Cynthia R. Davis

Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

CONTEXT Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. OBJECTIVE Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. DESIGN, SETTING, AND SUBJECTS We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. RESULTS Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = -0.4, P < .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P < .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66-33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72-19.60), high triglycerides (OR = 3.89, 95% CI = 1.16-13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18-9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. CONCLUSIONS Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.

Diet quality is associated with circulating C-reactive protein but not irisin levels in humans

OBJECTIVE Adherence to a healthy diet has been shown to decrease the incidence of obesity and associated comorbidities. C-reactive protein (CRP) is an established inflammatory marker and irisin was recently identified as a molecule which may play a role in energy regulation and obesity but whether diet alters irisin levels remains unknown. We aimed to investigate the association between circulating irisin, leptin, and CRP levels and dietary quantity and quality using the Alternate Healthy Eating Index (AHEI) and the Alternate Mediterranean Diet Score (aMED). MATERIALS/METHODS The study evaluated dietary data and biomarker levels of 151 participants between 2009 and 2011 (71 male vs. 80 female, over 35 years old, obese 43.7%). AHEI and aMED scores were calculated based on data derived from self-administered 110-item food-frequency questionnaires estimating usual nutrient intake over the past year. Cross-sectional associations between dietary quantity, quality, body composition by bioelectric impedance, and biomarker levels including irisin, leptin, and CRP after fasting were assessed. RESULTS CRP, but not irisin, was negatively correlated with AHEI (r=-0.34) and aMED (r=-0.31). Irisin was positively correlated with BMI (r=0.22), fat mass (r=0.21), waist circumference (r=0.24), waist-hip ratio (r=0.20), leptin (r=0.32), and CRP (r=0.25). Participants with the highest AHEI scores tended to have 11.6% lower concentrations of irisin (P for trend =0.09), but they were not significant after adjustment for potential confounders. Better diet quality was associated with lower CRP concentrations (P for trend=0.02) in multivariate model. Percentage of energy from carbohydrate was inversely associated with CRP. CONCLUSIONS Unlike CRP, irisin is not associated with dietary quality or quantity.

Early Life Adversity Is Associated With Elevated Levels of Circulating Leptin, Irisin, and Decreased Levels of Adiponectin in Midlife Adults

CONTEXT Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known. OBJECTIVES The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP). DESIGN/SUBJECTS/SETTING: This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP. RESULTS Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity. CONCLUSION Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity.

Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk

BACKGROUND AND AIMS There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. METHODS We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. RESULTS PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. CONCLUSIONS Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk.

Early life adversity and/or posttraumatic stress disorder severity are associated with poor diet quality, including consumption of trans fatty acids, and fewer hours of resting or sleeping in a US middle-aged population: A cross-sectional and prospective study

BACKGROUND Early life adversity (ELA) and post-traumatic stress disorder (PTSD) are associated with poorer psychological and physical health. Potential underlying mechanisms and mediators remain to be elucidated, and the lifestyle habits and characteristics of individuals with ELA and/or PTSD have not been fully explored. We investigated whether the presence of ELA and/or PTSD are associated with nutrition, physical activity, resting and sleeping and smoking. METHODS A cross-sectional sample of 151 males and females (age: 45.6±3.5 years, BMI: 30.0±7.1 kg/m(2)) underwent anthropometric measurements, as well as detailed questionnaires for dietary assessment, physical activity, resting and sleeping, smoking habits and psychosocial assessments. A prospective follow-up visit of 49 individuals was performed 2.5 years later and the same outcomes were assessed. ELA and PTSD were evaluated as predictors, in addition to a variable assessing the combined presence/severity of ELA-PTSD. Data were analyzed using analysis of covariance after adjusting for several socioeconomic, psychosocial and anthropometric characteristics. RESULTS Individuals with higher ELA or PTSD severity were found to have a poorer diet quality (DASH score: p=0.006 and p=0.003, respectively; aHEI-2010 score: ELA p=0.009), including further consumption of trans fatty acids (ELA p=0.003); the differences were significantly attenuated null after adjusting mainly for education or income and/or race. Further, individuals with higher ELA severity reported less hours of resting and sleeping (p=0.043) compared to those with zero/lower ELA severity, and the difference remained significant in the fully adjusted model indicating independence from potential confounders. When ELA and PTSD were combined, an additive effect was observed on resting and sleeping (p=0.001); results remained significant in the fully adjusted model. They also consumed more energy from trans fatty acids (p=0.017) tended to smoke more (p=0.008), and have less physical activity (PTSD p=0.024) compared to those with no or lower ELA and PTSD severity. Adjustments for sociodemographic factors and/or BMI rendered results of the above lifestyle parameters non-significant. The analysis of the prospective data showed similar trends to the cross-sectional analysis, further supporting the conclusions, although statistical significance of results was lower due to the lower number of participants. CONCLUSION Fewer hours of resting and sleeping and poorer diet quality are linked to ELA and/or PTSD, indicating that these pathways might underlie the development of several metabolic abnormalities in individuals with ELA and/or PTSD. Differences in terms of diet quality are significantly attenuated by race and/or education and/or income, whereas differences in other lifestyle habits of individuals with and without ELA and/or PTSD, such as physical activity, are mostly explained by confounding sociodemographic variables and/or body mass index.

Metabolic pathways link childhood adversity to elevated blood pressure in midlife adults

Childhood adversity is a risk factor for adult health outcomes, including obesity and hypertension. This study examines whether childhood adversity predicted mean arterial pressure through mechanisms of central obesity and leptin, adiponectin, and/or insulin resistance, and including dietary quality. 210 Black/African Americans and White/European Americans, mean age=45.8; ±3.3 years, were studied cross-sectionally. Path analyses were used to specify a chain of predictive variables in which childhood adversity predicted waist-hip ratio and dietary quality, circulating levels of hormones, and in turn, mean arterial pressure, adjusting for race, gender, and antihypertensive medications. Direct paths were found between childhood adversity, waist-hip ratio, and leptin levels and between leptin and dietary quality to mean arterial pressure. Systolic and diastolic blood pressures were similarly predicted. Early adversity appears to developmentally overload and dysregulate endocrine systems through increased risk for obesity, and through a direct impact on leptin that in turn, impacts blood pressure.

Attachment and the metabolic syndrome in midlife: the role of interview-based discourse patterns.

Objective Adult attachment discourse patterns and current family relationship quality were examined as correlates of health behaviors and number of metabolic syndrome (MetS) criteria met, and as mediators of the link between childhood adversity and these health outcomes. Methods A sample of 215 white/European American and black/African American adults aged 35 to 55 years were examined using a cross-sectional study design. Discourse was assessed with the Adult Attachment Interview, using coherence (a marker of attachment security), unresolved trauma/loss (a marker of disorganized cognitions related to trauma or loss), and idealization (minimizing stressful experiences and their impact) scores. Relationship quality, adverse childhood experiences, and current depressive symptoms were assessed, as were health behaviors of diet, exercise, and smoking. MetS includes obesity, elevated blood pressure, elevated fasting glucose, high triglycerides, and low high-density lipoprotein cholesterol. Results Using path analysis and including childhood adversity severity and depressive symptoms in the model, both Adult Attachment Interview coherence and unresolved trauma/loss were directly linked to the number of MetS criteria (r = 0.186 and r = 0.170, respectively). Idealization was indirectly linked to MetS through poor diet (r = 0.183). The final model explained 21% of the variance in scores for the number of MetS criteria met. Conclusions Insecure adult attachment is associated with increased risk of MetS.