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1.
Endocr J ; 64(5): 515-520, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28321053

RESUMO

Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Adulto , Fatores Etários , Idade de Início , Comorbidade , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Hipertensão/genética , Incidência , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Autorrelato
2.
Tohoku J Exp Med ; 243(1): 35-39, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28924074

RESUMO

Carbohydrate-restricted diets are prevalent not only in obese people but also in the general population to maintain appropriate body weight. Here, we report that extreme carbohydrate restriction for one day affects the subsequent blood glucose levels in healthy adults. Ten subjects (median age 30.5 years, BMI 21.1 kg/m2, and HbA1c 5.5%), wearing with a continuous glucose monitoring device, were given isoenergetic test meals for 4 consecutive days. On day 1, day 2 (D2), and day 4 (D4), they consumed normal-carbohydrate (63-66% carbohydrate) diet, while on day 3, they took low-carbohydrate/high-fat (5% carbohydrate) diet. The daily energy intake was 2,200 kcal for males and 1,700 kcal for females. On D2 and D4, we calculated the mean 24-hr blood glucose level (MEAN/24h) and its standard deviation (SD/24h), the area under the curve (AUC) for glucose over 140 mg/dL within 4 hours after each meal (AUC/4h/140), the mean amplitude of the glycemic excursions (MAGE), the incremental AUC of 24-hr blood glucose level above the mean plus one standard deviation (iAUC/MEAN+SD). Indexes for glucose fluctuation on D4 were significantly greater than those on D2 (SD/24h; p = 0.009, MAGE; p = 0.013, AUC/4h/140 after breakfast and dinner; p = 0.006 and 0.005, and iAUC/MEAN+SD; p = 0.007). The value of MEAN/24h and AUC/4h/140 after lunch on D4 were greater than those on D2, but those differences were not statistically significant. In conclusion, consumption of low-carbohydrate/high-fat diet appears to cause higher postprandial blood glucose on subsequent normal-carbohydrate diet particularly after breakfast and dinner in healthy adults.


Assuntos
Dieta com Restrição de Carboidratos , Glucose/metabolismo , Saúde , Período Pós-Prandial , Adulto , Glicemia/metabolismo , Feminino , Humanos , Masculino
3.
Clin Exp Nephrol ; 19(6): 1179-83, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25824109

RESUMO

BACKGROUND: Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. However, these markers are influenced by alterations in hemoglobin and albumin metabolism. Thus, conditions such as anemia, chronic renal failure, hypersplenism, chronic liver diseases, hyperthyroidism, hypoalbuminemia, and pregnancy need to be considered when interpreting HbA1c or GA values. Using data from patients with normal albumin and hemoglobin metabolism, we previously established a linear regression equation describing the GA value versus the HbA1c value to calculate an extrapolated HbA1c (eHbA1c) value for the accurate evaluation of glycemic control. In this study, we investigated the difference between the measured HbA1c and the eHbA1c values for patients with various conditions. METHODS: Data sets for a total of 2461 occasions were obtained from 731 patients whose HbA1c and GA values were simultaneously measured. We excluded patients with missing data or changeable HbA1c levels, and patients who had received transfusions or steroids within the previous 3 months. Finally, we included 44 patients with chronic renal failure (CRF), 10 patients who were undergoing hemodialysis (HD), 7 patients with hematological malignancies and a hemoglobin level of less than 10 g/dL (HM), and 12 patients with chronic liver diseases (CLD). RESULTS: In all the groups, the eHbA1c values were significantly higher than the measured HbA1c values. The median difference was 0.75 % (95 % CI 0.40-1.10 %, P for the difference is <0.001) in the CRF group, 0.80 % (95 % CI 0.30-1.65 %, P for the difference is 0.041) in the HD group, 0.90 % (95 % CI 0.90-1.30 %, P for the difference is 0.028) in the HM group, and 0.85 % (95 % CI 0.40-1.50 %, P for the difference is 0.009) in the CLD group. CONCLUSIONS: We found that the measured HbA1c values were lower than the eHbA1c values in each of the groups.


