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Biomedical subjects

Torben Jørgensen

Publications and source records attributed to Torben Jørgensen.

At least 37 records · Page 2Linked to original sources

The association between hypoechogenicity or irregular echo pattern at thyroid ultrasonography and thyroid function in the general population.

OBJECTIVE: Patients with overt hypothyroidism show decreased echogenicity of the thyroid at ultrasonography (US). The aim of this study was to investigate the association between echogenicity of the thyroid/irregular echo pattern, and thyroid function in the general population, i.e. subjects without overt thyroid disease. DESIGN: A cross-sectional investigation of 4649 randomly selected adult subjects. METHODS: Blood samples were analysed for serum TSH, thyroid hormones and thyroid autoantibodies. US of the thyroid was performed. RESULTS: Participants with decreased echogenicity (n=379) had a higher mean TSH (1.65 mU/l) compared with subjects with normal echogenicity (1.21 mU/l, P<0.0001). The association was stronger in subjects with markedly decreased echogenicity (4.20 mU/l, P<0.0001). A similar association was seen when the subjects were divided into subgroups according to the level of TSH; more subjects with high levels of TSH had decreased echogenicity (P<0.0001). Likewise, more subjects with high levels of TSH had an irregular echo pattern (P<0.0001). Subjects with decreased echogenicity had a higher risk of having thyroid autoantibodies than subjects without decreased echogenicity (P<0.0001). This association was stronger when echogenicity was markedly decreased. CONCLUSIONS: We demonstrated an association between hypoechogenicity at thyroid US and higher levels of serum TSH even in subjects without overt thyroid disease, suggesting decreased echogenicity as an early sign of thyroid dysfunction. Irregular echo pattern, whether accompanied by hypoechogenicity or not, was another possible marker of thyroid failure. This indicates a possible use of thyroid US in detecting early and subclinical thyroid dysfunction.

Adolescent↗

A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes.

Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp of the P2 promoter and the associated exon 1D of HNF4A for variations associated with diabetes in 114 patients with type 2 diabetes, 72 MODYX probands, and 85 women with previous gestational diabetes mellitus. A -192c/g mutation was found in five patients. We screened 1,587 diabetic subjects and 4,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total cholesterol compared with matched control subjects. Furthermore, the mutation disrupted the binding of an unidentified sequence-specific DNA binding complex present in human islet extracts. Also, two novel linked polymorphisms in the P2 promoter at positions -1107g/t and -858c/t were identified. These variants were not significantly associated with type 2 diabetes or any pre-diabetic traits. In conclusion, a rare, novel mutation that disrupts a protein binding site in the pancreatic HNF4A promoter associates with late-onset diabetes.

Adult↗

The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility: the DAMAGE study.

The short-chain l-3-hydroxyacyl-CoA dehydrogenase (SCHAD) protein is involved in the penultimate step of mitochondrial fatty acid oxidation. Previously, it has been shown that mutations in the corresponding gene (HADHSC) are associated with hyperinsulinism in infancy. The presumed function of the SCHAD enzyme in glucose-stimulated insulin secretion led us to the hypothesis that common variants in HADHSC on chromosome 4q22-26 might be associated with development of type 2 diabetes. In this study, we have performed a large-scale association study in four different cohorts from the Netherlands and Denmark (n = 7,365). Direct sequencing of HADHSC cDNA and databank analysis identified four tagging single nucleotide polymorphisms (SNPs) including one missense variant (P86L). Neither the SNPs nor haplotypes investigated were associated with the disease, enzyme function, or any relevant quantitative measure (all P > 0.1). The present study provides no evidence that the specific HADHSC variants or haplotypes examined do influence susceptibility to develop type 2 diabetes. We conclude that it is unlikely that variation in HADHSC plays a major role in the pathogenesis of type 2 diabetes in the examined cohorts.

3-Hydroxyacyl CoA Dehydrogenases↗

Hypertension is associated with an increased risk for hysterectomy: a Danish cohort study.

