Liselotte Petersen

Longitudinal study of the long-term relation between physical activity and obesity in adults

BACKGROUND: Earlier observational studies of the relation between physical activity and obesity are inconsistent and ambiguous, showing a clear cross-sectional inverse relation, and a prospective association only when physical activity at the time of follow-up is included.OBJECTIVE: To examine the long-term effect of leisure time physical activity (LTPA) on subsequent development of obesity and the effect of body weight on later physical inactivity in a population-based longitudinal setting taking into account the effects of historical changes on future changes as well as pertinent confounders.DESIGN: The study included 3653 women and 2626 men aged 20–78 y selected at random within sex–age strata from the general population of Copenhagen. At two surveys, 5 y apart, LTPA, body mass index (BMI) (weight/height2, kg/m2), several possible confounders and modifying factors were assessed. Obesity (defined as BMI ≥30 kg/m2) and LTPA was assessed at the 3rd survey 10 y later. Odds ratios (with 95% confidence limits) for developing obesity between the last two surveys were estimated by logistic regression analysis, taking into account baseline and preceding changes in BMI and LTPA. A similar analysis of odds ratios for physical inactivity as outcome at the 3rd survey was conducted.RESULTS: Compared to physical inactivity, the odds ratios of development of obesity among women with medium and high level of activity were 0.81 (0.53, 1.25) and 1.16 (0.73, 1.84), respectively, and among men, the odds ratios were 1.28 (0.71, 2.33) and 1.65 (0.91, 2.99), respectively. Compared to median BMI, the odds ratio of later physical inactivity among women with high BMI was 1.91 (1.39, 2.61), and among men the odds ratio was 1.50 (1.01, 2.22). The associations were not confounded or modified by age, pre-existing diseases, smoking, alcohol intake, educational level, occupational physical activity or by familial predisposition to obesity.CONCLUSION: This study did not support that physical inactivity as reported in the freely living adult population in the long term is associated with the development of obesity, but the study indicates that obesity may lead to physical inactivity.

A comprehensive assessment of parental age and psychiatric disorders

IMPORTANCE There has been recent interest in the findings that the offspring of older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders. However, the offspring of younger parents are also at risk for some adverse mental health outcomes. OBJECTIVE To determine the association between maternal and paternal age and a comprehensive range of mental health disorders. DESIGN, SETTING, AND PARTICIPANTS A comprehensive, population-based record linkage study using the Danish Psychiatric Central Research Register from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons born in Denmark from January 1, 1955, through December 31, 2006, were followed up during the study period. EXPOSURES Maternal and paternal age at the time of offsprings birth. MAIN OUTCOMES AND MEASURES We examined a broad range of International Classification of Diseases-defined mental disorders, including substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related, and somatoform disorders; eating disorders; specific personality disorders; and a range of developmental and childhood disorders. The incidence rate ratios for each mental disorder outcome were estimated by log linear Poisson regression with adjustments for the calendar period, age, sex, and age of the other parent. RESULTS The cohort was observed for 42.7 million person-years, during which 218 441 members of the cohort had their first psychiatric contact for any psychiatric disorder. Based on the overall risk of psychiatric disorders, the offspring of younger and older parents were at increased risk compared with those of parents aged 25 to 29 years. When the offspring were examined for particular disorders, the nature of the relationship changed. For example, the offspring of older fathers were at an increased risk of schizophrenia and related disorders, mental retardation, and autism spectrum disorders. In contrast, the offspring of young mothers (and to a lesser extent young fathers) were at an increased risk for substance use disorders, hyperkinetic disorders, and mental retardation. CONCLUSIONS AND RELEVANCE The offspring of younger mothers and older fathers are at risk for different mental health disorders. These differences can provide clues to the complex risk architecture underpinning the association between parental age and the mental health of offspring.

Physical activity in leisure-time and risk of cancer: 14-year follow-up of 28 000 Danish men and women.

Aim: The preventive effect of physical activity on risk of cancer in general remains controversial. This study aimed at assessment of the associations between leisure- time physical activity and incidence of cancer in the general population of adult men and women. Methods: 13,216 women and 18,718 men aged 20—93 years selected from the general population participated in a health examination including a questionnaire with information on physical activity, smoking, alcohol intake, postmenopausal hormones, and socioeconomic status. Incident cases of cancers where recorded during a follow-up period of 14 years. The six most frequent cancer cases in both sexes were included in this analysis. Results: A highly significant inverse association was seen between vigorous physical activity in leisure time and cancer of the ovary, adjusted rate ratio being 0.33 (95% CI 0.16—0.67; p=0.001) for the most physical active women. In men there was a highly significant increase for non-melanoma skin cancer, with adjusted rate ratio of 1.72 (95% CI 1.23—2.40; p=0.001), for the most active men and vigorous activity was associated with a non-significant lower risk of colon cancer, the adjusted rate ratio being 0.72 (95% CI 0.47—1.11; p=0.06). Conclusion: Generally, there were no, or only weakly, inverse associations between physical activity in leisure time and incidence of cancer, except for cancer of the ovary.

