Subcutaneous adipose tissue distribution and telomere length.

Background Overweight and obese individuals have a reduced life expectancy due to cardiovascular disease (CVD), type 2 diabetes, stroke and cancer. Systemic inflammation and premature telomere shortening have been discussed as potential mechanisms linking these conditions. We investigated the relation of subcutaneous adipose tissue (SAT) distribution to leukocyte relative telomere length (RTL). Methods We measured RTL in 375 participants of the observational STYJOBS/EDECTA cohort (ClinicalTrials.gov Identifier NCT00482924) using a qPCR based method. SAT distribution was determined by lipometry yielding a percent body fat value and SAT thicknesses at 15 standardized locations across the entire body. A correlation analysis between RTL, age, sex, lipometry data and conventional body measures (body mass index [BMI], waist-, hip circumference, waist-to-hip ratio, waist-to-height ratio) was calculated. The strongest determinants of RTL were determined by a stepwise multiple regression analysis. Results RTL was not associated with age or sex. RTL was significantly negatively correlated with BMI, percent body fat, waist-, hip circumference and waist-to-height ratio. Furthermore, RTL correlated with SAT at the following locations: neck, triceps, biceps, upper back, front chest, lateral chest, upper abdomen, lower abdomen, lower back, hip, front thigh, lateral thigh, rear thigh and calf. Stepwise regression analysis revealed nuchal and hip SAT as the strongest predictors of RTL. No significant association was seen between RTL and waist-to-hip ratio. Conclusions RTL is negatively associated with parameters describing body fat composure. Nuchal and hip SAT thicknesses are the strongest predictors of RTL. Central obesity appears to correlate with premature genomic aging.

N-terminal pro-B-type natriuretic peptide in early and advanced phases of obesity.

BACKGROUND: Increased plasma amino-terminal-cleavage-fragment of NP (NT-proBNP) is an established indicator for heart failure. Moreover, obese adults had low circulating NT-proBNP suggesting an obesity-related dysregulation (natriuretic handicap). Secretion and/or clearance of NT-proBNP were discussed to be impaired in obesity. As only older adults were investigated so far, it remains unclear when during the evolution of obesity the state of a natriuretic handicap develops, and whether NT-proBNP may still serve as a relevant cardiac marker in obese juveniles. METHODS: We analysed NT-proBNP in juvenile (n=274, 10-18 years) and middle-aged (n=277, 18-50 years) normal weight (n=213) and obese (n=338) probands together with complex anthropometry, carotis sonography, clinical, and laboratory parameters. RESULTS: NT-proBNP showed a significant gender and age interaction. Adult females had significant higher NT-proBNP than adult males, and higher levels than juvenile females. Adult males had lower levels than juvenile males. Only a weak age and weight interaction was seen with obese juveniles which showed higher NT-proBNP than obese adults. Moreover, normal weight probands had higher NT-proBNP than overweight and obese. In a multiple regression including all probands, gender, creatinine and uric acid were the best predictors for NT-proBNP. In adults, female gender is the strongest driver for increased NT-proBNP. CONCLUSIONS: These results argue against an essential influence of obesity to B-type cardiac natriuretic hormone system regulation in the absence of heart failure, and suggest NT-proBNP as a useful cardiac marker irrespective of age and obesity.

GLP-2 and leptin are associated with hyperinsulinemia in non-obese female migraineurs.

OBJECTIVE: Impaired insulin metabolism has been implicated in migraine. However, to date only some putative effects, especially regarding the involvement of adipocytokines and glucagon-like peptides (GLPs), have been described. The aim of the present study was to investigate adipocytokines and GLPs in non-obese female migraineurs. METHODS: Various parameters of the insulin metabolism and body measurements were determined in 84 non-obese female subjects. RESULTS: We found highly significantly increased insulin levels with an odds ratio of 10.62 for migraine. Leptin and GLP-2 levels were also increased and correlated with insulin. Logistic regression analysis of leptin and GLP-2 revealed odds ratios of 3.79 and 4.26 for migraine, respectively, when comparing the lowest with the highest quartile of the test variable in the complete study cohort. DISCUSSION: We show that non-obese female migraineurs suffer from hyperinsulinemia, which is associated with elevated leptin and GLP-2 levels. Increased leptin and GLP-2 are risk factors for migraine. Our data suggest that migraine is associated with a higher risk for insulin resistance and its clinical consequences.

Increased dopamine is associated with the cGMP and homocysteine pathway in female migraineurs.

