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1.
  • Andersen, Zorana J., et al. (författare)
  • Long-term Exposure to Ambient Air Pollution and Incidence of Brain Tumor : the European Study of Cohorts for Air Pollution Effects (ESCAPE)
  • 2018
  • Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20:3, s. 420-432
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.Methods: In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.Results: Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89–3.14 per 10–5/m3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38–2.71 per 10–5/m3) and all other pollutants were lower for nonmalignant than for malignant brain tumors.Conclusion: We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.
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2.
  • Andersen, Zorana J., et al. (författare)
  • Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project
  • 2017
  • Ingår i: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women.METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2.5μm, ≤10μm, and 2.5–10μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m(3)}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m(3)], PMcoarse[1.20 (95% CI: 0.96, 1.49 per 5 μg/m(3)], and NO(2) [1.02 (95% CI: 0.98, 1.07 per 10 μg/m(3)], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m(3), p=0.04].CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women.
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3.
  • Beelen, Rob, et al. (författare)
  • Effects of long-term exposure to air pollution on natural-cause mortality : an analysis of 22 European cohorts within the multicentre ESCAPE project
  • 2014
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 383:9919, s. 785-795
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. Methods We used data from 22 European cohort studies, which created a total study population of 367 251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and between 10 mu m and 2.5 mu m (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buff er. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. Findings The total study population consisted of 367 251 participants who contributed 5 118 039 person-years at risk (average follow-up 13.9 years), of whom 29 076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 mu g/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I-2 p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 mu g/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 mu g/m(3) (1.07, 1.01-1.13). Interpretation Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value.
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4.
  • Fuks, Kateryna B., et al. (författare)
  • Arterial blood pressure and long-term exposure to traffic-related air pollution : an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
  • 2014
  • Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 122:9, s. 896-905
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Long-term exposure to air pollution is hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country-specific. OBJECTIVES: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. METHODS: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated with BP lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. RESULTS: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in non-medicated participants (0.35 mmHg [95% CI: 0.02-0.68] and 0.22 mmHg [95% CI: 0.04-0.40] per 4,000,000 vehicles × m/day, respectively). The estimated odds ratio for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled air pollutants and BP were not clearly associated. CONCLUSIONS: In this first comprehensive meta-analysis of European population-based cohorts we observed a weak positive association of high residential traffic exposure with BP in non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent.
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5.
  • Fuks, Kateryna B., et al. (författare)
  • Long-term exposure to ambient air pollution and traffic noise and incident hypertension in seven cohorts of the European study of cohorts for air pollution effects (ESCAPE)
  • 2017
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:13, s. 983-990
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims We investigated whether traffic-related air pollution and noise are associated with incident hypertension in European cohorts. Methods and results We included seven cohorts of the European study of cohorts for air pollution effects (ESCAPE). We modelled concentrations of particulate matter with aerodynamic diameter <= 2.5 mu m (PM2.5), <= 10 mu m (PM10), >2.5, and <= 10 mu m (PMcoarse), soot (PM2.5 absorbance), and nitrogen oxides at the addresses of participants with land use regression. Residential exposure to traffic noise was modelled at the facade according to the EU Directive 2002/49/EC. We assessed hypertension as (i) self-reported and (ii) measured (systolic BP >= 140mmHg or diastolic BP >= 90mmHg or intake of BP lowering medication (BPLM). We used Poisson regression with robust variance estimation to analyse associations of traffic-related exposures with incidence of hypertension, controlling for relevant confounders, and combined the results from individual studies with random-effects meta-analysis. Among 41 072 participants free of self-reported hypertension at baseline, 6207 (15.1%) incident cases occurred within 5-9 years of follow-up. Incidence of self-reported hypertension was positively associated with PM2.5 (relative risk (RR) 1.22 [95%-confidence interval (CI): 1.08; 1.37] per 5 mu g/m(3)) and PM2.5 absorbance (RR 1.13 [95% CI: 1.02; 1.24] per 10(-5) m(-1)). These estimates decreased slightly upon adjustment for road traffic noise. Road traffic noise was weakly positively associated with the incidence of self-reported hypertension. Among 10 896 participants at risk, 3549 new cases of measured hypertension occurred. We found no clear associations with measured hypertension. Conclusion Long-term residential exposures to air pollution and noise are associated with increased incidence of self-reported hypertension.
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6.
  • Nagel, Gabriele, et al. (författare)
  • Air pollution and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
  • 2018
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:7, s. 1632-1643
  • Tidskriftsartikel (refereegranskat)abstract
    • Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancersof the stomach and upper aerodigestive tract (UADT). We investigated the association of long-term exposure to ambient airpollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land-useregression models for particulate matter (PM) below 10mm (PM10), below 2.5mm (PM2.5), between 2.5 and 10mm (PMcoarse),PM2.5absorbance and nitrogen oxides (NO2and NOX) as well as approximated by traffic indicators. Cox regression modelswith adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined withrandom effects meta-analyses. During average follow-up of 14.1 years of 305,551 individuals, 744 incident cases of gastriccancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5mg/m3of PM2.5was 1.38 (95% CI 0.99; 1.92)for gastric and 1.05 (95% CI 0.62; 1.77) for UADT cancers. No associations were found for any of the other exposures consid-ered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influencemarkedly the effect estimate for PM2.5and gastric cancer. Higher estimated risks of gastric cancer associated with PM2.5wasfound in men (HR 1.98 [1.30; 3.01]) as compared to women (HR 0.85 [0.5; 1.45]). This large multicentre cohort study showsan association between long-term exposure to PM2.5and gastric cancer, but not UADT cancers, suggesting that air pollutionmay contribute to gastric cancer risk.
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7.
  • Pedersen, Marie, et al. (författare)
  • Is There an Association Between Ambient Air Pollution and Bladder Cancer Incidence? Analysis of 15 European Cohorts
  • 2018
  • Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 4:1, s. 113-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Ambient air pollution contains low concentrations of carcinogens implicated in the etiology of urinary bladder cancer (BC). Little is known about whether exposure to air pollution influences BC in the general population. Objective: To evaluate the association between long-term exposure to ambient air pollution and BC incidence. Design, setting and participants: We obtained data from 15 population-based cohorts enrolled between 1985 and 2005 in eight European countries (N = 303 431; mean follow-up 14.1 yr). We estimated exposure to nitrogen oxides (NO2 and NOx), particulate matter (PM) with diameter <10 mu m (PM10), <2.5 mu m (PM2.5). between 2.5 and 10 mu m (PM2.5-10). PM2.5 absorbance (soot), elemental constituents of PM, organic carbon, and traffic density at baseline home addresses using standardized land-use regression models from the European Study of Cohorts for Air Pollution Effects project. Outcome measurements and statistical analysis: We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and meta-analyses to estimate summary hazard ratios (HRS) for BC incidence. Results and limitations: During follow-up, 943 incident BC cases were diagnosed. In the meta-analysis, none of the exposures were associated with BC risk. The summary HRs associated with a 10-mu g/m(3) increase in NO2 and 51-mu g/m(3) increase in PM2.5 were 0.98 (95% confidence interval [CI] 0.89-1.08) and 0.86 (95% CI 0.63-1.18), respectively. Limitations include the lack of information about lifetime exposure. Conclusions: There was no evidence of an association between exposure to outdoor air pollution levels at place of residence and risk of BC. Patient summary: We assessed the link between outdoor air pollution at place of residence and bladder cancer using the largest study population to date and extensive assessment of exposure and comprehensive data on personal risk factors such as smoking. We found no association between the levels of outdoor air pollution at place of residence and bladder cancer risk.
