circumference) were significantly and positively associated with PFV at baseline. Over an average interval of 4.7 years, median PFV increased significantly from 64.1 cm3 (IQR, 47.2-90.0 cm3) to 73.6 cm3 (IQR, 53.3-98.1 cm3; P<0.001). Current smoking and heart rate were significantly and independently associated with changes in PFV (B=3.336, P<0.001 and B=6.409, P=0.003, respectively). CONCLUSIONS: PFV increased significantly over time in a population-based observational study of Japanese men. PFV change was significantly and independently associated with smoking status and heart rate, suggesting that quitting smoking might help reduce PFV, which could be expected to decrease the risk of coronary artery disease.
Assuntos
Tecido Adiposo/patologia , Pericárdio/patologia , Tecido Adiposo/diagnóstico por imagem , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Frequência Cardíaca , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Fatores de Risco , Fumar , Tomografia Computadorizada por Raios XRESUMO
The prevalence of obesity is increasing globally in patients with diabetes. This study aimed to examine 12-year trends of increasing obesity in Japanese patients with diabetes, and their clinical features. The study used results of the Shiga Diabetes Clinical Survey, which recorded medical performance in diabetic patients in 2000, 2006 and 2012. Data were analyzed from 14,205, 14,407 and 21,449 adult patients in these three years, respectively. Overweight and obesity prevalence and the clinical features of diabetes patients were examined, stratified by body mass index (BMI) and age. The prevalence of overweight (BMI 25-30 kg/m2) and obesity (BMI ≥30 kg/m2) were 27.0% and 5.1% in 2000, 28.9% and 7.3% in 2006 and 30.9% and 10.0% in 2012. Glycemic control, blood pressure and serum lipid profile improved over 12 years in all BMI categories. However, glycemic and triglyceride control were insufficient in obese patients aged <65 years (hemoglobin A1c 7.5 ± 1.4%, triglyceride 197.7 ± 178.4 mg/dL in 2012). The percentage of patients who used antihypertensive and lipid-lowering drugs increased and patients with higher BMI had increased frequency of using these drugs, both in young and old age groups. Higher BMI was significantly and positively associated with albuminuria. In summary, overweight and obesity have increased in Japanese diabetic patients, particularly for younger generations. Findings suggest that obesity may lead to poorer glycemic control, blood pressure and lipid profiles. Overweight and obesity are important modifiable risk factors for diabetes, suggesting that more active weight-control interventions are warranted.
Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Índice de Massa Corporal , Peso Corporal/fisiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobinas Glicadas , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Prevalência , Adulto JovemRESUMO
OBJECTIVE: The association between insulin resistance (IR) and coronary artery calcification (CAC) has been uncertain after adjustment for metabolic syndrome components. We aimed to evaluate whether IR is associated with CAC prevalence or progression independently of metabolic syndrome components. APPROACH AND RESULTS: We conducted a population-based study in a random sample of Japanese men aged 40 to 79 years and determined IR using the homeostasis model assessment of insulin resistance (HOMA-IR). The associations of HOMA-IR and other diabetic parameters per 1-SD increase with CAC prevalence and progression were evaluated using multivariable logistic regression. Of 1006 total participants at baseline (mean age, 64±10 years), CAC prevalence was observed in 646 (64.2%), and of 789 participants at follow-up (mean duration, 4.9±1.3 years), CAC progression was observed in 365 (46.3%). After adjustment for covariates including metabolic syndrome components, higher HOMA-IR was independently associated with CAC prevalence (adjusted odds ratio 1.34, 95% confidence interval 1.10-1.63; P=0.003) and progression (odds ratio 1.32, 95% confidence interval 1.09-1.60; P=0.004). In participants without diabetes mellitus, positive associations were similarly observed (prevalence: odds ratio 1.29, 95% confidence interval 1.04-1.60; P=0.022; and progression: odds ratio 1.25, 95% confidence interval 1.01-1.55; P=0.042), whereas glucose and hemoglobin A1c were not associated with CAC prevalence and progression. CONCLUSIONS: Higher IR was associated with CAC prevalence and progression independently of metabolic syndrome components in Japanese men and also in those without diabetes mellitus. Among diabetic measures, IR and fasting insulin, but not glucose and hemoglobin A1c, predicted CAC progression in men without diabetes mellitus.
