RESUMO
AIMS: To investigate, in a 26-week, open-label, randomized, treat-to-target trial, the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily vs insulin glargine (IGlar) once daily in adults with Type 2 diabetes, inadequately controlled on basal insulin. METHODS: Participants were randomized (1:1) to IDegAsp once daily or IGlar once daily in combination with existing oral antidiabetic drugs. IDegAsp once daily was administered with the main evening meal or the largest meal of the day (agreed at baseline); dosing time was maintained throughout the trial. Participants titrated their insulin dose weekly to a mean pre-breakfast self-measured plasma glucose target [3.9-4.9 mmol/l (70-89 mg/dl)]. RESULTS: IDegAsp once daily was non-inferior to IGlar once daily in reducing HbA1c after 26 weeks [mean estimated treatment difference IDegAsp once daily - IGlar once daily: -0.03% (95% CI -0.20, 0.14)]. The evening meal glucose increment was significantly lower with IDegAsp once daily vs IGlar once daily [estimated treatment difference IDegAsp once daily - IGlar once daily: -1.32 mmol/l (95% CI -1.93, -0.72); P < 0.05]. The overall confirmed hypoglycaemia rate was higher with IDegAsp once daily (estimated rate ratio 1.43; 95% CI 1.07, 1.92; P < 0.05). The rate of nocturnal hypoglycaemia did not significantly differ between the IDegAsp and IGlar groups [estimated rate ratio 0.80 (95% CI 0.49, 1.30); not significant]. CONCLUSIONS: In participants with Type 2 diabetes inadequately controlled on basal insulin, IDegAsp once daily improved glycaemic control and was non-inferior to IGlar once daily. IDegAsp led to higher rates of overall hypoglycaemia than IGlar, with no significant difference in rates of nocturnal hypoglycaemia.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Combinação de Medicamentos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina Glargina/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Resultado do TratamentoRESUMO
Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 µg/ml with a high inoculum (â¼5 × 107 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76-12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.
Assuntos
Antibacterianos/farmacologia , Bacteriemia/microbiologia , Cefazolina/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bacteriemia/epidemiologia , Cefazolina/uso terapêutico , Clindamicina/farmacologia , Eritromicina/farmacologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Falha de Tratamento , beta-Lactamases/genéticaRESUMO
Methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) often persists despite appropriate antibiotic therapy. It is unclear what microbiological factors contribute to poor clinical outcomes in persistent MRSAB (pMRSAB). We aimed to identify clinical and microbiological risk factors for in-hospital mortality in pMRSAB. We analysed MRSAB cases prospectively collected between 2009 and 2016 at 11 hospitals in Korea, defining cases of pMRSAB as MRSAB lasting ≥5 days despite administration of effective antibiotics. The first blood isolates from the pMRSAB cases were tested for staphylococcal cassette chromosome mec type, staphylococcal protein A type, accessary gene regulator (agr) type, genes for Panton-Valentine leukocidin and phenol-soluble modulin-mec, vancomycin minimum inhibitory concentration, vancomycin heteroresistance, and agr functionality. We also collected clinical information for each case. Of 960 MRSAB cases, 152 pMRSAB were finally eligible. Univariable analysis revealed that in-hospital mortality was significantly associated with Charlson's comorbidity-weighted index (CCWI) score, Pitt bacteremia score, sequential organ failure assessment score, presentation with septic shock, pneumonia, agr dysfunction, and vancomycin heteroresistance. Bone and joint infections were negatively associated with in-hospital mortality. Multivariable analysis revealed the following independent risk factors for in-hospital mortality: CCWI score [adjusted odds ratio (aOR), per one point, 1.25; 95% confidence interval (CI), 1.08-1.44; P = 0.003), Pitt bacteremia score (aOR, per one point, 1.33; 95% CI, 1.09-1.62; P = 0.005), non-eradicated foci of infection (aOR, 3.12; 95% CI, 1.18-8.27; P = 0.022), and agr dysfunction (aOR, 2.48; 95% CI, 1.12-5.47; P = 0.025). agr dysfunction is an independent risk factor for in-hospital mortality in pMRSAB.
