Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Infra-slow fluctuations in simultaneous EEG-fMRI

Abstract Brain activity fluctuations occur in multiple spatial and temporal scales. Functional magnetic resonance imaging (fMRI) has shown that infra slow fluctuations (ISF) of blood oxygen level-dependent signal (BOLD) are organized into well-defined areas called resting state networks (RSN). ISFs have also been detected in full-band EEG (fbEEG) data and in recent years, many have combined these two modalities to enable more accurate measurements of brain fluctuations. In simultaneous EEG-fMRI measurements the ISFs of BOLD signal have been found to be correlated with amplitude envelopes of faster electrophysiological data, suggesting the same underlying neuronal dynamics. Also direct correlations have been found in task related studies but not previously in resting state studies. Understanding the relation between EEG and BOLD signal in resting state might prove beneficial in the research of baseline activity fluctuations of the brain. Functional connectivity (FC) of the RSNs has been found to vary in different tasks and in some diseases, but also in resting state in healthy people. Despite numerous studies, no clear cause for these variations has yet been found. To research these open questions we performed simultaneous fbEEG-fMRI studies. The measurements from both modalities were analyzed with independent component analysis to improve the comparability of these results. Correlation analysis revealed that the EEG ISFs correlate with BOLD signal both temporally and spatially. These correlations showed spatiotemporal variability that was related to the strength of RSN functional connectivity. These results indicate that the ISFs of EEG and BOLD reflect a common source of fluctuations. The understanding of the correlations between ISFs in EEG and fMRI BOLD signals gives basic information of brain dynamics and of the variables that affect it. A better understanding of the background of brain activity helps in the development of more effective treatments for various neurological diseases as the knowledge of the mechanisms behind them grows. The ability to measure RSN activity with EEG more accurately can help in the development of new methods for early diagnosis of diseases.Tiivistelmä Aivojen toiminta vaihtelee monissa avaruudellisissa ja ajallisissa mittakaavoissa. Toiminnallisissa magneettikuvauksissa (TMK) on havaittu, että veren happipitoisuudesta riippuvan (engl. BOLD) signaalin erittäin hitaat vaihtelut ovat järjestäytyneet hyvin määriteltyihin alueisiin, joita kutsutaan lepotilahermoverkostoiksi. Erittäin hitaita vaihteluita on havaittu myös täysikaistaisesta aivosähkökäyrästä (fbEEG). Viime vuosina nämä kaksi menetelmää on usein yhdistetty tarkemman mittaustuloksen aikaansaamiseksi. Samanaikaisissa EEG-TMK-mittauksissa BOLD signaalin erittäin hitaiden vaihteluiden on huomattu korreloivan nopeampien elektrofysiologisten värähtelyjen amplitudien verhokäyrien kanssa, mikä viittaa samaan perustana olevaan neuraaliseen dynamiikkaan. Myös suoria korrelaatioita on löydetty tehtäviin liittyvissä tutkimuksissa, mutta ei aiemmin lepotilatutkimuksissa. Lepotilan EEG:n ja BOLD-signaalin suhteen ymmärrys voi osoittautua hyödylliseksi aivojen perustilan aktiivisuuden vaihteluiden tutkimisessa. Hermoverkostojen toiminnallisen liittyvyyden on todettu huojuvan tietyissä tehtävissä ja joissain sairauksissa, mutta myös lepotilassa terveillä henkilöillä. Runsaasta tutkimuksesta huolimatta ei liittyvyyden huojunnalle ole vielä löytynyt selkeää aiheuttajaa. Näiden avoimien kysymysten tutkimiseksi suoritimme yhdenaikaisia fbEEG-TMK-mittauksia. Kummankin modaliteetin mittaustuloksia analysoitiin itsenäisten komponenttien analyysillä tulosten vertailtavuuden parantamiseksi. Korrelaatioanalyysit osoittivat, että EEG:n erittäin hitaat vaihtelut korreloivat ajallisesti ja avaruudellisesti TMK:n BOLD-signaalin kanssa. Näissä korrelaatioissa esiintyi sekä paikkaan että aikaan liittyvää huojuntaa, joka oli yhteydessä lepotilahermoverkostojen toiminnallisen liittyvyyden vahvuuteen. Nämä tulokset viittaavat siihen, että samat tekijät tuottavat EEG:n ja TMK:n BOLD-signaalien hitaat vaihtelut. EEG:n ja TMK:n signaalien erittäin hitaiden vaihteluiden välisen korrelaation ymmärtäminen antaa perustason tietoa aivojen toiminnan dynamiikasta sekä siihen vaikuttavista tekijöistä. Parempi ymmärrys aivotoiminnan taustoista auttaa kehittämään tehokkaampia hoitoja neurologisiin sairauksiin, kun tieto mekanismeista niiden takana tarkentuu. Mahdollisuus mitata lepotilahermoverkostojen toimintaa EEG:llä aiempaa tarkemmin voi auttaa kehittämään uusia menetelmiä sairauksien varhaiseen diagnostiikkaan