Assuntos
Doença da Artéria Coronariana/epidemiologia , Resistência à Insulina , Síndrome Metabólica/epidemiologia , Calcificação Vascular/epidemiologia , Adulto , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Glicemia/análise , Distribuição de Qui-Quadrado , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Progressão da Doença , Jejum/sangue , Hemoglobinas Glicadas/análise , Humanos , Insulina/sangue , Japão/epidemiologia , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Análise Multivariada , Razão de Chances , Prevalência , Medição de Risco , Fatores de Risco , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico por imagemRESUMO
Despite the growing epidemic worldwide, diabetes is an incurable disease. We have been focusing on why diabetes manifests refractoriness to any therapy. We recently found that abnormal bone marrow-derived cells (BMDCs), namely, Vcam-1+ST-HSCs, was a key mechanism for diabetic complications. We then hypothesize that those aberrant BMDCs sustainedly impair pancreatic ß cells. Here we show that eliminating abnormal BMDCs using bone marrow transplantation results in controlling serum glucose in diabetic mice, in which normoglycemia is sustained even after cessation of insulin therapy. Alternatively, abnormal BMDCs exhibiting epigenetic alterations are treated with an HDAC inhibitor, givinostat, in diabetic mice. As a result, those mice are normoglycemic along with restored insulin secretion even following the cessation of both insulin and givinostat. Diabetic cell fusion between abnormal BMDCs and resident cells is significantly blocked by the combination therapy in the pancreatic islets and thymus while surgical ablation of the thymus completely eliminates therapeutic protection in diabetic mice. In conclusion, diabetes is an epigenetic stem cell disorder with thymic disturbances. The combination may be applied to patients aiming at complete remission from diabetes in clinical medicine.
Assuntos
Diabetes Mellitus Experimental , Insulina , Animais , Camundongos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Estreptozocina , Insulina Regular HumanaRESUMO
AIMS: This study aimed to evaluate changes in glycemic control and diabetes treatment by age group in Japanese patients with type 2 diabetes. METHODS: The study included the results of approximately 40,000 patients/year using cross-sectional and retrospective analyses from 2012 to 2019. RESULTS: There was little change in the glycemic control status in all age groups during the study period. However, by age group, patients aged ≤ 44 years continued to have the highest glycated hemoglobinA1c (HbA1c) values during the study period (7.4 % ± 1.7 % in 2012 and 7.4 % ± 1.5 % in 2019), especially in insulin-treated patients (8.3 % ± 1.9 % in 2012 and 8.4 % ± 1.8 % in 2019). Biguanides and dipeptidyl peptidase-4 inhibitors were widely prescribed. Sulfonylurea and insulin use showed a decreasing trend, but older patients had a higher percentage of prescriptions. Sodium glucose transporter 2 inhibitors were prescribed rapidly, especially in younger patients. CONCLUSIONS: There were no obvious changes in glycemic control over time in the study period. The mean HbA1c level was higher in younger patients, which suggested that improvement is required. In older patients, there was a trend toward greater emphasis on management to avoid hypoglycemia. Different treatment strategies based on age showed different drug choices.
Assuntos
Diabetes Mellitus Tipo 2 , Controle Glicêmico , Hipoglicemiantes , Padrões de Prática Médica , Idoso , Humanos , Glicemia/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , População do Leste Asiático/estatística & dados numéricos , Hemoglobinas Glicadas/análise , Controle Glicêmico/tendências , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Estudos Retrospectivos , Padrões de Prática Médica/tendências , Fatores EtáriosRESUMO
AIM: Diabetes mellitus is a well-known risk factor for onset and progression of periodontal disease. However, the continuous relationship between glycemic control and the number of natural teeth has not been well characterized in large-scale studies. We aimed to determine whether the glycated hemoglobin A1c (HbA1c) level and fasting plasma glucose (FPG) are associated with the number of natural teeth. METHODS: A cross-sectional study: A database comprising employment-based health insurance claim and medical check-up data from 706,150 participants between April 2015 and March 2016 in Japan. The exclusion criteria included missing data regarding dental receipts, number of natural teeth, HbA1c, smoking status, and age < 20 years. Ultimately, 233,567 individuals were analyzed. The participants were allocated to five groups according to their HbA1c and three groups according to their FPG, and then the number of natural teeth were compared. RESULTS: Higher HbA1c was associated with fewer teeth in participants ≥ 30 years of age (P for trend < 0.001). Higher FPG was associated with fewer teeth between 30 and 69 years of age (P for trend < 0.001). Participants with impaired fasting glucose was already at risk for fewer teeth between 40 and 69 years of age than those with normal FPG. CONCLUSIONS: Glycemic control is strongly associated with the number of natural teeth in the real-world setting. Furthermore, there are continuous relationships of HbA1c and FPG with number of natural teeth including individual with impaired fasting glucose. These data emphasize the importance of glycemic control and appropriate oral care for the protection against tooth loss. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00533-2.