Assuntos
Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Proteínas de Bactérias/genética , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/mortalidade , Transativadores/genética , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Toxinas Bacterianas/genética , Exotoxinas/genética , Feminino , Mortalidade Hospitalar , Humanos , Sequências Repetitivas Dispersas/genética , Leucocidinas/genética , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Proteína Estafilocócica A/genética , Resultado do Tratamento , Resistência a Vancomicina/genéticaRESUMO
UNLABELLED: A daughter's bone mineral density (BMD) is significantly correlated with her mother's BMD, but the daughter's body mass index (BMI) could modulate this association. Maternal inheritance dominantly affects daughters with a lower BMI, but BMI could compensate for hereditary influences in daughters with a higher BMI in terms of daughter's BMD. INTRODUCTION: Achieving optimal peak bone mass at a young age is the best way to protect against future osteoporosis and subsequent fractures. Although environmental components influence bone mass accrual, but peak bone mass is largely programmed by inheritance. The aims of this study were to investigate the influence of maternal inheritance on the daughter's bone mass and to assess whether these influences differ according to the daughter's body mass index (BMI). METHODS: We used data obtained from the 2010 Korean National Health and Nutrition Examination Survey V and included 187 mother-daughter pairs. Bone mineral density (BMD) was measured at the lumbar spine (LS), femur neck (FN), and total hip (TH) by using dual-energy X-ray absorptiometry (DXA). The daughter group was stratified into two groups according to the mean BMI (21.4 kg/m(2)). RESULTS: The daughters' BMD correlated significantly with both their BMI and their mothers' Z-score for each skeletal site. In the daughters with a lower BMI (≤21.4 kg/m(2)), the BMDs at the FN and TH were affected more by the mothers' Z-score than by the daughters' BMI. Meanwhile, the influence of the daughters' BMI on their BMD was higher than that of their mothers' Z-score in daughters with a higher BMI (>21.4 kg/m(2)). Moreover, the mothers' Z-scores were a significant predictor of their daughters having Z-scores < -1.0 only in daughters with a lower BMI. CONCLUSIONS: This study suggests that maternal inheritance is an important determinant of the daughters' bone mass, but that this hereditary factor may vary according to the daughters' BMI.
Assuntos
Índice de Massa Corporal , Densidade Óssea/genética , Absorciometria de Fóton , Adulto , Feminino , Colo do Fêmur/diagnóstico por imagem , Quadril/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Mães , Núcleo Familiar , Inquéritos Nutricionais , República da Coreia , Adulto JovemRESUMO
SUMMARY: Our study showed that serum osteocalcin levels are closely related to glucose metabolism in men of all ages and younger women. This association disappeared in postmenopausal women in which increases bone turnover rates. The association between serum osteocalcin levels and glucose homeostasis should be interpreted according to age and sex. INTRODUCTION: Osteocalcin, a marker of bone formation, appears to be associated with glucose homeostasis. We investigated the age- and sex-specific association of serum osteocalcin level with variables related to glucose metabolism. METHODS: This study was based on cross-sectional analysis from 719 participants aged 20-85 years after excluding patients taking antidiabetic or antiosteoporotic drugs. The subjects were divided into four groups according to age and sex as follows: men <50 years (n = 131), men ≥50 years (n = 191), women <50 years (n = 108), and women ≥50 years (n = 279). Anthropometric and biochemical variables including insulin resistance (HOMA-IR) and ß cell function (HOMA-ß) from a 75-g oral glucose tolerance test, and serum 25-OH-vitamin D and parathyroid hormone levels were measured. RESULTS: The serum osteocalcin level was significantly higher in women aged ≥50 years compared with women <50 years (20.4 ± 7.8 vs. 17.9 ± 6.8 ng/ml, p < 0.001), but there was no difference between men aged ≥50 years and men <50 years (16.4 ± 5.9 vs. 16.8 ± 6.0 ng/ml, p = 0.905). The participants diagnosed with diabetes had lower serum osteocalcin levels than normal or prediabetic participants. Multivariable regression analyses including HOMA-IR and HOMA-ß indicated that serum osteocalcin levels had a negative and independent association with HbA1c levels in men and women aged <50 years, but not in women ≥50 years. CONCLUSIONS: Low osteocalcin levels are associated with impaired glucose metabolism in men and premenopausal women. The osteocalcin levels may be determined by factors related to bone metabolism in postmenopausal women. Our data suggest that the serum levels of osteocalcin associated with glucose homeostasis should be interpreted according to age and sex.
