RESUMEN
OBJECTIVE: Low density lipoprotein cholesterol (LDL-C) is an independent and modifiable risk factor for development of cardiovascular disease (CVD). Postprandial lipid metabolism has been linked to CVD, but little is known about the postprandial LDL-C profile in patients with type-2 diabetes (T2DM). We aimed to study the postprandial levels of LDL-C in T2DM patients. MATERIAL AND METHODS: After an overnight fast, 74 T2DM patients, mean age approximately 60 years, were served a standard fat-rich meal of 3515 kJ containing 54% fat, 13 % protein and 33 % carbohydrates. Only drinking water was allowed postprandially. Blood samples were drawn at times 0 (fasting), 1.5, 3.0, 4.5 and 6.0 h (postprandial). In all samples, LDL-C was measured with modified beta quantification (separation by ultracentrifugation followed by measurement of infranate high density lipoprotein cholesterol (HLD-C) using a homogeneous assay). RESULTS: At all postprandial times, levels of LDL-C showed highly significant (p < 0.005) decreases compared to time 0 (mean [95% CI] maximum change in LDL-C levels at 3.0 h: -0.16 mmol/L [-0.12; -0.20]; p < 0.001). Independently of fasting LDL-C levels and ongoing statin therapy, LDL-C decreased significantly more in female compared to male patients postprandially (mean [95% CI] maximum unadjusted change versus time 0 in LDL-C for men [n=56] at 3.0 h: -0.14 mmol/L [-0.19; -0.10], p < 0.001; for women [n=18] at 4.5 h: -0.26 mmol/L [-0.35; -0.18], p < 0.001; -0.14 mmol/L [-0.24; -0.05], p = 0.005 between genders for the mean [95% CI] fasting adjusted difference at 4.5 h in the change versus time 0 in LDL-C; gender by time interaction: p = 0.007 (repeated measures mixed model)). CONCLUSIONS: In T2DM patients served a fat-rich meal, levels of LDL-C decreased significantly more in women compared to men postprandially, irrespective of fasting levels or ongoing statin therapy. This might have implications in the atherosclerotic process and on any difference in the risk of CVD between genders.
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LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Periodo Posprandial/fisiología , Complicaciones de la Diabetes/sangre , Grasas de la Dieta , Ayuno/sangre , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lípidos/sangre , MasculinoRESUMEN
AIM: Metformin is the 'drug-of-first-choice' in obese patients with type 2 diabetes mellitus (T2DM) due to its antihyperglycaemic and cardiovascular protective potentials. In non-obese patients with T2DM, insulin secretagogues are empirically used as first choice. In this investigator-initiated trial, we evaluated the effect of metformin vs. an insulin secretagogue, repaglinide on glycaemic regulation and markers of inflammation and insulin sensitivity in non-obese patients with T2DM. METHODS: A single-centre, double-masked, double-dummy, crossover study during 2 x 4 months involved 96 non-obese (body mass index < or = 27 kg/m(2)) insulin-naïve patients with T2DM. At enrolment, previous oral hypoglycaemic agents (OHA) were stopped and patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either repaglinide 2 mg thrice daily followed by metformin 1 g twice daily or vice versa each during 4 months with 1-month washout between interventions. RESULTS: End-of-treatment levels of haemoglobin A(1c) (HbA(1c)), fasting plasma glucose, mean of seven-point home-monitored plasma glucose and fasting levels of high-sensitivity C-reactive protein and adiponectin were not significantly different between treatments. However, body weight, waist circumference, fasting serum levels of insulin and C-peptide were lower and less number of patients experienced hypoglycaemia during treatment with metformin vs. repaglinide. Both drugs were well tolerated. CONCLUSIONS: In non-obese patients with T2DM, overall glycaemic regulation was equivalent with less hypoglycaemia during metformin vs. repaglinide treatment for 2 x 4 months. Metformin was more effective targeting non-glycaemic cardiovascular risk markers related to total and abdominal body fat stores as well as fasting insulinaemia. These findings may suggest the use of metformin as the preferred OHA also in non-obese patients with T2DM.