Waist circumference in relation to history of amount and type of alcohol: results from the Copenhagen City Heart Study

OBJECTIVE: To examine the long-term association between the amount and type of alcohol consumed and subsequent high waist circumference.DESIGN: Prospective population study with baseline assessment of alcohol intake, body mass index, smoking habit, physical activity, education, income and deliveries, and after 10 y, examination of waist circumference.SUBJECTS: A sample of 2916 men and 3970 women aged 20–83 y from Copenhagen City Heart Study, Denmark.MEASUREMENTS: A large waist circumference defined as a waist circumference more than 102 cm in men and 88 cm in women.RESULTS: The odds ratios of having a high waist circumference after 10 y showed a linear increase in both men and women, and they were 1.65 (95% confidence interval (CI) 1.07–2.55) in men and 2.16 (0.86–5.14) in women who drank more than 28 beverages per week of total alcohol compared to those who drank one to six beverages per week. Men drinking more than 21 beers per week had odds ratio of having a large waist circumference after 10 y of 1.63 (0.99–2.67) and women drinking more than 14 beers per week had odds ratio of 2.53 (0.92–6.34), compared to men and women who drank no beer. Also for spirits, there was an increase in both men and women. No linear trend was found for wine in either men or women.CONCLUSIONS: Moderate-to-high consumption of alcohol and of beer and spirits was associated with later high waist circumference, whereas moderate-to-high wine consumption may have the opposite effect.

Paternal Age at Birth of First Child and Risk of Schizophrenia

OBJECTIVE Greater paternal age is associated with increased risk of schizophrenia, and it has been hypothesized that de novo mutations in paternal germ cells are responsible for this association. An alternative hypothesis is that selection into late fatherhood accompanies a predisposition to schizophrenia. However, direct evidence of either hypothesis is lacking. If de novo mutations are responsible, greater paternal age at conception should increase the risk of schizophrenia. Conversely, if selection into late fatherhood is responsible for the association, greater age at which the father had his first child should increase the risk of schizophrenia. The authors aimed to distinguish between these two measures of paternal age. METHOD A total of 2.2 million people born in Denmark between 1955 and 1992 were followed up until first diagnosis with schizophrenia. Incidence rate ratios were estimated in a Cox regression. RESULTS Among second- or later-born children, greater paternal age increased the risk of schizophrenia. However, when paternal age at the time of the fathers first child was accounted for, the risk of schizophrenia did not depend on paternal age at the birth of later children. In contrast, the risk of schizophrenia increased significantly with increasing paternal age at the time of the fathers first child. CONCLUSIONS Factors related to greater paternal age when the fathers first child was born, and not the fathers age at conception of later children, are responsible for the association between paternal age and the risk of schizophrenia. These findings do not support the de novo mutation hypothesis.

Does educational level influence the effects of smoking, alcohol, physical activity, and obesity on mortality? A prospective population study.

Objectives: This study aims at examining whether the relation between established risk factors and mortality differs with socioeconomic status as measured by level of education. Methods: A population-based sample of 14,399 women and 16,236 men aged 20 - 93 years from Copenhagen was stratified into three educational levels measured as basic schooling, and the effect of smoking habits, alcohol consumption, physical activity, and body mass index, respectively, on mortality was assessed. Results: Those with the lowest level of education were most frequently heavy smokers, heavy drinkers, physically inactive, and obese. During a mean follow up of 16 years 10,952 subjects died. Compared with subjects with the lowest educational level, women with the highest educational level had a relative risk of 0.80 (95% CI; 0.70 - 0.91), and men of 0.71 (0.65 - 0.78). Heavy smoking compared with never smoking implied a more than twofold increased risk at all three educational levels among both men and women. The relation between alcohol intake and mortality was J-shaped on all three educational levels. There were decreasing risk functions describing the relations between physical activity and mortality on all three strata. Further, subjects who were either very lean or obese had increased risks of death compared with those of normal weight at all educational levels in both genders. Conclusions: The difference in distribution of the main known risk factors may be part of the explanation for the differences in mortality risk. However, these risk factors seem to influence mortality equally at different educational levels. Therefore, social inequalities in mortality do not seem to be explained only by differences in effect of lifestyle risk factors, but are also related to the social rank or unexamined factors within.