OBJECTIVE: To assess whether hypertension is a risk factor for hysterectomy, endometrial resection, and myomectomy. STUDY DESIGN: Self-report questionnaires were collected from 81% of 1959 Danish women aged 30 or 40 years selected at random in 1976-1991, in four different cohort studies. Baseline data included standardized information about cardiovascular diseases, hypertension, use of medicine, gynecologic history, social background, and life style factors. Weight, height and blood pressure were measured. The women were followed via central registers to assess the incidence of hysterectomy, endometrial resection, and myomectomy performed for benign diagnoses. Cox regression analyses were used to control for confounding. RESULTS: The average time to follow-up was 15 years, and 135 operations performed for benign diagnoses were identified. Women with a history of hypertension had a double risk of having an operation compared to women without hypertension, independent of confounders. CONCLUSION: Hypertension seems to be a risk factor for hysterectomy performed for benign diagnoses, and thus contributes to women undergoing hysterectomy having an increased risk of cardiovascular diseases. It might be relevant to pay increased attention to the blood pressure in candidates for hysterectomy, as optimal antihypertensive treatment could decrease their otherwise increased risk of cardiovascular disease years after hysterectomy.

Adult↗

N-terminal pro brain natriuretic peptide is inversely related to metabolic cardiovascular risk factors and the metabolic syndrome.

We wanted to investigate the relationship of N-terminal pro brain natriuretic peptide (Nt-proBNP) to metabolic and hemodynamic cardiovascular (CV) risk factors in the general population. From a population-based sample of 2656 people 41, 51, 61, or 71 years of age, we selected 2070 patients without previous stroke or myocardial infarction who did not receive any CV, antidiabetic, or lipid-lowering treatment in 1993 to 1994. Traditional CV risk factors, 24-hour blood pressures, left ventricular (LV) mass, and ejection fraction by echocardiography, pulse wave velocity, urine albumin/creatinine ratio (UACR), and serum Nt-proBNP were measured in 1993 to 1994. The metabolic syndrome was defined in accordance with the definition of the European Group for the Study of Insulin Resistance (EGIR). Higher log(Nt-proBNP) was in multiple regression analysis related to female gender (beta=-0.37), older age (beta=0.32), higher clinic pulse pressure (beta=0.20), lower serum total cholesterol (beta=-0.15), lower LVEF (beta=-0.08, all P<0.001), lower log(serum insulin) (beta=-0.07), lower log(plasma glucose) (beta=-0.06, both P<0.01, lower log(serum triglyceride) (beta=-0.06), lower body mass index (beta=-0.05); lower heart rate (beta=-0.05), higher logUACR (beta=0.04, all P<0.05) and higher log(LV mass index) (beta=0.04, P=0.07), adjusted R2=0.35, P<0.001). The metabolic syndrome was associated with lower Nt-proBNP (35 pg/mL versus 48 pg/mL; P<0.001) and shifted the positive relationship between pulse pressure and Nt-proBNP to the right (ie, higher blood pressure for a given level of Nt-proBNP). The metabolic syndrome was associated with lower Nt-proBNP levels and shifted the positive relationship between Nt-proBNP and pulse pressure to the right, creating a possible link between the metabolic syndrome and hypertension.

Adult↗

Prognosis of migraine and tension-type headache: a population-based follow-up study.

OBJECTIVE: To determine the prognosis of migraine and tension-type headache and to identify prognostic factors. METHODS: Of 740 persons (aged 25 to 64 years) examined in a 1989 Danish cross-sectional headache study, 673 were eligible for follow-up in 2001. All interviews at baseline and at follow-up were conducted by medical doctors and based on the 1988 IHS-criteria. RESULTS: A total of 549 persons (81.6%) participated in the follow-up study. Of 64 migraineurs at baseline, 42% had experienced remission, 38% had low migraine frequency, and 20% had more than 14 migraine days per year (poor outcome) at follow-up. Poor outcome was associated with high migraine frequency at baseline and age at onset younger than 20 years. Among 146 subjects with frequent episodic tension-type headache and 15 with chronic tension-type headache at baseline, 45% experienced infrequent or no tension-type headache (remission), 39% had frequent episodic tension-type headache, and 16% experienced chronic tension-type headache (poor outcome) at follow-up. Poor outcome was associated with baseline chronic tension-type headache, coexisting migraine, not being married, and sleeping problems. CONCLUSIONS: The prognosis of migraine, frequent episodic tension-type headache, and chronic tension-type headache was favorable.

Adult↗

[Epidemiology and gallstones].

Gallstones are more frequent in women than in men due to pregnancy. Increasing age, familial history of the disease, unhealthy lifestyle, overweight, dyslipidemia, type 2 diabetes and high plasma insulin levels are all associated with gallstones. Few asymptomatic stones develop complications. Asymptomatic gallstones should not be treated, but there are difficulties in delimiting the symptoms that are specific to gallstones, and persistent pain after cholecystectomy is frequent. The introduction of laparoscopic cholecystectomy has led to an increase in the cholecystectomy rate and greater regional variation.

