Higher homocysteine and lower betaine increase the risk of microangiopathy in patients with diabetes mellitus carrying the GG genotype of PEMT G774C.

BACKGROUND: Diabetes represents one of the greatest medical and socioeconomic threats worldwide. The pathogenesis involved is complicated. The effect of methyl donors and genetic polymorphisms in metabolic enzymes on the risk of microangiopathy in patients with diabetes is not well understood. This study investigates the association of homocysteine, choline and betaine levels and phosphatidylethanolamine N-methyltransferase (PEMT) G774C (rs12325817) genotypes with the risk of diabetes and its related microangiopathic complications. METHODS: Between January 2009 and June 2010, 184 diabetic patients and 188 non-diabetic control subjects were enrolled in the hospital-based case-control study. Serum concentrations of betaine and choline were determined by high-performance liquid chromatography (HPLC)-mass spectrometry. Serum concentrations of homocysteine were assayed using HPLC. PEMT gene mutations were detected by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: After adjustment for potential confounders, serum total homocysteine had a significant dose-dependent positive association, and serum choline had an inverse association with the risks of diabetes and its microangiopathic complications (both p < 0.001). Although serum betaine was not associated with the risk of diabetes, it had a significant inverse association with diabetic microangiopathy. Compared with GG genotype, the CC genotype of PEMT G774C was associated with a decreased risk of diabetes (OR 0.559, 95% CI 0.338, 0.926) and its microangiopathy (OR 0.452, 95% CI 0.218, 0.937). CONCLUSION: The GG genotype of the PEMT G774C polymorphism, higher levels of serum homocysteine and lower levels of serum betaine are associated with an increased risk of microangiopathy in patients with diabetes.

Neck circumference as an independent predictive contributor to cardio-metabolic syndrome.

BACKGROUND: The predictive potentials of neck circumference (NC) for cardio-metabolic risks remain uncertain. The aim of this study was to investigate whether NC independently contributes to the prediction of cardio-metabolic risks beyond body mass index (BMI), waist circumference (WC) and waist to hip ratio (WHpR) in a large Chinese population. METHODS: A total of 4201 participants (2508 men and 1693 women) aged 20-85 were recruited from the Health Examination Centre between May 2009 and April 2010, anthropometric indices, biochemical and clinical parameters were measured. Receiver operating characteristic, partial correlation and logistic regression analyses were employed to evaluate the association of the anthropometric indices to cardio-metabolic risks separately by gender. RESULTS: Neck circumference was positively correlated with SBP and DBP (r=0.250 and 0.261), fasting blood glucose (FBP) (r=0.177), TG (r=0.240), TC (r=0.143) and LDL-C (r=0.088) and negatively correlated with HDL-C (r=-0.202) in males (all P<0.01). Similar results were found in females with the exception of TC. The AUCs of NC for metabolic abnormalities ranged from 0.558 (Increased LDL-C) to 0.683 (MS-rf) in men and 0.596 (Increased LDL-C) to 0.703 (MS-rf) in women (P<0.01). The NC of ≥37 cm for men and ≥33 cm for women were the best cut-off points for metabolic syndrome. The adjusted ORs (95% CIs) of NC in men and women respectively were 1.29 (1.12-1.48) and 1.44 (1.20-1.72) for metabolic syndrome risk factors (MS-rf), 1.15 (1.01-1.32) and 1.22 (1.03-1.46) for high BP, 1.16 (1.02-1.33) and 1.42 (1.18-1.71) for increased TG, and 1.26 (1.06-1.50) and 1.32 (1.06-1.65) for increased FBP; the adjusted OR of NC in women for decreased HDL-C was 1.29 (1.10-1.51). CONCLUSIONS: Neck circumference was significantly associated with cardio-metabolic risk factors and independently contributed to the prediction of cardio-metabolic risks beyond the classical anthropometric indices in adults of China.