Setor K Kunutsor1, Lyanne M Kieneker2, Stephan J L Bakker2, Richard W James3, Robin P F Dullaart4. 1. School of Clinical Sciences, University of Bristol, Bristol, UK. Electronic address: skk31@cantab.net. 2. Department of Nephrology Medicine, University of Groningen and University Medical Center, Groningen, The Netherlands. 3. Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 4. Department of Endocrinology, University of Groningen and University Medical Center, Groningen, The Netherlands.
Abstract
OBJECTIVE: High-density lipoprotein cholesterol (HDL-C) is an established risk marker for cardiovascular disease and consistently associated with type 2 diabetes risk. Serum paraoxonase-1 (PON-1) - an anti-oxidant constituent of HDL - is inversely associated with cardiovascular disease risk, but its relationship with incident type 2 diabetes is uncertain. We aimed to investigate the prospective association between PON-1 and type 2 diabetes risk. METHODS: PON-1 was measured as its arylesterase activity at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) prospective study of 5947 predominantly Caucasian participants aged 28-75years with no pre-existing diabetes, that recorded 500 type 2 diabetes cases during a median follow-up of 11.2years. RESULTS: Serum PON-1 was positively correlated with HDL-C (r=0.17; P<0.001). In analyses adjusted for conventional diabetes risk factors, the hazard ratio (95% CI) for type 2 diabetes per 1 standard deviation increase in PON-1 was 1.07 (0.98 to 1.18; P=0.13), which remained non-significant (1.02 (0.93 to 1.12) P=0.65) after additional adjustment for potential confounders. The association was unchanged on further adjustment for HDL-C (1.05 (0.96 to 1.15; P=0.29). However, in subsidiary analyses in the same set of participants, serum HDL-C concentration was inversely and independently associated with risk of type 2 diabetes. CONCLUSIONS: Incident type 2 diabetes is associated with HDL cholesterol but not with its anti-oxidant constituent - PON-1 - in a large cohort of apparently healthy men and women. The current data question the importance of PON-1 activity for the development of diabetes.
OBJECTIVE: High-density lipoprotein cholesterol (HDL-C) is an established risk marker for cardiovascular disease and consistently associated with type 2 diabetes risk. Serum paraoxonase-1 (PON-1) - an anti-oxidant constituent of HDL - is inversely associated with cardiovascular disease risk, but its relationship with incident type 2 diabetes is uncertain. We aimed to investigate the prospective association between PON-1 and type 2 diabetes risk. METHODS:PON-1 was measured as its arylesterase activity at baseline in the Prevention of Renal and Vascular End-stage Disease (PREVEND) prospective study of 5947 predominantly Caucasian participants aged 28-75years with no pre-existing diabetes, that recorded 500 type 2 diabetes cases during a median follow-up of 11.2years. RESULTS: Serum PON-1 was positively correlated with HDL-C (r=0.17; P<0.001). In analyses adjusted for conventional diabetes risk factors, the hazard ratio (95% CI) for type 2 diabetes per 1 standard deviation increase in PON-1 was 1.07 (0.98 to 1.18; P=0.13), which remained non-significant (1.02 (0.93 to 1.12) P=0.65) after additional adjustment for potential confounders. The association was unchanged on further adjustment for HDL-C (1.05 (0.96 to 1.15; P=0.29). However, in subsidiary analyses in the same set of participants, serum HDL-C concentration was inversely and independently associated with risk of type 2 diabetes. CONCLUSIONS: Incident type 2 diabetes is associated with HDL cholesterol but not with its anti-oxidant constituent - PON-1 - in a large cohort of apparently healthy men and women. The current data question the importance of PON-1 activity for the development of diabetes.
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