RESUMO
Familial partial lipodystrophy (FPLD) 3 is a rare genetic disorder caused by peroxisome proliferator-activated receptor γ gene (PPARG) mutations. Most cases have been reported in Western patients. Here, we describe a first pedigree of FPLD 3 in Japanese. The proband was a 51-year-old woman. She was diagnosed with fatty liver at age 32 years, dyslipidemia at age 37 years, and diabetes mellitus at age 41 years. Her body mass index was 18.5 kg/m2, and body fat percentage was 19.2%. On physical examination, she had less subcutaneous fat in the upper limbs than in other sites. On magnetic resonance imaging, atrophy of subcutaneous adipose tissue was seen in the upper limbs and lower legs. Fasting serum C-peptide immunoreactivity was high (3.4 ng/mL), and the plasma glucose disappearance rate was low (2.07%/min) on an insulin tolerance test, both suggesting apparent insulin resistance. The serum total adiponectin level was low (2.3 µg/mL). Mild fatty liver was seen on abdominal computed tomography. On genetic analysis, a P495L mutation in PPARG was identified. The same mutation was also seen in her father, who had non-obese diabetes mellitus, and FPLD 3 was diagnosed. Modest increases in body fat and serum total adiponectin were seen with pioglitazone treatment. Attention should be paid to avoid overlooking lipodystrophy syndromes even in non-obese diabetic patients if they show features of insulin resistance.
Assuntos
Diabetes Mellitus , Resistência à Insulina , Lipodistrofia Parcial Familiar , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Lipodistrofia Parcial Familiar/tratamento farmacológico , Lipodistrofia Parcial Familiar/genética , Lipodistrofia Parcial Familiar/diagnóstico , PPAR gama/genética , Pioglitazona/uso terapêutico , Resistência à Insulina/genética , Adiponectina , População do Leste Asiático , MutaçãoRESUMO
BACKGROUND: Ghrelin is involved in feeding regulation and energy metabolism and is also known to inhibit insulin secretion (ß). However, few clinical studies have demonstrated the relationship between ß and ghrelin dynamics. This study tested the hypothesis that, in oral glucose tolerance tests (OGTT), ghrelin dynamics are associated with ß. METHODS: Subjects were 1145 healthy individuals <40 years old who tested normal on the 75-g OGTT. The following indicators and the ghrelin suppression ratio (GSR) during OGTT were calculated: insulin sensitivity (SI) [1/homoeostasis model assessment of insulin resistance, insulin sensitivity index-Matsuda and 1/fasting insulin (1/FIRI)]; and ß [Stumvoll first-phase index (Stumvoll-1), Stumvoll second-phase index and insulinogenic index]. From nine combinations of SI and ß, combinations that produce hyperbolic relationships were identified. RESULTS: Stumvoll-1 and 1/FIRI showed a hyperbolic relationship in nonobese subjects, and the product of Stumvoll-1 and 1/FIRI was used as the disposition index (DI). When analyzed by BMI quartiles, post-loading glucose and insulin levels at each time point increased from Q1 (low BMI) through Q4 (high BMI), whereas the DI, ghrelin levels at each time point, and GSR decreased from Q1 to Q4. On multivariate and bivariate analysis, GSR and DI were positive and independent, and fasting ghrelin and FIRI were negatively and independently correlated. CONCLUSIONS: Ghrelin dynamics were associated with beta cell function in subjects with normal glucose tolerance. Glucose intolerance in obesity may be due not only to insulin resistance but also to impaired beta cell function associated with abnormalities of ghrelin dynamics.
