The Impact of Gestational Diabetes Mellitus on Cerebral Blood Flow and Cerebrovascular Function After Pregnancy

Gestational Diabetes Mellitus (GDM) currently affects approximately 14% of all pregnancies worldwide. Importantly, the health-related consequences of GDM extend well beyond pregnancy, such that women with a history of GDM have a 40% increased risk of cerebrovascular diseases and a 67% increased risk of dementia, compared to women with a history of uncomplicated pregnancy. Women with a history of GDM have impaired skin microvascular function, compared with women with a history of uncomplicated pregnancy. Therefore, it's likely that GDM results in impaired brain blood vessel function, yet there is little-to-no information regarding the effects of GDM on brain blood vessel health and function after pregnancy.

Therefore, the purpose of the study is to evaluate the effects of GDM on brain blood flow and brain blood vessel function in healthy women with either a history of GDM or uncomplicated pregnancy.

In this study, the investigators will use two different types of ultrasound to non-invasively measure brain blood flow. Brain blood vessel function will be evaluated by examining the brain blood flow responses to increases in carbon dioxide (the increases in carbon dioxide are similar to what is experienced during a breath hold). Additionally, the investigators will compare the brain blood flow results to skin microvascular function to explore potential mechanisms behind possible impairments in brain blood vessel function. Skin microvascular function will be assessed using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) on dime sized areas of the forearm. Finally, for screening purposes and to further explore potential mechanisms behind any potential impairments in brain blood vessel function, the investigators will perform blood draws to determine the metabolic health of the participants and to analyze for substances that influence blood vessel function.

Study Overview

• Status: Recruiting
• Conditions: Postpartum Women; Gestational Diabetes Mellitus (GDM); Uncomplicated Pregnancy
• Intervention / Treatment: Drug: Intradermal Microdialysis; Other: Brain Blood Flow Tests; Other: Local Heating

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Anna Reid-Stanhewicz, PHD; Phone Number: 319-467-1732; Email: anna-stanhewicz@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Iowa Bioscience Innovation Facility
      • Contact: Anna Stanhewicz, P.h.D; Phone Number: 3194671732; Email: anna-stanhewicz@uiowa.edu
      • Contact: Claire Goebel, B.S.; Phone Number: 5158359904; Email: cgoebl@uiowa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

INCLUSION CRITERIA:

• Post-partum women
• 18 years or older
• Delivered within 5 years from the study visit
• History of gestational diabetes diagnosed by an obstetrician and confirmed according to the American College of Obstetricians and Gynecologists criteria for gestational diabetes OR history of uncomplicated pregnancy (defined as no history of gestational diabetes, hypertensive pregnancy, or other gestational disorder).

EXCLUSION CRITERIA: We exclude participants from both groups for:

• Skin diseases
• Current tobacco use
• Diagnosed or suspected hepatic or metabolic disease including diabetes
• Diagnosed with depression or other mood-related disorders, asthma, chronic obstructive pulmonary disease, cystic fibrosis, or pulmonary fibrosis
• Use of prescribed NSAIDs, statins or other cholesterol-lowering medication, antihypertensive medication, carbonic anhydrase inhibitors, corticosteroids, thyroid medications, antidepressants or mood stabilizers, diuretics, phenothiazines, or benzodiazepines
• History of preeclampsia or gestational hypertension,
• History or family history of panic disorder,
• Currently pregnant
• Body mass index <18.5 kg/m2,
• Allergy to materials used during the experiment (e.g. latex), known allergies to study drugs.
• History of heavy alcohol use/binge drinking,
• Have planned procedures with radiological contrast,
• Have a major dental procedure/surgery coming up, such as a dental extraction
• Anatomy of the middle cerebral artery or internal carotid artery that prevents adequate ultrasonography and/or and data collection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Vascular Tests; All women will complete the same protocol, regardless of pregnancy history.

Drug: Intradermal Microdialysis; A total of three microdialysis sites will be perfused with ringer's solution, L-NAME, or ketorolac (one drug per site). After a baseline period, all three sites will undergo tests of blood vessel function including an acetylcholine dose-response protocol and a test of maximal skin blood flow with sodium nitroprusside.; Other: Brain Blood Flow Tests; Participants will complete CO2 breathing procedures to evaluate brain blood vessel health.; Other: Local Heating; A dime-sized heater will be placed on the skin to evaluate cutaneous microvascular function

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stepped hypercapnia-induced change in middle cerebral artery velocity	Middle cerebral artery velocity responses to stepped concentrations of inhaled carbon dioxide gas	During the study visit, an average of 5 hours
Hypercapnia-induced change in internal carotid artery diameter	Internal carotid artery shear-mediated dilation response to inhaled carbon dioxide	During the study visit, an average of 5 hours
Change in microvascular blood flow response to increasing concentrations of acetylcholine	Cutaneous vascular vasodilator responses to acetylcholine perfusion in lactated Ringer's, ketorolac, and L-NAME treated microdialysis sites.	During the study visit, an average of 5 hours

Collaborators and Investigators

• Sponsor: Anna Stanhewicz, PhD

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2025
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): April 15, 2028

Study Registration Dates

• First Submitted: March 12, 2025
• First Submitted That Met QC Criteria: March 28, 2025
• First Posted (Actual): April 4, 2025

Study Record Updates

• Last Update Posted (Actual): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 8, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pregnancy; Postpartum; Gestational Diabetes; Brain Blood Flow
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes, Gestational
• Other Study ID Numbers: 202410260

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No