Uncarboxylated matrix Gla-protein: A biomarker of vitamin K status and cardiovascular risk.

BACKGROUND: Dephosphorylated uncarboxylated matrix Gla-protein (dp-ucMGP) is a biomarker of functional vitamin K status. High plasma dp-ucMGP concentrations reflect a low vitamin K status and have been related to vascular calcification. Our aims were to assess plasma levels of dp-ucMGP and their association with cardiovascular risk in a general population. METHODS: Plasma dp-ucMGP measurements were performed using the IDS-iSYS InaKtif MGP assay in 491 consecutive participants in a Danish general population study (229 males and 262 females, aged 19-71 years). Multivariable linear and logistic regressions were used to assess the association between dp-ucMGP levels and cardiovascular risk factors. RESULTS: Mean ± standard deviation (SD) for dp-ucMGP was 465 ± 181 pmol/L, and upper 95th percentile was 690 pmol/L. In logistic regression analyses, an increase in dp-ucMGP category (<300, 300-399, 400-499, ≥500 pmol/L) was positively associated with obesity, odds ratio (OR) 2.27 (95% confidence interval (CI) 1.54-3.33), history of cardiovascular disease, OR 1.77 (CI 1.02-3.05), and above-median estimated pulse wave velocity (ePWV), OR 1.54 (CI 1.21-1.96), when adjusted for age, sex, and lifestyle factors. 1 SD increase in diastolic and systolic blood pressure (BP) corresponded to a 5.5% (CI 2.9-8.0%) and 4.7% (CI 2.1-7.4%) increase in dp-ucMGP, respectively, when adjusted for age and sex. CONCLUSION: Plasma dp-ucMGP levels were positively associated with obesity, BP, ePWV, and history of cardiovascular disease. These findings support that dp-ucMGP is a biomarker of cardiovascular risk, and that vitamin K status could play a role in vascular calcification. The strong association with obesity deserves further attention.

Identification of urine metabolites associated with 5-year changes in biomarkers of glucose homoeostasis.

AIM: Metabolomics provides information on pathogenetic mechanisms and targets for interventions, and may improve risk stratification. During the last decade, metabolomics studies were used to gain deeper insight into the pathogenesis of diabetes mellitus. However, longitudinal metabolomics studies of possible subclinical states of disturbed glucose metabolism are limited. Therefore, the aim of this study was to analyze the associations between baseline urinary metabolites and 5-year changes in continuous markers of glucose homoeostasis, including fasting glucose, HbA1c and homoeostasis model assessment of insulin resistance (HOMA-IR) index values. METHODS: Urine metabolites in 3986 participants at both baseline and 5-year follow-up of the population-based Inter99 study were analyzed by 1H-NMR spectroscopy. Linear regression and analyses of covariance models were used to detect associations between urine metabolites and 5-year changes in markers of glucose homoeostasis. RESULTS: Higher baseline levels of urinary alanine, betaine, N,N-dimethylglycine (DMG), creatinine and trimethylamine were associated with an increase in HbA1c from baseline to follow-up. In contrast, formic acid and trigonelline levels were associated with a decrease in HbA1c over time. Analyses of 5-year changes in fasting glucose and HOMA-IR index showed similar findings, with high baseline levels of lactic acid, beta-d-glucose, creatinine, alanine and 1-methylnicotinamide associated with increases in both parameters. CONCLUSION: Several urine metabolites were found to be associated with detrimental longitudinal changes in biomarkers of glucose homoeostasis. The identified metabolites point to mechanisms involving betaine and coffee metabolism as well as the possible influence of the gut microbiome.

Poor agreement in questionnaire-based diagnostic criteria for adult atopic dermatitis is a challenge when examining cardiovascular comorbidity.