Assuntos
Grelina/sangue , Glucose/metabolismo , Povo Asiático , Glicemia/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Secreção de Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Japão , Masculino , Adulto JovemRESUMO
OBJECTIVES: It is well-known that the complement system plays an essential role in host immunity. Observational studies have indicated that complement system-related molecules such as complement factor B (CfB) and other components are correlated with obesity and/or insulin resistance parameters. In this study, we investigated the role of adipocyte-derived CfB in adipose tissue metabolism. METHODS: We investigated the expression level of complement system-related genes in adipocytes. To understand the role of CfB in adipocyte, we performed Cfb overexpression in 3T3-L1 preadipocytes and generated adipocyte-specific Cfb transgenic mice. RESULTS: Cfb expression was markedly enhanced in 3T3-L1 adipocytes co-cultured with macrophages following endotoxin stimulation. In Cfb-overexpressing cells, the expression of adipocyte differentiation/maturation-related genes encoding peroxisome proliferator-activated receptor γ (Pparγ), adipocyte Protein 2 and perilipin was significantly enhanced. Cfb transgenic mice showed a marked increase in the expression of genes encoding Pparγ, perilipin, sterol regulatory element-binding protein 1 c, and Cd36 in the subcutaneous adipose tissue. CONCLUSIONS: CfB plays a crucial role in late-phase of adipocyte differentiation and subsequent lipid droplet formation.
Assuntos
Adipócitos/imunologia , Tecido Adiposo/imunologia , Diferenciação Celular/imunologia , Fator B do Complemento/imunologia , Imunidade Inata/imunologia , Gotículas Lipídicas/imunologia , Células 3T3-L1 , Adipócitos/citologia , Adipogenia/imunologia , Tecido Adiposo/citologia , Animais , Proliferação de Células , Células Cultivadas , Masculino , Camundongos , Camundongos TransgênicosRESUMO
Changes in imaging findings and hormone levels before and after pheochromocytoma rupture, as well as detailed histopathology of resected tumors, have rarely been reported. A 52-year-old woman developed hypertension and diabetes mellitus in 2014, but despite treatment with antihypertensive and hypoglycemic drugs, good control was not achieved. On April 2, 2016, the patient started to have headaches and palpitations, and on April 6, she visited our hospital. Plain computed tomography (CT) of the abdomen showed a 4-cm, isodense mass in the left adrenal gland, and the patient was hospitalized for further examination. Because the patient had hypertension, tachycardia, and hyperglycemia on admission, therapies for those were started. Catecholamine levels were markedly elevated. However, after the patient developed left flank pain on Day 4, antihypertensive and insulin therapies were no longer required. Plain CT then showed heterogeneous high density areas in the left adrenal mass. On Day 7, 3 meta-iodobenzylguanidine scintigraphy showed no abnormal uptake. On Day 8, contrast CT showed low density areas within the left adrenal tumor and contrast enhancement of the tumor margins, and catecholamine levels were markedly decreased. Elective left adrenal tumor resection was performed on Day 49. The capsule of the resected tumor was ruptured. Histopathology showed widespread hemorrhagic necrosis and viable cell components in the tumor margins. Positive chromogranin A staining of the tumor cells confirmed a diagnosis of pheochromocytoma. This patient displayed remarkable changes in imaging findings and hormone levels before and after pheochromocytoma rupture. Pheochromocytoma rupture and hemorrhagic necrosis were confirmed histopathologically.
Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Adrenalectomia , Catecolaminas/sangue , Feocromocitoma/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Hormônio Adrenocorticotrópico/sangue , Feminino , Humanos , Hidrocortisona/sangue , Pessoa de Meia-Idade , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Resultado do TratamentoRESUMO
Conflicting data have been published on the effects of aldosterone excess on glucose metabolism. Specifically, there are limited data on whether adrenalectomy in patients with aldosterone-producing adenomas (APA) can improve glucose metabolism. In this study we evaluated changes in glucose metabolism, before and after surgery for APA. The subjects were 61 patients treated with unilateral adrenalectomy, localized by adrenal venous sampling. A 75g-oral glucose tolerance test (OGTT) was performed before and 1 year after adrenalectomy. Patients with diabetes mellitus or a serum cortisol level >3 µg/dL after a 1 mg dexamethasone suppression test, were excluded. Using the 75g-OGTT data, insulin secretion and insulin resistance (or sensitivity) indices were calculated. The results showed that immunoreactive insulin levels during the OGTT increased significantly after adrenalectomy, whereas plasma glucose levels, before and after surgery, were comparable. The insulinogenic index significantly increased after surgery (0.5 [0.4-0.8] to 0.8 [0.4-1.1], p < 0.001). The disposition index remained largely unchanged (806.2 [489.4-1,138.9] to 686.6 [479.4-922.1], p = 0.25). The homeostatic model assessment of insulin resistance increased significantly (1.0 [0.6-1.5] to 1.5 [1.0-2.2], p < 0.001) and the ISImatsuda decreased significantly (6.9 [4.5-10.4] to 5.2 [3.4-7.9], p < 0.001). Changes in these indices were not correlated with changes in potassium and aldosterone levels before and after surgery. In conclusion, insulin secretion increased after adrenalectomy for APA, indicating that aldosterone excess inhibits insulin secretion. However, because of a parallel increase in insulin resistance, plasma glucose levels remained unchanged.
