Associations Between C-Reactive Protein, Insulin Sensitivity, and Resting Metabolic Rate in Adults: A Mediator Analysis

Objective: Long-term positive energy balance promotes the development of obesity, a main risk factor for type 2 diabetes mellitus (T2DM). While an association between increased resting metabolic rate (RMR) and insulin sensitivity (IS) was shown previously, the underlying mechanisms remain unclear. Aim of the mediator analysis was to investigate the role of inflammation within the association between RMR and IS.Methods: Anthropometric, clinical, and lifestyle data were collected according to standard operating procedures. RMR was measured using indirect calorimetry. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as an IS parameter and C-reactive protein (CRP) was measured to represent the inflammatory status. Statistical analyses were performed using SPSS.Results: The analysis included 782 adults (517 females) with a mean age of 32.4 ± 12.0 years and a mean body mass index (BMI) of 24.6 ± 5.2 kg/m2. Regression analysis indicated a significant evidence for associations between RMR and HOMA-IR (ß = 39.3 ± 7.3 kcal/d; p ≤ 0.001) and CRP and HOMA-IR (ß = 0.5 ± 0.1; p ≤ 0.001) after adjustment for fat-free mass, sex, age, and study site. Results of the mediator analysis did not support the hypothesis that CRP is a mediator for the association between RMR and HOMA-IR. These results did not change after participant stratification according to sex or BMI.Conclusion: A significant evidence for an association between RMR and IS was shown in a large cohort. However, the inflammatory status, determined via CRP levels, was not a mediator within this association

Effects of genetic loci associated with central obesity on adipocyte lipolysis

Objectives: Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis. Subjects and Methods: Fasting subcutaneous adipose tissue biopsies were collected from 789 volunteers (587 women and 202 men, body mass index (BMI) range 17.7–62.3 kg/m2). We quantified subcutaneous adipocyte lipolysis, both spontaneous and stimulated by the catecholamine isoprenaline or a cyclic AMP analogue. DNA was extracted from peripheral blood mononuclear cells and genotyping of SNPs associated with WHRadjBMI conducted. The effects on adipocyte lipolysis measures were assessed for SNPs individually and combined in a SNP score. Results: The WHRadjBMI-associated loci CMIP, PLXND1, VEGFA and ZNRF3-KREMEN1 demonstrated nominal associations with spontaneous and/or stimulated lipolysis. Candidate genes in these loci have been reported to influence NFκB-signaling, fat cell size and Wnt signalling, all of which may influence lipolysis. Significance: This report provides evidence for specific WHRadjBMI-associated loci as candidates to modulate adipocyte lipolysis. Additionally, our data suggests that genetically increased central fat accumulation is unlikely to be a major cause of altered lipolysis in abdominal adipocytes

Treatment of thyroid dysfunctions decreases the risk of cerebrovascular events in men but not in women: results of the MONICA/KORA Cohort Study

OBJECTIVE:Thyroid disorders are well known to be associated with cardiovascular diseases. Some studies have shown that the negative effects of thyroid disorders are partially reversible after adequate treatment. The aim of this analysis was to assess the risk of incident ischemic cerebrovascular diseases in study participants treated for thyroid dysfunctions in a population-based cohort study. METHODS:For the presented analyses data from 8564 male and 8714 female individuals aged 25 to 74 years of the MONICA/KORA cohort were used (median follow-up 14.0 years). A combined binary variable "thyroid disorder" (TDC) was created utilizing data on self-reported physician-treated thyroid disorders and information about medication use. To examine the association between TDC and incident ischemic cerebrovascular events, we performed multiple adjusted Cox proportional hazard regression models and calculated hazard ratios and corresponding 95% confidence intervals (HR, 95%CI). RESULTS:During follow-up between 1984 and 2008/2009, 514 incident fatal and non-fatal ischemic cerebrovascular events occurred in men and 323 in women. At baseline, 3.5% of men and 15.6% of women reported TDC. In the fully adjusted model, males who reported TDC had a significantly reduced risk of ischemic cerebrovascular events (HR = 0.52, 95%CI = 0.29-0.92). A similar result was obtained in men, when we utilized information on thyroid hormones use only. For the total study population and for women with TDC we found no association with ischemic cerebrovascular events. CONCLUSIONS:In our longitudinal analyses subjects with treated thyroid diseases had no increased risk of incident ischemic cerebrovascular events. Surprisingly in males, even a significantly reduced risk of incident ischemic cerebrovascular events was found, a result that deserves further clarification

Safety and efficacy of a lifestyle intervention for pregnant women to prevent excessive maternal weight gain: a cluster-randomized controlled trial

Background: Excessive gestational weight gain (GWG) is associated with short- and long-term health problems among mothers and their offspring. There is a strong need for effective intervention strategies targeting excessive GWG to prevent adverse outcomes. Methods: We performed a cluster-randomized controlled intervention trial in eight gynecological practices evaluating the feasibility and effectiveness of a lifestyle intervention presented to all pregnant women; 250 healthy, pregnant women were recruited for the study. The intervention program consisted of two individually delivered counseling sessions focusing on diet, physical activity, and weight monitoring. The primary outcome was the proportion of pregnant women exceeding weight gain recommendations of the Institute of Medicine (IOM). Secondary outcome variables were maternal weight retention and short-term obstetric and neonatal outcomes. Results: The intervention resulted in a lower proportion of women exceeding IOM guidelines among women in the intervention group (38\%) compared with the control group (60\%) (odds ratio (OR): 0.5; 95\% confidence interval (CI): 0.3 to 0.9) without prompting an increase in the proportion of pregnancies with suboptimal weight gain (19\% vs. 21\%). Participants in the intervention group gained significantly less weight than those in the control group. Only 17\% of the women in the intervention group showed substantial weight retention of more than 5 kg compared with 31\% of those in the control group at month four postpartum (pp) (OR: 0.5; 95\% CI: 0.2 to 0.9). There were no significant differences in obstetric and neonatal outcomes. Conclusions: Lifestyle counseling given to pregnant women reduced the proportion of pregnancies with excessive GWG without increasing suboptimal weight gain, and may exert favorable effects on pp weight retention

