RESUMEN
AIM: In patients with type 2 diabetes mellitus (T2DM) a progressive thinning in the central retinal thickness (CRT) is mainly related to neuroretinal degeneration and occurs before the decline in visual acuity or capillary density. We investigated the change in CRT by optical coherence tomography (OCT) in T2DM patients after 12 weeks of treatment with dapagliflozin or glibenclamide. METHODS: Ninety-seven patients (57 ± 7 years) with T2DM and clinical or subclinical atherosclerosis were randomized 1:1 to dapagliflozin (10 mg/day) or glibenclamide (5 mg/day) on top of metformin XR 1.5 g/day. OCT was obtained in all patients enrolled in the study, both at the time of randomization and at the end of the study. RESULTS: Baseline and post-treatment values of fasting glucose and glycated hemoglobin were equivalent in the two arms. There was no difference in change in diabetic retinopathy status after therapy. The center subfield thickness changed by +2(6)µm in the dapagliflozin group and by -1(7) µm in the glibenclamide group (P = 0.001). CONCLUSION: A short-term treatment with dapagliflozin may increase CRT as compared with equivalent glycemic control with glibenclamide.
Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Gliburida , Retina/efectos de los fármacos , Compuestos de Bencidrilo/uso terapéutico , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Gliburida/uso terapéutico , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
We compared the effect of dapagliflozin versus glibenclamide on the ratio of lean-to total mass in patients with type 2 diabetes mellitus, carotid subclinical atherosclerosis, HbA1c 7.0-9.0% and 40-70 years-old. Ninety-eight patients (61% male; mean age 57 ± 7 years) were randomized into dapagliflozin 10 mg/day or glibenclamide 5 mg/day on top of metformin. Body composition was measured by Dual Energy X-Ray at randomization and after 12 weeks of treatment. Glycemic control was equivalent in both groups. Dapagliflozin decreased total body mass (-2741 g [95% CI: -3360 to 1945]; p < 0.001) and lean mass (-347 g [95% CI: -761 to -106]; p < 0.001), while glibenclamide increased total body mass (1060 g [95% CI: 140 to 1836]; p < 0.001) and lean mass (929 g [95% CI: 575 to 1283]; p < 0.001) for the differences between arms. The lean-to-total mass ratio increased by 1.2% in the dapagliflozin group and 0,018% in the glibenclamide group (p < 0.001). Dapagliflozin reduced the risk of a negative balance in the lean-to total mass ratio [OR: 0.16 (95% CI: 0.05 to 0.45); p < 0.001] even after adjustment for baseline lean-to total mass ratio, waist circumference, HOMAIR, HbA1c, mean of the two hands handgrip strength and gait speed [OR: 0.13 (95% CI: 0.03-0.57); p < 0.007]. In conclusion, under equivalent glycemic control, dapagliflozin reduced total body mass but increased the ratio of lean-to-total mass when compared with glibenclamide.
Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Composición Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Gliburida/uso terapéutico , Hipoglucemiantes/uso terapéutico , Absorciometría de Fotón/métodos , Adulto , Anciano , Glucemia/análisis , Peso Corporal , Enfermedades de las Arterias Carótidas , Femenino , Hemoglobina Glucada/análisis , Fuerza de la Mano , Humanos , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: The glucose-lowering independent effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on arterial wall function has not yet been clarified. This study aims to assess whether SGLT2i treatment can attenuate endothelial dysfunction related to type 2 diabetes mellitus (T2D) compared with glucose-lowering equivalent therapy. METHODS: In a prospective, open-label, single-center, randomized clinical trial, 98 patients with T2DM and carotid intima-media thickness above the 75th percentile were randomized 1:1 to 12 weeks of therapy with dapagliflozin or glibenclamide in addition to metformin in glucose-lowering equivalent regimens. The coprimary endpoints were 1-min flow-mediated dilation (FMD) at rest and 1-min FMD after 15 min of ischemia followed by 15 min of reperfusion time (I/R). RESULTS: Ninety-seven patients (61% males, 57 ± 7 years) completed the study. The median HbA1c decreased by - 0.8 (0.7)% and -0.7 (0.95)% following dapagliflozin and glibenclamide, respectively. The first coprimary endpoint, i.e., rest FMD changed by + 3.3(8.2)% and - 1.2(7.5)% for the dapagliflozin and glibenclamide arms, respectively (p = 0.0001). Differences between study arms in the second coprimary endpoint were not significant. Plasma nitrite 1 min after rest FMD was higher for dapagliflozin [308(220) nmol/L] than for glibenclamide (258[110] nmol/L; p = 0.028). The resistive indices at 1 min [0.90 (0.11) vs. 0.93 (0.07); p = 0.03] and 5 min [0.93 (0.07) vs. 0.95 (0.05); p = 0.02] were higher for the glibenclamide group than for the dapagliflozin group. Plasma biomarkers for inflammation and oxidative stress did not differ between the treatments. CONCLUSIONS: Dapagliflozin improved micro- and macrovascular endothelial function compared to glibenclamide, regardless of glycemic control in patients with T2DM and subclinical carotid atherosclerotic disease.
Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Glucemia/efectos de los fármacos , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Glucósidos/uso terapéutico , Gliburida/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Vasodilatación/efectos de los fármacos , Adulto , Anciano , Compuestos de Bencidrilo/efectos adversos , Biomarcadores/sangre , Glucemia/metabolismo , Brasil , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Quimioterapia Combinada , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Glucósidos/efectos adversos , Gliburida/efectos adversos , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: Diabetes is one of the leading causes of cardiovascular mortality. Over the last years, mortality has decreased significantly, more in individuals with diabetes than in healthy ones. That is mostly due to the control of other cardiovascular risk factors. The objective of our study was to analyze the dyslipidemia control in two diabetes cohorts. METHODS: Patients from two distinct cohorts were studied, 173 patients from the BHS (Brasília Heart Study) and 222 patients from the BDS (Brazilian Diabetes Study). The data on dyslipidemia control were studied in both different populations. All patients had diabetes. RESULTS: There are significant differences concerning comorbidities between the LDL-C and BDS groups. The average glycated hemoglobin is of 8.2 in the LDL-C > 100 group in comparison with 7.7 and 7.5 in the 70-100 and < 70 groups, respectively (p = 0.024). There is a higher percentage of hypertensive patients with LDL between 70-100 (63.9%), when comparing the < 70 and > 100 groups (54.3% and 54.9%, respectively; p = 0.005). Diastolic pressure is higher in the group with LDL > 100, with an average of 87 mmHg, in comparison with 82.6 mmHg and 81.9 mmHg in the 70-100 and < 70 groups, respectively (p = 0.019). The group with LDL > 100 has the greatest percentage of smokers (8.7%) in comparison with the groups with LDL between 70-100 and < 70 (5.6% and 4.3%, respectively; p = 0.015). There is also a difference in the previous incidence of coronaropathy. In the group with LDL < 70, 28.3% of patients had already experienced a previous infarction, compared with 11.1% and 10.6% in the 70-100 and > 100 groups, respectively (p < 0.001). CONCLUSIONS: The data in our study have shown that the dyslipidemia control in diabetic patients is inadequate and there is a tendency of direct association between lack of blood glucose control and lack of dyslipidemia control, in addition to the association with other cardiovascular risk factors, such as diastolic hypertension and smoking. This worsened control might be related to the plateau in the descending curve of mortality, and investments in this regard can improve the cardiovascular health in diabetic patients.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/complicaciones , Simvastatina/uso terapéutico , Presión Sanguínea , Brasil/epidemiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Comorbilidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/mortalidad , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , Dislipidemias/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Triglicéridos/sangreRESUMEN