Assuntos
Aldosterona/metabolismo , Hiperaldosteronismo/metabolismo , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/fisiopatologia , Neoplasias do Córtex Suprarrenal/cirurgia , Adrenalectomia , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/fisiopatologia , Adenoma Adrenocortical/cirurgia , Adulto , Aldosterona/sangue , Glicemia/análise , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperaldosteronismo/sangue , Hiperaldosteronismo/etiologia , Hiperaldosteronismo/prevenção & controle , Insulina/sangue , Secreção de Insulina , Japão , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Potássio/sangue , Período Pré-Operatório , Estudos RetrospectivosRESUMO
BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for coronary heart disease, and previous studies indicated the involvement of low-grade inflammation in the pathogenesis of CKD. METHODS: The study was designed to (i) identify and confirm genes and their products upregulated in mesangial cells cocultured with endotoxin-stimulated macrophages and (ii) determine the clinical relevance of genes and proteins upregulated in mesangial cells under inflammatory conditions by an epidemiological approach. RESULTS: DNA microarray analysis revealed upregulated expression of many genes and their products including several cytokines and chemokines, as well as the inflammatory marker, lipocalin 2 gene. The gene expression and protein upregulation of lipocalin 2 were synergistically affected by endotoxin and tumor necrosis factor (TNF)-α stimulation. In human studies, lipocalin 2 level was significantly associated with creatinine (r = 0.419, P < 0.001) and negatively associated with eGFR (r = -0.365, P < 0.001). Multiple logistic regression analysis revealed a significant association between lipocalin 2 and soluble tumor necrosis factor receptor 2 (sTNF-R2), eGFR and uric acid in general subjects attending regular annual medical check-up (n = 420). When subjects with diabetes were excluded from the analysis, lipocalin 2 remained associated with sTNF-R2, eGFR and uric acid. CONCLUSIONS: Since an activated TNF system, as demonstrated by elevated sTNF-R2, and elevated uric acid were recently implicated in an elevated CKD risk, we conclude that inflammation could play an important role in the pathogenesis of CKD, and that lipocalin 2 is a potential universal marker for impaired kidney function. Furthermore, the results obtained by the current microarray analysis could improve the understanding of gene profiles associated with the pathophysiology of CKD under inflammatory conditions.
