Expression of the central obesity and Type 2 Diabetes mellitus genes is associated with insulin resistance in young obese children.

OBJECTIVES: The assessment of the health consequences associated with obesity in young children is challenging. The aims of this study were: (1) to compare insulin resistance indices derived from OGTT in obese patients and healthy control (2) to analyze central obesity and Type 2 Diabetes genes expression in obese children, with special attention to the youngest group (< 10 years old). PATIENTS AND METHODS: The study included 49 children with obesity (median age 13.5 years old), and 25 healthy peers. Biochemical blood tests and expression of 11 central obesity and 33 Type 2 Diabetes genes was assessed. RESULTS: A significant difference in insulin resistance between obese and non-obese adolescents was observed in all studied indices (mean values of the insulin levels: 24.9 vs. 9.71 mIU/L in T0, 128 vs. 54.7 mIU/L in T60 and 98.7 vs. 41.1 mIU/L in T120 respectively; AUC: 217 vs. 77.2 ng/ml*h, mean values of B% (state beta cell function), S% (insulin sensitivity), and IR were 255 (±97) vs. 135 (±37.8), 46.6 (±37.3) vs. 84.2 (±29.6) and 3 (±1.55) vs. 1.36 (±0,56); HIS, WBIS and ISIBel median 3.89, 44.7, 0.73 vs. 8.57, 110, 2.25. All comparisons differed significantly p<0.001). Moreover, insulin sensitivity was significantly better in the older obese group (>10 years old): median AUC 239 vs. 104 ng/ml*h, and HIS, WBIS and ISIBel 3.57, 38, 0.67 vs. 6.23, 75.6, 1.87 respectively in the obese older compared to the obese younger subgroup, p<0.05. The expression of 64% of the central obesity genes and 70% of Type 2 Diabetes genes was higher in the obese compared to control groups. The differences were more pronounced in the younger obese group. CONCLUSION: Insulin resistance may develop in early stage of childhood obesity and in very young children may be associated with higher expression of the central obesity and Type 2 Diabetes genes.

Nɛ-homocysteinyl-lysine isopeptide is associated with progression of peripheral artery disease in patients treated with folic acid.

OBJECTIVE: Folic acid (FA) administration can reduce plasma total homocysteine (tHcy); however, it fails to decrease cardiovascular events and progression of peripheral artery disease (PAD). Nɛ-homocysteinyl-lysine isopeptide (Nɛ-Hcy-Lys) is formed during catabolism of homocysteinylated proteins. We sought to investigate factors that determine the presence of Nɛ-Hcy-Lys in PAD patients with hyperhomocysteinemia receiving FA. PATIENTS AND METHODS: We studied 131 consecutive PAD patients with tHcy > 15 µmol l(-1) taking FA 0.4 mg d(-1) for 12 months. Serum Nɛ-Hcy-Lys was determined by high-performance liquid chromatography (HPLC). We also measured interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), asymmetric dimethylarginine (ADMA) and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)). RESULTS: FA administration resulted in a 70.5% decrease in tHcy (p < 0.0001). However, serum Nɛ-Hcy-Lys was detectable in 28 (21.4%) patients on FA who were more frequently current smokers and survivors of ischaemic stroke (p < 0.001). They had higher tHcy by 46.0%, PAI-1 by 51.7%, 8-iso-PGF(2α) by 59.1% and ADMA by 26.4% (all, p < 0.0001). The presence of Nɛ-Hcy-Lys was associated with lower ankle-brachial index (ABI) values (p < 0.001) and higher prevalence of cardiovascular events (p < 0.001) following therapy. CONCLUSION: The presence of Nɛ-Hcy-Lys in one-fifth of hyperhomocysteinemic individuals with PAD despite FA treatment is associated with progression of PAD and with increased ADMA formation, oxidative stress and hypofibrinolysis.