Clinical Care and Delivery: Paraoxonase 1 phenotype distribution and activity differs in subjects with newly diagnosed Type 2 diabetes (the CODAM Study)

S.W. van den Berg, E.H.J. Jansen, M. Kruijshoop, P.K. Beekhof, E.E. Blaak, C.J.H. van der Kallen, M.M.J. van Greevenbroek, E.J.M. Feskens

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Abstract

Aims Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-bound enzyme, which was recently found to be expressed in the islets of Langerhans. A substitution (Q/R) at position 192 results in enzymes with different activity. Oxidation has been implicated in the onset of diabetes, and it can be hypothesized that PON1 may have a protective effect on diabetes. Our aim was to compare PON1 activities and PON1 Q/R phenotypes in subjects with different degrees of glucose intolerance. Methods We examined 566 members of the Cohort study of Diabetes and Atherosclerosis Maastricht (CoDAM), including subjects with normal glucose tolerance (NGT, n = 298), impaired glucose regulation (IGR, n = 128), newly diagnosed Type 2 diabetes (nDM, n = 78) and treated, that is to say known, Type 2 diabetes (kDM, n = 64). PON1 activity was measured in serum using paraoxon and diazoxon as substrates. The PON1 phenotype was determined using two-dimensional enzyme analysis. Results The RR-phenotype was significantly more frequent in nDM compared with NGT subjects (14.1 vs. 6.0%, P = 0.05). Adjusted for the PON1 phenotype, subjects with nDM had significant lower PON1 activity towards paraoxon and diazoxon than subjects with NGT. Adjusted odds ratios comparing the RR-variant with the QQ-variant were 2.17 [95% confidence interval (CI): 0.90¿5.24] for impaired glucose tolerance, 2.84 (95% CI: 1.03¿7.83) for nDM, 2.13 (95% CI; 0.61¿7.42) for kDM and 2.65 (95% CI: 1.10¿6.40) for total diabetes mellitus. Conclusions An aberrant PON1 phenotype distribution and PON1 activity were observed in early diabetes. In addition, the higher state of oxidative stress may affect the future development of complications.
Original languageEnglish
Pages (from-to)186-193
JournalDiabetic medicine
Volume25
Issue number2
DOIs
Publication statusPublished - 2008

Fingerprint

Aryldialkylphosphatase
Type 2 Diabetes Mellitus
Phenotype
Confidence Intervals
Paraoxon
Glucose Intolerance
Enzymes
Glucose
HDL Lipoproteins
Islets of Langerhans
Atherosclerosis
Diabetes Mellitus
Oxidative Stress
Cohort Studies
Antioxidants
Odds Ratio

Keywords

  • low-density-lipoprotein
  • impaired glucose-tolerance
  • coronary-heart-disease
  • islet beta-cells
  • serum paraoxonase
  • oxidative stress
  • insulin-resistance
  • gene polymorphism
  • iron stores
  • follow-up

Cite this

van den Berg, S.W. ; Jansen, E.H.J. ; Kruijshoop, M. ; Beekhof, P.K. ; Blaak, E.E. ; van der Kallen, C.J.H. ; van Greevenbroek, M.M.J. ; Feskens, E.J.M. / Clinical Care and Delivery: Paraoxonase 1 phenotype distribution and activity differs in subjects with newly diagnosed Type 2 diabetes (the CODAM Study). In: Diabetic medicine. 2008 ; Vol. 25, No. 2. pp. 186-193.
@article{05fe429525ab4e67aac22b531d89aab4,
title = "Clinical Care and Delivery: Paraoxonase 1 phenotype distribution and activity differs in subjects with newly diagnosed Type 2 diabetes (the CODAM Study)",
abstract = "Aims Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-bound enzyme, which was recently found to be expressed in the islets of Langerhans. A substitution (Q/R) at position 192 results in enzymes with different activity. Oxidation has been implicated in the onset of diabetes, and it can be hypothesized that PON1 may have a protective effect on diabetes. Our aim was to compare PON1 activities and PON1 Q/R phenotypes in subjects with different degrees of glucose intolerance. Methods We examined 566 members of the Cohort study of Diabetes and Atherosclerosis Maastricht (CoDAM), including subjects with normal glucose tolerance (NGT, n = 298), impaired glucose regulation (IGR, n = 128), newly diagnosed Type 2 diabetes (nDM, n = 78) and treated, that is to say known, Type 2 diabetes (kDM, n = 64). PON1 activity was measured in serum using paraoxon and diazoxon as substrates. The PON1 phenotype was determined using two-dimensional enzyme analysis. Results The RR-phenotype was significantly more frequent in nDM compared with NGT subjects (14.1 vs. 6.0{\%}, P = 0.05). Adjusted for the PON1 phenotype, subjects with nDM had significant lower PON1 activity towards paraoxon and diazoxon than subjects with NGT. Adjusted odds ratios comparing the RR-variant with the QQ-variant were 2.17 [95{\%} confidence interval (CI): 0.90¿5.24] for impaired glucose tolerance, 2.84 (95{\%} CI: 1.03¿7.83) for nDM, 2.13 (95{\%} CI; 0.61¿7.42) for kDM and 2.65 (95{\%} CI: 1.10¿6.40) for total diabetes mellitus. Conclusions An aberrant PON1 phenotype distribution and PON1 activity were observed in early diabetes. In addition, the higher state of oxidative stress may affect the future development of complications.",
keywords = "low-density-lipoprotein, impaired glucose-tolerance, coronary-heart-disease, islet beta-cells, serum paraoxonase, oxidative stress, insulin-resistance, gene polymorphism, iron stores, follow-up",
author = "{van den Berg}, S.W. and E.H.J. Jansen and M. Kruijshoop and P.K. Beekhof and E.E. Blaak and {van der Kallen}, C.J.H. and {van Greevenbroek}, M.M.J. and E.J.M. Feskens",
year = "2008",
doi = "10.1111/j.1464-5491.2007.02328.x",
language = "English",
volume = "25",
pages = "186--193",
journal = "Diabetic medicine",
issn = "0742-3071",
publisher = "Wiley",
number = "2",

