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1.
Diabetes Obes Metab ; 20(4): 954-962, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29205856

RESUMO

AIMS: To describe the real-world use and effectiveness of IDegLira, a fixed-ratio combination of the basal insulin degludec, and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide. MATERIALS AND METHODS: This European, multicentre, retrospective chart review comprised adults (n = 611) with type 2 diabetes, who started IDegLira ≥6 months before data collection. Clinical characteristics were assessed at baseline (defined as the most recent recording during the 6 months before the first IDegLira prescription) and 3, 6, 9 and 12 months (± 45 days for each time point) after commencing IDegLira, where data were available. RESULTS: Baseline regimens included non-injectable medications (19%), basal insulin (19%), GLP-1RA (10%), free combination therapy (insulin/GLP-1RA, 24%) and multiple daily-dose insulin injections (MDI, 28%), all ± oral antidiabetic drugs. After 6 months, significant glycated haemoglobin (HbA1c) reductions were observed in patients overall and in all subgroups (-10 mmol/mol [-0.9%] overall; P < .0001), and a significant reduction in mean body weight (-0.7 kg; P < .05) was observed in patients overall and in patients receiving MDI (-2.4 kg; P < .0001). The mean IDegLira dose was 22, 30 and 32 dose steps at initiation, and at 6 and 12 months follow-up, respectively. In total, only 67 patients reached the maximum 50 dose steps, with most coming from the free combination therapy (n = 31) or MDI (n = 15) baseline regimen groups. Hypoglycaemia rates were reduced by 82% (rate ratio 0.18; P < .0001) in the 6-month period after vs before IDegLira initiation. Overall, a total of 12 patients experienced 15 events in the 6 months after IDegLira initiation. CONCLUSION: In real-world practice, after 6 months and at a moderate dose, IDegLira resulted in substantial reductions in HbA1c and body weight, with a reduced risk of hypoglycaemia.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina de Ação Prolongada/uso terapêutico , Liraglutida/uso terapêutico , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Combinação de Medicamentos , Europa (Continente) , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/administração & dosagem , Liraglutida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
2.
Diabetes Obes Metab ; 20(3): 689-697, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29106039

RESUMO

AIMS: To evaluate the clinical effectiveness of switching to insulin degludec (IDeg) in insulin-treated patients with either type 1 diabetes (T1DM) or type 2 diabetes (T2DM) under conditions of routine clinical care. MATERIALS AND METHODS: This was a multicentre, retrospective, chart review study. In all patients, basal insulin was switched to IDeg at least 6 months before the start of data collection. Baseline was defined as the most recent recording during the 3-month period before first prescription of IDeg. Values are presented as mean [95%CI]. RESULTS: T1DM (n = 1717): HbA1c decreased by -2.2 [-2.6; -2.0] mmol/mol (-0.20 [-0.24; -0.17]%) at 6 months vs baseline (P < .001). Rate ratio of overall (0.79 [0.69; 0.89]), non-severe nocturnal (0.54 [0.42; 0.69]) and severe (0.15 [0.09; 0.24]) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period (P < .001 for all). Total daily insulin dose decreased by -4.88 [-5.52; -4.24] U (-11%) at 6 months vs baseline (P < .001). T2DM (n = 833): HbA1c decreased by -5.6 [-6.3; -4.7] mmol/mol (-0.51 [-0.58; -0.43] %) at 6 months vs baseline (P < .001). Rate ratio of overall (0.39 [0.27; 0.58], P < .001), non-severe nocturnal (0.10 [0.06; 0.16], P < .001) and severe (0.075 [0.01; 0.43], P = .004) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period. Total daily insulin dose decreased by -2.48 [-4.24; -0.71] U (-3%) at 6 months vs baseline (P = .006). Clinical outcomes for T1DM and T2DM at 12 months were consistent with results at 6 months. CONCLUSIONS: This study demonstrates that switching patients to IDeg from other basal insulins improves glycaemic control and significantly reduces the risk of hypoglycaemia in routine clinical practice.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Administração Oral , Idoso , Peso Corporal/efeitos dos fármacos , Esquema de Medicação , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Insulinas/administração & dosagem , Insulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
3.
Diabetes Obes Metab ; 19(6): 858-865, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28124817