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Carbamatos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Piperidinas/uso terapéutico , Adiponectina/sangre , Biomarcadores/análisis , Glucemia/análisis , Peso Corporal/efectos de los fármacos , Péptido C/sangre , Proteína C-Reactiva/análisis , Carbamatos/efectos adversos , Estudios Cruzados , Método Doble Ciego , Femenino , Hemoglobina Glucada/análisis , Humanos , Hiperglucemia/complicaciones , Hipoglucemiantes/efectos adversos , Insulina/sangre , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Cooperación del Paciente , Piperidinas/efectos adversos , Estudios Prospectivos , Relación Cintura-CaderaRESUMEN
BACKGROUND: Diabetic nephropathy is a chronic, progressive kidney disease with a mean rate of decline of in glomerular filtration rate (GFR) of 10 to 12 mL/min/year (natural history). The introduction of aggressive antihypertensive treatment has improved the renal prognosis during the last decades. To examine whether remission and regression of diabetic nephropathy are possible in type 1 diabetic patients, we analyzed data from a prospective observational cohort study that was started in 1983. METHODS: We measured GFR with a 51Cr-EDTA plasma clearance technique every year for seven years (range 3 to 14 years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria> 200 microg/min, presence of diabetic retinopathy, and no evidence of other kidney or renal tract disease. Blood pressure, albuminuria, glycosylated hemoglobin A1c, and serum cholesterol were measured every three to four months during the study. In total, 271 patients received antihypertensive treatment, 179 patients predominantly with angiotensin-converting enzyme inhibitors. Remission was defined as albuminuria <200 microg/min sustained for at least one year and a decrease of at least 30% from preremission levels (surrogate endpoint), and regression as a rate of decline in GFR (DeltaGFR) equal to the natural aging process: < or =1 mL/min/year during the entire observation period (principal end point). RESULTS: The total number of patients who obtained remission was 92 (31%), with a duration of remission of [median (range)] 3.4 (1.0 to 14.1) years, and regression 67 (22%). The patients were stratified in quintiles by the average value of office mean arterial blood pressure (mean +/- SE): 93 +/- 0.5, 99 +/- 0.2, 103 +/- 0.1, 107 +/- 0.2, and 113 +/- 0.4 mm Hg. The prevalence of patients obtaining remission/regression was 58/42, 33/32, 25/11, 20/20, and 17/7% in each quintile, respectively. Spontaneous remission and regression occurred in 10 and 14 patients from the persistent normotensive group (N = 30), none of whom had ever received antihypertensive treatment. In all 301 consecutive patients, the (mean +/- SE) DeltaGFR was 4.0 +/- 0.2 mL/min/year during the investigation period. CONCLUSIONS: Our study suggests that aggressive antihypertensive treatment in type 1 diabetic patients can induce remission and regression in a sizable fraction of patients with diabetic nephropathy. Lower arterial blood pressure, reduced albuminuria, and better glycemic control were predictors of regression of diabetic nephropathy.
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Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/fisiopatología , Adulto , Albuminuria/orina , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Remisión EspontáneaRESUMEN
BACKGROUND: Diabetic nephropathy is a major cause of renal failure. The decline in glomerular filtration rate (GFR) is highly variable, ranging from 2 to 20, with a median of 12 mL/min/year. The risk factors of losing filtration power (progression promoters) have not been clearly identified. Furthermore, information on optimal arterial blood pressure, glycemic control, and cholesterol levels are lacking. METHODS: We measured GFR with (51)Cr-EDTA plasma clearance technique, blood pressure, albuminuria, glycosylated hemoglobin A1c, and serum cholesterol every year for seven years (range 3 to 14 years) in 301 consecutive type 1 diabetic patients with diabetic nephropathy recruited consecutively during 1983 through 1997. Diabetic nephropathy was diagnosed clinically if the following criteria were fulfilled: persistent albuminuria> 200 microg/min, presence of diabetic retinopathy, and no evidence of other kidney or renal tract disease. In total, 271 patients received antihypertensive treatment at the end of the observation period. RESULTS: Mean arterial blood pressure was 102 +/- 0.4 (SE) mm Hg. The average decline in GFR was 4.0 +/- 0.2 mL/min/year and even lower (1.9 +/- 0.5 mL/min/year) in the 30 persistently normotensive patients, none of whom had ever received antihypertensive treatment (P < 0.01). A multiple linear regression analysis revealed a significant positive correlation between the decline in GFR and mean arterial blood pressure, albuminuria, glycosylated hemoglobin A(1c), and serum cholesterol during follow-up (R(adj)(2) = 0.29, P < or = 0.001). No threshold level for blood pressure, glycosylated hemoglobin A(1c), or serum cholesterol was demonstrated. A two-hit model with mean arterial blood pressure and glycosylated hemoglobin A(1c) below and above the median values (102 mm Hg and 9.2%, respectively) revealed a rate of decline in GFR of only 1.5 mL/min/year in the lowest stratum compared with 6.1 mL/min/year in the highest stratum (P < 0.001). CONCLUSIONS: The prognosis of diabetic nephropathy has improved during the past decades, predominantly because of effective antihypertensive treatment. Genuine normotensive patients have a slow progression of nephropathy. Several modifiable variables have been identified as progression promoters.