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Clinical Care and Delivery: Paraoxonase 1 phenotype distribution and activity differs in subjects with newly diagnosed Type 2 diabetes (the CODAM Study). / van den Berg, S.W.; Jansen, E.H.J.; Kruijshoop, M.; Beekhof, P.K.; Blaak, E.E.; van der Kallen, C.J.H.; van Greevenbroek, M.M.J.; Feskens, E.J.M.

In: Diabetic medicine, Vol. 25, No. 2, 2008, p. 186-193.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Clinical Care and Delivery: Paraoxonase 1 phenotype distribution and activity differs in subjects with newly diagnosed Type 2 diabetes (the CODAM Study)

AU - van den Berg, S.W.

AU - Jansen, E.H.J.

AU - Kruijshoop, M.

AU - Beekhof, P.K.

AU - Blaak, E.E.

AU - van der Kallen, C.J.H.

AU - van Greevenbroek, M.M.J.

AU - Feskens, E.J.M.

PY - 2008

Y1 - 2008

N2 - Aims Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-bound enzyme, which was recently found to be expressed in the islets of Langerhans. A substitution (Q/R) at position 192 results in enzymes with different activity. Oxidation has been implicated in the onset of diabetes, and it can be hypothesized that PON1 may have a protective effect on diabetes. Our aim was to compare PON1 activities and PON1 Q/R phenotypes in subjects with different degrees of glucose intolerance. Methods We examined 566 members of the Cohort study of Diabetes and Atherosclerosis Maastricht (CoDAM), including subjects with normal glucose tolerance (NGT, n = 298), impaired glucose regulation (IGR, n = 128), newly diagnosed Type 2 diabetes (nDM, n = 78) and treated, that is to say known, Type 2 diabetes (kDM, n = 64). PON1 activity was measured in serum using paraoxon and diazoxon as substrates. The PON1 phenotype was determined using two-dimensional enzyme analysis. Results The RR-phenotype was significantly more frequent in nDM compared with NGT subjects (14.1 vs. 6.0%, P = 0.05). Adjusted for the PON1 phenotype, subjects with nDM had significant lower PON1 activity towards paraoxon and diazoxon than subjects with NGT. Adjusted odds ratios comparing the RR-variant with the QQ-variant were 2.17 [95% confidence interval (CI): 0.90¿5.24] for impaired glucose tolerance, 2.84 (95% CI: 1.03¿7.83) for nDM, 2.13 (95% CI; 0.61¿7.42) for kDM and 2.65 (95% CI: 1.10¿6.40) for total diabetes mellitus. Conclusions An aberrant PON1 phenotype distribution and PON1 activity were observed in early diabetes. In addition, the higher state of oxidative stress may affect the future development of complications.

AB - Aims Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-bound enzyme, which was recently found to be expressed in the islets of Langerhans. A substitution (Q/R) at position 192 results in enzymes with different activity. Oxidation has been implicated in the onset of diabetes, and it can be hypothesized that PON1 may have a protective effect on diabetes. Our aim was to compare PON1 activities and PON1 Q/R phenotypes in subjects with different degrees of glucose intolerance. Methods We examined 566 members of the Cohort study of Diabetes and Atherosclerosis Maastricht (CoDAM), including subjects with normal glucose tolerance (NGT, n = 298), impaired glucose regulation (IGR, n = 128), newly diagnosed Type 2 diabetes (nDM, n = 78) and treated, that is to say known, Type 2 diabetes (kDM, n = 64). PON1 activity was measured in serum using paraoxon and diazoxon as substrates. The PON1 phenotype was determined using two-dimensional enzyme analysis. Results The RR-phenotype was significantly more frequent in nDM compared with NGT subjects (14.1 vs. 6.0%, P = 0.05). Adjusted for the PON1 phenotype, subjects with nDM had significant lower PON1 activity towards paraoxon and diazoxon than subjects with NGT. Adjusted odds ratios comparing the RR-variant with the QQ-variant were 2.17 [95% confidence interval (CI): 0.90¿5.24] for impaired glucose tolerance, 2.84 (95% CI: 1.03¿7.83) for nDM, 2.13 (95% CI; 0.61¿7.42) for kDM and 2.65 (95% CI: 1.10¿6.40) for total diabetes mellitus. Conclusions An aberrant PON1 phenotype distribution and PON1 activity were observed in early diabetes. In addition, the higher state of oxidative stress may affect the future development of complications.

KW - low-density-lipoprotein

KW - impaired glucose-tolerance

KW - coronary-heart-disease

KW - islet beta-cells

KW - serum paraoxonase

KW - oxidative stress

KW - insulin-resistance

KW - gene polymorphism

KW - iron stores

KW - follow-up

U2 - 10.1111/j.1464-5491.2007.02328.x

DO - 10.1111/j.1464-5491.2007.02328.x

M3 - Article

VL - 25

SP - 186

EP - 193

JO - Diabetic medicine

JF - Diabetic medicine

SN - 0742-3071

IS - 2

ER -