| 11. |
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| 12. |
- Franks, Paul W.
(författare)
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Body Weight and Risk of Early Death
- 2013
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Ingår i: Obesity. - : Wiley-Blackwell. - 1930-7381 .- 1930-739X. ; 21:9, s. 1743-1743
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
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| 14. |
- Franks, Paul W., et al.
(författare)
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Gene-diet interaction analysis, fine mapping and genomic annotation of the FADS1-2-3 gene cluster reveals regulatory potential in diabetes
- 2017
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 60:1, s. S163-S163
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: Polymorphisms at the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) have been associated with multiple metabolic and anthropometric traits in Greenlandic Inuit. We systematically assessed whether loci in the FADS region modify the association between dietary fat intake and cardiometabolic traits and functionally annotated top variants to estimate causal loci.Materials and methods: Data analyses consisted of: 1) interaction analyses between the six candidate genetic variants; 2) gene-centric joint analyses to detect interaction signals in the FADS region; 3) haplotype-centric joint tests across 30 haplotype blocks in the FADS1- 3 region to refine interaction signals: 4) functional annotation of top loci. These analyses were undertaken in Swedish adults from the GLACIER Study (N=5,160); data on gene variation (Metabochip array) and height, body weight, fasting and 2hr-glucose, triglycerides, and HDL-, LDL- and total cholesterol were available. Dietary intakes of n3, n-6 and total polyunsaturated fatty acids (PUFA) were calculated from food-frequency questionnaires. Results were adjusted for multiple testing.Results: SNP-level multiplicative interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pinteraction=0.007) and between rs174602 and n-3 PUFA intake on total cholesterol (Pinteraction=0.015). Gene-centric analyses demonstrated evidence for joint main and interaction effects for FADS on body weight (Pn-3.joint = 0.018, Pn-6.joint = 0.021, PPUFA.joint = 0.024) and on BMI (Pn-3.joint = 0.031, Pn-6.joint = 0.029, PPUFA.joint = 0.033) irrespective of types of fatty acid intake. An interaction was detected for FADS1-3 and n-3 PUFA on triglycerides (Pint=0.005). The haplotype analyses revealed three blocks (Pint ≤0.011) that drive the interaction between FADS1-3 and n-3 PUFA on triglycerides. Genomic annotation showed that the rs5792235 variant demonstrated the highest functionality score (Figure).Conclusion: The association between FADS1-3 variants and triglycerides may be modified by PUFA intake. The intronic rs5792235 variant is a potential causal variant in the region. It is likely that the region harbours multiple causal loci.
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| 15. |
- 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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| 16. |
- Franks, Paul W., et al.
(författare)
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Interaction Between Physical Activity and Genetic Factors in Complex Metabolic Disease
- 2008
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Ingår i: Energy Metabolism and Obesity. - Totowa : Humana Press. - 9781588296719 - 9781603271394 ; , s. 155-173
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Obesity and diabetes have become increasingly prevalent during the past century. Concomitant with this rise, the consumption of trans-fatty acids and processed carbohydrates is likely to have increased and physical activity levels declined. However, the rates at which obesity and diabetes have increased differ across people of varying ethnicities living in the same environment, suggesting the presence of interaction between ethnic-specific factors, such as genes, and changing environments and lifestyles. Quantifying these interactions is difficult because the interaction effect is often small, and precise measurement of lifestyle factors, such as diet and habitual physical activity, is difficult. Conventional interaction studies aim to test whether the magnitude of the association between the lifestyle exposures and the disease outcome is different in those who carry the variant allele at a given locus by comparison with those who do not. Because exercising skeletal muscle is a major site for glucose and lipid metabolism, variants in the genes that are located within muscle and that are up-regulated in response to physical activity present interesting candidates for testing in studies of gene x physical activity interaction in diabetes. However, numerous methodological limitations seriously hinder attempts to test such hypotheses. This chapter describes (1) a brief review of studies that provide evidence of gene x physical activity interaction in diabetes (and related traits), (2) functional evidence for interaction between genetic factors and physical activity in metabolic dysregulation, and (3) some common methodological issues that face the study of gene x environment interaction in human populations.
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| 17. |
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| 18. |
- 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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| 19. |
- 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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