The rising prevalences of type 2 diabetes and obesity constitute major threats to human health globally. Powerful social and economic factors influence the distribution of these diseases among and ...within populations. These factors act on a substrate of individual predisposition derived from the composite effects of inherited DNA variation and a range of environmental exposures experienced throughout the life course. Although "Western" lifestyle represents a convenient catch-all culprit for such exposures, effective treatment and prevention will be informed by characterization of the most critical, causal environmental factors. In this Review, we examine how burgeoning understanding of the genetic basis of type 2 diabetes and obesity can highlight nongenetic exposures that drive development of these conditions.
Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. ...Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics) of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment.
An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one ENMO, Euclidian norm of the high-pass filtered signals HFEN, and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g HFEN+) were derived for each experimental condition and compared against the reference acceleration (forward kinematics) of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22-65 yr), and wrist in 63 women (20-35 yr) in whom daily activity-related energy expenditure (PAEE) was available.
In the robot experiment, HFEN+ had lowest error during (vertical plane) rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively). ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN).
In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice of metric explains different degrees of variance in daily human physical activity.
Few studies have compared the validity of objective measures of physical activity energy expenditure (PAEE) in pregnant and non-pregnant women. PAEE is commonly estimated with accelerometers attached ...to the hip or waist, but little is known about the validity and participant acceptability of wrist attachment. The objectives of the current study were to assess the validity of a simple summary measure derived from a wrist-worn accelerometer (GENEA, Unilever Discover, UK) to estimate PAEE in pregnant and non-pregnant women, and to evaluate participant acceptability.
Non-pregnant (N = 73) and pregnant (N = 35) Swedish women (aged 20-35 yrs) wore the accelerometer on their wrist for 10 days during which total energy expenditure (TEE) was assessed using doubly-labelled water. PAEE was calculated as 0.9×TEE-REE. British participants (N = 99; aged 22-65 yrs) wore accelerometers on their non-dominant wrist and hip for seven days and were asked to score the acceptability of monitor placement (scored 1 least through 10 most acceptable).
There was no significant correlation between body weight and PAEE. In non-pregnant women, acceleration explained 24% of the variation in PAEE, which decreased to 19% in leave-one-out cross-validation. In pregnant women, acceleration explained 11% of the variation in PAEE, which was not significant in leave-one-out cross-validation. Median (IQR) acceptability of wrist and hip placement was 9(8-10) and 9(7-10), respectively; there was a within-individual difference of 0.47 (p<.001).
A simple summary measure derived from a wrist-worn tri-axial accelerometer adds significantly to the prediction of energy expenditure in non-pregnant women and is scored acceptable by participants.
Since 2005, disease-related human genetic diversity has been intensively characterized using genome-wide association studies (GWAS). Understanding how and by whom this work was performed may yield ...valuable insights into the generalizability of GWAS discoveries to global populations and how high-impact genetics research can be equitably sustained in the future.
We mined the NHGRI-EBI GWAS Catalog (2005-2022) for the most burdensome non-communicable causes of death worldwide. We then compared (i) the geographic, ethnic and socioeconomic characteristics of study populations; (ii) the geographic and socioeconomic characteristics of the regions within which researchers were located and (iii) the extent to which male and female investigators undertook and led the research.
The research institutions leading the work are often US-based (37%), while the origin of samples is more diverse, with the Nordic countries having contributed as much data to GWAS as the United States (~17% of data). The majority of first (60%), senior (75%) and all (66%) authors are male; although proportions vary by disease and leadership level, male co-authors are the ubiquitous majority. The vast majority (91%) of complex trait GWAS has been performed in European ancestry populations, with cohorts and scientists predominantly located in medium-to-high socioeconomically ranked countries; apart from East Asians (~5%), other ethnicities rarely feature in published GWAS. See: https://hugofitipaldi.shinyapps.io/gwas_results/ to browse all results.
Most GWAS cohorts are of European ancestry residing outside the United States, with a smaller yet meaningful proportion of East Asian ancestry. Papers describing GWAS research are predominantly authored by male scientists based in medium-to-high income countries.
Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted ...complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions.
We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates.
We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 × 10(-4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent with experiment-wide 33% false discovery rates.
We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples.
