Increased sLRP1 and decreased atrial natriuretic peptide plasma levels in newly diagnosed T2DM patients are normalized after optimization of glycemic control

Front Endocrinol (Lausanne). 2023 Aug 10:14:1236487. doi: 10.3389/fendo.2023.1236487. eCollection 2023.

Abstract

Background: Low-density lipoprotein receptor-related protein 1 (LRP1) negatively modulates circulating atrial natriuretic peptide (ANP) levels. Both molecules are involved in the regulation of cardiometabolism.

Objectives: To evaluate soluble LRP1 (sLRP1) and ANP levels in people with newly diagnosed type 2 diabetes mellitus (T2DM) and determine the effects of metabolic optimization.

Methods: This single-center longitudinal observational study recruited patients with newly diagnosed T2DM (n = 29, HbA1c > 8.5%), and 12 healthy control, age- and sex-matched volunteers. sLRP1 and ANP levels were measured by immunoassays at T2DM onset and at one year after optimization of glycemic control (HbA1c ≤ 6.5%).

Results: T2DM had higher sLRP1 levels than the control group (p = 0.014) and lower ANP levels (p =0.002). At 12 months, 23 T2DM patients reached the target of HbA1c ≤ 6.5%. These patients significantly reduced sLRP1 and increased ANP levels. Patients who did not achieve HbA1c < 6.5% failed to normalize sLRP1 and ANP levels. There was an inverse correlation in the changes in sLRP1 and ANP (p = 0.031). The extent of sLRP1 changes over 12 months of metabolic control positively correlated with those of total cholesterol, LDL cholesterol, TG, TG/HDLc, and apolipoprotein B.

Conclusions: Newly diagnosed T2DM patients have an increased sLRP1/ANP ratio, and increased sLRP1 and decreased ANP levels are normalized in the T2DM patients that reached an strict glycemic and metabolic control. sLRP1/ANP ratio could be a reliable marker of cardiometabolic function.

Keywords: ANP; T2DM; hypoglycemic treatments; metabolic control; sLRP1.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins B
  • Atrial Natriuretic Factor
  • Diabetes Mellitus, Type 2* / diagnosis
  • Glycated Hemoglobin
  • Glycemic Control*
  • Humans

Substances

  • Atrial Natriuretic Factor
  • Glycated Hemoglobin
  • Apolipoproteins B

Grants and funding

The economic support to develop this project was received from: Fundació MARATÓ TV3 with the grant 201521-10 (to VLl-C). Instituto de Salud Carlos III (ISCIII) and co-financed with ERDFs with the grantsPI16-00471 (to JS-Q), PI17-00232 (to JJ), PI20-00334 (to JLS-Q), FIS PI18/01584 and FIS PI21/01523 (to VLl-C). Fundación BBVA Ayudas a equipos de investigación 2019 (“Translational Molecular Imaging for Detection of Cholesterol Entrapment in the Vasculature with 68Ga-labeled LRP1-derived Peptides”) (to VLl-C). AB-A is a predoctoral fellow (FI19/00205) granted by the Programme_Contratos predoctorales de formación de investigación en salud_ from the Instituto de Salud Carlos III (ISCIII) and co-financed with ERDFs. The team is part of CIBER Enfermedades Cardiovasculares (CIBERCV; CB16/11/00276 to DV, XG-M and VLl-C), and CIBER Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM; CB07/08/0016 to JJ, JS-Q, and AP) run by the Instituto de Salud Carlos III. VLl-C and JJ are members of Redes de investigación (Enfermedades Metabólicas y Cáncer RED2018-102799-T), a project run by MINECO. VLl-C, AB-A and DV are members of the Quality Research Group from Generalitat de Catalunya 2017 SGR 946 and JJ, SB and JS-Q of the 2017-SGR-1149group. VLl-C, EG, AB-A, SB and JS-Q are members of the Spanish Atherosclerosis Society Vascular Biology Group. IR-SANTPAU is a centre of CERCA Programme/Generalitat de Catalunya.