RESUMEN
Aims- To study serum Lp(a) levels and other metabolic cardiovascular risk factors in children with type I diabetes mellitus (DM) in comparison with sex and age matched nondiabetic children. To determine the influence of diabetes control on serum lipoprotein (a) concentrations. Design- Transversal observational study. Target population: diabetic group: 70 type I DM children with microalbuminuria and no macro-microvascular nor neurological complications, aged from 8 to 15 years; 30 boys, 40 girls. Mean duration of type I DM was 8 ñ 4 years. Non diabetic group: composed by 123 healthy children with no family history of DM, aged from 8 to 15 years, 53 boys, 70 girls. Methods- The lipids profile include: total cholesterol (TC) and triglyceride (TG), cholesterol high-density lipoproteins (C-HDL) cholesterol very-low-density lipoproteins (C-LDL) and cholesterol low-density lipoproteins (C-LDL). ApoAI, APOAII and ApoB, Lp(a) and fructosamine. Results- Fructosamine concentration in diabetic children was 340 ñ 108 uM/1 in 240 ñ 25 uM/I nondiabetic children. Lp(a) serum levels did not significantly differ among both groups 17 ñ 16 mg/dl in diabetics 19 ñ 18 mg/dl in controls. Multivariate analysis showed that in the diabetic children the worsening of metabolic control as reflected by fructosamine, was positively correlated with the increase in total Lp(a) serum concentration. Conclusions- In children aged 8-15 years with uncomplicated IDDM lasting less than 15 years duration (Lp(a) serum levels are positively correlated with the poorest metabolic control
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Diabetes Mellitus Tipo 1/metabolismo , Lipoproteína(a)/sangre , Enfermedades Cardiovasculares/etiología , Colesterol/sangre , Estudios Transversales , Factores de Riesgo , Apolipoproteínas/aislamiento & purificación , Triglicéridos/sangreRESUMEN
The propensity of an individual to develop type I (insulin dependent) diabetes mellitus is directly related to specipic HLA clase II proteins, specially those from DR and DQ regions. Genetic susceptibility to insulin dependent diabetes arises from a preestablished conformation of alpha and ß chains of DQ and ß chain of DR. Since the classic demonstration by McDevitt and colleagues that DQ ß chain aspartate at position 57 was protective against the development of the disease, many populations have been surveyed to study the association between the incidence Type I diabetes and determined frequencies of DR and DQ haplotypes. The assocation between these markers and susceptibility to Type I diabetes is well established in caucasians at the present time. However, little information is available for Latin American populations, that share a mixture of european, african and native genes. Our group is studying genetic markers of three Latin American populations (Argentina, Perú and Chile) and their possible association to the different incidence of Type I diabetes mellitus in each country
Asunto(s)
Humanos , Diabetes Mellitus Tipo 1/genética , Complejo Mayor de Histocompatibilidad/genética , Antígenos HLA-DP/aislamiento & purificación , Antígenos HLA-DQ/aislamiento & purificación , Antígenos HLA-DR/aislamiento & purificación , Haplotipos/genética , Estudios de Casos y Controles , Susceptibilidad a Enfermedades/genética , Antígenos de Histocompatibilidad Clase II/genética , Marcadores Genéticos/genéticaRESUMEN
Insulin dependent diabetes mellitus (IDDM) is strongly associated with particular HLA-DQ alpha/beta markers in white population. The heterodimers confirmation composed of a DQ alpha chain with an arginine at residue 52 (Arg52) combined to a DQ beta chain lacking an aspartic acid at residue 57 (non asp57) increase markedly the risk to develop IDDM. To confirm this association, 63 IDDM patients from Santiago de Chile registry, 20 IDDM patients from Temuco registry and 74 unrelated helathy non diabetic control subjects were studied. With polymerase chain reaction (PCR) and sequence specific oligonucleotide probes the individuals were typed for their HLA-DQA1 and DQB1 alleles, their DQA1/DQB1 genotype and heterodimers conformation were compared. In diabetic population both markers Arg52 homocygote and non Asp57 homocygote were increased regard to control subjects (R/R: 0.76 and 0.85 vs 0.33; ND/ND: 0.78 and 0.75 vs 0.50, p<0.05). A high relative risk (RR) was determined for both homocygote markers in IDDM groups.compared. Arg52 DQ alpha (R)/non Asp57 DQ beta (ND) heterodimers were strongly associated with susceptibility to IDDM. A high RR was observed in patients with four susceptibility DQ heterodimers (RR1: 13.7 in IDDM-Santiago and RR2: 18.6 in IDDM-Temuco, p<0.00003). The HLA-DQ alpha/beta markers and their risk heterodimers are increased in our diabetic population and could be considered as susceptibility markers to develop IDDM