BACKGROUND: The group of catecholamines, which include dopamine, adrenaline, and noradrenaline, are neurotransmitters which have been considered to play a role in the pathogenesis of migraine. However, the impact of catecholamines, especially dopamine on migraine as well as the exact mechanisms is not clear to date as previous studies have yielded in part conflicting results. OBJECTIVE: This study aimed to produce a comprehensive examination of dopamine in migraineurs. METHODS: Catecholamines and various parameters of the homocysteine, folate, and iron metabolism as well as cyclic guanosine monophosphate (cGMP) and inflammatory markers were determined in 135 subjects. RESULTS: We found increased dopamine levels in the headache free period in female migraineurs but not in male patients. Increased dopamine is associated with a 3.30-fold higher risk for migraine in women. We found no significant effects of aura symptoms or menstrual cycle phases on dopamine levels. Dopamine is strongly correlated with cGMP and the homocysteine-folate pathway. CONCLUSION: We show here that female migraineurs exhibit increased dopamine levels in the headache free period which are associated with a higher risk for migraine.

Effects of a hyperbaric environment on subcutaneous adipose tissue topography (SAT-top).

The physiological reactions of the body in scuba diving situation can be simulated in a pressure chamber by increasing the ambient pressure. In this study the influence of a hyperbaric environment of 6 bar on the changes of the subcutaneous adipose tissue (SAT) thicknesses on different body sites in 68 voluntary men with undersea diving experience was investigated. Measurements of SAT-topography (SAT-Top) were performed with the optical device Lipometer before and after hyperbaric exposure. We observed a significant increase of the SAT-layers of the upper body zones, upper abdomen (+24.5%), lower abdomen (+21%) and front chest (+19%) after hyperbaric exposure. This increase of volume can be assumed to the nitrogen accumulation in fat cells at increased ambient pressures. In conclusion we describe for the first time in detail the influence of a hyperbaric environment on quantitative and topographic changes of SAT.

Telomere shortening associates with elevated insulin and nuchal fat accumulation.

Obesity and relative leucocyte telomere length (RTL) are both linked to accelerated aging and premature mortality. We examined if nuchal subcutaneous adipose tissue (SAT) thickness, a surrogate marker of central trunk-weighted obesity, is an independent predictor of RTL that provides information beyond BMI, metabolic and inflammatory markers. RTL and nuchal SAT thickness were determined in 362 participants of the STYJOBS/EDECTA study (STYrian Juvenile Obesity Study, Early DEteCTion of atherosclerosis), which included overweight individuals and matched eutrophic controls. Fasting plasma samples were used for the measurement of leptin, resistin, adiponectin, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), liver enzymes, creatinine, cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, oxidized LDL, triglycerides, homocysteine and uric acid. Furthermore, all participants underwent carotid artery ultrasound. Obese individuals had markedly higher body mass index (BMI), nuchal SAT thickness, hip and waist circumferences and carotid intima media thickness (IMT) than eutrophic controls. In addition, they showed typical biochemical abnormalities related to energy metabolism, systemic inflammation and liver function. RTL was inversely correlated with nuchal SAT thickness, IMT, hs-CRP, alkaline phosphatase, insulin, resistin, and leptin. Positive correlations were seen with homocysteine and creatinine. Stepwise linear regression analyses identified nuchal SAT thickness and insulin as the only significant predictors of RTL. In conclusion, nuchal SAT thickness is a robust predictor of RTL that provides information beyond traditional obesity-related metabolic and inflammatory biomarkers. This suggests an important role of fat depots at the neck for accelerated telomere shortening.

Subcutaneous adipose tissue topography and metabolic disturbances in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. Central obesity plays a major role in the pathophysiology of PCOS. However, there is little information on the impact of subcutaneous adipose tissue (SAT) on metabolic disturbances in PCOS. The aim of this study was to investigate whether SAT topography influences insulin resistance, impaired glucose tolerance and metabolic parameters in women with PCOS. METHODS: 36 women aged 16-41 years with PCOS and 87 healthy women aged 20-34 years were examined using lipometry, metabolic and hormonal measurements, oral glucose tolerance tests, hirsutism scores, and questionnaires. The homeostasis model assessment (HOMA) index was used for determination of insulin resistance. RESULTS: SAT measurement points on the trunk showed significant positive correlation with the HOMA index. A negative correlation between calf SAT and the HOMA index was seen. Multiple regression analysis detected a positive association between the HOMA index and lower-abdomen SAT and upper-back SAT, whereas hip SAT showed a negative association with the HOMA index. In overweight/obese patients with PCOS, lower-abdomen and upper-back SAT showed significant positive correlations with insulin resistance. There was no correlation of SAT topography with insulin resistance in lean women with PCOS. Compared with PCOS women with normal glucose tolerance, patients with glucose intolerance had significantly increased trunk obesity and decreased leg fat. Increased SAT layers on the trunk were related to an unfavorable serum lipid profile, whereas increased leg fat correlated positively with HDL cholesterol. CONCLUSIONS: Increased SAT layers on the trunk are associated with insulin resistance, impaired glucose tolerance and an unfavorable lipid profile in women suffering from PCOS. Increased thickness of leg SAT emerges as being protective against metabolic disturbances in PCOS.