Assuntos
Envelhecimento/sangue , Glicemia/metabolismo , Osteocalcina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Estudos Transversais , Feminino , Teste de Tolerância a Glucose/métodos , Hemoglobinas Glicadas/análise , Homeostase/fisiologia , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Adulto JovemRESUMO
We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Resistência à Insulina , Pirazóis/uso terapêutico , Tiazolidinas/uso terapêutico , Administração Oral , Glicemia/análise , Terapia Combinada/efeitos adversos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/terapia , Dieta para Diabéticos , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Método Duplo-Cego , Exercício Físico , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/epidemiologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Incidência , Cooperação do Paciente , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , República da Coreia/epidemiologia , Tiazolidinas/administração & dosagem , Tiazolidinas/efeitos adversos , Fatores de TempoRESUMO
OBJECTIVE: The association of low vitamin D status with mild cognitive impairment (MCI), a preclinical condition that can lead to dementia, has not yet been fully explored. Our aim was to investigate the association between vitamin D status and the future risk of MCI and dementia in older adults. DESIGN, SETTING AND PARTICIPANTS: We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Four hundred and twelve elderly participants who completed evaluations of cognitive function and metabolic parameters in 2005-2006 and 2010-2011 were analysed. MAJOR OUTCOME MEASURE: The rate of development of MCI or dementia during the study period was compared according to baseline vitamin D status. Binary logistic regression analysis was performed to investigate any independent association between vitamin D status and the risks of MCI or dementia. RESULTS: Among 405 subjects that remained after excluding seven demented subjects at baseline, 338 subjects remained unchanged or improved in their diagnosis for cognitive function during the study period, whereas 67 subjects showed progression to MCI or dementia. When analyzing 236 subjects whose baseline mini-mental state examination (MMSE) scores were <27, severe vitamin D deficiency at baseline, defined as <25 nmol/l, was independently associated with the progression of cognitive impairment. Among 297 subjects who were normal at baseline, 50 acquired MCI and 247 remained normal. Severe vitamin D deficiency was also independently associated with the development of MCI when analyzing 145 subjects whose baseline MMSE scores were <27. CONCLUSION: Severe vitamin D deficiency was independently associated with the future risk of MCI as well as dementia, especially in older adults whose baseline MMSE scores had decreased only modestly.
Assuntos
Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/sangue , Demência/sangue , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
UNLABELLED: Dietary vitamin C intake showed significant positive associations with BMD in postmenopausal women, especially with vitamin D deficiency. INTRODUCTION: Although there is a positive role of vitamin C in osteoblastogenesis, debate remains about the contribution of vitamin C to bone mineral density (BMD) in humans. METHODS: Data were derived from the Fourth Korean National Health and Nutrition Examination Survey. Dietary information was assessed using a 24-h dietary recall questionnaire. BMD was measured by dual-energy X-ray absorptiometry at the lumbar and hip. RESULTS: A total of 1,196 postmenopausal women aged 50 years and older were stratified into tertiles by daily dietary vitamin C intake. After adjusting for traditional confounders, dietary vitamin C intake tertile was significantly positively associated with BMD at all sites (R = 0.513 for lumbar spine (LS) and R = 0.657 for femoral neck (FN), P < 0.05 for each). The subjects with osteoporosis had significantly lower dietary vitamin C intake than did subjects without osteoporosis (74.4 ± 66.2 vs 94.1 ± 78.6 mg/day for LS and 65.5 ± 56.6 vs 94.3 ± 79.2 mg/day for FN, respectively, P < 0.001). The multiple-adjusted odds ratio for osteoporosis for dietary vitamin C <100 mg/day was 1.790 (95 % CI 1.333-2.405, P < 0.001). However, the significant association between vitamin C intake and BMD was only observed in subjects with vitamin D deficiency and aged 50-59 years or >70 years. CONCLUSION: Dietary vitamin C intake was positively associated with BMD in postmenopausal women, and inadequate vitamin C intake could increase the risk of osteoporosis.