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8.
  • Raaschou-Nielsen, Ole, et al. (författare)
  • Outdoor air pollution and risk for kidney parenchyma cancer in 14 European cohorts
  • 2017
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:7, s. 1528-1537
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have indicated weakly increased risk for kidney cancer among occupational groups exposed to gasoline vapors, engine exhaust, polycyclic aromatic hydrocarbons and other air pollutants, although not consistently. It was the aim to investigate possible associations between outdoor air pollution at the residence and the incidence of kidney parenchyma cancer in the general population. We used data from 14 European cohorts from the ESCAPE study. We geocoded and assessed air pollution concentrations at baseline addresses by land-use regression models for particulate matter (PM10 , PM2.5 , PMcoarse , PM2.5 absorbance (soot)) and nitrogen oxides (NO2 , NOx ), and collected data on traffic. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses to calculate summary hazard ratios (HRs). The 289,002 cohort members contributed 4,111,908 person-years at risk. During follow-up (mean 14.2 years) 697 incident cancers of the kidney parenchyma were diagnosed. The meta-analyses showed higher HRs in association with higher PM concentration, e.g. HR=1.57 (95%CI: 0.81-3.01) per 5μg/m(3) PM2.5 and HR=1.36 (95%CI: 0.84-2.19) per 10(-5) m(-1) PM2.5 absorbance, albeit never statistically significant. The HRs in association with nitrogen oxides and traffic density on the nearest street were slightly above one. Sensitivity analyses among participants who did not change residence during follow-up showed stronger associations, but none were statistically significant. This study provides suggestive evidence that exposure to outdoor PM at the residence may be associated with higher risk for kidney parenchyma cancer; the results should be interpreted cautiously as associations may be due to chance.
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9.
  • Wang, Meng, et al. (författare)
  • Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts : Results from the ESCAPE and TRANSPHORM projects
  • 2014
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 66, s. 97-106
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Associations between long-term exposure to ambient particulate matter (PM) and cardiovascular (CVD) mortality have been widely recognized. However, health effects of long-term exposure to constituents of PM on total CVD mortality have been explored in a single study only. Aims: The aim of this study was to examine the association of PM composition with cardiovascular mortality. Methods: We used data from 19 European ongoing cohorts within the framework of the ESCAPE (European Study of Cohorts for Air Pollution Effects) and TRANSPHORM (Transport related Air Pollution and Health impacts Integrated Methodologies for Assessing Particulate Matter) projects. Residential annual average exposure to elemental constituents within particle matter smaller than 2.5 and 10 pm (PM2.5 and PM10) was estimated using Land Use Regression models. Eight elements representing major sources were selected a priori (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc). Cohort-specific analyses were conducted using Cox proportional hazards models with a standardized protocol. Random-effects metaanalysis was used to calculate combined effect estimates. Results: The total population consisted of 322,291 participants, with 9545 CVD deaths. We found no statistically significant associations between any of the elemental constituents in PM2.5 or PM10 and CVD mortality in the pooled analysis. Most of the hazard ratios (HRs) were close to unity, e.g. for PM10 Fe the combined HR was 0.96 (0.84-1.09). Elevated combined HRs were found for PM2.5 Si (1.17, 95% Cl: 0.93-1.47), and S in PM2.5 (1.08,95% Cl: 0.95-1.22) and PM10 (1.09,95% Cl: 0.90-132). Conclusion: In a joint analysis of 19 European cohorts, we found no statistically significant association between long-term exposure to 8 elemental constituents of particles and total cardiovascular mortality.
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10.
  • Abdulhadi, Nadia, et al. (författare)
  • Patient-provider interaction from the perspectives of type 2 diabetes patients in Muscat, Oman : a qualitative study
  • 2007
  • Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 7, s. 162-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients' expectations and perceptions of the medical encounter and interactions are important tools in diabetes management. Some problems regarding the interaction during encounters may be related to a lack of communication skills on the part of either the physician or the patient. This study aimed at exploring the perceptions of type 2 diabetes patients regarding the medical encounters and quality of interactions with their primary health-care providers. Methods: Four focus group discussions ( two women and two men groups) were conducted among 27 purposively selected patients ( 13 men and 14 women) from six primary health-care centres in Muscat, Oman. Qualitative content analysis was applied. Results: The patients identified some weaknesses regarding the patient-provider communication like: unfriendly welcoming; interrupted consultation privacy; poor attention and eye contact; lack of encouraging the patients to ask questions on the providers' side; and inability to participate in medical dialogue or express concerns on the patients' side. Other barriers and difficulties related to issues of patient-centeredness, organization of diabetes clinics, health education and professional competency regarding diabetes care were also identified. Conclusion: The diabetes patients' experiences with the primary health-care providers showed dissatisfaction with the services. We suggest appropriate training for health-care providers with regard to diabetes care and developing of communication skills with emphasis on a patient-centred approach. An efficient use of available resources in diabetes clinics and distributing responsibilities between team members in close collaboration with patients and their families seems necessary. Further exploration of the providers' work situation and barriers to good interaction is needed. Our findings can help the policy makers in Oman, and countries with similar health systems, to improve the quality and organizational efficiency of diabetes care services.
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11.
  • Agardh, Carl-David, et al. (författare)
  • Altered endothelial/pericyte ratio in Goto-Kakizaki rat retina
  • 1997
  • Ingår i: Journal of Diabetes and its Complications. - 1873-460X .- 1056-8727. ; 11:3, s. 158-162
  • Tidskriftsartikel (refereegranskat)abstract
    • The Goto-Kakizaki (GK) rat represents a model of hereditary non-insulin-dependent diabetes mellitus (NIDDM), characterized by nonobesity, mild hyperglycemia from early life, impaired glucose tolerance test results, and a markedly defective insulin response to glucose. The rats develop signs of both nephropathy and neuropathy, but, to our knowledge, retinal changes have not been reported so far in this model of NIDDM. Hence, the aim of the present study was to assess whether morphological vascular changes could be demonstrated in retinal vessel preparations of GK rats. The endothelial/pericyte ratio was found to be higher in GK rats aged 8 months as well as after 24-30 months compared to their matched controls (2.3 +/- 0.2 versus 2.0 +/- 0.1; p < 0.01, and 2.6 +/- 0.2 versus 1.9 +/- 0.1; p < 0.001, respectively). Furthermore, in 24 to 30-months-old GK rats, the endothelial/pericyte ratio was higher than in 8 month old GK rats (p < 0.05). Thus, the GK rat appears to be a suitable model for experimental studies of chronic complications, including diabetic retinopathy, in NIDDM.
