Acute, local metformin does not improve acetylcholine-mediated microvascular dilation in postpartum women with a history of gestational diabetes

Adam Corkery; Grace Maurer; Claire Goebel; Diana Jalal; Brian O'Neill; Anna Stanhewicz

doi:10.1152/physiol.2026.41.S1.2299356

Abstract only Gestational diabetes mellitus (GDM), a disorder characterized by new onset glucose intolerance during gestation that typically resolves upon delivery, is associated with postpartum microvascular dysfunction. Metformin (MET) improves vascular function in individuals with diabetes-related disorders, which is likely due to MET’s ability to directly improve nitric oxide-mediated vasodilation. It is unclear, however, whether MET can improve GDM-associated microvascular dysfunction in postpartum women with a healthy metabolic profile. Therefore, the purpose of this study was to determine if acute MET, delivered via intradermal microdialysis, would improve cutaneous microvascular dilation responses to acetylcholine (ACh) in healthy women with a history of GDM. We hypothesized that acute MET would improve both peak cutaneous vascular conductance (CVC = red blood cell flux/mean arterial pressure) to ACh and result in an overall greater CVC response to an ACh dose-response protocol. 9 healthy women with a history of GDM who were < 5 years postpartum (age: 34 ± 5 years; fasting glucose: 82 ± 9 mg/dL; hemoglobin A1c: 5.2 ± 0.2 %) participated in 1 experimental visit. Intradermal microdialysis was utilized at 2 individual sites on the ventral forearm to simultaneously perfuse lactated Ringer’s solution (Ringer’s) or 5 mM MET at 2 μL/minute. After an initial baseline period, ACh was co-perfused with Ringer’s and MET in ascending doses (10-10 through 10-1 M) to evaluate ACh-mediated dilation. Cutaneous red blood cell flux was continuously measured via laser-Doppler flowmetry, and CVC was calculated and normalized to maximum (%CVCmax; 28mM sodium nitroprusside + 43°C). Repeated measures ANOVAs were used to calculate differences between the Ringer’s and MET sites during baseline, peak %CVCmax, and the overall ACh dose-response. There was no difference in %CVCmax between the Ringer’s and MET sites at baseline (Ringer’s: 10.1 ± 3.2 vs. MET: 10.1 ± 3.4 %CVCmax; p = 0.95). Similarly, MET did not augment the peak CVC response to ACh (Ringer’s: 73.9 ± 21.7 vs. MET: 88.0 ± 10.3 %CVCmax; p = 0.09). Finally, there was not an overall difference in %CVCmax between microdialysis sites across the ACh dose-response (p = 0.12). Acute, local treatment with MET did not improve ACh-mediated dilation, suggesting that acute MET may not directly improve cutaneous microvascular function in healthy postpartum women with a history of GDM. Future studies should determine if longer-term oral treatment with MET could improve microvascular function in this high-risk population. This work was supported by NIH HL169201 (AES) and DK112751 (ATC). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Acute, local metformin does not improve acetylcholine-mediated microvascular dilation in postpartum women with a history of gestational diabetes

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