Assuntos
Ácido Ascórbico/farmacologia , Densidade Óssea/efeitos dos fármacos , Dieta/estatística & dados numéricos , Pós-Menopausa/fisiologia , Vitamina D/análogos & derivados , Absorciometria de Fóton/métodos , Idoso , Ácido Ascórbico/administração & dosagem , Densidade Óssea/fisiologia , Estudos Transversais , Feminino , Articulação do Quadril/fisiologia , Humanos , Vértebras Lombares/fisiologia , Pessoa de Meia-Idade , Inquéritos Nutricionais , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/etiologia , Osteoporose Pós-Menopausa/fisiopatologia , Osteoporose Pós-Menopausa/prevenção & controle , Pós-Menopausa/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/fisiopatologiaRESUMO
The aim of the present study was to assess the efficacy and safety of teneligliptin in combination with metformin in Korean patients with type 2 diabetes mellitus who were inadequately controlled with metformin monotherapy. Patients [glycated haemoglobin (HbA1c) 7.0-10.0%, on stable metformin ≥1000 mg/day] were randomized 2 : 1 to receive 20 mg teneligliptin plus metformin (n = 136) or placebo plus metformin (n = 68). The primary endpoint was the change in HbA1c levels from baseline to week 16. The mean baseline HbA1c was 7.9% in the teneligliptin group and 7.8% in the placebo group. The differences between the teneligliptin and placebo groups regarding changes in HbA1c and fasting plasma glucose levels were -0.78 % and -1.24 mmol/l (22.42 mg/dl), respectively, at week 16. The incidence of adverse events was similar between the groups. The addition of teneligliptin once daily to metformin was effective and generally well tolerated in Korean patients with type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Pirazóis/uso terapêutico , Tiazolidinas/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada/métodos , Jejum , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , República da Coreia/etnologiaRESUMO
AIMS: This study was designed to assess the efficacy and safety of a dipeptidyl peptidase-4 inhibitor, gemigliptin versus sitagliptin added to metformin in patients with type 2 diabetes. METHODS: We conducted a double-blind, randomized, active-controlled trial in 425 Asian patients with inadequately controlled type 2 diabetes being treated with metformin alone. Eligible patients were randomized into three groups: 50 mg gemigliptin qd, 25 mg gemigliptin bid or sitagliptin 100 mg qd added to ongoing metformin treatment for 24 weeks. Haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance tests were performed at baseline and 24 weeks after starting the treatment regimen. RESULTS: Twenty-four weeks later, adding gemigliptin (50 mg/day) to ongoing metformin therapy significantly improved glycaemic control. Reduction in HbA1c caused by 50 mg gemigliptin qd (-0.77% ± 0.8) was non-inferior to that caused by 100 mg sitagliptin qd (-0.8% ± 0.85). Proportion of patients achieving HbA1c <7% while taking 25 mg gemigliptin bid (50%) or 50 mg gemigliptin qd (54.07%) was comparable to the results with 100 mg sitagliptin qd (48.87%). There were significant decreases in FPG, postprandial glucose and AUC0-2 h glucose, as well as increases in GLP-1 and ß cell sensitivity to glucose (supported by homeostasis model assessment of ß-cell function, postprandial 2-h c-peptide and insulinogenic index) in patients receiving gemigliptin treatment with their metformin therapy. There was no increased risk of adverse effects with this dose of gemigliptin compared with sitagliptin 100 mg qd. CONCLUSIONS: Addition of gemigliptin 50 mg daily to metformin was shown to be efficacious, well tolerated and non-inferior to sitagliptin in patients with type 2 diabetes mellitus.
