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  • 1.
    Blomstrand, Peter
    et al.
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Sjöblom, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Mats
    Acad Hlth and Care, Sweden.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain2018In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, article id 113Article in journal (Refereed)
    Abstract [en]

    Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight amp;lt; 25 kg/m(2), overweight 25-29 kg/m(2), and obesity amp;gt;= 30 kg/m(2) ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/e (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p amp;lt; 0.05 vs. p amp;lt;0.05). Corresponding results in the control group were 58% (6%) vs. -22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p amp;lt;0.05 vs. p amp;lt;0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n =187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n =179) (p amp;lt;0.05). Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.

  • 2.
    Carlsson, Axel C.
    et al.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Jennersjö, Pär
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Larsson, Anders
    Uppsala University, Sweden.
    Arnlov, Johan
    Uppsala University, Sweden; Dalarna University,Falun Sweden.
    Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, no 1, p. 40-Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease. Methods: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used. Results: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality. Conclusions/Interpretations: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

  • 3.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Bjarnegård, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Sagittal abdominal diameter is a more independent measure compared with waist circumference to predict arterial stiffness in subjects with type 2 diabetes - a prospective observational cohort study2013In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 12Article in journal (Refereed)
    Abstract [en]

    Background

    Anthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.

    Methods

    Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old.

    Results

    There were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

    Conclusions

    We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

  • 4.
    Grundvold, Irene
    et al.
    Oslo University Hospital, Norway.
    Bodegard, Johan
    AstraZeneca Nord, Sweden.
    Nilsson, Peter M.
    Lund University, Sweden.
    Svennblad, Bodil
    Uppsala University, Sweden.
    Johansson, Gunnar
    Uppsala University, Sweden.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Sundström, Johan
    Uppsala University, Sweden; Uppsala University, Sweden.
    Body weight and risk of atrial fibrillation in 7,169 patients with newly diagnosed type 2 diabetes; an observational study2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, no 5Article in journal (Refereed)
    Abstract [en]

    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" (greater than 1 BMI unit), " stable weight" (+/- 1 BMI unit) and " weight loss" (less than 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.

  • 5.
    Vavruch, Camilla
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Serum leptin levels are independently related to the incidence of ischemic heart disease in a prospective study of patients with type 2 diabetes2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, no 62Article in journal (Refereed)
    Abstract [en]

    Background: New and clinically useful markers of cardiovascular risk are of essence in type 2 diabetes since ischemic heart disease is a major cause of death in these patients. Methods: We analyzed baseline data from 476 men and 244 women who participated in "Cardiovascular Risk factors in Patients with Diabetes -a Prospective study in Primary care" study. All participants had type 2 diabetes and were 55-66 years old at recruitment during year 2005 to 2008. Except for established traditional risk markers for vascular disease, we also estimated vascular complications non-invasively by performance of carotid-femoral pulse-wave velocity (PWV, with applanation-tonometry) and intima-media thickness of carotid arteries (IMT, with B-mode ultrasound). Patients were followed for incidence of ischemic heart disease mortality and morbidity until end of the year 2012, using the national Swedish Cause of Death and Hospitalization Registries. Results: During the follow-up period of a median of 6 years 47 men and 10 women died or were hospitalized for ischemic heart disease including myocardial infarction. Leptin levels were positively related to the hazard ratio (HR) in men (HR for each log 10 unit 4.9, CI 1.99 to 11.8) and women (HR 11.5, CI 1.47 to 89.7). Leptin predicted ischemic heart disease independently of age, HbA1c, BMI, systolic blood pressure and LDL-cholesterol/HDL-cholesterol ratio (men: HR 12.9 CI 3.2-53, women: HR 19.9, CI 1.2-327) This finding of increased risk related to high leptin levels was also statistically significant when carotid-femoral PWV and IMT were both added to the equations in men (hazard ratio 9.2 CI 2.1-41). Conclusions: Our data support the use of serum leptin in type 2 diabetes to add independent prognostic information in terms of ischemic heart disease when compared with traditional cardiovascular risk factors. In the men of the cohort this prognostic information was in addition also to data on IMT and PWV, two non-invasive measurements of the extent of vascular disease. The power to detect a similar relationship in women was less strong due to lower incidence of cardiovascular disease. Trial registration: ClinicalTrials. gov:

  • 6.
    Wijkman, Magnus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Diastolic orthostatic hypertension and cardiovascular prognosis in type 2 diabetes: a prospective cohort study2016In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 15, no 83, p. 1-10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In patients with type 2 diabetes, the prognostic impact of an orthostatic rise in blood pressure is not known. Therefore, the aim of this study was to determine the prognostic implications of the diastolic orthostatic blood pressure response in a cohort of patients with type 2 diabetes. We also evaluated associations between different orthostatic blood pressure responses and markers of subclinical cardiovascular organ damage.

    METHODS: Office blood pressures were measured in the sitting and in the standing position in 749 patients with type 2 diabetes who participated in the CARDIPP study (Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care). Diastolic orthostatic hypertension was defined as a rise of diastolic blood pressure ≥10 mmHg and diastolic orthostatic hypotension was defined as a drop of diastolic blood pressure ≥10 mmHg. Recruitment took place between the years 2005-2008, and patients were followed until any of the primary outcome events (cardiovascular death or hospitalization for either myocardial infarction or stroke) occurred or until December 31st, 2014. Measurements of aortic pulse wave velocity and of carotid intima-media thickness were performed at base-line.

    RESULTS: Diastolic orthostatic hypertension was found in 140 patients (18.7 %) and was associated with significantly lower risk of cardiovascular events (crude hazard ratio compared with patients with normal systolic and diastolic orthostatic blood pressure response: 0.450, 95 % C.I. 0.206-0.987, P = 0.046). Diastolic orthostatic hypotension was found in 31 patients (4.1 %) and was associated with higher values for aortic pulse wave velocity and carotid intima-media thickness, compared with patients with normal systolic and diastolic orthostatic blood pressure response.

    CONCLUSIONS: Diastolic orthostatic hypertension is common in patients with type 2 diabetes, and may be a novel marker for decreased cardiovascular risk in these patients.

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