| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant : a 14-cohort meta-analysis
- 2011
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Ingår i: Diabetes. - Alexandria : American diabetes association. - 0012-1797 .- 1939-327X. ; 60:9, s. 2407-2416
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants.RESEARCH DESIGN AND METHODS We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes.RESULTS We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: -0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant.CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.
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| 2. |
- Kilpeläinen, Tuomas O, et al.
(författare)
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Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
- 2011
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Ingår i: PLoS medicine. - : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) =0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio =1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio =1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.
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| 3. |
- Almqvist, Catarina, et al.
(författare)
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LifeGene - A large prospective population-based study of global relevance
- 2011
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Ingår i: European Journal of Epidemiology. - Stockholm : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 26:1, s. 67-77
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Tidskriftsartikel (refereegranskat)abstract
- Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.
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| 4. |
- Franks, Paul
(författare)
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Gene × Environment Interactions in Type 2 Diabetes.
- 2011
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Ingår i: Current Diabetes Reports. - : Springer Science and Business Media LLC. - 1539-0829 .- 1534-4827.
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Tidskriftsartikel (refereegranskat)abstract
- People vary genetically in their susceptibility to the effects of environmental risk factors for many diseases. Genetic variation also underlies the extent to which people respond appropriately to clinical therapies. Defining the basis to the interactions between the genome and the environment may help elucidate the biologic basis to diseases such as type 2 diabetes, as well as help target preventive therapies and treatments. This review examines 1) some of the most current evidence on gene × environment interactions in relation to type 2 diabetes; 2) outlines how the availability of information on gene × environment interactions might help improve the prevention and treatment of type 2 diabetes; and 3) discusses existing and emerging strategies that might enhance our ability to detect and exploit gene × environment interactions in complex disease traits.
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| 5. |
- Franks, Paul, et al.
(författare)
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Gene-Lifestyle and Gene-Pharmacotherpy Interactions in Obesity and Its Cardiovascular Consequences.
- 2011
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Ingår i: Current Vascular Pharmacology. - : Bentham Science Publishers Ltd.. - 1570-1611 .- 1875-6212. ; 9:4, s. 401-456
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a highly prevalent complex trait that raises the risk of other chronic diseases such as type 2 diabetes, certain cancers, sleep apnea, and cardiovascular disease, and shortens lifespan. Clinical intervention studies focused on weight loss and epidemiological studies of obesity indicate that genetic variation may modify the relationship between lifestyle behaviors and weight loss or weight gain. Similar observations have also emerged from pharmacogenetic studies. The literature includes several reports from these studies, but few examples of interactions have been adequately replicated. In this review we introduce the topics of population genetics research and gene x environment interaction. We also provide a systematic review of the published literature on gene x lifestyle (physical activity and dietary factors) and gene x drug interactions in relation to obesity. Finally, we overview the scope and findings from these studies and discuss some of their strengths and limitations.
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| 6. |
- Franks, Paul W., et al.
(författare)
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Interaction Between Exercise and Genetics in Type 2 Diabetes Mellitus : An Epidemiological Perspective
- 2011
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Ingår i: Exercise Genomics. - TOTOWA : Humana Press. - 9781607613541 - 9781607613558 ; , s. 73-100
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes mellitus is a heterogeneous disease characterized by an inability to transport glucose from the blood into the cells. The disease has genetic and lifestyle determinants and probably results from the interaction of these risk factors. While this notion is widely accepted and endorsed, the available evidence is far from concrete. In this chapter the evidence that implicates physical inactivity and common genetic variation in type 2 diabetes risk will be described. Then, the fundamental concepts of gene × exercise interactions in type 2 diabetes will be defined by summarizing the evidence from epidemiological studies and clinical trials that have tested related hypotheses. The penultimate section of this chapter discusses the strengths and limitations of existing studies of interaction and outlines some of the common methodological hurdles inherent when testing hypotheses of gene × exercise interactions. The chapter concludes with a short section looking forward to where this field of research is heading and the possibilities for clinical translation.
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| 7. |
- Gradmark, Anna, 1981-, et al.