Assuntos
Proteínas de Fase Aguda/genética , Lipocalinas/genética , Proteínas Proto-Oncogênicas/genética , Insuficiência Renal Crônica/metabolismo , Proteínas de Fase Aguda/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/metabolismo , Linhagem Celular , Técnicas de Cocultura , Creatinina/sangue , Feminino , Humanos , Inflamação/metabolismo , Lipocalina-2 , Lipocalinas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Tipo II do Fator de Necrose Tumoral/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/imunologia , TranscriptomaRESUMO
Aims: The present study aimed to clarify the relationships between novel and traditional anthropometric indices and insulin sensitivity (SI) in young and middle-aged Japanese persons with normal glucose tolerance (NGT), and middle-aged Japanese persons with NGT and glucose intolerance. Methods: Plasma glucose and insulin levels were measured in 1270 young (age <40 years) and 2153 middle-aged persons with NGT (n = 1531) and glucose intolerance (n = 622) during a 75-g oral glucose tolerance test. Height (Ht), weight, and waist circumference (WC) were measured. The body mass index (BMI), WC, and the WC/Ht ratio were used as traditional anthropometric indices. A body shape index (ABSI) and the body roundness index (BRI) were calculated as novel indices. Indices of SI (Matsuda index and 1/homeostasis model assessment of insulin resistance) were calculated and compared with anthropometric indices. Results: The ABSI showed a weak correlation with SI indices in all groups. The BRI showed almost the same correlation with SI indices as the BMI, WC, and WC/Ht in all groups. The inverse correlation between each of the anthropometric indices other than ABSI and SI indices was weak in young persons, at 0.16-0.27 (Spearman's ρ values), but strong in middle-aged persons, at 0.38-1.00. On receiver-operating characteristic (ROC) curve analysis for detection of insulin resistance, the ABSI had a lower area under the ROC curve (AUC) than the other anthropometric indices, and the BRI and the WC/Ht ratio showed similar AUCs. The AUCs for the BRI and WC/Ht ratio were the highest in middle-aged men with NGT and glucose intolerance. Conclusions: The BRI, not the ABSI, was better correlated with SI in young and middle-aged Japanese persons. The BRI and WC/Ht ratio were comparable in their correlations with SI and the detection of insulin resistance in the participants of the present study.
Assuntos
Intolerância à Glucose , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Humanos , Adulto , Índice de Massa Corporal , Obesidade/diagnóstico , Fatores de Risco , Intolerância à Glucose/diagnóstico , Japão , Antropometria , Circunferência da CinturaRESUMO
Context: The role of hepatic steatosis (HS) in the initial stages of developing type 2 diabetes remains unclear. Objective: We aimed to clarify the impact of HS indexed by Fatty Liver Index (FLI) and high-normal fasting plasma glucose (FPG) as risk factors for incident prediabetes in a nonobese cohort. Methods: Data from 1125 participants with ADA-defined normal glucose metabolism (median age 52 years; BMI 23.1 kg/m2) were used for retrospective analysis. In the entire population, correlation between normal FPG and FLI was evaluated by multiple regression adjusted for age and sex. Follow-up data from 599 participants in whom 75-g OGTT was repeated 3.7 years later showed that 169 developed prediabetes. This was analyzed by the multivariate Cox proportional hazards model. Results: In the entire population, FLI was positively correlated with FPG (Pâ <â 0.01): mean FLI increased from 15.8 at FPG 4.2 mmol/L to 31.6 at FPG 5.5 mmol/L. Analysis of the 599 participants (2061 person-years) by Cox model, adjusted for sex, age, family history of diabetes, ISIMATSUDA, and Stumvoll-1, clarified an increased risk of prediabetes with high-normal FPG and FLI. Risk was increased 2.2 times with FLIâ ≥â 16.5 vs FLIâ <â 16.5, Pâ <â 0.001, and increased 2.1 times in participants with FPGâ ≥â 5.3 mmol/L, Pâ <â 0.001. Cutoff values (unadjusted) were obtained by ROC at the point of the largest Youden's index using the entire range of the variables. Conclusion: Even among nonobese individuals, HS indexed by FLI and a high-normal FPG (≥ 5.3 mmol/L) are risk factors for prediabetes, independently from insulin.
RESUMO
AIMS/INTRODUCTION: This study examined the association between the severity of diabetic polyneuropathy (DPN) based on the Baba classification, and sarcopenia and its related factors. MATERIALS AND METHODS: The participants were 261 patients with type 2 diabetes mellitus. DPN was classified as stages 0-4 according to the Baba classification. Sarcopenia was diagnosed based on measurements of the skeletal mass index, grip strength and walking speed, using the Asia Working Group for Sarcopenia 2019 diagnostic criteria. RESULTS: The median age of the participants was 67 years, the proportion of men was 58.6%, the median estimated duration of diabetes was 10 years and the median values for glycated hemoglobin were 10.3%. With regard to DPN, the prevalence of Baba classification stages 0-2 was 90.8% (n = 237), and that of stage 3 or 4 was 9.2% (n = 24). The prevalence of sarcopenia was 19.9%. A trend toward an increase in the frequency of slow walking speed was seen as the stage of DPN progressed. The frequencies of sarcopenia and slow walking speed were higher in the group with the Baba classification stages 3 and 4 than in the group with stages 0-2. On multiple logistic regression analyses, however, DPN was not significantly related to sarcopenia and walking speed. CONCLUSIONS: Although severe DPN might be related to sarcopenia, the frequency of severe DPN is low in the clinical setting, indicating that its contribution to sarcopenia is modest.
Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Sarcopenia , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Humanos , Japão/epidemiologia , Masculino , Condução Nervosa/fisiologia , Sarcopenia/complicações , Sarcopenia/diagnóstico , Sarcopenia/epidemiologiaRESUMO
A 54-year-old man had been drinking approximately 1.2 L of soy milk (equivalent to approximately 310 mg of isoflavones) per day for the previous 3 years. He then developed erectile dysfunction and gynecomastia. On an examination in our department in May, blood tests showed low gonadotropin and testosterone levels, indicative of secondary hypogonadism. He stopped drinking soy milk on his own in June of that year. When he was admitted in August, blood tests showed an improved gonadal function. Secondary hypogonadism caused by the excessive intake of isoflavones in soy milk was diagnosed. In men, an excessive intake of isoflavones may cause feminization and secondary hypogonadism.
Assuntos
Hipogonadismo , Isoflavonas , Ingestão de Alimentos , Gonadotropinas , Humanos , Hipogonadismo/induzido quimicamente , Isoflavonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Testosterona/efeitos adversosRESUMO
Aims: The present study aimed to clarify the relationships between diabetic family history (FH), and dysglycemic response to the oral glucose tolerance test (OGTT), insulin secretion, and insulin sensitivity in young Japanese persons with normal glucose tolerance (NGT). Methods: We measured plasma glucose (PG) and immunoreactive insulin levels in 1,309 young Japanese persons (age <40 years) with NGT before and at 30, 60, and 120 min during a 75-g OGTT. Dysglycemia during OGTT was analyzed by k-means clustering analysis. Body mass index (BMI), blood pressure (BP), and lipids were measured. Insulin secretion and sensitivity indices were calculated. Results: PG levels during OGTT were classified by k-means clustering analysis into three groups with stepwise decreases in glucose tolerance even among individuals with NGT. In these clusters, proportion of males, BMI, BP and frequency of FH were higher, and lipid levels were worse, together with decreasing glucose tolerance. Subjects with a diabetic FH showed increases in PG after glucose loading and decreases in insulinogenic index and Matsuda index. Conclusions: Dysglycemic response to OGTT by k-means clustering analysis was associated with FH in young Japanese persons with NGT. FH was also associated with post-loading glucose, insulinogenic index, and Matsuda index.
RESUMO
Associations of arterial stiffness with glucose, insulin, and proinsulin dynamics during the oral glucose tolerance test (OGTT) remain under debate. The aim of this study was to investigate whether plasma glucose (PG), insulin, and proinsulin (Pro) contribute to arterial stiffness, measured by pulse wave velocity (PWV), in young Japanese persons. PG, immunoreactive insulin (IRI), and Pro levels were determined in 1193 young Japanese subjects (<40 years of age) with normal glucose tolerance or nondiabetic hyperglycemia before and at 30, 60, and 120 min during a 75-g OGTT. Participants were divided into two groups according to the median PWV. Background factors, PG, IRI, and Pro levels during the OGTT, and insulin sensitivity (SI) indices in each group were compared. Several multiple regression analysis models were used to evaluate factors contributing to PWV. All IRI and Pro levels before and after glucose loading and the area under the curve (AUC) values for IRI and Pro increased with higher PWV. 1/HOMA-IR and ISI-Matsuda as measures of SI decreased with higher PWV. The IRI AUC and Pro level before glucose loading (Pro0) were independently associated with PWV, in addition to male sex, heart rate, and mean blood pressure. The IRI AUC had a stronger relationship with PWV than Pro0. The IRI AUC had an independent relationship with PWV, whereas both SI indices did not. Postloading insulinemia, but not reduced SI, was independently associated with arterial stiffness in young Japanese persons.