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12.
  • Agardh, Carl-David, et al. (författare)
  • Varning för okritisk användning av överviktskirurgi vid typ 2-diabetes
  • 2012
  • Ingår i: Läkartidningen. - Stockholm : Läkartidningen förlag. - 0023-7205 .- 1652-7518. ; 109:25, s. 1208-1209
  • Tidskriftsartikel (refereegranskat)abstract
    • Överviktskirurgi diskuteras nu som ett behandlingsalternativ även för patienter med typ 2-diabetes där BMI inte överstiger nuvarande indikationsgräns 35 kg/m2. Artikelförfattarna vill varna för en sådan utveckling i avvaktan på kritisk värdering av denna typ av kirurgi.
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13.
  • Agardh, Emilie E., et al. (författare)
  • Alcohol and type 2 diabetes : The role of socioeconomic, lifestyle and psychosocial factors
  • 2019
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 47:4, s. 408-416
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: We investigate (a) alcohol consumption in association with type 2 diabetes, taking heavy episodic drinking (HED), socioeconomic, health and lifestyle, and psychosocial factors into account, and (b) whether a seemingly protective effect of moderate alcohol consumption on type 2 diabetes persists when stratified by occupational position.METHODS: This population-based longitudinal cohort study comprises 16,223 Swedes aged 18-84 years who answered questionnaires about lifestyle, including alcohol consumption in 2002, and who were followed-up for self-reported or register-based diabetes in 2003-2011. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated in a multivariable-adjusted logistic regression model for all participants and stratified by high and low occupational position. We adjusted for HED, socioeconomic (occupational position, cohabiting status and unemployment), health and lifestyle (body mass index (BMI), blood pressure, smoking, physical inactivity, poor general health, anxiety/depression and psychosocial (low job control and poor social support) characteristics one by one, and the sets of these factors.RESULTS: Moderate consumption was inversely associated with type 2 diabetes after controlling for health and lifestyle (OR=0.47; 95% CI: 0.29-0.79) and psychosocial factors (OR=0.40; 95% CI: 0.22-0.79) when compared to non-drinkers. When adjusting for socioeconomic factors, there was still an inverse but non-significant association (OR=0.59; 95% CI: 0.35-1.00). In those with high occupational position, there was no significant association between moderate consumption and type 2 diabetes after adjusting for socioeconomic (OR=0.67; 95% CI: 0.3-1.52), health and lifestyle (OR=0.70; 95% CI: 0.32-1.5), and psychosocial factors (OR=0.75; 95% CI: 0.23-2.46). On the contrary, in those with low occupational position, ORs decreased from 0.55 (95% CI: 0.28-1.1) to 0.35 (95% CI: 0.15-0.82) when adjusting for psychosocial factors, a decrease that was solely due to low job control. HED did not influence any of these associations.CONCLUSIONS: Moderate alcohol consumption is associated with a lower risk of type 2 diabetes, after adjusting for HED, health and lifestyle, and psychosocial characteristics. The association was inverse but non-significant after adjusting for socioeconomic factors. When stratified by occupational position, there was an inverse association only in those with low occupational position and after adjusting for low job control.
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14.
  • Andersson, Camilla, et al. (författare)
  • A longitudinal assessment of inter-sectoral participation in a community-based diabetes prevention programme
  • 2005
  • Ingår i: Social Sciences & Medicine. - : Elsevier BV. - 0277-9536. ; 61:11, s. 2407-2422
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the development of inter-sectoral participation in the three intervention municipalities of Stockholm Diabetes Prevention Programme (SDPP) case studies with a longitudinal assessment were conducted using the spidergram method, document analysis and group discussions. At three time points, the members of the local steering committees assessed the extent of participation from narrow to wide inter-sectoral participation in five key areas: planning, resources, leadership, network and implementation. Wide participation of various interest groups was recognised in planning and implementing activities whereas local resources, the representation of the leadership and the extent of the network were perceived as more restricted. Expert involvement varied during the programme period but was not regarded as exerting control over the local programmes. Participation within the local steering committees decreased, with a stronger focus on the project co-ordinator and other local partners in latter years. The extent of partner engagement increased due to focusing on activities approaching multi-sector collaboration and institutionalisation. Overall, communication and shared responsibility appeared critical in influencing both the development and perception of participation. In conclusion, to understand the dynamic process of participation at different times, areas and levels, the development and use of evaluation designs combining different methods and information sources throughout the lifespan of a project are recommended. 
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15.
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16.
  • Aweko, Juliet, et al. (författare)
  • Patient and Provider Dilemmas of Type 2 Diabetes Self-Management : A Qualitative Study in Socioeconomically Disadvantaged Communities in Stockholm
  • 2018
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 15:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies comparing provider and patient views and experiences of self-management within primary healthcare are particularly scarce in disadvantaged settings. In this qualitative study, patient and provider perceptions of self-management were investigated in five socio-economically disadvantaged communities in Stockholm. Twelve individual interviews and four group interviews were conducted. Semi-structured interview guides included questions on perceptions of diabetes diagnosis, diabetes care services available at primary health care centers, patient and provider interactions, and self-management support. Data was analyzed using thematic analysis. Two overarching themes were identified: adopting and maintaining new routines through practical and appropriate lifestyle choices (patients), and balancing expectations and pre-conceptions of self-management (providers). The themes were characterized by inherent dilemmas representing confusions and conflicts that patients and providers experienced in their daily life or practice. Patients found it difficult to tailor information and lifestyle advice to fit their daily life. Healthcare providers recognized that patients needed support to change behavior, but saw themselves as inadequately equipped to deal with the different cultural and social aspects of self-management. This study highlights patient and provider dilemmas that influence the interaction and collaboration between patients and providers and hinder uptake of self-management advice.
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17.
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18.
  • Beelen, Rob, et al. (författare)
  • Long-term Exposure to Air Pollution and Cardiovascular Mortality An Analysis of 22 European Cohorts
  • 2014
  • Ingår i: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 25:3, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and 10 mu m to 2.5 mu m (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 mu g/m(3) and for PM10, 1.22 (0.91-1.63) per 10 mu g/m(3). Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
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19.
