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1.
  • Sabale, Ugne, et al. (författare)
  • Healthcare utilization and costs following newly diagnosed type-2 diabetes in Sweden : A follow-up of 38,956 patients in a clinical practice setting
  • 2015
  • Ingår i: Primary Care Diabetes. - 1751-9918 .- 1878-0210. ; 9:5, s. 330-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To describe healthcare resource use patterns and estimate healthcare costs of newly diagnosed Type 2 diabetes mellitus (T2DM) patients in Sweden. Methods: Patients with a newly diagnosed T2DM between 1999 and 2009 were identified from 84 Swedish primary care centres. Healthcare resource use data, excluding pharmaceuticals, were extracted from electronic patient records and a national patient register, and reported as per patient mean number of primary care contacts, laboratory tests and hospitalizations. Per patient mean healthcare costs are reported as annual and cumulative costs. Results: During a median (maximum) of 4.6 (9.0) years follow-up; 38,956 patients (183,513 patient years) on average made 81 primary care contacts, was hospitalized 2.14 times, and took 31 laboratory tests. Mean per patient annual healthcare costs were (sic)4128 (95% CI, 4054-4199) the first year after diagnosis, (sic)2708 (95% CI, 2641-2776) the second year, and (sic)3030 (95% CI, 2854-3204) in year 9 (2012 values). Mean per patient cumulative healthcare costs were (sic)26,503 (95% CI, 26,025-26,970) at 9 years of follow-up. Hospitalizations accounted for the majority of healthcare costs. Conclusions: Although newly diagnosed T2DM patients require a substantial amount of healthcare services in primary care, hospitalizations account for the majority of healthcare costs.
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2.
  • Carlsson, Axel C, et al. (författare)
  • Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach
  • 2019
  • Ingår i: Upsala Journal of Medical Sciences. - TAYLOR & FRANCIS LTD. - 0300-9734.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate amp;lt;60 mg/mL/1.73 m(2) and/or urinary albumin-creatinine ratio amp;gt;= 3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline. Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.
3.
  • Grundvold, Irene, et al. (författare)
  • Body weight and risk of atrial fibrillation in 7,169 patients with newly diagnosed type 2 diabetes; an observational study
  • 2015
  • Ingår i: Cardiovascular Diabetology. - 1475-2840 .- 1475-2840. ; 14, s. 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obesity, type 2 diabetes and atrial fibrillation (AF) are closely associated, but the underlying mechanisms are not fully understood. We aimed to explore associations between body mass index (BMI) or weight change with risk of AF in patients with type 2 diabetes. Methods: A total of 7,169 participations with newly diagnosed type 2 diabetes were stratified according to baseline BMI, and after a second BMI measurement within 18 months, further grouped according to relative weight change as "weight gain" (> 1 BMI unit), " stable weight" (+/- 1 BMI unit) and " weight loss" (< 1 BMI unit). The mean follow-up period was 4.6 years, and the risk of AF was estimated using adjusted Cox regression models. Results: Average age at diabetes diagnosis was 60 years and the patients were slightly obese (mean BMI 30.2 kg/m(2)). During follow-up, 287 patients developed incident AF, and those with overweight or obesity at baseline had 1.9 fold and 2.9-fold higher risk of AF, respectively, than those with normal BMI. The 14% of the patients with subsequent weight gain had 1.5-fold risk of AF compared with those with stable weight or weight loss. Conclusions: In patients with newly diagnosed type 2 diabetes, baseline overweight and obesity, as well as modest weight increase during the first 18 months after diagnosis, were associated with a substantially increased risk of incident AF. Patients with type 2 diabetes may benefit from efforts to prevent weight gain in order to reduce the risk of incident AF.
4.
  • Kalkan, Almina, et al. (författare)
  • Increased healthcare utilization costs following initiation of insulin treatment in type 2 diabetes A long-term follow-up in clinical practice
  • 2017
  • Ingår i: Primary Care Diabetes. - Elsevier. - 1751-9918 .- 1878-0210. ; 11:2, s. 184-192
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. Methods: Patients newly initiated on insulin (n = 2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. Results: The total mean annual healthcare cost increased from 1656 per patient 2 years before insulin initiation to 3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was 13,823 in the insulin group compared to 9989 in the NIAD group. Conclusions: Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe. This is an open access article under the CC BY-NC-ND license.
5.
  • Carlsson, Axel C, et al. (författare)
  • Association between circulating endostatin, hypertension duration, and hypertensive target-organ damage
  • 2013
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 62:6, s. 1146-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with ≥5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.
6.
  • Ekström, Magnus Pär, et al. (författare)
  • The association of body mass index, weight gain and central obesity with activity-related breathlessness : The Swedish Cardiopulmonary Bioimage Study
  • 2019
  • Ingår i: Thorax. - BMJ Publishing Group. - 0040-6376. ; 74:10, s. 958-964
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m2) is rapidly increasing globally and its impact on breathlessness is unclear. Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score ≥1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex. Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m2; and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness. Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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7.