BACKGROUND: The association between atopic dermatitis (AD) and cardio-metabolic risk factors is not yet established. Furthermore, no validated questionnaire-based method of identifying adults with AD is currently available. OBJECTIVES: To assess the cardio-metabolic risk in adults with a history of AD using 3 different questionnaire-based diagnostic criteria. METHODS: We utilized data from a general population study including questionnaire data and objective measurements of 9656 Danish adults. To identify adults with a history of AD, we used a question regarding physician-diagnosed AD and 2 versions of the UK Working Party Diagnostic Criteria. Associations between AD status and cardio-metabolic endpoints were estimated using survey weighted logistic and linear regression analysis. RESULTS: We identified 462 (4.8%) adults with self-reported physician-diagnosed AD, whereas 903 (9.4%) and 226 (2.3%) had AD according to the UK Working Party Criteria when at least 2 and 3of 4 minor criteria were fulfilled. The populations were not comparable in terms of occurrence of cardio-metabolic risk factors. For example, the prevalence of obesity was lower in participants with physician-diagnosed AD but overall higher in UK 2/4 and UK 3/4. CONCLUSION: Due to the heterogeneity in the captured study populations in terms of the studied outcomes and absence of a gold standard, no conclusions regarding the cardio-metabolic risk in adults with AD in a general population could be made. This study serves as an example of the challenges that are often encountered in questionnaire-based epidemiologic studies and highlights the need of better definitions for this patient group.

Estimating the causal effect of body mass index on hay fever, asthma and lung function using Mendelian randomization.

BACKGROUND: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). METHODS: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or ß-estimates with 95% confidence interval (CI). RESULTS: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: ß=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: ß=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m2 higher BMI. CONCLUSIONS: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Association studies of genetic scores of serum vitamin B12 and folate levels with symptoms of depression and anxiety in two danish population studies.

BACKGROUND/OBJECTIVES: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety. SUBJECTS/METHODS: The study included 4126 participants from two Danish population-based studies. Serum vitamin B12 and folate were measured. Weighed allele scores were calculated as the sum of weights (genetic effect sizes) for 12 and two variants increasing circulating levels of vitamin B12 and folate, respectively. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety. RESULTS: An increased weighed allele score for serum vitamin B12 was associated with decreased odds of a SCL-90-R score above the 90th percentile (OR 0.540 (95%CI 0.302-0.967)) in Health2006 but not in Inter99, in the pooled analysis (OR 0.817 (95%CI 0.331-2.018)) or with other outcomes. The weighed allele score for serum folate was not associated with any of the measured outcome variables: SCL-90-R scores of depression (pooled OR 0.603 (95%CI 0.101-3.602)), anxiety (pooled OR 0.619 (95%CI 0.110-3.495)), combined score or history of doctor-diagnosed depression or anxiety. CONCLUSION: Our results do not provide evidence for a causal effect of circulating folate or vitamin B12 on the risk of depression or anxiety. However, we cannot rule out small to moderate effects, and thus large scale studies are needed.

Mendelian randomisation study of the associations of vitamin B12 and folate genetic risk scores with blood pressure and fasting serum lipid levels in three Danish population-based studies.

BACKGROUND/OBJECTIVES: The aim was to examine the association of genetic risk scores (GRSs) of vitamin B12 and folate-associated variants with blood pressure and lipids. SUBJECTS/METHODS: The study included 12 532 adults from three population-based studies (Inter99, Health2006 and Dan-MONICA10) conducted in Denmark. GRSs were calculated by summarising the number of vitamin B12 and folate increasing alleles. Weighted GRSs were calculated as the sum of weights for each allele corresponding to genetic effects sizes. RESULTS: GRSs for serum vitamin B12 and folate were associated with serum vitamin B12 and folate, respectively. The ß coefficients (95% confidence interval (CI), P-value) for regression of log-transformed serum B12/folate on the weighted GRSs were 0.57 (0.54, 0.61), P<0.001 and 0.85 (0.70, 1.01), P<0.01. No associations were observed between the vitamin B12 GRSs and any of the blood pressure and lipid-related outcomes in the combined analyses. Increasing number of folate increasing alleles was associated with increased high-density lipoprotein (HDL) cholesterol concentrations (ß coefficient (95% CI, P-value) for regression of log-transformed HDL on the weighted GRSs, 0.081 (0.015, 0.148), P=0.017), but not with blood pressure, triglyceride, and low-density lipoprotein and total cholesterol levels. CONCLUSIONS: GRSs were not associated with blood pressure and lipid levels, except for an association between the GRS for folate and HDL cholesterol. Further studies are needed to determine whether a causal association between folate and HDL cholesterol exists.