Genetic Polymorphisms and Weight Loss in Obesity: A Randomised Trial of Hypo-Energetic High- versus Low-Fat Diets

Objectives: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. Design: Randomised, parallel, two-arm, open-label multi-centre trial. Setting: Eight clinical centres in seven European countries. Participants: 771 obese adult individuals. Interventions: 10-wk dietary intervention to hypo-energetic (−600 kcal/d) diets with a targeted fat energy of 20%–25% or 40%–45%, completed in 648 participants. Outcome Measures: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. Results: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from −0.6 to 0.8 kg, and homozygotes, from −0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to −1.6 kg in heterozygotes, and from 3.8 kg to −2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. Conclusions: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet.

Physical activity in relation to development and maintenance of obesity in men with and without juvenile onset obesity.

OBJECTIVE: To examine long-term effects of leisure time physical activity (ltpa) and occupational physical activity (opa) on later obesity, and to examine the effect of body weight on later physical inactivity in men with and without juvenile onset obesity.DESIGN: Population-based longitudinal study of obese and nonobese men, who were identified as draftees of median age of 19 y in 1943–77 and later examined at general health surveys in 1982–84, and in 1991–93.SETTING: Copenhagen and adjacent regions, Denmark.PARTICIPANTS: In all, 1143 juvenile obese men with a BMI ≥31 kg/m2 (corresponding to 35% overweight by an originally used national standard) at draft board examination, and, as a nonobese control group, 1278 men selected as a 0.5% random sample of the approximately 255 600 men examined at the draft board and thus representing the study population.MAIN OUTCOME MEASURES: Obesity, defined as BMI ≥30 kg/m2, and physical inactivity at the last survey.RESULTS: In the cross-sectional analyses, there were strong concurrent inverse associations between ltpa and prevalence of obesity in both groups, whereas there was no relation to opa. In logistic regression analyses of obesity at the last survey, including both ltpa and opa as well as age, BMI at draft board examination, BMI at first follow-up, length of education, smoking and drinking habits, there were no significant effects of ltpa and opa on the risk of development of obesity in the nonobese group or maintenance of obesity in the obese group. Similar analyses of physical inactivity at the last follow-up as outcome showed a significant direct effect of BMI at first follow-up, with a significant trend in the nonobese group, but not in the obese group and no effects on opa.CONCLUSION: There is no long-term influence of physical activity on development and maintenance of obesity in men, whereas greater body weight increases risk of later physical inactivity during leisure time.

Several obesity- and nutrient-related gene polymorphisms but not FTO and UCP variants modulate postabsorptive resting energy expenditure and fat-induced thermogenesis in obese individuals: the NUGENOB study.

Background:Part of the heterogeneity of the obesity phenotype may originate from genetic differences between obese individuals that may influence energy expenditure (EE).Objective:To examine if common single-nucleotide polymorphisms (SNPs) in genes related to obesity-associated phenotypes are associated with postabsorptive resting energy expenditure (REE) and postprandial REE in obese individuals.Design and methods:Postabsorptive REE and 3-h postprandial REE (liquid test meal containing 95% fat, energy content 50% of estimated REE) were measured in 743 obese individuals from eight clinical centres in seven European countries. The analysis assessed the association of genotypes of 44 SNPs in 28 obesity-related candidate genes with postabsorptive REE and postprandial REE taking into consideration the influence of body composition, habitual physical activity, insulin sensitivity, circulating thermogenic hormones and metabolites.Results:After adjustment for fat-free mass (FFM), age, sex and research centre, SNPs in CART, GAD2, PCSK1, PPARG3, HSD11B1 and LIPC were significantly associated with postabsorptive REE. SNPs in GAD2, HSD11B1 and LIPC remained significantly associated with postabsorptive REE after further adjustment for fat mass (FM). SNPs in CART, PPARG2 and IGF2 were significantly associated with postprandial REE after similar adjustments. These associations with postprandial REE remained significant after further adjustment for FM. FTO, UCP2 and UCP3 variants were not associated with postabsorptive or postprandial REE.Conclusions:Several gene polymorphisms associated with obesity-related phenotypes but not FTO and UCP variants may be responsible for some of the inter-individual variability in postabsorptive REE and fat-induced thermogenesis unaccounted for by FFM, FM, age and sex. The association between FTO and obesity that has been reported earlier may not be mediated directly through modulation of EE in obese individuals.

Obesity-related polymorphisms and their associations with the ability to regulate fat oxidation in obese Europeans: the NUGENOB study.

Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single‐nucleotide polymorphisms (SNPs) in 26 candidate genes for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, −178 A>C CD36 (rs2232169) (P = 0.02), −22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0.01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with −174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related to fat oxidation. At the same time, the results are not adjusted for multiple testing, thus none of the associations can be considered statistically significant. The results should therefore only be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandial fat oxidation.