The association between plasma metabolites and future risk of all-cause mortality

Background: Metabolite profiles provide snapshots of the overall effect of numerous exposures accumulated over life courses, which may lead to health outcomes in the future. Objective: We hypothesized that the risk of all-cause mortality is linked to alterations in metabolism earlier in life, which are reflected in plasma metabolite profiles. We aimed to identify plasma metabolites associated with future risk of all-cause mortality. Methods: Through metabolomics, 110 metabolites were measured in 3833 individuals from the Malm\uf6 Diet and Cancer—Cardiovascular Cohort (MDC-CC). A total of 1574 deaths occurred within an average follow-up time of 22.2 years. Metabolites that were significantly associated with all-cause mortality in MDC-CC were replicated in 1500 individuals from Malm\uf6 Preventive Project re-examination (MPP), among whom 715 deaths occurred within an average follow-up time of 11.3\ua0years. Results: Twenty two metabolites were significantly associated with all-cause mortality in MDC-CC, of which 13 were replicated in MPP. Levels of trigonelline, glutamate, dimethylglycine, C18-1-carnitine, C16-1-carnitine, C14-1-carnitine, and 1-methyladenosine were associated with an increased risk, while levels of valine, tryptophan, lysine, leucine, histidine, and 2-aminoisobutyrate were associated with a decreased risk of all-cause mortality. Conclusion: We used metabolomics in two Swedish prospective cohorts and identified replicable associations between 13 metabolites and future risk of all-cause mortality. Novel associations between five metabolites—C18-1-carnitine, C16-1-carnitine, C14-1-carnitine, trigonelline, and 2-aminoisobutyrate—and all-cause mortality were discovered. These findings suggest potential new biomarkers for the prediction of mortality and provide insights for understanding the biochemical pathways that lead to mortality

N-1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism

Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N-1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at similar to 18 h of fasting and being lowest similar to 3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.Peer reviewe

Plasma Metabolites Associate with All-Cause Mortality in Individuals with Type 2 Diabetes

Alterations in the human metabolome occur years before clinical manifestation of type 2 diabetes (T2DM). By contrast, there is little knowledge of how metabolite alterations in individuals with diabetes relate to risk of diabetes complications and premature mortality. Metabolite profiling was performed using liquid chromatography-mass spectrometry in 743 participants with T2DM from the population-based prospective cohorts The Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) and The Malmö Preventive Project (MPP). During follow-up, a total of 175 new-onset cases of cardiovascular disease (CVD) and 298 deaths occurred. Cox regressions were used to relate baseline levels of plasma metabolites to incident CVD and all-cause mortality. A total of 11 metabolites were significantly (false discovery rate (fdr) <0.05) associated with all-cause mortality. Acisoga, acylcarnitine C10:3, dimethylguanidino valerate, homocitrulline, N2,N2-dimethylguanosine, 1-methyladenosine and urobilin were associated with an increased risk, while hippurate, lysine, threonine and tryptophan were associated with a decreased risk. Ten out of 11 metabolites remained significantly associated after adjustments for cardiometabolic risk factors. The associations between metabolite levels and incident CVD were not as strong as for all-cause mortality, although 11 metabolites were nominally significant (p < 0.05). Further examination of the mortality-related metabolites may shed more light on the pathophysiology linking diabetes to premature mortality

Servervirtualisering idag : En undersökning om servervirtualisering hos offentliga verksamheter i Sverige

I dagens läge saknas en sammanställning av hur servervirtualisering är implementerat och hur det fungerar hos olika verksamheter i Sverige. Detta arbete har därför, genom en enkätundersökning, besvarat frågeställningen: "Hur ser servervirtualiseringen ut hos kommuner och landsting i Sverige?" Resultaten visade bl.a. att servervirtualisering är väl implementerat av kommuner och landsting i Sverige. Resultaten var dessutom väldigt lika mellan dessa organisationer. Det genomförda arbetet ger olika typer av verksamheter stöd vid planering och implementering av servervirtualisering.At present, there’s no summary of how server virtualization is implemented and how it works in different companies in Sweden. This work will therefore, through a survey, try to answer the question: "How is server virtualization implemented by municipality and county councils in Sweden?" Our results show that server virtualization is well implemented by municipality and county councils in Sweden. The results are also very similar between these organizations. Finalized work provides different types of companies support in planning and implementation of server virtualization