Gut transit time is a key modulator of host-microbiome interactions, yet this is often overlooked, partly because reliable methods are typically expensive or burdensome. The aim of this single-arm, ...single-blinded intervention study is to assess (1) the relationship between gut transit time and the human gut microbiome, and (2) the utility of the 'blue dye' method as an inexpensive and scalable technique to measure transit time.
We assessed interactions between the taxonomic and functional potential profiles of the gut microbiome (profiled via shotgun metagenomic sequencing), gut transit time (measured via the blue dye method), cardiometabolic health and diet in 863 healthy individuals from the PREDICT 1 study.
We found that gut microbiome taxonomic composition can accurately discriminate between gut transit time classes (0.82 area under the receiver operating characteristic curve) and longer gut transit time is linked with specific microbial species such as
,
spp and
spp (false discovery rate-adjusted p values <0.01). The blue dye measure of gut transit time had the strongest association with the gut microbiome over typical transit time proxies such as stool consistency and frequency.
Gut transit time, measured via the blue dye method, is a more informative marker of gut microbiome function than traditional measures of stool consistency and frequency. The blue dye method can be applied in large-scale epidemiological studies to advance diet-microbiome-health research. Clinical trial registry website https://clinicaltrials.gov/ct2/show/NCT03479866 and trial number NCT03479866.
Energy balance and obesity Romieu, Isabelle; Dossus, Laure; Barquera, Simón ...
CCC. Cancer causes & control/CCC, Cancer causes & control,
03/2017, Volume:
28, Issue:
3
Journal Article
Peer reviewed
Open access
Purpose
The aim of this paper is to review the evidence of the association between energy balance and obesity.
Methods
In December 2015, the International Agency for Research on Cancer (IARC), Lyon, ...France convened a Working Group of international experts to review the evidence regarding energy balance and obesity, with a focus on Low and Middle Income Countries (LMIC).
Results
The global epidemic of obesity and the double burden, in LMICs, of malnutrition (coexistence of undernutrition and overnutrition) are both related to poor quality diet and unbalanced energy intake. Dietary patterns consistent with a traditional Mediterranean diet and other measures of diet quality can contribute to long-term weight control. Limiting consumption of sugar-sweetened beverages has a particularly important role in weight control. Genetic factors alone cannot explain the global epidemic of obesity. However, genetic, epigenetic factors and the microbiota could influence individual responses to diet and physical activity.
Conclusion
Energy intake that exceeds energy expenditure is the main driver of weight gain. The quality of the diet may exert its effect on energy balance through complex hormonal and neurological pathways that influence satiety and possibly through other mechanisms. The food environment, marketing of unhealthy foods and urbanization, and reduction in sedentary behaviors and physical activity play important roles. Most of the evidence comes from High Income Countries and more research is needed in LMICs.
Context:
We have previously found that visceral fat is a stronger predictor for cardiovascular risk factors than body mass index (BMI).
Objective:
This study sought to investigate the prevalence of ...diabetes in elderly men and women in relation to objectively assessed visceral fat volume.
Design and Setting:
The cohort consisted of a population-based sample of 705 men and 688 women, all age 70 y at the time of examination.
Main Outcome Measures:
Associations between body fat estimates, plasma glucose level, and diabetes prevalence were investigated using multivariable-adjusted statistical models.
Results:
The prevalence of type 2 diabetes was 14.6% in men and 9.1% in women (P < .001). Mean BMI was slightly higher in men than in women (27.3 vs 26.6 kg/m2; P = .01), with a greater difference in mean visceral fat mass (1987 vs 1077 g; P < .001). After adjustment for physical activity and smoking, men had about/approximately twice the odds of having type 2 diabetes compared with women (odds ratio OR, 1.95; 95% confidence interval CI, 1.38–2.76). The inclusion of BMI in this model did not change the risk associated with male sex (OR, 1.93; 95% CI, 1.34–2.77). However, when visceral fat was included as a covariate, male sex was not associated with increased risk of type 2 diabetes (OR, 0.77; 95% CI, 0.51–1.18).
Conclusions:
The higher prevalence of type 2 diabetes in older men than in older women was associated with larger amount of visceral fat in men. In contrast, differences in BMI was not associated with this difference.
In 1393 individuals, all 70 years old, the prevalence of diabetes was a higher among men than women, and this difference was explained by a higher amount of visceral fat.
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