Uncarboxylated matrix Gla-protein: A biomarker of vitamin K status and cardiovascular risk.

BACKGROUND: Dephosphorylated uncarboxylated matrix Gla-protein (dp-ucMGP) is a biomarker of functional vitamin K status. High plasma dp-ucMGP concentrations reflect a low vitamin K status and have been related to vascular calcification. Our aims were to assess plasma levels of dp-ucMGP and their association with cardiovascular risk in a general population. METHODS: Plasma dp-ucMGP measurements were performed using the IDS-iSYS InaKtif MGP assay in 491 consecutive participants in a Danish general population study (229 males and 262 females, aged 19-71 years). Multivariable linear and logistic regressions were used to assess the association between dp-ucMGP levels and cardiovascular risk factors. RESULTS: Mean ± standard deviation (SD) for dp-ucMGP was 465 ± 181 pmol/L, and upper 95th percentile was 690 pmol/L. In logistic regression analyses, an increase in dp-ucMGP category (<300, 300-399, 400-499, ≥500 pmol/L) was positively associated with obesity, odds ratio (OR) 2.27 (95% confidence interval (CI) 1.54-3.33), history of cardiovascular disease, OR 1.77 (CI 1.02-3.05), and above-median estimated pulse wave velocity (ePWV), OR 1.54 (CI 1.21-1.96), when adjusted for age, sex, and lifestyle factors. 1 SD increase in diastolic and systolic blood pressure (BP) corresponded to a 5.5% (CI 2.9-8.0%) and 4.7% (CI 2.1-7.4%) increase in dp-ucMGP, respectively, when adjusted for age and sex. CONCLUSION: Plasma dp-ucMGP levels were positively associated with obesity, BP, ePWV, and history of cardiovascular disease. These findings support that dp-ucMGP is a biomarker of cardiovascular risk, and that vitamin K status could play a role in vascular calcification. The strong association with obesity deserves further attention.

Discounts on fruit and vegetables combined with a space management intervention increased sales in supermarkets.

BACKGROUND/OBJECTIVES: To examine the effects of two interventions on consumer purchases of fruits and vegetables (F&V) on the Danish island of Bornholm: a 20% discount on F&V combined with improved shelf-space allocation, and improved shelf-space allocation alone. SUBJECTS/METHODS: A space management intervention to promote F&V sales was performed in two large discount supermarkets on Bornholm in Denmark for 3 months (September-November 2012). In addition, a 20% discount on F&V was introduced for 3 months in one of the supermarkets ('space + price'). The effect was evaluated using sales data from the two intervention supermarkets and three control supermarkets from the same supermarket chain but in Odsherred, Denmark (control area). Both the effect on sales of fresh F&V and potential unhealthy substitution effects were evaluated using multi-level regression analyses. RESULTS: During the price intervention period, the index number for sales of fresh vegetables increased by 22.2% (P=0.001) in the 'space + price' intervention supermarket compared with the control supermarkets. Furthermore, the index number for the sale of organic fresh fruit and vegetables increased by 12.1% (P=0.04) and the sale of the total amount of fruit and vegetables (fresh, frozen, dried and canned) increased by 15.3% (P=0.01) compared with the control supermarkets. In the 'space only' intervention supermarket no significant increase in the sale of fruit and vegetables was found. No unhealthy substitution effects were found. CONCLUSIONS: In conclusion, a 20% price reduction on F&V significantly increased sales of F&V. The effect was most pronounced on vegetables and no negative/unhealthy substitution effects were found.

The effect of GWAS identified BMI loci on changes in body weight among middle-aged Danes during a five-year period.

