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Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes : a comparative cross-sectional study

Melin, Eva O. LU ; Dereke, Jonatan LU orcid and Hillman, Magnus LU (2020) In Lipids in Health and Disease 19(1).
Abstract

Background: The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods: Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked... (More)

Background: The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods: Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed. Results: In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P < 0.001), and triglycerides (P < 0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD. Conclusions: Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.

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; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Extracellular newly identified receptor for advanced glycation end products (EN-RAGE), Inflammation, Soluble receptor for advanced glycation end products (sRAGE), Type 1 diabetes
in
Lipids in Health and Disease
volume
19
issue
1
article number
223
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85092609307
  • pmid:33054750
ISSN
1476-511X
DOI
10.1186/s12944-020-01397-2
language
English
LU publication?
yes
id
f1d9385a-ff17-4391-9a73-2ab9f462600c
date added to LUP
2020-11-04 14:06:18
date last changed
2024-03-05 12:38:31
@article{f1d9385a-ff17-4391-9a73-2ab9f462600c,
  abstract     = {{<p>Background: The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods: Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed. Results: In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P &lt; 0.001), and triglycerides (P &lt; 0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values &lt; 0.043), were associated with AHD. Conclusions: Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.</p>}},
  author       = {{Melin, Eva O. and Dereke, Jonatan and Hillman, Magnus}},
  issn         = {{1476-511X}},
  keywords     = {{Atherosclerosis; Extracellular newly identified receptor for advanced glycation end products (EN-RAGE); Inflammation; Soluble receptor for advanced glycation end products (sRAGE); Type 1 diabetes}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Lipids in Health and Disease}},
  title        = {{Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes : a comparative cross-sectional study}},
  url          = {{http://dx.doi.org/10.1186/s12944-020-01397-2}},
  doi          = {{10.1186/s12944-020-01397-2}},
  volume       = {{19}},
  year         = {{2020}},
}