The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects, and associates with increased cardio-metabolic risk in children.

BACKGROUND AND AIMS: 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM in a cohort of Italian adults with T2DM and in non-diabetic controls. To add further insight into the role of VDR gene we explored whether this association begins early in life in overweight/obese children, or becomes manifest only in adulthood. METHODS AND RESULTS: As many as 1788 adults and 878 children were genotyped for the rs11568820 polymorphism. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin-resistance and secretion were also calculated. The AA genotype was significantly more frequent in adults with T2DM compared to controls (7.5% vs. 4.6%, P = 0.037), and conferred a higher risk of T2DM (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of ß-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk. CONCLUSIONS: Our study demonstrates for the first time that VDR gene AA carriers have higher risk of T2DM and impaired insulin secretion. In children, the association between AA homozygous and high-normal 2h glucose suggests that mild alterations associated with this genotype may appear early in life.

Could ADMA levels in young adults born preterm predict an early endothelial dysfunction?

BACKGROUND: Sporadic data present in literature report how preterm birth and low birth weight are risk factors for the development of cardiovascular diseases in later life. High levels of asymmetric dimethylarginine (ADMA), a strong inhibitor of nitric oxide synthesis, are associated with the future development of adverse cardiovascular events and cardiac death. AIMS: 1) to verify the presence of a statistically significant difference between ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) and 2) to seek correlations between ADMA levels in ex-ELBW and anthropometric and clinical parameters (gender, chronological age, gestational age, birth weight, and duration of stay in Neonatal Intensive Care Unit). METHODS: Thirty-two ex-ELBW subjects (11 males [M] and 21 females [F], aged 17-29years, mean age 22.2 ± 2.3 years) were compared with 25 C (7 M and 18F). ADMA levels were assessed by high-performance liquid chromatography with highly sensitive laser fluorescent detection. RESULTS: ADMA levels were reduced in ex-ELBW subjects compared to C (0.606+0.095 vs 0.562+0.101 µmol/L, p<0.05), and significantly correlated inversely with gestational age (r=-0.61, p<0.00001) and birth weight (r=-0.57, p<0.0002). CONCLUSIONS: Our findings reveal a significant decrease in ADMA levels of ex-ELBW subjects compared to C, underlining a probable correlation with preterm birth and low birth weight. Taken together, these results may underlie the onset of early circulatory dysfunction predictive of increased cardiovascular risk.

Gender-specific aspects in primary and secondary prevention of cardiovascular disease.

Gender differences in biological substrates of disease determine different clinical manifestations of CV disease with important implications for prevention, diagnosis and therapy in the two sexes. In women, the activity of sex hormones reduces the influence of CV risk factors during the reproductive age, and delays the onset of CHD of 2 decades compared to men. However, women as men suffer from CV events, and in women mortality from all CV causes and have greater than the sum of the others 7 causes of death together. Women are more likely than men to die of a first myocardial infarction a probability of developing heart failure or a second infarction than their male counterparts. The levels of lipid components vary in different ages of life and in the two genders. TC and LDL increase in men between 35 and 50 years of age. On the contrary LDL levels do not change significantly in fertile women in which they have a lower predictive value for CHD than in men, HDL levels are higher in premenopausal women than in men of the same age and their role in predicting CHD is considerably higher in women. High triglycerides and Lp(a) are more important as a risk factor in women than in men. Because of the greater incidence of cardiovascular diseases in men until the early 80s, the information about the importance of risk factors associated with an increased risk of cardiovascular events has been gathered mainly in men and transferred to women. Most studies on lipid-lowering therapy did not have the adequate statistical power to show significant reductions in CV events in women. Regarding the indications for use of statins in daily practice, current data suggest that in secondary prevention statins are equally effective in both genders while in primary prevention the CV benefits of lipid-lowering therapy in women are less clear than in men and therefore should be used according to the degree of risk calculated from the available score systems.