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Nefropatías Diabéticas/fisiopatología , Adulto , Albuminuria/etiología , Presión Sanguínea , Colesterol/sangre , Progresión de la Enfermedad , Ácido Edético/sangre , Femenino , Tasa de Filtración Glomerular , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Evaluación de la Discapacidad , Testimonio de Experto/legislación & jurisprudencia , Enfermedades Pulmonares Obstructivas/diagnóstico , Mediciones del Volumen Pulmonar , Alemania , Humanos , Enfermedades Pulmonares Obstructivas/clasificación , Enfermedades Pulmonares Obstructivas/etiologíaRESUMEN
Methodically it is very simple to determine fractional CO-uptake (FCO) from inspiratory and mean expiratory CO-concentrations. In two longitudinal studies the single-breath-TCO (49 patients) and FCO (813 patients) have been compared. The oscillations of DCO are smaller than those of TCO, but it remains unclear which method for determination of CO-transfer has a higher validity.
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Pruebas Respiratorias , Monóxido de Carbono , Enfermedades Pulmonares/diagnóstico , Relación Ventilacion-Perfusión/fisiología , Estudios Transversales , Volumen Espiratorio Forzado/fisiología , Humanos , Estudios Longitudinales , Enfermedades Pulmonares/fisiopatología , Intercambio Gaseoso Pulmonar/fisiologíaRESUMEN
Without reasonable doubt Mr. X. suffers from a chronic obstructive bronchitis and Mr. Y. from pulmonary emphysema. With relation to the new occupational disease no. 4111 the safe diagnosis of chronic obstructive bronchitis and of pulmonary emphysema is very difficult. The various aspects are described here.
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Bronquitis/diagnóstico , Enfisema/diagnóstico , Enfermedades Profesionales/clasificación , Enfermedades Profesionales/diagnóstico , Anciano , Bronquitis/clasificación , Enfermedad Crónica , Diagnóstico Diferencial , Enfisema/clasificación , Humanos , MasculinoRESUMEN
AIMS: To elucidate the putative factors involved in the blunted nocturnal blood pressure reduction in hypertensive Type 2 diabetic patients with diabetic nephropathy. METHODS: Extracellular fluid volume and fluid shift from interstitial to plasma volume (haematocrit), sympathetic nervous activity (plasma noradrenaline and adrenaline) and the internal 'body clock' (serum melatonin) were investigated in 31 hypertensive Type 2 diabetes mellitus (DM) patients with diabetic nephropathy (24 males, age 60 (45-73) years). All variables, except extracellular volume, were measured repeatedly with the patients lying awake in bed from 21:30 to 23:00 h (baseline) and during sleep from 23:00 to 07:00 h. Using the median nocturnal blood pressure reduction (8.4%) as a guide, the patients were divided into groups; group 1 with the highest and group 2 with the lowest nocturnal blood pressure reduction. RESULTS: Haematocrit decreased from baseline to the sleep period in group 1 by a mean (95% confidence interval (CI)) of 1.7 (0.3-3.1)%, but it increased by 0.5 (-1.0-1.9)% in group 2, mean difference (95% CI), -2.1 (-4.0 to -0.2)% (P = 0.029). Noradrenaline decreased from baseline to the sleep period, mean (95% CI), by 13.3 (0.0-25.0)% in group 1 but rose by 7.7 (-9.7-28.4)% in group 2, mean difference (95% CI), -19.6 (-35-0.0)% (P = 0.049). The nocturnal blood pressure change correlated to the nocturnal change in both noradrenaline (r = 0.51, P = 0.004) and haematocrit (r = 0.42, P = 0.018). Adrenaline remained constant in both groups. Extracellular fluid volume and plasma melatonin levels were comparable in the two groups. CONCLUSION: Sustained adrenergic activity during sleep is associated with blunted nocturnal blood pressure reduction in hypertensive Type 2DM patients with diabetic nephropathy, probably mediated through a lack of peripheral vasodilatation whereas changes in extracellular fluid volume distribution and melatonin secretion have no impact.
