Does a history of hypertensive disorders of pregnancy help predict future essential hypertension? Findings from a prospective pregnancy cohort study.

Hypertensive disorder of pregnancy (HDP) is considered an important determinant in the prediction of future hypertension. The aim of this study is to examine whether HDP improves prediction of future hypertension, over prediction based on established risk factors measured during pregnancy. We used a community based cohort study of 2117 women who received antenatal care at a major hospital in Brisbane between 1981 and 1983 and had blood pressure assessed 21 years after the index pregnancy. Of these 2117 women, 193 (9.0%) experienced HDP and 345 (16.3%) had hypertension at 21 years postpartum. For women with HDP, the odds of being hypertensive at 21 years postpartum were 2.46 (95% CI 1.70, 3.56), adjusted for established risk factors including age, education, race, alcohol, cigarettes, exercise and body mass index. Addition of HDP did not improve the prediction model that included these established risk factors, with the area under the curve of receiver operator (AUROC) increasing from 0.710 to 0.716 (P-value for difference in AUROC=0.185). Our findings suggest that HDP is strongly and independently associated with future hypertension, and women who experience this condition should be counselled regarding lifestyle modification and careful ongoing blood pressure monitoring. However, the development of HDP during pregnancy does not improve our capacity to predict future hypertension, over risk factors identifiable at the time of pregnancy. This suggests that counseling regarding lifestyle modification and ongoing blood pressure monitoring might reasonably be provided to all pregnant and postpartum women with identifiable risk factors for future hypertension.

Insulin promoter DNA methylation correlates negatively with insulin gene expression and positively with HbA(1c) levels in human pancreatic islets.

AIMS/HYPOTHESIS: Although recent studies propose that epigenetic factors influence insulin expression, the regulation of the insulin gene in type 2 diabetic islets is still not fully understood. Here, we examined DNA methylation of the insulin gene promoter in pancreatic islets from patients with type 2 diabetes and non-diabetic human donors and related it to insulin expression, HbA(1c) levels, BMI and age. METHODS: DNA methylation was analysed in 25 CpG sites of the insulin promoter and insulin mRNA expression was analysed using quantitative RT-PCR in pancreatic islets from nine donors with type 2 diabetes and 48 non-diabetic donors. RESULTS: Insulin mRNA expression (p = 0.002), insulin content (p = 0.004) and glucose-stimulated insulin secretion (p = 0.04) were reduced in pancreatic islets from patients with type 2 diabetes compared with non-diabetic donors. Moreover, four CpG sites located 234 bp, 180 and 102 bp upstream and 63 bp downstream of the transcription start site (CpG -234, -180, -102 and +63, respectively), showed increased DNA methylation in type 2 diabetic compared with non-diabetic islets (7.8%, p = 0.03; 7.1%, p = 0.02; 4.4%, p = 0.03 and 9.3%, p = 0.03, respectively). While insulin mRNA expression correlated negatively (p < 1 × 10(-6)), the level of HbA(1c) correlated positively (p ≤ 0.01) with the degree of DNA methylation for CpG -234, -180 and +63. Furthermore, DNA methylation for nine additional CpG sites correlated negatively with insulin mRNA expression (p ≤ 0.01). Also, exposure to hyperglycaemia for 72 h increased insulin promoter DNA methylation in clonal rat beta cells (p = 0.005). CONCLUSIONS/INTERPRETATIONS: This study demonstrates that DNA methylation of the insulin promoter is increased in patients with type 2 diabetes and correlates negatively with insulin gene expression in human pancreatic islets.