Injection lipolysis for reduction of saddlebag trochanteric bulges--half-side controlled pilot study.

BACKGROUND: Phosphatidylcholine, a lecithin extracted from soybeans can reduce serum cholesterol to some extent. Intravenous use may prevent fat embolism in polytrauma patients. When injected intralesionally in a formulation containing also deoxycholate and ethanol it is supposed to act as "fat burner" to reduce undesired fat deposits; there is little evidence-based scientific support for this indication. OBJECTIVE: To evaluate the capability of phosphatidylcholine + deoxycholate + ethanol (PPC/DC/E) to reduce body fat with a half-side pilot study for the reduction of saddlebag trochanteric bulges. METHODS: PPC/DC/E was injected into the right posterior trochanteric areas three times at weeks 0, 3 and 6. Treatment areas and the same regions of the contralateral side as a control were evaluated by sonography. Tape measurements were taken and the thickness of the subcutaneous adipose tissue (SAT) was measured with an optical device (Lipometer) at baseline and at week 8 and week 20 (2 and 14 weeks after completing therapy). RESULTS: In this half-side trial, no significant reduction of subcutaneous fat was achieved after three treatments with PPC/DC/E when compared to the untreated side.Transient inflammatory reactions occurred in all patients. LIMITATIONS: Only the commercially available formulation containing the three components was tested. CONCLUSION: The off-label use of PPC/DC/E as a "fat burner" did not produce measurable reduction of undesired trochanteric fat deposits.

Subcutaneous fat patterns in type-2 diabetic men and healthy controls.

The optical device LIPOMETER enables the non-invasive, quick, and save determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). In the present paper we focus on SAT-Top of male type-2 diabetes patients (N=21), describing very precisely their special SAT development and their SAT-Top deviation from a healthy control group (N=111), applying factor analysis and ROC curves. Factor analysis revealed three independent subcutaneous body fat compartments, which can be summarised as "upper body", "lower trunks" and "legs". The upper body SAT-Top is much more pronounced in diabetic men compared to their healthy controls (p<0.001). Furthermore, high diagnostic power by ROC curve analysis was achieved by different measurement sites of the upper body and summary measures of upper body obesity (sum2, which is the sum of neck and biceps, provides: area index =0.86, sensitivity =81%, specificity =90.1%, at an optimal cutoff value of 18.8 mm), ascribing a higher diabetes probability to subjects with a more upper body SAT-Top pattern. Calculating new ROC curves for diabetic patients with HBA1C values >8 (N=17) and their healthy controls (N=111) we received improved discrimination power for several SAT-Top body sites, especially for sum2, showing an area index of 0.91, a sensitivity of 94.1%, and a specificity of 90.1% at the optimal cutoff value of 18.8 mm. Concluding, the exact and complete description of the especial type 2 diabetic SAT pattern, which differs strongly from the SAT-Top of healthy controls, suggests the LIPOMETER technique combined with advanced statistical methods such as factor analysis and ROC curve analysis as a possible detecting tool for this disease.

Generation of carbon monoxide and iron from hemeproteins in the presence of 7,8-dihydroneopterin.

