Markus Laimer

Metabolic side effects of antipsychotic medication.

The use of second‐generation antipsychotics (SGAs) is associated with metabolic side effects including weight gain, diabetes mellitus and an atherogenic lipid profile. These adverse effects are not only the risk factors for cardiovascular disease, insulin resistance and diabetes mellitus leading to increased morbidity and mortality but may also impair the patients adherence to treatment.

Markers of chronic inflammation and obesity: a prospective study on the reversibility of this association in middle-aged women undergoing weight loss by surgical intervention

Background: Human adipose tissue expresses and releases proinflammatory cytokines and these measures of chronic inflammation have recently been associated with obesity.Hypothesis: To test whether the proinflammatory state is reversible in subjects undergoing weight loss by surgical measures.Subjects and Methods: Twenty morbidly obese women participated in this prospective study. Subjects were examined for fat mass, high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) before and 1 y after Swedish adjustable gastric banding.Results: Anthropometric measures displayed a significant reduction of the body mass index (BMI) from 41.6±5.4 to 30.8±6.1 kg/m2 and the fat mass from 53.9±10.3 to 29.8±12.1 kg (mean±s.d.). Hs-CRP levels decreased significantly from 1.33±1.21 mg/dl in pre-gastric banding subjects to 0.40±0.61 mg/dl in post-gastric banding subjects, respectively. IL-6 and TNF-α levels did not differ significantly between pre- and post-gastric banding subjects.Conclusions: We speculate that in these patients the marked reduction in C-reactive protein might be beneficial in reducing their cardiovascular risk and is not solely mediated by IL-6 and TNF-α.

Effect of pronounced weight loss on the nontraditional cardiovascular risk marker matrix metalloproteinase-9 in middle-aged morbidly obese women

OBJECTIVE:Obesity is associated with increased morbidity and mortality from atherosclerotic disease. Nontraditional cardiovascular risk factors such as C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in obese subjects and weight loss is associated with an attenuation of these risk factors. Matrix metalloproteinase-9 (MMP-9) has been linked to plaque rupture, and is, thus, a candidate marker of future myocardial events. The aim of this study was to determine the influence of weight loss on MMP-9 plasma concentrations.METHODS AND RESULTS:CRP, IL-6 and MMP-9 were analyzed from samples of 45 morbidly obese, middle-aged women before gastric banding and 1 y postsurgical treatment in this prospective study. The body mass index (BMI) of subjects decreased from 42.5±4.9 to 32.3±5.3 kg/m2 1 y after gastric banding. In parallel, both MMP-9 and CRP were reduced by 23 and 41%, respectively. A positive relationship was found between BMI and MMP-9 (r=0.312, P<0.05), and between CRP and IL-6 (r=0.508, P<0.05), whereas no correlation was found between CRP and MMP-9.CONCLUSIONS:We conclude that weight loss is associated with a pronounced decrease in the nontraditional cardiovascular risk markers MMP-9 and CRP, which could indicate future beneficial effects of weight loss on the cardiovascular risk in weight loosing subjects.

Influence of Visceral Obesity and Liver Fat on Vascular Structure and Function in Obese Subjects

Endothelial dysfunction and increased intima–media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 ± 4.3 kg/m²), we determined (i) endothelial function as flow‐mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = −0.577, P < 0.0001 and r = −0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r2 = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r2 = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.

Effect of bariatric surgery on both functional and structural measures of premature atherosclerosis

AIMS To bridge the beneficial metabolic effects of pronounced weight loss on one side and the data on morbidity and mortality on the other side, we investigated the impact of profound weight loss on structural and functional markers of early atherosclerosis. METHODS AND RESULTS Thirty-seven obese adults were examined before and 18 months after bariatric surgery. Carotid intima-media thickness (CIMT), brachial flow-mediated dilation (FMD), nitroglycerine-mediated dilation, and abdominal fat distribution were assessed by high-resolution ultrasound. Surgery resulted in a body mass index decrease of 9.1 +/- 4.9 kg/m(2) with concomitant improvements in glucose and lipid metabolism. Carotid intima-media thickness diminished from 0.56 +/- 0.09 to 0.53 +/- 0.08 mm (n = 37; P = 0.004). Flow-mediated dilation improved from 5.81 +/- 3.25 to 9.01 +/- 2.93% (n = 25; P < 0.001). Both CIMT and FMD were associated with intra-abdominal fat diameter. CONCLUSION The present results demonstrate that bariatric surgery-induced diminution of visceral fat improves both functional and structural markers of early atherosclerosis, providing a link between the weight loss-associated improvements of traditional and non-traditional risk factors and the reduced long-term morbidity and mortality after bariatric surgery.