Adult↗

Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population.

CONTEXT: Increasing prevalence of overweight in the population is a major concern globally; and in the United States, nearly one third of adults were classified as obese at the end of the 20th century. Few data have been presented regarding an association between variations in thyroid function seen in the general population and body weight. OBJECTIVE: The aim of this study was to investigate the association between thyroid function and body mass index (BMI) or obesity in a normal population. DESIGN: A cross-sectional population study (The DanThyr Study) was conducted. PARTICIPANTS: In all, 4649 participants were investigated, and 4082 were eligible for these analyses after exclusion of subjects with previous or present overt thyroid dysfunction. MAIN OUTCOME MEASURES: The study examined the association between category of serum TSH or serum thyroid hormones and BMI or obesity in multivariate models, adjusting for possible confounding. RESULTS: We found a positive association between BMI and category of serum TSH (P < 0.001) and a negative association between BMI and category of serum free T(4) (P < 0.001). No association was found between BMI and serum free T(3) levels. The difference in BMI between the groups with the highest and lowest serum TSH levels was 1.9 kg/m(2), corresponding to a difference in body weight of 5.5 kg among women. Similarly, the category of serum TSH correlated positively with weight gain during 5 yr (P = 0.04), but no statistically significant association was found with weight gain during 6 months (P = 0.17). There was an association between obesity (BMI > 30 kg/m(2)) and serum TSH levels (P = 0.001). CONCLUSIONS: Our results suggest that thyroid function (also within the normal range) could be one of several factors acting in concert to determine body weight in a population. Even slightly elevated serum TSH levels are associated with an increase in the occurrence of obesity.

Adolescent↗

The prevalence of the metabolic syndrome in a danish population of women with previous gestational diabetes mellitus is three-fold higher than in the general population.

CONTEXT: Diabetes and obesity, components of the metabolic syndrome, are common characteristics of women with prior gestational diabetes mellitus (GDM). Due to increasing incidence of diabetes and obesity, the metabolic syndrome might comprise a major health problem among these women. OBJECTIVE: The objective was to estimate the prevalence of the metabolic syndrome by three different criteria [World Health Organization 1999 (WHO), The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults 2001, and European Group for the Study of Insulin Resistance 2002] among women with previous GDM. DESIGN: We conducted a follow-up study of a Danish cohort of women admitted in 1978-1996 to the Diabetes and Pregnancy Center, Rigshospitalet, Copenhagen University Hospital, with diet-treated GDM. The follow-up took place in 2000-2002 at median 9.8 yr (interquartile range 6.4-17.2) after pregnancy. Results were compared with a control group of 1000 age-matched women from a population-based sample (Inter99). PARTICIPANTS: Four hundred eighty-one women at median age 43 yr (interquartile range 38-48) participated. MAIN OUTCOME MEASURES: The main outcome measures were body mass index (BMI), glucose tolerance, blood pressure, lipid profile, and insulin resistance. RESULTS: Independent of the criteria, the prevalence of the metabolic syndrome was three times higher in the prior GDM group, compared with the control group (e.g. WHO: 38.4 vs. 13.4%, P < 0.0005). Age- and BMI-adjusted odds ratio for having the WHO-defined metabolic syndrome was 3.4 (95% confidence interval 2.5-4.8) for the prior GDM group vs. the control group. Obese women (BMI > 30 kg/m(2)) with previous GDM had a more than 7-fold increased prevalence of the metabolic syndrome (WHO), compared with normal-weight prior GDM women (BMI < 25 kg/m(2)). In glucose-tolerant women, the prevalence was doubled in the prior GDM group, compared with control group. CONCLUSION: The prevalence of the metabolic syndrome was three times as high in women with prior diet-treated GDM, compared with age-matched control subjects.

Adult↗

Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.

