Biomedical subjects

Torben Jørgensen

Publications and source records attributed to Torben Jørgensen.

At least 19 recordsLinked to original sources

PubMed2007

The functional Pro129Thr variant of the FAAH gene is not associated with various fat accumulation phenotypes in a population-based cohort of 5,801 whites.

Food intake and weight gain are influenced by endocannabinoids whose actions are regulated by the fatty acid amide hydrolase (FAAH) enzyme. The homozygous Thr/Thr genotype of the functional Pro129Thr variant (rs324420) in the gene encoding FAAH was recently reported to associate with overweight and obesity in white and black populations. We investigated the Pro129Thr variant in relation to overweight and obesity in a relatively large population-based study sample of Danish whites (n=5,801). In case-control studies of obesity, a borderline association with the major Pro allele was identified; however, after correction for multiple testing, no association was found. Furthermore, a possible association between the major Pro allele and obesity was not supported by studies of obesity-related quantitative traits. In conclusion, in a large study sample, we were unable to find robust evidence of an association of the Pro129Thr FAAH variant with overweight, obesity, and any related quantitative traits among the examined whites.

Adult↗

PubMed2006

Diet and exercise intervention in a general population--mediators of participation and adherence: the Inter99 study.

BACKGROUND: Drop-out rates are high in many lifestyle programmes. To promote adherence, the aim of this study was to identify mediators of participation in a diet and exercise (DE) intervention in a general population. METHODS: Data were baseline data from a randomized non-pharmacological clinical trial in Copenhagen during 1999-2001. The participation rate was 53.3%. Participants at high risk of ischaemic heart disease (IHD) and who were offered participation in a DE counselling group intervention were included (N = 2022). Clinical characteristics, and demographic, psychosocial and lifestyle factors were measured. RESULTS: Mediators of acceptance of participation were awareness of an unhealthy lifestyle or a bad health, low self-rated care of own health, perceived susceptibility of cardiovascular disease (CVD; overall and associated with lifestyle), high degree of motivation towards dietary changes and low self-efficacy about increasing physical activity. Overweight and impaired glucose tolerance (IGT)/screen-detected diabetes predicted acceptance whereas an absolute risk score for IHD was inverse associated with acceptance. Mediators of high adherence were low self-efficacy about changing dietary habits and perceived susceptibility of CVD and furthermore screen-detected diabetes and overweight predicted high adherence. CONCLUSION: Awareness of unhealthy lifestyle, perceived susceptibility of disease and motivation towards lifestyle changes were important mediators of participation. Screen-detected diabetes/IGT predicted participation and adherence whereas overweight individuals were more likely to accept but also to drop out of the course. The use of an absolute risk score in health promotion should be further evaluated.

Adult↗

PubMed2006

Relationships between the functional PPARalpha Leu162Val polymorphism and obesity, type 2 diabetes, dyslipidaemia, and related quantitative traits in studies of 5799 middle-aged white people.

Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor capable of regulating the expression of genes involved in peroxisomal and mitochondrial beta-oxidation pathways. The common Leu162Val polymorphism in the gene encoding PPARalpha has inconsistently shown association with quantitative traits related to obesity, type 2 diabetes, and dyslipidaemia. We genotyped the Leu162Val polymorphism in 1383 patients with type 2 diabetes and 4401 control subjects with normal glucose tolerance (NGT) without showing any association between diabetes and genotype. In addition, the Leu162Val polymorphism was not associated with WHO-defined obesity or dyslipidaemia in case-control settings involving 961 obese and 2563 lean subjects and 1399 dyslipidaemic and 4399 normolipidaemic subjects, respectively. Quantitative trait studies of metabolic variables were carried out in 5799 middle-aged, treatment-naïve subjects showing a difference in fasting serum triglyceride concentrations among homozygous Val-carriers (Leu/Leu+Leu/Val, n=5782, 1.33+/-1.35 mmol/l vs. Val/Val, n=17, 2.22+/-2.4 mmol/l, p=0.007). Similarly, Val/Val was associated with increased fasting serum total cholesterol concentrations (p=0.01). In conclusion, in a relative large-scale study of middle-aged whites we found no evidence of association between the PPARalpha Leu162Val polymorphism and obesity or type 2 diabetes. If replicated, the Val162Val variant may, however, confer an increase in fasting levels of serum lipids.

