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1.  Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population 
Biomarker Insights  2014;9:91-100.
The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers.
doi:10.4137/BMI.S19876
PMCID: PMC4269129  PMID: 25574132
biomarkers; epidemiologic studies; risk factors; urokinase plasminogen activator receptor
2.  Why public health people are more worried than excited over e-cigarettes 
BMC Medicine  2014;12(1):226.
The research field on e-cigarettes is characterized by severe methodological problems, severe conflicts of interest, relatively few and often small studies, inconsistencies and contradictions in results, and a lack of long-term follow-up. Therefore, no firm conclusions can be drawn on the harm of e-cigarettes, but they can hardly be called safe. Experimental studies indicate negative health effects and, amongst others, the major ingredient propylene glycol warrants concern. Growing evidence raises doubt about the efficacy of e-cigarettes as a smoking cessation aid. Unfortunately, it seems that many smokers use e-cigarettes with the intention to quit but switch to long-term use of e-cigarettes or dual use. Use is spreading rapidly to minors, ex-smokers, and never-smokers. It is questionable whether the potential health benefits obtained by some smokers outweigh the potential harm by use of non-smokers, of undermining of complete cessation, smokers’ dual use, and of eventual re-normalization of smoking. Even if e-cigarettes are significantly less harmful than conventional cigarettes, the product may have a very negative impact on public health if its use is spread to a large part of the population.
doi:10.1186/s12916-014-0226-y
PMCID: PMC4260246  PMID: 25488431
Electronic cigarettes; ENDS; Harm reduction; Public health; Smoking; Vaping
3.  Cause-Specific Mortality According to Urine Albumin Creatinine Ratio in the General Population 
PLoS ONE  2014;9(3):e93212.
Background
Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality.
Methods
We included a total of 9,125 individuals from two population-based studies, Monica10 and Inter99, conducted in 1993–94 and 1999–2001, respectively. Urine albumin creatinine ratio was measured from spot urine samples by standard methods. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2010. There were a total of 920 deaths, and the median follow-up was 11.3 years.
Results
Multivariable Cox regression analyses with age as underlying time axis showed statistically significant positive associations between UACR status and risk of all-cause mortality, endocrine nutritional and metabolic diseases, mental and behavioural disorders, diseases of the circulatory system, and diseases of the respiratory system with hazard ratios 1.56, 6.98, 2.34, 2.03, and 1.91, for the fourth UACR compared with the first, respectively. Using UACR as a continuous variable, we also found a statistically significant positive association with risk of death caused by diseases of the digestive system with a hazard ratio of 1.02 per 10 mg/g higher UACR.
Conclusion
We found statistically significant positive associations between baseline UACR and death from all-cause mortality, endocrine nutritional and metabolic diseases, and diseases of the circulatory system and possibly mental and behavioural disorders, and diseases of the respiratory and digestive system.
doi:10.1371/journal.pone.0093212
PMCID: PMC3968135  PMID: 24675825
4.  Vitamin D Status and Chronic Obstructive Pulmonary Disease: A Prospective General Population Study 
PLoS ONE  2014;9(3):e90654.
Objectives
Vitamin D deficiency is common among persons with chronic obstructive pulmonary disease (COPD). Whether vitamin D affects the development and deterioration of COPD or is a consequence of the disease lacks clarity. We investigated the association between vitamin D status and prevalent and incident COPD in the general population.
Methods
We included a total of 12,041 individuals from three general population studies conducted in 1993–94, 1999–2001, and 2006–2008, respectively, with vitamin D measurements. Information on COPD was obtained from the Danish National Patient Register and The Danish Registry of Causes of Death.
Results
There were 85 prevalent and 463 incident cases of COPD (median follow-up 9.7 years). We found a statistically significant inverse association between vitamin D status and prevalent COPD with odds ratio = 0.89 (95% confidence interval, CI: 0.79, 1.0), but no statistically significant association with incident COPD with a hazard ratio = 0.98 (95% CI: 0.94, 1.0), respectively, per 10 nmol/l higher vitamin D status, when adjusted for possible confounders.
Conclusions
We found a statistically significant inverse cross-sectional association between vitamin D status and COPD, but no association between vitamin D status and incident COPD.
doi:10.1371/journal.pone.0090654
PMCID: PMC3942472  PMID: 24594696
5.  Vitamin D Status, Filaggrin Genotype, and Cardiovascular Risk Factors: A Mendelian Randomization Approach 
PLoS ONE  2013;8(2):e57647.
