Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: an observational study
Author(s)
Type
Journal Article
Abstract
Aims
Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes.
Materials and Methods
Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9–5.8) years follow-up.
Results
Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107–1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035–1.531) p = 0.0213), albuminuria (OR 1.277 (1.124–1.454), p = 0.0002; HR 1.608 (1.208–2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006–1.037) p = 0.0068; HR 1.324 (1.089–1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081–1.818), p = 0.0109).
Conclusions
Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.
Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes.
Materials and Methods
Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9–5.8) years follow-up.
Results
Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107–1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035–1.531) p = 0.0213), albuminuria (OR 1.277 (1.124–1.454), p = 0.0002; HR 1.608 (1.208–2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006–1.037) p = 0.0068; HR 1.324 (1.089–1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081–1.818), p = 0.0109).
Conclusions
Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.
Date Issued
2024-07-01
Date Acceptance
2024-05-21
Citation
Diabetes/Metabolism Research and Reviews, 2024, 40 (5)
ISSN
1520-7552
Publisher
Wiley
Journal / Book Title
Diabetes/Metabolism Research and Reviews
Volume
40
Issue
5
Copyright Statement
© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38850100
Subjects
AUTOPHAGY
diabetes mellitus
diabetic retinopathy
Endocrinology & Metabolism
GLUCOSE
GUT HORMONE
Life Sciences & Biomedicine
microvascular disease
NEUROPEPTIDE-Y
pancreatic polypeptide
RECEPTOR
RISK
Science & Technology
visceral adiposity
VISCERAL FAT
Publication Status
Published
Coverage Spatial
England
Article Number
e3829
Date Publish Online
2024-06-08