Assuntos
Hemoglobinas Glicadas/análise , Falência Renal Crônica/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Glicemia/metabolismo , Feminino , Taxa de Filtração Glomerular , Produtos Finais de Glicação Avançada , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Gravidez , Diálise Renal , Albumina Sérica/análise , Albumina Sérica Glicada
4.
Endocr J ; 61(6): 553-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24681757

RESUMO

Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. These markers are influenced by either altered hemoglobin metabolism or albumin metabolism. We investigated the correlation between HbA1c and GA by collecting only data that had not been affected by the turnover of either HbA1c or GA and proposed a novel equation for accurately estimating the extrapolated HbA1c (eHbA1c) value based on the GA value. Data sets for a total of 2461 occasions were obtained from 731 patients (including non-diabetes patients) whose HbA1c and GA values were simultaneously measured. Data sets obtained from patients undergoing hemodialysis, patients with hematological malignancies, pregnancy, chronic liver diseases, hyperthyroidism, steroid treatment or a blood transfusion during the past 3 months, or patients without albumin, hemoglobin, eGFR, or urinary protein measurements and data sets with an eGFR of less than 30 mL/min/1.73 m(2), a hemoglobin level of less than 10 mg/dL, an albumin level of below 3.0 g/mL, or a urinary protein level of 3+ were excluded. Finally, we selected 284 data sets. We then analyzed these data sets, performed a scatter plot to examine the correlation between HbA1c and GA, and established an equation describing the resulting correlation. Based on all the data points, the resulting equation was HbA1c = 0.216 × GA + 2.978 [R(2) = 0.5882, P < 0.001].


Assuntos
Hemoglobinas Glicadas/metabolismo , Modelos Teóricos , Albumina Sérica/metabolismo , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Produtos Finais de Glicação Avançada , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Albumina Sérica Glicada
5.
BMC Endocr Disord ; 13: 38, 2013 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-24090279

RESUMO

BACKGROUND: Obesity is associated with insulin resistance, development of diabetes, and coronary heart disease. There is limited information on the contribution of previous obesity on the risk of coronary heart disease. We aimed to examine the effect of previous history of obesity on the occurrence of coronary heart disease in patients with diabetes. METHODS: We carried out a retrospective chart analysis of 315 type 2 diabetic patients without obesity and without atherosclerotic cardiovascular events at their initial hospital visit (men/women 236/79; mean ± standard deviation; age 53.1 ± 6.6 years; maximal body mass index before enrollment (MAXBMI) 26.6 ± 3.4 kg/m2; decrease of the BMI at enrollment from MAXBMI (deltaBMI) 4.23 ± 2.62 kg/m2) to investigate the association of previous obesity (MAXBMI larger than 30 kg/m2) with the long-term incidence of cardiovascular events. Of 315 patients, forty-eight were previously obese. RESULTS: After median follow-up of 13.9 years, 48 patients developed coronary heart disease. The Kaplan-Meier analysis exhibited that coronary heart disease occurred more frequently in previously obese patients than in subjects in the reference category (22 kg/m2 < or = MAXBMI < 25 kg/m2) and that the effect lasted proportionally over follow-up periods. Multivariate Cox regression models showed that hazard ratios and corresponding 95% confidence intervals of coronary heart disease for patients with previous obesity compared with subjects in the reference category were 2.52 and 1.15 to 5.50 (p value = 0.020) after adjustment for age, sex, smoking status, systolic blood pressure, total cholesterol and HDL cholesterol. In this cohort, deltaBMI strongly correlated with MAXBMI and also behaved as a risk factor. The hazard ratios and 95% confidence intervals by the increment of one standard deviation of deltaBMI after adjustment for age, sex, smoking status, systolic blood pressure, total cholesterol and HDL cholesterol were 1.38 and 1.08 to 1.79 (p value = 0.013). CONCLUSIONS: Previous obesity and/or large body weight loss before admission might act as an increased risk for coronary heart disease.

6.
Endocr J ; 60(8): 951-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23665775

RESUMO

A 73-year-old woman with malignant insulinoma was treated with 100 µg/day octreotide for unresected insulinoma and liver metastases. The daily administration of the drug induced hyperglycemia after dinner in addition to existing fasting hypoglycemia possibly because this drug suppressed both insulin and glucagon secretion and its blood concentration was unstable. After replacing a daily injection of octreotide with a monthly injection of octreotide long-acting repeatable (LAR), blood glucose levels stabilized within the normal range. The findings of the present study showed that octreotide LAR could be useful for the long-term treatment of unresectable insulinomas.