Assuntos
Povo Asiático , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Piperidonas/uso terapêutico , Pirazinas/uso terapêutico , Pirimidinas/uso terapêutico , Triazóis/uso terapêutico , Adolescente , Adulto , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Método Duplo-Cego , Jejum , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Comportamento de Redução do Risco , Fosfato de Sitagliptina , Resultado do TratamentoRESUMO
AIMS: The study investigated the clinical equivalence in reducing haemoglobin A1c (A1C) between glimepiride/metformin sustained release (GM-SR) 2/500 mg, a fixed-dose combination, once daily and glimepiride/metformin (GM) 1/250 mg, a fixed-dose combination, twice daily in patients with type 2 diabetes (T2D). METHODS: A multicentre, randomised, double-blind, double-dummy study was conducted in 14 hospitals in Korea. Inclusion criteria were age 30-75 years, T2D diagnosis no longer than 10 years previously, A1C between 7% and 10%, and body mass index <40 kg/m(2) . A total of 207 subjects were randomised into the GM-SR group (n=101) or the GM group (n=106). Participants were assessed at baseline, 8 weeks and 16 weeks after treatment. RESULTS: After 16 weeks treatment, no difference in baseline-adjusted changes of A1C (primary efficacy variable) was observed between the two groups (-0.59% for GM-SR group vs. -0.61% for GM group, 95% CI: -0.17 to 0.21; p=0.84). In addition, there were no significant differences in secondary efficacy parameters between the two groups, including changes in A1C up to week 8, changes in fasting plasma glucose (FPG) and 2-h-postprandial plasma glucose up to week 8 and week 16, response rate, drug compliance and hypoglycaemic events. However, there was a difference in baseline-adjusted changes of FPG between the two groups (-1.01 mmol/l for GM-SR group vs. -1.52 mmol/l for GM group, p=0.01 in the intention to treat set). CONCLUSIONS: GM-SR 2/500 mg once daily was as effective as GM 1/250 mg twice daily in lowering A1C. In addition, no difference was noted in hypoglycaemic events between the two groups.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Compostos de Sulfonilureia/administração & dosagem , Adulto , Idoso , Glicemia/metabolismo , Preparações de Ação Retardada , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Esquema de Medicação , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Adesão à Medicação , Metformina/efeitos adversos , Pessoa de Meia-Idade , Compostos de Sulfonilureia/efeitos adversos , Resultado do TratamentoRESUMO
AIM: Individuals requiring insulin therapy for type 2 diabetes often require escalation of their regimen to achieve glycaemic control. Optimal management strategies for uncontrolled type 2 diabetes would improve glycaemic control without hypoglycaemia and weight gain. This study compared the efficacy and tolerability of adding sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, and an up to 20% increase in insulin dose in patients with uncontrolled type 2 diabetes on insulin therapy. METHODS: We conducted a 24-week, randomized, active-competitor, parallel-group study in subjects with uncontrolled type 2 diabetes [haemoglobin A1c (HbA1c) = 7.5-11%] currently using insulin therapy. Subjects were randomly assigned to either the sitagliptin adding (100 mg daily, n = 70) or an insulin-increasing arm (≥ 10% at week 12 and ≥ 10% at week 24, n = 70) while continuing other medications. RESULTS: Average baseline HbA1c was 9.2% in both groups. HbA1c decreased more at 24 weeks in the sitagliptin adding than the insulin-increasing arm (-0.6 ± 0.1% vs. -0.2 ± 0.1%, p < 0.01). Insulin was increased by 25% at 24 weeks in the insulin-increasing group. Hypoglycaemic events were less common and less severe in sitagliptin adding arm than insulin-increasing arm (7.0 vs. 14.3 events per patient-year, p < 0.05). Weight was stable in the sitagliptin adding subjects (68.6 ± 11.6 vs. 68.1 ± 11.4 kg) but increased in the insulin-increasing subjects (66.2 ± 10.6 vs. 67.4 ± 9.7 kg, p < 0.05). Other adverse events occurred at similar rates in both arms. CONCLUSIONS: Compared to a 25% increase in insulin dose, adding sitagliptin to an insulin-based regimen was more effective at lowering HbA1c and associated with less hypoglycaemia and weight gain over 24 weeks. CLINICAL TRIAL NUMBER: NCT01100125.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Pirazinas/administração & dosagem , Triazóis/administração & dosagem , Adulto , Idoso , Peso Corporal , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Jejum/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pirazinas/efeitos adversos , Fosfato de Sitagliptina , Triazóis/efeitos adversos , Circunferência da CinturaRESUMO
