High pro-neurotensin levels in individuals with type 1 diabetes associate with the development of cardiovascular risk factors at follow-up

Flavia Agata Cimini,Marco Giorgio Baroni,Ilaria Barchetta,Laura Bertoccini,Valentina Ceccarelli,Olle Melander,Maria Gisella Cavallo

doi:10.1007/s00592-021-01783-x

Abstract

AimsNeurotensin (NT) is a gut hormone that promotes lipids absorption and controls appetite. Elevated circulating pro-NT, the stable precursor of NT, is associated with cardiovascular (CV) disease, metabolic syndrome (MS) and type 2 diabetes (T2D). Features of MS and insulin resistance are reported also in type 1 diabetes (T1D), with detrimental impact on the overall CV risk profile. Aims of the study were to evaluate plasma pro-NT in T1D patients and to test whether its levels are associated with and/or predictive of CV risk factors and overall risk profile.MethodsFor this longitudinal retrospective study, we analyzed clinical data from 41 T1D individuals referring to the diabetes outpatient clinics at Sapienza University of Rome, Italy, collected at the baseline and after 10 years. Fasting plasma pro-NT levels were measured in T1D subjects at the baseline and in 34 age-, sex-, BMI-comparable healthy individuals recruited in the same period.ResultsPro-NT did not differ significantly between patients and controls (median[range] pro-NT: 156.3 [96.6–198.2] vs. 179.4 [139.7–230.7] pmol/L, p = 0.26). In T1D, greater fasting pro-NT associated with poor glycemic control at baseline and predicted increased waist circumference, reduced insulin sensitivity, dyslipidemia and hypertension at 10-year follow-up. High pro-NT predicted 10-year very-high CV risk with adjusted OR = 11 (95%C.I.: 1.4–94.5; p = 0.029).ConclusionsIn T1D individuals, elevated pro-NT levels predict the development of adverse metabolic profile, which translates in higher CV risk profile at 10-year follow-up. Pro-NT represents a novel predictor/marker of CV risk factors in adults with T1D.

Highlights

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by the immune-mediated destruction of pancreatic β-cells, chronic hyperglycemia and the development of micro- and macro-vascular complications.Individuals with T1D have an almost threefold higher mortality compared to the general population [1] largely due to premature cardiovascular (CV) disease [2, 3]
Several pathophysiological mechanisms, partially overlapping those occurring in type 2 diabetes (T2D) and metabolic syndrome (MS), have been demonstrated in T1D [6, 7]; among them, altered secretion pattern of gut peptide hormones, including amylin, ghrelin and glucosedependent insulinotropic polypeptide (GIP), was found in T1D individuals [8, 9]
Plasma pro-NT levels were comparable between T1D subjects and controls

Summary

Introduction

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by the immune-mediated destruction of pancreatic β-cells, chronic hyperglycemia and the development of micro- and macro-vascular complications.Individuals with T1D have an almost threefold higher mortality compared to the general population [1] largely due to premature cardiovascular (CV) disease [2, 3]. Individuals with pro-NT levels above the median value at baseline (high-proNT; median pro-NT in the T1D group = 161.8 pmol/L) showed significantly greater waist circumference (p = 0.03), LDL-cholesterol (p = 0.02), triglycerides (p = 0.01), FBG (p = 0.01), HbA1c (p = 0.04), insulin requirement (p = 0.04), and lower AST/ALT ratio the whole high-proNT cohort in the category at very high CV risk (Table 3).

Results

Conclusion