The ß(2)-adrenergic receptor (ADRB2) influences regulation of energy balance by stimulating catecholamine-induced lipolysis in adipose tissue. The rare functional ADRB2rs1800888(Thr164Ile) polymorphism could therefore influence risk of obesity and subsequently diabetes.
We tested the hypothesis that the ADRB2rs1800888(Thr164Ile) polymorphism associates with risk of obesity and diabetes and compared effect sizes with those of FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238).
We conducted a population-based cohort study in Copenhagen, Denmark.
We genotyped more than 64,000 individuals from the Danish general population.
We evaluated body mass index (BMI), obesity (BMI =30 kg/m(2)), and diabetes.
Rare allele frequencies were 0.02 for T for ADRB2rs1800888(Thr164Ile), 0.40 for A for FTOrs9939609, 0.25 for C for MC4Rrs17782313, and 0.20 for T for TMEM18rs6548238. For rare vs. common homozygotes, odds ratio for obesity was 3.32 (95% confidence interval = 1.08-10.19) for ADRB2rs1800888(Thr164Ile), 1.42 (1.35-1.52) for FTOrs9939609, 1.18 (1.06-1.30) for MC4Rrs17782313, and 1.28 (1.10-1.50) for TMEM18rs6548238 (common vs. rare). Corresponding odds ratios for diabetes were 1.85 (0.24-14.29), 1.22 (1.07-1.39), 0.96 (0.80-1.16), and 1.61 (1.17-2.22), respectively. After adjustment for BMI, only TMEM18rs6548238 remained associated with diabetes. BMI was increased in rare vs. common homozygotes in FTOrs9939609, MC4Rrs17782313, and TMEM18rs6548238 (common vs. rare) but not in ADRB2rs1800888(Thr164Ile).
Our results suggest that ADRB2rs1800888(Thr164Ile) rare vs. common homozygotes are not significantly associated with an increase in BMI measured continuously but may be associated with an increased risk of obesity. Also, TMEM18rs6548238 associated with risk of diabetes after adjustment for BMI. These findings need confirmation in other studies.
During the past 15 years there has been an exponential increase in the number of prescriptions for lipid-lowering drugs. Uncertainties remain about the long-term impact of these medications on cancer, which is particularly bothersome given that the duration of these treatments may extend for several decades.
To explore the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence.
Using the administrative health databases of the Régie de l'Assurance-Maladie du Québec we performed a nested case-control study. We selected a cohort of 6721 beneficiaries of the health care plan of Quebec who were free of cancer for at least 1 year at cohort entry, 65 years and older, and treated with lipid-modifying agents. Cohort members were selected between 1988 and 1994 and were followed up for a median period of 2.7 years. From the cohort, 542 cases of first malignant neoplasm were identified, and 5420 controls were randomly selected. Users of HMG-CoA reductase inhibitors were compared with users of bile acid-binding resins as to their risk of cancer. Specific cancer sites were also considered.
Users of HMG-CoA reductase inhibitors were found to be 28% less likely than users of bile acid-binding resins to be diagnosed as having any cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific cancer sites under study were found to be not or inversely associated with the use of HMG-CoA reductase inhibitors.
The results of our study provide some degree of reassurance about the safety of HMG-CoA reductase inhibitors.
Comment In: Arch Intern Med. 2001 Jun 11;161(11):146011386902
INTRODUCTION: Publications on prospective follow-up studies of Danish child psychiatric cohorts are scarce. Such studies are necessary in order to be able to inform patients about the natural course and prognosis of child psychiatric disorders. MATERIALS AND METHODS: Baseline data is obtained from 110 children, ie. 91 boys and 19 girls (4-13 years old) assessed in 2 child and adolescent psychiatric outpatient clinics in Denmark. As part of the baseline assessment, the children were clinically diagnosed and covered most of the child psychopathological spectrum. Baseline information included demographic data, assessment of symptom-load by means of The Child Behavior Checklist (CBCL) and a global function score. The children in the cohort were assessed once a year using the CBCL and the Teachers Report Form (TRF). RESULTS: The symptom-load is declining, although still high during the follow-up period. The decline in total behaviour problem scores was greater in the group of children diagnosed with emotional and behavioural disorders compared to those with neuropsychiatric disorders (Attention deficits and Autism spectrum disorders). CONCLUSION: In spite of the relatively small sample size, this follow-up study identifies important issues of prognostic value in this clinical child psychiatric outpatient population. The material may be useful as a 'treatment as usual' group in future clinical outcome studies.