  • Gudjonsdottir, Hrafnhildur, et al. (författare)
  • Cohort Profile : The Stockholm Diabetes Prevention Programme (SDPP)
  • 2022
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 51:6, s. e401-e413
  • Tidskriftsartikel (refereegranskat)abstract
    • The Stockholm Diabetes Prevention Programme (SDPP) was established in the mid-1990s as a baseline for a community-based intervention aimed at primary prevention of type 2 diabetes (T2D). The intervention was found to be ineffective, but the cohort continues to contribute to our understanding of the pathogenesis of T2D and cardiometabolic risk factors.The cohort comprises 15 070 men and 19 416 women, born between 1938 and 1961, resident in five municipalities in Stockholm County, Sweden, at baseline. A sub-cohort answered a screening survey (10 236 men and 16 481 women), and a sub-cohort of those participated in a clinical examination (3128 men and 4821 women) at baseline (clinical cohort).The clinical cohort has been followed up after 10 years, when 2383 men and 3329 women participated, and after 20 years, when 1752 men and 2545 women participated.Socioeconomic, demographic and health-related register information was collected for all. The screening survey contains self-reported information on own and familial T2D. For the clinical cohort, we conducted oral glucose tolerance tests, drew blood and took blood pressures and anthropometric measurements. The participants also filled in questionnaires on lifestyle and psychosocial conditions.Data are available on request after ethical approval; information is available on the study webpage [Stockholm-Diabetes-Prevention-Programme-(SDPP)(regionstockholm.se)].
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20.
  • Gustafsson, Amanda Jabin, et al. (författare)
  • Ryanodine receptor-operated activation of TRP-like channels can trigger critical Ca2+ signaling events in pancreatic beta-cells
  • 2005
  • Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 19:2, s. 301-303
  • Tidskriftsartikel (refereegranskat)abstract
    • There is little information available concerning the link between the ryanodine (RY) receptors and the downstream Ca(2+) signaling events in beta-cells. In fura-2 loaded INS-1E cells, activation of RY receptors by 9-methyl 5,7-dibromoeudistomin D (MBED) caused a rapid rise of [Ca(2+)]i followed by a plateau and repetitive [Ca(2+)]i spikes on the plateau. The [Ca(2+)]i plateau was abolished by omission of extracellular Ca(2+) and by SKF 96365. In the presence of SKF 96365, MBED produced a transient increase of [Ca(2+)]i, which was abolished by thapsigargin. Activation of RY receptors caused Ca(2+) entry even when the ER Ca(2+) pool was depleted by thapsigargin. The [Ca(2+)]i plateau was not inhibited by nimodipine or ruthenium red, but was inhibited by membrane depolarization, La(3+), Gd(3+), niflumic acid, and 2-aminoethoxydiphenyl borate, agents that inhibit the transient receptor potential channels. The [Ca(2+)]i spikes were inhibited by nimodipine and ryanodine, indicating that they were due to Ca(2+) influx through the voltage-gated Ca(2+) channels and Ca(2+)-induced Ca(2+) release (CICR). Activation of RY receptors depolarized membrane potential as measured by patch clamp. Thus, activation of RY receptors leads to coherent changes in Ca(2+) signaling, which includes activation of TRP-like channels, membrane depolarization, activation of the voltage-gated Ca(2+) channels and CICR.
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21.
  • Hedman, Christina, 1964- (författare)
  • Insulin and IGF-I in type 1 diabetes
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Patients with type I diabetes have alterations in the GH/IGF system with reduced levels of circulating IGF-I, as well as other disturbances in the components of the IGF system.Alterations of both local and circulating IGF-I and its binding proteins (IGFBPs) have been associated with metabolic and vascular manifestations of diabetes and also with atherosclerosis. Short-acting insulin analogues have been developed in order to obtain more physiologic insulin profiles than with human regular insulin when injected subcutaneously.We examined the effects on the IGF system of good glycaemic control, of two diets with different amount of protein and of the short-acting insulin analogue lispro in continuous subcutaneous insulin infusion (CSII) (pump therapy). We also compared the free insulin profiles of the insulin analogues lispro and aspart. As a new tool we used the combination of two different insulin assays that detect human insulin only, or both human insulin and analogues.This thesis shows that the circulating IGF system exhibits several pronounced aberrations in patients with type I diabetes, even if glycaemic control is normal or near normal. These abnormalities are not, or are only weakly, related to glycaemic control estimated by HbA1c. In contrast, they are related to the presence of residual p-cell function, indicating that portal insulin delivery is required for a normal IGF system. Treatment with insulin analogue lispro, despite giving higher peripheral insulin peaks than human regular insulin, does not alter the levels of IGF-I and IGFBP-I in patients with good glycaemic control and longstanding, Cpeptide negative type 1 diabetes treated with CSII. Furthermore, IGFBP-I levels do not differ after a single s c injection of each of the insulin analogues aspart and lispro. A two-fold increase in protein intake, from 10E% to 20E%, in patients with longstanding type 1 diabetes does not affect the altered IGF system.The free insulin profiles of insulin analogues aspart and lispro resemble each other, but insulin lispro showed a slightly faster uptake, reached the maximum peak concentration earlier, and showed a more rapid decline than did insulin aspart. These differences are, however, small in comparison with the large differences in the insulin profiles between lispro and human regular insulin. The accumulated evidence suggests that possible differences between these insulin analogues are of little or no clinical importance.The combination of insulin assays that detect human insulin alone, or both human insulin and analogues provides a new tool for studying insulin pharmacokinetics. Using this technique, it is possible to separately assess the contribution of insulin analogues (lispro and aspart) and human insulin to the free insulin profiles.
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22.
  • Howl, John, et al. (författare)
  • Bioportide : an emergent concept of bioactive cell penetrating peptides
  • 2012
  • Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 69:17, s. 2951-2966
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell-penetrating peptides (CPPs) have proven utility for the highly efficient intracellular delivery of bioactive cargoes that include peptides, proteins, and oligonucleotides. The many strategies developed to utilize CPPs solely as pharmacokinetic modifiers necessarily requires them to be relatively inert. Moreover, it is feasible to combine one or multiple CPPs with bioactive cargoes either by direct chemical conjugation or, more rarely, as non-covalent complexes. In terms of the message-address hypothesis, this combination of cargo (message) linked to a CPP (address) as a tandem construct conforms to the sychnological organization. More recently, we have introduced the term bioportide to describe monomeric CPPs that are intrinsically bioactive. Herein, we describe the design and biochemical properties of two rhegnylogically organized monometic CPPs that collectively modulate a variety of biological and pathophysiological phenomena. Thus, camptide, a cell-penetrant sequence located within the first intracellular loop of a human calcitonin receptor, regulates cAMP-dependent processes to modulate insulin secretion and viral infectivity. Nosangiotide, a bioportide derived from endothelial nitric oxide synthase, potently inhibits many aspects of the endothelial cell morphology and movement and displays potent anti-angiogenic activity in vivo. We conclude that, due to their capacity to translocate and target intracellular signaling events, bioportides represent an innovative generic class of bioactive agents.
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23.