This study was performed to determine the effects of dietary fat sources, i.e., beef tallow, soybean oil, olive oil and coconut oil (each 3% in feed), on the growth performance, meat quality and gene expression in growing-finishing pigs. A total of 72 crossbred pigs (Landrace×Large White×Duroc) were used at 71±1 kg body weight (about 130 d of age) in 24 pens (320×150 cm) in a confined pig house (three pigs per pen) with six replicate pens per treatment. The growing diet was given for periods of 14±3 d and the finishing diet was given for periods of 28±3 d. The fat type had no significant effect either on growth performance or on chemical composition or on meat quality in growing-finishing pigs. Dietary fat type affected fatty acid composition, with higher levels of unsaturated fatty acids (UFAs) and monounsaturated fatty acids (MUFAs) in the olive oil group. Microarray analysis in the Longissimus dorsi identified 6 genes, related to insulin signaling pathway, that were differentially expressed among the different feed groups. Real time-PCR was conducted on the six genes in the longissimus dorsi muscle (LM). In particular, the genes encoding the protein kinase, cAMP-dependent, regulatory, type II, alpha (PRKAR2A) and the catalytic subunit of protein phosphatase 1, beta isoform (PPP1CB) showed the highest expression level in the olive oil group (respectively, p<0.05, p<0.001). The results of this study indicate that the type of dietary fat affects fatty acid composition and insulin signaling-related gene expression in the LM of pigs.
RESUMO
AIMS/HYPOTHESIS: New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). METHODS: The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A-CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls. RESULTS: Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34-1.79, p = 4.17 x 10(-9)) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29-1.72, p = 1.05 x 10(-7)) in the CDKN2A-CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09-1.49, p = 0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01-1.38, p = 0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07-1.43, p = 0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03-2.43, p = 0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A-CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM. CONCLUSIONS/INTERPRETATION: Some of the type 2 diabetes-associated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.
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Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Variação Genética , Genoma Humano , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Mapeamento Cromossômico , Feminino , Humanos , Coreia (Geográfico) , Masculino , Gravidez , Proteínas/genética , Proteínas de Ligação a RNA/genéticaRESUMO
AIMS: To evaluate the efficacy, safety and treatment satisfaction with biphasic insulin aspart 30 (BIAsp30) in elderly patients with type 2 diabetes. METHODS: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 0 Therapy Korea study was a 6-month, prospective, observational study. No study-specific interventions were involved except the collection of data. All patients with type 2 diabetes not adequately controlled on their previous therapy, and who were prescribed BIAsp30 as monotherapy, or in combination with oral hypoglycaemic agents, were eligible for the study. This subgroup analysis was based on the outcomes in patients > or years (n = 1720). RESULTS: BIAsp30 treatment was associated with significant mean reductions in haemoglobin A1c, fasting plasma glucose and post-prandial plasma glucose levels of 1.2 +/- 1.6%, 2.3 +/- 3.5 mmol/l and 4.8 +/- 5.3 mmol/l at 6 months (p < 0.0001 for all), from baseline levels of 9.1 +/- 1.7%, 10.7 +/- 3.4 mmol/l and 16.7 +/- 5.0 mmol/l, respectively. The rate of hypoglycaemia declined from 3.02 to 1.31 episodes per patient year, between baseline and study end. The proportion of patients reporting adverse drug reactions was low (0.3 and 0.1% at 3 and 6 months, respectively). Body weight gain was mild at <0.1 kg at 3 months, and 0.3 kg at 6 months. As compared to the previous treatment, >80% of patients were rated as being either 'very satisfied' or 'satisfied' with BIAsp30 treatment. CONCLUSIONS: In this subanalysis of Korean elderly patients with type 2 diabetes inadequately controlled on their previous therapies, treatment with BIAsp30 offered improvements in glycaemic control and was well tolerated. Body weight gain was minimal with BIAsp30, and treatment satisfaction among these patients appeared to be high.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Adulto , Idoso , Insulinas Bifásicas , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Aspart , Insulina Isófana , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Prandial , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To assess the outcome of Staphylococcus aureus bacteraemia (SAB) according to factors associated with necessity for longer treatment in conjunction with the duration of treatment. METHODS: We prospectively collected the data of patients with SAB consecutively during 12 to 39 months from 11 hospitals. If multiple episodes of SAB occurred in one patient, only the first episode was enrolled. Factors associated with necessity for longer treatment were defined as follows: persistent bacteraemia, metastatic infection, prosthesis and endocarditis. If any of the factors were present, then the case was defined as longer antibiotic treatment warranted (LW) group; those without any factors were defined as shorter antibiotic treatment sufficient (SS) group. Poor