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  • 1.
    Afghahi, Henri
    et al.
    Department of Medicine, Kärnsjukhuset, Sweden.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eliasson, Björn
    Gothenburg University.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjörnsdottir, Soffia
    Gothenburg University.
    Hadimeri, Henrik
    Gothenburg University.
    Svensson, Maria K
    Gothenburg University.
    Risk factors for the development of albuminuria and renal impairment in type 2 diabetes—the Swedish National Diabetes Register (NDR)2010In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 26, no 4, p. 1236-1243Article in journal (Refereed)
    Abstract [en]

    Background. The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register. Methods. Three thousand and six hundred sixty-seven patients with T2D aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C-G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes. Results. Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C-G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD). Conclusions. Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C-G) had an impact on interpretation of data, especially with regard to body composition and gender.

  • 2.
    Andersson, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Karlström, Brita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Fredén, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Petersson, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Öhrvall, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    A two-year clinical lifestyle intervention program for weight loss in obesity2008In: Food & nutrition research, ISSN 1654-661X, Vol. 52, p. 1656-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In recent randomised prospective studies, lifestyle intervention induced a weight loss of approximately 5%. OBJECTIVE: To describe and evaluate a 2-year on-going group intervention program in clinical practice in terms of weight loss and changes in metabolic risk factors, i.e. sagital abdominal diameter (SAD), triglycerides, fasting blood glucose and blood pressure. DESIGN: The aim of the intervention program was to motivate lifestyle changes concerning food intake and physical activity. The emphasis was on lifestyle modification, followed up at regular visits during 2 years. Subjects evaluated were 100 women with mean BMI 37.6 kg/m(2) and 26 men with mean BMI 36.5 kg/m(2). RESULTS: One hundred of 151 enrolled women and 26 of 36 men completed the program. Mean weight decreased by 3.8 kg in women (from 103.5 to 99.7, p<0.001) and 4.4 kg in men (from 116.5 to 112.1, p<0.05), respectively. SAD decreased by 5% (p=0.001 in women, p=0.01 in men), and triglycerides by 16% in women (p=0.01) and 24% in men (p=0.001), however systolic and diastolic blood pressure increased slightly but significantly. CONCLUSION: It is possible to perform a clinical lifestyle intervention program for outpatients on an ongoing basis with weight loss, lowered SAD and triglycerides, and a similar or lower dropout rate compared to clinical trials.

  • 3.
    Arnlov, J
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, L
    Department of Medical Sciences.
    Zethelius, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Andren, B
    Department of Medical Sciences.
    Hales, C N
    Department of Medical Sciences.
    Vessby, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lithell, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Several factors associated with the insulin resistance syndrome are predictors of left ventricular systolic dysfunction in a male population after 20 years of follow-up.2001In: Am Heart J, ISSN 1097-6744, Vol. 142, no 4, p. 720-4Article in journal (Refereed)
  • 4.
    Ax, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Garmo, Hans
    Regional Cancer Center , Uppsala University Hospital , Uppsala , Sweden.
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Becker, Wulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns and Prostate Cancer Risk: Report from the Population Based ULSAM Cohort Study of Swedish Men2014In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 66, no 1, p. 77-87Article in journal (Refereed)
    Abstract [en]

    Dietary pattern analyses have increased the possibilities to detect associations between diet and disease. However, studies on dietary pattern and prostate cancer are scarce. Food intake data in the Uppsala Longitudinal Study of Adult Men cohort was determined by 7-day food records. Adherence to a modified Mediterranean Diet Score (mMDS) and a low carbohydrate-high protein (LCHP) score were grouped as low, medium, or high in the whole study population (n = 1,044) and in those identified as adequate reporters of energy intake (n = 566), respectively. Prostate cancer risk was analyzed with Cox proportional hazard regression (median follow-up 13years) and competing risk of death was considered. There were no associations between dietary patterns and prostate cancer (n = 133) in the whole study population. Among adequate reporters the mMDS was not associated with prostate cancer (n = 72). The LCHP score was inversely related to prostate cancer in adequate reporters, adjusted hazard ratios; 0.55 (0.32-0.96) for medium and 0.47 (0.21-1.04) for high compared to low adherent participants (P-for-trend 0.04). Risk relations were not attributable to competing risk of death. In this study, a LCHP diet was associated with lower prostate cancer incidence. Relations emerged in adequate reporters, underscoring the importance of high-quality dietary data.

