Disclosure of Type 1 diabetes at work among Finnish workers.

AIMS: To determine which self-management factors and psychosocial work factors were associated with disclosing diabetes to colleagues, line managers and occupational health personnel among workers with Type 1 diabetes. METHODS: A total of 767 working-aged respondents with Type 1 diabetes completed a Finnish cross-sectional survey named 'People with Type 1 Diabetes in Worklife'. Factor analysis was carried out, followed by logistic regressions to estimate the associations between self-management factors, psychosocial work factors and the likelihood of disclosure separately to colleagues, line managers and occupational health personnel. The models were adjusted for sociodemographic, diabetes-related and work-related variables. RESULTS: A total of 52% of the respondents had disclosed their diabetes to their colleagues, 45% to occupational health personnel and 28% to their line manager. Receiving social support and having good psychosocial work ability were significantly associated with disclosure to colleagues, line managers and occupational health personnel. Relations at work were associated with disclosure to colleagues and the line manager. Furthermore, opportunity to self-manage diabetes at work was associated with disclosure to colleagues. CONCLUSIONS: Line managers and colleagues have a remarkable role to play in providing workplace support to workers with Type 1 diabetes. Disclosure of Type 1 diabetes should be encouraged as line managers can provide workers with the right support, implement work adaptations and facilitate job retention. As only half of respondents disclosed their Type 1 diabetes at work, further research is required into the reasons for and consequences of not disclosing a diagnosis.

Work ability among Finnish workers with type 1 diabetes.

BACKGROUND: Work ability represents the balance between individual resources, health status and job demands. As far as we are aware, these issues have not been examined in working people with type 1 diabetes (T1D). AIMS: To examine how work-related and diabetes-related factors are associated with work ability among male and female workers. METHODS: Questionnaires were mailed to a random sample of 2500 people with T1D from the Medication Reimbursement Register of The Social Insurance Institution of Finland. The associations of the predictors of poor work ability were examined in a logistic regression analysis. RESULTS: The final sample comprised 767 working people aged 18-64 with T1D; overall response rate 49%. One in every three working men and women with T1D had poor work ability. High job demands and low job control were associated with poor work ability in both genders. Physical work and low worktime control were significantly associated with poor work ability in men but not in women with T1D. A self-reported high value of glycosylated haemoglobin was the only diabetes-related variable associated with poor work ability in both men and women. CONCLUSIONS: Work-related factors and poor glycaemic control were associated with poor work ability in individuals with T1D. Thus, job control and worktime control should be taken into account in supporting the work ability of workers with T1D.

Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice--potential role of TRPA1 in osteoarthritis.

OBJECTIVES: Intra-articularly injected monosodium iodoacetate (MIA) induces joint pathology mimicking osteoarthritis (OA) and it is a widely used experimental model of OA. MIA induces acute inflammation, cartilage degradation and joint pain. Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation. Here, we tested the hypothesis that TRPA1 would be involved in the development of MIA-induced acute inflammation, cartilage changes and joint pain. METHODS: The effects of pharmacological blockade (by TCS 5861528) and genetic depletion of TRPA1 were studied in MIA-induced acute paw inflammation. Cartilage changes (histological scoring) and joint pain (weight-bearing test) in MIA-induced experimental OA were compared between wild type and TRPA1 deficient mice. The effects of MIA were also studied in primary human OA chondrocytes and in mouse cartilage. RESULTS: MIA evoked acute inflammation, degenerative cartilage changes and joint pain in wild type mice. Interestingly, these responses were attenuated in TRPA1 deficient animals. MIA-induced paw inflammation was associated with increased tissue levels of substance P; and the inflammatory edema was reduced by pretreatment with catalase, with the TRPA1 antagonist TCS 5861528 and with the neurokinin 1 receptor antagonist L703,606. In chondrocytes, MIA enhanced interleukin-1 induced cyclooxygenase-2 (COX-2) expression, an effect that was blunted by pharmacological inhibition and genetic depletion of TRPA1. CONCLUSIONS: TRPA1 was found to mediate acute inflammation and the development of degenerative cartilage changes and joint pain in MIA-induced experimental OA in the mouse. The results reveal TRPA1 as a potential mediator and drug target in OA.

