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1.
Arterioscler Thromb Vasc Biol ; 40(10): 2508-2515, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32757650

RESUMEN

OBJECTIVE: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.8 years, 38.0% males), and 63 children (age 8.8±4.0 years, 50.8% males) were studied. Genetic characterization was available in 129 (96%). The majority (91%) were true homozygotes (true HoFH, n=79, 43.0% children, 46.8% males) or compound heterozygotes (compound heterozygous familial hypercholesterolemia, n=39, 51.3% children, 46.2% males) with putative pathogenic variants in the LDLR. True HoFH due to LDLR variants had higher total (P=0.015) and LDL (low-density lipoprotein)-cholesterol (P=0.008) compared with compound heterozygous familial hypercholesterolemia. Children with true HoFH (n=34) tended to be diagnosed earlier (P=0.051) and had a greater frequency of xanthomas (P=0.016) than those with compound heterozygous familial hypercholesterolemia (n=20). Previous major cardiovascular events were present in 25 (48%) of 52 children (missing information in 2 cases), and in 43 (67%) of 64 adults with LDLR variants. Children who are true HoFH had higher frequency of major cardiovascular events (P=0.02), coronary heart (P=0.013), and aortic/supra-aortic valve diseases (P=0.022) than compound heterozygous familial hypercholesterolemia. In adults, no differences were observed in major cardiovascular events according to type of LDLR variant. From 118 subjects with LDLR variants, 76 (64%) had 2 likely pathogenic or pathogenic variants. In 89 subjects with 2 LDLR variants, those with at least one null allele were younger (P=0.003) and had a greater frequency of major cardiovascular events (P=0.038) occurring at an earlier age (P=0.001). CONCLUSIONS: There was a high frequency of cardiovascular disease even in children. Phenotype and cardiovascular complications were heterogeneous and associated with the type of molecular defect.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , LDL-Colesterol/sangre , Homocigoto , Hiperlipoproteinemia Tipo II/genética , Mutación , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Factores de Edad , Apolipoproteína B-100/genética , Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Niño , Preescolar , Estudios Transversales , Europa (Continente)/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiología , Masculino , México/epidemiología , Persona de Mediana Edad , Fenotipo , Proproteína Convertasa 9/genética , Receptores de LDL/genética , Estudios Retrospectivos , Factores de Riesgo , América del Sur/epidemiología , Adulto Joven
2.
J Diabetes Complications ; 23(6): 376-9, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18849173

RESUMEN

AIM: The aim of this study was to compare the efficacy of glimepiride/metformin combination versus glibenclamide/metformin for reaching glycemic control in patients with uncontrolled type 2 diabetes mellitus. PATIENTS AND METHODS: A randomized, double-blind, multicenter clinical trial was performed in 152 uncontrolled type 2 diabetic patients. Serum fasting and postprandial glucose, hemoglobin A1c (A1C), high-density lipoprotein cholesterol, and triglycerides were measured. After random allocation, all patients received two pills of glimepiride (1 mg)/metformin (500 mg) or glibenclamide (5 mg)/metformin (500 mg) po once a day. Dosage was increased to a maximum of four pills in order to reach the glycemic control goals (fasting glucose or=1% reduction). Statistical analyses were carried out using chi-square, ANOVA, or Student's t test. The protocol was approved by an ethics committee and met all requirements needed to perform research in human subjects; all patients gave written informed consent. RESULTS: Each study group included 76 patients. No significant differences in basal clinical and laboratory characteristics between groups were found. At the end of the study, A1C concentration was significantly lower in the glimepiride/metformin group (P=.025). A higher proportion of patients from the glimepiride group (44.6% vs. 26.8%, P<.05) reached the goal of A1C <7% at 12 months of treatment. A higher proportion of hypoglycemic events were observed in the glibenclamide group (28.9% vs. 17.1%, P<.047). CONCLUSION: Glimepiride/metformin demonstrated being more efficacious than glibenclamide/metformin at reaching the glycemic control goals with less hypoglycemic events in patients with uncontrolled type 2 diabetes mellitus.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gliburida/administración & dosificación , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Compuestos de Sulfonilurea/administración & dosificación , Glucemia/efectos de los fármacos , Índice de Masa Corporal , Combinación de Medicamentos , Femenino , Gliburida/efectos adversos , Humanos , Hiperglucemia/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Compuestos de Sulfonilurea/efectos adversos , Resultado del Tratamiento
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