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Presión Sanguínea , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Nefropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/fisiopatología , Hipertensión/fisiopatología , Sueño/fisiología , Sistema Nervioso Simpático/fisiopatología , Anciano , Ritmo Circadiano , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Diástole , Epinefrina/sangre , Femenino , Tasa de Filtración Glomerular , Frecuencia Cardíaca , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Volumen Plasmático , Análisis de Regresión , Sístole , VigiliaAsunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Captopril/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Albuminuria/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Estudios de Seguimiento , Humanos , Riñón/fisiopatología , Estudios Prospectivos , Factores de TiempoRESUMEN
Plasma clearance of 51Cr-EDTA is widely used to assess the glomerular filtration rate (GFR) in diabetic nephropathy. Originally, the ratio between the intravenously injected amount of tracer and the total area under the plasma concentration curve was used for the calculation of total 51Cr-EDTA plasma clearance (C(T)). Simplified methods, using the final mono-exponential part of the plasma curve, have been suggested, e.g. four samples, taken 180 to 240 min after injection (C(IV)), or using one sample taken at 240 min (C(I)). Our aim was to evaluate the agreement between measurements of GFR and rate of decline in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (IDDM) patients with microalbuminuria or diabetic nephropathy. GFR was measured after a single intravenous injection of 3.7 MBq 51Cr-EDTA by determining the radioactivity in venous blood samples taken 5, 7, 10, 15, 30, 45, 60, 90, 120, 150, 180, 200, 220, and 240 min after the injection. Rate of decline in GFR was assessed using 12 (6-17) determinations of GFR over a period of time of 8 (4-10) years. Mean (SD) GFRT was 123 (21) ml x min(-1) compared to GFR(IV) 123 (21) ml x min(-1) (NS) and GFR(I) 115 (17) ml x min(-1) (p < 0.00001). The mean difference (95% limits of agreement) between GFR(T) and GFR(IV) was +0.6 (-16.6 to +17.7) ml x min(-1), and between GFR(T) and GFR(I) +8.0 (-6.0 to +22.2) ml x min(-1). The difference between GFR(T) and GFR(I) was significantly correlated with their mean value (r = 0.56, p < 0.00001), indicating increasing underestimation by GFR(I) with increasing GFR levels. The mean (SD) rate of decline in GFR(T) was 2.3 (3.9) ml x min(-1) x year(-1), compared to a mean rate of decline in GFR(IV) of 2.4 (3.6) ml x min(-1) x year(-1) (NS), and a mean rate of decline in GFR(I) of 2.2 (3.5) ml x min(-1) x year(-1) (NS). The mean difference (95% limits of agreement) between rate of decline in GFR(T) and rate of decline in GFR(IV) was +0.16 (-1.59 to +1.91) ml x min(-1) x year(-1), and between rate of decline in GFR(T) and rate of decline in GFR(I) -0.01 (-1.64 to +1.61) ml x min(-1) x year(-1), respectively. In conclusion, our cross-sectional study revealed a close agreement between GFR(T) and GFR(IV) with acceptable limits of agreement (precision), while GFR(I) lacked accuracy. However, a close agreement between rate of decline in GFR(T) and rate of decline in GFR(IV), and between rate of decline in GFR(T) and rate of decline in GFR(I), with acceptable limits of agreement (precision), suggests that both simplified methods are applicable for long-term follow-up.