Processorbelastning med MPLS och IP-routing

Denna uppsats har haft examensarbetet “MPLS kontra traditionell IP-routing - enjämförelse av resursåtgång” av Sebastian Viking och Anton Öhlin som stöd. Derasarbete jämförde processoranvändning vid routing med, respektive utan, MPLS.Resultatet påvisade att MPLS gav högre processorbelastning gentemot traditionell IProuting,tvärtemot vad teorin för MPLS säger. På grund av uppenbara motsägelsermellan teori och praktik ämnade detta arbete skapa en hypotes som undersöks deduktivtmed målet att bekräfta dess utsaga: På grund av MPLS, respektive IP:s implementation iunderliggande hårdvaruarkitektur, kommer ingen märkbar skillnad iprocessorbelastning att uppvisas vid tester där en routers uppgift är att förmedla paket.Vi har därför återskapat deras tester för att verifiera äktheten i deras resultat. Resultetfrån våra egna tester visade ingen uppenbar olikhet mellan routingteknikerna IP medCEF, respektive MPLS. Presenterat resultat visar därmed på att hypotesen, som stöds avteknikernas teori, bevisats i praktiken från denna undersökning.This paper was based on the thesis "MPLS kontra traditionell IP routing - enjämnförelse av resursåtgång" by Sebastian Viking and Anton Öhlin. Their workcompared the CPU usage when performing routing with, and without, MPLS. Theresults demonstrates that MPLS provides higher processor load over traditional IProuting, contrary to the theory of MPLS. Due to the apparent contradictions betweentheory and practice has this work intended to create a hypothesis examined deductivelywith the aim to confirm its statement: Because of MPLS, and IP's, implementation ofthe underlying hardware architecture should no noticeable difference in processor usagebe presentated at tests where a router's job is to convey the package. Therefore, we recreatedtheir tests to confirm the authenticity of their results. The results from the testsin this paper showed no significant difference between IP routing technologies withCEF, and MPLS. Presented results thus confirm the hypothesis supported by thetheories behind the techniques used

Altered Acylcarnitine Metabolism Is Associated With an Increased Risk of Atrial Fibrillation

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the pathogenesis is not completely understood. The application of metabolomics could help in discovering new metabolic pathways involved in the development of the disease. Methods and Results We measured 112 baseline fasting metabolites of 3770 participants in the Malmö Diet and Cancer Study; these participants were free of prevalent AF. Incident cases of AF were ascertained through previously validated registers. The associations between baseline levels of metabolites and incident AF were investigated using Cox proportional hazard models. During 23.1 years of follow-up, 650 cases of AF were identified (incidence rate: 8.6 per 1000 person-years). In Cox regression models adjusted for AF risk factors, 7 medium- and long-chain acylcarnitines were associated with higher risk of incident AF (hazard ratio [HR] ranging from 1.09; 95% CI, 1.00-1.18 to 1.14, 95% CI, 1.05-1.24 per 1 SD increment of acylcarnitines). Furthermore, caffeine and acisoga were also associated with an increased risk (HR, 1.17; 95% CI, 1.06-1.28 and 1.08; 95% CI, 1.00-1.18, respectively), while beta carotene was associated with a lower risk (HR, 0.90; 95% CI, 0.82-0.99). Conclusions For the first time, we show associations between altered acylcarnitine metabolism and incident AF independent of traditional AF risk factors in a general population. These findings highlight metabolic alterations that precede AF diagnosis by many years and could provide insight into the pathogenesis of AF. Future studies are needed to replicate our finding in an external cohort as well as to test whether the relationship between acylcarnitines and AF is causal

Altered asparagine and glutamate homeostasis precede coronary artery disease and type 2 diabetes

Context: Type 2 diabetes mellitus (T2DM) is accompanied by an increased risk for coronary artery disease (CAD), but the overlapping metabolic disturbances preceding both diseases are insufficiently described. Objective:Wehypothesized that alterations in metabolism occur years before clinical manifestation of T2DM and CAD and that these alterations are reflected in the plasma metabolome. We thus aimed to identify plasma metabolites that predict future T2DM and CAD. Design: Through use of targeted liquid chromatography-mass spectrometry, 35 plasma metabolites (amino acid metabolites and acylcarnitines) were quantified in 1049 individuals without CAD and diabetes, drawn from a population sample of 5386 in the Malmo Preventive Project (mean age, 69.5 years; 31% women). The sample included 204 individuals who developed T2DM, 384 who developed CAD, and 496 who remained T2DM and CAD free during a mean follow-up of 6.1 years. Results: In total, 16 metabolites were significantly associated with risk for developing T2DM according to logistic regression models. Glutamate (OR, 1.96; P = 5.4e-12) was the most strongly associated metabolite, followed by increased levels of branched-chain amino acids. Incident CAD was predicted by three metabolites: glutamate (OR, 1.28; P = 6.6e-4), histidine (OR, 0.76; P = 5.1e-4), and asparagine (OR, 0.80; P = 2.2e-3). Glutamate (OR, 1.48; P = 1.6e-8) and asparagine (OR, 0.75; P = 1.8e-5) were both associated with a composite endpoint of developing T2DM or CAD. Conclusion: Several plasma metabolites were associated with incidence of T2DM and CAD; elevated glutamate and reduced asparagine levels were associated with both diseases. We thus discovered associations that might help shed additional light on why T2DM and CAD commonly co-occur