Publications

<b><i>Objective</i></b><b> </b>Prospective associations between omega-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize prospective associations between biomarkers of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), and T2D risk through an individual participant-level pooled analysis. <p><b><i>Research Design and Methods </i></b>Our analysis incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline.</p> <p><i>De novo</i> harmonized analyses were performed in each cohort following a pre-specified protocol and cohort-specific associations were pooled using inverse variance-weighted meta-analysis.</p> <p><b><i>Results</i></b><b> </b>A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per inter-quintile range (difference between the 90<sup>th</sup> and 10<sup>th</sup> percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89) and 0.81 (0.75, 0.88), respectively (all <i>P</i><0.001). ALA was not associated with T2D, 0.97 (0.92, 1.02) per inter-quintile range. Associations were robust across pre-specified subgroups as well as in sensitivity analyses. </p> <p><b><i>Conclusions </i></b><a></a><a>Higher circulating biomarkers of seafood-derived omega-3 fatty acids, including EPA, DPA, DHA, and their sum were associated with lower risk of T2D in a global consortium of prospective studies. </a>The biomarker of plant-derived ALA was not significantly associated with T2D risk. </p>

Nicht von Pappe: Ein papierbasierter indirekter ELISA-Test wurde entwickelt (siehe Bild) und zum Nachweis von Kaninchen-IgG und dem gp41-Hüllprotein von HIV-1 genutzt. Das Verfahren kombiniert die Empfindlichkeit und Spezifität des ELISA-Tests mit den geringen Kosten und der einfachen Anwendung papierbasierter Analysesysteme. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Background Population‐based research on vitamin D has increased dramatically in recent years. Such studies are typically reliant on assay procedures to measure reliable and comparable levels of 25‐hydroxyvitamin D [25( OH )D] concentrations. Methods Concentrations of 25( OH )D 3 and 25( OH )D 2 were measured using LC ‐ MS / MS in 5,915 participants (aged 31 years) of Northern Finland Birth Cohort 1966. Blood samples were assayed in batches over a course of 18 months. As anomalies were present in the measurements, 200 samples were reassayed using Diasorin RIA . Agreement between measurements was assessed by Passing–Bablok regression and limits of agreement (LoA). To harmonize LC ‐ MS / MS with Diasorin RIA measurements, formulae were derived from the LoA. Results Concentrations measured by LC ‐ MS / MS were much higher than those measured by Diasorin RIA , with a mean difference of 12.9 ng/ ml . Constant variation was evident between batch measurements after log transformation. Statistical formula was applied separately for each batch of LC ‐ MS / MS measurements, enabling us to remove both the constant and proportional bias that was evident prior to the transformation. Conclusion Despite the introduction of schemes/programs to improve accuracy of assays to measure 25( OH )D, significant differences can still happen. In these instances, methods to harmonize measurements based on a relatively small number of replicates can be successfully applied to establish confidence and to enable between‐study comparisons.

Objective To evaluate the amount of self-reported physical activity in young adults born prematurely compared with those born at term. Study design Unimpaired participants of the Preterm Birth Study (Preterm Birth and Early Life Programming of Adult Health and Disease) birth cohort study were studied at age 23.3 ± 1.2 (SD) years: 118 born early preterm ( Results Adults born early preterm reported a 31.5% (95% CI, 17.4-43.2) lower volume of leisure time physical activity (in metabolic equivalents [MET] h/year) and had a 2.0-fold increased OR (1.2-3.3) of being in the least active quintile than controls. Lower amounts of conditioning, nonconditioning, and commuting physical activity all contributed to the difference. In addition, early preterm participants undertook less vigorous physical activity (≥6 MET). No differences in physical activity were found between the late preterm and control groups. Adjustments for potential early life confounders and current mediating health characteristics did not change the results. Conclusions Young adults born early preterm engage less in leisure time physical activities than peers born at term. This finding may in part underlie the increased risk factors of cardiometabolic and other noncommunicable diseases in adults born preterm. Low physical activity is a risk factor for several noncommunicable diseases and amenable to prevention.

Abstract Objective To assess the association of dietary fatty acids with cardiovascular disease mortality and total mortality among patients with type 2 diabetes. Design Prospective, longitudinal cohort study. Setting Health professionals in the United States. Participants 11 264 participants with type 2 diabetes in the Nurses’ Health Study (1980-2014) and Health Professionals Follow-Up Study (1986-2014). Exposures Dietary fat intake assessed using validated food frequency questionnaires and updated every two to four years. Main outcome measure Total and cardiovascular disease mortality during follow-up. Results During follow-up, 2502 deaths including 646 deaths due to cardiovascular disease were documented. After multivariate adjustment, intake of polyunsaturated fatty acids (PUFAs) was associated with a lower cardiovascular disease mortality, compared with total carbohydrates: hazard ratios comparing the highest with the lowest quarter were 0.76 (95% confidence interval 0.58 to 0.99; P for trend=0.03) for total PUFAs, 0.69 (0.52 to 0.90; P=0.007) for marine n-3 PUFAs, 1.13 (0.85 to 1.51) for α-linolenic acid, and 0.75 (0.56 to 1.01) for linoleic acid. Inverse associations with total mortality were also observed for intakes of total PUFAs, n-3 PUFAs, and linoleic acid, whereas monounsaturated fatty acids of animal, but not plant, origin were associated with a higher total mortality. In models that examined the theoretical effects of substituting PUFAs for other fats, isocalorically replacing 2% of energy from saturated fatty acids with total PUFAs or linoleic acid was associated with 13% (hazard ratio 0.87, 0.77 to 0.99) or 15% (0.85, 0.73 to 0.99) lower cardiovascular disease mortality, respectively. A 2% replacement of energy from saturated fatty acids with total PUFAs was associated with 12% (hazard ratio 0.88, 0.83 to 0.94) lower total mortality. Conclusions In patients with type 2 diabetes, higher intake of PUFAs, in comparison with carbohydrates or saturated fatty acids, is associated with lower total mortality and cardiovascular disease mortality. These findings highlight the important role of quality of dietary fat in the prevention of cardiovascular disease and total mortality among adults with type 2 diabetes.

Background— Genome-wide association (GWA) studies have identified several susceptibility loci for metabolic syndrome (MetS) component traits, but have had variable success in identifying susceptibility loci to the syndrome as an entity. We conducted a GWA study on MetS and its component traits in 4 Finnish cohorts consisting of 2637 MetS cases and 7927 controls, both free of diabetes, and followed the top loci in an independent sample with transcriptome and nuclear magnetic resonance-based metabonomics data. Furthermore, we tested for loci associated with multiple MetS component traits using factor analysis, and built a genetic risk score for MetS. Methods and Results— A previously known lipid locus, APOA1/C3/A4/A5 gene cluster region (SNP rs964184 ), was associated with MetS in all 4 study samples ( P =7.23×10 −9 in meta-analysis). The association was further supported by serum metabolite analysis, where rs964184 was associated with various very low density lipoprotein, triglyceride, and high-density lipoprotein metabolites ( P =0.024–1.88×10 −5 ). Twenty-two previously identified susceptibility loci for individual MetS component traits were replicated in our GWA and factor analysis. Most of these were associated with lipid phenotypes, and none with 2 or more uncorrelated MetS components. A genetic risk score, calculated as the number of risk alleles in loci associated with individual MetS traits, was strongly associated with MetS status. Conclusions— Our findings suggest that genes from lipid metabolism pathways have the key role in the genetic background of MetS. We found little evidence for pleiotropy linking dyslipidemia and obesity to the other MetS component traits, such as hypertension and glucose intolerance.

Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.