  • Hukic, Dzana Sudic, et al. (författare)
  • Troponin T levels associated with genetic variants in NOTCH2 and MTNR1B in women with psychosis
  • 2017
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 250, s. 217-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychosis patients have increased prevalence of metabolic disorders, which increase the risk for cardiovascular disease. Elevated troponin T level is an early biomarker of cardiovascular damage. We tested for association between troponin T levels and genetic risk variants of elevated blood glucose level in psychosis. Glucose and troponin T levels correlated positively. MTNR1B rs10830963 and NOTCH2 rs10923931 associated with troponin T levels in women, adjusted for glucose levels. These findings may indicate metabolic genetic influences on troponin T levels among women with psychosis.
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24.
  • Johansson, Hans-Erik, 1960- (författare)
  • The Impact of Bariatric Surgery on Obesity related Metabolic Traits with Specific Emphasis on Glucose, Insulin and Proinsulin
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Hyperproinsulinemia is associated with type 2 diabetes (T2DM) and obesity and is a predictor for future coronary heart disease. This thesis examines the effect of bariatric surgery on glucometabolic status including insulin and proinsulin responses after meal. Further we explored longitudinally the effects of bariatric surgery on glucose, insulin and proinsulin secretion as well as lipids, liver enzymes and magnesium concentrations. We explored by a standardised meal test the postprandial dynamics of proinsulin and insulin and effects on glucose and lipids in patients treated with gastric bypass (RYGBP) surgery and in patients treated with bileopancreatic diversion with duodenal switch surgery (BPD-DS). Comparisons were made to morbidly obese patients and normal weight controls (NW). RYGBP surgery markedly lowers fasting and postprandial proinsulin concentrations although BMI was higher compared to NW-controls. BPD-DS surgery induces a large weight loss and normalises postprandial responses of glucose, proinsulin and insulin and markedly lowers triglycerides. We evaluated non-diabetic morbidly obese patients who underwent bariatric surgery followed-up for up to four years after surgery. Long-term follow-up showed that RYGBP surgery is not only characterized by markedly and sustained lowered BMI but also lowered concentrations of proinsulin, insulin, ALT and increased HDL-C possibly via reduced hepatic insulin resistance. We also examined how magnesium status is affected by bariatric surgery as magnesium has been shown to be inversely related to glucose and to insulin resistance. The serum magnesium concentrations increased by 6% after RYGBP and 10% after BPD-DS. In summary, RYGBP and BPD-DS surgery results in marked weight loss, alterations in insulin and proinsulin dynamics, lowered fasting and postprandial proinsulin concentrations and improved glucometabolic and magnesium status.
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25.
  • Kalinovich, Anastasia, et al. (författare)
  • Treatment with a β-2-adrenoceptor agonist stimulates glucose uptake in skeletal muscle and improves glucose homeostasis, insulin resistance and hepatic steatosis in mice with diet-induced obesity
  • 2020
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63:8, s. 1603-1615
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Chronic stimulation of beta(2)-adrenoceptors, opposite to acute treatment, was reported to reduce blood glucose levels, as well as to improve glucose and insulin tolerance in rodent models of diabetes by essentially unknown mechanisms. We recently described a novel pathway that mediates glucose uptake in skeletal muscle cells via stimulation of beta(2)-adrenoceptors. In the current study we further explored the potential therapeutic relevance of beta(2)-adrenoceptor stimulation to improve glucose homeostasis and the mechanisms responsible for the effect.Methods C57Bl/6N mice with diet-induced obesity were treated both acutely and for up to 42 days with a wide range of clenbuterol dosages and treatment durations. Glucose homeostasis was assessed by glucose tolerance test. We also measured in vivo glucose uptake in skeletal muscle, insulin sensitivity by insulin tolerance test, plasma insulin levels, hepatic lipids and glycogen.Results Consistent with previous findings, acute clenbuterol administration increased blood glucose and insulin levels. However, already after 4 days of treatment, beneficial effects of clenbuterol were manifested in glucose homeostasis (32% improvement of glucose tolerance after 4 days of treatment,p < 0.01) and these effects persisted up to 42 days of treatment. These favourable metabolic effects could be achieved with doses as low as 0.025 mg kg(-1) day(-1)(40 times lower than previously studied). Mechanistically, these effects were not due to increased insulin levels, but clenbuterol enhanced glucose uptake in skeletal muscle in vivo both acutely in lean mice (by 64%,p < 0.001) as well as during chronic treatment in diet-induced obese mice (by 74%,p < 0.001). Notably, prolonged treatment with low-dose clenbuterol improved whole-body insulin sensitivity (glucose disposal rate after insulin injection increased up to 1.38 +/- 0.31%/min in comparison with 0.15 +/- 0.36%/min in control mice,p < 0.05) and drastically reduced hepatic steatosis (by 40%,p < 0.01) and glycogen (by 23%,p < 0.05).Conclusions/interpretation Clenbuterol improved glucose tolerance after 4 days of treatment and these effects were maintained for up to 42 days. Effects were achieved with doses in a clinically relevant microgram range. Mechanistically, prolonged treatment with a low dose of clenbuterol improved glucose homeostasis in insulin resistant mice, most likely by stimulating glucose uptake in skeletal muscle and improving whole-body insulin sensitivity as well as by reducing hepatic lipids and glycogen. We conclude that selective beta(2)-adrenergic agonists might be an attractive potential treatment for type 2 diabetes. This remains to be confirmed in humans.
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26.
  • Larsson, Martin, et al. (författare)
  • Diabetes negatively affects cortical and striatal GABAergic neurons: an effect that is partially counteracted by exendin-4.
  • 2016
  • Ingår i: Bioscience reports. - 1573-4935. ; 36:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetic (T2D) patients often develop early cognitive and sensorimotor impairments. The pathophysiological mechanisms behind these problems are largely unknown. Recent studies demonstrate that dysfunctional γ-aminobutyric acid (GABAergic) neurons are involved in age-related cognitive decline. We hypothesized that similar, but earlier dysfunction is taking place under T2D in the neocortex and striatum (two brain areas important for cognition and sensorimotor functions). We also hypothesized that the T2D-induced effects are pharmacologically reversible by anti-diabetic drugs targeting the glucagon-like peptide-1 receptor (GLP-1R). We determined the effect of T2D on cortical and striatal GABAergic neurons positive for glutamic acid decarboxylase-67 (GAD67), calbindin (CB), parvalbumin (PV) and calretinin (CR) by using immunohistochemistry and quantitative microscopy. Young and middle-aged T2D Goto-Kakizaki (GK) (a model of spontaneous T2D) and Wistar rats were used. Furthermore, we determined the therapeutic potential of the GLP1-R agonist exendin-4 (Ex-4) by treating middle-aged GK rats for 6weeks with 0.1μg/kg Ex-4 twice daily. We show that T2D reduced the density of GAD67-positive neurons in the striatum and of CB-positive neurons in both striatum and neocortex. T2D also increased the average volume of PV-positive interneurons in the striatum. Ex-4 treatment increased the density of CB-positive neurons in the striatum of GK rats. Our data demonstrate that T2D negatively affects GAD67 and CB-positive GABAergic neurons in the brain during aging, potentially identifying some of the pathophysiological mechanisms to explain the increased prevalence of neurological complications in T2D. We also show a specific, positive effect of Ex-4 on striatal CB-positive neurons, which could be exploited in therapeutic perspective.