SUMMARY OBJECTIVE Diabetes is one of the leading causes of cardiovascular mortality. Over the last years, mortality has decreased significantly, more in individuals with diabetes than in healthy ones. That is mostly due to the control of other cardiovascular risk factors. The objective of our study was to analyze the dyslipidemia control in two diabetes cohorts. METHODS Patients from two distinct cohorts were studied, 173 patients from the BHS (Brasília Heart Study) and 222 patients from the BDS (Brazilian Diabetes Study). The data on dyslipidemia control were studied in both different populations. All patients had diabetes. RESULTS There are significant differences concerning comorbidities between the LDL-C and BDS groups. The average glycated hemoglobin is of 8.2 in the LDL-C > 100 group in comparison with 7.7 and 7.5 in the 70-100 and < 70 groups, respectively (p = 0.024). There is a higher percentage of hypertensive patients with LDL between 70-100 (63.9%), when comparing the < 70 and > 100 groups (54.3% and 54.9%, respectively; p = 0.005). Diastolic pressure is higher in the group with LDL > 100, with an average of 87 mmHg, in comparison with 82.6 mmHg and 81.9 mmHg in the 70-100 and < 70 groups, respectively (p = 0.019). The group with LDL > 100 has the greatest percentage of smokers (8.7%) in comparison with the groups with LDL between 70-100 and < 70 (5.6% and 4.3%, respectively; p = 0.015). There is also a difference in the previous incidence of coronaropathy. In the group with LDL < 70, 28.3% of patients had already experienced a previous infarction, compared with 11.1% and 10.6% in the 70-100 and > 100 groups, respectively (p < 0.001). CONCLUSIONS The data in our study have shown that the dyslipidemia control in diabetic patients is inadequate and there is a tendency of direct association between lack of blood glucose control and lack of dyslipidemia control, in addition to the association with other cardiovascular risk factors, such as diastolic hypertension and smoking. This worsened control might be related to the plateau in the descending curve of mortality, and investments in this regard can improve the cardiovascular health in diabetic patients.
RESUMO OBJETIVO O diabetes é importante causa de mortalidade cardiovascular. Nos últimos anos, a mortalidade diminuiu substancialmente, mais em diabéticos do que em não diabéticos, em grande parte devido ao controle de outros fatores de risco cardiovasculares. Nosso estudo tem como objetivo analisar o controle de dislipidemia em duas coortes de diabéticos. MÉTODOS Foram estudados pacientes de duas coortes distintas, sendo 173 pacientes do BHS (Brasília Heart Study) e 222 pacientes do BDS (Brazilian Diabetes Study). Os dados sobre controle de dislipidemia foram estudados nas duas populações diferentes. Todos os pacientes eram diabéticos. RESULTADOS Há diferenças significativas em relação às comorbidades entre os grupos de LDL-C no BDS. A média de hemoglobina glicada é de 8,2 no grupo com LDL-C > 100, comparado com 7,7 e 7,5 nos grupos 70-100 e < 70, respectivamente (p = 0,024). Há maior porcentagem de pacientes hipertensos com LDL entre 70-100 (63,9%), quando comparado aos grupos < 70 e > 100 (54,3% e 54,9%, respectivamente; p = 0,005). A pressão diastólica é mais elevada no grupo com LDL > 100, com média de 87 mmHg, comparado com 82,6 mmHg e 81,9 mmHg nos grupos 70-100 e < 70, respectivamente (p = 0,019). O grupo com LDL > 100 tem maior porcentagem de tabagistas (8,7%) quando comparado aos grupos com LDL entre 70-100 e < 70 (5,6% e 4,3%, respectivamente; p = 0,015). Há, também, diferença na incidência prévia de coronariopatia. No grupo com LDL < 70, 28,3% dos pacientes já apresentaram infarto prévio, comparados com 11,1% e 10,6% nos grupos 70-100 e > 100, respectivamente (p < 0,001). CONCLUSÃO Os dados do nosso estudo mostram que o controle de dislipidemia em diabéticos é inadequado, e há uma tendência de associação direta entre descontrole glicêmico e descontrole de dislipidemia, além de associação com outros fatores de risco cardiovascular, como hipertensão diastólica e tabagismo. Esse pior controle pode estar relacionado ao platô no descenso da curva de mortalidade, e o investimento nesse quesito pode melhorar a saúde cardiovascular dos diabéticos.
