Effect of diet and physical exercise treatment on insulin resistance syndrome of schoolchildren.

BACKGROUND: Insulin resistance syndrome (IRS) of schoolchildren may contribute to cardiovascular diseases (CVD) of young adults. The investigation of different steps, baseline screening parameters and treatment of IRS may help the prevention. METHODS: Schoolchildren (53 boys and 61 girls age 5-17 years) because of adverse family history of CVD, hypertension, and obesity were investigated. Patients were divided into 3 groups according to baseline plasma glucose level (PGL) 120 and 180 min. after glucose consumption (GC): (1) PGL < or = 5.5 mmol/L 180 min. after GC, (2) PGL > or = 5.5 mmol/L 180 min. but < or = 7.8 mmol/L 120 min. after GC (3) PGL > or = 7.8 mmol/L 120 min. after GC. Body mass index (BMI), blood pressure (BP) and parameters of glucose and lipid metabolism were measured at baseline and after two year's lifestyle modification. RESULTS: No significant difference was found in the prevalence of cardiovascular risk factors (CRF) between groups 2 and 3. Fasting PGL > 5.5 mmol/L was found in 1, 2, and 6 cases; HOMA index > 4.4 in 7 (24%), 21 (37%), and 9 (35%) subjects; OGIS index < 400 in 3(10%), 29(51%) and 11 (42%) schoolchildren of groups 1, 2, 3, respectively. Lifestyle modification significantly improved BMI, systolic BP, serum triglyceride and HDL-cholesterol levels and insulin sensitivity. CONCLUSIONS: PGL measured 180 minutes after GC may define an important subgroup of pre-diabetic children. The similar prevalance of CRF in both praediabetic groups underlines the importance of this subgroup. Lifestyle modification for two years improves CRF in this population.

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients.

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.

Polymorphism in the promoter region of the apolipoprotein A5 gene is associated with an increased susceptibility for coronary artery disease.

Although triglycerides (TG) are a major risk factor for coronary artery disease (CAD), their exact role is still controversial. Recently, a T/C polymorphism in the promoter region of the apoA5 gene at position 1131 has been found that is associated with an increased plasma TG concentration. We investigated the role of this polymorphism in 308 Hungarian patients with CAD referred to coronary bypass surgery, and in 310 controls recruited from the same area. The prevalence of the apoA5-1131C allele was significantly higher among CAD patients than among controls (10.9% versus 5.7%; P < 0.001, Odds ratio (OR) = 1.99 (1.30-3.04)). Controls carrying the rare C allele had in average 23.0% (P < 0.001), subjects with CAD 13.8% (P < 0.001) higher TG levels compared to common allele homozygotes. The polymorphism was not associated with other conventional CAD risk factors or laboratory data of the patients. In logistic regression models adjusted for age, gender, presence of diabetes, BMI, smoking, LDL-C, HDL-C and hypertension a significantly increased risk of developing CAD was found in patients carrying the apoA5-1131C allele (P < 0.001; OR = 1.98 (1.14-3.48)), suggesting that this allele variant is an independent genetic risk factor for CAD.