OBJECTIVE: Genome-wide association studies have identified genetic variants associating with BMI, however, it is un-clarified whether the same variants also influence body weight fluctuations. METHODS: Among 3,982 adult individuals that attended both a baseline and a five-year follow-up examination in the Danish Inter99 intervention study, a genetic risk score (GRS) was constructed based on 30 BMI variants to address whether it is associated with body weight changes. Moreover, it was examined whether the effect of lifestyle changes was modulated by the GRS. RESULTS: The GRS associated strongly with baseline body weight, with a per risk allele increase of 0.45 (0.33-0.58) kg (P = 2.7 × 10(-12) ), corresponding to a body weight difference of 3.41 (2.21-4.60) kg comparing the highest (≥ 30 risk alleles) and lowest (≤ 26 risk alleles) risk allele tertile. No association was observed with changes in body weight during the five years. Changes in lifestyle, including physical activity, diet and smoking habits associated strongly with body weight changes, however, no interactions with the GRS was observed. CONCLUSION: The GRS associated with body weight cross-sectionally, but not with changes over a five-year period. Body weight changes were influenced by lifestyle changes, however, independently of the GRS.

Dairy product intake in relation to glucose regulation indices and risk of type 2 diabetes.

BACKGROUND AND AIM: A high intake of dairy has been linked to lower risk of type 2 diabetes (T2D). The relationship between dairy intake and glucose metabolism is still not well understood. The aim of this study was to investigate the relation between the intake of total dairy and dairy subgroups and T2D and measures of glucose metabolism. METHODS AND RESULTS: A total of 5953 Danish men and women aged 30-60 years without baseline diabetes or cardiovascular diseases were included in this prospective analysis. The dairy intake at baseline was categorised into low-fat dairy, full-fat dairy, milk and milk products, cheese and fermented dairy. Fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), HbA1c, insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B) were considered at 5-year follow-up. In the maximally-adjusted model (demographics, lifestyle factors, dietary factors and waist), cheese intake was inversely associated with 2hPG (ß = -0.048, 95% CI -0.095; -0.001). Fermented dairy intake was inversely associated with FPG (ß = -0.028, 95% CI -0.048; -0.008) and HbA1c (ß = -0.016, 95% CI -0.030; -0.001). Total dairy intake and the dairy subgroups were not related to HOMA-IR and HOMA-B in the maximally-adjusted model. Furthermore, there was no significant association between intake of total dairy or any of the dairy subgroups and incidence of T2D. CONCLUSION: Our data suggest a modest beneficial effect of cheese and fermented dairy on glucose regulation measures; however, this did not translate into a significant association with incident T2D.

Determinants of vitamin D status in a general population of Danish adults.

BACKGROUND AND AIMS: Danish legislation regarding food fortification has been very restrictive and vitamin D deficiency is thought to be common in Denmark due to inadequate dietary intakes and the fact that in Denmark (latitude 56°N) vitamin D is only synthesized in the skin after exposure to solar radiation during summertime (April-September). The purpose of this study was to evaluate the vitamin D status of a general adult population in Denmark and, in addition, associations between vitamin D status and distinct lifestyle factors were studied. METHODS: A random sample of 6784 persons from a general population aged 30-60 years participated in a health examination in 1999-2001. Serum samples from all participants were stored and levels of 25-hydroxyvitamin D (25(OH)D) were measured by HPLC in 2009. The method was compared to another HPLC method. Information on dietary intake of vitamin D and other lifestyle factors were obtained by questionnaires. A total of 6146 persons defined as ethnic Danes and with successful measurements of 25(OH)D were included in the analyses. RESULTS: The overall prevalence of vitamin D deficiency (25(OH)D<25 nmol/l) and insufficiency (25(OH)D<50 nmol/l) were 13.8% and 52.2%, respectively. A marked seasonal fluctuation was seen in serum levels of 25(OH)D - median values of 25(OH)D were lowest in February and highest in August. In multiple logistic regression models (n=5506), low vitamin D status was significantly associated with obesity (BMI≥30), daily smoking and a sedentary lifestyle. However, measurements of 25(OH)D were not associated with the estimated dietary intake of vitamin D. Comparison of two HPLC methods demonstrated considerable differences in accuracy. DISCUSSION AND CONCLUSIONS: Our results suggest that poor vitamin D status is common among adults in a Northern European country without food fortification with vitamin D. Methodological issues are, however, of great importance when using cut-off values to define poor vitamin D status. In addition, we demonstrated that low serum levels of 25(OH)D were associated with several lifestyle factors.

