Functional and proteomic alterations of plasma high density lipoproteins in type 1 diabetes mellitus

Shankarappa Manjunatha, Klaus Distelmaier, Surendra Dasari, Rickey E. Carter, Yogish C Kudva, K Sreekumaran Nair

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective Higher HDL-cholesterol (HDL-C) is linked to lower cardiovascular risk but individuals with type 1 diabetes mellitus (T1DM) with normal or high HDL-C have higher cardiovascular events compared to age matched non-diabetic controls (ND). We determined whether altered HDL functions despite having normal HDL-C concentration may explain increased cardiovascular risk in T1DM individuals. We also determined whether irreversible posttranslational modifications (PTMs) of HDL bound proteins occur in T1DM individuals with altered HDL functions. Methods T1DM with poor glycemic control (T1D-PC, HbA1c ≥ 8.5%, n = 15) and T1DM with good glycemic control (T1D-GC, HbA1c ≤ 6.6%, n = 15) were compared with equal numbers of NDs, ND-PC and ND-GC respectively, matched for age, sex and body mass index (BMI). We measured cholesterol efflux capacity (CEC) of HDL in the serum using J774 macrophages, antioxidant function of HDL as the ability to reverse the oxidative damage of LDL and PON1 activity using commercially available kit. For proteomic analysis, HDL was isolated by density gradient ultracentrifugation and was analyzed by mass spectrometry and shotgun proteomics method. Results Plasma HDL-C concentrations in both T1DM groups were similar to their ND. However, CEC (%) of T1D-PC (16.9 ± 0.8) and T1D-GC (17.1 ± 1) were lower than their respective ND (17.9 ± 1, p = 0.01 and 18.2 ± 1.4, p = 0.02). HDL antioxidative function also was lower (p 

Original languageEnglish (US)
Pages (from-to)1421-1431
Number of pages11
JournalMetabolism: Clinical and Experimental
Volume65
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Type 1 Diabetes Mellitus
Proteomics
HDL Cholesterol
Cholesterol
Ultracentrifugation
Firearms
Post Translational Protein Processing
high density lipoprotein-1
Mass Spectrometry
Body Mass Index
Antioxidants
Macrophages
Serum
Proteins

Keywords

  • Functions
  • High density lipoproteins
  • Posttranslational modifications
  • Proteomics
  • Type 1 diabetes mellitus

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Functional and proteomic alterations of plasma high density lipoproteins in type 1 diabetes mellitus. / Manjunatha, Shankarappa; Distelmaier, Klaus; Dasari, Surendra; Carter, Rickey E.; Kudva, Yogish C; Nair, K Sreekumaran.

In: Metabolism: Clinical and Experimental, Vol. 65, No. 9, 01.09.2016, p. 1421-1431.

Research output: Contribution to journalArticle

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abstract = "Objective Higher HDL-cholesterol (HDL-C) is linked to lower cardiovascular risk but individuals with type 1 diabetes mellitus (T1DM) with normal or high HDL-C have higher cardiovascular events compared to age matched non-diabetic controls (ND). We determined whether altered HDL functions despite having normal HDL-C concentration may explain increased cardiovascular risk in T1DM individuals. We also determined whether irreversible posttranslational modifications (PTMs) of HDL bound proteins occur in T1DM individuals with altered HDL functions. Methods T1DM with poor glycemic control (T1D-PC, HbA1c ≥ 8.5{\%}, n = 15) and T1DM with good glycemic control (T1D-GC, HbA1c ≤ 6.6{\%}, n = 15) were compared with equal numbers of NDs, ND-PC and ND-GC respectively, matched for age, sex and body mass index (BMI). We measured cholesterol efflux capacity (CEC) of HDL in the serum using J774 macrophages, antioxidant function of HDL as the ability to reverse the oxidative damage of LDL and PON1 activity using commercially available kit. For proteomic analysis, HDL was isolated by density gradient ultracentrifugation and was analyzed by mass spectrometry and shotgun proteomics method. Results Plasma HDL-C concentrations in both T1DM groups were similar to their ND. However, CEC ({\%}) of T1D-PC (16.9 ± 0.8) and T1D-GC (17.1 ± 1) were lower than their respective ND (17.9 ± 1, p = 0.01 and 18.2 ± 1.4, p = 0.02). HDL antioxidative function also was lower (p ",
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N2 - Objective Higher HDL-cholesterol (HDL-C) is linked to lower cardiovascular risk but individuals with type 1 diabetes mellitus (T1DM) with normal or high HDL-C have higher cardiovascular events compared to age matched non-diabetic controls (ND). We determined whether altered HDL functions despite having normal HDL-C concentration may explain increased cardiovascular risk in T1DM individuals. We also determined whether irreversible posttranslational modifications (PTMs) of HDL bound proteins occur in T1DM individuals with altered HDL functions. Methods T1DM with poor glycemic control (T1D-PC, HbA1c ≥ 8.5%, n = 15) and T1DM with good glycemic control (T1D-GC, HbA1c ≤ 6.6%, n = 15) were compared with equal numbers of NDs, ND-PC and ND-GC respectively, matched for age, sex and body mass index (BMI). We measured cholesterol efflux capacity (CEC) of HDL in the serum using J774 macrophages, antioxidant function of HDL as the ability to reverse the oxidative damage of LDL and PON1 activity using commercially available kit. For proteomic analysis, HDL was isolated by density gradient ultracentrifugation and was analyzed by mass spectrometry and shotgun proteomics method. Results Plasma HDL-C concentrations in both T1DM groups were similar to their ND. However, CEC (%) of T1D-PC (16.9 ± 0.8) and T1D-GC (17.1 ± 1) were lower than their respective ND (17.9 ± 1, p = 0.01 and 18.2 ± 1.4, p = 0.02). HDL antioxidative function also was lower (p 

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