Less is more: Removing a modality of an expected olfactory‐visual stimulation enhances brain activation

Abstract In recent years, multisensory integration of visual and olfactory stimuli has extensively been explored resulting in the identification of responsible brain areas. As the experimental designs of previous research often include alternating presentations of unimodal and bimodal stimuli, the conditions cannot be regarded as completely independent. This could lead to effects of an expected but surprisingly missing sensory modality. In our experiment, we used a common functional magnetic resonance imaging (fMRI) study design with alternating strong unimodal and bimodal olfactory‐visual food stimuli, in addition to a slight overhang of the bimodal stimuli in an effort to examine the effects of removing a visual or olfactory congruent stimulus for older people (41–83 years). Our results suggest that the processing of olfactory and visual stimuli stays intact over a wide age‐range and that the utilization of strong stimuli does not lead to superadditive multisensory integration in accordance with the principle of inverse effectiveness. However, our results demonstrate that the removal of a stimulus modality leads to an activation of additional brain areas. For example, when the visual stimulus modality is missing, the right posterior superior temporal gyrus shows higher activation, whereas the removal of the olfactory stimulus modality leads to higher activation in the amygdala/hippocampus and the postcentral gyrus. These brain areas are related to attention, memory, and the search of the missing stimulus. Consequently, careful attention must be paid to the design of a valid, multimodal sensory experiment while also controlling for cognitive expectancy effects that might confound multimodal results

Targeted LC-ESI-MS2 characterization of human milk oligosaccharide diversity at 6 to 16 weeks post-partum reveals clear staging effects and distinctive milk groups

Many molecular components in human milk (HM), such as human milk oligosaccharides (HMOs), assist in the healthy development of infants. It has been hypothesized that the functional benefits of HM may be highly dependent on the abundance and individual fine structures of contained HMOs and that distinctive HM groups can be defined by their HMO profiles. However, the structural diversity and abundances of individual HMOs may also vary between milk donors and at different stages of lactations. Improvements in efficiency and selectivity of quantitative HMO analysis are essential to further expand our understanding about the impact of HMO variations on healthy early life development. Hence, we applied here a targeted, highly selective, and semi-quantitative LC-ESI-MS2 approach by analyzing 2 × 30 mature human milk samples collected at 6 and 16 weeks post-partum. The analytical approach covered the most abundant HMOs up to hexasaccharides and, for the first time, also assigned blood group A and B tetrasaccharides. Principal component analysis (PCA) was employed and allowed for automatic grouping and assignment of human milk samples to four human milk groups which are related to the maternal Secretor (Se) and Lewis (Le) genotypes. We found that HMO diversity varied significantly between these four HM groups. Variations were driven by HMOs being either dependent or independent of maternal genetic Se and Le status. We found preliminary evidence for an additional HM subgroup within the Se- and Le-positive HM group I. Furthermore, the abundances of 6 distinct HMO structures (including 6'-SL and 3-FL) changed significantly with progression of lactation. Graphical abstract

Age‐related metabolite profiles and their relation to clinical outcomes in young adults, middle‐aged individuals, and older people

AbstractAge is a significant risk factor for common noncommunicable diseases, yet the physiological alterations of aging are poorly understood. We were interested in metabolic patterns between cross‐sectional cohorts of different age ranges with particular emphasis on waist circumference. We recruited three cohorts of healthy subjects with different age ranges (adolescents 18–25 years, adults 40–65 years, and older citizens 75–85 years) and stratified these based on waist circumference. Using targeted LC‐MS/MS metabolite profiling, we analyzed 112 analytes in plasma (amino acids, acylcarnitines, and derivatives). We associated age‐related alterations with various anthropometric and functional parameters such as insulin sensitivity and handgrip strength. Strongest age‐dependent increases were found for fatty acid‐derived acylcarnitines. Amino acid‐derived acylcarnitines displayed increased associations with BMI and adiposity. Some essential amino acids changed in opposite directions, being lower at increased age and higher with increasing adiposity. τ‐methylhistidine was elevated in older subjects, especially on an adiposity background, suggesting an increased protein turnover. Both aging and adiposity are associated with impaired insulin sensitivity. Skeletal muscle mass decreased with age and increased with adiposity. Profound differences in the metabolite signatures during healthy aging and elevated waist circumference/body weight were found. Opposite changes in skeletal muscle mass as well as possible differences in insulin signaling (relative insulin deficiency in older subjects versus hyperinsulinemia associated with adiposity), might be underlying origins for the observed metabolite signatures. We describe novel associations between metabolites and anthropometric factors during aging which underlines the complex interplay of aging, insulin resistance, and metabolic health.In this study, cohorts of different age ranges and with different waist circumferences were selected and plasma was collected. Targeted LC‐MS/MS was used to analyze amino acids, acylcarnitines, and derivatives. Age and the degree of adiposity affected metabolite concentrations and anthropometrics differently. The differences in insulin levels and insulin action, in addition to different tissue masses, may be responsible for unique metabolite patterns, associated with different metabolic processes. image </p