Vries, R. de

Social Support and Social Rhythm Regularity in Elderly Patients With Major Depressive Disorder (Article)

2013-03-27T00:00:00Z

Objective: According to the social zeitgeber theory, the lack of social support (SS) may decrease circadian rhythm regularity. However, the effect of SS on social rhythms in major depression has never been investigated. The objective of this study was to investigate the relation between SS and social rhythms in elderly patients with major depression. Methods: Case-control study on the relation of SS with social rhythm regularity in 213 elderly patients with major depressive disorder (MDD) and 183 elderly healthy comparison subjects (HCs). Social rhythm regularity was studied using the social rhythm metric (SRM-5), in which a lower score represents less regularity. SS was assessed with the social support list (SSL). Results: Patients with MDD displayed lower SRM-5 scores than HCs (4.94 ± 0.94 versus 5.38 ± 1.12; p = 0.003), as well as lower SSL-interactions (60.0 ± 13.7 versus 70.5 ± 11.6; p <0.001), higher SSL-discrepancies (56.3 ± 15.5 versus 39.4 ± 7.2; p <0.001), and higher SSL-negative interactions (11.0 ± 4.5 versus 8.9 ± 1.9; p <0.001). In HCs, social support was negatively correlated with SRM-5 (SSL-interactions, r = -0.30; SSL-discrepancies, r = -0.23; SSL-negative interactions, r = -0.44). In MDD, SS was not correlated with SRM-5 (all r ≤ 0.03; all p >0.05). Conclusions: Patients with MDD showed lower social rhythm regularity as well as lower measures of SS than HCs. In HCs, high SS was correlated with low social rhythm regularity, suggesting that increases in SS in combination with a healthy organization of circadian rhythms allow the social rhythms to become less rigid. Interestingly, in MDD, no correlation was found, suggesting that patients have a blunted response to social stimuli and may, therefore, benefit from treatment that increases the susceptibility to SS.

Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus (Article)

2010-11-01T00:00:00Z

Purpose: Plasma apolipoprotein M (apoM) is potentially anti-atherogenic, and has been found to be associated positively with plasma total, LDL and HDL cholesterol in humans. ApoM may, therefore, be intricately related to cholesterol metabolism. Here, we determined whether plasma apoM is affected by statin or fibrate administration in patients with diabetes mellitus. Methods: Fourteen type 2 diabetic patients participated in a placebo-controlled crossover study which included three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), and their combination. Results: ApoM was decreased by 7% in response to simvastatin (P< 0.05 from baseline and placebo), and remained unchanged during bezafibrate and combined simvastatin. +. bezafibrate administration. Plasma apoM concentrations correlated positively with apoB-containing lipoprotein measures at baseline and during placebo (P< 0.02 to P< 0.001), but these relationships were lost during all lipid lowering treatment periods. Conclusions: This study suggests that, even though plasma apoM is lowered by statins, apoM metabolism is to a considerable extent independent of statin- and fibrate-affected pathways involved in cholesterol homeostasis.

Plasma lecithin:cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men (Article)

2010-01-01T00:00:00Z

Lecithin:cholesterol acyltransferase (LCAT) is instrumental in high-density lipoprotein (HDL) maturation, but high LCAT levels do not predict low cardiovascular risk. LCAT may affect antioxidative or anti-inflammatory properties of HDL. We determined the relationship of plasma high-sensitivity C-reactive protein (CRP) with LCAT activity and evaluated whether LCAT activity modifies the decreasing effect of HDL cholesterol (HDL-C) on CRP, as an estimate of its anti-inflammatory properties. Plasma HDL-C, apolipoprotein (apo) A-I and LCAT activity (exogenous substrate method) were measured in 260 nondiabetic men without cardiovascular disease. CRP was correlated inversely with HDL-C and apo A-I, and positively with LCAT activity (P < 0.01 to 0.001). Multivariate regression analysis demonstrated that age- and smoking-adjusted plasma CRP levels were associated negatively with HDL-C (β = - 0.224, P < 0.001) and positively with LCAT activity (β = 0.119, P = 0.034), as well as with the interaction between HDL-C and LCAT activity (β = 0.123, P = 0.026). There was also an interaction between apo A-I and LCAT activity on CRP (β = 0.159, P = 0.005). These relationships remained similar after adjustment for apo B-containing lipoproteins. In conclusion, the inverse relationship of HDL-C with CRP is attenuated by LCAT activity at higher HDL-C levels. It is hypothesized that LCAT could mitigate HDL's anti-inflammatory or antioxidative properties at higher HDL-C concentrations.