(författare)
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Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women
- 2011
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Ingår i: BMC Pregnancy and Childbirth. - London : Springer Science and Business Media LLC. - 1471-2393 .- 1471-2393. ; 44:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Overweight and obesity during pregnancy raise the risk of gestational diabetes and birth complications. Lifestyle factors like physical activity may decrease these risks through beneficial effects on glucose homeostasis. Here we examined physical activity patterns and their relationships with measures of glucose homeostasis in late pregnancy compared to non-pregnant women. Methods: Normal weight and overweight women without diabetes (N=108; aged 25-35 years) were studied; 35 were pregnant (in gestational weeks 28-32) and 73 were non-pregnant. Insulin sensitivity and beta-cell response were estimated from an oral glucose tolerance test. Physical activity was measured during 10-days of free-living using a combined heart rate sensor and accelerometer. Total (TEE), resting (REE), and physical activity (PAEE) energy expenditure were measured using doubly-labeled water and expired gas indirect calorimetry. Results: Total activity was associated with reduced first-phase insulin response in both pregnant (Regression r2=0.11; Spearman r=-0.47; p=0.007) and non-pregnant women (Regression r2=0.11; Spearman; r=-0.36; p=0.002). Relative to non-pregnant women, pregnant women were estimated to have secreted 67% more insulin and had 10% lower fasting glucose than non-pregnant women. Pregnant women spent 13% more time sedentary, 71% less time in moderate-to-vigorous intensity activity, had 44% lower objectively measured total activity,and 12% lower PAEE than non-pregnant women. Correlations did not differ significantly for any comparison between physical activity subcomponents and measures of insulin sensitivity or secretion. Conclusions: Our findings suggest that physical activity conveys similar benefits on glucose homeostasis in pregnant and non-pregnant women, despite differences in subcomponents of physical activity.
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| 8. |
- Gradmark, Anna, 1981-, et al.
(författare)
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Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women
- 2011
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aims Overweight and obesity during pregnancy raise the risk of gestational diabetes and birth complications. Lifestyle factors such as physical activity may decrease these risks through beneficial effects on systemic glucose homeostasis. Here we examined physical activity patterns and their relationships with measures of glucose homeostasis in late pregnancy compared to non-pregnant women. Methods Normal weight and overweight women without diabetes (N=108; aged 25-35 years) were studied; 35 were pregnant (in gestational weeks 28-32) and 73 were non-pregnant. An oral glucose tolerance test was conducted from which insulin sensitivity and β-cell response were estimated. Physical activity was measured during 10-days of free-living using a combined heart rate sensor and accelerometer. Total (TEE), resting (REE), and physical activity (PAEE) energy expenditure were measured using doubly-labeled water and expired gas indirect calorimetry. Results Total activity (counts/day) was associated with a reduced first-phase insulin response in both pregnant (r=-0.47; 95% CI: -0.70- to -0.15) and non-pregnant women (r=-0.36; 95% CI: -0.56- to -0.12). Pregnant women were estimated to have secreted more insulin (p=0.002) and had lower fasting glucose than non-pregnant women (p<0.0001). Measures of overall physical activity intensity were similar in both groups (p=0.547), but pregnant women spent more time sedentary (p<0.0001), less time in moderate-to-vigorous intensity activity (p<0.0001), had lower objectively measured total activity, and had lower physical activity energy expenditure (PAEE) than non-pregnant women (p=0.045). Conclusions Our findings suggest that physical activity conveys similar benefits on glucose homeostasis in pregnant and non-pregnant women, despite differences in subcomponents of physical activity.