Assuntos
Glicemia/metabolismo , Insulinoma/tratamento farmacológico , Octreotida/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Glicemia/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Insulinoma/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Octreotida/efeitos adversos , Octreotida/sangue , Neoplasias Pancreáticas/patologia
7.
J Diabetes Investig ; 14(7): 874-882, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37026171

RESUMO

AIMS/INTRODUCTION: Research on the incidence and underlying mechanisms of rapid renal function decline in patients with type 2 diabetes mellitus with preserved renal function and normoalbuminuria is limited. This study aimed to investigate the involvement of hemoglobin level as a risk factor for rapid decliners among patients with type 2 diabetes with preserved renal function and normoalbuminuria. MATERIALS AND METHODS: This was a retrospective observational study of 242 patients with type 2 diabetes with a baseline estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 and normoalbuminuria (<30 mg/gCr), followed up for >1 year. The annual rate of estimated glomerular filtration rate decline during the follow-up period was calculated using least square regression analysis; rapid decliners defined at ≥3.3%/year. Risk factors associated with rapid decliners were identified using a logistic regression analysis of variables previously identified as risk factors of rapid decliners. RESULTS: The median follow-up period was 6.7 years, and 34 patients showed rapid decliners. On multivariate analysis, lower baseline hemoglobin level was a risk factor of rapid decliners (odds ratio 0.69, 95% confidence interval 0.47-0.99; P = 0.045). Furthermore, the baseline hemoglobin levels were correlated positively with iron and ferritin levels, implying that an impaired iron metabolism might cause lower hemoglobin levels in rapid decliners. CONCLUSIONS: In patients with type 2 diabetes with preserved renal function and normoalbuminuria, lower hemoglobin levels were a risk factor for rapid decliners, where disturbed iron metabolism might precede the development of diabetic kidney disease.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Taxa de Filtração Glomerular , Progressão da Doença , Fatores de Risco , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Albuminúria/complicações , Estudos Retrospectivos , Rim , Hemoglobinas
9.
Endocr J ; 58(1): 13-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21084770

RESUMO

Since there is increasing evidence that postprandial hyperglycemia is a risk factor for the development of macrovascular complications, it is important to predict postprandial hyperglycemia in the early stages of glucose intolerance, and routine medical checkups provide a good opportunity to do so. The aim of this study was to evaluate the usability of 1,5-anhydroglucitol (1,5-AG) in routine medical checkups. The subjects were 77 Japanese men who participated in a routine medical checkup. First, we performed 75 g oral glucose tolerance tests (OGTTs), and examined the changes in glucose and 1,5-AG levels measured at 0, 30, 60, 90, 120, and 180 minutes (min). 1,5-AG levels did not significantly change until 90 min after the glucose load. Second, a linear regression analysis showed an inverse correlation between the 2-hour post-challenge glucose (2h-PG) and baseline 1,5-AG levels during the OGTT (P = 0.001, r(2) = 0.13), and the correlation was still significant after adjustment for age (2h-PG = 170 + 0.83 × (age in years) - 3.23 × (1,5-AG), P = 0.002, adjusted r(2) = 0.12). Finally, to investigate the test characteristics of 1,5-AG levels as a predictor of a 2h-PG level ≥200 mg/dL, we plotted a receiver operating characteristic (ROC) curve. The area under the ROC curve was 0.78, and the maximal sum of sensitivity and specificity (78% and 72%, respectively) was obtained at a 1,5-AG cutoff level of <14.2µg/mL. We conclude that 1,5-AG values may provide an ancillary predictor of 2h-PG of 75 g OGTTs in routine medical checkups.