Changes in glucose metabolism in people with different glucose metabolism disorders at baseline: follow-up results of a Finnish national diabetes prevention programme.

AIM: To examine changes in glucose metabolism (fasting and 2-h glucose) during follow-up in people with impaired fasting glucose in comparison with changes in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes at baseline, among those who participated in a diabetes prevention programme conducted in Finland. METHODS: A total of 10 149 people at high risk of Type 2 diabetes took part in baseline examination. Of 5351 individuals with follow-up ≥ 9 months, 1727 had impaired glucose metabolism at baseline and completed at least one lifestyle intervention visit. Most of them (94.6%) were overweight/ obese. RESULTS: Fasting glucose decreased during follow-up among overweight/obese people in the combined impaired fasting glucose and impaired glucose tolerance group (P = 0.044), as did 2-h glucose in people in the isolated impaired glucose tolerance group (P = 0.0014) after adjustment for age, sex, medication and weight at baseline, follow-up time and changes in weight, physical activity and diet. When comparing changes in glucose metabolism among people with different degrees of glucose metabolism impairment, fasting glucose concentration was found to have increased in those with isolated impaired glucose tolerance (0.12 mmol/l, 95% Cl 0.05 to 0.19) and it decreased to a greater extent in those with screening-detected Type 2 diabetes (-0.54 mmol/l, 95% Cl -0.69 to -0.39) compared with those with impaired fasting glucose (-0.21 mmol/l, 95% Cl -0.27 to -0.15). Furthermore, 2-h glucose concentration decreased in the isolated impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.04 to -0.60), in the combined impaired fasting glucose and impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.07 to -0.58) and in the screening-detected Type 2 diabetes group (-1.52, 95% Cl -1.96 to -1.08) compared with those in the impaired fasting glucose group (0.26 mmol/l, 95% Cl 0.10 to 0.43). Results were statistically significant even after adjustment for covariates (P < 0.001 in all models). CONCLUSIONS: Changes in glucose metabolism differ in people with impaired fasting glucose from those in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes.

Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis.

BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by ß-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful.

Family history of diabetes and effectiveness of lifestyle counselling on the cardio-metabolic risk profile in individuals at high risk of Type 2 diabetes: 1-year follow-up of the FIN-D2D project.

AIMS: To investigate whether a positive family history of diabetes is associated with the effectiveness of lifestyle counselling on cardio-metabolic risk factors and glucose tolerance status in a 1-year follow-up in a cohort of Finnish men and women at high risk for Type 2 diabetes. METHODS: Altogether, 10,149 individuals who had high risk of Type 2 diabetes participated in the implementation programme of the national diabetes prevention programme at baseline. One-year follow-up data were available for 2798 individuals without diabetes. Family history of diabetes was based on self-report. Lifestyle interventions were individual or groups sessions on lifestyle changes. The effectiveness of lifestyle intervention was measured as changes in cardiovascular risk factors, glucose tolerance status and incidence of Type 2 diabetes. RESULTS: Family history was associated with the effectiveness of lifestyle intervention in men, but not in women. During the 1-year follow-up, body weight, BMI, systolic blood pressure, total cholesterol, LDL cholesterol and score for 10-year risk for fatal cardiovascular disease (SCORE) decreased and glucose tolerance status improved more in men without a family history of diabetes than in men with a family history of diabetes. Of the participating men and women, 10% and 5% developed Type 2 diabetes, respectively. Family history was not related to the incidence of Type 2 diabetes in either gender. CONCLUSIONS: Men without a family history of diabetes were more successful in responding to lifestyle counselling with regard to cardio-metabolic measurements and glucose tolerance than those with a family history of diabetes. Similar results were not seen in women. In keeping with findings from earlier studies, the prevention of Type 2 diabetes is not influenced by a family history of diabetes.

Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes.

OBJECTIVES: To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes. DESIGN: Two observational prospective cohort studies. SETTING: Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively. SUBJECTS: Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997. RESULTS: During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes. CONCLUSIONS: IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.

Pentraxin 3 (PTX3) is associated with cardiovascular risk factors: the Health 2000 Survey.

Pentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors and to predict adverse outcomes in individuals with cardiovascular disease (CVD). Despite being a member of the same pentraxin protein family as C-reactive protein (CRP), PTX3 probably reflects different aspects of CVD pathogenesis. In this study, we assessed plasma PTX3 correlates and determinants in the Health 2000 Survey population, which comprised n = 403 insulin-resistant subjects, n = 845 hypercholesterolaemic subjects and n = 311 hypertensive subjects, all aged between 46 and 76 years. In insulin-resistant subjects the PTX3 concentration was found to correlate directly with age, pulse pressure and indoleamine 2,3-dioxygenase (IDO) enzyme activity and inversely with total and low-density lipoprotein (LDL) cholesterol. In hypercholesterolaemic subjects, the PTX3 concentration correlated directly with HDL cholesterol, systolic blood pressure and pulse pressure, whereas in hypertensive subjects, the PTX3 concentration correlated directly with systolic blood pressure, pulse pressure and IDO activity. No correlation was observed between the concentrations of PTX3 and CRP, adiposity indicators or indicators of subclinical atherosclerosis in any of the subject groups. PTX3 concentration variations were attributed to variations in LDL cholesterol and IDO activity in insulin-resistant subjects and to pulse pressure in hypercholesterolaemic and hypertensive subjects. These results indicate that, in individuals at high risk of CVD, the PTX3 concentration is associated with cardiovascular risk factors but not with subclinical atherosclerosis.

Pre-eclampsia is a risk factor of carotid artery atherosclerosis.

BACKGROUND: A history of pre-eclampsia has been shown to be associated with an increased risk of subsequent coronary artery disease. The intima-media thickness of carotid arteries and the detection of plaques are useful measures as regards preclinical atherosclerosis. The aim of this study was to examine whether women with a history of pre-eclampsia more often show signs of atherosclerosis compared with 2 control groups. METHODS: We used data from a large Finnish cross-sectional health examination survey. We had women with previous pre-eclampsia (n = 35) or pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests and physical examination were performed. Information on reproductive and medical history was obtained at the home interview. Carotid atherosclerosis was assessed by ultrasonography. RESULTS: The women with previous pre-eclampsia had significantly (p = 0.008) more atherosclerotic plaques than the healthy parous controls. The intima-media thickness in the women with previous pre-eclampsia also tended to be higher than in the other groups, although the differences did not reach statistical significance. In logistic regression analysis, advanced age (OR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI: 1.50-8.79; p = 0.004) were independent risk factors as regards plaque, and in linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010-0.014; p < 0.001), HDL cholesterol (estimate: -0.049; 95% CI: -0.088 to -0.010; p = 0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000-0.009; p = 0.043) and high-sensitivity C-reactive protein (estimate: -0.003; 95% CI: -0.007 to -0.000; p = 0.048) were independent risk factors with respect to intima-media thickness. CONCLUSIONS: Our data suggest that pre-eclampsia is an independent risk factor as regards developing plaque later in life.

Indoleamine 2,3-dioxygenase activity associates with cardiovascular risk factors: the Health 2000 study.

Indoleamine 2,3-dioxygenase (IDO) is an important immunomodulator suppressing the activation of T lymphocytes, and its level in blood is increased in several autoimmune and inflammatory diseases. We have previously shown that this activity associates with several signs and risk factors of atherosclerosis in 24 to 39-year-old females. Now we repeat this analysis in an older population (n = 921, age range 46-76 years), i.e. in a population with more advanced atherosclerosis. IDO activity had a significant positive correlation in both sexes with carotid artery intima/media thickness (IMT), an early marker of atherosclerosis. In females, a significant negative correlation with HDL cholesterol and a positive correlation with triglycerides levels was observed. The association with IMT did not remain significant after adjustment with classical risk factors of atherosclerosis. It is thus concluded that IDO is a sensitive marker of atherosclerosis--or the inflammatory response associated with it--but does not have an independent role in the pathogenesis of this disease.

