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  • 1. Carlsson, Axel C
    et al.
    Nowak, Christoph
    Lind, Lars
    Östgren, Carl Johan
    Nyström, Fredrik H
    Sundström, Johan
    Carrero, Juan Jesus
    Riserus, Ulf
    Ingelsson, Erik
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska Institutet.
    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 approach2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, p. 1-7Article in journal (Refereed)
    Abstract [en]

    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 <60 mg/mL/1.73 m2 and/or urinary albumin-creatinine ratio ≥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.

  • 2.
    Olai, Lena
    et al.
    Dalarna University, School of Education, Health and Social Studies, Caring Science/Nursing.
    Borgquist, Lars
    Svärdsudd, Kurt
    Health problems in elderly patients during the first post-stroke year2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 3, p. 381-327Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A wide range of health problems has been reported in elderly post-stroke patients.

    AIM: The aim of this study was to analyse the prevalence and timing of health problems identified by patient interviews and scrutiny of primary health care and municipality elderly health care records during the first post-stroke year.

    METHODS: A total of 390 consecutive patients, ≥65 years, discharged alive from hospital after a stroke event, were followed for 1 year post-admission. Information on the health care situation during the first post-stroke year was obtained from primary health care and municipal elderly health care records and through interviews with the stroke survivors, at 1 week after discharge, and 3 and 12 months after hospital admission.

    RESULTS: More than 90% had some health problem at some time during the year, while based on patient record data only 4-8% had problems during a given week. The prevalence of interview-based health problems was generally higher than record-based prevalence, and the ranking order was moderately different. The most frequently interview-reported problems were associated with perception, activity, and tiredness, while the most common record-based findings indicated pain, bladder and bowel function, and breathing and circulation problems. There was co-occurrence between some problems, such as those relating to cognition, activity, and tiredness.

    CONCLUSIONS: Almost all patients had a health problem during the year, but few occurred in a given week. Cognitive and communication problems were more common in interview data than record data. Co-occurrence may be used to identify subtle health problems.

  • 3. Tonkonogi, Aleksandra
    et al.
    Carlsson, Axel C
    Helmersson-Karlqvist, Johanna
    Larsson, Anders
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 3, p. 174-178Article in journal (Refereed)
    Abstract [en]

    AIM: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes.

    METHODS: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n = 91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7-13.4 years), 33 participants died of cardiovascular causes.

    RESULTS: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03-2.24, P = 0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk.

    CONCLUSION: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.

  • 4. Velders, Matthijs A
    et al.
    Calais, Fredrik
    Dahle, Nina
    Fall, Tove
    Hagström, Emil
    Leppert, Jerzy
    Nowak, Christoph
    Tenerz, Åke
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska institutet.
    Hedberg, Pär
    Cathepsin D improves the prediction of undetected diabetes in patients with myocardial infarction2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 3, p. 187-192Article in journal (Refereed)
    Abstract [en]

    Background: Newer therapeutic agents for type 2 diabetes mellitus can improve cardiovascular outcomes, but diabetes remains underdiagnosed in patients with myocardial infarction (MI). We sought to identify proteomic markers of undetected dysglycaemia (impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) to improve the identification of patients at highest risk for diabetes. Materials and methods: In this prospective cohort, 626 patients without known diabetes underwent oral glucose tolerance testing (OGTT) during admission for MI. Proximity extension assay was used to measure 81 biomarkers. Multivariable logistic regression, adjusting for risk factors, was used to evaluate the association of biomarkers with dysglycaemia. Subsequently, lasso regression was performed in a 2/3 training set to identify proteomic biomarkers with prognostic value for dysglycaemia, when added to risk factors, fasting plasma glucose, and glycated haemoglobin A1c. Determination of discriminatory ability was performed in a 1/3 test set. Results: In total, 401/626 patients (64.1%) met the criteria for dysglycaemia. Using multivariable logistic regression, cathepsin D had the strongest association with dysglycaemia. Lasso regression selected seven markers, including cathepsin D, that improved prediction of dysglycaemia (area under the receiver operator curve [AUC] 0.848 increased to 0.863). In patients with normal fasting plasma glucose, only cathepsin D was selected (AUC 0.699 increased to 0.704). Conclusions: Newly detected dysglycaemia, including manifest diabetes, is common in patients with acute MI. Cathepsin D improved the prediction of dysglycaemia, which may be helpful in the a priori risk determination of diabetes as a motivation for confirmatory OGTT.

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