  • 5.
    Ax, Erika Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Wulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns and prostate cancer risk: a population based cohort study in elderly Swedish men2013In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 27, no S1, p. 847.8-Article in journal (Other academic)
  • 6.
    Basu, Samar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men2011In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 4, no 2, p. 164-168Article in journal (Refereed)
    Abstract [en]

    Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL-6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 -0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease.

  • 7.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 1, p. 35-40Article in journal (Refereed)
    Abstract [en]

    Introduction

    Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated.

    Aims

    To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men.

    Methods

    Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors.

    Results

     During winter, insulin sensitivity (M/I, unit = 100 × mg × min-1 × kg-1/(mU × L-1)) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29–0.82, P < 0.0001) per 10°C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results.Read More:http://informahealthcare.com/doi/abs/10.3109/03009734.2011.628422

    Conclusions

    Insulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients.

  • 8.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Garmo, Hans
    Lindbäck, Johan
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Maximum likelihood estimation of correction for dilution bias in simple linear regression using replicates from subjects with extreme first measurements2008In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 27, no 22, p. 4397-4407Article in journal (Refereed)
    Abstract [en]

    The least-squares estimator of the slope in a simple linear regression model is biased towards zero when the predictor is measured with random error. A corrected slope may be estimated by adding data from a reliability study, which comprises a subset of subjects from the main study. The precision of this corrected slope depends on the design of the reliability study and estimator choice.Previous work has assumed that the reliability study constitutes a random sample from the main study. A more efficient design is to use subjects with extreme values on their first measurement. Previously, we published a variance formula for the corrected slope, when the correction factor is the slope in the regression of the second measurement on the first. In this paper we show that both designs improve by maximum likelihood estimation (MLE). The precision gain is explained by the inclusion of data from all subjects for estimation of the predictor's variance and by the use of the second measurement for estimation of the covariance between response and predictor. The gain of MLE enhances with stronger true relationship between response and predictor and with lower precision in the predictor measurements. We present a real data example on the relationship between fasting insulin, a surrogate market, and true insulin sensitivity measured by a gold-standard euglycaemic insulin clamp, and simulations, where the behavior of profile-likelihood-based confidence intervals is examined. MLE was shown to be a robust estimator for non-normal distributions and efficient for small sample situations.

  • 9.
    Berglund, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Garmo, Hans
    Regional Oncologic Center, University Hospital, Uppsala.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Correction for regression dilution bias using replicates from subjects with extreme first measurements2007In: Statistics in Medicine, ISSN 0277-6715, E-ISSN 1097-0258, Vol. 26, no 10, p. 2246-2257Article in journal (Refereed)
    Abstract [en]

    The least squares estimator of the slope in a simple linear regression model will be biased towards zero when the predictor is measured with random error, i.e. intra-individual variation or technical measurement error. A correction factor can be estimated from a reliability study where one replicate is available on a subset of subjects from the main study. Previous work in this field has assumed that the reliability study constitutes a random subsample from the main study.We propose that a more efficient design is to collect replicates for subjects with extreme values on their first measurement. A variance formula for this estimator of the correction factor is presented. The variance for the corrected estimated regression coefficient for the extreme selection technique is also derived and compared with random subsampling. Results show that variances for corrected regression coefficients can be markedly reduced with extreme selection. The variance gain can be estimated from the main study data. The results are illustrated using Monte Carlo simulations and an application on the relation between insulin sensitivity and fasting insulin using data from the population-based ULSAM study.In conclusion, an investigator faced with the planning of a reliability study may wish to consider an extreme selection design in order to improve precision at a given number of subjects or alternatively decrease the number of subjects at a given precision.