Combined spatiotemporal ICA (stICA) for continuous and dynamic lag structure analysis of MREG data

Abstract This study investigated lag structure in the resting-state fMRI by applying a novel independent component (ICA) method to magnetic resonance encephalography (MREG) data. Briefly, the spatial ICA (sICA) was used for defining the frontal and back nodes of the default mode network (DMN), and the temporal ICA (tICA), which is enabled by the high temporal resolution of MREG (TR=100ms), was used to separate both neuronal and physiological components of these two spatial map regions. Subsequently, lag structure was investigated between the frontal (DMNvmpf) and posterior (DMNpcc) DMN nodes using both conventional method with all-time points and a sliding-window approach. A rigorous noise exclusion criterion was applied for tICs to remove physiological pulsations, motion and system artefacts. All the de-noised tICs were used to calculate the null-distributions both for expected lag variability over time and over subjects. Lag analysis was done for the three highest correlating denoised tICA pairs. Mean time lag of 0.6 s (± 0.5 std) and mean absolute correlation of 0.69 (± 0.08) between the highest correlating tICA pairs of DMN nodes was observed throughout the whole analyzed period. In dynamic 2 min window analysis, there was large variability over subjects as ranging between 1–10 sec. Directionality varied between these highly correlating sources an average 28.8% of the possible number of direction changes. The null models show highly consistent correlation and lag structure between DMN nodes both in continuous and dynamic analysis. The mean time lag of a null-model over time between all denoised DMN nodes was 0.0 s and, thus the probability of having either DMNpcc or DMNvmpf as a preceding component is near equal. All the lag values of highest correlating tICA pairs over subjects lie within the standard deviation range of a null-model in whole time window analysis, supporting the earlier findings that there is a consistent temporal lag structure across groups of individuals. However, in dynamic analysis, there are lag values exceeding the threshold of significance of a null-model meaning that there might be biologically meaningful variation in this measure. Taken together the variability in lag and the presence of high activity peaks during strong connectivity indicate that individual avalanches may play an important role in defining dynamic independence in resting state connectivity within networks

Measuring physical activity in free-living conditions:comparison of three accelerometry-based methods