RESUMO

AIMS: To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n = 210). RESULTS: Mean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once-weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [-0.04; 0.28]95%CI , 1.30 mmol/mol [-0.41; 3.01]95%CI ). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was -1.0 kg vs -2.0 kg for once-weekly vs twice-weekly titration. Rates of severe or blood glucose-confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient-year of exposure (PYE) for once-weekly, 0.76 events/PYE for twice-weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once-weekly and twice-weekly titration, respectively. CONCLUSION: A pragmatic titration algorithm with once-weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice-weekly adjustments based on 3 preceding PG values in insulin-naïve patients.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Liraglutida/administração & dosagem , Metformina/administração & dosagem , Tiazolidinedionas/administração & dosagem , Idoso , Algoritmos , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Pioglitazona , Resultado do Tratamento
4.
Clin Chem ; 62(12): 1612-1620, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27756762

RESUMO

BACKGROUND: Diabetes has been linked epidemiologically to increased cancer incidence and mortality. Growth differentiation factor 15 (GDF-15) is increased in patients with diabetes and has recently been linked to the occurrence of cancer. We investigated whether circulating GDF-15 concentrations can predict the incidence of malignant diseases in a diabetic patient cohort already facing increased risk for cancer. METHODS: We prospectively enrolled a total of 919 patients with type 2 diabetes and no history of malignant disease, who were clinically followed up for 60 months. GDF-15, N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline; an additional 4 cardiovascular biomarkers were determined for a subpopulation (n = 259). Study end point was defined as the first diagnosis of any type of cancer during the follow-up period. RESULTS: During a median follow-up of 60 months, 66 patients (7.2%) were diagnosed with cancer. Baseline circulating GDF-15 concentrations were higher in patients that developed cancer over the follow-up period when compared to cancer-free patients. Increased GDF-15 concentrations were significantly associated with cancer incidence [crude hazard ratio (HR) per 1-IQR (interquartile range) increase 2.13, 95% CI 1.53-2.97, P < 0.001]. This effect persisted after multivariate adjustment with an adjusted HR of 1.86 (95% CI 1.22-2.84; P = 0.004). Among the 4 additionally tested cardiovascular markers in the subpopulation, only troponin T and C-terminal proendothelin-1 showed a significant association with future cancer incidence with unadjusted HRs of 1.71 (95% CI 1.28-2.28, P < 0.001) and 1.68 (95% CI 1.02-2.76, P = 0.042), respectively. CONCLUSIONS: Increased circulating concentrations of GDF-15 are associated with increased cancer incidence in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Fator 15 de Diferenciação de Crescimento/sangue , Neoplasias/sangue , Neoplasias/complicações , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico
5.
N Engl J Med ; 362(16): 1463-76, 2010 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-20228402

RESUMO

BACKGROUND: The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS: In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS: After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)


Assuntos
Doenças Cardiovasculares/prevenção & controle , Cicloexanos/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fenilalanina/análogos & derivados , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Glicemia/análise , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Cicloexanos/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Exercício Físico , Feminino , Seguimentos , Intolerância à Glucose/dietoterapia , Intolerância à Glucose/terapia , Humanos , Hipoglicemiantes/efeitos adversos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nateglinida , Fenilalanina/efeitos adversos , Fenilalanina/uso terapêutico , Modelos de Riscos Proporcionais , Fatores de Risco , Tetrazóis/uso terapêutico , Falha de Tratamento , Valina/análogos & derivados , Valina/uso terapêutico , Valsartana
6.
N Engl J Med ; 362(16): 1477-90, 2010 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-20228403