The separate and combined effects of the PPARG Pro(12)Ala polymorphism and the KCNJ11 Glu(23)Lys polymorphisms on risk of type 2 diabetes were investigated in relatively large-scale, case-control studies. Separate effects of the variants were examined among 1187/1461 type 2 diabetic patients and 4791/4986 middle-aged, glucose-tolerant subjects. The combined analysis involved 1164 type 2 diabetic patients and 4733 middle-aged, glucose-tolerant subjects. In the separate analyses, the K allele of the KCNJ11 Glu(23)Lys associated with type 2 diabetes (odds ratio, 1.19; P = 0.0002), whereas the PPARG Pro(12)Ala showed no significant association with type 2 diabetes. The combined analysis indicated that the two polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and we found no evidence for a synergistic interaction between them. Analysis of a model with equal additive effects of the two variants showed that the odds ratio for type 2 diabetes increased with 1.14/risk allele (P = 0.003). Together, the two polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. In conclusion, our results showed no evidence of a synergistic interaction between the KCNJ11 Glu(23)Lys and PPARG Pro(12)Ala polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes.

Adult↗

PGC-1alpha Gly482Ser polymorphism associates with hypertension among Danish whites.

PGC-1alpha is a coactivator of numerous transcription factors and is expressed in tissues with high energy demands and abundant in mitochondria. It is induced in the myocardium on fasting and physical exercise, and cardiac-specific overexpression stimulates mitochondrial biogenesis in mice. The common Gly482Ser polymorphism of PGC-1alpha has previously shown association with arterial hypertension among Austrian men. Thus, we aimed at investigating this relationship in the Danish white population. The Gly482Ser polymorphism was genotyped in a total of 2562 Danish white subjects using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and a GenoView locked nucleic acid assay (LNA), and the relationships of this variant with blood pressure levels and arterial hypertension were analyzed. Furthermore, we performed a combined analysis of the data from the present study in combination with previously published results. The Ser/Ser genotype was significantly associated with a reduced risk of hypertension and with lower systolic, diastolic, and mean arterial blood pressure levels, predominantly among women. Finally, in a combined analysis using data obtained in both sexes, the Ser/Ser genotype group had an estimated odds ratio of 0.70 (95% confidence interval, 0.56 to 0.86) for hypertension compared with Gly/X carriers (P=0.001). In conclusion, the Ser allele of PGC-1alpha Gly482Ser confers a significantly reduced risk of hypertension in whites. Further studies are needed to elucidate the differential role of this polymorphism in men and women.

Adult↗

The functional Thr130Ile and Val255Met polymorphisms of the hepatocyte nuclear factor-4alpha (HNF4A): gene associations with type 2 diabetes or altered beta-cell function among Danes.

HNF4A encodes an orphan nuclear receptor that plays crucial roles in regulating hepatic gluconeogenesis and insulin secretion. The aim of the present study was to examine two rare missense polymorphisms of HNF4A, Thr130Ile and Val255Met, for altered function and for association with type 2 diabetes (T2D). We have examined these polymorphisms 1) by in vitro transactivation studies and 2) by genotyping the variants in 1409 T2D patients and in 4726 glucose-tolerant Danish white subjects. When tested in COS7 cells, both the Thr130Ile and the Val255Met variants showed a significant decrease in transactivation activity compared with wild-type (73% of wild-type, P = 0.02, and 76%, P = 0.04, respectively). The Thr130Ile variant had a significantly increased carrier frequency among T2D patients compared with glucose-tolerant subjects [odds ratio, 1.26 (1.01-1.57); P = 0.04]. The rare Val255Met polymorphism had a similar frequency among T2D patients and glucose-tolerant subjects. Heterozygous glucose-tolerant carriers of the variant showed, however, decreased levels of fasting serum C-peptide (76%; P = 0.03) and decreased fasting serum triglyceride (58%; P = 0.02). In conclusion, The Thr130Ile and the Val255Met polymorphisms decrease the transcriptional activity of HNF4A, and the Thr130Ile polymorphism associates with T2D, whereas the Val255Met variant associates with a decrease in fasting serum C-peptide.

Adult↗

Has the prevalence of migraine and tension-type headache changed over a 12-year period? A Danish population survey.

OBJECTIVE: The present study aims to compare the prevalence of primary headaches in Denmark in two periods as only few replicate studies have re-evaluated the prevalence of primary headaches. STUDY DESIGN AND SETTING: The 2001 study is a replicate of a cross-sectional survey of primary headaches in 1989, and compares 297 subjects aged 25-36 years from the general population, with the 294 comparable subjects invited in 1989. Medical doctors diagnosed all headaches using IHS-classification. RESULTS: The participation rate was 75% in 1989 and 70% in 2001. The prevalence of migraine did not change significantly (11-15%), while the prevalence of tension-type headache (79-87%), especially of frequent tension-type headache (29-37%) increased significantly. The prevalence of chronic tension-type headache (2-5%) tended to increase. The proportion of the migraineurs with migraine 14 days or more per year increased (12-38%). Female gender was a risk factor for both primary headaches. The majority of migraineurs (92-94%) also reported coexistent tension-type headache. CONCLUSION: The prevalence of tension-type headache but not of migraine increased. The increase in migraine and tension-type headache frequency suggests a higher individual and societal impact of primary headaches now, than 12 years ago.