The effects of adding group-based lifestyle counselling to individual counselling on changes in plasma glucose levels in a randomized controlled trial: the Inter99 study.

AIM: This study aimed to assess whether group-based lifestyle counselling offered to a high-risk population subgroup had any effect beyond individual multifactorial interventions on fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) changes. METHODS: In a population-based study of 6784 participants, 4053 were determined to be at high risk based on a risk estimate of ischaemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolaemia, obesity, impaired glucose tolerance). Of these subjects, 90% were randomized to high-intensity intervention (group A) and 10% to low-intensity intervention (group B). All participants went through health examinations, risk assessments and individual lifestyle counselling. Participants in group A were further offered group-based lifestyle counselling. The intervention was repeated after 1 and 3 years. A total of 2738 participants free of diabetes at baseline (1999-2001) and with at least one FPG and/or 2hPG measurement during 5 years of follow-up were included in the analyses. Differences in changes of plasma glucose between groups A and B were analyzed using multilevel linear regression. RESULTS: For FPG, crude 5-year changes were significantly different between the two groups (group A: -0.003 mmol/L vs group B: -0.079 mmol/L; P=0.0427). After adjusting for relevant confounders, no differences in FPG changes were observed (P=0.116). Also, no significant differences in the 5-year changes in 2hPG between the two groups were observed (group A: - 0.127 mmol/L vs group B: -0.201 mmol/L; P=0.546). CONCLUSION: Offering additional group-based intervention to a high-risk population subgroup had no clinical effects on changes in plasma glucose beyond those of individualized multifactorial interventions.

Does a population-based multifactorial lifestyle intervention increase social inequality in physical activity? The Inter99 study.

AIM: To examine the effect of a multifactorial lifestyle intervention on 5-year change in physical activity (PA) and to explore whether length of education had an impact on the effect of the intervention. METHODS: Two random samples (high intervention group A, n=11 708; low intervention group B, n=1308) were invited for a health examination, assessment of absolute risk of ischemic heart disease and individual lifestyle counselling. The participation rate was 52.5%. High-risk individuals in group A were also offered group-based counselling on diet and PA and/or smoking cessation. High-risk individuals in group B were referred to usual care. All high-risk individuals were reinvited for examination and counselling after 1 and 3 years, and all participants were reexamined after 5 years. The control group (group C, n=5264, response rate 61.1%) answered a mailed questionnaire. Change in self-reported PA from baseline to 5-year follow-up was the main outcome. Level of education was classified as no vocational training, ≤4 years and >4 years. Data were analysed using longitudinal linear regression models with random intercepts. RESULTS: In men, the high-intensity intervention had a beneficial effect on PA level after 5 years. The age- or time-related decrease in PA was approximately 30 min/week less compared to men in the control group (p<0.0001). Level of education had no significant impact on the effect of the intervention neither in men (p=0.39) nor in women (p=0.32). CONCLUSION: A population-based multifactorial lifestyle intervention did not influence social inequality in PA.

Impact of size at birth and prematurity on adult anthropometry in 4744 middle-aged Danes - The Inter99 study.

Low birth weight is related to increased risk of developing cardiovascular disease and type 2 diabetes in adult life. Since obesity is closely associated with type 2 diabetes and cardiovascular disease, the relationship between size at birth and adult anthropometry is of interest as a mediator of the relationship between birth weight and metabolic diseases. The aim of this study was, therefore, to examine the effect of size at birth and prematurity on measures of adult anthropometry taking adult socio-economic status and lifestyle variables into account. Midwife records with information on mother's age and parity as well as weight, length and maturity at birth were traced in 4744 Danes born between 1939 and 1970. Measures of adult anthropometry (weight, height, body mass index (BMI), waist circumference, hip circumference and waist/hip ratio) had previously been recorded together with information on socio-economic factors, lifestyle and parental diabetes status. Mother's age, parity and diabetes status were associated with offspring birth weight. Size at birth was positively associated with adult height and weight, but only weakly associated with BMI and not associated with waist/hip ratio when adjusted for socio-economic and lifestyle factors. Infants born preterm were less growth restricted at birth and grew to be taller and heavier compared with term infants born small for gestational age. Altogether, this study does not find evidence that obesity or a central fat distribution is mediating the relationship between low birth weight and risk of cardiovascular disease or type 2 diabetes in later life.