Conjugated bile acids associate with altered rates of glucose and lipid oxidation after Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) induces a more favorable metabolic profile than expected by weight loss alone. In this study, we investigated the effect of RYGB on serum bile acid levels and their relation to clinical outcomes. METHODS: We included 30 obese patients who underwent RYGB (BMI = 46.1 ± 5.9 kg/m(2)). Clinical measurements and laboratory determinations were performed before surgery and 1 year after surgery. Fasting serum bile acids were measured by an enzymatic method and individual bile acids were quantified by HLPC-tandem mass spectrometry. Indirect calorimetry was performed to measure the rates of energy expenditure and substrate oxidation. RESULTS: Fasting total serum bile acid levels increased twofold after RYGB (pre, 3.68 ± 2.03 vs. post, 7.06 ± 9.65 µmol/l, +92 %, p = 0.002). This increase in total bile acids was accompanied by a decrease in conjugated bile acids, which correlated with decreased glucose oxidation (r = 0.571, p = 0.002) and with increased lipid oxidation (r = -0.626, p = 0.0004). The change in taurine-conjugated bile acids correlated with altered DIO2 mRNA expression in adipose tissue (r = -0.498, p = 0.013) potentially linking bile acid conjugation to substrate oxidation through DIO2. CONCLUSIONS: Fasting serum bile acid levels increase after RYGB. More specifically, changes in bile acid conjugation after RYGB associate with altered energy metabolism.

Association of metabolic syndrome with Alzheimer disease: a population-based study.

OBJECTIVE: To assess the association of metabolic syndrome (MetS) with Alzheimer disease (AD). METHODS: The authors derived subjects from a population-based study of 980 randomly selected elderly subjects. After exclusion of all non-Alzheimer dementia cases, the final study population included 959 subjects (337 men and 622 women) aged 69 to 78 years. The presence of MetS was defined according to the National Cholesterol Education Program (Adult Treatment Panel III) criteria, and the diagnosis of AD was based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS: Of the study subjects, 418 (43.6%) had MetS. Probable or possible AD was diagnosed in 45 subjects (4.7%). AD was more frequently detected in subjects with MetS than in subjects without MetS (7.2 vs 2.8%; p < 0.001). The prevalence of AD was higher in women with MetS vs women without the syndrome (8.3 vs 1.9%; p < 0.001), but in men with MetS, the prevalence of AD was not increased (3.8 vs 3.9%; p = 0.994). In univariate logistic regression analysis, MetS was significantly associated with AD (odds ratio [OR] 2.71; 95% CI 1.44 to 5.10). In multivariate logistic regression analysis including also apolipoprotein E4 phenotype, education, age, and total cholesterol, MetS was significantly associated with AD (OR 2.46; 95% CI 1.27 to 4.78). If only nondiabetic subjects were included in the multivariate analysis, MetS was still significantly associated with AD (OR 3.26; 95% CI 1.45 to 7.27). CONCLUSION: Metabolic syndrome is associated with Alzheimer disease in elderly subjects.

Regulation of metallothionein gene transcription. Identification of upstream regulatory elements and transcription factors responsible for cell-specific expression of the metallothionein genes from Caenorhabditis elegans.

Metallothioneins are small, cysteine-rich proteins that function in metal detoxification and homeostasis. Metallothionein transcription is controlled by cell-specific factors, as well as developmentally modulated and metal-responsive pathways. By using the nematode Caenorhabditis elegans as a model system, the mechanism that controls cell-specific metallothionein transcription in vivo was investigated. The inducible expression of the C. elegans metallothionein genes, mtl-1 and mtl-2, occurs exclusively in intestinal cells. Sequence comparisons of these genes with other C. elegans intestinal cell-specific genes identified multiple repeats of GATA transcription factor-binding sites (i.e. GATA elements). In vivo deletion and site-directed mutation analyses confirm that one GATA element in mtl-1 and two in mtl-2 are required for transcription. Electrophoretic mobility shift assays show that the C. elegans GATA transcription factor ELT-2 specifically binds to these elements. Ectopic expression of ELT-2 in non-intestinal cells of C. elegans activates mtl-2 transcription in these cells. Likewise, mtl-2 is not expressed in nematodes in which elt-2 has been disrupted. These results indicate that cell-specific transcription of the C. elegans metallothionein genes is regulated by the binding of ELT-2 to GATA elements in these promoters. Furthermore, a model is proposed where ELT-2 constitutively activates metallothionein expression; however, a second metal-responsive factor prevents transcription in the absence of metals.