OBJECTIVE: Schizophrenia is associated with a shortened life expectancy and increased somatic comorbidity with, e.g., cardiovascular disorders. One major risk factor for these disorders is the metabolic syndrome, which has been reported to have a higher frequency in schizophrenic patients. Our objective was to study the prevalence of metabolic syndrome in a population-based birth cohort. METHOD: The study sample consisted of 5613 members of the Northern Finland 1966 Birth Cohort who participated in the field study from 1997 to 1998. Subjects were divided into 4 diagnostic categories (DSM-III-R): (1) schizophrenia (N = 31), (2) other functional psychoses (N = 22), (3) nonpsychotic disorders (N = 105), and (4) no psychiatric hospital treatment (N = 5455, comparison group). Subjects were assessed for the presence of metabolic syndrome according to the criteria of the National Cholesterol Education Program. RESULTS: The prevalence of metabolic syndrome was higher in subjects with schizophrenia compared with the comparison group (19% vs. 6%, p = .010). The prevalence of metabolic syndrome in subjects with other psychoses was 5%. After controlling for sex, the results of logistic regression analysis showed that the risk of metabolic syndrome in schizophrenia was 3.7 (95% CI = 1.5 to 9.0). CONCLUSIONS: The high prevalence of metabolic syndrome in schizophrenia even at such a relatively young age underscores the need to select antipsychotic medications with no or little capability to induce metabolic side effects. Also, developing comprehensive efforts directed at controlling weight and diet and improving physical activity are needed.
5-a reductase inhibitors (5-ARI) have been suggested to increase the risk of male breast cancer. The aim of this study was to study the risk of breast cancer in men on 5-ARI, in men with benign prostatic hyperplasia (BPH) not on 5-ARI, and in men without BPH.
We performed a population-based cohort study in Sweden with data from The Prescribed Drug Register, The Patient Register, and The Cancer Register. Men on 5-ARI, men on a-blockers, or men who had undergone a transurethral resection of the prostate (TUR-P) prior to or during 2006-2008 were included as exposed to BPH and a specific treatment thereof. For each exposed man, five unexposed men were selected. Risk of breast cancer was calculated in Cox proportional hazard models.
There were 124,183 exposed men and 545,293 unexposed men, and during follow-up (median 6 years), 99 men with breast cancer were diagnosed. Compared to unexposed men, men on 5-ARI had a hazard ratio (HR) of breast cancer of 0.74 (95% confidence interval (CI) 0.27-2.03), men on a-blockers had HR 1.47 (95% CI 0.73-2.95), and men with a TUR-P had HR 1.99 (95% CI 1.05-3.75).
No increased risk of breast cancer was observed for men on 5-ARI. However, the increased risk of breast cancer among men who had undergone a TUR-P, a strong indicator of BPH, suggests that the endocrine milieu conducive to BPH is associated with male breast cancer.
Cites: Cancer Causes Control. 2014 Nov;25(11):1577-8225135615
Cites: N Engl J Med. 2003 Jul 17;349(3):215-2412824459
The aim was to clarify the associations among subjective symptoms, clinical signs of temporomandibular disorders (TMD), and radiographic findings in the mandibular condyles of elderly people during a 5-year follow-up.
As part of a comprehensive medical survey of a random sample born in 1904, 1909, and 1914 (Helsinki Aging Study), 364 subjects living in Helsinki participated in the dental part of the examination during 1990 and 1991; after 5 years, 103 of these were reexamined. Comprehensive data on TMD were available for 94 subjects, and radiographic data were available for 88. TMD were assessed by Helkimo's anamnestic and clinical indices, and radiographic status was assessed by panoramic radiographs.