Background
Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome.
Methods
Three population based studies were included, Monica10 (2,656 individuals aged 40–71 years), Inter99 (6,784 individuals aged 30–60 years), and Health2006 (3,471 individuals aged 18–69 years) conducted in 1993–94, 1999–2001, and 2006–2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies.
Results
Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference.
Conclusion
Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.
doi:10.1371/journal.pone.0057647
PMCID: PMC3584055  PMID: 23460889
6.  Vitamin D Status and Cause-Specific Mortality: A General Population Study 
PLoS ONE  2012;7(12):e52423.
Background
Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality.
Methods
We included a total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, conducted in 1993–94 and 1999–2001, respectively. Vitamin D status was assessed as serum 25-hydroxyvitamin D. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2009. There were a total of 832 deaths (median follow-up 10.3 years).
Results
Multivariable Cox regression analyses with age as underlying time axis and vitamin D quartiles showed significant associations between vitamin D status and death caused by diseases of the respiratory system, the digestive system, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (ptrend = 0.0042), 0.28 (ptrend = 0.0040), and 0.21 (ptrend = 0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by neoplasms or diseases of the circulatory system.
Conclusion
The associations of vitamin D status and cause-specific mortality suggest that we also look elsewhere (than to cardiovascular disease and cancer) to explain the inverse association between vitamin D status and mortality.
doi:10.1371/journal.pone.0052423
PMCID: PMC3527503  PMID: 23285034
7.  Social disparities in children’s exposure to second hand smoke at home: a repeated cross-sectional survey 
Environmental Health  2012;11:65.
Background
Exposure to second hand smoke (SHS) is an important preventable cause of morbidity and mortality in children. We hypothesised that there has been a growth in social inequality in children’s exposure to SHS at home over time. The purpose of this study was to investigate temporal change in smoking in homes including children, focusing on the socioeconomic differences.
Methods
Data is from a repeated cross-sectional survey, ‘Health Profiles of the Capital Region of Denmark’ conducted in 2007 and 2010, in 29 municipalities. The response rate was 52.3%, in both surveys. Our study included persons aged 25 to 64, living with children ≤15 years of age; N=9,289 in 2007 and 12,696 in 2010. Analyses were weighted for size of municipality and for non-response, which was higher among men and among persons who were younger, had a lower income, were living alone, were unemployed, and/or were of an ethnicity other than Danish. Regression analyses were used to investigate smoking in homes including children across parent/adult education levels, focusing on temporal changes.
Results
There were significant large socioeconomic differences in both 2007 and 2010. In 2010 it was more than 11 times more likely for a child to be exposed to SHS at home if the parent had very low education than if they were highly educated (p<0.001). Smoking in a home with children decreased from 16.2% in 2007 to 10.9% in 2010. The odds of a temporal decrease in domestic smoking did not differ significantly across parent education levels (p=0.40).
Conclusions
Marked social inequalities in children’s exposure to SHS and a significant temporal decrease in exposure, independent of the education level of the parent/adult, were found in repeated large cross-sectional population-based studies. Social disparities have persisted over time, but not increased. Both clinical and population policy interventions will be needed in order to control child SHS exposure. We call for legislative protection of children from tobacco smoke inside their home as a supplement to parental education and support for smoking cessation.
doi:10.1186/1476-069X-11-65
PMCID: PMC3544183  PMID: 22984822
Second hand smoke; Environmental tobacco smoke pollution; Involuntary smoking; Passive smoking; Child; Child welfare; Social classes; Socioeconomic status
8.  The relationship between changes in health behaviour and initiation of lipid-lowering and antihypertensive medications in individuals at high risk of ischaemic heart disease 
BMC Public Health  2012;12:626.
Background
It has been hypothesised that health conscious individuals tend to take better care of themselves by greater adherence to preventive medications. We examined, whether long-term changes in dietary habits and physical activity were associated with initiation of lipid-lowering and antihypertensive medications.
Methods
The study population consisted of two subsamples from the population-based cohort Inter99 study (1999-2006) in Copenhagen, Denmark: one with systolic blood pressure > 140 mmHg (N = 557) and one with total cholesterol > 7 mmol/L (N = 314). At a health examination, individuals completed a questionnaire about health behaviour and had their blood pressure and cholesterol measured at baseline and after five years. Data on medications were obtained through linkage to the Registry of Medical Product Statistics.