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27.
  • Lindmark, Stina, 1965- (författare)
  • Neurohormonal mechanisms in insulin resistance and type 2 diabetes
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Insulin resistance usually occurs early in the development of type 2 diabetes. An altered balance in the autonomic nervous system and in certain endocrine and inflammatory pathways, might contribute to the development of insulin resistance. In diabetes, hyperglycemia further aggravates insulin resistance as well as beta cell dysfunction but the mechanisms causing this phenomenon, i.e. glucotoxicity, are not fully understood. Insulin resistance can be demonstrated in healthy first-degree relatives of type 2 diabetes patients who also have a high risk of developing type 2 diabetes. Relatives and control subjects without family history of diabetes were studied with respect to insulin sensitivity and the activity in the autonomic nervous system (ANS) and in the cortisol axis. Levels of sex hormones, leptin and cytokines were analysed. Abdominal adipose tissue distribution was determined with computed tomography. Male relatives had decreased testosterone levels and increased leptin levels. There was an inverse relationship between insulin sensitivity and leptin levels, and in males a positive association between insulin sensitivity and testosterone levels. A tendency to lower parasympathetic reactivity was found in the relatives using heart rate variability assessment. The sympathetic/parasympathetic ratio during stress provocation was inversely correlated to insulin sensitivity, measured with glucose clamp. The insulin-resistant subjects also exhibited an overall blunted reactivity in the ANS. Cortisol reactivity after stimulation with ACTH and CRH was lower in the relatives. The amount of visceral adipose tissue (VAT) was associated with insulin resistance and with heart rate at rest and during controlled breathing and it also correlated with heart rate and sympathetic/parasympathetic ratio after an orthostatic manoeuvre. Type 2 diabetic subjects with good and poor glycemic control, respectively, and matched healthy control subjects were examined with respect to insulin sensitivity, cortisol axis activity and blood levels of leptin, sex hormones and the adipocyte-secreted inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Biopsies were taken from subcutaneous adipose tissue for determination of adipocyte size. Diabetes subjects were more insulin-resistant than controls and diabetics with poor control exhibited the highest degree of insulin resistance. This group also had the highest levels of TNF-α, morning serum cortisol and non-esterified fatty acids (NEFA). In correlation analyses, significant associations were seen between glycemic level and insulin resistance, TNF-α, IL- 6 and serum cortisol levels. Insulin resistance was positively correlated to NEFA levels, TNF-α and ACTH-stimulated cortisol levels. Adipocyte size was associated with insulin resistance and levels of IL-6 and leptin. The findings support a connection between insulin resistance and VAT amount, activity in the ANS and blood levels of hormones and adipocyte-derived molecules. Dysregulation in the complex interplay between such factors may contribute to the early pathogenesis of insulin resistance and type 2 diabetes. Adipokines and the cortisol system can also potentially aggravate hyperglycemia in patients with manifest type 2 diabetes.
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28.
  • Martinell, Mats, 1971- (författare)
  • Diabetes Mellitus at the Time for Diagnosis : Studies on Prognostic Factors
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim for this thesis was to identify prognostic factors for chronic diabetes complications that exist at the time of diabetes diagnosis.Low level of education (<12 years) and low income (<60% of median) was found to increase the risk to have high (>70 mmol/mol) HbA1c at the time of diagnosis with 34 % and 35 %, respectively.Prevalence of diabetic retinopathy (DR) was 12% in a cohort of patients newly diagnosed with diabetes. Diabetic macular edema was present in 11% of patients with type 2 diabetes (T2D) and 13% of those with Latent Autoimmune Diabetes in Adults (LADA). Low beta cell function and low level of education increased the risk for DR with 110% and 43%, respectively. For every unit of increase in body mass index, the risk for DR was reduced by 3%.The cellular immunology of LADA patients was a mixture of that observed in both type 1 (T1D) and T2D patients. Compared to patients with T1D, LADA patients had more B-regulatory lymphocytes and antigen presenting cells capable of producing interleukine-35. This indicates a higher anti-inflammatory capacity in LADA patients compared to type T1D patients.By imputing age, body mass index, HbA1c at diagnosis, beta cell function and insulin resistance in a cluster analysis, five distinct diabetes clusters were identified. The four clusters representing T2D patients differed in incidence of DR, nephropathy and non-alcoholic fatty liver disease. This was replicated with similar results in three geographically separate populations.By studying socioeconomic background and factors present at the time of diagnosis we can better predict prognosis for chronic diabetes complications. These findings may facilitate better-targeted diabetes screening programs and more individually tailored treatment regimes.
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29.
  • Mohanty, Soumitra, et al. (författare)
  • Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder
  • 2022
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity. Patients with diabetes have an increased susceptibility to infections. Here the authors show that high glucose impairs innate immunity through reduced levels of the antimicrobial peptide psoriasin and impaired epithelial barrier function, resulting in an increased risk of urinary tract infection.
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30.
  • Olsson, Eric, et al. (författare)
  • Diabetes and glucose disturbances in patients with psychosis in Sweden
  • 2015
  • Ingår i: BMJ Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication.METHOD:We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ(2) test, and factors associated with antidiabetic treatment were evaluated with logistic regression.RESULTS:Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1-6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness.CONCLUSIONS:The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.
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31.
  • Quynh, Nguyen Thi Thu, et al. (författare)
  • Effects of galnon, a non-peptide galanin-receptor agonist, on insulin release from rat pancreatic islets
  • 2005
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 328:1, s. 213-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Galanin is a neurotransmitter peptide that suppresses insulin secretion. The present study aimed at investigating how a non-peptide galanin receptor agonist, galnon, affects insulin secretion from isolated pancreatic islets of healthy Wistar and diabetic Goto-Kakizaki (GK) rats. Galnon stimulated insulin release potently in isolated Wistar rat islets; 100 microM of the compound increased the release 8.5 times (p<0.001) at 3.3 mM and 3.7 times (p<0.001) at 16.7 mM glucose. Also in islet perifusions, galnon augmented several-fold both acute and late phases of insulin response to glucose. Furthermore, galnon stimulated insulin release in GK rat islets. These effects were not inhibited by the presence of galanin or the galanin receptor antagonist M35. The stimulatory effects of galnon were partly inhibited by the PKA and PKC inhibitors, H-89 and calphostin C, respectively, at 16.7 but not 3.3 mM glucose. In both Wistar and GK rat islets, insulin release was stimulated by depolarization of 30 mM KCl, and 100 microM galnon further enhanced insulin release 1.5-2 times (p<0.05). Cytosolic calcium levels, determined by fura-2, were increased in parallel with insulin release, and the L-type Ca2+-channel blocker nimodipine suppressed insulin response to glucose and galnon. In conclusion, galnon stimulates insulin release in islets of healthy rats and diabetic GK rats. The mechanism of this stimulatory effect does not involve galanin receptors. Galnon-induced insulin release is not glucose-dependent and appears to involve opening of L-type Ca2+-channels, but the main effect of galnon seems to be exerted at a step distal to these channels, i.e., at B-cell exocytosis.