  • 10.
    Bjorklund, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, L
    Zethelius, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Berglund, L
    Lithell, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Prognostic significance of 24-h ambulatory blood pressure characteristics for cardiovascular morbidity in a population of elderly men2004In: J Hypertens, Vol. 22, no 9, p. 1691-1697Article in journal (Refereed)
  • 11.
    Björklund, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Isolated ambulatory hypertension predicts cardiovascular morbidity in elderly men2003In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 107, no 9, p. 1297-302Article in journal (Refereed)
    Abstract [en]

    Background— Little is known about isolated ambulatory hypertension, a state with elevated ambulatory but normal office blood pressure (BP). This study aimed to investigate the prognostic significance of isolated ambulatory hypertension for cardiovascular morbidity in a population of elderly men.

    Methods and Results— At baseline, 24-hour ambulatory BP and metabolic and cardiac risk profiles were evaluated in 578 untreated 70-year-old men, participants of a population-based cohort. Subjects with isolated ambulatory hypertension (office BP <140/90 and daytime BP ≥135/85) and sustained hypertension (office BP ≥140/90 and daytime BP ≥135/85) had increased plasma glucose, body mass index, and echocardiographically determined left ventricular relative wall thickness compared with normotensive subjects (office BP <140/90 and daytime BP <135/85). Seventy-two cardiovascular morbid events (2.37 per 100 person-years at risk) occurred over 8.4 years of follow-up. The prognostic value of isolated ambulatory and sustained hypertension was assessed with Cox proportional hazard regression. Multivariate models adjusting for serum cholesterol, smoking, and diabetes demonstrated that both isolated ambulatory hypertension (hazard ratio [HR], 2.77; 95% CI, 1.15 to 6.68) and sustained hypertension (HR, 2.94; 95% CI, 1.49 to 5.82) were independent predictors of cardiovascular morbidity. In a multivariate model with continuous BP variables, ambulatory daytime systolic BP (HR for 1 SD increase, 1.47; 95% CI, 1.09 to 1.97) was associated with an adverse outcome independently of office systolic BP.

    Conclusions— In the present study, isolated ambulatory hypertension as well as sustained hypertension predicted cardiovascular morbidity. The findings suggest that 24-hour ambulatory BP monitoring may disclose important prognostic information also in subjects characterized as normotensive according to office BP.

  • 12. Björklund, Kristina
    et al.
    Lind, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Berglund, Lars
    Lithell, Hans
    Prognostic significance of 24-h ambulatory blood pressure characteristics for cardiovascular morbidity in a population of elderly men.2004In: J Hypertens, ISSN 0263-6352, Vol. 22, no 9, p. 1691-7Article in journal (Refereed)
  • 13. Butwicka, Agnieszka
    et al.
    Frisen, Louise
    Almqvist, Catarina
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lichtenstein, Paul
    Risks of Psychiatric Disorders and Suicide Attempts in Children and Adolescents With Type 1 Diabetes: A Population-Based Cohort Study2015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 3, p. 453-459Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To assess the risk of psychiatric disorders and suicide attempts in children with type 1 diabetes and their healthy siblings. RESEARCH DESIGN AND METHODS We performed a population-based case-cohort study of individuals born in Sweden between 1973 and 2009. Children with type 1 diabetes (n = 17,122) and their healthy siblings (n = 18,847) were identified and followed until their 18th birthday. Their risk of psychiatric disorders was compared with that of matched control subjects. RESULTS The risk of psychiatric morbidity in children with type 1 diabetes compared with the general population was tripled within 6 months after the onset of diabetes (hazard ratio [HR] 3.0 [95% CI 2.7-3.4]) and doubled within the total observation period (HR 2.1 [95% CI 2.0-2.2]). An increased risk was noted in suicide attempts (HR 1.7 [95% CI 1.4-2.0]) and in most categories of psychiatric disorders. The risk of psychiatric disorders in probands declined from HR 2.7 (95% CI 2.2-3.3) for those in the cohort born 1973-1986 to 1.9 (95% CI 1.8-2.0) in those born 1997-2009. The risk for any psychiatric disorders among siblings of patients with type 1 diabetes was estimated to be HR 1.1 (95% CI 1.0-1.1), and there was no increased risk in any of the specific category of disorders. CONCLUSIONS Children with type 1 diabetes are at high risk of psychiatric disorders, which seems to be a consequence of the disease rather than due to a common familial etiology. The results support recommendations on comprehensive mental health surveillance in children with type 1 diabetes, especially in recently diagnosed children.