outcome was defined as a composite of 90-day mortality or 30-day recurrence. Duration of antibiotic administration was classified as <14 or ≥14 days in the SS group and <28 or ≥28 days in the LW group. RESULTS: Among 2098 cases, the outcome was analysed in 1866 cases, of which 591 showed poor outcome. The SS group accounted for 964 cases and the LW group for 852. On multivariate analysis, age over 65 years, pneumonia, higher Sequential Organ Failure Assessment (SOFA) score and chronic liver diseases were risk factors for poor outcome. Administration of antibiotics less than the recommendation was associated with poor outcome, but this significance was observed only in the LW group (adjusted odds ratio = 1.68; 95% confidence interval, 1.00-2.83; p 0.05). CONCLUSIONS: Inappropriately short antibiotic treatment was associated with poor outcome in the LW group. Vigilant evaluation for risk factors to determine the duration of treatment may improve the outcome among patients with SAB.
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Anti-Infecciosos/administração & dosagem , Bacteriemia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Infecções Estafilocócicas/mortalidade , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To determine whether hearing loss is associated with social frailty in older adults. METHODS: Cross-sectional analysis of cohort study data. Hearing was measured using of Pure-tone audiometry. Hearing loss was determined based on the average of hearing thresholds at 0.5, 1, and 2 kHz in the ear that had better hearing. Social frailty was defined based on the summation of the following 5 social components (1. Neighborhood meeting attendance 2. Talking to friend(s) sometimes 3.Someone gives you love and affection 4. Living alone 5. Meeting someone every day). Participants who had no correspondence to the components were considered non-social frailty; those with 1-2 components were considered social prefrailty; and those having 3 or more components were considered social frailty. RESULTS: The prevalence of non-social frailty, social prefrailty, social frailty was 27.6%, 60.7% and 11.7% respectively. Of the five questions, two components (Neighborhood meeting attendance and Presence of someone who shows love and affection to the participants) were associated with hearing loss (p < 0.001). Compared to non-social frailty, the odds ratio of social frailty for hearing loss was 2.24 (95% CI 1.48-3.38) after adjusting for age, residential area, economic status, smoking, depressive disorder and MMSE, and 2.17 (95% CI 1.43-3.30) after further adjustments with physical frailty. CONCLUSION: Hearing loss was associated with social frailty even after controlling confounding factors even including physical frailty.
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Fragilidade , Perda Auditiva/epidemiologia , Vida Independente , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , MasculinoRESUMO
AIM: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study aims to assess the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice. METHODS: This was a 6-month, prospective, multinational, multiethnic observational study involving 21 977 patients from 13 countries (India, Iraq, Jordan, Kuwait, Lebanon, Qatar, Romania, Russia, Saudi Arabia, South Africa, South Korea, Turkey and the United Arab Emirates). The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs) from prior treatment with OAD (n = 8583), insulin (n = 5942), OAD + insulin (n = 4673) or diet (i.e. treatment naive) (n = 1707). One thousand and seventy-two patients had incomplete or no information on previous treatment. RESULTS: At 3 and 6 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-1.33 and -1.81%), fasting plasma glucose (-3.02 and -3.74 mmol/l) and postprandial plasma glucose (-4.76 and -5.82 mmol/l) (p < 0.001). A significantly greater proportion of patients achieved target HbA(1c) of less than 7% at 3 months (15.3%) and 6 months (27.7%) compared with baseline (4.8%) (p < 0.001). Overall, the mean HbA(1c) at 6 months was lowered in patients regardless of prior treatment: -2.15% (OAD), -1.45% (insulin), -1.47% (OAD + insulin) and -2.35% (treatment naive). In the overall cohort, the rate of total hypoglycaemia was reduced from 5.4 events per patient-year at baseline to 2.2 events per patient-year at study end (p < 0.001). Among prior treatment subgroups, the rates of total hypoglycaemia were reduced from 2.5 to 2.1 events per patient-year in the OAD group, from 9.6 to 2.2 events per patient-year in the insulin group and from 7.6 to 2.5 events per patient-year in the OAD + insulin group but were increased from 1.0 to 1.8 events per patient-year in the treatment-naive group (p < 0.001). There were 444 adverse drug reactions (ADRs), including 13 serious ADRs: lipodystrophy (three events), symptoms of generalized hypersensitivity (two events), acute painful neuropathy (one event), worsening of diabetic retinopathy (one event), oedema (one event) and unspecified ADRs (five events). CONCLUSION: The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in patients with poorly controlled type 2 diabetes mellitus.