Retinol‐binding Protein 4, Visceral Fat, and the Metabolic Syndrome: Effects of Weight Loss

Retinol‐binding protein 4 (RBP‐4) has been reported to be associated with visceral‐fat accumulation and parameters of the metabolic syndrome (MetS). In this study, we investigated the relationship between RBP‐4, visceral fat, and the MetS during pronounced weight loss after bariatric surgery. Thirty‐six subjects were examined before and 2 years after surgery. Abdominal‐fat distribution was determined by ultrasound, metabolic parameters, and serum RBP‐4 levels by standard methods. After surgery BMI decreased by 9.07 kg/m2, visceral‐fat diameter (VFD) decreased by 60.6%, and RBP‐4 serum levels by 16.6%. Change of RBP‐4 levels was associated with reductions of waist (r = 0.364, P = 0.037), waist‐to‐hip ratio (WHR) (r = 0.415, P = 0.016), and VFD (r = 0.425, P = 0.010). MetS, as defined by International Diabetes Federation (IDF), was present in 19 patients at baseline and in nine patients at follow‐up. Change in RBP‐4 levels was the best predictor for the diagnosis of MetS at follow‐up. In the subgroup without MetS at baseline, the decrease in RBP‐4 levels (–28.1% vs. −6.3%, P = 0.020) and reduction in VFD (–66.9% vs. −55.0%, P = 0.038) were significantly greater compared to the subgroup with MetS. We demonstrate a marked decrease of RBP‐4 levels after bariatric surgery, which correlates with reduction in visceral‐fat mass. Furthermore, the extent of changes in RBP‐4 levels differs according to the severity of the MetS.

Effects of pronounced weight loss on Adiponectin oligomer composition and metabolic parameters

Objective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters.

Cholesteryl Ester Transfer Protein in Metabolic Syndrome

Objective: Low high‐density lipoprotein cholesterol (HDL‐C), hypertriglyceridemia, and small dense‐low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG‐rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL‐C and small dense‐LDL. The aim of this study was to investigate the role of CETP in subjects with MS.

Body adiposity index and other indexes of body composition in the SAPHIR study: association with cardiovascular risk factors.

The accuracy of anthropometric surrogate markers such as the body adiposity index (BAI) and other common indexes like the body mass index (BMI), waist‐to‐hip ratio (WHR) and waist‐to‐height ratio (WHtR) to predict metabolic sequelae is essential for its use in clinical practice.

The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome.

The metabolic syndrome is associated with low high‐density lipoprotein–cholesterol (HDL‐C) and decreased low‐density lipoprotein (LDL) particle size. The Taq1B‐polymorphism in the cholesteryl ester–transfer protein (CETP)‐gene influences HDL‐C, CETP concentration, and LDL‐size. We investigated the effect of the Taq1B‐polymorphism on the risk of the metabolic syndrome in 1,503 participants (973 men, 530 women) of the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk study. CETP concentration was determined in a subgroup (n = 486) by an enzyme‐linked immunosorbent assay. Prevalence of the metabolic syndrome was 16.7% (18.5% in men, 13.5% in women). The Taq1B‐polymorphism influenced significantly CETP concentrations, HDL‐C levels, and LDL‐size (P < 0.001 for all). The relative risk of the metabolic syndrome was reduced by 32% (odds ratio (OR) 0.68 (95% CI: 0.51–0.89), P = 0.005) in carriers of the B2 variant. This risk reduction persisted after adjustment for age and sex (OR 0.69 (0.53–0.92), P = 0.01) and after further adjustment for body mass index, waist‐to‐hip ratio, blood pressure, insulin resistance (IR), HDL‐C, and triglycerides (TGs) (OR 0.43 (0.26–0.72), P = 0.001). Furthermore, the risk reduction was more pronounced in men than in women. We conclude that CETP plays an important role in the metabolic syndrome, possibly involving novel functions of CETP.