Asunto(s)
Humanos , Masculino , Femenino , Simvastatina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Dislipidemias/complicaciones , Anticolesterolemiantes/uso terapéutico , Triglicéridos/sangre , Presión Sanguínea , Brasil/epidemiología , Comorbilidad , Prevalencia , Factores de Riesgo , Estudios de Cohortes , Diabetes Mellitus Tipo 2/mortalidad , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dislipidemias/prevención & control , Dislipidemias/tratamiento farmacológico , Dislipidemias/epidemiología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIMS: Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ. METHODS: HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (nâ¯=â¯94) and peak CKMB (nâ¯=â¯393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers. RESULTS: HDL-C above the median (35â¯mg/dL) was associated with higher peak CKMB [255 (145-415) vs. 136 (84-287) UI/L; p = 0.02], higher MI mass [17 (9-21) vs. 10 (6-14) g; p < 0.01] and lower left ventricular ejection fraction [47 (34-53) vs. 51 (43-59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p < 0.01) and MI mass (p < 0.01) only in reperfused patients with time to reperfusion <4â¯h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p < 0.01) and improved dP/dt max (p = 0.02). CONCLUSIONS: In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.
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HDL-Colesterol/sangre , Daño por Reperfusión Miocárdica/prevención & control , Revascularización Miocárdica , Miocardio/patología , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Animales , Biomarcadores/sangre , Forma MB de la Creatina-Quinasa/sangre , Modelos Animales de Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/diagnóstico por imagen , Daño por Reperfusión Miocárdica/patología , Revascularización Miocárdica/efectos adversos , Estudios Prospectivos , Ratas Wistar , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
The occlusion of a coronary artery by a thrombus generated on a ruptured atherosclerotic plaque has been pursued in the last decades as a determining event for the clinical outcome after myocardial infarction (MI). Yet, MI causes a cell death wave front, which triggers an inflammatory response to clear cellular debris, and which in excess can double the myocardial lesion and influence the clinical prognosis in the short and long term. Accordingly, proper, timely regulated inflammatory response has now been considered a second pivotal player in cardiac recovery after MI justifying the search for pharmacological strategies to modulate inflammatory effectors. This chapter reviews the key events and the main effectors of inflammation after myocardial ischemic insult, as well as the contribution of this phenomenon to the progression of atherosclerosis.
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Inflamación/complicaciones , Infarto del Miocardio/complicaciones , Miocardio/patología , Animales , Aterosclerosis/etiología , Aterosclerosis/inmunología , Aterosclerosis/patología , Humanos , Inflamación/inmunología , Inflamación/patología , Infarto del Miocardio/inmunología , Infarto del Miocardio/patología , Miocardio/inmunologíaRESUMEN
BACKGROUND: The transport of lipids from the artery wall is one of the most essential anti-atherogenic functions of high-density lipoprotein (HDL). Recent reports of changes in the HDL composition, during myocardial infarction (MI), suggest that this function may be altered. METHODS: Forty-one consecutive patients with ST-segment elevation MI enrolled at the Brasilia Heart Study were selected. The following HDL-related measures were determined upon admission (D1) and on the fifth day (D5) after MI: C-reactive protein, CETP and PLTP activity, HDL composition, efflux of cholesterol from J774 macrophages to HDL, and transfer of unesterified and esterified cholesterol, triglycerides and phospholipids from a donor nanoemulsion to HDL. RESULTS: From D1 to D5, the activity of CETP decreased by 25%, but PLTP activity remained unchanged. Esterified cholesterol (-23%) and phospholipid (-9.5%) contents of HDL decreased. Transfer of triglycerides (-36.5%) and esterified cholesterol (-14.7%) to HDL from nanoemulsions was reduced, but other lipids transfers were unchanged. Cholesterol efflux to HDL was also diminished by 8.5% (p=0.04) on D5 compared to D1. It was more pronounced in patients above the 75th percentile of C-reactive protein. CONCLUSIONS: After an MI, a simultaneous decrease in lipid transfer to HDL and in the capacity of HDL to efflux cholesterol from cells occurs. Thus, HDL with inferior atheroprotective properties may be generated in the acute post-MI period.