Aged↗

PubMed2006

Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects.

CONTEXT: The type 2 iodothyronine deiodinase (D2) catalyzes the conversion of T(4) to the active form of thyroid hormone, which is a critical regulator of thermogenesis and glucose metabolism. A Thr92Ala polymorphism in the gene encoding D2 (DIO2) has been reported to associate with insulin resistance. OBJECTIVE: The aim of the present study was to assess the impact of the DIO2 Thr92Ala variant on type 2 diabetes (T2D), obesity, and related quantitative metabolic traits including measures of insulin resistance. Because DIO2 is activated through a beta-adrenergic receptor-dependent pathway, we further hypothesized that variation in the ADRB genes interacts with DIO2 Thr92Ala variant to influence metabolic traits. DESIGN AND PATIENTS: The DIO2 polymorphism was genotyped in a total of 7342 white subjects including 1405 T2D patients. RESULTS: We detected no significant association of the DIO2 Thr92Ala polymorphism with T2D or obesity. We observed nominal significant associations of genotype with increased area under the serum insulin curve during an oral glucose tolerance test (P = 0.03) and elevated fasting plasma glucose (P = 0.02) in homozygous Ala92 allele carriers, the latter strengthened by epistasis with the ADRB2 Gly16Arg variant in a double recessive model (P = 0.004). However, after permutation procedure, performed to correct for multiple hypothesis testing, the associations did not reach study-wide significance. CONCLUSIONS: The DIO2 Thr92Ala variant does not confer an increased risk of T2D, obesity, or insulin resistance.

Adult↗

PubMed2006

Association between neuromedin U gene variants and overweight and obesity.

BACKGROUND: Neuromedin U (NMU) is an anorexic neuropeptide expressed in the hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice overexpressing Nmu are hypophagic and lean. OBJECTIVE: Our objective was to investigate whether variants in NMU are associated with human obesity. DESIGN: The coding region of NMU was analyzed for variants in obese Czech children and obese Danish adults. Identified missense variants were investigated for cosegregation with obesity in families or association with obesity in the general population. SETTING: The study was performed at Steno Diabetes Center, Denmark, and Department of Pediatrics, Charles University, Czech Republic. SUBJECTS AND METHODS: A total of 289 Czech children and adolescents with early-onset obesity and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean and unrelated Czech subjects. RESULTS: The rare NMU Arg165Trp variant cosegregated with childhood obesity in a Czech family. Homozygous carriers of the Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2-0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval, 0.7-1.1) among 3265 overweight and obese subjects (body mass index >or= 25 kg/m2) [odds ratio, 2.5 (1.2-5.3); P = 0.01]. CONCLUSION: Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.

Adolescent↗

PubMed2006

Variation in CAPN10 in relation to type 2 diabetes, obesity and quantitative metabolic traits: studies in 6018 whites.

The first type 2 diabetes (T2D) gene to be identified in a genome wide scan followed by positional cloning was CAPN10 encoding the cysteine protease calpain-10. Subsequently, a large number of studies have investigated variation in CAPN10 in relation to T2D. Two CAPN10 single nucleotide polymorphisms (SNPs), the SNP43 (rs3792267) and the SNP44 (rs2975760), have been associated with T2D in some, but not all studies conducted in a wide range of ethnicities. We investigated the two SNPs for association with T2D in a relatively large, homogenous population of Danish whites (n = 1359 T2D cases, n = 4659 normoglycemic and glucose-tolerant control subjects), however, no significant associations of the SNP43 or the SNP44 variant with T2D were found. Neither were the two variants associated with obesity, and no association of either variant with diabetes-related quantitative traits was found in a study involving a population-based sample of 5698 middle-aged subjects. Meta-analyses, however, of the present and previously published studies involving 15,368 (SNP43) or 13,628 (SNP44) subjects yielded odds ratios of 1.09 (95% CI 1.02-1.16, p = 0.007) and 1.15 (1.07-1.23, p = 0.0002), respectively, for association with T2D. In conclusion, in a relatively large study sample of whites we found no consistent evidence of association of the CAPN10 SNP43 or SNP44 with T2D, obesity, or related quantitative traits, although meta-analyses of these two CAPN10 SNPs demonstrated an association with T2D.

