Abstract
BACKGROUND: Plasma Volume Status (PVS), an index that quantifies the deviation of an individual's plasma volume from the expected volume, plays an important role in cardiovascular homeostasis. Although PVS expansion is well recognized in conditions like heart failure and chronic kidney disease, its relationship with type 2 diabetes (T2D) and antidiabetic treatment remains uncertain. METHODS: We conducted an observational study comparing PVS in adults with T2D and healthy controls matched for sex, age, and BMI. In a separate analysis of a larger T2D cohort, we investigated the association between PVS and different antidiabetic therapies. PVS was calculated using established formulas incorporating hematocrit, body weight, and sex. RESULTS: PVS was significantly expanded in individuals with T2D compared with healthy controls, with a mean difference of + 3.73% (95% CI 0.24 to 7.22, p = 0.041). Among individuals with T2D (n = 638 ), treatment with SGLT2 inhibitors was associated with a significantly lower PVS compared with the diet/metformin reference group (mean difference - 3.40%, 95% CI - 6.14 to - 0.66%, p = 0.015). The greatest reduction was observed under combined SGLT2i + GLP-1RA therapy (-6.50%, 95% CI - 12.25 to -0.75%, p = 0.004), while individuals on GLP-1RA showed non-significant lower PVS values (-2.10%, 95% CI - 5.48 to 1.28%). In contrast, those treated with DPP-4 inhibitors exhibited a significantly higher PVS (+ 4.15%, 95% CI + 0.05 to + 8.85, p = 0.008). No significant difference in PVS was found between insulin-treated individuals and those on diet/metformin. CONCLUSIONS: T2D is associated with a modest but significant increase in PVS. Among antidiabetic agents, SGLT2 inhibitors -alone or in combination with GLP-1 RA- were associated with a contraction in PVS, suggesting favourable hemodynamic effects. Conversely, DPP4 inhibitors were linked to more expanded plasma volume. These findings highlight the differential hemodynamic impact of glucose-lowering therapies and support further prospective research to evaluate their role in cardiovascular protection in T2D.