Assuntos
Glicemia/metabolismo , Desoxiglucose/sangue , Teste de Tolerância a Glucose/métodos , Hiperglicemia/diagnóstico , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade
12.
J Diabetes Investig ; 10(5): 1341-1346, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30663265

RESUMO

AIMS/INTRODUCTION: It is suspected that Helicobacter pylori is associated with extradigestive diseases including diabetes. So far, a number of studies have examined the association between H. pylori and diabetes, and the results were conflicting. The aim of the present study was to examine the association between H. pylori infection, eradication and diabetes. MATERIALS AND METHODS: The present cross-sectional study was carried out using data from annual health checkups carried out at the Toranomon Hospital Health Management Center. The status of H. pylori infection, determined by serum antibodies and history of eradication, was categorized into three groups as "never," "current" and "past." The association between H. pylori infection and diabetes was examined using logistic regression. RESULTS: Of 21,634 participants, 6,530 (30.2%) had a current or past history of H. pylori infection, and 1,184 (5.5%) were identified as having diabetes. Multivariate adjusted odds ratios for diabetes compared with the "never" group were 1.36 (95% confidence interval 1.10-1.67) for the "current" group and 0.92 (95% confidence interval 0.79-1.07) for the "past" group. The association between H. pylori infection and diabetes was also observed among participants without a history of eradication. CONCLUSIONS: We found that current H. pylori infection was associated with an increased risk of diabetes, and the increased risk was not observed among participants after eradication. The results were concordant with the hypothesis that H. pylori infection increases the risk of diabetes. Further studies are necessary to validate the present results.


Assuntos
Antibacterianos/uso terapêutico , Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Biomarcadores , Estudos Transversais , Feminino , Seguimentos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
13.
Diabetes Res Clin Pract ; 147: 37-46, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29522788

RESUMO

AIMS: In this study, we applied quantitative proteomic analysis to identify urinary proteins associated with diabetic nephropathy (DN). METHODS: Two-dimensional image-converted analysis of liquid chromatography and mass spectrometry detected the proteins differentially excreted between normoalbuminuric and macroalbuminuric patients with type 2 diabetes mellitus (T2DM) (n = 6 each). Urinary levels of excreted proteins were measured by multiple reaction monitoring (MRM) analysis using an independent sample set (n = 77). Urinary afamin levels were measured by ELISA in T2DM and DN patients enrolled in this cohort study (n = 203). RESULTS: One-hundred-four proteins displayed significant alterations in excretion. Nine of these candidates were validated by MRM analysis. Among them, the levels of afamin, CD44 antigen, and lysosome-associated membrane glycoprotein 2, which have not previously been implicated in DN, were significantly associated with both the urinary albumin to creatinine ratio (ACR) and eGFR. We further measured afamin levels in urine collected from T2DM patients who did not yet have significant kidney disease (ACR < 300 mg/g or eGFR change rate ≤ 3.3%/year). The urinary afamin to creatinine ratio (Afa/Cre) was significantly higher in patients who progressed to a more severe DN stage or had early renal decline than in patients who did not. CONCLUSIONS: Afa/Cre was significantly increased in T2DM patients who subsequently developed DN. Afa/Cre may be useful to predict patients with T2DM at high risk of nephropathy before the development of macroalbuminuria or reduced kidney function, although further validation studies in a larger population are needed.


Assuntos
Proteínas de Transporte/urina , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/diagnóstico , Glicoproteínas/urina , Proteômica/métodos , Albumina Sérica Humana/urina , Estudos de Coortes , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/urina , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Endocr J ; 55(5): 913-23, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18612182

RESUMO

PURPOSE OF THE STUDY: Tight glycemic control is important for the prevention of microvascular complications in diabetic patients. We examined the reliability of using blood glucose levels measured at various time-points relative to a meal as an index of glycemic control in Japanese diabetic outpatients. Basic procedures followed: We examined the correlation between the fasting blood glucose (FBG) level; the one-hour (1-h), two-hour (2-h), and three-hour (3-h) post breakfast blood glucose (PBBG) levels, the 1 h, 2 h, and 3 h post lunch blood glucose (PLBG) levels and the hemoglobin A1c (HbA1c) levels in Japanese diabetic outpatients. A total of 11451 patient-visits to the Marunouchi Hospital between January 2002 and December 2002 were included in the study. The main findings: The blood glucose levels measured at all of the above time-points were significantly correlated with the HbA1c level. As calculated using local polynomial regression fitting, the FPG, 1-h, 2-h, and 3-h PBBG levels that corresponded to an HbA1c level of 6.5% were 132 mg/dL, 174 mg/dL, 170 mg/dL, and 143 mg/dL, respectively. The FPG and 2-h PBBG levels exhibited a good sensitivity and specificity for predicting a glycemic control corresponding to an HbA1c<5.8%, while the FPG and 3-h PBBG levels exhibited fair sensitivity and specificity for predicting glycemic control corresponding to an HbA1c<6.5%. The principal conclusions: The FBG, 2-hPBBG, and 3-hPBBG levels can be used as rough estimates of glycemic control in Japanese diabetic outpatients.