Blood Glucose↗

PubMed2006

Increase in incidence of hyperthyroidism predominantly occurs in young people after iodine fortification of salt in Denmark.

CONTEXT: To prevent goiter and nodular hyperthyroidism, iodine fortification (IF) of salt was introduced in Denmark in 1998. We prospectively registered all new cases of overt hyperthyroidism in two areas of Denmark before and for the first 6 yr after iodine fortification. METHODS: We used a computer-based register of all new cases of hyperthyroidism in two population subcohorts with moderate iodine deficiency (Aalborg, n = 310,124) and mild iodine deficiency (Copenhagen, n = 225,707), respectively. Data were obtained 1) before IF (1997-1998); 2) during voluntary IF (1999-2000); 3) during the early (2001-2002) period of mandatory IF; and 4) during the late (2003-2004) period with mandatory IF. RESULTS: The overall incidence rate of hyperthyroidism increased [baseline, 102.8/100,000/year; voluntary IF, 122.8; early mandatory IF, 140.7; late mandatory IF, 138.7 (P for trend <0.001)]. Hyperthyroidism increased in both sexes (P < 0.001) and in all age groups: 0-19, 20-39, 40-59, and 60+ yr (P for trend <0.001). The increase was relatively highest in young adults aged 20-39 yr: late mandatory IF (percent increase from baseline), age 20-39, 160%, P < 0.001; age 40-59, 29%, P < 0.01; age 60+ yr, 13%, P = not significant. CONCLUSION: Even a cautious iodization of salt results in an increase in the incidence rate of hyperthyroidism. Contrary to current concepts, many of the new cases were observed in young subjects, and are presumably of autoimmune origin. Furthermore, monitoring is expected to show a decrease in the number of elderly subjects suffering from nodular hyperthyroidism.

Adolescent↗

PubMed2006

The association between atopy and factors influencing folate metabolism: is low folate status causally related to the development of atopy?

BACKGROUND: Deficiency of folate has been associated with several disorders characterized by enhanced activation of the cellular immune system (non-allergic th1 type immune response). Whether folate status is also associated with atopic disease (allergic th2 type immune response) is unknown. We aimed at examining the association between atopy and markers of impaired folate metabolism, i.e. MTHFR(C677T) genotype, plasma total homocysteine, and dietary intakes of methionine, folates, and vitamins B12, B6, and B2. METHODS: Cross-sectional population-based study of 1,671 male and female residents of Copenhagen County, Denmark, aged 30-60 years participating in a health examination during 1999-2001. Atopy was defined as positive levels of specific IgE against a panel of inhalant allergens. MTHFR(C677T) genotype was determined by PCR followed by restriction fragment length polymorphism analyses. Total homocysteine was measured by fluorescent polarization immunoassay. Dietary vitamin intakes were estimated from a semi-quantitative food frequency questionnaire. RESULTS: The prevalence of atopy was associated with MTHFR(C677T) genotype. TT individuals had a significantly higher risk of atopy compared with CC/CT individuals [odds ratio 1.76, 95% confidence interval (95% CI) 1.19-2.60]. Additionally, gene-diet interaction effects were identified. Dietary markers were negatively associated with risk of atopy in persons with the TT genotype. Total homocysteine was not related to atopy (odds ratio per 5 mumol/l = 1.12, 95% CI 0.98-1.29). CONCLUSIONS: The results suggest that an impaired folate metabolism may be causally related to the development of atopy.

Adult↗

PubMed2006

Model of hospital-supported discharge after stroke.