Abstract We examined the agreement in time spent on different physical activity (PA) levels using (1) mean amplitude deviation (MAD) of raw acceleration from the hip, (2) wrist-worn Polar Active, and (3) hip-worn Actigraph counts using Freedson’s cut-points among adults under free-living conditions. PA was measured in 41 volunteers (mean age 47.6 years) for 14 days. Two MET-based threshold sets were used for MAD and Polar Active for sedentary time (ST) and time spent in light (LPA), moderate (MPA), and vigorous (VPA) PA. Actigraph counts were divided into PA classes, ≤100 counts/min for ST and Freedson’s cut-points for LPA, MPA, and VPA. Analysis criteria were simultaneous use of devices for at least 4 days of >500 min/d. The between-method differences were analyzed using a repeated measures analysis of variance test. Bland-Altman plots and ROC graphs were also employed. Valid data were available from 27 participants. Polar Active produced the highest amount of VPA with both thresholds (≥5 and ≥6 MET; mean difference 17.9–30.9 min/d, P <0.001). With the threshold 3–6 MET for MPA, Polar Active indicated 19.2 min/d more than MAD (95% CI 5.8–32.6) and 51.0 min/d more than Actigraph (95% CI 36.7–65.2). The results did not differ with 3.5–5 MET for MPA [F(1.44, 37.43) = 1.92, P = 0.170]. MAD and Actigraph were closest to each other for ST with the threshold <1.5 MET (mean difference 22.2 min/d, 95% CI 7.1–37.3). With the threshold <2 MET, Polar Active and Actigraph provided similar results (mean difference 7.0 min/d, 95% CI −17.8–31.7). Moderate to high agreement (area under the ROC curve 0.806–0.963) was found between the methods for the fulfillment of the recommendation for daily moderate-to-vigorous PA of 60 min. In free-living conditions the agreement between MAD, Polar Active, and Actigraph for measuring time spent on different activity levels in adults was dependent on the activity thresholds used and PA intensity. ROC analyses showed moderate to high agreement for the fulfillment of the recommendation for daily MVPA. Without additional statistical adjustment, these methods cannot be used interchangeably when measuring daily PA, but any of the methods can be used to identify persons with insufficient daily amount of MVPA

Fitness, fatness, physical activity, and autonomic function in midlife

Abstract Purpose: Although low cardiorespiratory fitness (CRF), physical inactivity, and obesity are associated with impaired autonomic function, they are also extensively interrelated. The present study aimed to assess the extent to which they contribute to autonomic function independently of each other. Methods: At the age of 46 yr, 1383 men and 1761 women without cardiorespiratory diseases and diabetes underwent assessments of vagally mediated heart rate (HR) variability (root mean square of successive differences in R-R interval (rMMSD)), peak HR during a submaximal step test (CRF), and 60-s HR recovery (HRR). Moderate-to-vigorous physical activity (MVPA; ≥3.5 METs, 2 wk) was measured by wrist-worn accelerometer and body fat percentage (Fat%) by bioimpedance Results: In men, CRF and Fat% were significantly associated with higher rMSSD (standardized β = 0.31 and -0.16) and HRR (β = 0.19 and -0.18), whereas higher MVPA was linked with higher HRR (β = 0.13) when including CRF, MVPA, and Fat% in the initial regression. After adjustments for other lifestyle and cardiometabolic factors, CRF remained significantly associated with rMMSD (β = 0.24) and HRR (β = 0.14), as did MVPA with HRR (β = 0.11). In women, CRF was associated with rMSSD (β = 0.23) and HRR (β = 0.15), and MVPA (β = 0.17) and Fat% (β = -0.07) with HRR, when CRF, MVPA, and Fat% were adjusted for each other. After further adjustments, CRF remained a significant determinant of rMSSD (β = 0.20) and HRR (β = 0.13), as did MVPA with HRR (β = 0.15). The final models explained 23% and 21% of variation in rMSSD and HRR in men, and 10% and 12% in women, respectively. Conclusions: CRF was a more important determinant of cardiac autonomic function than MVPA and body fat. Furthermore, MVPA but not body fat was independently associated with cardiac autonomic function in both men and women

Dose-response relation of self-reported and accelerometer-measured physical activity to perceived health in middle age:the Northern Finland Birth Cohort 1966 study

