RESUMEN
BACKGROUND: A thiazide diuretic used in combination with benazepril is superior to amlodipine plus benazepril in reducing albuminuria in hypertensive patients with diabetes. However, calcium channel blockers have diverse characteristics. Thus, we investigated whether combining an angiotensin receptor blocker with either azelnidipine or a thiazide diuretic produced similar reductions in albuminuria in hypertensive diabetic patients for the same levels of blood pressure achieved. METHODS: Hypertensive patients with type 2 diabetes and albuminuria (30-600 mg/g creatinine) under antihypertensive treatment (mean age 67.0±7.6 years) were instructed to stop all antihypertensive treatment and take a combination of olmesartan (20 mg/day) and amlodipine (5 mg/day) for 3 months (run-in period). Then, patients were randomly assigned to receive either olmesartan plus azelnidipine (16 mg/day; n=71) or olmesartan plus trichlormethiazide (1 mg/day; n=72) for an additional 6 months. The primary end point was urinary excretion of albumin at 6 months after randomization. RESULTS: At the time of randomization, urinary albumin was 116.0 and 107.8 mg/g creatinine (geometric mean) in the azelnidipine and diuretic arms, respectively, and was reduced to a similar extent [79.8 (95% confidence interval 66.4-96.0) and 89.7 (74.6-107.7) mg/g creatinine, respectively, after adjustment for baseline values]. Blood pressure did not differ between the two groups throughout the study period. CONCLUSIONS: Azelnidipine is equally effective as a thiazide diuretic in reducing urinary albumin when used in combination with olmesartan.
Asunto(s)
Albuminuria/tratamiento farmacológico , Ácido Azetidinocarboxílico/análogos & derivados , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dihidropiridinas/uso terapéutico , Hipertensión/tratamiento farmacológico , Imidazoles/uso terapéutico , Enfermedades Renales/prevención & control , Tetrazoles/uso terapéutico , Adulto , Anciano , Albuminuria/diagnóstico , Albuminuria/etiología , Antihipertensivos/uso terapéutico , Ácido Azetidinocarboxílico/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/etiología , Diabetes Mellitus Tipo 2/complicaciones , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hipertensión/complicaciones , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Adulto JovenAsunto(s)
Insuficiencia Suprarrenal/complicaciones , Clorpromazina/efectos adversos , Hiponatremia/etiología , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Insuficiencia Suprarrenal/tratamiento farmacológico , Anciano , Dispepsia/etiología , Humanos , Hidrocortisona/administración & dosificación , Hiponatremia/tratamiento farmacológico , Síndrome de Secreción Inadecuada de ADH/etiología , Masculino , Solución Salina Hipertónica/administración & dosificación , Resultado del TratamientoRESUMEN
Basic fibroblast growth factor (bFGF) stimulates angiogenesis and induces neural cell regeneration. We investigated the effects of bFGF on diabetic neuropathy in streptozotocin-induced diabetic rats. Diabetic rats were treated with human recombinant bFGF as follows: 1) intravenous administration, 2) intramuscular injection into thigh and soleus muscles with cross-linked gelatin hydrogel (CGH), and 3) intramuscular injection with saline. Ten or 30 days later, the motor nerve conduction velocity (MNCV) of the sciatic-tibial and caudal nerves, sensitivity to mechanical stimuli, sciatic nerve blood flow (SNBF), and retinal blood flow (RBF) were measured. Delayed MNCV in the sciatic-tibial and caudal nerves, hypoalgesia, and reduced SNBF in diabetic rats were all ameliorated by intravenous administration of bFGF after 10, but not 30, days. Intramuscular injection of bFGF with CGH also improved sciatic-tibial MNCV, hypoalgesia, and SNBF after 10 and 30 days, but caudal MNCV was not improved. However, intramuscular injection of bFGF with saline had no significant effects. bFGF did not significantly alter RBF in either normal or diabetic rats. These observations suggest that bFGF could have therapeutic value for diabetic neuropathy and that CGH could play important roles as a carrier of bFGF.
Asunto(s)
Inductores de la Angiogénesis/uso terapéutico , Diabetes Mellitus Experimental/fisiopatología , Neuropatías Diabéticas/prevención & control , Factor 2 de Crecimiento de Fibroblastos/uso terapéutico , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Reactivos de Enlaces Cruzados , Combinación de Medicamentos , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Gelatina/administración & dosificación , Inyecciones Intramusculares , Masculino , Conducción Nerviosa/efectos de los fármacos , Ácido Poliglutámico/administración & dosificación , Ratas , Ratas Wistar , Vasos Retinianos/efectos de los fármacos , Vasos Retinianos/fisiopatologíaRESUMEN
Diabetic neuropathy is based on the impairment of nerve blood flow and the metabolic disorder. Although the vasodilating agents and anticoagulants improve nerve function and symptoms in diabetic neuropathy, more effective treatments are needed. Because endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood, many studies have shown that transplantation of EPCs improves circulation to ischemic tissues. In this study, we have demonstrated that therapeutic neovascularization using human umbilical cord blood-derived EPCs reversed diabetic neuropathy. EPCs were isolated and expanded on day 7 of culture from cord blood mononuclear cells. Unilateral intramuscular injection of EPCs into hindlimb skeletal muscles significantly ameliorated impaired sciatic motor nerve conduction velocity and sciatic nerve blood flow in the EPC-injected side of streptozotocin-induced diabetic nude rats compared with the saline-injected side of diabetic nude rats. Histological study revealed an increased number of microvessels in hindlimb skeletal muscles in the EPC-injected side of diabetic rats. These findings suggest that transplantation of EPCs from cord blood may be a useful treatment for diabetic neuropathy.