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Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Insulinas Bifásicas , Diabetes Mellitus Tipo 2/sangue , Medicina de Família e Comunidade , Humanos , Hipoglicemia/metabolismo , Insulina/sangue , Insulina/uso terapêutico , Insulina Aspart , Insulina Isófana , Resultado do TratamentoRESUMO
The aim of this study was to compare the prevalence and pattern of metabolic syndrome in children and adolescents in the interval between the Korean National Health and Nutrition Examination Surveys (KNHANES) in 1998 and 2001. Two nationwide surveys (KNHANES) were conducted in Korea in 1998 and 2001. A stratified multistage probability sampling design was used to ensure representation of the entire Korean population. The National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III)-derived definition was used for the definition of metabolic syndrome. A total of 1763 (mean age+/-SD of 14.6+/-2.8 yr) and 1245 (14.1+/-2.8 yr) Korean children and adolescents in the age range 10-19 yr participated in the studies of 1998 and 2001, respectively. The prevalence of metabolic syndrome in male children and adolescents increased significantly from 5.7% in 1998 to 9.0% in 2001. However, there was no increase in females (5.1% in 1998 and 4.9% in 2001). Of the 5 components of metabolic syndrome, low HDL-cholesterolemia showed the highest increase in males and females during the 3 yr. Hypertriglyceridemia increased next in both genders. In contrast, the proportion of female subjects meeting the fasting glucose criterion decreased over the same period. As dyslipidemia was the principal contributor to the increase in metabolic syndrome in Korean male children and adolescents during the 3 yr, a strategy of dietary pattern change and the encouragement of physical activity should be introduced to these groups at a national level.
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Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Criança , Gorduras na Dieta/efeitos adversos , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Estilo de Vida , Masculino , Síndrome Metabólica/prevenção & controle , Fatores de RiscoRESUMO
AIMS: The aim of this analysis was to assess the efficacy and safety of intensifying insulin therapy from a basal-only regimen to biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes previously failing to reach glycaemic targets. METHODS AND PATIENTS: The analysis is based on data from a subpopulation of the Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study, which was a 6-month observational study in 15 countries. This subanalysis included patients previously receiving long-acting analogue insulin (AB; n = 348), or human basal insulin (long and intermediate acting) (HB; n = 3414), who were transferred to BIAsp 30. Efficacy end-points included change in glycated haemoglobin (HbA(1c)), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), from baseline to the end of the study. Episodes of hypoglycaemia, adverse events, and physician and patient satisfaction were also recorded. End-points were considered separately by previous basal regimen (AB or HB). RESULTS: After 6 months' treatment with BIAsp 30, HbA(1c) was significantly lowered in both groups (-1.60% and -1.42% in the AB and HB groups; p < 0.0001 compared with baseline). Reductions in FPG and PPG were also statistically significant in both groups. The rate (events/patient/year) of overall hypoglycaemia remained relatively constant in patients switching from AB, but it was statistically lower in patients switching from HB (change from baseline -3.8; p < 0.001). CONCLUSION: In routine clinical practice, patients with type 2 diabetes who are failing to reach glycaemic targets on basal insulin can achieve better glycaemic control without an increase in overall hypoglycaemia by intensifying with BIAsp 30.