Background-The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. Methods and Results-This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (nϭ30) were compared with healthy controls (nϭ153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (ϩ0.49, ϩ0.45 SD, respectively). HRV and total power were lower among cases (both Ϫ0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (ϩ0.89, ϩ0.51, and ϩ0.72 SD). Lower HRV was associated with higher normetanephrine output (rϭϪ0.19; Pϭ0.03). Among former cases (MS 5 years previously, nϭ23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. Conclusions-Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.

SummaryThis report describes the social distribution of central obesity and the metabolic syndrome at the Whitehall II study phase 3 examination, and assesses the contribution of health related behaviours to their distribution. Cross-sectional analyses were conducted utilising data collected in 1991-1993 from 4978 men and 2035 women aged 39-63 years who completed an oral glucose tolerance test. There was an inverse social gradient in prevalence of the metabolic syndrome. The odds ratio (95 % confidence interval) for having the metabolic syndrome comparing lowest with highest employment grade was: men 2.2 (1.6-2.9), women 2.8 (1.6-4.8). Odds ratios for occupying the top quintile of the following variables, comparing lowest with highest grade, were, for waist-hip ratio: men 2.2 (1.8-2.8), women 1.6 (1.1-2.4); postload glucose: men 1.4 (1.1-1.8), women 1.8 (1.2-2.6); triglycerides: men 1.6 (1.2-2.0), women 2.2 (1.5-3.3); fibrinogen: men 1.7 (1.4-2.3), women 1.9 (1.2-2.8). Current smoking status, alcohol consumption and exercise level made a small contribution (men 11%, women 9 %) to the inverse association between socioeconomic status and metabolic syndrome prevalence. In conclusion, central obesity, components of the metabolic syndrome and plasma fibrinogen are strongly and inversely associated with socioeconomic status. Our findings suggest the metabolic syndrome may contribute to the biological explanation of social inequalities in coronary risk. Health related behaviours appear to account for little of the social patterning of metabolic syndrome prevalence. [Diabetologia (1997[Diabetologia ( ) 40: 1341[Diabetologia ( -1349

The aim of the present cross-sectional study was to examine the agreement and disagreement between a 7 d diet diary (7DD) and a self-administered machine-readable food-frequency questionnaire (FFQ) asking about diet in the previous year, and to validate both methods with biomarkers of nutrient intake. The subjects were an age-and employment-grade-stratified random subsample of London-based civil servants (457 men and 403 women), aged 39 -61 years, who completed both a 7DD and a FFQ at phase 3 follow-up (1991 -1993) of the Whitehall II study. Mean daily intakes of dietary energy, total fat, saturated, monounsaturated and polyunsaturated fatty acids, linoleic acid, total carbohydrate excluding fibre, sugars, starch, dietary fibre, protein, vitamin C, vitamin E (as a-tocopherol equivalents), folate, carotenes (as total b-carotene activity), Fe, Ca, Mg, K and alcohol were measured. Serum cholesteryl ester fatty acids (CEFA), plasma a-tocopherol and b-carotene were also measured as biomarkers. Estimates of mean energy intake from the two methods were similar in men, and some 10 % higher according to the FFQ in women. Compared with the 7DD, the FFQ tended to overestimate plant-derived micronutrient intakes (carotenes from FFQ v. 7DD men 2713 (SD 1455) v. 2180 (SD 1188) mg/d, women 3100 (SD 1656) v. 2221 (SD 1180) mg/d, both differences P,0 : 0001) and to underestimate fat intake. Against plasma b-carotene/cholesterol, carotene intake was as well estimated by the FFQ as the 7DD (Spearman rank correlations, men 0 : 32 v. 0 : 30, women 0 : 27 v. 0 : 22, all P#0 : 0001, energy-adjusted data). Ranking of participants by other nutrient intakes tended to be of the same order according to the two dietary methods, e.g. rank correlations for CEFA linoleic acid against FFQ and 7DD estimates respectively, men 0 : 38 v. 0 : 41, women 0 : 53 v. 0 : 62, all P#0 : 0001, energy-adjusted % fat). For a-tocopherol there were no correlations between plasma level and estimated intakes by either dietary method. Quartile agreement for energy-adjusted nutrient intakes between the two self-report methods was in the range 37 -50 % for men and 32 -44 % for women, and for alcohol, 57 % in both sexes. Disagreement (misclassification into extreme quartiles of intake) was in the range 0 -6 % for both sexes. The dietary methods yielded similar prevalences (about 34 %) of low energy reporters. The two methods show satisfactory agreement, together with an expected level of systematic differences, in their estimates of nutrient intake. Against the available biomarkers, the machine-readable FFQ performed well in comparison with the manually coded 7DD in this study population. For both methods, regression-based adjustment of nutrient intake to mean dietary energy intake by gender appears on balance to be the optimal approach to data presentation and analysis, in view of the complex problem of low energy reporting.