RESUMO
Aim: To examine the trends in the management of patients with diabetes over an 18-year period in Japan. Participants and methods: We recorded the height, body mass, laboratory data, diabetes treatment, and screening status of diabetic complications from the data collected during the Shiga Diabetes Clinical Survey, which has been performed every 6 years since 2000. We then evaluated the management of patients with diabetes in Shiga Prefecture. The study included 17,870, 18,398, 24,243, and 26,624 participants in each of the 4 years of measurements. Results: The mean age and body mass index (BMI) of the participants gradually increased. The percentage of patients with BMI of ≥ 25 kg/m2 was higher in younger patients. Glycemic control significantly improved over 18 years (hemoglobin A1c: 7.3% ± 1.4% in 2000 to 7.1% ± 1.1% in 2018, P for trend < 0.001). The mean hemoglobin A1c levels were higher in younger patients than in elderly patients and increased from 2012 to 2018 in patients aged ≥ 65 years. The proportion of participants who underwent screening for albuminuria and diabetic retinopathy increased. The mean blood pressure and low-density lipoprotein cholesterol concentration decreased. Conclusions: Glycemic control has been maintained at an acceptable level since the previous survey. Although glycemic control has become less strict in elderly patients with diabetes, glycemic control is poorer in younger patients than in elderly patients. Obesity is an increasingly important problem, particularly in younger patients. The frequency of screening for diabetic complications and the control of blood pressure should be improved. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00573-2.
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BACKGROUND: Tooth loss is associated with nutritional status and significantly affects quality of life, particularly in older individuals. To date, several studies reveal that a high BMI is associated with tooth loss. However, there is a lack of large-scale studies that examined the impact of obesity on residual teeth with respect to age and tooth positions. OBJECTIVE: We assessed the impact of obesity on the number and position of residual teeth by age groups using large scale of Japanese database. METHODS: This was a cross-sectional study of 706150 subjects that were included in the database that combined the data from health insurance claims and health check-up, those lacking information about BMI, HbA1c level, smoking status, and the number of residual teeth were excluded. Thus, a total of 233517 aged 20-74 years were included. Subjects were classified into 4 categories based on BMI, and the number of teeth was compared between age-groups. The percentage of subjects with residual teeth in each position was compared between groups with obesity (BMI ≥25.0 kg/m2) and non-obesity. Logistic regression analysis was performed to clarify whether obesity predicts having <24 teeth. RESULTS: Higher BMI was associated with fewer teeth over 40s (P for trend <0.0001 when <70s). Obesity was associated with the reduction of residual teeth in the maxillary; specifically, the molars were affected over the age 30. Smoking status further affected tooth loss at positions that were not affected by obesity alone. After adjusting for age, sex, smoking status, and HbA1c ≥6.5%, obesity remained an independent predictive factor for having <24 teeth (ORs: 1.35, 95% CIs: 1.30-1.40). CONCLUSIONS: We found that an increase in BMI was associated with a decrease in the number of residual teeth from younger ages independently of smoking status and diabetes in the large scale of Japanese database.