7,8-Dihydroneopterin and neopterin are secreted by human and primate macrophages after activation by interferon-gamma in a ratio of 2:1. 7,8-Dihydroneopterin is known to suppress radical-mediated processes, but it is also able in the presence of iron ions to generate superoxide radical anion and hydroxyl radicals from molecular oxygen. Effects of 7,8-dihydroneopterin were investigated on (met)myoglobin and (met)hemoglobin. Addition of 7,8-dihydroneopterin to heme proteins in air-saturated solution resulted in dose-dependent cleavage of the porphyrin moiety. The liberation of non-heme iron and carbon monoxide originating from the cleaved porphyrin was quantified. Both were generated at equimolar concentrations with a linear correlation coefficient of 0.9. Addition of ferrous iron significantly accelerated the pteridine-mediated cleaving of the porphyrin. However, the total yield of porphyrin cleaved was controlled by the pterin rather than by the ferrous ion concentration. 7,8-Dihydroneopterin is assumed to reduce the heme iron in intact protein molecules, thereby preparing the conditions for binding of oxygen and carbon monoxide as ligands. Beyond that, it is concluded that hydroxyl radicals might be generated via reduction of molecular oxygen to superoxide anion in the autoxidation process and dismutation to hydrogen peroxide and subsequent Fenton reaction.

Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin.

CONTEXT: There is growing evidence that adiponectin, the most abundant adipocytokine of adipose tissue cells, plays a crucial role in advanced atherosclerosis. OBJECTIVE: The objective of the study was to evaluate the role of adiponectin in early atherosclerosis. DESIGN: One hundred forty obese juveniles (mean age, 13.5 +/- 4.4 yr) and 100 age-matched, healthy, normal-weight controls from the STYrian Juvenile Obesity Study were investigated. We measured adipocytokines, inflammatory biomarkers, parameters of insulin resistance, and lipid subfractions. Intima-media thickness (IMT) of common carotid arteries was determined by ultrasonography. Furthermore, lipometric measurements were performed in obese juveniles to determine the topographic distribution of sc adipose tissue (SAT). RESULTS: Compared with controls, the group of obese juveniles exhibited a significantly increased IMT (P < 0.001) and elevated high-sensitive C-reactive protein (P < 0.001), indicating early stages of atherosclerosis. Serum levels of adiponectin were highly significantly negatively correlated with carotid IMT, even after controlling for common cardiovascular risk factors (P < 0.001; r = -0.34). Furthermore, adiponectin was positively correlated with high-density lipoprotein-free cholesterol and serum apolipoprotein-A1 and negatively with triglycerides, insulin resistance, uric acid, and serum transaminases. By a multiple regression analysis, adiponectin was shown to be the strongest predictive variable for carotid IMT. Finally, adiponectin was found positively correlated with SAT thickness of the rear and inner thigh in boys and negatively with the SAT thickness of the neck in girls. CONCLUSION: In summary, our study describes an influence of SAT topography on adiponectin serum levels and provides first evidence that incipient atherosclerosis is associated with low serum levels of this adipocytokine.

Differences of subcutaneous adipose tissue topography between type-2 diabetic men and healthy controls.

Men with noninsulin-dependent diabetes mellitus (type 2 DM) provide a different subcutaneous body fat distribution and a concentration of fatness on the upper trunk compared with healthy subjects. However, subcutaneous fat distribution is always measured in an inaccurate and/or very simplified way (e.g., by caliper), and to date, there exists no study reporting on the exact and complete subcutaneous adipose tissue distribution of type 2 DM men. A new optical device, the LIPOMETER, enables the nonivasive, quick, and safe determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Tops of 21 men with clinically proven type 2 DM (mean age of 57.5 +/- 6.7 years) and 111 healthy controls of similar age (mean age 59.0 +/- 5.4 years) were measured. In this paper, we describe the precise SAT-Top differences of these two groups and we present the multidimensional SAT-Top information condensed in a two-dimensional factor value plot. In type 2 DM men, especially in the upper trunk, SAT-Top is significantly increased (up to +50.7% at the neck) compared with their healthy controls. One hundred eleven of the 132 individuals (84.1%) are correctly classified (healthy or type 2 DM) by their subcutaneous fat pattern by stepwise discriminant analysis.

Normal weight estonian prepubertal boys show a more cardiovascular-risk-associated adipose tissue distribution than austrian counterparts.

Objective. Risk phenotypes for cardiovascular disease (CVD) differ markedly between countries, like the reported high difference in CVD mortality in Austria and Estonia. Hitherto, the goal of this study was to find out risk profiles in body fat distribution yet present in childhood, paving the way for later clinical end points. Methods. he subcutaneous adipose tissue (SAT) distribution patterns in 553 Austrian (A) and Estonian (E) clinically healthy normal weight boys aged 11.1 (±0.8) years were analysed. We applied the patented optical device Lipometer which determines the individual subcutaneous adipose tissue topography (SAT-Top). Results. Total body fat did not differ significantly between E and A boys. A discriminant analysis using all Lipometer data, BMI, and the total body fat (TBF) yielded 84.6% of the boys correctly classified in Estonians and Austrians by 9 body sites. A factor analysis identified the SAT distribution of E as critically similar to male adult patients with coronary heart disease (CHD). Conclusions. We show in normal weight Estonian boys a highly significant decreased fat accumulation on the lower body site compared to age matched Austrian males. This SAT-Top phenotype may play an important role for the increased cardiovascular risk seen in the Estonian population.