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Colesterol/metabolismo , Lípidos , Lipoproteínas HDL/metabolismo , Macrófagos/metabolismo , Infarto del Miocardio/metabolismo , Aterosclerosis , Transporte Biológico , Línea Celular , HumanosRESUMEN
Serum parathyroid hormone (PTH) has been found to be associated with cardiovascular mortality in the elderly, but little is known about the mechanisms underlying this association. This study investigated the association between PTH and structural and functional changes of the heart and arterial wall in a cohort of very elderly individuals. Healthy individuals aged 80 years or more (n = 90) underwent evaluation of serum PTH, cardiac morphology and function by Doppler echocardiography, endothelium dependent and independent vasodilatation by brachial reactivity, carotid stiffness and intima-media thickness by ultrasound, and coronary calcification by computed tomography. Participants with PTH levels above the median 5.8 pmol/L had higher left ventricular mass index (P = .02), relative wall thickness (P = .02), left atrial volume index (P = .03), and shorter deceleration time of E mitral wave (P = .04). Serum PTH levels (odds ratio, 1.027; P = .032) and systolic blood pressure (odds ratio, 1.032; P = .008) were independently associated with left ventricular hypertrophy. No difference was found between PTH groups in flow- or nitrate-mediated brachial artery dilatation, coronary artery calcification, intima-media thickness, or arterial stiffness. Elevation of serum PTH in the very elderly is associated with concentric left ventricular hypertrophy, but no association with arterial wall structure or function was found in this study.
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Hiperparatiroidismo/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Anciano de 80 o más Años , Presión Sanguínea , Estudios de Cohortes , Ecocardiografía Doppler , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , SístoleRESUMEN
OBJECTIVE: To verify the existence of association between plasma levels of pro- or anti-inflammatory mediators and atherosclerotic burden at coronary and carotid arteries in individuals aged of 80 or more years old. METHODS: Healthy individuals aged between 80 and 102 years old (n = 178) underwent evaluation of plasma cytokines and acute phase proteins, intima-media thickness (IMT) and presence of plaques in carotid arteries by ultrasound and coronary artery calcification (CAC) by cardiac computed tomography. RESULTS: There was no association between CAC and carotid plaques (p = 0.8), maximum (p = 0.06) or mean IMT (p = 0.2). No association was found between the presence of carotid plaques and CRP (p = 0.4), TNF-α (p = 0.8) or IL-10 (p = 0.2). Likewise, individuals in the first three quartiles for CRP, TNF-α or IL-10 had similar values of CAC, mean and maximum IMT. In contrast, individuals above the 75th percentile for CRP or for TNF-α had enhanced maximum IMT (p = 0.017 and p < 0.0001) and CAC (p = 0.026 and p = 0.01) and subjects with IL-10 levels above the 75th percentile had lower maximum IMT (p = 0.027) and CAC (p = 0.006) as compared with those below this percentile. There was no difference in mean IMT for individuals above or below the 75th percentile for CRP, TNF-α or IL-10. CONCLUSION: In very old individuals, CAC and maximum IMT were positively associated with systemic inflammatory activity only in those above the 75th percentile. The markers of atherosclerotic burden at coronary and carotid arteries were not related to each other and were distinctly associated with pro- and anti-inflammatory mediators, suggesting that atherosclerosis development is different in these vascular beds.