Assuntos
Perda de Dente , Adulto , Idoso , Estudos Transversais , Hemoglobinas Glicadas , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Qualidade de Vida , Perda de Dente/complicações , Perda de Dente/epidemiologia , Adulto JovemRESUMO
AIMS: The roles of urinary albumin, eGFRcystatin (eGFRcys), and eGFRcreatinine (eGFRcre) in the progression of coronary artery calcification (CAC) remain unclear. Therefore, the present study investigated the relationship between kidney function and CAC progression. METHODS: A total of 760 Japanese men aged 40-79 years were enrolled in this population-based study. Kidney function was measured using eGFRcre, eGFRcys, and the urine albumin-to-creatinine ratio. CAC scores were calculated using the Agatston method. CAC progression was defined as an annual increase of ï¼10 Agatston units (AU) among men with 0ï¼CACï¼100 AU at baseline, that of ï¼10% among those with CAC ≥ 100 AU, and any progression for those with CAC=0 at baseline. The relative risk (RR) of CAC progression based on kidney function was assessed using a robust Poisson regression model. RESULTS: The mean follow-up period was 4.9 years. CAC progression was detected in 45.8% of participants. Positive associations between CAC progression and albuminuria (ï¼30mg/g) (RR: 1.29; 1.09 to 1.53; p=0.004) and low eGFRcys (ï¼60ml/min/1.73m2) (RR: 1.27; 1.05 to 1.53; p=0.012) remained significant after adjustments for age, the follow-up time, and computerized tomography type. Following further adjustments for hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and lifestyle factors, CAC progression was associated with albuminuria (RR: 1.20; 1.01 to 1.43; p=0.04) and low eGFRcys (RR: 1.19; 0.99 to 1.43; p=0.066), but not with eGFRcre. CONCLUSION: CAC progression was associated with albuminuria; however, its relationship with eGFRcys was weakened by adjustments for risk factors.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Calcificação Vascular , Albuminas , Albuminúria/complicações , Doença da Artéria Coronariana/complicações , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Rim , Masculino , Fatores de RiscoRESUMO
AIM: We aimed to determine whether SGLT2 inhibitor dapagliflozin treatment affects body composition and amino acid (AA) metabolism. METHODS: Fifty-two overweight patients treated by oral antidiabetic agents were randomly assigned to dapagliflozin (Dapa) or a standard treatment (Con) and followed for 24â¯weeks. The primary outcome was the change in body mass (BM) between baseline and week 24. Body composition, intrahepatic triglyceride (IHTG) content, and plasma AA concentrations were examined as secondary outcomes. RESULTS: The change in BM was significantly larger in the Dapa than in the Con group, with a difference in the mean change of -1.72â¯kg (95â¯%CI: -2.85, -0.59; Pâ¯=â¯0.004) between the groups. Total fat mass was reduced by dapagliflozin treatment, but fat-free mass was maintained. IHTG content was significantly reduced in the Dapa than in the Con (Pâ¯=â¯0.033). Changes in AAs showed small differences between the groups, but only serine concentrations were significantly reduced in the Dapa. Intra-group analysis showed that positive associations were observed between changes in branched chain AA concentrations and body composition only in the Dapa. CONCLUSIONS: Dapagliflozin treatment causes a reduction in BM mainly by reducing fat mass. AA metabolism shows subtle changes with dapagliflozin treatment.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Tipo 2/complicações , Glucosídeos , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Japão , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Diabetic neuropathy is an incurable disease. We previously identified a mechanism by which aberrant bone marrow-derived cells (BMDCs) pathologically expressing proinsulin/TNF-α fuse with residential neurons to impair neuronal function. Here, we show that CD106-positive cells represent a significant fraction of short-term hematopoietic stem cells (ST-HSCs) that contribute to the development of diabetic neuropathy in mice. The important role for these cells is supported by the fact that transplantation of either whole HSCs or CD106-positive ST-HSCs from diabetic mice to non-diabetic mice produces diabetic neuronal dysfunction in the recipient mice via cell fusion. Furthermore, we show that transient episodic hyperglycemia produced by glucose injections leads to abnormal fusion of pathological ST-HSCs with residential neurons, reproducing neuropathy in nondiabetic mice. In conclusion, we have identified hyperglycemia-induced aberrant CD106-positive ST-HSCs underlie the development of diabetic neuropathy. Aberrant CD106-positive ST-HSCs constitute a novel therapeutic target for the treatment of diabetic neuropathy.