Serum 25-hydroxyvitamin D and self-reported mental health status in adult Danes.

BACKGROUND/OBJECTIVES: Vitamin D receptors and vitamin D-metabolising enzymes are present in the brain and in the central nervous system at sites responsible for the regulation of emotions and behaviour. This raises the hypothesis that low vitamin D is related to poor mental health. Our aim was to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and the self-reported symptoms and diagnosis of depression and anxiety in the adult general population. SUBJECTS/METHODS: Serum 25(OH)D was measured in three Danish population-based studies, including 5308 adults aged 18-64 years. After 5 years, 2004 participants were re-examined. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety was recorded by using a questionnaire. RESULTS: Serum 25(OH)D was not associated with SCL average scores for depression and anxiety when analysed by quantile median regression adjusted for sex, age and other potential confounders. The ß-coefficient and 95% confidence interval (CI) per 10 nmol/l serum 25(OH)D were 0.00 (-0.00 to 0.01) and P=0.23 for depression and -0.00 (-0.01 to 0.00) and P=0.19 for anxiety. Furthermore, no evidence of an association was observed with longitudinal changes (combining depression and anxiety score: ß (95% CI)=0.00 (-0.00 to 0.00), P=0.90), with scores >90 percentiles (odds ratio (OR) (95% CI)=1.02 (0.98-1.07), P=0.32), or with self-reported history (OR (95% CI)=1.02 (0.97-1.07), P=0.47) or incidence (OR (95% CI)=1.02 (0.92-1.12), P=0.77) of doctor-diagnosed depression and/or anxiety. CONCLUSIONS: Our results suggest that low serum 25(OH)D is not associated with self-reported symptoms/diagnosis of depression and anxiety.

No association between vitamin D and atopy, asthma, lung function or atopic dermatitis: a prospective study in adults.

Studies suggest that vitamin D may be involved in the pathogenesis of allergic disorders, asthma and decreased lung function. However, results are inconsistent and only few prospective studies have examined adults. The purpose of this study was to investigate the association of serum 25-hydroxy vitamin D (s25(OH)D) with atopy, atopic dermatitis (AD), asthma, wheezing and impaired lung function in a prospective study of Danish adults. A random sample of 3471 persons was examined in 2006-2008. Of these, 2308 were re-examined 5 years later. s25(OH)D and specific IgE against four common inhalant allergens were measured by standard procedures. Wheezing, asthma and AD were assessed from questionnaires and lung function was measured by spirometry. We found no statistically significant associations between s25(OH)D and prevalence or incidence of atopy, AD, asthma or wheezing. Associations with lung function were inconsistent. We conclude that vitamin D status does not influence these conditions in adults.

The association of serum 25-OH vitamin D with atopy, asthma, and lung function in a prospective study of Danish adults.

