ABSTRACT
AIM: To examine DNA methylation profiles in a longitudinal comparison of pre-diabetes mellitus (Pre-DM) subjects who transitioned to type 2 diabetes mellitus (T2DM). METHODS: We performed DNA methylation study in bisulphite converted DNA from Pre-DM (n = 11) at baseline and at their transition to T2DM using Illumina Infinium HumanMethylation27 BeadChip, that enables the query of 27578 individual cytosines at CpG loci throughout the genome, which are focused on the promoter regions of 14495 genes. RESULTS: There were 694 CpG sites hypomethylated and 174 CpG sites hypermethylated in progression from Pre-DM to T2DM, representing putative genes involved in glucose and fructose metabolism, inflammation, oxidative and mitochondrial stress, and fatty acid metabolism. These results suggest that this high throughput platform is able to identify hundreds of prospective CpG sites associated with diverse genes that may reflect differences in Pre-DM compared with T2DM. In addition, there were CpG hypomethylation changes associated with a number of genes that may be associated with development of complications of diabetes, such as nephropathy. These hypomethylation changes were observed in all of the subjects. CONCLUSION: These data suggest that some epigenomic changes that may be involved in the progression of diabetes and/or the development of complications may be apparent at the Pre-DM state or during the transition to diabetes. Hypomethylation of a number of genes related to kidney function may be an early marker for developing diabetic nephropathy.
ABSTRACT
Over the last 30 years, cardiovascular diseases (CVDs), including stroke and myocardial infarction, have increased in developing countries. Serum lipids and diet of the Fulani, a rural Nigerian population, were previously studied. Despite their consumption of a diet rich in saturated fat, the overall blood lipid profiles of Fulani men and women are generally favourable. However, Fulani males in the same study had mean serum levels of homocysteine, an emerging risk factor for CVD, that exceeded the upper limit of the homocysteine reference range. The authors were interested in knowing if these findings in the Fulani nomads were representative of the biochemical parameters of CVD risk in other ethnic groups in the same region of Nigeria. To address this question, the nutrient content of diets of 55 men, aged 20-75 years, and 77 women, aged 20-70 years, who were inhabitants of a large urban centre in northern Nigeria, was assessed, and their serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and homocysteine were determined. These data were compared with those of the same rural Fulani population studied previously. Urban subjects consumed more calories than rural subjects (men: 2061 vs 1691 kcal; women: 1833 vs 1505 kcal) and had a significantly higher mean body mass index (BMI) and percentage of body fat than rural subjects. Both urban males and females had carbohydrate intakes that were greater than those of Fulani pastoralists (men: 56% vs 33% total calories; women: 51% vs 38% total calories), but had a significantly lower dietary intake of total fat and saturated fat (men: 36% vs 51% of total calories; women: 40% vs 51% of total calories). With the exception of HDL-cholesterol levels, which were significantly lower in the rural population, the blood lipid profiles of rural subjects were more favourable compared to those of urban subjects. Both urban and rural males had homocysteine levels above the upper limit of the reference range for healthy adults (urban males--12.7 micromol/L; rural males-15.2 micromol/L). The dietary intakes of folate and vitamin B12 were lower for rural Fulani subjects, and this was reflected in their significantly lower serum concentrations of these two vitamins. Results of this study suggest that, although the lipid profiles of urban and rural men and women in northern Nigeria indicate a relatively low risk for CVD, their elevated serum homocysteine levels are a cause for concern. The high homocysteine levels among rural men and women could be explained in part at least by their marginal status with respect to folate and vitamin B12.