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32.
  • Röhl, Samuel, et al. (författare)
  • Noninvasive in vivo Assessment of the Re-endothelialization Process Using Ultrasound Biomicroscopy in the Rat Carotid Artery Balloon Injury Model.
  • 2019
  • Ingår i: Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. - : Wiley. - 1550-9613. ; 38:7, s. 1723-1731
  • Tidskriftsartikel (refereegranskat)abstract
    • Ultrasound biomicroscopy (UBM), or ultra high-frequency ultrasound, is a technique used to assess the anatomy of small research animals. In this study, UBM was used to assess differences in intimal hyperplasia thickness as a surrogate measurement of the re-endothelialization process after carotid artery balloon injury in rats.Ultrasound biomicroscopic data from 3 different experiments and rat strains (Sprague Dawley, Wistar, and diabetic Goto-Kakizaki) were analyzed. All animals were subjected to carotid artery balloon injury and examined with UBM (30-70 MHz) 2 and 4 weeks after injury. Re-endothelialization on UBM was defined as the length from the carotid bifurcation to the most distal visible edge of the intimal hyperplasia. En face staining with Evans blue dye was performed at euthanasia 4 weeks after injury, followed by tissue harvesting for histochemical and immunohistochemical evaluations.A significant correlation (Spearman r=0.63; P<.0001) was identified when comparing all measurements of re-endothelialization obtained from UBM and en face staining. The findings revealed a similar pattern for all rat strains: Sprague Dawley (Spearman r=0.70; P<.0001), Wistar (Spearman r=0.36; P<.081), and Goto-Kakizaki (Spearman r=0.70; P<.05). A Bland-Altman test showed agreement between en face staining and UBM. Immunohistochemical staining confirmed the presence of the endothelium in the areas detected as re-endothelialized by the UBM assessment.Ultrasound biomicroscopy can be used for repeated in vivo assessment of re-endothelialization after carotid artery balloon injury in rats.
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33.
  • Salehi, S Albert, et al. (författare)
  • Dysfunction of the islet lysosomal system conveys impairment of glucose-induced insulin release in the diabetic GK rat
  • 1999
  • Ingår i: Endocrinology. - 0013-7227. ; 140:7, s. 3045-3053
  • Tidskriftsartikel (refereegranskat)abstract
    • Accumulated evidence links an important signal involved in glucose-stimulated insulin release to the activation of the islet lysosomal glycogenolytic enzyme acid glucan-1,4-alpha-glucosidase. We have analyzed the function of the lysosomal system/lysosomal enzyme activities in pancreatic islets of young (6-8 weeks), spontaneously diabetic, GK (Goto-Kakizaki) rats and Wistar control rats in relation to glucose-induced insulin release. The insulin secretory response to glucose was markedly impaired in the GK rat, but was restored by the adenylate cyclase activator forskolin. Islet activities of classical lysosomal enzymes, e.g.. acid phosphatase, N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, and cathepsin D, were reduced by 20-35% in the GK rat compared with those in Wistar controls. In contrast, the activities of the lysosomal alpha-glucosidehydrolases, i.e.. acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase, were increased by 40-50%. Neutral alpha-glucosidase (endoplasmic reticulum) was unaffected. Comparative analysis of liver tissue showed that lysosomal enzyme activities were of the same magnitude in GK and Wistar rats. Notably, in Wistar rats, the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase were approximately 15-fold higher in islets than in liver. Other lysosomal enzymes did not display such a difference. Normalization of glycemia in GK rats by phlorizin administered for 9 days did not influence either the lysosomal alpha-glucosidehydrolase activities or other lysosomal enzyme activities in GK islets. Finally, the pseudotetrasaccharide acarbose, which accumulates in the lysosomal system, inhibited acid glucan-1,4-alpha-glucosidase activity in parallel with its inhibitory action on glucose-induced insulin release in intact Wistar islets, whereas no effect was recorded for either parameter in intact GK islets. In contrast, acarbose inhibited the enzyme activity equally in islet homogenates from both GK and Wistar rats, showing that the catalytic activity of the enzyme itself in disrupted cells was unaffected. We propose that dysfunction of the islet lysosomal/vacuolar system is an important defect impairing the transduction mechanisms for glucose-induced insulin release in the GK rat.
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34.
  • Svensson, Annika M., et al. (författare)
  • Effects of glucagon-like peptide-1-(7-36)-amide on pancreatic islet and intestinal blood perfusion in Wistar rats and diabetic GK rats
  • 2007
  • Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 112:5-6, s. 345-351
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to evaluate the effects of GLP-1 [glucagon-like peptide-1-(7-36)-amide] on total pancreatic, islet and intestinal blood perfusion in spontaneously hyperglycaemic GK rats and normal Wistar rats using a microsphere technique. GK rats had hyperglycaemia and increased pancreatic and islet blood flow. Blood glucose concentrations were not affected when measured shortly (8 min) after GLP-1 administration in either GK or Wistar rats. GLP-1 had no effects on baseline pancreatic or islet blood flow in Wistar rats, but did prevent the blood flow increase normally seen following glucose administration to these animals. In GK rats, administration of GLP-1 decreased both pancreatic and islet blood flow. Glucose administration to the GK rats decreased pancreatic and islet blood flow. This decrease was not affected by pre-treatment with GLP-1. We conclude that administration of GLP-1 leads to a decrease in the augmented blood flow seen in islets of diabetic GK rats. The GLP-1-induced action on islet blood perfusion may modulate output of islet hormones and contribute to the antidiabetogenic effects of the drug in Type 2 diabetes (non-insulin-dependent diabetes).
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35.
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36.
  • Timm, Linda, et al. (författare)
  • "I Did Not Believe You Could Get Better" : Reversal of Diabetes Risk Through Dietary Changes in Older Persons with Prediabetes in Region Stockholm
  • 2019
  • Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes risk can be controlled and even reversed by making dietary changes. The aim of this study was to improve the understanding of how older persons with a high risk of developing Type 2 diabetes manage and relate to information about diabetes risk over a ten-year period. Fifteen qualitative interviews were conducted among participants from the Stockholm Diabetes Prevention Program (SDPP). The participants were asked to recall the health examinations conducted by the SDPP related to their prediabetes and to describe their experiences and potential changes related to diet and physical activity. Data were analyzed using qualitative content analysis. The main theme found was that T2D (type 2 diabetes) risk is not perceived as concrete enough to motivate lifestyle modifications, such as changing dietary patterns, without other external triggers. Diagnosis was recognized as a reason to modify diet, and social interactions were found to be important for managing behavior change. Diagnosis was also a contributing factor to lifestyle modification, while prognosis of risk was not associated with efforts to change habits. The results from this study suggest that the potential of reversing prediabetes needs to be highlighted and more clearly defined for older persons to serve as motivators for lifestyle modification.