  • Sundelöf, Johan, et al. (författare)
  • Cystatin C Levels are Positively Correlated with both A beta(42) and Tau Levels in Cerebrospinal Fluid in Persons with Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls
  • 2010
  • Ingår i: Journal of Alzheimer's Disease. - IOS Press. - 1387-2877. ; 21:2, s. 471-478
  • Tidskriftsartikel (refereegranskat)abstract
    • Cystatin C is suggested to be involved in neurodegeneration and the development of Alzheimer's disease (AD) by binding to soluble amyloid-beta (A beta) peptides. Studies of cystatin C levels in cerebrospinal fluid (CSF) in relation to risk of AD are conflicting and relations between cystatin C, A beta(42), and tau levels in CSF in AD, mild cognitive impairment (MCI), and healthy controls are unknown. The objective of this study was to investigate cystatin C, A beta(42), and tau levels in CSF in AD, MCI, and controls. As a secondary aim, the relationships between cystatin C, A beta(42), and tau levels across disease groups were investigated. Cystatin C, A beta(42), total tau, and phosphorylated tau levels in CSF were analyzed by turbidimetry (cystatin C) and xMAP Luminex technology (A beta and tau) in persons with AD (n = 101), MCI (n = 84), and healthy control subjects (n = 28). Mean cystatin C levels were similar in cases of AD (5.6 mu mol/L +/- 1.7), MCI (5.4 mu mol/L +/- 1.48), and controls (5.6 mu mol/L +/- 1.6). However, CSF cystatin C levels were strongly and positively correlated with total tau and phosphorylated tau levels (r = 0.61-0.81, p < 0.0001) and A beta(42) (r = 0.35-0.65, p < 0.001) independent of age, gender, and APOE genotype. Mean CSF cystatin C levels did not differ between patients with AD and MCI and healthy controls. Interestingly, cystatin C levels were positively correlated with both tau and A beta(42) levels in CSF independent of age, gender, and APOE genotype.
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8.
  • Sundelöf, Johan, et al. (författare)
  • Higher Cathepsin B Levels in Plasma in Alzheimer's Disease Compared to Healthy Controls
  • 2010
  • Ingår i: Journal of Alzheimer's Disease. - IOS Press. - 1387-2877. ; 22:4, s. 1223-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • Cathepsin B is suggested to be involved in amyloid-beta (A beta) processing and Alzheimer's disease (AD). Studies of cathepsin B levels in plasma and cerebrospinal fluid (CSF) have not been previously performed. We examined cathepsin B levels in plasma and CSF samples in persons with AD, mild cognitive impairment (MCI), and healthy controls in order to test the hypothesis that cathepsin B levels can discriminate persons with AD or MCI from healthy controls. Cathepsin B, Cystatin C, A beta(1-40) and A beta(1-42), total tau, phosphorylated tau, and albumin levels in plasma and CSF were analyzed by ELISA (Cathepsin B) turbidimetry (cystatin C), xMAP Luminex technology (A beta(1-40) and A beta(1-42) and tau), and Cobas C501 analyzer (albumin) in persons with AD (n=101), MCI (n - 84), and healthy control subjects (n - 28). Plasma cathepsin B levels were higher in persons with AD compared to healthy controls, both in unadjusted models and in multivariable models adjusting for age, gender, APOE genotype, cystatin C, and albumin levels: Odds ratio (OR) for AD per 1 SD of plasma cathepsin B; 2.04, 95% confidence interval (CI); 1.01-4.14, p = 0.05. There was no difference between diagnostic groups in cathepsin B levels in CSF: OR for AD per 1 SD of CSF cathepsin B; 0.93, 95% CI; 0.37-2.30, p = 0.87. Plasma cathepsin B levels were higher in persons with AD compared to healthy controls whereas there was no difference between diagnostic groups in cathepsin B levels in CSF. Further investigation of cathepsin B as a predictor of AD is warranted.
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9.
  • Figarska, Sylwia M., et al. (författare)
  • Associations of Circulating Protein Levels With Lipid Fractions in the General Population
  • 2018
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - LIPPINCOTT WILLIAMS & WILKINS. - 1079-5642 .- 1524-4636. ; 38:10, s. 2505-2518
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population.Approach and Results: We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate &lt;0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels.Conclusions: Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.
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10.
  • Ganna, Andrea, et al. (författare)
  • Multilocus Genetic Risk Scores for Coronary Heart Disease Prediction
  • 2013
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 33:9, s. 2267-2272
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective-Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. Approach and Results-We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events; hazard ratios for fourth versus first quartile, 1.54 and 1.52; P&lt;0.001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9%; P=0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Conclusions-Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.
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