RESUMEN
AIMS: To determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24-h BP monitoring (cohort 1) or seated office measurements (cohort 2). RESULTS: Empagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p < 0.001 vs placebo), without increasing heart rate. Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: -2.3 mmHg; cohort 2: -2.3 mmHg), mean arterial pressure (MAP; cohort 1, -2.3 mmHg; cohort 2, -2.1 mmHg) and double product (cohort 1, -385 mmHg × bpm; cohort 2, -369 mmHg × bpm) all p < 0.001 vs placebo. There was a trend towards a reduction in the ambulatory arterial stiffness index (AASI) with empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011). CONCLUSIONS: Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance.
Asunto(s)
Arteriosclerosis/prevención & control , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Glucósidos/uso terapéutico , Hipertensión/prevención & control , Hipoglucemiantes/uso terapéutico , Anciano , Arteriosclerosis/complicaciones , Arteriosclerosis/epidemiología , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/efectos adversos , Biomarcadores , Presión Sanguínea/efectos de los fármacos , Monitoreo Ambulatorio de la Presión Arterial , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Glucósidos/administración & dosificación , Glucósidos/efectos adversos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Riesgo , Resistencia Vascular/efectos de los fármacos , Rigidez Vascular/efectos de los fármacosRESUMEN
AIMS: To investigate the pharmacodynamics, efficacy and safety of empagliflozin as adjunct to insulin in patients with type 1 diabetes. METHODS: A total of 75 patients with glycated haemoglobin (HbA1c) concentrations of ≥7.5 to ≤10.5% (≥58 to ≤91 mmol/mol) were randomized to receive once-daily empagliflozin 2.5 mg, empagliflozin 10 mg, empagliflozin 25 mg, or placebo as adjunct to insulin for 28 days. Insulin dose was to be kept as stable as possible for 7 days then adjusted, at the investigator's discretion, to achieve optimum glycaemic control. The primary exploratory endpoint was change from baseline in 24-h urinary glucose excretion (UGE) on day 7. RESULTS: Empagliflozin significantly increased 24-h UGE versus placebo on days 7 and 28. On day 28, adjusted mean differences with empagliflozin versus placebo in changes from baseline in: HbA1c were -0.35 to -0.49% (-3.8 to -5.4 mmol/mol; all p < 0.05 vs. placebo); total daily insulin dose -0.07 to -0.09 U/kg (all p<0.05 vs placebo); and weight were -1.5 to -1.9 kg (all p < 0.001 vs. placebo). In the placebo, empagliflozin 2.5, 10 and 25 mg groups, respectively, adverse events were reported in 94.7, 89.5, 78.9 and 100.0% of patients, and the rate of symptomatic hypoglycaemic episodes with glucose ≤3.0 mmol/l not requiring assistance was 1.0, 0.4, 0.5 and 0.8 episodes per 30 days. CONCLUSIONS: In patients with type 1 diabetes, empagliflozin for 28 days as adjunct to insulin increased UGE, improved HbA1c and reduced weight with lower insulin doses compared with placebo and without increasing hypoglycaemia.
Asunto(s)
Compuestos de Bencidrilo/administración & dosificación , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucósidos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Adulto , Austria , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/orina , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Quimioterapia Combinada , Femenino , Alemania , Hemoglobina Glucada/efectos de los fármacos , Glucosuria/orina , Humanos , Hipoglucemia/inducido químicamente , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacosRESUMEN
Chronic hyperglycaemia (e.g. type 2 diabetes mellitus (T2DM) and prediabetes) in humans is associated with an increased risk of cardiovascular (CV) complications, and, vice versa, the presence of CV complications (e.g. myocardial infarction, stroke or intermittent claudication) among patients heightens the risk of T2DM or prediabetes. In both cases (i.e. chronic hyperglycaemia and CV complications), significant diagnostic and treatment challenges resulting from a broad range of factors may serve as barriers to reducing the deleterious societal impact of T2DM and prediabetes. These challenges often include clinicians: failing to intervene early and aggressively enough among patients with T2DM to achieve CV risk factor control; failing to efficaciously identify T2DM patients with already established CV complications; and failing proactively to assess individuals at high risk for T2DM. This review discusses the apparent symbiosis between CV disease and T2DM, with a focus on identifying patients with established T2DM or at risk for T2DM; traditional and novel risk factors and markers for CV disease in T2DM; challenges related to diagnosing CV disease in T2DM; and organization of T2DM care in order to prevent CV complications. These are issues that require attention because identifying patients at high risk for T2DM can halt or reduce their further glycaemic deterioration if addressed properly, and because novel markers and non-invasive tests could be applied in patients with T2DM as a means of detecting and possibly treating unrecognized CV disease in time. Furthermore, several approaches for T2DM care can be effective in controlling the CV risk factors contributing to CV complications.
Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Humanos , Estado Prediabético/diagnóstico , Estado Prediabético/epidemiología , Factores de RiesgoRESUMEN
AIMS: Few studies have compared structured vs. standard care on the effects of modifying several cardiovascular (CV) risk factors in subjects with Type 2 diabetes. Because of the complexity of the disease, we hypothesized that structured care with a multi-interventional approach is necessary to effectively reach treatment goals and to reduce CV risk. METHODS: An open 2-year parallel-group study in 120 patients (age 59 +/- 10 years, 31 females) with Type 2 diabetes (median duration 4 years) was conducted. The patients were randomized to standard care (follow-up by their general practitioner) or to structured care at a hospital outpatient clinic consisting of an initial 6 months' lifestyle programme followed by targeted intensified pharmacological treatment to reach prespecified goals for glycaemic, lipid and blood pressure (BP) control. The primary outcome was change in the estimated 10-year absolute risk for fatal coronary heart disease (CHD). RESULTS: One hundred and six patients completed the study. Improvements were greater among patients receiving structured rather than standard care for systolic BP, triglycerides, glucose and glycated haemoglobin (HbA(1c)) (P < 0.05), as well as for the estimated 10-year CHD-risk (17.9% to 14.5% vs. 18.3% to 19.6%) and the prevalence of a CHD risk >or= 20% (38% to 22% vs. 39% to 45%). Most of the reduction in estimated CHD risk (77%) in the structured care group was obtained during the period (6-24 months) with intensified pharmacological treatment (P < 0.01). CONCLUSIONS: This study shows that 2 years of structured care combining lifestyle and pharmacological interventions improved several CV risk factors and reduced the estimated 10-year absolute risk for CHD in patients with Type 2 diabetes.
Asunto(s)
Servicio de Cardiología en Hospital/estadística & datos numéricos , Enfermedad de la Arteria Coronaria/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/prevención & control , Servicio de Cardiología en Hospital/normas , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Medición de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVE: Coronary artery disease (CAD) is prevalent in patients with type 2 diabetes mellitus (T2DM) and because it is often asymptomatic and extensive in comparison with CAD in subjects without diabetes, it represents a diagnostic challenge. The objective of the study was to investigate the prevalence of CAD in asymptomatic T2DM patients utilizing angiography and to investigate its association with cardiovascular (CV) risk factors, the metabolic syndrome and markers of inflammation. MATERIAL AND METHODS: Eighty-two patients with T2DM without symptoms of CAD, and with >or=1 CV risk factor (hypertension, dyslipidaemia, premature familial CAD, smoking or microalbuminuria) underwent a diagnostic stress test and coronary angiography irrespective of stress test results. Stenosis detected in the main coronary arteries >or=50% of lumen diameter was categorized as one-, two- or three-vessel disease. Inflammatory markers were analysed in fasting samples. RESULTS: Fifteen men and two women had significant CAD (21%) (1-vessel disease, n=10; 2- or 3-vessel disease, n=7). Patients with 2- or 3-vessel disease were significantly older and had a longer duration of diabetes, but the prevalence of other traditional CV risk factors or the metabolic syndrome was similar among those with 1-vessel and those with 2- or 3-vessel disease. Sensitivity for CAD of the stress test was low (0.35). The mean level of the pro-inflammatory marker interleukin-6 was elevated in patients with 2- to 3-vessel CAD as compared to patients with no or 1-vessel CAD (p<0.05). CONCLUSIONS: Significant CAD was found in 21% of asymptomatic patients with T2DM with >or=1 CV risk factor. Inflammatory markers may be helpful in identifying patients that are likely to have significant CAD, but larger studies are warranted.
Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Complicaciones de la Diabetes/diagnóstico por imagen , Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Inflamación/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Comorbilidad , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/fisiopatología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/epidemiología , Complicaciones de la Diabetes/fisiopatología , Prueba de Esfuerzo , Femenino , Humanos , Inflamación/sangre , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Noruega/epidemiología , Prevalencia , Factores de Riesgo , Distribución por SexoRESUMEN
BACKGROUND: Cardiovascular (CV) disease is associated with increased levels of glucose, but the prevalence of dysglycaemia in CV diseases is not fully known. The study examined the prevalence of unknown dysglycaemia and its association with inflammation in Caucasian patients with ischaemic vascular complications, i.e. coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD). MATERIALS AND METHODS: This case-controlled study involved 149 patients (mean age 68 years) hospitalized for CAD, PAD or CVD and 59 control-subjects (CTR) free from CV-disease. The prevalence of dysglycaemia according to WHO/ADA criteria (impaired fasting glycaemia, impaired glucose tolerance or diabetes mellitus) was assessed by a 75-g oral glucose tolerance test. Inflammatory parameters were analyzed in fasting samples. RESULTS: Dysglycaemia was found in 49%, 55% and 57% of patients with CAD, CVD and PAD, respectively; all were significantly higher than among the controls (29%). The odds ratio (95% CI) for being dysglycaemic were 1.7 (1.04-2.77), 1.9 (1.19-3.06) and 2.0 (1.25-3.19) for CAD, CVD and PAD, respectively. Inflammatory markers (the total leucocyte count, soluble tumour necrosis factor-receptor type I, C-reactive protein) were elevated in patient groups and tended to increase with increasing blood glucose levels in all groups. The levels of the anti-inflammatory cytokine transforming growth factor-beta1 and insulin-like growth factor binding protein 3 were lowered in patients with CAD and, in patients with PAD, the former was inversely related to the levels of the blood glucose. CONCLUSIONS: Undiagnosed dysglycaemia was common in patients with ischaemic CV manifestations regardless of vascular bed involved. Inflammation was associated in a dosage-related manner to glucose levels.