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Nefropatías Diabéticas/fisiopatología , Ácido Edético , Tasa de Filtración Glomerular , Radioisótopos de Cromo , Estudios Transversales , Nefropatías Diabéticas/sangre , Ácido Edético/sangre , Ácido Edético/farmacocinética , Femenino , Humanos , Estudios Longitudinales , MasculinoRESUMEN
OBJECTIVE: To evaluate the effect of the ACE inhibitor ramipril as compared with placebo on left ventricular mass index (LVMI) in normotensive, nonalbuminuric NIDDM patients with left ventricular hypertrophy (LVH). Patients with NIDDM are characterized by excessive cardiovascular morbidity and mortality, and LVH, an independent risk factor for cardiac events, is often present in NIDDM patients. RESEARCH DESIGN AND METHODS: A total of 38 normotensive, nonalbuminuric (albuminuria < 100 mg/24 h) NIDDM patients with LVH (LVMI > 131 g/m2 in men and > 100 g/m2 in women) were enrolled in a 6-month randomized, double-blind parallel group study to compare the effects of ramipril (5 mg/day) with placebo on LVMI (echocardiography, Vingmed CFM725, Diasonics Sonotron), QTc dispersion determined as the interlead variation in QTc interval on standard electrocardiogram (ECG), and 24-h ambulatory blood pressure (A&D TM2420, Tokyo, Japan). A total of 16 ramipril (10 men, 60 +/- 9 years [mean +/- SD]) and 15 placebo-treated (8 men, 55 +/- 10 years) patients completed the study, and their data are presented. RESULTS: Ambulatory blood pressure was almost identical at baseline (132/76 +/- 3/1 vs. 133/74 +/- 5/2 mmHg [mean +/- SEM]) and remained stable during follow-up (134/76 +/- 3/1 vs. 136/74 +/- 6/2 mmHg) in the ramipril and placebo group, respectively. LVMI was comparable at baseline (137.1 +/- 7.0 vs. 129.6 +/- 3.7 g/m2) in the ramipril and placebo group, respectively, and decreased significantly more in the ramipril group as compared with the placebo group (17.6 +/- 3.0 vs. 5.7 +/- 4.6 g/m2, respectively, 11.9 [0.7-23.1] g/m2, mean difference [95% CI]; P = 0.037). QTc dispersion was comparable at baseline (60.2 [5.5] vs. 64.1 [6.5] ms) and did not change significantly during follow-up: -2.5 [7.0] vs. -12.2 [9.5] ms; mean difference 9.8 (-14.2 to 33.8 ms) in the ramipril and placebo group, respectively. CONCLUSIONS: Ramipril induces regression of LVH in normotensive, nonalbuminuric NIDDM patients, independent of reduction in systemic blood pressure.
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Antihipertensivos/uso terapéutico , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Ramipril/uso terapéutico , Anciano , Albuminuria/fisiopatología , Biomarcadores/sangre , Biomarcadores/orina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertrofia Ventricular Izquierda/complicaciones , Masculino , Persona de Mediana Edad , Valores de Referencia , Resultado del TratamientoRESUMEN
Endothelial dysfunction is a prevalent phenomenon in non-insulin dependent diabetic (NIDDM) patients with hypertension and albuminuria, and may contribute to the development and progression of cardiovascular disease, which is the main cause of the high morbidity and mortality observed in these patients. Therefore the aim of our study was to evaluate whether inhibition of angiotensin-converting enzyme (with lisinopril 10-20 mg day-1) could ameliorate endothelial dysfunction more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg day-1), usually in combination with a diuretic. We performed a 12-month prospective, randomized, double-blind, parallel study in 43 hypertensive NIDDM patients with diabetic nephropathy (21 treated with lisinopril and 22 with atenolol). The following variables were measured: 24-h ambulatory blood pressure (ABP); transcapillary escape rate of albumin (TERalb; i.e. initial disappearance of intravenously injected 125I-labelled human serum albumin); serum concentrations of von Willebrand factor (vWF), using ELISA, and urinary albumin excretion rate (UAE). Data are presented for 32 patients (16 lisinopril and 16 atenolol; age 60 years, SD 8; 25 males) out of 35 who completed the study and had valid measurements of TERalb. At baseline the two groups were comparable; TERalb (8.5 (SEM 0.6) vs. 7.2 (0.4)%); vWF (2.09 (range 0.82-4.34) vs. 1.97 (0.95-3.86) IU ml-1; UAE 916 (x/divided by antilog SEM 1.3) vs. 1444 (1.2), and mean ABP 110 (SEM 3) vs. 113 (2) mmHg, in the lisinopril and atenolol group, respectively. During follow up, the mean ABP was equally reduced in the lisinopril and atenolol group, by 12 (SEM 2) vs. 10 (2) mmHg, respectively, TERalb decreased in the lisinopril group by 0.6 (SEM 0.7)%, whereas it increased in the atenolol group 1.5 (0.5)%; the mean difference was 2.2% (95% CI, 0.5 to 3.9; p = 0.015). UAE was reduced by 45% (95% CI, 25 to 60) in the lisinopril group vs. 10% (-15 to 30) in the atenolol group (p = 0.014). Serum vWF was not changed during follow up in either group. Our study suggests that lisinopril has both reno- and vasculoprotective properties in hypertensive NIDDM patients with diabetic nephropathy.