Association of Abdominal Obesity with Lumbar Disc Degeneration – A Magnetic Resonance Imaging Study

Purpose

To evaluate whether midsagittal (abdominal) obesity in magnetic resonance imaging (MRI), waist circumference (WC) and body fat percentage are associated with lumbar disc degeneration in early adulthood.

Methods

We obtained the lumbar MRI (1.5-T scanner) of 325 females and 233 males at a mean age of 21 years. Lumbar disc degeneration was evaluated using Pfirrmann classification. We analysed the associations of MRI measures of obesity (abdominal diameter (AD), sagittal diameter (SAD), ventral subcutaneous thickness (VST), and dorsal subcutaneous thickness (DST)), WC and body fat percentage with disc degeneration sum scores using ordinal logistic regression.

Results

A total of 155 (48%) females and 147 (63%) males had disc degeneration. AD and SAD were associated with a disc degeneration sum score of ≥3 compared to disc degeneration sum score of 0–2 (OR 1.67; 95% confidence interval (CI) 1.20–2.33 and OR 1.40; 95% CI 1.12–1.75, respectively) among males, but we found no association among females. WC was also associated with disc degeneration among males (OR 1.03 per one cm; 95% CI 1.00–1.05), but not among females.

Conclusion

Measures of abdominal obesity in MRI and waist circumference were associated with disc degeneration among 21-year-old males.     

Depression-Related Work Disability: Socioeconomic Inequalities in Onset,Duration and Recurrence

Objective

Depression is a major cause of disability in working populations and the reduction of socioeconomic inequalities in disability is an important public health challenge. We examined work disability due to depression with four indicators of socioeconomic status.

Methods

A prospective cohort study of 125 355 Finnish public sector employees was linked to national register data on work disability (>9 days) due to depressive disorders (International Classification of Diseases, codes F32–F34) from January 2005 to December 2011. Primary outcomes were the onset of work disability due to depressive disorders and, among those with such disability, return to work after and recurrent episodes of work disability due to depression.

Results

We found a consistent inverse socioeconomic gradient in work disability due to depression. Lower occupational position, lower educational level, smaller residence size, and rented (vs. owner-occupied) residence were all associated with an increased risk of work disability. Return to work was slower for employees with basic education (cumulative odds ratio = 1.21, 95% CI: 1.05–1.39) compared to those with higher education. Recurrent work disability episodes due to depression were less common among upper-grade non-manual workers (the highest occupational group) than among lower-grade non-manual (hazard ratio = 1.16, 95% CI: 1.07–1.25) and manual (hazard ratio = 1.14, 95% CI: 1.02–1.26) workers.

Conclusions

These data from Finnish public sector employees show persistent socioeconomic inequalities in work disability due to depression from 2005 to 2011 in terms of onset, recovery and recurrence.     

ALOX5 gene variants affect eicosanoid production and response to fish oil supplementation

The objective of this study was to determine whether 5-lipoxygenase (ALOX5) gene variants associated with cardiovascular disease affect eicosanoid production by monocytes. The study was a randomized, double-masked, parallel intervention trial with fish oil (5.0 g of fish oil daily, containing 2.0 g of eicosapentaenoic acid [EPA] and 1.0 g of docosahexaenoic acid [DHA]) or placebo oil (5.0 g of corn/soy mixture). A total of 116 subjects (68% female, 20-59 years old) of African American ancestry enrolled, and 98 subjects completed the study. Neither ALOX5 protein nor arachidonic acid-derived LTB4, LTD4, and LTE4 varied by genotype, but 5-hydroxyeicosatetraenoate (5-HETE), 6-trans-LTB4, 5-oxo-ETE, 15-HETE, and 5,15-diHETE levels were higher in subjects homozygous for the ALOX5 promoter allele containing five Sp1 element tandem repeats ("55" genotype) than in subjects with one deletion (d) (three or four repeats) and one common ("d5" genotype) allele or with two deletion ("dd") alleles. The EPA-derived metabolites 5-HEPE and 15-HEPE and the DHA-derived metabolite 17-HDoHE had similar associations with genotype and increased with supplementation; 5-HEPE and 15-HEPE increased, and 5-oxo-ETE decreased to a greater degree in the 55 than in the other genotypes. This differential eicosanoid response is consistent with the previously observed interaction of these variants with dietary intake of omega-3 fatty acids in predicting cardiovascular disease risk.     