BACKGROUND: Besides the important skeletal functions, it has been suggested that vitamin D is involved in the pathogenesis of allergy and asthma and related to lung function. However, previous studies are inconclusive. OBJECTIVE: The purpose of this study was to investigate associations of serum levels of 25-hydroxy vitamin D (25(OH)D) with atopy, asthma, and lung function in a prospective study of Danish adults. METHODS: This study included 4999 adults aged 30-60 years in 1999-2001. Three thousand and thirty-two of those included at baseline also participated at a follow-up examination 5 years later, and 3727 answered a 10-year follow-up questionnaire. Serum levels of (25(OH)D) were measured by high-performance liquid chromatography (HPLC) at baseline. No information on use of vitamin D supplements was available. Specific IgE against four common antigens was measured. Information about doctor-diagnosed asthma was obtained from questionnaires, and lung function (FEV1 and forced vital capacity) was measured by spirometry. RESULTS: We found no significant associations of 25(OH)D with atopy and doctor-diagnosed asthma. However, we found that low levels of 25(OH)D were associated with lower FEV1 percentage predicted (FEV1%pred) in the cross-sectional analyses. The odds ratio (OR) of FEV1%pred < 80% among participants in the highest quartile of 25(OH)D compared with those in the lowest was 0.66 (95% confidence interval (CI): 0.49-0.74). In contrast, prospective analyses indicated an association between high levels of 25(OH)D at baseline and adverse changes in lung function. OR (95%CI) of incident FEV1%pred < 80% was 1.73 (1.06-2.82) in the highest quartile of 25(OH)D compared with the lowest. CONCLUSIONS AND CLINICAL RELEVANCE: Our data indicates that 25(OH)D levels do not influence the development of asthma and allergy among adults. Further, the results did not consistently support that 25(OH)D levels associate with lung function. Randomized controlled trials are needed to further address this issue.

Atopy and cause-specific mortality.

BACKGROUND: Atopy is the familial or personal propensity to develop immunoglobulin E (IgE) antibodies against common environmental allergens and is associated with high risk of allergic disease. It has been proposed that atopy may have effects on risk of cardiovascular disease and cancer. OBJECTIVES: We investigated the association of atopy with all-cause and cause-specific mortality. METHODS: We included a total of 14 849 individuals from five Danish population-based cohorts with measurements of atopy defined as serum-specific IgE positivity against inhalant allergens. Participants were followed by linkage to the Danish Registry of Causes of Death to obtain information on mortality status and cause of death (median follow-up time 11.3 years). The relative mortality risk was estimated by Cox regression and expressed as hazard ratios, HRs (95% confidence intervals, CIs). RESULTS: A total of 1776 person died during follow-up. The mortality risk for atopics vs. non-atopics was: for all-cause mortality (HR = 1.03, 95% CI: 0.90, 1.17); neoplasms (HR = 0.86, 95% CI: 0.69, 1.06); endocrine, nutritional and metabolic disorders (HR = 1.48, 95% CI: 0.71, 3.08); mental and behavioural disorders (HR = 2.26, 95% CI: 1.18, 4.30); diseases of the nervous system (HR = 1.36, 95% CI: 0.65, 2.87); diseases of the circulatory system (HR = 1.00, 95% CI: 0.78, 1.29); diseases of the respiratory system (HR = 0.94, 95% CI: 0.55, 1.60); and diseases of the digestive system (HR = 1.75, 95% CI: 1.03, 2.98). CONCLUSIONS & CLINICAL RELEVANCE: We found no statistically significant association between atopy and all-cause mortality. However, atopy was associated with a significantly higher risk of dying from mental and behavioural disorders and gastrointestinal diseases, particularly liver diseases, and a lower risk of dying from breast cancer, but these associations were not statistically significant when applying the Bonferroni adjusted significance level. Further studies are needed to confirm our findings.

IgE antibodies to alpha-gal in the general adult population: relationship with tick bites, atopy, and cat ownership.

