Biomedical subjects

Claus Holst

Publications and source records attributed to Claus Holst.

13 recordsLinked to original sources

PubMed2006

Genotype-by-nutrient interactions assessed in European obese women. A case-only study.

BACKGROUND: The development of obesity is influenced by both genetic and environmental risk factors. Whereas changes in the environment appear to be responsible for the increasing prevalence of obesity, genetic factors interacting with environmental factors would contribute to explain obesity onset and severity. AIM: To explore epidemiologic genotype-by-nutrient interactions in obesity. METHODS: A total of 42 polymorphisms of 26 candidate genes for obesity were genotyped in 549 adult obese women recruited from eight European centres in a case-only study. The nutritional variables assessed in this study were the dietary fibre intake (grams per day), the ratio of dietary polyunsaturated fat to saturated fat (P:S ratio) and the percentage of energy derived from fat in the diet as calculated from a weighed three-day food record (%E). Under the assumption of genotype-nutrient independence in the population, the odds ratio calculated in a sample of obese women would indicate the existence of genotype-by-nutrient interactions, measured as deviations from the multiplicative effects of the genetic and the nutrient factors separately. RESULTS: No new but confirmaty evidences for genotype-by-nutrient interactions in obesity were detected in this case-only study. The test of interaction between fibre intake and the -514 C > T polymorphism of the hepatic lipase gene (LIPC) yielded P-values of 0.01 across different statistical models. Likewise, the -11377G > C polymorphism of the adiponectin gene (ADIPOQ) and the -681 C > G polymorphism of the PPARG3 gene might interact with the percentage of energy derived from fat in the diet for the development of obesity (P-values in the range of 0.01-0.05 across different statistical models). The P-values were not adjusted for multiple testing, so these results should be considered with caution. CONCLUSIONS: Although the use of obese-only samples is theoretically a useful approach to detect interactions, few genotype-by-nutrient interactions have been suggested in obese European women after the analysis of candidate polymorphisms and the selected nutrient variables. The most remarkable multiplicative interaction found in this study refers to the combination of the hepatic lipase gene polymorphism -514 C > T and fibre intake.

Adiponectin↗

PubMed2006

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.

Journal Article↗

PubMed2006

Fat oxidation before and after a high fat load in the obese insulin-resistant state.

BACKGROUND: Obesity may be associated with a lowered use of fat as a fuel, which may contribute to the enlarged adipose tissue stores. AIM: The aim of the present study was to study fatty acid use in the fasting state and in response to a high fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113). METHODS: Subjects from eight European centers underwent a test meal challenge containing 95 en% fat [energy content 50% of estimated resting energy expenditure (EE)]. Fasting and postprandial fat oxidation and circulating metabolites and hormones were determined over a 3-h period. RESULTS: Postprandial fat oxidation (as percent of postprandial EE, adjusted for fat mass, age, gender, center, and energy content of the meal) decreased with increasing body mass index (BMI) category (P < 0.01), an effect present only in those obese subjects with a relatively low fasting fat oxidation (below median, interaction BMI category x fasting fat oxidation, P < 0.001). Fasting fat oxidation increased with increasing BMI category (P < 0.001), which was normalized after adjustment for fat-free mass and fat mass. Furthermore, insulin resistance was positively associated with postprandial fat oxidation (P < 0.05) and negatively associated with fasting fat oxidation (expressed as percent of EE), independent of body composition. CONCLUSIONS: The present data indicate an impaired capacity to regulate fat oxidation in the obese insulin-resistant state, which is hypothesized to play a role in the etiology of both obesity and insulin resistance.

Adult↗

PubMed2006

Birth cohort effect on the obesity epidemic in Denmark.

BACKGROUND: In Denmark, the obesity epidemic has developed in phases. To investigate if this has been a birth cohort phenomenon, we explored the secular trend in the prevalence of obesity among boys and young men. METHODS: We calculated body mass index (BMI; kg/m) over time for 163,835 Danish boys examined at ages 7-11 years and for 708,342 male draftees examined at age 19 years. Obesity was defined according to age-specific criteria for boys and as BMI >or=31 kg/m for men. We examined trends in the prevalence of obesity from 1930 through 1999, expressing time as the subjects' year of measurement and as year of birth. RESULTS: When expressed by year of measurement, 4 phases in the prevalence of obesity emerged for the boys and the young men, but they occurred at different times. However, when expressed by year of birth, the 2 stable periods and the 2 periods with sharp increases in obesity occurred in the same birth years. An increased prevalence of obesity was identified for birth cohorts from the early 1940s to the mid-1950s and from the late 1960s onward. CONCLUSIONS: The trends in the prevalence of obesity were similar in boys and young men only when expressed by year of birth, which suggests that early life may be a susceptible period for developing obesity. Specifically, the increased prevalence of obesity observed for birth cohorts from the early 1940s to the mid-1950s and from the late 1960s onward suggests that changes in the early life of these cohorts resulted in an increase in obesity at later ages.

