Neurotransmitter Levels (Dopamine, Epinephrine, Norepinephrine, Serotonin) and Associations with Lipid Profiles in Patients with Prediabetes or Newly Diagnosed Type 2 Diabetes Mellitus

Neurotransmitters play a pivotal role not only in central nervous system signaling but also in the regulation of systemic energy metabolism, insulin sensitivity, and cardiovascular function. The contribution of neuroendocrine dysregulation to the development of type 2 diabetes mellitus (T2DM) is increasingly being recognized; however, the interplay between neurotransmitter levels and lipid/insulin resistance profiles in T2DM and prediabetes (PreDM) remains poorly characterized. We evaluated serum dopamine (DA), norepinephrine (NE), epinephrine (EPI), and serotonin (ST) in 110 individuals with PreDM (<i>n</i> = 40) or newly diagnosed T2DM (<i>n</i> = 70). Extended metabolic profiling included HbA1c, lipid panels, and insulin resistance indices (triglyceride-to-glucose index (TyG), TyG-derived indices). Neurotransmitter levels were compared across body mass index (BMI) categories, gender, and glycosylated hemoglobin A1c (HbA1c) quartiles. We applied multivariable linear regression (MLR) adjusted for body mass index (BMI), age, sex, lipids, penalized logistic regression (predicting T2DM status), and exploratory Spearman correlations with False Discovery Rate (FDR) correction. All four neurotransmitters were significantly higher in T2DM versus PreDM (<i>p</i> < 0.001). In T2DM patients, DA and NE levels increased across HbA1c quartiles, and NE levels were significantly higher in quartile 3 compared to quartile 2 (<i>p</i> = 0.045). In multivariable models, T2DM status was the only consistent predictor of neurotransmitter elevations. Logistic regression identified ST (OR = 8.70) and NE (OR = 3.76) as key discriminators of T2DM status, in addition to HbA1c. Exploratory correlation analyses in T2DM showed trends between EPI and insulin resistance indices (TyG adjusted for waist circumference (TyG-WC), TyG adjusted for waist-to-height ratio (TyG-WHtR)) and between DA and low-density lipoprotein cholesterol (LDL-C), although these did not survive to FDR correction. Neurotransmitter levels are elevated in T2DM and correlate with glycemic and metabolic profiles, suggesting early neuroendocrine involvement in the pathogenesis of diabetes. Serotonin and norepinephrine may serve as adjunctive biomarkers for disease stratification, meriting further prospective and mechanistic investigation.