Higher Serum Leptin Levels Are Associated with Impaired Vascular Reactivity in Patients with Type 2 Diabetes Mellitus

Background/Objectives: Endothelial dysfunction represents an early stage of vascular injury in type 2 diabetes mellitus (T2DM) and contributes to increased cardiovascular risk. Leptin, a hormone involved in metabolic and inflammatory regulation, has been implicated in vascular dysfunction. However, its association with digital thermal monitoring (DTM)-derived peripheral vascular reactivity in T2DM remains unclear. Methods: This cross-sectional study enrolled 88 patients with T2DM to investigate the association between serum leptin levels and peripheral vascular reactivity, assessed using the digital thermal monitoring-derived vascular reactivity index (VRI). Based on the VRI values, patients were categorized as having good (VRI ≥ 2.0), intermediate (VRI of 1.0-1.9), or poor (VRI < 1.0) vascular reactivity. Serum leptin levels were quantified using an enzyme immunoassay. Results: Patients with poor vascular reactivity were older and had higher total cholesterol, triglyceride, fasting glucose, glycated hemoglobin, urine albumin-to-creatinine ratio, and leptin levels. In the primary parsimonious multivariable logistic regression model adjusted for age, sex, body mass index (BMI) and eGFR, higher serum leptin levels were associated with vascular reactivity dysfunction. Linear regression analysis also showed that log-transformed leptin levels were negatively associated with VRI. Exploratory analyses, including poor vascular reactivity models and penalized regression models, showed generally consistent findings but were interpreted cautiously because of the limited number of outcome events. Conclusions: Higher serum leptin levels were associated with impaired DTM-derived peripheral vascular reactivity in clinically stable patients with T2DM after adjustment for age, sex, BMI, and eGFR. These findings should be interpreted cautiously and require validation in larger prospective studies.