Five-year change in physical activity is associated with changes in cardiovascular disease risk factors: the Inter99 study.

OBJECTIVE: To evaluate whether five-year changes in self-reported physical activity level were associated with changes in waist circumference, weight, serum lipids and blood pressure. METHODS: In the Inter99 study (1999-2006) in Copenhagen, Denmark, 4039 men and women (30-60 years) answered questions on lifestyle and provided blood samples and anthropometric measures at baseline and after five years. Multiple regression analyses were performed with five-year value of each cardiovascular biomarker as outcome and change in physical activity level as explanatory variable. RESULTS: Approximately 50% of the study population were men (n=2023). Change in physical activity level was inversely associated with change in weight (p<0.0001), waist (p<0.0001), diastolic blood pressure (p=0.04), total cholesterol (p=0.006), LDL (p=0.007), triglycerides (p=0.02) and with a composite risk score "the Copenhagen risk score" (p<0.0001), and positively associated with HDL in men (p=0.01). CONCLUSION: Five-year changes in physical activity level were significantly associated with relevant changes in weight, waist circumference, diastolic BP and serum lipids in a population-based cohort of adult men and women. Change in physical activity level induced a significant change in HDL concentration in men only. Women's use of hormone replacement therapy may partly explain this gender difference.

Can lifestyle factors explain why body mass index and waist-to-hip ratio increase with increasing tobacco consumption? The Inter99 study.

BACKGROUND: The relationship between smoking, lifestyle, and weight, body mass index (BMI) and waist-to-hip ratio (WH ratio) is complex, and not fully understood. METHODS: In total, 6784 subjects (2408 daily smokers) were included in a population-based study (the Inter99 study) in Denmark. Weight, height, and waist and hip circumference were measured. Self-reported tobacco consumption and lifestyle variables (dietary quality, energy intake, physical activity in leisure time and alcohol consumption) were registered. RESULTS: Daily smokers had a significantly lower BMI and significantly higher WH ratio than never smokers (P<0.001). Unhealthy lifestyle increased with increasing tobacco consumption (P<0.001 for all variables). Both BMI and WH ratio increased with increasing tobacco consumption. The association between increasing WH ratio and increasing tobacco consumption was largely explained by sociodemographic factors, rather than lifestyle factors. However, neither sociodemographic nor lifestyle factors could fully explain the increased BMI associated with heavier smoking. CONCLUSIONS: Sociodemographic and lifestyle factors could not fully explain why BMI increased with increasing daily tobacco consumption, but these factors did largely explain the increasing WH ratio. The relationship between BMI and tobacco consumption is complex, and the public needs to be informed that smoking is not a 'diet'.

Relative validity of a food frequency questionnaire used in the Inter99 study.

