Reinhard Möller

Body fat distribution of overweight females with a history of weight cycling

Weight cycling may cause a redistribution of body fat to the upper body fat compartments. We investigated the distribution of subcutaneous adipose tissue (SAT) in 30 overweight women with a history of weight-cycling and age-matched controls (167 normal weight and 97 overweight subjects). Measurements of SAT were performed using an optical device, the Lipometer. The SAT topography describes the thicknesses of SAT layers at 15 anatomically well-defined body sites from neck to calf. The overweight women with a history of weight cycling had significantly thicker SAT layers on the upper body compared to the overweight controls, but even thinner SAT layers on their legs than the normal weight women. An android fat pattern was attributed to overweight females and, even more pronounced, to the weight cyclers. The majority of normal weight women showed a gynoid fat pattern. Using stepwise discriminant analysis, 89.0% of all weight cyclers and overweight controls could be classified correctly into the two groups. These findings show the importance of normal weight maintenance as a health-promoting factor.

Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome

Variants in the fat mass and obesity-associated gene (FTO) are associated with obesity and type 2 diabetes mellitus. Women with polycystic ovary syndrome (PCOS) are frequently affected by obesity and impaired glucose tolerance. The aim of this study was to investigate the impact of FTO variants (rs9939609) on metabolic and endocrine parameters in PCOS women. We genotyped the single nucleotide polymorphism rs9939609 (T/A) in 288 PCOS women and performed metabolic and hormonal measurements, oral glucose tolerance test, hirsutism score, and lipometry. The A/T + A/A genotype showed an increased prevalence in overweight/obese PCOS patients (odds ratio [OR] = 1.91, P = .028) and in PCOS women with impaired glucose tolerance (OR = 3.23, P = .009). The A allele was associated with a significant increase in free testosterone (P = .042), weight (P = .024), body mass index (P = .011), 2-hour glucose (P = .047), 1-hour insulin (P = .032), and AUCins (area under the curve insulin) (P = .038). In a logistic regression analysis, the A allele was associated with free testosterone (P = .025; OR = 1.54; 95% confidence interval, 1.06-2.25; B = 0.86). Total body fat (percentage) (P = .016), total fat mass (P = .013), visceral adipose tissue mass (P = .044), and subcutaneous fat mass (P = .011) were significantly increased in PCOS women carrying the A allele. We demonstrated that variants within the FTO gene influence hyperandrogenemia and anthropometric parameters in women with PCOS, indicating an important role of FTO variants not only in obesity and diabetes but also in hyperandrogenism in women with PCOS.

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 (β = −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.

The Lipid Accumulation Product Is Associated with Impaired Glucose Tolerance in PCOS Women

BACKGROUND Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances. Lipid accumulation product (LAP) is an emerging cardiovascular risk factor. We aimed to investigate the association of LAP with impaired glucose tolerance (IGT) in PCOS and control women. METHODS The LAP was calculated as [waist circumference (centimeters) - 58] × [triglycerides (millimoles per liter)] in 392 PCOS and 140 body mass index (BMI)-matched control women within the same age range. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed. RESULTS PCOS women had significantly higher LAP levels than control women in age-adjusted analyses [22.2 (10.9-46.2) and 18.2 (10.7-36.3), respectively, P = 0.001). In PCOS and control women, age, BMI, blood pressure, fasting and stimulated glucose, fasting and stimulated insulin, and free testosterone progressively increased, whereas SHBG decreased across LAP quartiles. In PCOS and control women, receiver operating characteristic curve analysis revealed that the best cutoff value for LAP to define the presence of IGT was 44.1 and 41.8, respectively [sensitivity 79.5%, specificity 80.5%, and area under the curve (AUC) 0.86 and sensitivity 82.3%, specificity 90.5%, and AUC 0.86, respectively]. In PCOS and control women, receiver operating characteristic curve analyses for BMI (0.77 and 0.54, respectively) and waist circumference (0.80 and 0.72, respectively) to define IGT revealed lower AUC. Odds ratios for IGT for PCOS women in the highest LAP, BMI, and waist-to-hip ratio quartile were 41.81 (5.52-316.54), 10.24 (2.94-35.63), and 18.45 (4.19-81.30), respectively, when compared with PCOS women in the lowest LAP, BMI, and WHR quartile, respectively. CONCLUSION LAP is an easily obtainable and cheap marker associated with IGT in PCOS and control women.

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.

Measurement of subcutaneous adipose tissue topography (SAT-Top) by means of a new optical device, LIPOMETER, and the evaluation of standard factor coefficients in healthy subjects.