Assuntos
Comunicação Celular , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/patologia , Células-Tronco Hematopoéticas/citologia , Hiperglicemia/complicações , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Transplante de Medula Óssea , Fusão Celular , Células Cultivadas , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/metabolismo , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE: Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing phenotype in patients with type 2 diabetes. However, it remains unclear whether its prognosis is poorer than that of other DKD phenotypes. RESEARCH DESIGN AND METHODS: A total of 2,953 Japanese patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, enrolled in an observational cohort study in 2004, were followed until 2015. On the basis of albuminuria (>30 mg/g creatinine) and reduced eGFR (<60 mL/min/1.73 m2) at baseline, participants were classified into the four DKD phenotypes-no-DKD, albuminuric DKD without reduced eGFR, nonalbuminuric DKD with reduced eGFR, and albuminuric DKD with reduced eGFR-to assess the risks of mortality, cardiovascular disease (CVD), and renal function decline. RESULTS: During the mean follow-up of 9.7 years, 113 patients died and 263 developed CVD. In nonalbuminuric DKD, the risks of death or CVD were not higher than those in no-DKD (adjusted hazard ratio 1.02 [95% CI 0.66, 1.60]) and the annual decline in eGFR was slower than in other DKD phenotypes. The risks of death or CVD in nonalbuminuric DKD without prior CVD were similar to those in no-DKD without prior CVD, whereas the risks in nonalbuminuric DKD with prior CVD as well as other DKD phenotypes were higher. CONCLUSIONS: Nonalbuminuric DKD did not have a higher risk of mortality, CVD events, or renal function decline than the other DKD phenotypes. In nonalbuminuric DKD, the presence of macrovascular complications may be a main determinant of prognosis rather than the renal phenotype.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Nefropatias Diabéticas/diagnóstico , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/urina , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Japão/epidemiologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mortalidade , PrognósticoRESUMO
BACKGROUND/OBJECTIVES: The association between carbohydrate intake and cardiovascular disease (CVD) risk has been investigated, but whether the quality of carbohydrate is more important than its amount is not known. We examined the associations between intake of dietary fibre (DF), carbohydrate, available carbohydrate, and starch with long-term CVD mortality in a Japanese population. SUBJECTS/METHODS: We prospectively followed 8925 participants (3916 men and 5009 women) aged 30-79 years without CVD at baseline who participated in the National Nutrition Survey in Japan. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for CVD mortality by quartiles of exposure variables. RESULTS: During 24 years of follow-up, 823 CVD deaths were observed. In men, the multivariable-adjusted HR for CVD mortality was lower in the highest quartile of DF intake (HR: 0.64; 95% CI: 0.47-0.87; Ptrend = 0.007) compared with the lowest quartile. This association was not significant in women. Multivariable-adjusted HR for total stroke mortality was lower in the highest quartile of DF intake (HR: 0.61; 95% CI: 0.38-0.98; Ptrend = 0.046) compared with the lowest quartile in women. Carbohydrate, available carbohydrate, and starch intake were not associated with CVD mortality. CONCLUSIONS: Higher intake of DF was associated significantly with a lower risk of CVD mortality in men and lower risk of stroke mortality in women. Intake of carbohydrate, available carbohydrate, and starch were not associated with the risk of CVD mortality in men or women.
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Doenças Cardiovasculares , Carboidratos , Dieta , Fibras na Dieta , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
AIMS: Ectopic fat accumulation is related to insulin resistance and diabetes mellitus (DM). However, the effect of fatty liver on DM in non-obese individuals has not been clarified. We investigated whether liver fat accumulation assessed by computed tomography (CT) is associated with the incidence of DM. METHODS: In a prospective population-based study, 640 Japanese men were followed up for 5 years. The liver to spleen (L/S) ratio of the CT attenuation value was used as the liver fat accumulation index. We calculated the odds ratio (OR) and 95% confidence interval (CI) for the DM incidence of per 1 standard deviation (SD) lower L/S and those of L/S < 1.0 compared with L/S ≥ 1.0, using logistic regression models. RESULTS: Both per 1 SD lower L/S and L/S < 1.0 were significantly associated with a risk for DM incidence (1 SD lower L/S: OR = 1.57, 95%CI = 1.14-2.16; L/S < 1.0: OR = 2.27, 95%CI = 1.00-5.14). The relationship between L/S and incidence of DM was consistent in the obese and non-obese groups, with thresholds of BMI 25 kg/m2, waist circumference 85 cm, or visceral adipose tissue 100 cm2. CONCLUSIONS: Liver fat accumulation assessed by CT was associated with the incidence of DM.