BACKGROUND: The carbohydrate alpha-gal epitope is present in many animal proteins, including those of red meat and animal immunoglobulins, such as cat IgA. Systemic anaphylaxis to the alpha-gal epitope has recently been described. OBJECTIVE: To investigate and compare the prevalence of alpha-gal-specific (s)IgE and its associated factors in the general adult population from two separated (Northern and Southern) European regions (Denmark and Spain, respectively). METHODS: Cross-sectional study of 2297 and 444 randomly selected adults from 11 municipalities in Denmark and one in Spain. Alpha-gal sIgE was assessed by ImmunoCAP to bovine thyroglobulin. Additional assessments included a panel of skin prick test (SPT) to common aeroallergens and epidemiological factors, including the history of tick bites in the Danish series. RESULTS: The prevalence of positive (≥ 0.1 kUA /L) sIgE to alpha-gal was 5.5% and 8.1% in the Danish and Spanish series, respectively. The prevalence of sIgE ≥ 0.35 kUA /L was 1.8% and 2.2% in Denmark and Spain, respectively. Alpha-gal sIgE positivity was associated with pet ownership in both series and, particularly, cat ownership (data available in the Danish series). Alpha-gal sIgE positivity was associated with atopy (SPT positivity) in both series, although it was not associated with SPT positivity to cat or dog dander. Alpha-gal sIgE positivity was strongly associated with a history of tick bites. CONCLUSIONS AND CLINICAL RELEVANCE: The prevalence of alpha-gal sIgE antibodies in these general adult European populations is similarly low. The presence of alpha-gal sIgE antibodies is associated with a history of tick bites, atopy, and cat ownership.

Filaggrin loss-of-function mutations and incident cancer: a population-based study.

BACKGROUND: Loss-of-function mutations in the filaggrin gene (FLG) could have opposing effects on cancer risk, as mutations are associated with both 10% higher serum vitamin D levels, which may protect against cancer, and with impaired skin barrier function, which may lead to higher cancer susceptibility. OBJECTIVES: To investigate the association of the FLG genotype and cancer types in four population-based cohorts. METHODS: A total of 13,376 individuals were genotyped for FLG mutations. Information on cancer was obtained from the Danish Cancer Registry. Persons with a history of cancer at baseline were excluded from prospective analyses. RESULTS: There were 1339 incident cancers (median follow-up 11·4 years). The hazard ratios (HRs) and 95% confidence intervals (CIs) for FLG mutation carriers vs. wild types were: for any cancer (HR 0·95, 95% CI 0·78-1·16), any cancer excluding nonmelanoma skin cancer (NMSC) (HR 1·05, 95% CI 0·84-1·31), head and neck cancer (HR 1·72, 95% CI 0·71-4·15), colorectal cancer (HR 0·82, 95% CI 0·44-1·52), bronchus and lung cancer (HR 1·34, 95% CI 0·77-2·33), breast cancer (HR 0·58, 95% CI 0·30-1·14), uterine cancer (HR 0·42, 95% CI 0·06-3·10), prostate cancer (HR 1·09, 95% CI 0·61-1·94), urinary cancer (HR 1·30, 95% CI 0·51-3·29), malignant melanoma (HR 1·03, 95% CI 0·41-2·58) and NMSC (HR 0·70, 95% CI 0·47-1·05). Among participants aged over 60 years at baseline, we found statistically significant lower risks of all cancers and NMSC among FLG mutation carriers. CONCLUSIONS: The only significant associations between FLG loss-of-function mutations and cancer were in subgroup analyses.

The association of the 'additional height index' with atopic diseases, non-atopic asthma, ischaemic heart disease and mortality: a population-based study.

