Dyslipidemia in Obesity: Mechanisms and Potential Targets

Obesity has become a major worldwide health problem. In every single country in the world, the incidence of obesity is rising continuously and therefore, the associated morbidity, mortality and both medical and economical costs are expected to increase as well. The majority of these complications are related to co-morbid conditions that include coronary artery disease, hypertension, type 2 diabetes mellitus, respiratory disorders and dyslipidemia. Obesity increases cardiovascular risk through risk factors such as increased fasting plasma triglycerides, high LDL cholesterol, low HDL cholesterol, elevated blood glucose and insulin levels and high blood pressure. Novel lipid dependent, metabolic risk factors associated to obesity are the presence of the small dense LDL phenotype, postprandial hyperlipidemia with accumulation of atherogenic remnants and hepatic overproduction of apoB containing lipoproteins. All these lipid abnormalities are typical features of the metabolic syndrome and may be associated to a pro-inflammatory gradient which in part may originate in the adipose tissue itself and directly affect the endothelium. An important link between obesity, the metabolic syndrome and dyslipidemia, seems to be the development of insulin resistance in peripheral tissues leading to an enhanced hepatic flux of fatty acids from dietary sources, intravascular lipolysis and from adipose tissue resistant to the antilipolytic effects of insulin. The current review will focus on these aspects of lipid metabolism in obesity and potential interventions to treat the obesity related dyslipidemia

Effects of Metformin on the Regulation of Free Fatty Acids in Insulin Resistance: A Double-Blind, Placebo-Controlled Study

Introduction. Impaired free fatty acid (FFA) metabolism is closely linked to insulin resistance. Our aim was to evaluate plasma FFA changes in insulin resistance in a physiological situation after improvement of insulin sensitivity by metformin. Methods. A double-blind, placebo-controlled intervention with metformin was carried out in patients with insulin resistance. Nineteen patients were randomized to receive metformin 850 mg b.i.d. during 6 weeks or placebo. Participants underwent a mental stress test and an oral glucose tolerance test (OGTT) before and after treatment. Results. Fasting plasma glucose, FFA, and HOMA-IR tended to decrease after metformin, suggesting improved insulin sensitivity. FFA concentrations during the mental stress test showed a similar pattern after metformin, albeit lower at all time points, in contrast to the placebo group. The decrease in fasting plasma FFAs was positively associated to the decrease in HbA1c (; ) and in fasting glucose (; ). The suppression of plasma FFAs during OGTT did not change by metformin or placebo. Conclusion. Metformin in insulin resistance did not lead to improved FFA dynamics despite a trend of improved insulin sensitivity. Metformin most likely decreases plasma FFAs mainly by suppressing fasting FFA concentrations and not by suppression of acute stress-induced lipolysis

Diurnal Triglyceridemia in Relation to Alcohol Intake in Men

__Abstract__ Fasting and postprandial triglyceride concentrations largely depend on dietary and lifestyle factors. Alcohol intake is associated with triglycerides, but the effect of alcohol on diurnal triglyceridemia in a free living situation is unknown. During three days, 139 men (range: 18-80 years) measured their own capillary triglyceride (cTG) concentrations daily on six fixed time-points before and after meals, and the total daily alcohol intake was recorded. The impact of daily alcohol intake (none; low, 30 g/day) on diurnal triglyceridemia was analyzed by the incremental area under the cTG curve (∆cTG-AUC) reflecting the mean of the six different time-points. Fasting cTG were similar between the alcohol groups, but a trend of increased cTG was observed in men with moderate and high alcohol intake after dinner and at bedtime (p for trend <0.001) which persisted after adjustment for age, smoking and body mass index. The ∆cTG-AUC was significantly lower in males with low alcohol intake (3.0 ± 1.9 mmol·h/L) (n = 27) compared to males with no (7.0 ± 1.8 mmol·h/L) (n = 34), moderate (6.5 ± 1.8 mmol·h/L) (n = 54) or high alcohol intake (7.2 ± 2.2 mmol·h/L) (n = 24), when adjusted for age, smoking and body mass index (adjusted p value < 0.05). In males, low alcohol intake was associated with decreased diurnal triglyceridemia, whereas moderate and high alcohol intake was associated with increased triglycerides after dinner and at bed time

Erythrocyte-Bound Apolipoprotein B in Relation to Atherosclerosis, Serum Lipids and ABO Blood Group

Introduction:Erythrocytes carry apolipoprotein B on their membrane, but the determining factors of erythrocyte-bound apolipoprotein B (ery-apoB) are unknown. We aimed to explore the determinants of ery-apoB to gain more insight into potential mechanisms.Methods:Subjects with and without CVD were included (N = 398). Ery-apoB was measured on fresh whole blood samples using flow cytometry. Subjects with ery-apoB levels ≤0.20 a.u. were considered deficient. Carotid intima media thickness (CIMT) was determined as a measure of (subclinical) atherosclerosis.Results:Mean ery-apoB value was 23.2% lower in subjects with increased CIMT (0.80±0.09 mm, N = 140) compared to subjects with a normal CIMT (0.57±0.08 mm, N = 258) (P = 0.007, adjusted P<0.001). CIMT and ery-apoB were inversely correlated (Spearman's r: -0.116, P = 0.021). A total of 55 subjects (13.6%) were considered ery-apoB deficient, which was associated with a medical history of CVD (OR: 1.86, 95% CI 1.04-3.33; adjusted OR: 1.55; 95% CI 0.85-2.82). Discontinuation of statins in 54 subjects did not influence ery-apoB values despite a 58.4% increase in serum apolipoprotein B. Subjects with blood group O had significantly higher ery-apoB values (1.56±0.94 a.u.) when compared to subjects with blood group A (0.89±1.15 a.u), blood group B (0.73±0.1.12 a.u.) or blood group AB (0.69±0.69 a.u.) (P-ANOVA = 0.002).Conclusion:Absence or very low values of ery-apoB are associated with clinical and subclinical atherosclerosis. While serum apolipoprotein B is not associated with ery-apoB, the ABO blood group seems to be a significant determinant

Association of cardiovascular risk factors with carotid intima media thickness in patients with rheumatoid arthritis with low disease activity compared to controls: A cross-sectional study

Objectives Rheumatoid arthritis (RA) has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT) in patients with RA. Methods Subjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound. Results In total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQ

Closure of midline laparotomies by means of small stitches : practical aspects of a new technique

Randomized studies support the closure of midline incisions with a suture length to wound length ratio (SL:WL) of more than 4, accomplished with small tissue bites and short stitch intervals to decrease the risk of incisional hernia and wound infection. We investigated practical aspects of this technique possibly hampering the introduction of this technique. Patient data, operative variables and SL:WL ratio were collected at two hospitals: Sundsvall Hospital (SH) and Erasmus University Medical Center (EMC). A structured implementation of the technique had been performed at SH but not at EMC. Personnel were interviewed by questionnaire. At each hospital, 18 closures were analyzed. Closure time was significantly longer (p = 0.023) at SH (median 18 minutes, range: 9-59) than at EMC (median 13 minutes, range: 5-23). An SL:WL ratio of more than 4 was achieved in 8 of 18 cases at EMC and in all 18 cases at SH. We conclude that calculation of an SL:WL ratio is easily performed. Suturing with the small bite-short stitch interval technique of SH required 5 minutes extra, outweighing the morbidity of incisional hernia. Without a structured implementation to suture with an SL:WL ratio of more than 4, a lower ratio is often achieved