**Background:** Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and perinatal morbidity and mortality worldwide. Women with pregestational diabetes mellitus (DM) are at particularly high risk, with preeclampsia incidence reaching 20% compared to ~7% in the general obstetric population. The DASH (Dietary Approach to Stop Hypertension) diet has been shown to reduce blood pressure in non-pregnant populations and may lower preeclampsia risk in women with cardiometabolic disorders, but its effect in women with pregestational DM had not been investigated. Additionally, polymorphisms in the FTO gene (associated with obesity and hypertension) and the ADRB2 gene (involved in vasodilation and blood pressure regulation) may modify dietary effects. This study aimed to investigate dietetic, phenotypic, and genotypic features influencing HDP development in women with pregestational DM randomized to a DASH diet or a traditional Brazilian diet.
**Methods:** This was a nutrigenetic sub-study of the DASDIA randomized controlled trial conducted at the Maternity School of the Federal University of Rio de Janeiro, Brazil (2016–2020). Seventy pregnant women with pregestational type 1 or type 2 DM were included (29 DASH, 41 traditional diet). Both diets had identical macronutrient composition (45–55% carbohydrates, 15–20% protein, 25–30% fat) and sodium content (2400 mg/day), but differed in fatty acid profile, fiber, calcium, magnesium, and potassium. All participants received insulin therapy as prescribed and those initiating prenatal care before 16 weeks received daily aspirin (100 mg) for preeclampsia prophylaxis. Blood pressure was measured at each prenatal visit; HDP was diagnosed per ACOG criteria (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg at or after 20 weeks, with proteinuria or end-organ dysfunction for preeclampsia). Genotyping for FTO (rs9939609 T/A, rs17817449 T/G) and ADRB2 (rs1042713 G/A, rs1042714 C/G) was performed by RT-PCR from buccal cell DNA. Linear mixed-effect models analyzed blood pressure trajectories; Cox proportional hazard models assessed time to HDP, adjusted for covariates with p ≤ 0.1 in univariate analysis. Post-hoc power analysis showed 26.16% power for the Cox models given the sample size.
**Key Results:** Sixteen women (22.86%) developed HDP: 9 (21.95%) in the traditional diet group and 7 (24.14%) in the DASH diet group (p = 0.87). Overall, there were 5 (7.14%) cases of gestational hypertension and 11 (15.71%) of preeclampsia, with no significant between-group differences. Three of ten women with chronic hypertension developed superimposed preeclampsia, all in the traditional diet group. Women with HDP delivered earlier than those without (36.9 vs. 38.0 weeks, p = 0.02). Phenotypic factors significantly associated with progression to HDP in adjusted Cox models were: black skin color (aHR 8.63, 95% CI 1.85–40.18, p = 0.01), history of preeclampsia in a previous pregnancy (aHR 11.66, 95% CI 2.22–61.07, p < 0.01), peak mean blood pressure > 100 mmHg during pregnancy (aHR 18.42, 95% CI 1.38–245.98, p = 0.03), SBP ≥ 114 mmHg in the third trimester (aHR 5.56, 95% CI 1.09–28.42, p = 0.04), DBP ≥ 70 mmHg in the first trimester (aHR 70.15, 95% CI 1.43–3450.19, p = 0.03), and HbA1c ≥ 6.41% in the third trimester (aHR 4.76, 95% CI 1.14–19.86, p = 0.03). No significant associations were found for FTO or ADRB2 polymorphisms with HDP progression in any genetic model or haplotype analysis. A borderline effect of the FTO rs9939609 A allele on higher blood pressure trajectory was observed in the traditional diet group but not the DASH diet group, though this did not reach statistical significance.
**Clinical Implications:** This study confirms that in women with pregestational DM, clinical risk factors—particularly black skin color, prior preeclampsia, early diastolic hypertension (DBP ≥ 70 mmHg in the first trimester), and poor third-trimester glycemic control (HbA1c ≥ 6.41%)—are strong predictors of HDP. The extremely high hazard ratio for first-trimester DBP (aHR 70.15) suggests that even modest blood pressure elevations below traditional diagnostic thresholds may identify high-risk women early. The finding that all women who developed HDP had at least one DBP > 80 mmHg and 75% had SBP > 130 mmHg supports the potential utility of ACC/AHA stage 1 hypertension criteria for risk stratification in this population. The lack of a significant difference between DASH and traditional diets may reflect the fact that both were healthy dietary patterns supervised by dietitians, and the study was underpowered (26.16%) to detect diet or gene effects. Notably, the absence of superimposed preeclampsia in the DASH group among women with chronic hypertension (0/6 vs. 3/3 in the traditional diet group) suggests a potential protective effect that warrants further investigation. Larger, adequately powered studies are needed to clarify whether gene-diet interactions influence HDP risk in this high-risk population.