OBJECTIVE: Intrauterine growth has been associated with atopic conditions. Growth and adult height have been associated with cardiovascular disease, cancers and mortality but are highly genetic traits. The objectives of the study were as follows: first, to define a height measure indicating an individual's height below or above that which could be expected based on parental height (genetic inheritance) and growth charts. It was named 'the additional height index' (AHI), defined as (attained-expected) height; second, to investigate possible associations of AHI with atopic versus non-atopic health outcomes and with ischaemic heart disease (IHD) and IHD mortality. DESIGN: General population-based study. SETTING: Research centre. PARTICIPANTS: A random sample of 2656 men and women living in greater Copenhagen took part in the MONICA10 study (the Danish monitoring trends and determinants of cardiovascular disease). In total, 1900 participants with information of parental height were selected. OUTCOME MEASURES: Atopic sensitisation (serum IgE), questionnaire information of atopic dermatitis, rhinoconjunctivitis, asthma or wheezing, and registry-based diagnoses of IHD/IHD mortality from National Registries. RESULTS: Increasing levels of AHI were inversely associated with non-atopic asthma, non-atopic wheezing, IHD and IHD mortality (IHD-all). For one SD increase of AHI, the OR or HR with CI in adjusted analyses was non-atopic asthma OR=0.52 (0.36 to 0.74), non-atopic wheezing OR=0.67 (0.51 to 0.89), and IHD-all HR=0.89 (0.78 to 1.01). The level of AHI was higher among individuals with atopic dermatitis, allergic rhinoconjunctivitis and atopic sensitisation (all p values <0.001) compared with individuals without those conditions; however, the associations were not confirmed in adjusted analyses. CONCLUSIONS: Individuals with childhood conditions that led them to attain tallness higher than expected from their parents' height may be at lower risk of non-atopic asthma/wheeze and IHD/IHD mortality but possibly at higher risk of atopic conditions. The measure of tallness below or above the expected height could be a sensitive alternative to normal height in epidemiological analyses.

Investigating the causal effect of vitamin D on serum adiponectin using a Mendelian randomization approach.

BACKGROUND/OBJECTIVES: The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach. SUBJECTS/METHODS: Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two Danish population-based studies: the Inter99 study (6405 adults, 30-60 years) conducted in 1999-2001, and the MONICA10 study (2656 adults, 41-71 years) conducted in 1993-1994. RESULTS: In the Inter99 study, serum 25(OH)D was positively associated with total adiponectin (the effect estimate in % per doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, P<0.001). Using variations in the vitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P=0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10 cohort, no significant association was observed between the serum concentrations of 25(OH)D and HMW adiponectin (the effect estimate in % per doubling of 25(OH)D was -1.51, 95% CI: -5.80, 2.98, P=0.50), although the instrumental variables analysis to some extent supported a positive causal association (the effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI: -3.67, 95.20, P=0.080). CONCLUSIONS: The results indicate a possible causal association between serum 25(OH)D and total adiponectin. However, the association was not replicated for HMW adiponectin. Thus, further studies are needed to confirm a causal relationship.

Quantifying cardiovascular disease risk factors in patients with psoriasis: a meta-analysis.

BACKGROUND: In a previous meta-analysis on categorical data we found an association between psoriasis and cardiovascular disease and associated risk factors. OBJECTIVES: To quantify the level of cardiovascular disease risk factors in order to provide additional data for the clinical management of the increased risk. METHODS: This was a meta-analysis of observational studies with continuous outcome using random-effects statistics. A systematic search of studies published before 25 October 2012 was conducted using the databases Medline, EMBASE, International Pharmaceutical Abstracts, PASCAL and BIOSIS. RESULTS: We included 59 studies with up to 18 666 cases and 50 724 controls. Psoriasis cases had a higher total cholesterol [weighted mean difference 8·83 mg dL(-1) , 95% confidence interval (CI) 2·94-14·72, P = 0·003 (= 0·23 mmol L(-1) )], higher low-density lipoprotein cholesterol [9·90 mg dL(-1) , 95% CI 1·56-18·20, P = 0·020 (= 0·25 mmol L(-1) )], higher triglyceride [16·32 mg dL(-1) , 95% CI 12·02-20·63, P < 0·001 (= 0·18 mmol L(-1) )], a higher systolic blood pressure (4·77 mmHg, 95% CI 1·62-7·92, P = 0·003), a higher diastolic blood pressure (2·99 mmHg, 95% CI 0·60-5·38, P = 0·014), higher body mass idex (0·73 kg m(-2) , 95% CI 0·37-1·09, P < 0·001), higher waist circumference (3·61 cm, 95% CI 2·12-5·10, P < 0·001), higher fasting glucose [3·52 mg dL(-1) , 95% CI 0·64-6·41, P = 0·017 (= 0·20 mmol L(-1) )], higher nonfasting glucose [11·70 mg dL(-1) , 95% CI 11·24-12·15, P < 0·001 (= 0·65 mmol L(-1) )] and a higher HbA1c [1·09 mmol mol(-1) , 95% CI 0·87-1·31, P < 0·001 (= 2·2%)]. CONCLUSIONS: From a preventive medicine perspective, the weighted mean differences between cases and controls are significant, and therefore relevant to the clinical management of patients with psoriasis.