Trunk weighted obesity, cholesterol levels and low grade inflammation are main determinants for enhanced thrombin generation.

OBJECTIVE: Endogenous thrombin generation (ETP) may be critically involved in obesity associated thromboembolism. METHODS: Three hundred and one participants of the STyrian Juvenile OBesity (STYJOBS)/Early DEteCTion of Atherosclerosis (EDECTA) study cohort (age, 16-58years) were analysed. ETP was measured by the new CE-IVD marked Siemens-Innovance(®) ETP test on a BCS-XP analyser, and correlated to clinical findings and extended lipometry-based anthropometric data, biomarkers, and coagulation parameters. RESULTS: In the overweight/obese study group, ETP and fibrinogen levels were significantly higher compared to controls (p<0.001). In a multiple stepwise regression including all subjects, subcutaneous adipose tissue thickness of upper back, cholesterol and ultrasensitive C-reactive protein were the best predictors for ETP. CONCLUSION: Trunk weighted obesity together with low grade inflammation and hypercholesterolemia enhance thrombin generation.

Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation.

The mechanisms underlying the pathogenesis of obesity-related atherosclerosis remain to be clarified. To investigate the preclinical phase, interleukin-6 (IL-6) plasma levels were analyzed together with clinical, anthropometric, inflammatory, and metabolic variables in a well-defined cohort of 677 young and middle-aged overweight/obese and normal-weight subjects. In the juvenile and adult overweight/obese study group, IL-6 levels were increased significantly compared with normal-weight, age-matched controls (P < 0.001). In both juveniles and adults, higher levels of IL-6 were observed in obese compared with overweight participants. Subjects with metabolic syndrome (MS) had significantly higher IL-6 levels than those without MS. In juveniles, leptin, and in adults, the waist-to-height ratio, turned out to be the best predictor of IL-6 plasma levels in a multiple stepwise regression model. Taken together, in every age group, interleukin-6 is associated positively with the grade of overweight. Interestingly, leptin, which is the best known adipokine, is associated predictively with interleukin-6 plasma levels only in juveniles, which may indicate an important role of this molecule in the initiation of obesity-related inflammation.

Rs9939609 variant of the fat mass and obesity-associated gene and trunk obesity in adolescents.

A common T/A polymorphism (rs9939609) in the fat mass and obesity associated (FTO) gene was found associated with early-onset and severe obesity in both adults and children. However, recent observations failed to find associations of FTO with obesity. To investigate the genetic background of early obesity, we analysed the single nucleotide polymorphism (SNP) rs9939609 of FTO in 371 styrian adolescents towards degree of obesity, subcutaneous adipose tissue (SAT)-distribution determined by lipometry, early metabolic and preatherosclerotic symptoms. The percentage of AA homozygotes for the rs9939609 SNP of FTO was significantly increased in the obese adolescents. Compared to the TT wildtype, AA homozygotes showed significantly elevated values of SAT thickness at the trunk-located lipometer measure points neck and frontal chest, body weight, body mass index, waist, and hip circumference. No associations were found with carotis communis intima media thickness, systolic, diastolic blood pressure, ultrasensitive C-reactive protein (US-CRP), homocystein, total cholesterol, triglycerides, HDL cholesterol, oxidized LDL, fasted glucose, insulin, HOMA-index, liver transaminases, uric acid, and adipokines like resistin, leptin, and adiponectin. Taken together, to the best of our knowledge we are the first to report that the rs9939609 FTO SNP is associated with trunk weighted obesity as early as in adolescence.

High density lipoprotein cholesterol level is a robust predictor of lipid peroxidation irrespective of gender, age, obesity, and inflammatory or metabolic biomarkers.