During the 5-year follow-up, reported anamnestic symptoms of TMD for men changed little (9%); among women, the change from baseline was 42%. When the unchanged indices were compared, the gender difference was obvious. At baseline, 5% of the women, but no men, had severe signs (clinical index III) of TMD. At the end of follow-up, none showed severe signs. Comparison of radiographic findings between baseline and follow-up showed no differences, nor did differences appear in associations between radiographic findings and anamnestic or clinical indices.
During the 5-year follow-up, signs and symptoms of TMD in these elderly individuals became milder or vanished. The radiographic status of the condyles remained stable, and no association appeared between radiographic findings and signs and symptoms of TMD.
In a longitudinal cohort study, organizational climate and long-term effects of exposure to nasty teasing (aggression) at work were investigated. The baseline consisted of a representative sample of Danish employees in 1995 with a response rate of 80% (N = 5,652). Of these, 4,647 participated in the follow-up in 2000 (response rate 84%). In 1995, 6.3% were subjected to nasty teasing with no significant gender difference. At baseline, we found significant associations among nasty teasing, a negative organizational climate, and psychological health effects. In the follow-up analyses, associations were found between exposure to nasty teasing at baseline and psychological health problems at follow-up, even when controlled for organizational climate and psychological health at baseline and nasty teasing at follow-up. Stratified for gender, the follow-up associations were significant for women but not for men. Low coworker support and conflicts at baseline and teasing at follow-up mediated the effects on men.
OBJECTIVES: Previous studies have suggested that abnormal levels of cortisol and testosterone might increase the risk of serious somatic diseases. To test this hypothesis, we conducted a 5-year follow-up study in middle-aged men. METHODS: A population-based cohort study conducted in 1995 amongst 141 Swedish men born in 1944, in whom a clinical examination supplemented by medical history aimed to disclose the presence of cardiovascular disease (CVD) (myocardial infarction, angina pectoris, stroke), type 2 diabetes and hypertension were performed at baseline and at follow-up in the year 2000. In addition, salivary cortisol levels were measured repeatedly over the day. Serum testosterone concentrations were also determined. Using the baseline data, an algorithm was constructed, which classified the secretion pattern of cortisol and testosterone from each individual as being normal or abnormal. RESULTS: By the end of follow-up, men with an abnormal hormone secretion pattern (n = 73) had elevated mean arterial pressure (P = 0.003), fasting insulin (P = 0.009) and insulin : glucose ratio (P = 0.005) compared with men with a normal secretion pattern (n = 68). Body mass index, waist circumference, and waist : hip ratio were significantly elevated in both groups. However, the 5-year incidence of CVD, type 2 diabetes, and hypertension were significantly higher (P
PURPOSE: To examine the age- and gender-specific 5-year incidence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) in citizens of Reykjavik. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: The cohort was a population-based random sample of citizens 50 years and older. Of 1379 eligible subjects, 1045 had a baseline examination in 1996; 846 of the 958 survivors (88.2%) had a 5-year follow-up examination in 2001. METHODS: The incidence of various characteristics of drusen and pigmentary changes that are typical of ARM were determined using the international classification and grading system for ARM and AMD. MAIN OUTCOME MEASURES: Early ARM and AMD were assessed by masked grading of stereo fundus photographs. RESULTS: Hypopigmentation developed at 5 years in 10.7% of people 50 to 59 years of age (95% confidence interval [CI], 6.9-14.4) and in 25.7% those 70 to 79 years of age (95% CI, 18.4-33.0) at baseline. Age-related macular degeneration developed in no one who was 50 to 59 years of age at baseline. Geographic atrophy (GA) developed in 4.6% (95% CI, 1.2-7.9) and exudative AMD in none of those who were 70 years and older at baseline. CONCLUSIONS: Geographic atrophy is the predominant type of AMD in Iceland, and the ratio of GA to neovascular AMD is higher than in racially similar populations.
To determine whether birth and care in the highest-level hospitals (level III) compared with birth in or postnatal transfer to lower-level hospitals (level II) are associated with 5-year morbidity in very preterm children.
A cohort study.
All surviving 5-year-old children born very preterm (gestational age