Assuntos
Glicemia/análise , Diabetes Mellitus/sangue , Hemoglobinas Glicadas/análise , Idoso , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Jejum , Feminino , Alimentos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo
15.
Intern Med ; 57(9): 1229-1240, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29279487

RESUMO

Objective To analyze the changes in the pharmacotherapy and glycemic control trends in elderly patients with type 2 diabetes mellitus (T2DM) in Japan. Methods We extracted the data of 7,590 patients (5,396 men and 2,194 women; median year of birth: 1945) with T2DM registered in the National Center Diabetes Database for the years 2005 to 2013, and conducted age-stratified (<65, 65-74, and ≥75 years of age) analyses. Results The hemoglobin A1c (HbA1c) levels declined from 2005 to 2013, and for those who received antihyperglycemic drug prescription, the HbA1c levels were lower in the older age group than in the younger age group. In the ≥75 age group, dipeptidyl peptidase-4 inhibitors (DPP4i) became the most frequently prescribed drug (49.1%) in 2013, and sulfonylureas remained the second-most frequently prescribed drug (37.8%) with decreased prescribed doses. The prescription ratio of oral drugs associated with a risk of hypoglycemia was higher in patients ≥75 years of age than in those <75 years of age (40.5% and 26.4%, respectively in 2013), although it showed a downward trend. The prescription rates of insulin for patients ≥75 years of age increased during the study period. Conclusion The pharmacotherapy trends for elderly patients with T2DM changed dramatically in Japan with the launch of DPP4i in 2009. Glycemic control in a considerable portion of the ≥75 age group in Japan was maintained at the expense of potential hypoglycemia by the frequent, although cautious, use of sulfonylureas, glinides and insulin.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hipoglicemiantes/classificação , Hipoglicemiantes/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Insulina/uso terapêutico , Japão , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Compostos de Sulfonilureia/uso terapêutico
16.
Cell Struct Funct ; 32(1): 69-78, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17634669

RESUMO

To analyze the functional differences of the insulin receptor substrate (IRS) family, the N-terminal fragments containing the pleckstrin homology (PH) domains and the phosphotyrosine-binding (PTB) domains of IRS (IRS-N) proteins, as well as intact IRS molecules, were expressed in Cos-1 cells, and insulin-induced tyrosine phosphorylation and subcellular distribution of IRS proteins were analyzed. In contrast to the distinct affinities toward phosphoinositides, these IRS-N fragments non-selectively inhibited insulin-induced tyrosine phosphorylation of IRS-1, IRS-2 and IRS-3, among which IRS3-N was most effective. The mutations of IRS-1 disrupting all the phosphoinositide-binding sites in both the PH and PTB domains significantly but not completely suppressed tyrosine phosphorylation of IRS-1, which was further inhibited by coexpression of all the IRS-N proteins examined. In contrast, the N-terminal PH domain-interacting region (PHIP-N) of PH-interacting protein (PHIP) did not impair tyrosine phosphorylation of either IRS molecule. The analysis using confocal microscopy also demonstrated that all the IRS-N proteins, but not PHIP-N, suppressed targeting of IRS-1 to the plasma membrane in response to insulin. Moreover, the phosphoinositide affinity-disrupting mutations of IRS-1 significantly impaired but did not completely abrogate the insulin-induced translocation of IRS-1 to the plasma membrane, which was further suppressed by IRS1-N overexpression. These findings suggest that both insulin-induced tyrosine phosphorylation and the cell surface targeting of IRS proteins may be regulated in a similar manner through a target molecule common to the members of the IRS family, and distinct from phosphoinositides or PHIP.