Adolescent↗

PubMed2005

The N363S polymorphism of the glucocorticoid receptor and metabolic syndrome factors in men.

OBJECTIVE: To test the associations between the N363S polymorphism of the glucocorticoid receptor gene (NR3C1) and factors related to the metabolic syndrome in middle-aged men with and without juvenile-onset obesity. RESEARCH METHODS AND PROCEDURES: This study included two groups of middle-aged men, who were originally identified at 20 years of age at the draft boards. One group (n = 208; age, 48 +/- 6 years) was selected on the basis of juvenile-onset obesity (BMI > or = 31 kg/m(2)). The other group consisted of mainly nonobese men randomly sampled from the same population in parallel with the obese men (n = 299; age, 50 +/- 7 years). The subjects were genotyped for the N363S polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Body composition was measured by DXA. Glucose metabolism was evaluated by an oral glucose tolerance test, and the Matsudas index was calculated as a proxy for insulin sensitivity. Serum triglycerides and total and high-density lipoprotein-cholesterol were measured in the fasting state. RESULTS: Among the men with juvenile-onset obesity, carriers (n = 17) of the 363S allele had a lower whole body fat percentage, after accounting for differences in BMI and higher Matsudas index, compared with the noncarriers. The difference in Matsudas index lost statistical significance after the difference in body fat was accounted for. In the randomly sampled men, these variables did not relate to genotype. No relationship between carriers and noncarriers was found in body fat distribution or serum lipids. DISCUSSION: This study suggests that, in men developing obesity early in life, the 363S allele is associated with less adiposity at a given BMI, leading to higher insulin sensitivity.

Absorptiometry, Photon↗

PubMed2004

Major increase in prevalence of overweight and obesity between 1987 and 2001 among Danish adults.

OBJECTIVE: The aim of the study was to examine the secular trends in the prevalence of obesity (BMI >or= 30.0 kg/m(2)) and overweight (25.0 <or= BMI < 30.0 kg/m(2)) in Danish adults between 1987 and 2001. RESEARCH METHODS AND PROCEDURES: The study included self-reported weight and height of 10,094 men and 9897 women 16 to 98 years old, collected in a series of seven independent cross-sectional surveys. Prevalence and changes in prevalence of obesity and overweight stratified by sex and age groups were determined. RESULTS: The prevalence of obesity more than doubled between 1987 and 2001, in men from 5.6% to 11.8% [odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.9 to 2.8, p < 0.0001] and in women from 5.4% to 12.5% (OR = 2.6, 95% CI = 2.1 to 3.2, p < 0.0001), with the largest increase among the 16- to 29-year-old subjects (men, from 0.8% to 7.5%, OR = 10.2, 95% CI = 4.1 to 25.3, p < 0.0001; women, from 1.4% to 9.0% OR = 7.0, 95% CI = 3.5 to 14.1, p < 0.0001). Between 1987 and 2001, the prevalence of overweight increased from 34% to 40% in men and from 17% to 27% in women. DISCUSSION: The prevalence of overweight and obesity in Denmark has increased substantially between 1987 and 2001, particularly among young adults, a development that resembles that of other countries. There is clearly a need for early preventive efforts in childhood to limit the number of obesity-related complications in young adults.

Adolescent↗

PubMed2004

Food and drinking patterns as predictors of 6-year BMI-adjusted changes in waist circumference.

Few studies have investigated the prospective associations between diet or drinking patterns and abdominal obesity; we therefore investigated whether food and beverage groups or patterns predicted 6-year changes in waist circumference (WC) and whether these associations were independent of concurrent changes in BMI as a measure of general obesity. The subjects were 2300 middle-aged men and women with repeated measurements of dietary intake, BMI and WC from 1982 to 1993. Intakes from ten food groups and from coffee, tea, wine, beer and spirits were assessed; gender-specific food factors were identified by factor analyses. Multiple linear regression analyses were done before and after adjustment for concurrent changes in BMI. A high intake of potatoes seemed to prevent gain in WC for men, while a high intake of refined bread was associated with gain in WC for women. The association persisted for refined bread, but not for potatoes, after adjustment for concurrent BMI changes. Among women, but not men, high intakes of beer and spirits were associated with gain in WC in both models. A high intake of coffee for women and moderate to high intake of tea for men were associated with gain in WC, but the associations were weakened, especially for women, after adjustment for BMI changes. None of the food factors was associated with WC changes. Based on the present study, we conclude that very few food items and no food patterns seem to predict changes in WC, whereas high intakes of beer and spirits among women, and moderate to high tea intake among men, may promote gain in WC.