The relationship of serum triglycerides, serum HDL, and obesity to the risk of wheezing in 85,555 adults.

BACKGROUND: Asthma has been linked to obesity and the presence of the metabolic syndrome. OBJECTIVE: To explore which components of the metabolic syndrome that were associated with wheezing, a main symptom of asthma. Further, to explore whether these associations were different in individuals with and without rhinitis symptoms. METHODS: We used data from the Ibermutuamur Cardiovascular Risk Assessment Plan (ICARIA) including 85,555 Spanish workers (median age = 34, range = 16-75 years) with assessments of self reported wheezing and rhinitis symptoms. Fasting blood samples were analysed for serum triglyceride (s-TG), HDL (s-HDL) and glucose; blood pressure, waist circumference (WC) and body mass index (BMI) were measured. RESULTS: In mutually adjusted analyses including all components of the metabolic syndrome and possible confounders, elevated WC (or BMI), elevated s-TG and low s-HDL were significantly associated with wheezing. Odds ratio (OR) with confidence interval (CI) were: elevated WC = 1.54 (1.46-1.62), elevated s-TG = 1.24 (1.18-1.30), low s-HDL = 1.17 (1.12-1.22). These associations were stronger in individuals without than in those with rhinitis symptoms, OR's (CI's) were WC = without rhinitis 1.70 (1.57-1.85) vs. with rhinitis 1.47 (1.37-1.58). Elevated s-TG = without rhinitis 1.36 (1.26-1.46) vs. with rhinitis 1.21 (1.13-1.29). Low s-HDL = without rhinitis 1.24 (1.15-1.34) vs. with rhinitis 1.11 (1.04-1.18). CONCLUSIONS: High s-TG and low s-HDL were associated with wheezing after adjustment for adiposity. This may substantiate elevated s-TG and lowered s-HDL as markers or inducers of inflammation associated disease. The study supports the notion that these biochemical markers have differential effects on different types of wheezing.

Serum 25(OH)D and incident type 2 diabetes: a cohort study.

BACKGROUND/OBJECTIVES: Mild to moderate vitamin D insufficiency has been proposed as a risk factor for several common chronic diseases including type 2 diabetes. This study aimed to examine the association between serum 25-hydroxy vitamin D (25(OH)D) and incident diabetes. SUBJECTS/METHODS: The MONICA10 cohort consists of 2656 participants (men and women aged 41-71 years) who participated in a 10-year follow-up examination during 1993-1994 as part of the MONICA 1 population survey. A total of 2571 participants free of diabetes at baseline and with successful measurement of serum 25(OH)D were included in the current study. The Danish National Diabetes register enabled identification of 288 cases of incident diabetes during follow-up (median: 16.4 years). Data were analysed by Cox proportional hazard models and associations were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Serum 25(OH)D was inversely associated with incident diabetes adjusted for potential confounders (HR per 25 nmol/l=0.83; 95% CI: 0.72-0.95; P=0.009). A statistically significant interaction was observed between 25(OH)D and waist circumference (WC) (P(interaction)=0.042) suggesting an association in persons with a high WC (HR (95%CI) per 25 nmol/l=0.74 (0.63-0.88), 218 incident cases) and not in persons with a normal WC (HR (95%CI) per 25 nmol/l=0.98 (0.78-1.24), 70 incident cases). CONCLUSIONS: Low serum 25(OH)D was associated independently with incident diabetes. The inverse association was only found in overweight-obese and not in normal weight individuals, suggesting that obesity may modify the effect of vitamin D status on the risk of diabetes.