RESUMO

BACKGROUND: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Intolerância à Glucose/tratamento farmacológico , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Glicemia/análise , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Cicloexanos/uso terapêutico , Diabetes Mellitus Tipo 2/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Exercício Físico , Feminino , Seguimentos , Intolerância à Glucose/dietoterapia , Intolerância à Glucose/terapia , Humanos , Hipoglicemiantes/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Nateglinida , Fenilalanina/análogos & derivados , Fenilalanina/uso terapêutico , Modelos de Riscos Proporcionais , Fatores de Risco , Tetrazóis/efeitos adversos , Valina/efeitos adversos , Valina/uso terapêutico , Valsartana
7.
Wien Med Wochenschr ; 163(23-24): 528-35, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23979353

RESUMO

UNLABELLED: Low density lipoprotein (LDL-C) levels determine the cardiovascular risk. Previous studies indicated an LDL-C target attainment of around 50%, but no Austrian wide analysis on results for the federal states was available. We therefore sought to detect potential differences. DESIGN: Open-label, non-interventional, longitudinal study, registered: www.clinicaltrials.gov NCT 01381679. In all, 746 statin treated patients not at LDL-C goal received intensified therapy for 12 months. The sample was split into nine subgroups, representing the federal states of Austria.We detected an east-west gradient for baseline LDL-C. Individual target values were achieved by 37.2% (range: 26.1-57.7%). After 12 months, LDL-C < 70 mg/l was achieved by 13.5% (5.9-38.5%). Univariate ANCOVA retrieved significant differences within the states (Upper Austria and Salzburg, p = 0.001 and p = 0.0015, respectively). Furthermore, the capacity of intensified lipid lowering therapy applied in practice was as high as -42% as compared to previous standard therapy (additional LDL-C reduction after switch from baseline therapy in Vorarlberg).


Assuntos
Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , LDL-Colesterol/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Idoso , Áustria , Estudos Transversais , Resistência a Medicamentos , Ezetimiba , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Retratamento , Topografia Médica
10.
Wien Klin Wochenschr ; 135(Suppl 1): 32-44, 2023 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-37101023

RESUMO

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Humanos , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia/tratamento farmacológico , Glicemia
11.
Eur J Clin Invest ; 41(12): 1292-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21615391

RESUMO

BACKGROUND: Patients with diabetes mellitus have a substantially increased risk of developing cardiovascular disease. However, the absolute risk greatly varies not only among patients, but the risk profile for an individual patient may also change over time. We investigated the prognostic role of repetitive measurements of Glycated haemoglobin A(1c) (HbA(1c) ) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with longstanding diabetes. MATERIALS AND METHODS: For this prospective, observational study data from 544 consecutive patients were collected between 2005 and 2008. HbA(1c) and NT-proBNP were measured at baseline and after 1 year. The median observation period was 40 months. Endpoints were all-cause mortality, cardiac, cardiovascular and all-cause hospitalizations. RESULTS: N-terminal pro-B-type natriuretic peptide concentrations significantly increased from 230 ± 385 to 280 ± 449 pg mL(-1) (P < 0·001); during the same time, HbA(1c) significantly decreased from 7·6 ± 1·5 to 7·3 ± 1·2 (P < 0·001). NT-proBNP was the best baseline predictor in a Cox regression model consisting of NT-proBNP, HbA(1c) , age, gender and duration of diabetes for all endpoints (P < 0·001). NT-proBNP at follow-up was the best predictor for the remaining period (P < 0·001, all endpoints). HbA(1c) at baseline and follow-up was predictive for all-cause hospitalizations (P = 0·005 both). In a third model that investigated the plasticity of both markers, changes in HbA(1c) concentration had no predictive value, but a change of NT-proBNP concentration was highly predictive (P = 0·025 all-cause mortality, P < 0·001 all other endpoints). CONCLUSIONS: N-terminal pro-B-type natriuretic peptide and HbA(1c) concentrations significantly diverged over a 1-year period. NT-proBNP was the most potent predictor of outcome at baseline and follow-up, and changes in NT-proBNP concentrations were linked to an altered risk profile, unlike changes in HbA(1c) levels.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/metabolismo , Peptídeo Natriurético Encefálico/sangue , Idoso , Biomarcadores/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Regressão , Fatores de Risco
12.
Eur J Cardiovasc Prev Rehabil ; 18(3): 399-405, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21450658