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| 9. |
- Gradmark, Anna, 1981-
(författare)
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Validation and application of objective measures of obesity and physical activity : studies in pregnant and non-pregnant adults and in infants
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Excess adipose tissue and low physical activity are two major determinants for chronic diseases such as type 2 diabetes and cardiovascular disease. Understanding these relationships requires accurate and precise measures of body composition and physical activity, and most existing observational studies lack such measures. Paper I to III in this thesis addresses the validity of measures of physical activity and abdominal adipose mass. In paper IV and V, we explore the relationships between obesity and physical activity on metabolic health in non-pregnant and pregnant women and their offspring. Methods and Results Two hundred men and women representative of the Northern Sweden EPIC cohort were recruited for Paper I. A questionnaire on physical activity (PAQ) was validated against objectively measured physical activity energy expenditure (PAEE). A categorical physical activity index (Cambridge index) calculated from PAQ showed strongest correlation with PAEE (r=0.33 p<0.05). In Paper II, abdominal adiposity were assessed in 29 adult men and women using anthropometric measurements, dual energy x-ray absorptiometry (DXA) and ultrasound and were compared to computed tomography (CT). Waist circumference showed the highest correlation with CT-assessed visceral (r=0.85, p<0.0001) and subcutaneous adipose tissue (r=0.86, p<0.0001). Adipose thickness was best assessed with ultrasound. In Paper III, the validity of a wrist-worn triaxial accelerometer was assessed in 32 pregnant and 74 non-pregnant women using double-labeled water method (DLW) as the criterion measure. The output from the accelerometer explained 24% (p <0.001) of the variation in PAEE in non-pregnant and 11% (p<0.05) in the pregnant women. In Paper IV, 35 pregnant and 73 non-pregnant women underwent a 75g oral glucose tolerance test and habitual energy expenditure and physical activity was assessed objectively. Total physical activity was inversely associated with early insulin response in both pregnant (r=-0.47, p=0.007) and non-pregnant (r=-0.36, p=0.004) women. In, Paper V, 32 women and their offspring (n=33) were studied 4 months post-partum. Body composition was quantified using DXA in the women and air-displacement plethysmography in the infants. Mid-pregnancy weight gain was significantly associated with infant fat mass (r=0.41, p=0.022), whereas late-pregnancy weight gain associated to infant fat-free mass (r=0.37, p=0.04). Conclusion This work describes new methods as well as conventional anthropometric estimates and a questionnaire, that provide relatively strong estimates of body composition and physical activity which could be used in larger studies. Pregnant women were shown to have more sedentary behavior than non-pregnant but physical activity appeared to have equal effect on glucose homeostasis in both groups, which may help guide lifestyle interventions in pregnancy. The impact of weight gain during the different trimesters seems to differentially affect the offspring’s body composition in early infancy, which might give us clues to when different aspects of fetal development and growth occur and how modifiable lifestyle behaviors might be intervened upon to improve long-term health.
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| 10. |
- Grontved, Anders, et al.
(författare)
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Association between plasma leptin and blood pressure in two population-based samples of children and adolescents
- 2011
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Ingår i: Journal of Hypertension. - 1473-5598. ; 29:6, s. 1093-1100
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Tidskriftsartikel (refereegranskat)abstract
- Objectives In this study we examined the association between leptin and blood pressure in a population-based study of Danish and Norwegian children and adolescents. Because of the putative bidirectional relationship between leptin and adiposity we formally tested (i) the mediating effect of body mass index in the association between leptin and blood pressure, and (ii) the mediating effect of leptin in the association between body mass index and blood pressure. Methods To examine these aims we used a cross-sectional random sample of children and adolescents from Denmark and Norway (n=1993) who had measures of leptin, anthropometry, blood pressure and other personal and biological risk factors for raised blood pressure available. Results Both body mass index and leptin were positively associated with blood pressure (P<0.001). The association with leptin was stronger in pre- and early-pubertal children compared to late-and post-pubertal adolescents (P<0.01 for interaction). The association between leptin and blood pressure was almost completely mediated by body mass index, whereas the association between body mass index and blood pressure was modestly mediated by leptin. Conclusion Leptin was strongly associated with blood pressure, a relationship that to a large extent was mediated by body mass index. Conversely, the association between body mass index and blood pressure was only modestly mediated by leptin. This indicates that the influence of adiposity on blood pressure is also driven by other biological risk factors beyond leptin. Such factors could include insulin, glucose, and triglycerides although residual confounding also could account for the observed relationships. J Hypertens 29:1093-1100 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
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