Assuntos
Resistência à Insulina , Rigidez Vascular , Glicemia , Humanos , Insulina , Japão , Masculino , Análise de Onda de PulsoRESUMO
Background: The aim of the study was to investigate the relationship between glucose effectiveness (Sg) and some metabolic parameters in male and female young Japanese. Methods: We measured plasma glucose and immunoreactive insulin levels in 1309 young Japanese persons (age <40 years) with normal glucose tolerance (NGT) before and at 30, 60, and 120 min during a 75 gram oral glucose tolerance test. We also measured serum adiponectin and high-sensitivity C-reactive protein (hsCRP) levels and oral glucose effectiveness (SgIO), and investigated factors related to SgIO. Results: The results of Spearman correlation analysis revealed that high-density lipoprotein cholesterol (HDL) and adiponectin were positively correlated with SgIO, whereas the proportion of males, body mass index, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure, triglycerides (TG), and hsCRP were inversely correlated with SgIO. The results of multiple regression analysis indicated negative correlations between SgIO and the proportion of males, WC, and SBP and a positive correlation with HDL. The results of multiple regression analysis excluding WC indicated negative correlations between SgIO and the proportion of males, SBP, and TG and positive correlations with HDL and adiponectin. Conclusions: Sg decreased with a subtle worsening of metabolic parameters, even in young persons with NGT. Decreased Sg may be involved in the development of glucose intolerance in individuals with worse metabolic parameters.
Assuntos
Glicemia , Síndrome Metabólica , Adiponectina/sangue , Adulto , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Humanos , Japão/epidemiologia , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologiaRESUMO
To date, there are very few clinical reports that have compared the effects of ezetimibe on lipid parameters between hypercholesterolemic patients with and without type 2 diabetes mellitus (T2DM). In this study, we recruited patients for hypercholesterolemic groups with T2DM (n = 42; men/women = 24/18; HbA1c = 6.7 ± 5.4%) and without T2DM (n = 21; men/women = 7/14; HbA1c = 5.3 ± 0.4%). Patients were prescribed ezetimibe at a dose of 10 mg/daily for the course of the 12-week study. At baseline and after 12 weeks of treatment, several lipid parameters, including serum low-density-lipoprotein cholesterol (LDL-C), non-high-density-lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP), and cholesterol synthesis/absorption-related markers, were measured. Compared with those at the baseline, the levels of LDL-C, non-HDL-C, campesterol, and sitosterol were significantly reduced after 12 weeks of ezetimibe treatment in both groups. After adjusting for confounding factors, such as age, gender, smoking, and BMI, the levels of LDL-C and non-HDL-C displayed significantly greater reductions in the patients with T2DM (-25.1 ± 13.6% in LDL-C, -20.5 ± 11.2% in non-HDL-C) than those without T2DM (-20.5 ± 7.8% in LDL-C, P < 0.05; -17.4 ± 7.6% in non-HDL-C, P < 0.05). The reduction of the level of cholestanol was significantly and positively correlated with those of LDL-C and non-HDL-C in the patients with T2DM. Taken together, these findings indicate that ezetimibe could reduce the levels of atherogenic lipoproteins to a greater extent in hypercholesterolemic patients with T2DM than in those without T2DM.