Abstract Background: Regular physical activity (PA) promotes health and decreases mortality. The positive relationship between PA and perceived health (PH) is well known. However, previous research in the field has often used self-reported PA measures. The aim of this population-based NFBC1966 birth cohort study was to assess the relationship between both self-reported and objectively measured PA and PH in midlife. Methods: A sample group of 6384 participants (2878 men, 3506 women, response rate 62%) aged 46 completed a questionnaire on PH and health behaviors, including items on weekly leisure time physical activity (LTPA) and daily sitting time (ST). PH was dichotomized as good (very good or good) and other (fair, poor, or very poor). PA was measured with a wrist-worn Polar Active (Polar Electro, Finland) accelerometer for 14 days (n = 5481, 98%) and expressed as daily average time spent in moderate to vigorous intensity PA (MVPA). Odds ratios (OR) and 95% confidence intervals for good PH were calculated using binary logistic regression and adjusted for relevant demographic, socioeconomic, and health characteristics, and ST. Results: The level of PA was positively associated with PH after adjustments with covariates and ST. There was a dose-response relationship across the PA quartiles according to the adjusted multivariable models. Self-reported LTPA was more strongly associated with good PH (OR from 1.72 to 4.33 compared to lowest PA quartile) than objectively measured PA (OR from 1.37 to 1.66 compared to lowest PA quartile). Conclusions: In this large population-based birth cohort study, we for the first time show a positive dose-response relationship of both self-reported and objectively measured PA to PH, the relationship being stronger for self-reported LTPA. Despite the cross-sectional design of this study, the results from this large sample suggest that both self-reported and objectively measured physical activity are strongly associated with PH, which is a predictor of morbidity and mortality, and regular PA should be encouraged in midlife

Drinking water quality and formation of biofilms in an office building during its first year of operation, a full scale study