OBJECTIVE: To evaluate the validity of the Inter99 food frequency questionnaire (FFQ) compared with a 28-days' diet history and biomarkers. SUBJECTS: A random sample of 13 016 individuals were drawn from a general population and invited for a health screening programme. Participation rate was 52.5%. All high-risk individuals were re-invited for assessment after 1 and 3 years and completed a 198-item FFQ at all three occasions. Participants attending for 3 years follow-up were invited to participate in the validation study, including a 28-days' diet history, a 24-h urine collection and a fasting blood sample. Overall, 264 subjects participated. RESULTS: Spearman's rank correlation coefficients between the two dietary methods ranged from 0.31(beta-carotene) to 0.64 (fruits) in men and from 0.31 (polyunsaturated fat and sodium) to 0.64 (fruits) for women. The proportion of individuals classified in the same or adjacent quintiles were, on average, 72% for men and 69% for women. Gross misclassification was found on average in 2%. The correlation coefficients of the residuals ranged from 0.27 (sodium) to 0.61 (fruits) for men and from 0.21 (sodium) to 0.62 (B12-vitamin) for women. Correlation coefficients between fruit and vegetable intake and carotenoids ranged from -0.08 (lycopene) to 0.44 (alpha-carotene). For the residuals the correlation coefficients ranged from -0.004 (lycopene) to 0.47 (alpha-carotene). CONCLUSION: The Inter99 FFQ and the residuals of the intake provide acceptable classification of individuals according to their dietary intakes and the FFQ gives a good quantitative measurement of key dietary components.

The Dietary Quality Score: validation and association with cardiovascular risk factors: the Inter99 study.

OBJECTIVE: To develop and assess the validity of the Dietary Quality Score (DQS) and investigate the association with cardiovascular risk factors. DESIGN: Cross-sectional population-based study. SETTING: Copenhagen County, Glostrup, Denmark. SUBJECTS: A random sample of 12,934 men and women aged 30-60 years were invited to a health examination. A total of 6542 participants were included in the statistical analysis. METHODS: The DQS was developed using eight questions from a 48-item food frequency questionnaire (FFQ) and validated using a 198-item FFQ. Associations between the DQS and fasting serum lipids, homocysteine, blood pressure and the absolute risk of ischaemic heart disease (IHD) were explored. RESULTS: A higher DQS was shown to be associated with higher dietary quality in general, including a low intake of fat, especially saturated fat; a high intake of fibre; various vitamins and minerals; and fruit, fish, vegetables and whole-grain products. A higher score according to the DQS was significantly negatively associated with total cholesterol (P=0.0031), triglyceride (P=0.0406), low-density lipoprotein-cholesterol (P=0.0071), homocysteine (P<0.0001) and the absolute risk of IHD (P<0.0001), adjusted for sex, age, smoking habits and physical activity level. CONCLUSIONS: The DQS is a simple, valid and quick tool to make a rough classification of individuals into groups with high, average and low dietary quality. The DQS is negatively associated with serum lipids, homocysteine and the absolute risk of IHD. SPONSORSHIP: The Inter99 study is supported economically by The Danish Medical Research Council, The Danish Centre for Evaluation and Health Technology Assessment, Novo Nordisk, Copenhagen County, The Danish Heart Foundation, The Danish Pharmaceutical Association, Augustinus Foundation, Ib Henriksen Foundation and Becket Foundation, Copenhagen County.

Overweight men's motivations and perceived barriers towards weight loss.

OBJECTIVE: To explore motivation and perceived barriers towards weight loss among Danish men. DESIGN: The study was of an explorative nature, using qualitative focus group interviews as a method. SETTING: Copenhagen, Denmark. SUBJECTS: Twenty-two overweight men, at the age of 25-44 years and motivated for weight loss, were recruited and distributed into four focus groups. The men were primarily unskilled workers. Overall 13 men participated and each group contained three or four participants. INTERVENTION: The interview guide was partly structured, partly unstructured and the themes of the interviews were motives and perceived barriers towards weight loss. RESULTS: Main barriers for losing weight appeared to be lack of motivation and the perception of the slimming diet. The men had a desire to have a lean appearance and avoid illness, but in all the interviews it appeared that the strongest motive for losing weight was a strong desire to become more effective and a greater asset for one's workplace. Overweight subjects were considered less effective and attractive for the labour market. CONCLUSION: This study indicates that if men from lower socioeconomic backgrounds are to be motivated to weight loss the focus should not be on leanness and good health but rather on increased effectiveness and performance, and the arena should include the working place. SPONSORSHIP: The Royal Veterinary and Agricultural University supplied the necessary equipment and conference rooms.