Assuntos
Azetidinas/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/análise , Doenças Cardiovasculares/prevenção & controle , Colestanol/sangue , Colesterol/análogos & derivados , Colesterol/sangue , Colesterol/metabolismo , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ezetimiba , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Fitosteróis/sangue , Sitosteroides/sangueRESUMO
BACKGROUND: Endocrine hormones are closely associated with homeostasis, so it is important to clarify hormone secretion dynamics in shock. Few reports, however, have examined the dynamics of endogenous hormone secretion relative to prognosis in cardiac arrest patients. Therefore, to clarify the roles of endocrine hormones in out-of-hospital cardiac arrest (OHCA) patients, the concentrations of anterior pituitary, thyroid, and adrenocortical hormones were measured, and their associations with return of spontaneous circulation (ROSC) were examined. METHODS: The subjects were OHCA patients transported to our Emergency Department. In addition to conventional clinical laboratory tests, the following were measured: serum TSH, serum free T3, serum free T4 (F-T4), plasma ACTH, serum cortisol, serum GH, serum IGF-1, plasma aldosterone concentration (PAC), and plasma renin activity. The primary endpoint was the presence or absence of ROSC, and the secondary endpoint was 24-hour survival. RESULTS: A total of 29 patients, 17 in the ROSC group and 12 in the non-ROSC group, were studied. There were associations between ROSC and low serum potassium, high F-T4, low cortisol, and low PAC on bivariate analyses. There were associations between ROSC and serum potassium, F-T4, and GH using the step-wise method. On multiple logistic regression analysis, a relationship between ROSC and high serum F-T4 level was identified by both methods. There were also associations between 24-hour survival and both low serum potassium and elevated blood glucose levels. CONCLUSIONS: The present findings suggest a possible relationship between the serum F-T4 level and ROSC in OHCA patients. A higher serum F-T4 level might cause an increase in the ß-adrenergic response in cardiomyocytes and increased responsiveness to catecholamines and was possibly associated with ROSC.
RESUMO
BACKGROUND: Body weight loss in patients with obesity improves abnormal glucose tolerance, dyslipidemia and hypertension; however, it is difficult to maintain this loss of body weight. The objective of this study was to examine factors involved in body weight loss and its maintenance in morbidly obese inpatients. METHOD: The subjects were 31 patients (11 males and 20 females) who were admitted to hospital for obesity management. Factors involved in body weight changes during hospitalization and after discharge were examined retrospectively. The mean age was 58.1 ± 13.6 years and body mass index (BMI) was 40.2 ± 10.2 kg/m2. Twenty-four patients were complicated with type 2 diabetes mellitus. Diet therapy was 23.8 ± 3.9 kcal/kg ideal body weight/day. RESULTS: Excess weight loss (EWL) during hospitalization varied from 4.2 to 61.7%. Since EWL was affected by duration of hospital stay, the subjects were divided by the median of EWL per day. The subjects with greater EWL per day had lower body weight, BMI and fat mass on admission in the entire (n = 31), diabetic (n = 24), and non-diabetic subjects (n = 7), respectively. EWL per day was not different between diabetic and non-diabetic subjects. Follow-up data revealed that BMI remained unchanged 3 months after discharge but modestly increased 1 year after discharge, irrespective of EWL per day during hospitalization. In diabetic subjects followed up 1 year after discharge (n = 15), the increase in body weight was smaller than that in non-diabetic subjects (n = 3). CONCLUSION: These results suggest that EWL in morbidly obese inpatients is greater than those with lower baseline BMI and fat mass. The presence of diabetes had no effects on EWL during hospitalization. EWL during hospitalization was not correlated with its maintenance after discharge. Diabetic patients displayed lesser degree of body weight gain after discharge, possibly due to the effects of anti-diabetic medications.
RESUMO
CONTEXT: Slight elevations in plasma glucose (PG) manifest in advance of diabetes onset, but abnormalities in immunoreactive insulin (IRI), proinsulin (Pro), and adiponectin dynamics during this stage remain poorly understood. OBJECTIVE: The objective of this work is to investigate whether IRI and Pro dynamics become abnormal as glucose tolerance deteriorates from within the normal range toward impaired glucose tolerance (IGT), as well as the relationship between PG, and these dynamics and serum adiponectin levels. DESIGN: A cross-sectional study was designed. SETTING: This study took place at Jichi Medical University in Japan. PARTICIPANTS AND MEASUREMENTS: PG, IRI, and Pro levels were determined in 1311 young Japanese individuals (age <â 40 years) with normal or IGT before and at 30, 60, and 120 minutes during a 75-g oral glucose tolerance test. Participants were assigned to 4 groups according to glucose tolerance, and then background factors, adiponectin levels, insulin sensitivity (SI), and insulin secretion (ß) indexes were determined. RESULTS: PG levels as well as IRI and Pro levels 60 and 120 minutes after glucose-loading increased incrementally with deteriorating glucose tolerance. All measures of ß and the SI measure index of insulin sensitivity (ISI)-Matsuda decreased incrementally. Serum adiponectin levels were not significantly different among the glucose tolerance groups, but were independently and negatively correlated with fasting glucose. CONCLUSIONS: Early ß decreased and postloading Pro levels became excessive in a progressive manner as glucose tolerance deteriorated from within the normal range toward IGT.