RESUMO

NT-proBNP is an excellent predictor of adverse events in patients with diabetes mellitus. Due to an aging population it is of interest to determine whether NT-proBNP can predict cardiac events with equal precision in subgroups with different ages. 1395 outpatients with diabetes mellitus were recruited for this prospective observational study. NT-proBNP, renal function, lipid status and other demographic variables were measured at baseline. The cohort was divided into three groups: Group I (609 patients under 60 years of age), group II (634 patients ranging from 60-75) and group III (152 patients older than 75). Patients were followed during a mean observation period of 11 months, 75 patients reached the defined endpoint, which was unplanned hospitalization due to a cardiac event. Mean age was 60 ± 30 years, mean HbA(1c) was 7.6% and mean NT-proBNP was 242 ± 437 pg/ml. In a multiple Cox regression model, age (hazard ratio (HR) 11.18, p < 0.01) and the absence of a cardiac disease (HR 0.49, p < 0.01) were important variables for short-term prognosis. The addition of the logarithm of NT-proBNP provided independent prognostic information (HR 1.81 p < 0.01) and significantly increased the explained variance of the model (χ(2 )= 22.93; d.f. = 1; p < 0.01). More importantly, the predictive power of this model was similar in different age-groups. The prognostic information of NT-proBNP was not influenced by age and this biomarker remained a reliable predictor of short-term cardiac events in patients with diabetes mellitus aged 75 years or older.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Medição de Risco , Idoso , Áustria/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Progressão da Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Precursores de Proteínas , Fatores de Risco
13.
Clin Endocrinol (Oxf) ; 72(6): 763-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19769621

RESUMO

OBJECTIVE: In type 1 diabetes mellitus (T1DM), the release of many hormones, not only from beta-cells, but also from adipocytes (adipokines) may be altered. After successful pancreas-kidney-transplantation (PKTx), T1DM patients can revert to a nondiabetic metabolism, but it is unclear whether alterations of adipokines are still present after PKTx. DESIGN, PATIENTS AND MEASUREMENTS: Concentrations of adipokines [visfatin, retinol-binding protein-4 (RBP-4), adiponectin, high molecular weight (HMW) adiponectin] were measured at fasting in 10 PKTx and in 19 T1DM. Nondiabetic healthy controls (CON, n = 9) and six nondiabetic patients after kidney transplantation (KTx) were examined as control groups. In PKTx, KTx and CON, indices of insulin sensitivity (OGIS) and beta cell function (adaptation index, AI) were calculated from 75 g oral glucose tolerance test (OGTT) data. RESULTS: Fasting serum visfatin (T1DM: 56 +/- 4 microg/l, PKTx: 42 +/- 6 microg/l, KTx: 39 +/- 3 microg/l, CON: 40 +/- 3 microg/l) and RBP-4 (T1DM: 490 +/- 26 microg/l, PKTx: 346 +/- 39 microg/l, KTx: 401 +/- 13 microg/l, CON: 359 +/- 36 microg/l) was increased by 40% and 36%, respectively (each P < 0.03) in T1DM only. Levels were positively correlated with HbA1c in all subjects (visfatin: r = 0.43, P < 0.004; RBP-4: r = 0.46, P < 0.03). Fasting plasma adiponectin was 80% higher in T1DM and in PKTx (T1DM: 18 +/- 2 mg/l, PKTx: 18 +/- 3 mg/l, KTx: 12 +/- 3 mg/l, CON: 10 +/- 1 mg/l; P < 0.04) and was positively correlated with diabetes duration (r = 0.37, P < 0.02). HMW/total adiponectin ratio was increased in T1DM (P < 0.02). PKTx displayed a normoglycaemic metabolism as insulin sensitive as CON, but AI was lower than in CON and KT (P < 0.01). CONCLUSIONS: T1DM after successful PKTx show normal fasting visfatin and RBP-4 levels and HMW-adiponectin/adiponectin-ratio, which are elevated in T1DM, whereas total adiponectin levels are similarly increased in T1DM and PKTx patients.