Humans spend most of their time indoors. The built environment with its systems (e.g. water system) should be designed and operated in a way that it is microbiologically safe in all stages of operation. Copper is a widely used material within indoor environments and may aid to maintain low bacterial counts in drinking water and touch surface environments depending on the surroun- ding circumstances e.g. water/air interface, biofilm formation or soiling. Basic knowledge of the composition of drinking water bacteria has been earlier limited only to a small cultivable fraction of bacteria. Next-generation sequencing (NGS) technologies help to reveal entire microbial communities and to date these approaches are also extended to cover studies on drinking water systems. This thesis focuses on the unique microbiological niches of drinking water and touch surface indoor environments utilizing up-to-date technologies and real-life environments with emphasis on environmental factors that shape such microbiota. The role of copper in both water and air interfaces is of special interest. NGS approach was utilised to evaluate the effect of copper pipelines on biofilm or water micro-biota under real-life circumstances (full-scale water system) and under controlled conditions (pilot-scale system). Copper was compared to another commonly used pipeline material, cross-linked polyethylene (PEX). Environmental conditions i.e. the effect of cold and hot water systems with different flow regimes and temperatures (full-scale), and disinfection and magnetic water treat- ment (pilot-scale) were studied by NGS or traditional analysis methods in which stagnated water represented the worst-case scenario for water quality. The microbiological effects of copper in touch surface environment were studied at different real-life facilities under varying environmental circumstances (e.g. usage profiles, cleaning). This thesis successfully revealed the active and dormant bacterial inhabitants of the drinking water system utilizing 16S ribosomal RNA gene amplicon sequencing and ribosomal RNA as a template. For public health relevance, Legionella spp. were suggested as inactive using the RNA approach. Operational conditions (stagnation, temperature) and increased disinfectant concen- tration were revealed as important environmental factors that shape drinking water bacterial populations. Moreover, the study emphasizes the importance of use of only fresh water for drinking water usage, in accordance with the current recommended practises. Based on this study, copper pipelines showed similar characteristics to PEX pipelines without antibacterial properties in drin- king water systems. At the air interface however, copper showed antibacterial properties with varying real-life circumstances. Thus, its usage as an antibacterial touch surface material can be recommended especially for small frequently touched items that were shown to possess the highest microbial counts.Ihmiset viettävät valtaosan ajastaan sisätiloissa. Koko rakennettu ympäristö järjestelmineen (esim. vesijärjestelmä) tulisi suunnitella ja huoltaa siten, että ympäristö olisi mikrobiologisesti turvallinen kaikissa käytön vaiheissa. Kupari on laajalti käytetty materiaali sisäympäristöissä ja voi edistää alhaisten bakteerimäärien ylläpitoa vesijärjestelmissä ja kosketuspinnoilla riippuen ympäröivistä olosuhteista kuten vesi- tai ilmafaasista, likaantumisesta tai biofilmin muodostumisesta. Aikaisem- mat tiedot juomavesien bakteeriyhteisöistä ovat pääosin rajoittuneet viljelymenetelmillä saatuihin tuloksiin. Syväsekvensointi (engl. next-generation sequencing, NGS) menetelmien avulla voidaan selvittää koko mikrobiyhteisö ja menetelmän käyttöä onkin viime aikoina laajennettu myös vesijärjestelmien tutkimukseen. Tämä tutkimus keskittyy rakennetun ympäristön juomavesijärjestelmien sekä kosketuspintojen mikrobiologisiin erityispiirteisiin. Tutkimuksessa hyödynnettiin todellisia elinolosuhteita ja uusia tutkimustekniikoita. Työn tavoitteena on selvittää ympäristötekijöiden – erityisesti kuparimateriaalin – vaikutuksia. NGS-menetelmää hyödynnettiin kuparisten putkimateriaalien vaikutuksia arvioitaessa sekä todellisissa elinolosuhteissa (täyden mittakaavan vesijärjestelmä) että kontrolloiduissa olosuhteissa (pilottimittakaavan vesijärjestelmä). Kupariputkia verrattiin toiseen yleisesti käytettyyn putki- materiaaliin, ristisilloitettuun polyeteeniin (engl. cross-linked polyethylene, PEX). Todellisissa olosuhteissa tutkittiin kylmä- ja lämminvesijärjestelmiä sekä käyttöolosuhteita, ja pilotti- mittakaavassa lisädesinfioinnin ja magneettisen vedenkäsittelyn vaikutuksia. Näissä tutkimuksissa käytettiin syväsekvensointi- tai perinteisiä analyysimenetelmiä, erityisesti seisoneet vesinäytteet edustivat pahinta mahdollista olosuhdetta. Kuparin soveltuvuutta antibakteeriseksi kosketus- pintojen materiaaliksi tutkittiin erityyppisissä rakennuksissa vaihtelevissa käytännön olosuhteissa kuten eri käyttäjäprofiileilla ja siivouskäytännöillä. Työssä pystyttiin selvittämään vesijärjestelmien aktiiviset ja lepotilassa olevat bakteerit käyttäen 16S ribosomaaliseen RNA geeniin perustuvaa sekvensointia ja ribosomaalista RNA:ta lähtöaineena. Kansanterveyden näkökulmasta Legionella-bakteerit eivät osoittaneet aktiivisuutta RNA menetel- mää hyödyntäen. Käyttöolosuhteet (seisotus, lämpötila) ja lisädesinfiointi olivat tärkeitä juoma- veden bakteeriyhteisöihin vaikuttavia tekijöitä. Tutkimus vahvistaa nykyistä suositusta käyttää ainoastaan juoksutettua vettä juomavetenä. Tutkimuksen mukaan kupariputket muistuttivat ominaisuuksiltaan PEX- putkia ilman antibakteerisia vaikutuksia. Sen sijaan sisäympäristön koske- tuspintojen materiaalina kuparilla oli antibakteerisia ominaisuuksia sisäympäristömme vaih- televissa olosuhteissa. Kuparin käyttöä kosketuspintojen antibakteerisena materiaalina voidaan suositella erityisesti pienille usein kosketuille, ja eniten kontaminoituneille, kosketuspinnoille

Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia

Abstract Activation of the hypoxia-inducible factor (HIF) pathway reprograms energy metabolism. Hemoglobin (Hb) is the main carrier of oxygen. Using its normal variation as a surrogate measure for hypoxia, we explored whether lower Hb levels could lead to healthier metabolic profiles in mice and humans (nn = 7175) and used Mendelian randomization (MR) to evaluate potential causality (n = 173,480). The results showed evidence for lower Hb levels being associated with lower body mass index, better glucose tolerance and other metabolic profiles, lower inflammatory load, and blood pressure. Expression of the key HIF target genes SLC2A4 and Slc2a1 in skeletal muscle and adipose tissue, respectively, associated with systolic blood pressure in MR analyses and body weight, liver weight, and adiposity in mice. Last, manipulation of murine Hb levels mediated changes to key metabolic parameters. In conclusion, low-end normal Hb levels may be favorable for metabolic health involving mild chronic activation of the HIF response