Results
Positive changes in physical activity (odds ratio =3.50; 95% CI 1.23-7.54) and in dietary habits (odds ratio = 2.08; 95% CI 1.03-4.21) were associated with an increased initiation of lipid-lowering medications. With respect to antihypertensives, no association was observed in terms of physical activity, but for diet, a positive trend in terms of initiation was observed among those with positive changes in dietary habits (odds ratio = 1.58; 95% CI 0.96-2.59).
Conclusion
Generally, we observed health conscious behaviour in terms of increased initiation of preventive medications among those who reported positive changes in health behaviour. This study therefore suggests that more attention should be given to identifying individuals and groups, who are less health conscious and thereby less likely to engage in either preventive medications or changes in health behaviours.
doi:10.1186/1471-2458-12-626
PMCID: PMC3538631  PMID: 22873800
9.  The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge 
PLoS ONE  2011;6(11):e27096.
Background and Aim
The first genome-wide association study on birth weight was recently published and the most significant associated birth weight lowering variant was the rs900400 C-allele located near LEKR1 and CCNL1. We aimed to replicate the association with birth weight in the Danish Inter99 study and furthermore to evaluate associations between rs900400 and indices of insulin secretion and insulin sensitivity obtained by oral glucose tolerance tests in adults from the Danish Inter99 study and the Finnish, Metabolic Syndrome in Men (METSIM) sample.
Methods
For 4,744 of 6,784 Inter99 participants, midwife journals were traced through the Danish State Archives and association of rs900400 with birth weight was examined. Associations between rs900400 and fasting serum insulin, fasting plasma glucose, insulinogenic index, homeostasis model assessment of insulin resistance (HOMA-IR) and disposition index were studied in 5,484 Danish and 6,915 Finnish non-diabetic individuals and combined in meta-analyses.
Results
The C-allele of rs900400 was associated with a 22.1 g lower birth weight ([−41.3;−3.0], P = 0.024) per allele. Moreover, in combined analyses of the Danish Inter99 study and the Finnish METSIM study we found that the birth weight lowering allele was associated with increased insulin release measured by the insulinogenic index (β = 2.25% [0.59; 3.91], P = 0.008) and with an increased disposition index (β = 1.76% [0.04; 3.49], P = 0.05).
Conclusion
The birth weight lowering effect of the C-allele of rs900400 located near LEKR1 and CCNL1 was replicated in the Danish population. Furthermore the C-allele was associated with increased insulin response following oral glucose stimulation in a meta-analysis based on Danish and Finnish non-diabetic individuals.
doi:10.1371/journal.pone.0027096
PMCID: PMC3208566  PMID: 22073261
10.  The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load 
BMC Medical Genetics  2011;12:4.
Background
A genome-wide association study (GWAS) using metabolite concentrations as proxies for enzymatic activity, suggested that two variants: rs2014355 in the gene encoding short-chain acyl-coenzyme A dehydrogenase (ACADS) and rs11161510 in the gene encoding medium-chain acyl-coenzyme A dehydrogenase (ACADM) impair fatty acid β-oxidation. Chronic exposure to fatty acids due to an impaired β-oxidation may down-regulate the glucose-stimulated insulin release and result in an increased risk of type 2 diabetes (T2D). We aimed to investigate whether the two variants associate with altered insulin release following an oral glucose load or with T2D.
Methods
The variants were genotyped using KASPar® PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT) in a random sample of middle-aged Danish individuals (n ACADS = 4,324; n ACADM = 4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (n ACADS = 8,313; n ACADM = 8,344).
Results
In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (β) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (β = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (β = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (β = 2.9% (0.5%;5.2%), P = 0.02). The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P = 0.21). rs11161510 of ACADM did not associate with any indices of glucose-stimulated insulin release or with T2D.
Conclusions
In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS was associated with reduced measures of glucose-stimulated insulin release during an OGTT, a finding which in part may be mediated through an impaired β-oxidation of fatty acids.
doi:10.1186/1471-2350-12-4
PMCID: PMC3022800  PMID: 21211036
11.  Do Gene Variants Influencing Adult Adiposity Affect Birth Weight? A Population-Based Study of 24 Loci in 4,744 Danish Individuals 
PLoS ONE  2010;5(12):e14190.