Plasma lecithin: Cholesterol acyltransferase activity is elevated in metabolic syndrome and is an independent marker of increased carotid artery intima media thickness (Article)

2008-12-01T00:00:00Z

Context: Lecithin:cholesterol acyltransferase (LCAT), which esterifies free cholesterol to cholesteryl esters, is required for normal plasma lipoprotein structure and is instrumental in high density lipoprotein (HDL) remodeling, but the relationship of variation in plasma LCAT activity with subclinical atherosclerosis is unclear. Objectives: The aim of the study was to determine the effect of the metabolic syndrome (MetS) on plasma LCAT activity and its relationship with carotid artery intima media thickness (IMT). Setting: The study was conducted at the vascular laboratory of a university medical center. Methods: In 74 subjects with MetS and 90 subjects without MetS (National Cholesterol Education Program Adult Treatment Panel III criteria), mean carotid artery IMT, plasma lipids, LCAT activity (exogenous substrate method), high-sensitive C-reactive protein, and homeostasis model assessment insulin resistance (HOMAir) were documented. Results: IMT was greater (P = 0.01) and plasma LCAT activity was higher (P < 0.001) in subjects with MetS compared to subjects without MetS. Similar increases in IMT and LCAT were found in MetS subjects without type 2 diabetes mellitus. Multiple linear regression analysis demonstrated that plasma LCAT activity was independently and positively related to HOMAir, plasma triglycerides, non-HDL cholesterol, and HDL cholesterol (all P < 0.001). After adjustment for age and sex, IMT was positively associated with LCAT activity (P < 0.01), independently of the presence of MetS (or alternatively of plasma lipids), HOMAir, and high-sensitive C-reactive protein. Conclusions: Plasma LCAT activity is elevated in MetS and may be a marker of subclinical atherosclerosis. Our findings do not support the contention that strategies to elevate LCAT are necessarily beneficial for cardioprotection. Copyright

Phospholipid transfer protein activity is determined by type 2 diabetes mellitus and metabolic syndrome, and is positively associated with serum transaminases (Article)

2008-03-01T00:00:00Z

Background: The extent to which plasma phospholipid transfer protein (PLTP) activity is affected by type 2 diabetes mellitus (DM) and metabolic syndrome (MetS) is still unknown. PLTP is synthesized in the liver, and elevated serum transaminases are considered to predict nonalcoholic fatty liver disease (NAFLD). In this study, we examined the relationship between plasma PLTP activity and liver enzymes in subjects with and without DM and MetS. Design: Plasma PLTP activity, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured in 71 subjects without DM or MetS, 21 without DM but with MetS, 26 with DM but without MetS and 55 with DM and MetS (WHO and NCEP-ATP III criteria). Results: After controlling for age, sex and alcohol intake, PLTP activity was positively related to both MetS (P < 0.001) and DM (P = 0.001). Serum ALT (P = 0.006) and AST (P = 0.04) were both associated with MetS, but only ALT was associated with DM (P < 0.001). In multiple linear regression models, serum ALT and AST were positively and independently associated with PLTP activity (P < 0.01 for all), even when the presence of MetS and DM was taken into account, as well as after controlling for glycated haemoglobin (HbA1c), insulin resistance, triglycerides, free fatty acids (FFA), C-reactive protein (CRP), leptin and adiponectin. Conclusions: Plasma PLTP activity is determined by MetS and by diabetes per se. Serum transaminases are independently associated with PLTP activity. We suggest that this lipid transfer protein may be a marker for NAFLD.

Increased cholesterol efflux from cultured fibroblasts to plasma from hypertriglyceridemic type 2 diabetic patients: Roles of pre β-HDL, phospholipid transfer protein and cholesterol esterification (Article)

2008-02-01T00:00:00Z

We tested whether hypertriglyceridemia associated with type 2 diabetes mellitus is accompanied by alterations in pre β-HDL, which are considered to be initial acceptors of cell-derived cholesterol, and by changes in the ability of plasma to promote cellular cholesterol efflux. In 28 hypertriglyceridemic and 56 normotriglyceridemic type 2 diabetic patients, and in 56 control subjects, we determined plasma lipids, HDL cholesterol and phospholipids, plasma pre β-HDL and pre β-HDL formation, phospholipid transfer protein (PLTP) activity, plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) and the ability of plasma to stimulate cholesterol efflux out of cultured human fibroblasts. HDL cholesterol and HDL phospholipids were lower, whereas plasma PLTP activity, EST and CET were higher in hypertriglyceridemic diabetic patients than in the other groups. Pre β-HDL levels and pre β-HDL formation were unaltered, although the relative amount of pre β-HDL (expressed as % of total plasma apo A-I) was increased in hypertriglyeridemic diabetic patients. Cellular cholesterol efflux to plasma from hypertriglyceridemic diabetic patients was increased compared to efflux to normotriglyceridemic diabetic and control plasma, but efflux to normotriglyceridemic diabetic and control plasma did not differ. Multiple linear regression analysis demonstrated that cellular cholesterol efflux to plasma was positively and independently related to pre β-HDL formation, PLTP activity and EST (multiple r = 0.48), but not to the diabetic state. In conclusion, cholesterol efflux from fibroblasts to normotriglyceridemic diabetic plasma is unchanged. Efflux to hypertriglyceridemic diabetic plasma is enhanced, in association with increased plasma PLTP activity and cholesterol esterification. Unaltered pre β-HDL formation in diabetic hypertriglyceridemia, despite low apo A-I, could contribute to maintenance of cholesterol efflux.

Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol (Article)

2008-01-01T00:00:00Z

Objective: We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. Design: In 76 subjects with and 94 subjects without MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined plasma (apo)lipoproteins, pre-β-HDL formation, phospholipid transfer protein (PLTP) activity, cholesterol esterification (EST), cholesteryl ester transfer (CET), adiponectin, and the ability of plasma from each subject to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single donor. Results: Apo E, PUP activity EST, and CET were higher (P = 0.04 to < 0.001), whereas adiponectin was lower in MetS subjects (P < 0.01). Pre-β-HDL and pre-β-HDL formation were not different between subjects with and without MetS. Cellular cholesterol efflux to plasma from MetS subjects was slightly higher versus plasma from subjects without MetS (8.8 ± 1.0 vs 8.5 ± 0.9%, P=0.05), but the difference was not significant after age, sex, and diabetes adjustment. Cellular cholesterol efflux was positively related to pre-β-HDL formation, EST, PLTP activity, and apo E (P < 0.05 for all by multiple linear regression analysis), without an independent association with MetS and diabetes status. Conclusions: The ability of plasma from MetS subjects to promote fibroblast cholesterol efflux is not defective, although HDL cholesterol is decreased. Higher cholesterol esterification, PLTP activity, and apo E levels may contribute to the maintenance of cholesterol efflux in MetS.

The ability of plasma to stimulate fibroblast cholesterol efflux is associated with the - 629C→A cholesteryl ester transfer protein promoter polymorphism: Role of lecithin:cholesterol acyltransferase activity (Article)

2008-01-01T00:00:00Z

A recent population-based study showed that cholesteryl ester transfer protein (CETP) gene variations, which relate to lower plasma CETP, may predict increased cardiovascular risk, in spite of higher HDL cholesterol. Among other functions, CETP activity contributes to cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport (RCT) process. We hypothesized that cellular cholesterol efflux stimulating capacity of plasma could be associated with CETP gene variation. In this study, we tested the extent to which the ability of plasma to promote cholesterol efflux from cultured human fibroblasts is associated with CETP gene variation. In 223 men, the - 629C→A CETP promoter polymorphism, plasma lipids, CETP mass, cholesteryl ester transfer (CET), lecithin:cholesterol acyltransferase (LCAT) activity and the ability of plasma to promote cholesterol efflux from human skin fibroblasts, obtained from a single normolipidemic donor, were determined. In - 629CC homozygotes (n = 52), cholesterol efflux, plasma CETP mass, CET and LCAT activity were higher, whereas HDL cholesterol was lower compared to - 629 AA homozygotes (n = 62) and - 629CA + AA carriers (n = 171) (P < 0.05 to P < 0.001). Univariate correlation analysis showed that cellular cholesterol efflux was related to CETP genotype (P = 0.04), plasma CET (P<0.05), LCAT activity (P < 0.001) and apo A-I (P < 0.05). Multiple linear regression analysis confirmed the independent association of cellular cholesterol efflux to plasma with CETP genotype. In conclusion, an association of cellular cholesterol efflux with the - 629C→A CETP polymorphism, possibly also involving LCAT activity, could provide a mechanism explaining why CETP gene variation, which relates to lower plasma CETP, does not confer diminished cardiovascular risk.

Corrigendum to "Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein activity are associated with leptin in type 2 diabetes mellitus" [Biochim. Biophys. Acta 1771 (2007) 113-118] (DOI:10.1016/j.bbalip.2006.11.003) (Article)

2007-04-01T00:00:00Z

Plasma cholesteryl ester transfer protein mass and phospholipid transfer protein activity are associated with leptin in type 2 diabetes mellitus (Article)

2007-01-01T00:00:00Z

Adipose tissue contributes to plasma levels of lipid transfer proteins and is also the major source of plasma adipokines. We hypothesized that plasma cholesteryl ester transfer protein (CETP) mass, phospholipid transfer protein (PLTP) activity and cholesteryl ester transfer (CET, a measure of CETP action) are determined by adipokine levels. In this study, relationships of plasma CETP mass, PLTP activity and CET with leptin, resistin and adiponectin were analyzed in type 2 diabetic patients and control subjects. Plasma PLTP activity (P < 0.001), CET (P < 0.001), leptin (P = 0.003), resistin (P < 0.001), high sensitive C-reactive protein (P = 0.005), and insulin resistance (HOMAir) (P < 0.001) were higher, whereas HDL cholesterol (P < 0.001) and plasma adiponectin (P < 0.001) were lower in 83 type 2 diabetic patients (32 females) than in 83 sex-matched control subjects. Multiple linear regression analysis demonstrated that in diabetic patients plasma leptin levels were related to plasma CETP mass (P = 0.018) and PLTP activity (P < 0.001), but not to the other adipokines measured. Plasma CET was inversely correlated with adiponectin in univariate analysis, but this association disappeared in multivariate models that included plasma lipids and CETP. In conclusion, both plasma CETP mass and PLTP activity are associated with plasma leptin in type 2 diabetes. The elevated CET in these patients is not independently related to any of the measured plasma adipokines.