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/complicaciones , Endotelio Vascular/fisiopatología , Hipertensión/tratamiento farmacológico , Lisinopril/uso terapéutico , Anciano , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Atenolol/farmacología , Atenolol/uso terapéutico , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Lisinopril/farmacología , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Estudios Prospectivos , Renina/sangreRESUMEN
The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/fisiopatología , Hipertensión Renal/tratamiento farmacológico , Riñón/efectos de los fármacos , Anciano , Albuminuria/tratamiento farmacológico , Albuminuria/fisiopatología , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Animales , Antihipertensivos/efectos adversos , Atenolol/efectos adversos , Atenolol/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/complicaciones , Método Doble Ciego , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hipertensión Renal/fisiopatología , Riñón/fisiología , Lisinopril/efectos adversos , Lisinopril/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Conejos , Método Simple Ciego , Factores de TiempoRESUMEN
The aim of our cross-sectional case-control study was to evaluate putative mechanisms of the increased cardiac morbidity and mortality in NIDDM patients with or without diabetic nephropathy. Fifty-one NIDDM patients with diabetic nephropathy (38 males, age 61 +/- 8 years, group 1), 53 NIDDM patients with normoalbuminuria (42 males, 61 +/- 7 years, group 2), and 22 non-diabetic control subjects (15 males, 58 +/- 8 years, group 3) were investigated. Previous antihypertensive treatment was withdrawn 2 weeks before the study. Left ventricular mass index (LVMI) and systolic function were determined by echocardiography. LVMI was elevated, mean +/- SE, in group 1: 157 +/- 6 g m(-2), and in group 2: 139 +/- 7 g m(-2), as compared with group 3: 95 +/- 5 g m(-2) (p < 0.001, for both), and in group 1 as compared with group 2 (p = 0.05). The prevalence of left ventricular hypertrophy (LVH) (LVMI > 131 g m(-2) in men and > 100 gm(-2) in women) was much higher in group 1: 75% (95% CI, 60-86), and group 2: 51% (95% CI, 37-65), as compared with group 3: 9% (95% CI, 1-29) (p < 0.001, for both), and in group 1 as compared with group 2 (p < 0.01). Shortening fraction of the left ventricle, % +/- SE, was relatively reduced in group 1: 32.5 +/- 1.1%, and group 2: 33.4 +/- 1.1%, as compared with group 3: 41.2 +/- 1.2% (p < 0.01, for both). In a subgroup of 26 normoalbuminuric normotensive NIDDM patients, LVMI was higher than in 14 normotensive non-diabetic control subjects: 137 +/- 10 g m(-2) vs 96 +/- 7 g m(-2), respectively (p < 0.005). The prevalence of LVH was 42% (95% CI, 23-63) and 14% (95% CI, 2-43) (p = 0.07) in these two groups, respectively. In conclusion, normotensive and hypertensive NIDDM patients with and without diabetic nephropathy frequently suffer from LVH and relatively reduced systolic function which may constitute independent risk factors for fatal and non-fatal cardiac events.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/patología , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/patología , Factores de Edad , Anciano , Albuminuria/metabolismo , Antihipertensivos/uso terapéutico , Presión Sanguínea , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Ecocardiografía , Femenino , Hemoglobina Glucada/metabolismo , Frecuencia Cardíaca , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Hemoglobinas , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio , Isquemia Miocárdica , Volumen Plasmático , Renina/sangre , Factores Sexuales , Sodio/orina , Factores de TiempoRESUMEN
Previous studies have shown that the part of mixed air (phase II) of CO2-expirograms is very sensitive and specific for diagnosing pulmonary emphysema. Model calculations show that the course of phase II can be understood by serial inhomogeneities in the lung trumpet only, without assuming parallel inhomogeneities. Vice versa a single number can be derived by model calculations to characterize the grade of pulmonary emphysema.