Background
Several obesity risk alleles affecting adult adiposity have been identified by the recent wave of genome wide association studies. We aimed to examine the potential effect of these variants on fetal body composition by investigating the variants in relation to birth weight and ponderal index of the newborn.
Methodology/Principal Findings
Midwife records from the Danish State Archives provided information on mother's age, parity, as well as birth weight, birth length and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. Twenty-four risk alleles showing genome-wide associations with adult BMI and/or waist circumference were genotyped. None of the 24 risk variants tested showed an association with birth weight or ponderal index after correction for multiple testing. Birth weight was divided into three categories low (≤10th percentile), normal (10th–90th percentile) and high birth weight (≥90th percentile) to allow for non-linear associations. There was no difference in the number of risk alleles between the groups (p = 0.57). No interactions between each risk allele and birth weight in the prediction of adult BMI were observed. An obesity risk score was created by summing up risk alleles. The risk score did not associate with fetal body composition. Moreover there was no interaction between the risk score and birth weight/ponderal index in the prediction of adult BMI.
Conclusion
24 common variants associated with adult adiposity did not affect or interact with birth weight among Danes suggesting that the effects of these variants predominantly arise in the post-natal life.
doi:10.1371/journal.pone.0014190
PMCID: PMC2995733  PMID: 21152014
12.  Family and Population-Based Studies of Variation within the Ghrelin Receptor Locus in Relation to Measures of Obesity 
PLoS ONE  2010;5(4):e10084.
Background
The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites.
Methodology/Principal Findings
In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p<0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27±4 kg/m2) versus non-carriers (mean BMI: 28±5 kg/m2) (p>0.05) could be shown.
Conclusions/Significance
In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.
doi:10.1371/journal.pone.0010084
PMCID: PMC2852411  PMID: 20404923
13.  Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY) 
BMC Medical Genetics  2010;11:42.
Background
Insulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood.
Methods
INS was sequenced in 116 maturity-onset diabetes of the young (MODYX) patients (n = 48 Danish and n = 68 Czech), 83 patients with gestational diabetes mellitus (GDM), 34 type 1 diabetic patients screened negative for glutamic acid decarboxylase (GAD), and 96 glucose tolerant individuals. The control group was randomly selected from the population-based sampled Inter99 study.
Results
One novel heterozygous mutation c.17G>A, R6H, was identified in the pre-proinsulin gene (INS) in a Danish MODYX family. The proband was diagnosed at 20 years of age with mild diabetes and treated with diet and oral hypoglycaemic agent. Two other family members who carried the INS R6H were diagnosed with diabetes when 51 years old and with GDM when 27 years old, respectively. A fourth mutation carrier had normal glucose tolerance when 20 years old. Two carriers of INS R6H were also examined twice with an oral glucose tolerance test (OGTT) with 5 years interval. They both had a ~30% reduction in beta-cell function measured as insulinogenic index. In a Czech MODYX family a previously described R46Q mutation was found. The proband was diagnosed at 13 years of age and had been treated with insulin since onset of diabetes. Her mother and grandmother were diagnosed at 14 and 35 years of age, respectively, and were treated with oral hypoglycaemic agents and/or insulin.
Conclusion
Mutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.
doi:10.1186/1471-2350-11-42
PMCID: PMC2848224  PMID: 20226046
14.  Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes 
Human Molecular Genetics  2009;19(3):535-544.
Epidemiological studies consistently show that circulating sex hormone binding globulin (SHBG) levels are lower in type 2 diabetes patients than non-diabetic individuals, but the causal nature of this association is controversial. Genetic studies can help dissect causal directions of epidemiological associations because genotypes are much less likely to be confounded, biased or influenced by disease processes. Using this Mendelian randomization principle, we selected a common single nucleotide polymorphism (SNP) near the SHBG gene, rs1799941, that is strongly associated with SHBG levels. We used data from this SNP, or closely correlated SNPs, in 27 657 type 2 diabetes patients and 58 481 controls from 15 studies. We then used data from additional studies to estimate the difference in SHBG levels between type 2 diabetes patients and controls. The SHBG SNP rs1799941 was associated with type 2 diabetes [odds ratio (OR) 0.94, 95% CI: 0.91, 0.97; P = 2 × 10−5], with the SHBG raising allele associated with reduced risk of type 2 diabetes. This effect was very similar to that expected (OR 0.92, 95% CI: 0.88, 0.96), given the SHBG-SNP versus SHBG levels association (SHBG levels are 0.2 standard deviations higher per copy of the A allele) and the SHBG levels versus type 2 diabetes association (SHBG levels are 0.23 standard deviations lower in type 2 diabetic patients compared to controls). Results were very similar in men and women. There was no evidence that this variant is associated with diabetes-related intermediate traits, including several measures of insulin secretion and resistance. Our results, together with those from another recent genetic study, strengthen evidence that SHBG and sex hormones are involved in the aetiology of type 2 diabetes.