BACKGROUND: Obesity related dyslipidemia, chronic inflammation and oxidative stress were associated with atherosclerotic sequels. We analysed oxidized low-density lipoprotein (oxLDL) plasma levels of 797 participants of the STyrian Juvenile OBesity (STYJOBS) / Early DEteCTion of Atherosclerosis (EDECTA) Study cohort aged from 5 to 50 years. The rationale of STYJOBS/EDECTA is to investigate the preclinical phase of obesity by a well defined cohort of young and middle aged overweight/obese and normal weight subjects. METHODS AND RESULTS: Plasma oxLDL was analysed by ELISA (Mercodia, Sweden). In the overweight/obese (OW/OB) study group, oxLDL levels were significantly increased compared to normal weighted controls (p<0.001). Probands with metabolic syndrome (MS) had significantly higher oxLDL levels than probands without MS; between overweight and obese participants, and between females and males, no significant difference was seen. In a multiple stepwise regression analysis including all study subjects, age, gender, anthropometric data, presence of metabolic syndrome, systolic, diastolic blood pressure, carotis communis intima media thickness, lipids, adipokines, metabolic, and inflammatory biomarkers, decreased high-density lipoprotein (HDL-cholesterol) and increased total cholesterol were the best predictors for increased oxLDL levels. CONCLUSION: Decreased HDL-cholesterol is an important determinant of lipid peroxidation irrespective of obesity, age, gender, SAT distribution, and inflammatory/metabolic biomarkers.

Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles.

Subcutaneous adipose tissue (SAT) topography contributes significantly to metabolic risk profiles and atherosclerotic vascular burden in obese adults. However, little information exists concerning individual risk profiles in early phases of obesity found in childhood and adolescence. Thus, the rationale of this study was to evaluate possible impacts of SAT topography in obese juveniles on adiponectin subfractions, with special emphasis on low molecular weight (LMW) adiponectin. To address this, we analysed associations between lipometry, early metabolic and preatherosclerotic symptoms and adiponectin subfractions in 71 obese juveniles and 75 normal weight controls of similar age and gender distribution. Compared to the controls, obese juveniles had a significantly decreased ratio between high molecular weight (HMW) and total adiponectin whereas the LMW/total adiponectin ratio was increased. The LMW/total adiponectin ratio correlated significantly positively with the SAT thickness of trunk-located lipometer measure points neck, biceps, upper back, lower back, body mass index (BMI), and waist circumference. Further significant positive correlations were seen with systolic blood pressure, intima media thickness (IMT) of common carotid arteries, and metabolic parameters such as HOMA-index, leptin, oxidized LDL (oxLDL), liver transaminases, and HDL-triglycerides. This remained stable after controlling for gender. A stepwise multiple regression analysis encompassing all these variables revealed a robust positive association between LMW/total adiponectin ratio and nuchal SAT thickness defined by the lipometer measure point neck. Taken together, our data provide the first evidence that nuchal SAT thickness is tightly positively associated with an increased LMW/total adiponectin ratio.

Preatherosclerosis and adiponectin subfractions in obese adolescents.

We evaluated total adiponectin, high-molecular weight (HMW), medium-molecular weight (MMW), low-molecular weight (LMW) adiponectin subfractions, clinical parameters, routine lab parameters, lipids, metabolic, inflammatory biomarkers, and intima-media thickness (IMT) of common carotid arteries in 70 obese juveniles and adolescents with preatherosclerosis and 55 normal weight controls of similar age and gender distribution. Compared with the controls, the obese probands had a significantly increased IMT (P < 0.001) and elevated ultra-sensitive C-reactive protein (P < 0.001) indicating early vascular burden. Total and HMW adiponectin were significantly decreased in the obese cohort. The ratio between HMW and total adiponectin was significantly decreased in obese probands whereas the LMW/total adiponectin ratio was increased. Overall, total-, HMW, and MMW adiponectin were significantly negatively correlated with carotid IMT. The HMW/total adiponectin ratio correlated significantly negatively, and the LMW/total adiponectin ratio significantly positively with the IMT. Furthermore, HMW adiponectin was significantly positively correlated with high-density lipoprotein (HDL)-cholesterol and serum apolipoprotein A1, and negatively with BMI, triglycerides, homeostatic model assessment (HOMA)-index, leptin, liver transaminases, and uric acid. This remained stable after controlling for gender. Multiple regression analysis of body measures and all other lab parameters showed the strongest correlation between HMW adiponectin and carotid IMT (beta = -0.35, P < 0.001). Taken together, our study provides the first evidence that preatherosclerosis in obese juveniles and adolescents is associated with altered subfractions of adiponectin, whereas after multiple testing the HMW subfraction showed a better correlation to IMT compared with total adiponectin.