Pro-Neurotensin/Neuromedin N and Risk of Incident Metabolic Syndrome and Diabetes Mellitus in the REGARDS Cohort.
The peptide neurotensin is implicated in insulin resistance, diabetes mellitus (DM), and cardiovascular disease.We studied the association of neurotensin’s stable precursor, pro-neurotensin/neuromedin N (pro-NT/NMN) with incident metabolic syndrome (MetS) and DM.We included 3,772 participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who completed the baseline exam (2003-2007), the follow-up exam (2013-2016), and had pro-NT/NMN measured by immunoassay. Weighted logistic regression models were fitted to incident DM, incident MetS, and each MetS component, separately, incorporating demographics, metabolic risk factors, HOMA-IR, and diet scores.Incident MetS was defined by ≥3 harmonized criteria at follow-up in those with <3 at baseline. Incident DM was defined by use of hypoglycemic drugs/insulin, fasting glucose ≥126 mg/dL, or random glucose ≥200 mg/dL, in those without these at baseline.Median [IQR] plasma pro-NT/NMN was 160 [118-218] pmol/L. 564 (of 2,770 without baseline MetS) participants developed MetS and 407 (of 3,030 without baseline DM) developed DM. Per standard deviation (SD) higher log-Pro-NT/NMN, the demographic-adjusted odds ratio (OR) and 95% confidence interval (CI) of incident MetS was 1.22 (1.11-1.35); 1.16 (1.00-1.35) for incident low HDL, and 1.25 (1.11-1.40) for incident dysglycemia. The association of pro-NT/NMN with MetS was attenuated in the model adding HOMA-IR (OR per SD log-pro-NT/NMN 1.14, 95% CI 1.00-1.30). There was no association with incident DM (OR per SD log-pro-NT/NMN 1.06, 95% CI 0.94-1.19).Pro-NT/NMN was associated with MetS and two components, dysglycemia and low HDL, likely explained by insulin resistance.
Authors: Charles D Nicoli, April P Carson, Timothy B Plante, D Leann Long, Leslie A McClure, Janin Schulte, Mary Cushman