Assuntos
Adipocinas/sangue , Citocinas/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/terapia , Nicotinamida Fosforribosiltransferase/sangue , Transplante de Pâncreas/reabilitação , Proteínas Plasmáticas de Ligação ao Retinol/análise , Adiponectina/sangue , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/terapia , Jejum/sangue , Feminino , Humanos , Transplante de Rim/reabilitação , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Transplante de Pâncreas/fisiologia , Regulação para Cima
14.
Eur Heart J ; 30(12): 1516-24, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19380349

RESUMO

AIMS: Obesity and type 2 diabetes are associated with increased cardiovascular risk and elevation of traditional and non-traditional risk markers. As bariatric surgery reduces overweight and improves metabolic derangement, we examined a cluster of established and emerging cardiovascular risk factors, such as soluble CD40 ligand (sCD40L) and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), which might improve prediction of future cardiovascular events because of their more direct involvement in plaque destabilization. METHODS AND RESULTS: Obese patients [n = 32, body mass index (BMI) 46.1 +/- 5.9 kg/m(2)] underwent clinical examinations and blood sampling for measurement of glucose and lipid parameters as well as non-traditional cardiovascular risk markers, i.e. high-sensitivity C-reactive protein, plasminogen activator inhibitor-1 (PAI-1), soluble cellular adhesion molecules (CAM), MMP-2, MMP-9, CD40L, and Lp-PLA(2) before and after 1 year following laparoscopic adjustable gastric banding (LAGB), respectively. In patients undergoing LAGB, blood pressure (P < 0.0001) and blood glucose (P = 0.02) were significantly lowered by approximately 16% as well as triglyceride levels by approximately 29% (P = 0.002). In addition to a decrease of the inflammatory and pro-thrombotic marker PAI-1 (P = 0.001), CAMs, and MMP-9 (P = 0.004) were reduced, whereas no change was observed for plasma levels of MMP-2, sCD40L, and Lp-PLA(2) after LAGB, respectively. Individual changes in (ICAM-1) intercellular adhesion molecule-1 (DeltaICAM-1) were related to changes in insulin (Deltafasting insulin) before and after LAGB (r = 0.36 and r = 0.38; both P = 0.04). E-selectin correlated positively with changes in BMI (r = 0.38; P = 0.04 and r = 0.36; P = 0.05), while Lp-PLA(2) concentration was negatively correlated with BMI (r =-0.41; P = 0.02) after 1 year. Changes were comparable in both overweight diabetic and non-diabetic subjects. CONCLUSION: LAGB not only induced weight loss but also an improvement in the subclinical pro-inflammatory state. However, concentrations of most of the non-traditional risk factors for plaque instability, i.e. MMP-9, sCD40L, and Lp-PLA(2) remained unchanged.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Aterosclerose/sangue , Ligante de CD40/sangue , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Obesidade Mórbida/sangue , Adulto , Aterosclerose/prevenção & controle , Aterosclerose/cirurgia , Cirurgia Bariátrica , Biomarcadores/sangue , Índice de Massa Corporal , Moléculas de Adesão Celular/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Angiopatias Diabéticas/prevenção & controle , Angiopatias Diabéticas/cirurgia , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Fatores de Risco
15.
Curr Med Res Opin ; 36(9): 1419-1425, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32568565