Assuntos
Proteínas de Transporte/metabolismo , Insulina/farmacologia , Fosfoproteínas/metabolismo , Tirosina/metabolismo , Motivos de Aminoácidos , Animais , Sítios de Ligação , Proteínas Sanguíneas/metabolismo , Células COS , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Membrana Celular/metabolismo , Chlorocebus aethiops , Humanos , Immunoblotting , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Microscopia Confocal , Mutagênese Sítio-Dirigida , Mutação , Fosfatidilinositóis/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/fisiologia , Fosforilação/efeitos dos fármacos , Fosfotirosina/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Receptor de Insulina/fisiologia
17.
Med Sci Monit Basic Res ; 23: 36-44, 2017 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-28242866

RESUMO

BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6%; fat, 43.2%). Self-monitoring blood glucose levels were measured at 0, 30, 60, and 120 min after the meal tests, and the increase in the postprandial area under the curve (AUC)0-120 min was determined. The HbA1c, glycated albumin, and 1,5-anhydroglucitol (AG) levels were measured, and continuous glucose monitoring was performed. RESULTS The increase in the postprandial AUC0-120 min was significantly smaller in the M+V group than in the L group after both meals. The 24-h average, 24-h standard deviations, 24-h AUC, and mean amplitude of glycemic excursion (MAGE) were similar for both groups and after both meals. The change in 1,5-AG was higher in the M+V group than in the L group. CONCLUSIONS The combination of M+V with basal therapy improved postprandial glucose excursion more effectively than L in T2DM patients.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidases e Tripeptidil Peptidases/administração & dosagem , Hipoglicemiantes/administração & dosagem , Inositol/análogos & derivados , Isoindóis/administração & dosagem , Idoso , Estudos Cross-Over , Humanos , Inositol/administração & dosagem , Insulina/sangue , Insulina de Ação Prolongada/administração & dosagem , Linagliptina/administração & dosagem , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Período Pós-Prandial/efeitos dos fármacos
18.
J Diabetes Investig ; 8(5): 661-671, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28150914

RESUMO

AIMS/INTRODUCTION: To identify candidate serum molecules associated with the progression of type 2 diabetes mellitus, differential serum proteomic analysis was carried out on a spontaneous animal model of type 2 diabetes mellitus without obesity, the Long-Evans Agouti (LEA) rat. MATERIALS AND METHODS: We carried out quantitative proteomic analysis using serum samples from 8- and 16-week-old LEA and control Brown Norway (BN) rats (n = 4/group). Differentially expressed proteins were validated by multiple reaction monitoring analysis using the sera collected from 8-, 16-, and 24-week-old LEA (n = 4/each group) and BN rats (n = 5/each group). Among the validated proteins, we also examined the possible relevance of the human homolog of serine protease inhibitor A3 (SERPINA3) to type 2 diabetes mellitus. RESULTS: The use of 2-D fluorescence difference gel electrophoresis analysis and the following liquid chromatography-multiple reaction monitoring analysis showed that the serum levels of five proteins were differentially changed between LEA rats and BN rats at all three time-points examined. Among the five proteins, SERPINA3N was increased significantly in the sera of LEA rats compared with age-matched BN rats. The serum level of SERPINA3 was also found to be significantly higher in type 2 diabetes mellitus patients than in healthy control participants. Furthermore, glycated hemoglobin, fasting insulin and estimated glomerular filtration rate were independently associated with the SERPINA3 levels. CONCLUSIONS: These findings suggest a possible role for SERPINA3 in the development of the early stages of type 2 diabetes mellitus, although further replication studies and functional investigations regarding their role are required.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Estado Pré-Diabético/sangue , Proteômica , Proteínas de Fase Aguda , Idoso , Animais , Biomarcadores , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Endogâmicos , Ratos Long-Evans , Serpinas/sangue
19.
World J Gastroenterol ; 22(11): 3252-60, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27004003