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37.
  • van Olmen, Josefien, et al. (författare)
  • Process evaluation of a pragmatic implementation trial to support self-management for the prevention and management of type 2 diabetes in Uganda, South Africa and Sweden in the SMART2D project
  • 2022
  • Ingår i: BMJ Open Diabetes Research & Care. - : BMJ Publishing Group Ltd. - 2052-4897. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Type 2 diabetes (T2D) and its complications are increasing rapidly. Support for healthy lifestyle and self-management is paramount, but not adequately implemented in health systems. Process evaluations facilitate understanding why and how interventions work through analyzing the interaction between intervention theory, implementation and context. The Self-Management and Reciprocal Learning for Type 2 Diabetes project implemented and evaluated community-based interventions (peer support program; care companion; and link between facility care and community support) for persons at high risk of or having T2D in a rural community in Uganda, an urban township in South Africa, and socioeconomically disadvantaged urban communities in Sweden.Research design and methods: This paper reports implementation process outcomes across the three sites, guided by the Medical Research Council framework for complex intervention process evaluations. Data were collected through observations of peer support group meetings using a structured guide, and semistructured interviews with project managers, implementers, and participants.Results: The countries aligned implementation in accordance with the feasibility and relevance in the local context. In Uganda and Sweden, the implementation focused on peer support; in South Africa, it focused on the care companion part. The community-facility link received the least attention. Continuous capacity building received a lot of attention, but intervention reach, dose delivered, and fidelity varied substantially. Intervention-related and context-related barriers affected participation.Conclusions: Identification of the key uncertainties and conditions facilitates focus and efficient use of resources in process evaluations, and context relevant findings. The use of an overarching framework allows to collect cross-contextual evidence and flexibility in evaluation design to adapt to the complex nature of the intervention. When designing interventions, it is crucial to consider aspects of the implementing organization or structure, its absorptive capacity, and to thoroughly assess and discuss implementation feasibility, capacity and organizational context with the implementation team and recipients. These recommendations are important for implementation and scale-up of complex interventions.
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38.
  • Weinmayr, Gudrun, et al. (författare)
  • Particulate matter air pollution components and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts of Air Pollution Effects (ESCAPE)
  • 2018
  • Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 120, s. 163-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Previous analysis from the large European multicentre ESCAPE study showed an association of ambient particulate matter < 2.5 mu m (PM2.5) air pollution exposure at residence with the incidence of gastric cancer. It is unclear which components of PM are most relevant for gastric and also upper aerodigestive tract (UADT) cancer and some of them may not be strongly correlated with PM mass. We evaluated the association between long-term exposure to elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in European adults.Methods: Baseline addresses of individuals were geocoded and exposure was assessed by land-use regression models for copper (Cu), iron (Fe) and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and industry; silicon (Si) for crustal material and potassium (K) for biomass burning. Cox regression models with adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined with random effects meta-analyses.Results: Ten cohorts in six countries contributed data on 227,044 individuals with an average follow-up of 14.9 years with 633 incident cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR) for an increase of 200 ng/m(3) of PM2.5_S was 1.92 (95%-confidence interval (95%-CI) 1.13; 3.27) for gastric cancer, with no indication of heterogeneity between cohorts (I-2= 0%), and 1.63 (95%-CI 0.88; 3.01) for PM2.5_Zn (I-2= 70%). For the other elements in PM2.5 and all elements in PM10 including PM10_S, non-significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No association was found between any of the elements and UADT cancer. The HR for PM2.5_S and gastric cancer was robust to adjustment for additional factors, including diet, and restriction to study participants with stable addresses over follow-up resulted in slightly higher effect estimates with a decrease in precision. In a two-pollutant model, the effect estimate for total PM2.5 decreased whereas that for PM2.5_S was robust.Conclusion: This large multicentre cohort study shows a robust association between gastric cancer and long-term exposure to PM2.5 S but not PM10 S, suggesting that S in PM2.5 or correlated air pollutants may contribute to the risk of gastric cancer.
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39.
  • Öberg, Anette I., et al. (författare)
  • Shikonin Increases Glucose Uptake in Skeletal Muscle Cells and Improves Plasma Glucose Levels in Diabetic Goto-Kakizaki Rats
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7, s. e22510-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. Methodology/Principal Findings: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally) once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin), plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. Conclusions/Significance: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.
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40.
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41.
  • Österlind, Jonas, et al. (författare)
  • Björknässtudien: Färre läkarbesök i primärvården
  • 2010
  • Ingår i: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 107:15, s. 976-980
  • Tidskriftsartikel (refereegranskat)abstract
    • Ett livsstilsförändrande program för bättre kost och ökad fysisk aktivitet, genomfört med enkla medel inom primärvården, minskade inte bara en rad riskfaktorer utan även vårdutnyttjandet.Andelen besök hos primärvårdsläkaren var under de tre första åren 21 procent lägre än i kontrollgruppen.Det är intressant med fortsatta undersökningar av livsstilsinterventioners effekt på vårdutnyttjande, dess hälsoekonomiska konsekvenser och effektens underliggande mekanism.
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42.
  • Österlind, Jonas, et al. (författare)
  • [The Swedish Björknäs study : fewer physician visits in primary health care. A randomized study of intensive life style intervention]
  • 2010
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:15, s. 976-980
  • Tidskriftsartikel (refereegranskat)abstract
    • Intensive lifestyle interventions can reduce incidence of type 2 diabetes and cardiovascular risk factors in high-risk individuals. We aimed to assess the effect of the lifestyle intervention used in the The Swedish Björknäs study, previously shown to reduce cardiovascular risk factors, on health care use. In 2003, 145 high-risk individuals were randomly assigned to either a 3 months intensive lifestyle modification undertaken in the primary care setting or control. In 2009, participants' medical records were reviewed. Primary outcome was primary care health use. Secondary outcome was hospital care use. Analysis was by intention to treat. Primary care physician visits were 21% (95% CI 2%; 36%) lower in the lifestyle group during the first three years. The difference was significant for all six years when adjusting for baseline (GLM Repeated Measures; p=0.019). There were no significant differences in visits to nurses in primary health care or hospital physicians and nurses, hospitalizations or hospital days. A program of intensive lifestyle modification can not only favourably influence cardiovascular risk factors but also reduce health care use in high-risk individuals.
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