Cholesterol efflux capacity of high-density lipoprotein was not associated with cognitive decline and brain structures in older people with diabetes mellitus.

AIMS/INTRODUCTION: To examine the association between cholesterol efflux capacity (CEC) of serum high-density lipoprotein (HDL) and cognitive function and brain structures in older people with diabetes mellitus. MATERIALS AND METHODS: Participants of a randomized placebo-controlled trial of 27-month vitamin B12 supplementation in older people with diabetes mellitus, which showed no effect on cognition, were further followed up at month 72. Cognitive tests included the Clinical Dementia Rating scale, Neuropsychological Test Battery in memory, executive function and psychomotor speed. Brain magnetic resonance imaging scans were carried out in a subset at baseline, month 27 and month 45. Fasting serum at baseline, month 9, month 27 and month 72 were analyzed for adenosine triphosphate-binding cassette transporter A1-mediated CEC of HDL and apolipoprotein A1 (ApoA1). RESULTS: Serum HDL cholesterol at baseline was associated with better executive and memory function at follow up. Serum ApoA1 was associated with a better memory Z-score at month 18. Serum CEC and ApoA1 were not associated with Clinical Dementia Rating scale, Neuropsychological Test Battery, hippocampal volume and white matter disease on magnetic resonance imaging at baseline and whole brain atrophy rates. They were also not associated with cognitive function at month 27 and 72 on multilevel modeling. CEC and ApoA1 decreased significantly from baseline to month 27. Faster decliners in CEC had a greater increase in brain peak width of skeletonized mean diffusivity. CONCLUSIONS: Higher serum HDL cholesterol was associated with more favorable changes in memory and executive function in older people with diabetes mellitus. However, this was not due to CEC or ApoA1. A decline in CEC was associated with small vessel disease in the brain.

Endothelial lipase and reverse cholesterol transport in type 2 diabetes mellitus.

UNLABELLED: Aims/Introduction: Endothelial lipase (EL) plays an important role in high-density lipoprotein (HDL) metabolism and experimental data suggest that EL might be proatherogenic. We have investigated whether serum EL concentration is associated with changes in serum capacity to induce cholesterol efflux and arterial stiffness in type 2 diabetes. MATERIALS AND METHODS: Serum EL was assayed by ELISA in 172 diabetic patients and 175 controls. The ability of serum to induce cholesterol efflux was measured using a cell culture system and arterial stiffness was determined by measuring pulse wave velocity (PWV) between carotid and femoral arteries. RESULTS: Diabetic patients had significantly higher C-reactive protein (CRP) and EL (27.7 ± 16.6 ng/mL vs 24.0 ± 11.3, P < 0.05). Cholesterol efflux to serum mediated through scavenger receptor class B type I was impaired (15.1 ± 2.5%vs 16.7 ± 3.1, respectively, P < 0.01). In controls, serum EL correlated with cholesterol efflux to serum (r = -0.16, P = 0.025), but only a trend was seen in the diabetic patients. Linear regression showed that in controls, HDL, serum EL and waist circumference were major independent determinants of cholesterol efflux; whereas in the diabetic cohort, the major independent determinants of cholesterol efflux were HDL, CRP and age. PWV was increased in the diabetic patients (P < 0.01), but no association between serum EL and PWV was seen in either groups. CONCLUSIONS: Serum EL was increased in diabetic patients, but impaired serum capacity to induce cholesterol efflux in these patients was mainly related to low HDL and subclinical inflammation. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00016.x, 2010).