Adult↗

PubMed2004

Large heterogeneity of the obesity epidemic in Danish adults.

OBJECTIVE: To examine to what extent the obesity epidemic is a general phenomenon in adults by assessing the secular change, by birth cohort and age, in the prevalence of obesity and median body mass index (BMI) in Danish men and women measured between 1964 and 1994. DESIGN: Multiple cross-sectional population surveys. SETTING: The greater Copenhagen area of Denmark. SUBJECTS: The study included 17,065 men (30 336 observations) and 13,417 women (24,065 observations), aged 20-84 years. MAIN OUTCOME MEASURES: Trends in median BMI and prevalence of obesity estimated from measured height and weight in 10-year age groups. RESULTS: In general the prevalence of obesity was increasing, although in an irregular way: among men in two phases, during the 1970s and 1990s and among women only during the 1990s. Great heterogeneity was observed between birth cohorts and age groups. There was only little indication of an increasing trend in obesity prevalence for women, except for the 55-64-year-olds. In men, the prevalence of obesity was increasing in all age groups except in the youngest ones, and it was statistically significant only for men aged 35-74 years. There was no significant linear change in median BMI in any group, except for an increasing trend among men aged 50 years and above. CONCLUSION: Although the overall Danish trend for obesity prevalence, similar to trends world-wide, showed a marked increase, the trend was very heterogeneous and generally neither uniform nor significantly positive; the changes were irregular, different among men and women, and different in the different age and birth cohorts. The obesity problem in middle-aged and older men of certain birth cohorts poses a specific public health challenge. Future studies of determinants behind the heterogeneity in the development of the obesity epidemic may provide clues to its causes.

Adult↗

PubMed2003

Birth weight and risk of breast cancer in a cohort of 106,504 women.

The possible association between prenatal factors and breast cancer has been discussed for more than a decade. Birth weight has been used commonly as a proxy measure for intrauterine growth. Whereas some previous studies have found support for an association between birth weight and breast cancer, others have been inconclusive or found no association. We investigated the relationship between birth weight and risk of female breast cancer in a cohort of 106,504 Danish women. Birth weights were obtained from school health records on girls born between 1930-1975. Information on breast cancer came from linking the cohort with the Danish Cancer Registry and the Danish Breast Cancer Cooperative Groups Registry. A total of 2,334 cases of primary breast cancer were diagnosed in the cohort during 3,255,549 person-years of follow-up among women with birth weight between 500-6,000 g. Of these, 922 (40%) were diagnosed with primary breast cancer at the age of 50 years or older. A significant association between birth weight and breast cancer was found equivalent to an increase in risk of 9% per 1,000 g increase in birth weight (95% CI 2-17). The increase was observed for all age groups, representing both pre- and post-menopausal women, and irrespective of tumor characteristics. Adjustment for age at first birth and parity did not influence the results. Birth weight is positively associated with risk of breast cancer, indicating that prenatal factors are important in the etiology of breast cancer.

Adolescent↗

PubMed2003

Alcohol use as predictor for infertility in a representative population of Danish women.

BACKGROUND: Our aim was to examine the association between use of alcohol and subsequent incidence of primary infertility. METHODS: The study subjects were chosen from a population-based cohort of Danish women aged 20-29 years. Eligible women were nulliparous and not pregnant (n = 7760). Information on alcohol intake and potential confounders (age, education, marital status, diseases in the reproductive organs, and cigarette smoking) was assessed at enrollment. The incidence of fertility problems during follow-up was obtained by record linkage with the Danish Hospital Discharge Register and the Danish Infertility Cohort Register. Main outcome measures were hazard ratios of infertility according to alcohol intake at baseline estimated in a multivariate Cox proportional hazards model. RESULTS: During a mean follow-up of 4.9 years, 368 women had experienced infertility. Alcohol intake at baseline was unassociated with infertility among younger women, but was a significant predictor for infertility among women above age 30. In this age group, the adjusted hazard ratio for consuming seven or more drinks per week was 2.26 (95% confidence interval: 1.19-4.32) compared with women consuming less than one drink per week. CONCLUSIONS: These findings suggest that alcohol intake is a predictor for infertility problems among women in the later reproductive age group.

Adult↗

PubMed2003

Intelligence test score and educational level in relation to BMI changes and obesity.

