Pro-Neurotensin/Neuromedin N and Risk of Incident Metabolic Syndrome and Diabetes Mellitus in the REGARDS Cohort.

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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.

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Authors: Charles D Nicoli, April P Carson, Timothy B Plante, D Leann Long, Leslie A McClure, Janin Schulte, Mary Cushman