Adult↗

Studies of the Gly482Ser polymorphism of the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) gene in Danish subjects with the metabolic syndrome.

The peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) is a novel transcriptional co-activator that holds an important role in lipid and glucose metabolism. PGC-1alpha is a candidate gene for the metabolic syndrome (MS) as well as type 2 diabetes. Recent studies suggested linkage between the chromosomal region of PGC-1alpha and fasting serum insulin levels, and associates a Gly482Ser polymorphism of the gene with type 2 diabetes and hypertension. In this study, we investigated whether the Gly482Ser variant is associated with the MS per se or other phenotypic traits related to this syndrome. The variant was examined, using PCR-RFLP, in the DanMONICA cohort comprising a population-based sample of 2349 subjects. MS was defined using the National Cholesterol Education Program -- Adult Treatment Panel III (NCEP-ATPIII) criteria. The allelic frequency of the Ser482 allele was 35.8% in the MS group and 35.6% in the non-MS group (P = 0.74). There were no significant differences across the three groups of genotypes with respect to any of the examined variables, including BMI, waist, fasting serum lipids, plasma glucose, serum insulin, HOMA estimates of insulin resistance and insulin secretion, 24-ambulatory blood pressure or left ventricular mass index. In conclusion, the Gly482Ser polymorphism of the PGC-1alpha gene is not associated with the metabolic syndrome, related quantitative traits or cardiac hypertrophy among Danish Caucasian subjects.

Adult↗

Smoking reduction intervention in a large population-based study. The Inter99 study.

BACKGROUND: Smoking reduction has been introduced as an alternative to smokers unable or unwilling to quit but has never been implemented in a population-based intervention. METHODS: Two thousand four hundred eight daily smokers in all motivational stages were included in a randomised population-based intervention study, in Copenhagen, Denmark. Smokers, unwilling or unable to quit, were encouraged to reduce their tobacco consumption. Furthermore, smokers in the high-intensity intervention were offered participation in smoking reduction groups. RESULTS: Twenty-three percent of those who attended both baseline and 1 year visit reported reduction by at least 5 g and 8% reported a halving or more. Halving of tobacco consumption was achieved significantly more often than in the background population, OR = 2.6 (1.6-4.4), even when assuming that non-participants had not reduced, OR = 1.7 (1.0-2.8). Reduction of at least 5 g doubled the probability of increased motivation to quit and a halving increased it more than four times. The reductions were not validated. Less than 2% attended the smoking reduction groups. CONCLUSION: The smoking reduction intervention was significant in self-reported reduction of tobacco consumption and subsequently increased motivation to quit. This may open new perspectives, with reduction as a first step towards cessation, a possible supplement to smoking cessation strategies.

Adult↗

Smoking cessation intervention in a large randomised population-based study. The Inter99 study.

BACKGROUND: Several large and well-conducted community interventions have failed to detect an effect on prevalence of smoking. METHODS: Two thousand four hundred eight daily smokers in all motivational stages were actively recruited and included in a randomised population-based intervention study in Copenhagen, Denmark. All smokers completed a questionnaire and underwent a health examination and a lifestyle consultation. Daily smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups. RESULTS: The validated abstinence rate at 1-year follow-up was 16.3% in the high intensity group and 12.7% in the low intensity group compared with a self-reported abstinence rate of 7.3% in the background population. The adjusted odds ratio of abstinence in the high intervention group was significantly higher, OR = 2.2 (1.6-3.0) than in the background population, also in the 'intention-to-treat' analyses, OR = 1.5 (1.1-2.0). Higher socioeconomic status, higher age at onset of daily smoking, and a higher wish to quit were predictors of success. CONCLUSION: In a population-based setting, using active recruitment and offering assistance to quit, it was possible to include many smokers and to achieve a significantly higher validated abstinence in the high intensity intervention than in the background population, even when using 'intention-to-treat' analyses.

Adult↗