OBJECTIVE: To investigate whether intelligence and education are related to subsequent BMI changes and development and persistence of obesity in men from young adulthood through middle-age. RESEARCH METHODS AND PROCEDURES: Subjects were selected among men (median age, 19 years; examined between 1956 and 1977) appearing at Danish draft boards: a group with juvenile-onset obesity, including all men with a BMI of >/=31.0 kg/m(2); and a nonobese group randomly selected as a 1% sample of the study population. The obese group and 50% of the nonobese group were invited to participate in follow-up studies between 1982 and 1984 and between 1992 and 1994. Among 907 men with juvenile-onset obesity and 883 nonobese men, age, examination region, intelligence test score, education, and BMI from baseline to first follow-up were analyzed by multiple linear and logistic regressions analyses. RESULTS: Education and intelligence, analyzed separately, were inversely related to BMI changes in both groups and to the development of obesity in the nonobese group. When adjusted for education, the association between intelligence score and BMI changes and development of obesity vanished, whereas the inverse relationship for education persisted only for BMI changes. Intelligence score was not associated with the persistence of obesity in the obese group, whereas inverse relationships were found for education. DISCUSSION: Intelligence test score was inversely related to risk of BMI changes and the risk of development of obesity, perhaps with education acting as a mediator or indicator of cognitive ability. Education, but not intelligence, was inversely associated with risk of remaining obese.

Adult↗

PubMed2003

Vital exhaustion as a risk factor for ischaemic heart disease and all-cause mortality in a community sample. A prospective study of 4084 men and 5479 women in the Copenhagen City Heart Study.

BACKGROUND: Vital exhaustion, a psychological measure characterized by fatigue and depressive symptoms, has been suggested to be an independent risk factor for ischaemic heart disease (IHD) but the generality of the phenomenon remains in question. The aim of this study is to describe prevalence of these symptoms in a community sample and determine whether they prospectively predict increased risk of IHD and all-cause mortality in men and women. METHODS: The study base was 4084 men and 5479 women aged 20-98 free of IHD examined in 1991-1993 in the Copenhagen City Heart Study. Events were ascertained through record linkage until 1998 for IHD and September 2000 for all-cause mortality. There were 483 first hospital admissions and deaths caused by IHD and 1559 deaths from all causes during follow-up. RESULTS: The 17 items on the vital exhaustion questionnaire were frequently endorsed with prevalence ranging from 6 to 47 per cent, higher in women. All but 4 of the 17 items were significantly associated with IHD with significant relative risks (RR) ranging between 1.36 (95% CI: 1.08, 1.72) and 2.10 (95% CI: 1.63, 2.71). Associations with all-cause mortality were also observed, but were weaker. RR of both IHD and all-cause mortality increased with increasing item sum score and were similar in men and women. For IHD, RR reached a maximum of 2.57 (95% CI: 1.65, 4.00) for subjects endorsing >9 items. The similar RR for all-cause mortality was 2.50 (95% CI: 2.09, 2.99). Multivariate adjustment for biological, behavioural, and socioeconomic risk factors did not substantially affect the association for IHD but attenuated the association with all-cause mortality. CONCLUSIONS: Measures of fatigue and depression were common symptoms in this population sample and convey increased risk of IHD and of all-cause mortality. We propose this knowledge begin to be implemented in risk assessment in clinical practice.

Adult↗

PubMed2002

Smoking reduction, smoking cessation, and mortality: a 16-year follow-up of 19,732 men and women from The Copenhagen Centre for Prospective Population Studies.

The authors investigated the association between changes in smoking habits and mortality by pooling data from three large cohort studies conducted in Copenhagen, Denmark. The study included a total of 19,732 persons who had been examined between 1967 and 1988, with reexaminations at 5- to 10-year intervals and a mean follow-up of 15.5 years. Date of death and cause of death were obtained by record linkage with nationwide registers. By means of Cox proportional hazards models, heavy smokers (>or=15 cigarettes/day) who reduced their daily tobacco intake by at least 50% without quitting between the first two examinations and participants who quit smoking were compared with persons who continued to smoke heavily. After exclusion of deaths occurring in the first 2 years of follow-up, the authors found the following adjusted hazard ratios for subjects who reduced their smoking: for cardiovascular diseases, hazard ratio (HR) = 1.01 (95% confidence interval (CI): 0.76, 1.35); for respiratory diseases, HR = 1.20 (95% CI: 0.70, 2.07); for tobacco-related cancers, HR = 0.91 (95% CI: 0.63, 1.31); and for all-cause mortality, HR = 1.02 (95% CI: 0.89, 1.17). In subjects who stopped smoking, most estimates were significantly lower than the heavy smokers'. These results suggest that smoking reduction is not associated with a decrease in mortality from tobacco-related diseases. The data confirm that smoking cessation reduces mortality risk.

Cause of Death↗