Asunto(s)
Pruebas Respiratorias , Dióxido de Carbono/fisiología , Enfisema Pulmonar/diagnóstico , Humanos , Alveolos Pulmonares/fisiopatología , Enfisema Pulmonar/clasificación , Enfisema Pulmonar/fisiopatología , Valores de ReferenciaRESUMEN
The Steno hypothesis suggests that albuminuria reflects widespread vascular damage (proliferative retinopathy and severe macroangiopathy) due to a generalized vascular (endothelial) dysfunction. We assessed this concept in NIDDM (non-insulin-dependent diabetic) patients with (13 female/ 39 male, age 60 +/- 7 years, group 1) and without (12 female /41 male, age 61 +/- 7 years, group 2) diabetic nephropathy compared to matched non-diabetic subjects (7 female/15 male, age 58 +/- 8 years, group 3). A 12-lead ECG was recorded and coded blindly using the Minnesota Rating Scale; the World Health Organization cardiovascular questionnaire was used to assess past and present evidence of myocardial infarction, angina pectoris, stroke, and peripheral vascular disease (digital systolic blood pressure determination). The degree of diabetic retinopathy was scored from fundus photography. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), plasma concentrations of prorenin (radioimmunoassay) and serum concentrations of von Willebrand factor (enzyme-linked immunoadsorbent assay). Prevalence of ischaemic heart disease (ECG reading) (49/20/5)% and peripheral vascular disease as indicated by reduced systolic blood pressure on big toe (69/30/ 14)% was significantly higher in group 1 vs group 2 (p < 0.01) and in group 2 vs group 3 (p < 0.01), respectively. The prevalence and severity of retinopathy was higher in group 1 vs 2 (p < 0.01). Transcapillary escape rate of albumin (%/h) was elevated in group 1 and 2 as compared to control subjects: 7.9 (4.3-13.7); 7.4 (3.7-16.4) vs 6.0 (3.4-8.7), (p < 0.005), respectively. Plasma prorenin activity (IU/ml) was raised in group 1 and group 2 as compared to group 3: 272 (59-2405); 192 (18-813), and 85 (28-246), p < 0.001, respectively. Serum von Willebrand factor (IU/ ml) was elevated in group 1 as compared to group 2 and 3: 2.07 (0.83-4.34); 1.60 (0.30-2.99) and 1.50 (1.00-2.38), p < 0.001, respectively. Our study demonstrated that NIDDM patients with and without albuminuria had increased transcapillary escape of albumin and raised prorenin activity, whereas only those with albuminuria had increased von Willebrand factor. Patients with NIDDM may have abnormal endothelial function in the absence of albuminuria.
Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/fisiopatología , Nefropatías Diabéticas/fisiopatología , Endotelio Vascular/fisiopatología , Anciano , Albuminuria/fisiopatología , Permeabilidad Capilar/fisiología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/sangre , Nefropatías Diabéticas/sangre , Retinopatía Diabética/sangre , Retinopatía Diabética/epidemiología , Retinopatía Diabética/fisiopatología , Precursores Enzimáticos/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Valores de Referencia , Renina/sangre , Albúmina Sérica/farmacocinética , Factor de von Willebrand/análisisRESUMEN
We assessed the prognosis of diabetic nephropathy during long-term antihypertensive treatment as compared to the prognosis during the natural history of this complication in a prospective study of all IDDM patients (N = 45) aged under 50 with onset of diabetes before the age of 31 who developed diabetic nephropathy between 1974 and 1978 at Steno Diabetes Center, and were followed until death or for at least 16 years [median 16 (4 to 21) years]. Antihypertensive treatment was started 3 (0 to 13) years after onset of diabetic nephropathy. Mean arterial blood pressure at start of antihypertensive treatment was 148/96 (sd 12/10) mm Hg and 143/86 (16/6) mm Hg during the whole interval of antihypertensive treatment (P < 0.01). The cumulative death rate was 45% (95% C.I. 38 to 52) 16 years after onset of diabetic nephropathy, in contrast to previous reports 88% and 94% 12 and 16 years after onset of diabetic nephropathy, respectively. The median survival time in our study exceeded 16 years as compared to five and seven years in untreated patients in the past. Uremia was the main cause of death (12 patients; 55%). In 1994 serum creatinine was 116 (74 to 311) mumol/liter in the 23 surviving patients. The preservation of kidney function and the prognosis of diabetic nephropathy has improved during the past two decades mainly because of effective antihypertensive treatment.