BACKGROUND AND PURPOSE: Readmission rate within 6 months after a stroke is 40% to 50%. The purpose of the project was to evaluate whether an interdisciplinary stroke team could reduce length of hospital stay, readmission rate, increase patient satisfaction and reduce dependency of help. METHODS: One hundred and ninety-eight patients with acute stroke were randomized into 103 patients whose discharge was supported by an interdisciplinary stroke team and 95 control patients who received standard aftercare. Baseline characteristics were comparable in the 2 groups. The patients were evaluated after 6 and 12 months regarding functional status and need for help. RESULTS: Length of hospital admission was insignificantly shorter in the intervention compared with the control group (35.2 versus 39.8 days). There was no significant difference in readmission, GP-visits, and primary health care services. Furthermore, there was no significant difference in functional scores or patient satisfaction. CONCLUSIONS: In this setting we could not show benefit of an interdisciplinary stroke team supporting patients at discharge perhaps because standard aftercare was very efficient already.

Aged↗

PubMed2006

Early lens aging is accelerated in subjects with a high risk of ischemic heart disease: an epidemiologic study.

BACKGROUND: Ischemic heart disease (IHD) is one of the most important causes of mortality and morbidity in the Western world. There is a relationship between aging of the lens of the human eye and cardiovascular disease. The present study was conducted to examine if the risk of ischemic heart disease could be estimated by fluorophotometric assessment of lens aging. METHODS: A total of 421 subjects were included. Risk of IHD was estimated from non-ocular data using the Precard software. Lens aging was quantified by lens fluorometry. RESULTS: The risk of IHD was strongly related to lens fluorophore accumulation (p = 0.001). The relationship between IHD and lens aging was attributable to tobacco smoking and dysglycemia. CONCLUSION: The risk of ischemic heart disease related to smoking and diabetes mellitus can be estimated using the aging of the lens of the eye as a biomarker for generalized tissue-damage.

Adult↗

PubMed2006

Serum ionised calcium and cardiovascular disease in 45-years old men and women followed for 18 years.

UNLABELLED: High level of total serum calcium within the normal range has been associated with increased cardiovascular risk. We wanted to evaluate whether the physiological active ionised form of calcium also was a risk factor for cardiovascular disease (CVD). METHODS: A total of 974 participants from a health survey in 1981 in Copenhagen had ionised serum calcium and different cardiovascular risk factors measured. The participants were followed until 1999 in The National Hospital Patients Registry and The National Death Registry in Denmark regarding the diagnosis ischemic heart disease (IHD) and a broader definition of CVD. Persons with ionised serum calcium in the highest quintile were compared with persons in the lower four quintiles. RESULTS: In a univariate analysis persons with ionised serum calcium in the highest quintile had increased risk of IHD (p=0.001) and CVD (p=0.02) compared to persons in the lower quintiles. The increased risk disappeared when gender and cardiovascular confounders were included in a Cox proportional hazards analysis (p=0.20 for IHD and p=0.50 for CVD, respectively). In a separate analysis of men and IHD the result remained insignificant (p=0.07). CONCLUSIONS: Serum ionised calcium in the upper quintile in women and men together did not seem to be a risk factor in development of IHD and CVD, but a non-significant tendency towards increased risk of IHD was observed in men with ionised calcium in the upper quintile compared to men in the lower four quintiles.

Calcium↗

PubMed2006

Mental vulnerability--a risk factor for ischemic heart disease.

OBJECTIVE: The purpose of this study is to examine whether mental vulnerability is a risk factor for the development of ischemic heart disease (IHD) after adjustment for well-established risk factors. METHODS: In three prospective cohort studies in Copenhagen County, Denmark, we recorded the level of mental vulnerability and possible risk factors to IHD at baseline. For follow-up, the sample was linked to relevant registries to identify all cases of fatal and nonfatal IHD. The relationship between mental vulnerability and IHD was examined using both Kaplan-Meir and Cox proportional hazard models adjusting for possible confounding factors. RESULTS: Mental vulnerability was significantly associated with the risk for IHD (medium mental vulnerability: hazard ratio 1.41, 95% confidence interval 1.04-1.91; and high mental vulnerability: hazard ratio 2.05; 95% confidence interval 1.46-2.88), after adjusting for confounders. CONCLUSION: Our results imply that mental vulnerability is an independent risk factor for IHD.

