Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β cells. Despite advances in medical care and glycemic control, individuals with T1D continue to have shorter lifespans compared to their peers without T1D and face an increased risk of cardiovascular disease (CVD). Consumption of a Western diet (WD), which is high in fat and sugars, is highly prevalent and further increases CVD risk, potentially contributing to the high incidence of CVD in patients with T1D. We hypothesize that the combination of T1D and WD consumption has a more deleterious effect on vasomotor function and arterial stiffness than WD consumption alone, irrespective of sex. Eight-week-old wild-type (control) and Akita (genetic T1D model), male and female mice were fed a WD for 20 weeks to induce obesity. All reported differences were considered significant at P< 0.05. At the end of WD feeding, female Akitas were heavier, whereas male Akitas weighed less than their corresponding controls. Akita mice also exhibited greater hyperglycemia compared with their respective control. Furthermore, glucose levels were higher in males than in females in the Akita group. Males showed higher insulin levels compared to females, and as expected, male Akitas exhibited lower insulin levels compared with male controls. Irrespective of sex, no significant differences were observed between genotypes in blood pressure (assessed via tail-cuff) or aortic pulse wave velocity. Vasodilatory responses to insulin, acetylcholine, and sodium nitroprusside (SNP) were assessed in isolated abdominal aortas and mesenteric arteries. Passive pressure-diameter curves were obtained to evaluate the mechanical properties of mesenteric arteries. Male Akitas exhibited impaired aortic vasodilatory responses to SNP (endothelium-independent) and increased vasocontractile responses to TXA2 agonist compared with controls. Endothelial-dependent vasodilation to insulin was lower in female Akitas compared with controls, but only in the aorta. Akitas presented with an increased modulus of elasticity in the mesenteric artery and calculated incremental pulse wave velocity at higher pressures. Proteomic analysis of the aortic tissue will be performed to identify potential markers and pathways associated with these findings. Overall, these results suggest that the combination of T1D and WD consumption leads to greater stiffness in resistance arteries compared with WD consumption alone. Moreover, vascular smooth muscle cell dysfunction in the abdominal aorta was observed exclusively in male Akita mice fed a WD, indicating a potential sexual dimorphism. These findings are clinically relevant for the treatment of CVD in patients with T1D and obesity. 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.
Beltran-Ornelas et al. (Fri,) studied this question.