doi:10.1093/hmg/ddp522
PMCID: PMC2798726  PMID: 19933169
15.  The Type 2 Diabetes Associated Minor Allele of rs2237895 KCNQ1 Associates with Reduced Insulin Release Following an Oral Glucose Load 
PLoS ONE  2009;4(6):e5872.
Background
Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1) have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897) on estimates of glucose stimulated insulin release.
Methodology/Principal Findings
Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses.
Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean±SD: (CC) 277±160 vs. (AC) 280±164 vs. (AA) 299±200 pmol/l, p = 0.008) after an oral glucose load, insulinogenic index (29.6±17.4 vs. 30.2±18.7vs. 32.2±22.1, p = 0.007), incremental area under the insulin curve (20,477±12,491 vs. 20,503±12,386 vs. 21,810±14,685, p = 0.02) among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228.
Conclusion
The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.
doi:10.1371/journal.pone.0005872
PMCID: PMC2689931  PMID: 19516902
16.  The effect of adding group-based counselling to individual lifestyle counselling on changes in dietary intake. The Inter99 study – a randomized controlled trial 
Background
Few studies have investigated the specific effect of single intervention components in randomized controlled trials. The purpose was to investigate the effect of adding group-based diet and exercise counselling to individual life-style counselling on long-term changes in dietary habits.
Methods
The study was a randomized controlled intervention study. From a general Danish population, aged 30 to 60 years (n = 61,301), two random sample were drawn (group A, n = 11,708; group B, n = 1,308). Subjects were invited for a health screening program. Participation rate was 52.5%. All participants received individual life-style counselling. Individuals at high risk of ischemic heart disease in group A were furthermore offered group-based life-style counselling. The intervention was repeated for high-risk individuals after one and three years. At five-year follow-up all participants were invited for a health examination. High risk individuals were included in this study (n = 2 356) and changes in dietary intake were analyzed using multilevel linear regression analyses.
Results
At one-year follow-up group A had significantly increased the unsaturated/saturated fat ratio compared to group B and in men a significantly greater decrease in saturated fat intake was found in group A compared to group B (net change: -1.13 E%; P = 0.003). No differences were found between group A and B at three-year follow-up. At five-year follow-up group A had significantly increased the unsaturated/saturated fat ratio (net change: 0.09; P = 0.01) and the fish intake compared to group B (net change: 5.4 g/day; P = 0.05). Further, in men a non-significant tendency of a greater decrease was found at five year follow-up in group A compared to group B (net change: -0.68 E%; P = 0.10). The intake of fibre and vegetables increased in both groups, however, no significant difference was found between the groups. No differences between groups were found for saturated fat intake in women.
Conclusion
Offering group-based counselling in addition to individual counselling resulted in small, but significantly improved dietary habits at five-year follow-up and a tendency of better maintenance, compared to individual counselling alone.
Trial registration
The Inter99 study was approved by the local Ethics Committee (KA 98 155) and is registered with ClinicalTrials.gov (registration number: NCT00289237).
doi:10.1186/1479-5868-5-59
PMCID: PMC2607304  PMID: 19025583
17.  Effect of screening and lifestyle counselling on incidence of ischaemic heart disease in general population: Inter99 randomised trial 
Objective To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level.
Design Randomised controlled community based trial.
Setting Suburbs of Copenhagen, Denmark
Participants 59 616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n=11 629) and a control group (n=47 987).
Intervention The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening.
Main outcome measures The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality.
Results 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58 308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58 940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the primary end point (hazard ratio for ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to 1.09; total mortality 1.00, 0.91 to 1.09).
Conclusion A community based, individually tailored intervention programme with screening for risk of ischaemic heart disease and repeated lifestyle intervention over five years had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years.
Trial registration Clinical trials NCT00289237.
doi:10.1136/bmj.g3617
PMCID: PMC4049194  PMID: 24912589

Results 1-17 (17)