# Gender-Related Differences in Cerebrovascular Reactivity to L–Arginine in Middle-Aged Type 1 Diabetes Patients

**Authors:** Grzegorz M. Kozera, Jolanta Neubauer-Geryk, Bogumił Wolnik, Sebastian Szczyrba, Leszek Bieniaszewski

PMC · DOI: 10.3390/ijms27041662 · International Journal of Molecular Sciences · 2026-02-09

## TL;DR

This study found that middle-aged women with type 1 diabetes have better cerebral blood vessel reactivity to L-arginine than men, suggesting a gender-based protective effect.

## Contribution

The study reveals gender-related differences in cerebral vasomotor reactivity to L-arginine in type 1 diabetes patients.

## Key findings

- Females showed higher L-arg VMR and baseline MCA flow velocity compared to males.
- The higher reactivity in females persisted after adjusting for age, BMI, and disease factors.
- Female gender appears to protect cerebral endothelial function in type 1 diabetes.

## Abstract

Type 1 diabetes (T1D) increases the risk for cerebral microangiopathy. However, the association between gender and cerebral microcirculatory dysfunction in T1D remains undetermined. Therefore, we have conducted a comparative analysis of cerebral endothelial-mediated microcirculatory parameters between middle-aged Caucasian females and males with type 1 diabetes. The present study examined the nitric oxide-induced vasomotor reactivity of middle cerebral arteries (MCA using transcranial Doppler and L–arginine infusion (L–arg VMR)). The study compared L–arg VMR between 23 males and 26 females with type 1 diabetes without a history of overt cerebrovascular disease. Mean L–arg VMR and baseline MCA flow velocity (V rest) were higher in females than in males (20.1 ± 5.4 vs. 14.6 ± 7.1% p < 0.01 and 73, 54–106 vs. 60.7–77 cm/s p < 0.01, respectively). Males were older than females (39.7 [range: 31.3–55.7] vs. 36.5 [range: 25.0–45.5] years, p = 0.02) and were characterized by later T1D onset and higher insulin/24 h, triglyceride levels and body mass index (BMI). Higher L–arg VMR in females persisted when co-variated with patients’ age, age of onset, BMI, triglyceride level and V rest. Cerebral vasomotor reactivity to L–arginine showed greater efficacy in middle-aged females than in males with T1D, independent of age and disease course. The protective effect of the female gender on cerebral endothelium function has been demonstrated in type 1 diabetes.

## Linked entities

- **Chemicals:** L–arginine (PubChem CID 232)
- **Diseases:** type 1 diabetes (MONDO:0005147)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}
- **Diseases:** renal insufficiency (MESH:D051437), microangiopathy (MESH:D014652), Diabetes (MESH:D003920), endothelial impairment (MESH:D020141), head trauma (MESH:D006259), coronary heart disease (MESH:D003327), injury to (MESH:D014947), hyperlipidemia (MESH:D006949), cerebral microbleeds (MESH:D002547), cerebral endothelial dysfunction (MESH:D002539), neurologic deficits (MESH:D009461), stenosis (MESH:D003251), Small vessel disease (MESH:D059345), psoriasis (MESH:D011565), Retinopathy (MESH:D058437), stroke (MESH:D020521), Overweight (MESH:D050177), hypercapnia (MESH:D006935), WMHs (MESH:D056784), obesity (MESH:D009765), cerebrovascular disease (MESH:D002561), rheumatologic diseases (MESH:D012216), hyperventilation (MESH:D006985), diabetic neuropathy (MESH:D003929), retinal injury (MESH:D012173), cerebral infarcts (MESH:D002544), diabetic retinopathy (MESH:D003930), orthostatic hypotension (MESH:D007024), hypertension (MESH:D006973), occlusion of extracranial arteries (MESH:D001157), arterial hypertension (MESH:D000081029), diabetic foot complications (MESH:D017719), cerebral and systemic microvascular injuries (MESH:D017566), carotid artery occlusion (MESH:D002340), albuminuria (MESH:D000419), lacunar infarctions (MESH:D059409), neuropathy (MESH:D009422), diabetic nephropathy (MESH:D003928), migraine (MESH:D008881), diabetic ketoacidosis (MESH:D016883), T1D (MESH:D003922), sleep deprivation (MESH:D012892), transient ischemic attack (MESH:D002546), nephropathy (MESH:D007674)
- **Chemicals:** TG (MESH:D014280), acetazolamide (MESH:D000086), cholesterol (MESH:D002784), NO (MESH:D009569), L (MESH:D007930), L-Arg (MESH:D001120), ACEI (-), creatinine (MESH:D003404), CO2 (MESH:D002245)
- **Species:** Nicotiana tabacum (American tobacco, species) [taxon 4097], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12941136/full.md

## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941136/full.md

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Source: https://tomesphere.com/paper/PMC12941136