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Estudos Epidemiológicos , Fígado Gorduroso/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Diabetes Mellitus Tipo 2/fisiopatologia , Fígado Gorduroso/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND & AIMS: Although accurate assessment of energy intake (EI) is critical in diabetes care, underreporting of EI on dietary records (DR) is often an issue. However, few studies have examined EI with doubly labeled water (DLW) in patients with diabetes mellitus. We aimed to investigate the impact of sex and obesity on the dissociation of DR from total energy expenditure (TEE) evaluated with DLW in patients with type 2 diabetes. METHODS: Fifty-two patients with type 2 diabetes aged 60-79 years were enrolled for the Clinical Evaluation of Energy Requirements in Patients with Diabetes Mellitus (CLEVER-DM) study at a single university hospital. TEE was measured over 14 days by the DLW method as standard. EI was calculated by assessment of 3-day DR by registered dietitians. RESULTS: The mean difference between EI and TEE was 238 ± 412 kcal/day (~10% of TEE). Neither EI nor TEE was significantly different between obese (body mass index (BMI) ≥25 kg/m2) and non-obese (BMI <25 kg/m2) patients. There was a negative correlation between EI/TEE ratio and BMI in women (R = -0.437, P = 0.033) but not in men (R = -0.174, P = 0.377). There was a significant difference in EI/TEE ratio between obese and non-obese patients among women (0.85 ± 0.15 vs. 1.01 ± 0.21, P = 0.045) but not men (0.85 ± 0.20 vs. 0.87 ± 0.17, P = 0.79). CONCLUSIONS: EI calculated by 3-day DR may underestimate habitual intake, which is assumed to be equal to TEE measured by the DLW method except in non-obese women with diabetes. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000023051.
Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Registros de Dieta , Ingestão de Energia , Metabolismo Energético , Feminino , Humanos , Masculino , Obesidade/epidemiologiaRESUMO
AIM: Computed tomography (CT) can directly provide information on body compositions and distributions, compared to anthropometric indices. It has been shown that various obesity indices are associated with carotid intima-media thickness (IMT). However, whether CT-based obesity indices are stronger than anthropometric indices in association with atherosclerosis remains to be determined in a general population. METHODS: We cross-sectionally assessed carotid IMT using ultrasound in 944 community-dwelling Japanese men free of stroke and myocardial infarction. CT image at the L4-L5 level was obtained to compute areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Anthropometric measures assessed included body mass index (BMI), waist circumference, and waist-to-hip ratio. Using multivariable linear regression, slopes of IMT per 20th to 80th percentile of each index were compared. We also compared the slope of index with simultaneous adjustment for BMI in the same model. RESULTS: Areas of VAT and SAT were positively associated with IMT, but not stronger than those of anthropometric indices in point estimates. Among all obesity indices, BMI was strongest in association with IMT after adjusting for age and lifestyle factors or further adjusting for metabolic factors. In simultaneous adjustment models, BMI, but not CT-based indices, remained significant and showed the strongest association. CONCLUSIONS: In community-dwelling Japanese men, anthropometric obesity indices, BMI in particular, were more strongly associated with carotid atherosclerosis than CT-based obesity indices. The association of general obesity with carotid atherosclerosis was strong and adding CT-based obesity measure did not considerably influence in the association.
Assuntos
Antropometria , Índice de Massa Corporal , Doenças das Artérias Carótidas/diagnóstico , Gordura Intra-Abdominal/patologia , Obesidade/fisiopatologia , Gordura Subcutânea/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos Transversais , Seguimentos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors reduce bodyweight (BW) by creating a negative energy balance. Previous reports have suggested that this BW reduction is mainly loss of body fat and that ~20% of the reduction is lean mass. However, the effects of sodium-glucose cotransporter 2 inhibitors on BW and body composition remain unclear. We examined these effects in Japanese patients with type 2 diabetes mellitus treated with insulin. MATERIALS AND METHODS: In this open-label, randomized controlled trial, 49 overweight patients (body mass index ≥23 kg/m2 ) with inadequate glycemic control (hemoglobin A1c >7.0%) receiving insulin treatment were randomly assigned to receive add-on ipragliflozin or no additional treatment (control group). Patients were followed for 24 weeks. The goal for all patients was to achieve glycated hemoglobin <7.0% without hypoglycemia. The primary end-point was a change in BW from baseline to week 24. Body composition was assessed with dual-energy X-ray absorptiometry and bioelectrical impedance analysis. RESULTS: BW change was significantly larger in the ipragliflozin group than in the control group (-2.78 vs -0.22 kg, P < 0.0001). Total fat mass was reduced evenly in the arms, lower limbs and trunk in the ipragliflozin group. Total muscle mass and bone mineral content were maintained, but muscle mass in the arms might have been affected by ipragliflozin treatment. CONCLUSIONS: Ipragliflozin treatment for 24 weeks resulted in reduced BW, mainly from fat mass loss. Muscle mass and bone mineral content were maintained. Further study is necessary to elucidate the long-term effects of ipragliflozin.