RESUMO

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 inhibition can be an effective treatment in patients with primary hypercholesterolemia, particularly in cases with concomitant coronary heart disease, peripheral artery occlusive disease or cerebrovascular occlusive disease for secondary prevention after an acute atherosclerotic ischemic event. The primary objective of the PEARL-AT study was to assess effectiveness and safety of alirocumab in a real-world setting in Austria. METHODS: Non-interventional, prospective study conducted across Austria between September 2016 and July 2018. 113 patients, for whom the decision for treatment with alirocumab according to the Austrian Summary of Product Characteristics (SmPC) was made, were enrolled and were followed-up over 24 weeks. The primary endpoint of the study was the average change of low density lipoprotein cholesterol (LDL-C) levels by week 24. RESULTS: In total, 112 patients with at least one post-baseline visit were included. Alirocumab was initiated using 75 mg (57.1%) and 150 mg (42.9%) every two weeks. Average LDL-C levels decreased by 75.0 mg/dl at week 24 in 87 patients with available LDL-C at baseline and week 24 (in 25 patients LDL-C was missing at least at one time point). The mean relative change of LDL-C was -50.0% (median: 57.8%, SD: 28.4). Throughout the study, 46 adverse events were documented in 21 (18.6%) patients. The most frequent adverse events were gastrointestinal disorders. CONCLUSIONS: The present data indicate a good overall efficacy of alirocumab in a real-world Austrian population. Effectiveness and safety were both in line with the clinical trial program as well as previous real-world observations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Inibidores de PCSK9 , Anticorpos Monoclonais Humanizados/efeitos adversos , LDL-Colesterol/sangue , Feminino , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Eur Heart J ; 29(18): 2259-64, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18650200

RESUMO

AIMS: This study evaluated the predictive value of NT-proBNP for patients with diabetes mellitus and compared the prognostic aptitude of this neurohumoral marker to traditional markers of cardiovascular events. METHODS AND RESULTS: A prospective observational study was conducted in 631 diabetic patients. The composite endpoint consisted of unplanned hospitalization for cardiovascular events or death within the observation period of 12 months. Of all variables analysed (age, gender, history of hypertension, ischaemic heart disease/any cardiac disease, smoking, duration of diabetes, body mass index, blood pressure, New York Heart Association-class, Dyspnoea score, Minnesota Living with Heart Failure Questionnaire, LDL-cholesterol, HbA(1c), creatinine, glomerular filtration rate), the logarithm of NT-proBNP gave the most potent information in a stepwise Cox regression analysis (P < 0.0001). Bootstrapping with 500 samples supports this result in 95% samples. The negative predictive value of a normal value (<125 pg/mL) of NT-proBNP for short-term cardiovascular events in diabetic patients is 98%. CONCLUSION: We have demonstrated a strong and independent correlation between NT-proBNP and short-term prognosis of cardiovascular events for patients with diabetes mellitus. With a high negative predictive value it can identify individuals who are not at intermediate risk for cardiovascular events. NT-proBNP proved to be of higher predictive value than traditional cardiovascular markers, in this unselected cohort.


Assuntos
Biomarcadores/metabolismo , Angiopatias Diabéticas/prevenção & controle , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Angiopatias Diabéticas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade
18.
Wien Klin Wochenschr ; 131(Suppl 1): 151-163, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30980144

RESUMO

Recent epidemiological investigations have shown that approximately 2-3% of all Austrians suffer from diabetes with renal involvement, i. e. 250,000 people in Austria are affected. The risk of occurrence and progression of this disease can be ameliorated by life style interventions as well as optimization of blood pressure, blood glucose levels and special drug classes. The present article represents the joint recommendations of the Austrian Diabetes Association and the Austrian Society for Nephrology for the diagnostics and treatment strategies of diabetic kidney disease.


Assuntos
Nefropatias Diabéticas , Dietoterapia/normas , Terapia por Exercício/normas , Guias de Prática Clínica como Assunto , Áustria , Pressão Sanguínea , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/terapia , Humanos , Estilo de Vida , Comportamento de Redução do Risco , Resultado do Tratamento
20.
Wien Klin Wochenschr ; 131(Suppl 1): 27-38, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30980148

RESUMO

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2 , Hipoglicemiantes/uso terapêutico , Guias de Prática Clínica como Assunto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/tratamento farmacológico , Estilo de Vida
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