Adult↗

PubMed2006

Doing mini-health technology assessments in hospitals: a new concept of decision support in health care?

OBJECTIVES: The purpose of this project was to evaluate local decision support tools used in the Danish hospital sector from a theoretical and an empirical point of view. METHODS: The use of local decision support was evaluated through questionnaires sent to all county health directors, all hospital managers, and all heads of clinical departments in cardiology, orthopedic surgery, and intensive care. In addition, respondents were asked to submit whatever decision support tools they were using (including mini-HTAs, other forms or checklists, and special procedures for decision making concerning new health technologies). A theoretical analysis of the decision support tools (decision theory) was performed as well as a comparison with the business case method used in private companies. Finally, the Danish mini-HTA was compared with foreign production and use of HTA and HTA-like assessments as local decision support. RESULTS: The response rate was high (87 percent, 94 percent, 85 percent, respectively). We collected sixty different forms (of which forty-nine were mini-HTAs) and twenty variants of written procedures. We found theoretical and empirical evidence that local involvement in the process of making the HTA could be important for the use of the results from the HTA and for the process of implementing the new technology. CONCLUSIONS: Doing mini-HTA in hospitals seems to balance the need for quality and depth with the limited time and resources for assessment.

Decision Support Techniques↗

PubMed2006

Representativeness in population-based studies: a detailed description of non-response in a Danish cohort study.

BACKGROUND: Decreasing rates of participation in population-based studies increasingly challenge the interpretation of study results, in both analytic and descriptive epidemiology. Consequently, estimates of possible differences between participants and non-participants are increasingly important for the interpretation of study results and generalization to the background population. METHODS: An age-specific, population-based cohort of 1,198 individuals was examined at age 40, 45, 51, and 60. Participants were compared with non-participants and when possible also with the background population using a wide range of detailed information on somatic and mental health collected at each examination, including data from a clinical examination, biochemical measurements, questionnaires, interviews, and public registers. RESULTS: Participation rates were higher than 80% at examinations at age 40, 45, and 51, but decreased to 65% at age 60. At the baseline investigation at age 40, analyses indicated that participants were representative of the cohort as well as the background population. However, the mortality rate was higher among non-participants in the succeeding 20 years. Among living cohort members at the 60-year examination, non-participants had lower socioeconomic status, higher hospitalization rate, and a worse overall health profile than participants. CONCLUSIONS: The detailed data presented reinforce the contention that the health profile of non-participants is typically worse than that of participants. The results also indicate that while data from public registers give easily accessible information about non-participants, these crude proxy measures of health may not be enough to document representativeness.

Adult↗

PubMed2006

Association between dietary glycemic index, glycemic load, and body mass index in the Inter99 study: is underreporting a problem?

BACKGROUND: The few studies examining the potential associations between glycemic index (GI), glycemic load (GL), and body mass index (BMI) have provided no clear pictures. Underreporting of energy intake may be one explanation for this. OBJECTIVE: We examined the associations between GI, GL, and BMI by focusing on the confounding factor of total energy intake and the effect of exclusion of low energy reporters (LERs). DESIGN: This was a cross-sectional study of 6334 subjects aged 30-60 y. Dietary intake was estimated from a food-frequency questionnaire. GI and GL were estimated by using white bread as the reference food. Underreporting of energy intake was assessed as reported energy intake divided by basal metabolic rate (EI/BMR); LERs were defined as those having an EI/BMR < 1.14. Univariate and multiple linear regression models were used to test for associations between GI, GL, and BMI. The confounders were sex, age, smoking, physical activity, alcohol intake, and energy intake. All analyses were conducted on 1) the entire population and 2) a subsample excluding LERs. RESULTS: In the univariate analyses of the entire population, GL was inversely associated with BMI. No association was observed for GI. After full adjustment (including energy intake), both GI and GL were positively associated with BMI. When LERs were excluded, GL was positively associated with BMI in all analyses, and GI was positively associated with BMI in the multiple analyses. CONCLUSIONS: We showed a positive association between GI, GL, and BMI. Energy adjustment and the exclusion of LERs significantly affected the results of the analysis; thus, we stress the importance of energy adjustment.