Metabolic Signatures of Adiposity in Young Adults: Mendelian Randomization Analysis and Effects of Weight Change

Background

Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood.

Methods and Findings

We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16–39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m²). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%–183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; R ² = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160%±2%; R ² = 0.92).

Conclusions

Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors'' Summary     

The Increased Risk for Autoimmune Diseases in Patients with Eating Disorders

Objective

Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder.

Methods

Patients (N = 2342) treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368) matched for age, sex, and place of residence. Data of 30 autoimmune diseases from the Hospital Discharge Register from 1969 to 2010 were analyzed using conditional and Poisson regression models.

Results

Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease (OR 1.7, 95% CI 1.5–2.0, P<0.001). The increase in endocrinological diseases (OR 2.4, 95% CI 1.8–3.2, P<0.001) was explained by type 1 diabetes, whereas Crohn''s disease contributed most to the risk of gastroenterological diseases (OR 1.8, 95% CI 1.4–2.5, P<0.001). Higher prevalence of autoimmune diseases among patients with eating disorders was not exclusively due to endocrinological and gastroenterological diseases; when the two categories were excluded, the increase in prevalence was seen in the patients both before the onset of the eating disorder treatment (OR 1.5, 95% CI 1.1–2.1, P = 0.02) and at the end of the follow-up (OR 1.4, 95% CI 1.1–1.8, P = 0.01).

Conclusions

We observed an association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our findings support the link between immune-mediated mechanisms and development of eating disorders. Future studies are needed to further explore the risk of autoimmune diseases and immunological mechanisms in individuals with eating disorders and their family members.     

Childhood Adversity as a Predictor of Non-Adherence to Statin Therapy in Adulthood

PurposeTo investigate whether adverse experiences in childhood predict non-adherence to statin therapy in adulthood.MethodsA cohort of 1378 women and 538 men who initiated statin therapy during 2008–2010 after responding to a survey on childhood adversities, was followed for non-adherence during the first treatment year. Log-binomial regression was used to estimate predictors of non-adherence, defined as the proportion of days covered by dispensed statin tablets <80%. In fully adjusted models including age, education, marital status, current smoking, heavy alcohol use, physical inactivity, obesity, presence of depression and cardiovascular comorbidity, the number of women ranged from 1172 to 1299 and that of men from 473 to 516, because of missing data on specific adversities and covariates.ResultsTwo in three respondents reported at least one of the following six adversities in the family: divorce/separation of the parents, long-term financial difficulties, severe conflicts, frequent fear, severe illness, or alcohol problem of a family member. 51% of women and 44% of men were non-adherent. In men, the number of childhood adversities predicted an increased risk of non-adherence (risk ratio [RR] per adversity 1.11, 95% confidence interval [CI] 1.01–1.21], P for linear trend 0.013). Compared with those reporting no adversities, men reporting 3–6 adversities had a 1.44-fold risk of non-adherence (95% CI 1.12–1.85). Experiencing severe conflicts in the family (RR 1.27, 95% CI 1.03–1.57]) and frequent fear of a family member (RR 1.27, 95% CI 1.00–1.62]) in particular, predicted an increased risk of non-adherence. In women, neither the number of adversities nor any specific type of adversity predicted non-adherence.ConclusionsExposure to childhood adversity may predict non-adherence to preventive cardiovascular medication in men. Usefulness of information on childhood adversities in identification of adults at high risk of non-adherence deserves further research.     

Association of ADIPOR2 gene variants with cardiovascular disease and type 2 diabetes risk in individuals with impaired glucose tolerance: the Finnish Diabetes Prevention Study

Background

Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).

Hypothesis

Systemic inflammation and glycemia influence circadian blood pressure variability.

Methods

Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP) and heart rate (HR) were recorded by telemetry every 5 minutes during both sleep (day) and active (night) periods. Pulse pressure (PP) was calculated (PP = SBP-DBP).

Results

[mean(SEM)]: The AD fed group displayed significant increase in body weight (after 90 days; p < 0.01). Fasting glucose, adipokine (leptin and adiponectin) concentrations significantly increased (at 90 and 172 days; all p < 0.05), along with a trend for increased concentrations of systemic pro-inflammatory cytokines (MCP-1 and TNF-α) on day 90. The AD fed group, with significantly higher FG, also exhibited significantly elevated circadian (24-hour) overall mean SBP, DBP, PP and HR (all p < 0.05).

Conclusion

These data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system) which generate abnormal CBPV.