Objective. To investigate the epidemiology and treatment of rheumatoid arthritis (RA) in a population broadly representative of employed adults in the US, using a retrospective cohort design. Methods. Incident and prevalent RA cohorts were defined from a sample of 4.66 million adults with complete followup data from the period of January 2005 through September 2008 in the Pharmetrics medical claims database. Demographics, comorbidity, and medical therapies were summarized using descriptive statistics. Results. Median duration in the database was 5.7 years. Age-and sex-adjusted incidence in 2006 was 0.71 per 1,000 persons at risk (n 5 3,992) and prevalence in 2005 was 0.63% (n 5 30,530). Within 12 months after diagnosis, 65%, 64%, and 20% of the incident cohort had been prescribed corticosteroids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and tumor necrosis factor (TNF) inhibitors, respectively. Median time to first anti-TNF prescription was 6 months; 31% switched to a second drug and 15% to a third. An aggressive subcohort (11% of incident patients) received more DMARDs (83%) and TNF inhibitors (43%), and was more likely to switch. Twenty-eight percent of incident patients received only symptomatic therapy over a minimum of 1.75 years of followup; these patients were older with more comorbidities and contraindications to methotrexate. Conclusion. In this insured population-based cohort, only two-thirds of newly diagnosed RA patients were prescribed a DMARD in year 1 and 28% received no antirheumatic therapy. Although limited by lack of clinical information and by left-censoring, administrative databases capture clinical practice and suggest that gaps exist in treatment options available to a significant number of patients.

Background: Progressive supranuclear palsy is a rare neurodegenerative movement disorder and little is known about its epidemiology.Objective: Estimate age-adjusted prevalence of progressive supranuclear palsy and describe antecedent diagnoses and progressive supranuclear palsy patient features in the 5 years before first diagnostic code.Methods: In a nested case-control study in the IBM MarketScan Commercial and Medicare Supplemental Databases, a large set of US insurance databases containing medical service and prescription drug claims from employer-based commercial and Medicare supplemental health insurance plans, progressive supranuclear palsy cases (identified via International Statistical Classification of Diseases 9th/10th revision codes) and controls were included if enrollment was ≥1 month in the study period (October 1, 2015–October 31, 2017). Two controls with no diagnosis codes for PSP were matched to cases on birth year, sex, enrollment time in the database, and pharmacy benefit eligibility. Controls were assigned a randomly selected index date from their eligibility period. Prevalence of progressive supranuclear palsy was estimated in 2016 among patients with ≥1 month of continuous enrollment in that year. Prevalence ratios for comorbidities (claim/diagnosis codes) were examined in the ≤ 5 years before index date (first progressive supranuclear palsy claim date).Results: Age-adjusted progressive supranuclear palsy prevalence was 2.95/100,000 in 2016. The most common diagnosis codes in cases vs. controls in the 5 years pre-index were gait abnormalities (79.3 vs. 21.8%), pain in joint (54.9 vs. 36.0%), Parkinson's disease (54.6 vs. 1.0%), fatigue (49.8 vs. 21.6%), and cerebrovascular disease (45.6 vs. 16.4%).Conclusions: In this large database analysis, based on preliminary analyses, the prevalence of diagnosed progressive supranuclear palsy was 2.95/100,000, which is lower than many prior studies. Typical symptoms suggestive of progressive supranuclear palsy were present before index date, indicating a potential delay in time to diagnosis. The identification of diagnostic codes for clinical features of progressive supranuclear palsy that occurred before index date may be used to develop predictive models to identify potential progressive supranuclear palsy patients earlier in their disease course.