Asunto(s)
Antihipertensivos/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Adulto , Anciano , Presión Sanguínea , Estudios de Cohortes , Creatinina/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/mortalidad , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/mortalidad , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive hypertensive insulin-dependent diabetes patients with nephropathy (mean age, 33 years) who had not been treated previously were all treated with captopril in combination with frusemide or bendrofluazide. The four patients who were refractory to this regimen also received nifedipine. Treatment was continued for a median of 8.9 years (range, 6.3 to 9.8, years). Renal function was assessed every 6 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and albuminuria by radioimmunoassay. Baseline values (+/- SE) were mean arterial blood pressure 146/93 +/- 3/1 mm Hg, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P < 0.01) and albuminuria (392 +/- 1.4 microns/min; P < 0.01), and the rate of decline in GFR was 4.4 +/- 0.7 mL/min/yr, in contrast to previous reports of 10 to 14 mL/min/yr (natural history). Univariate analysis revealed a significant correlation between the rate of decline in GFR and mean arterial blood pressure (r = 0.58, P = 0.01), albuminuria (r = 0.67, P < 0.01), hemoglobin A1c (r = 0.69, P < 0.01), and serum total cholesterol concentration (r = 0.51, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Nefropatías Diabéticas/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Adulto , Albuminuria/tratamiento farmacológico , Bendroflumetiazida/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Captopril/uso terapéutico , Colesterol/sangre , Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Quimioterapia Combinada , Femenino , Furosemida/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Riñón/efectos de los fármacos , Riñón/fisiopatología , Análisis de los Mínimos Cuadrados , Masculino , Persona de Mediana Edad , Nifedipino/uso terapéutico , Pronóstico , Estudios Prospectivos , Análisis de RegresiónRESUMEN
Nondiabetic hypertensive patients lacking the normal nocturnal decline in arterial blood pressure have enhanced cardiovascular complications. Since cardiovascular morbidity and mortality are increased in non-insulin-dependent diabetes mellitus (NIDDM), we performed a prospective cross-sectional case-controlled study comparing the diurnal variation in arterial blood pressure, prevalence of dippers, cardiac autonomic nervous function (beat-to-beat variation during deep breathing), and extracellular fluid volume (51Cr-labeled EDTA) in 55 NIDDM patients with diabetic nephropathy (group 1), 55 NIDDM patients with normoalbuminuria (group 2), and 22 nondiabetic control subjects (group 3). All antihypertensive treatments were withdrawn at least 2 weeks before the study. The nocturnal blood pressure reduction (daytime-to-nighttime)/daytime (mean +/- SE) was impaired in group 1 (6.6 +/- 1.5%) and group 2 (11.1 +/- 1.4%) as compared with group 3 (17.6 +/- 1.7%), and it was impaired in group 1 as compared with group 2 (P < 0.05 for each comparison). The prevalence of dippers (95% confidence interval) was lower in group 1 (42% [29-56]) as compared with group 2 (58% [44-71]; P = 0.08) and group 3 (86% [65-97]; P < 0.001) and in group 2 as compared with group 3 (P < 0.01). Abolished beat-to-beat variation was more prevalent in group 1 (63% [50-76]) as compared with group 2 (15% [7-27]) and with group 3 (5% [0-23]) (P < 0.001). Nocturnal blood pressure reduction was associated with beat-to-beat variation during deep breathing (r = 0.22, P < 0.01). Extracellular fluid volume (mean +/- SE) was higher in group 1 (15.9 +/- 0.5 l/m2) as compared with group 3 (14.1 +/- 0.8 l/m2) (P < 0.05) with group 2 between the two (15.1 +/- 0.4 l/m2).(ABSTRACT TRUNCATED AT 250 WORDS)