The quantification of obesity in respect to subcutaneous adipose tissue and fat distribution is a matter of interest. We recently reported on a new optical device, LIPOMETER, and its ability to measure the thickness of subcutaneous adipose tissue and its advantages compared with other methods. To describe the subcutaneous adipose tissue distribution of the human body in a precise, reproducible, and comparable manner, 15 well‐defined body sites distributed from neck to calf on the right body side were used. This set of sites defines subcutaneous adipose tissue topography (SAT‐Top). To visualize SAT‐Top for subjects or groups, special SAT‐Top plots were used. Subcutaneous adipose tissue distribution can be recognized easily with these techniques. SAT‐Top of 590 healthy men and women was measured. Factor analysis was used to extract the essential information from these 590*15 intercorrelated single measurements and to provide standard factor coefficients for later applications. As an example of how to use the results of factor analysis, the strong SAT‐Top deviation of women with clinically proven type‐2 diabetes mellitus (NIDDM) from healthy controls is described. Am. J. Hum. Biol. 12:231–239, 2000.

Estimating percentage total body fat and determining subcutaneous adipose tissue distribution with a new noninvasive optical device LIPOMETER

A newly developed optical device was applied to measure the subcutaneous adipose tissue (SAT) thickness of 20 healthy women and 18 healthy men at specified body sites. These measurements were used to derive equations to estimate percentage total body fat (TBF%). Total body electrical conductivity (TOBEC) was employed as a reference method; caliper techniques and measurements of absorbances of infrared light in fat versus lean tissue were also compared. The LIPOMETER results show good agreement with TOBEC data (r = 0.96). The technique allows the precise determination of the distribution of SAT thickness at specified body sites. The method also permits the construction of profiles of SAT thicknesses, e.g., the profiles are significantly different between women and men. Based on the normal profiles of healthy subjects, patients with proven type‐2 diabetes mellitus were also evaluated. The patients showed significantly different profiles. By linear discriminant analysis, classification functions were extracted with good predictive accuracy classification of subjects according to the presence or absence of type‐2 diabetes mellitus. The data suggest that measurement of SAT thickness might aid in the diagnosis and/or classification of metabolic disorders. Am. J. Hum. Biol. 12:221–230, 2000.

Lipid profile in normal weight migraineurs – evidence for cardiovascular risk

Background:  Recent studies suggest that migraine is associated with metabolic disorders. In particular, migraine may be associated with cardiovascular risk; however, an association of migraine with cardiovascular risk factors like hypercholesterolemia has been proposed, but previous studies have yielded in part conflicting results. The aim of the present study is to evaluate the lipid profile in normal weight migraine patients.

Oxidative stress is associated with migraine and migraine-related metabolic risk in females.

Background and purpose:  Oxidative stress is discussed to be implicated in the pathophysiology of migraine. However, data are in part controversial and the possible underlying mechanisms remain elusive to date. The aim of this study was to investigate the oxidative stress status of female patients with migraine and its implications on migraine‐related metabolic alterations.

Fatty liver index in polycystic ovary syndrome.

INTRODUCTION Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances and might be affected by hepatic steatosis. The fatty liver index (FLI) was developed as a simple and accurate predictor of hepatic steatosis. We aimed to analyze the association of FLI with endocrine and metabolic parameters in a cohort of PCOS and control women. METHODS FLI was calculated using body mass index (BMI), waist circumference, triglycerides, and gamma-glutamyl transferase in 611 PCOS and 139 BMI-matched control women within the same age range. Elevated FLI was defined as >60. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed. RESULTS PCOS women had significantly higher FLI levels than control women in age-adjusted analyses (11.4 (4.3-48.8) and 8.8 (3.9-35.0), respectively, P=0.001), whereas fibrosis indices were similar (aspartate amino transferase-to-platelet ratio index) or lower (FIB-4) respectively. In binary logistic regression analysis adjusted for age, odds ratio (OR) for elevated FLI was 2.52 (1.31-4.85), P=0.006, for PCOS women when compared with controls. PCOS women with high FLI levels had an adverse anthropometric, metabolic, and endocrine risk profile. The prevalence of elevated FLI was 88.7% in PCOS women with metabolic syndrome (MS) and 11.3% in PCOS women without MS (P<0.001). In control women, elevated FLI was present in 66.7% of women with MS and 30.8% of women without MS. CONCLUSION High FLI levels are a common finding in obese PCOS women and are closely linked to MS. FLI calculation might be a useful tool for identifying PCOS patients at high risk for metabolic and hepatic disturbances.