RESUMO

AIM: To determine the bowel symptoms associated with diabetes and diabetes-related factors after excluding gastrointestinal (GI) organic diseases. METHODS: Participants were 4738 (603 diabetic and 4135 non-diabetic) patients who underwent colonoscopy and completed a questionnaire. On the day of pre-colonoscopy, 9 symptoms (borborygmus, abdominal distension, increased flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were prospectively evaluated on a 7-point Likert scale. The test-retest reliability of the bowel symptom scores from the baseline and second questionnaires was analyzed using kappa statistics. Associations between bowel symptom scores and diabetes or diabetes-related factors were analyzed by a rank-ordered logistic model adjusted for related confounders, and odds ratios (ORs) were estimated. RESULTS: In multivariate analysis, constipation [adjusted odds ratio (AOR) = 1.57, CI: 1.33-1.85, P < 0.01] and hard stools (AOR = 1.56, CI: 1.33-1.84, P < 0.01) were associated with diabetes, and fecal urgency (AOR = 1.16, CI: 0.99-1.37, P = 0.07) and incomplete evacuation (AOR = 1.16, CI: 1.00-1.36, P = 0.06) were marginally associated with diabetes. These symptoms remained associated even after excluding organic GI diseases on colonoscopy. Test-retest reliability of symptom score with a mean duration of 3.2 mo was good (mean kappa, 0.69). Associations of symptoms with diabetes-related factors were found; constipation with HbA1c ≥ 8.0% (AOR = 2.11, CI: 1.19-3.73), body mass index (BMI) < 25 (AOR = 2.11, CI: 1.22-3.66), and insulin use (AOR = 1.90, CI: 1.08-3.36); hard stools with diabetes duration (AOR = 1.03, CI: 1.00-1.07); fecal urgency with BMI < 25 (AOR = 1.73, CI: 1.00-2.98); and incomplete evacuation with BMI < 25 (AOR = 2.60, CI: 1.52-4.43), serum creatinine level (AOR = 1.27, CI: 1.10-1.47), and insulin use (AOR = 1.92, CI: 1.09-3.38). CONCLUSION: Diabetes is associated with constipation, hard stools, fecal urgency, and incomplete evacuation, and poor glycemic control, duration, leanness, and nephropathy affect the risk of these symptoms.


Assuntos
Constipação Intestinal/etiologia , Defecação , Complicações do Diabetes/etiologia , Diarreia/etiologia , Fezes/química , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Colonoscopia , Constipação Intestinal/diagnóstico , Constipação Intestinal/fisiopatologia , Estudos Transversais , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/fisiopatologia , Diarreia/diagnóstico , Diarreia/fisiopatologia , Feminino , Dureza , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
20.
J Diabetes Complications ; 30(4): 681-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26896334

RESUMO

AIMS: This study aimed to evaluate whether the pronounced elevation in blood pressure during severe hypoglycemia is associated with subsequent renal insufficiency. METHODS: We conducted a 3-year cohort study to assess the clinical course of renal function in type 2 diabetes patients with or without blood pressure surge during severe hypoglycemia. RESULTS: Of 111 type 2 diabetes patients with severe hypoglycemia, 76 exhibited an extremely high systolic blood pressure before treatment, whereas 35 demonstrated no such increase (179.1 ± 27.7 mmHg vs. 131.1 ± 20.2 mmHg, P<0.001). At 12h after treatment, systolic blood pressure did not differ significantly (131.5 ± 30.7 mmHg vs. 123.5 ± 20.7 mmHg; P=0.39). The estimated glomerular filtration rate (GFR) before and at the time of severe hypoglycemia did not significantly differ between both groups. A multivariate Cox proportional hazards regression analysis revealed that blood pressure surge during severe hypoglycemia was independently associated with a composite outcome of a more than 15 mL/min/1.73 m(2) decrease in the estimated GFR and initiation of chronic dialysis (hazard ratio, 2.68; 95% confidence interval, 1.12-6.38; P=0.02). CONCLUSIONS: Renal function after severe hypoglycemia was significantly worse in type 2 diabetes patients with blood pressure surge during severe hypoglycemia than those without blood pressure surge.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/fisiopatologia , Hipertensão/etiologia , Hipoglicemia/fisiopatologia , Rim/fisiopatologia , Insuficiência Renal/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/terapia , Progressão da Doença , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Hospitais Urbanos , Humanos , Hipertensão/prevenção & controle , Hipoglicemia/prevenção & controle , Japão , Masculino , Diálise Renal , Insuficiência Renal/complicações , Insuficiência Renal/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Índice de Gravidade de Doença , Análise de Sobrevida
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