Adult↗

PubMed2006

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors.

BACKGROUND: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. METHODS: In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. RESULTS: Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). CONCLUSION: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.

Adult↗

PubMed2006

Lack of association between thyroid autoantibodies and parity in a population study argues against microchimerism as a trigger of thyroid autoimmunity.

BACKGROUND: Thyroid autoimmunity is more common in females than in males. One possible explanation for this female preponderance may be the effect of oestrogens on the immune system. It has also been suggested that foetal microchimerism involving transfer of foetal cells into maternal tissue during pregnancy may play an important role. OBJECTIVE: We investigated the association between the presence of circulating thyroid autoantibodies and previous pregnancy, parity and the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) in a population cohort. METHODS: We examined 3712 women randomly selected from the general population. Serum was analysed for thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) using assays based on an RIA technique (DYNO test). Data were analysed in logistic regression models to adjust for possible confounders. Women previously treated for thyroid disease or with pregnancy within 1 year prior to the study were excluded from the analyses. RESULTS: In both univariate and multivariate models and whether the presence of TPO-Ab and Tg-Ab was investigated alone or in combination, findings were negative with respect to an association between circulating thyroid antibodies and previous pregnancy, number of pregnancies, parity and previous abortion. There was no association between thyroid autoantibodies and use of OCs. Women aged 60-65 years receiving HRT now or previously had a lower prevalence of Tg-Ab (univariate, P = 0.01; multivariate, P = 0.02). No such association was observed between HRT and TPO-Ab. CONCLUSION: In this population study there was no association between previous pregnancy, parity and thyroid antibodies, which argues against the role of microchimerism as a trigger of thyroid autoimmunity. Exogenous oestrogens may reduce aspects of autoimmunity.

Adolescent↗

PubMed2006

The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives.

OBJECTIVE: Denmark was an area of iodine deficiency, and mandatory iodine fortification of table salt and salt in bread (13 p.p.m. iodine) was initiated in 2000/2001. The Danish investigation on iodine intake and thyroid disease (DanThyr) is the monitoring of the iodine fortification program. DESIGN AND METHODS: DanThyr consists of three main parts: a study of population cohorts initialized before (n=4649) and after (n=3570) iodization of salt, a prospective identification of incident cases of overt hyper- and hypothyroidism in a population of around 550,000 people since 1997, and compilation of data from the national registers on the use of thyroid medication, thyroid surgery, and radioiodine therapy. Studies were carried-out in parallel in subcohorts living in areas with differences in iodine content of ground water. RESULTS: The study showed profound effects of even small differences in iodine intake level on the prevalence of goiter, nodules, and thyroid dysfunction. Mild and moderate iodine deficiency was associated with a decrease in serum TSH with age. Other environmental factors were also important for goiter development (increase in risk, smoking and pregnancy; decrease in risk, oral contraception and alcohol consumption), and the individual risk depended on the genetic background. Environmental factors had only a minor influence on the prevalence of thyroid autoantibodies in the population. There were more cases of overt hypothyroidism in mild than in moderate iodine deficiency caused by a 53% higher incidence of spontaneous (presumably autoimmune) hypothyroidism. On the other hand, there were 49% more cases of overt hyperthyroidism in the area with moderate iodine deficiency. The cautious iodine fortification program, aiming at an average increase in iodine intake of 50 mug/day has been associated with a 50% increase in incidence of hyperthyroidism in the area with the most severe iodine deficiency. The incidence is expected to decrease in the future, but there may be more cases of Graves' hyperthyroidism in young people. CONCLUSION: A number of environmental factors influence the epidemiology of thyroid disorders, and even relatively small abnormalities and differences in the level of iodine intake of a population have profound effects on the occurrence of thyroid abnormalities. Monitoring and adjustment of iodine intake in the population is an important part of preventive medicine.

Adult↗