RESUMO
A 38-year-old woman who consulted a local doctor with chief complaints of sudden palpitations, headaches, and chest pain is herein presented. After admission, pheochromocytoma crisis was suspected. Since the patient had a history of acute heart failure and had once survived an episode of cardiac arrest, a rapid decrease in the catecholamine levels was needed. After resuscitation, pharmacological therapy with agents such as phentolamine and landiolol was administered, and continuous hemodiafiltration (CHDF) was performed to reduce the catecholamine levels. Elective surgery was then performed, and a positive outcome was achieved. This case suggests that the preoperative use of CHDF to control pheochromocytoma crisis may therefore be effective.
Assuntos
Neoplasias das Glândulas Suprarrenais/terapia , Hemodiafiltração/métodos , Feocromocitoma/terapia , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Catecolaminas/sangue , Dor no Peito/etiologia , Feminino , Cefaleia/etiologia , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/etiologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Feocromocitoma/sangue , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
AIM: Prebeta1-HDL is involved in the initial step of cholesterol efflux from peripheral cells and plays an important role in reverse cholesterol transport. We studied the effect of pitavastatin on the HDL subfraction profile, prebeta1-HDL concentration and its disappearance rate. METHODS: Twenty-nine hypercholesterolemic patients were treated with pitavastatin at 2 mg/day for 4 weeks, and plasma levels of total cholesterol (TC), triglyceride, HDL-cholesterol (C), HDL(2)-C, HDL(3)-C, prebeta1-HDL, LCAT activity, and CETP mass were assayed. The prebeta1-HDL disappearance rate was determined as the difference in prebeta1-HDL concentration before and after incubation at 37 degrees C for 90 min divided by the pre-incubation prebeta1-HDL concentration. RESULTS: Pitavastatin led to significant decreases in TC by 26.9% and LDL-C by 39.8%. HDL-C and HDL(2)-C increased significantly by 6.0% and 9.0%, respectively, but there was no significant change in HDL(3)-C. Prebeta1-HDL concentration significantly decreased (-8.7%; p<0.05); however, its disappearance rate significantly increased (13.0%; p<0.05). There were significant decreases in both LCAT activity and CETP mass. CONCLUSION: Although pitavastatin decreased plasma prebeta1-HDL concentration, it increased the prebeta1-HDL disappearance rate. These data suggest that pitavastatin might promote the early step of reverse cholesterol transport.
Assuntos
HDL-Colesterol/metabolismo , Inibidores Enzimáticos/administração & dosagem , Lipoproteínas de Alta Densidade Pré-beta/metabolismo , Quinolinas/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
We report a case of a woman with diabetes mellitus caused by a genetic defect in ABCC8-coding sulfonylurea receptor 1 (SUR1), a subunit of the ATP-sensitive potassium (KATP) channel protein. She was diagnosed with diabetes at 7 days after birth. After intravenous insulin drip for 1 month, her hyperglycaemia remitted. At the age of 13 years, her diabetes relapsed, and after that she had been treated by intensive insulin therapy for 25 years with relatively poor glycaemic control. She was switched to oral sulfonylurea therapy and attained euglycaemia. In addition, her insulin secretory capacity was ameliorated gradually. LEARNING POINTS: Genetic testing should be considered in any individuals or family with diabetes that occurred within the first year or so of life.Sulfonylurea can achieve good glycaemic control in patients with KATP channel mutations by restoring endogenous insulin secretion, even if they were treated with insulin for decades.Early screening and genetic testing are important to improve the prognosis of patients with neonatal diabetes mellitus arising from ABCC8 or KCNJ11 mutation.