Dataset Information

Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy?

ABSTRACT:

Objective

To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy.

Research design and methods

Prospective study of 117 pregnant women with type 1 diabetes. Antihypertensive therapy, mainly methyldopa, was given to obtain blood pressure <135/85 mmHg and urinary albumin excretion <300 mg/24 h. Blood pressure and A1C were recorded during pregnancy. The pregnancy outcome was compared with recently published studies of pregnant women with microalbuminuria or diabetic nephropathy.

Results

Antihypertensive therapy was given in 14 of 100 women with normoalbuminuria, 5 of 10 women with microalbuminuria, and all 7 women with diabetic nephropathy. Mean systolic blood pressure during pregnancy was 120 mmHg (range 101-147), 122 mmHg (116-135), and 135 mmHg (111-145) in women with normoalbuminuria, microalbuminuria, and diabetic nephropathy, respectively (P = 0.0095). No differences in mean diastolic blood pressure or A1C were detected between the groups. No women with microalbuminuria developed preeclampsia. The frequency of preterm delivery was 20% in women with normoalbuminuria and microalbuminuria in contrast to 71% in women with diabetic nephropathy (P < 0.01) where the median gestational age was 258 days (220-260). Compared with previous studies using less stringent antihypertensive therapeutic strategy and less strict metabolic control, gestational age was longer and birth weight was larger in our study.

Conclusions

With intensified antihypertensive therapy and strict metabolic control, comparable pregnancy outcome was seen in type 1 diabetic women with microalbuminuria and normoalbuminuria. Although less severe than in previous studies, diabetic nephropathy was associated with more adverse pregnancy outcome.

SUBMITTER: Nielsen LR

PROVIDER: S-EPMC2606826 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Publications

Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy?

Nielsen Lene Ringholm LR Damm Peter P Mathiesen Elisabeth R ER

Diabetes care 20081022 1

<h4>Objective</h4>To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy.<h4>Research design and methods</h4>Prospective study of 117 pregnant women with type 1 diabetes. Antihypertensive therapy, mainly methyldopa, was given to obtain blood pressure <135/85 mmHg and urinary albumin excretion <300 mg/24 h. Blood pressure and A1C were recorded during pregna ...[more]

PMID: 18945922

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Project description:ImportanceLimited information exists regarding the impact of pharmacotherapy in pregnancy due to ethical concerns of unintended fetal harm. Yet, maternal prescriptive drug use for chronic conditions such as hypertension is common.ObjectiveTo investigate potential causal relationships between perturbing maternal genetic variants influencing antihypertensive drug targets and perinatal outcomes among offspring using mendelian randomization (MR).Design, setting, and participantsThis 2-sample MR study used individual-level single-nucleotide variation (SNV) outcome data from mother-father-offspring trios with complete genetic and phenotypic information from the Norwegian Mother, Father and Child Cohort Study (MoBa) and summary-level SNV exposure data from UK Biobank participants sourced from the Integrative Epidemiology Unit OpenGWAS project. Pregnant individuals were recruited across Norway during their routine ultrasonography examination at 18 weeks' gestation between June 1999 and December 2008, and mothers, fathers, and offspring were followed up after birth. Novel genetic instruments for maternal antihypertensive drug targets that act via systolic blood pressure (SBP) were derived from individual-level data analyzed in January 2018. Two-sample multivariable MR analysis of these maternal drug targets and offspring outcomes were performed between January 2023 and April 2024.ExposuresMaternal genetic variants associated with drug targets for treatments of hypertension, as specified in the National Health Service dictionary of medicines and devices.Main outcomes and measuresOffspring outcomes were Apgar score at 1 minute and 5 minutes, offspring developmental score at 6 months, birth length, birth weight z score, gestational age, head circumference, and congenital malformation. Maternal hypertensive disorders of pregnancy were a positive control.ResultsThe MoBa sample contained 29 849 family trios, with a mean (SD) maternal age of 30.2 (18.6) years and a mean (SD) paternal age of 32.8 (13.1) years; 51.1% of offspring were male. Seven independent SNVs were identified as influencing maternal SBP via the antihypertensive drug target instruments. For higher levels of maternal SBP acting through the CACNB2 calcium channel blocker target, the estimated change in gestational age was 3.99 days (95% CI, 0.02-7.96 days) per 10-mm Hg decrease in SBP. There was no evidence of differential risk for measured perinatal outcomes from maternal SBP acting through drug targets for multiple hypertensive subclasses, such as between the ADRB1 β-adrenoceptor-blocking target and risk of congenital malformation (estimated odds ratio, 0.28 [95% CI, 0.02-4.71] per 10-mm Hg decrease in SBP). Maternal and paternal SBP acting through the EDNRA vasodilator antihypertensive target did not have a potential causal effect on birth weight z score, with respective β estimates of 0.71 (95% CI, -0.09 to 1.51) and 0.72 (95% CI, -0.08 to 1.53) per 10-mm Hg decrease in SBP.Conclusions and relevanceThe findings provided little evidence to indicate that perturbation of maternal genetic variants for SBP that influence antihypertensive drug targets had potential causal relationships with measures of perinatal development and health within this study. These findings may be triangulated with existing literature to guide physicians and mothers in decisions about antihypertensive use during pregnancy.

Project description:Validation of predicted gene expression of human mesangial cells after 24h Tacrolimus stimulus Objective: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. Materials and Methods: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology. We searched for features in interference between the DN molecular model and the tacrolimus MoA molecular model already holding annotation evidence as diagnostic or prognostic biomarker in the context of DN. Results: Thirty nine molecular features were shared between the DN molecular model, holding 252 molecular features and the tacrolimus MoA molecular model, holding 209 molecular features, with six additional molecular features affected by tacrolimus in mesangial cells. Significantly affected molecular pathways by both molecular model sets included cytokine-cytokine receptor interactions, adherens junctions, TGF-beta signaling, MAPK signaling, and calcium signaling. Molecular features involved in inflammation and immune response contributing to DN progression were significantly downregulated by tacrolimus (e.g. the tumor necrosis factor alpha (TNF), interleukin 4, or interleukin 10). On the other hand, pro-fibrotic stimuli being detrimental to renal function were induced by tacrolimus like the transforming growth factor beta 1 (TGFB1), endothelin 1 (EDN1), or type IV collagen alpha 1 (COL4A1). Conclusion: Patients with DN and elevated TNF levels might benefit from tacrolimus treatment regarding maintaining GFR and reducing inflammation. TGFB1 and EDN1 are proposed as monitoring markers to assess degree of renal damage. Next to this stratification approach, the use of drug combinations consisting of tacrolimus in addition to ACE inhibitors, angiotensin receptor blockers, TGFB1- or EDN1-receptor antagonists might warrant further studies. comparison of gene expression of human mesangial cells after 24h Tacrolimus vs. Ctrl; 4 independent experiments were conducted (4xTacrolimus 24h and 4x ctrl. 24h with Drug solvent (DMSO))

Dataset Information

Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy?

Objective

Research design and methods

Results

Conclusions

Publications

Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy?

Similar Datasets

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