  • 14.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Goodman, Anna
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Koupil, Ilona
    Birth Weight is not Associated With Risk of Fracture: Results from Two Swedish Cohort Studies2014In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 29, no 10, p. 2152-2160Article in journal (Refereed)
    Abstract [en]

    Development and growth in utero has been suggested to influence bone health. However, the relationship with risk of fracture in old age is largely unknown. Using Cox proportional hazards regression, we studied the association between birth weight and fractures at ages 50-94 among 10,893 men and women (48% women) from the Uppsala Birth Cohort Study (UBCoS, born 1915-29) and 1334 men from the Uppsala Longitudinal Study of Adult Men (ULSAM, born 1920-24). Measured birth weight was collected from hospital or midwives' records and fractures from the Swedish National Patient Register. We observed 2796 fractures (717 of these were hip fractures) in UBCoS and 335 fractures (102 hip fractures) in ULSAM. In UBCoS, the hazard ratio (HR) per 1 kg increase in birth weight, adjusted for sex and socioeconomic status at birth, was 1.01 [95% confidence interval (CI), 0.94-1.09] for any fracture and 1.06 (95% CI, 0.91-1.23) for hip fracture. Estimates in ULSAM were similar. We did not observe a differential association of birth weight with fractures occurring before age 70 or after age 70 years. Neither birth weight standardized for gestational age nor gestational duration was associated with fracture rate. In linear regression, birth weight was not associated with bone mineral density among 303 men who were 82-years-old in ULSAM but showed positive associations with total body bone mineral content (β per kg increase in birth weight, adjusted for social class and age, 133; 95% CI, 30-227). This association was attenuated after further adjustment for body mass index and height (β, 41; 95% CI, -43-126). We conclude that birth weight is associated with bone mineral content but this association does not translate into an association with risk of fracture in men and women aged 50-94 years.

  • 15.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eeg-Olofsson, Katarina
    Eliasson, Björn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjörnsdottir, Soffia
    A new model for 5-year risk of cardiovascular disease in Type 1 diabetes: from the Swedish National Diabetes Register (NDR)2011In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 28, no 10, p. 1213-1220Article in journal (Refereed)
    Abstract [en]

    Aims: We assessed the association between risk factors and cardiovascular disease in an observational study of patients with Type 1 diabetes from the Swedish National Diabetes Register.

    Methods: A derivation sample of 3661 patients, aged 30-65 years, 6.1% with previous cardiovascular disease, baseline 2002, and 197 cardiovascular disease events when followed for 5 years until 2007. A separate validation data set of 4484 patients, baseline 2003, 201 cardiovascular disease events when followed for 4 years.

    Results: Adjusted hazard ratios at Cox regression for fatal/non-fatal cardiovascular disease were: diabetes duration 2.76 (2.21-3.44); onset age 1.47 (1.21-1.78); log ratio total cholesterol:HDL cholesterol 1.26 (1.09-1.45); log HbA(1c) 1.19 (1.03-1.38); log systolic blood pressure 1.17 (1.01-1.34) (1 SD increase in continuous variables); smoker 1.76 (1.27-2.46); macroalbuminuria (> 200 mu g/min) 1.52 (1.10-2.10); previous cardiovascular disease 3.51 (2.54-4.84). All eight variables were used to elaborate a risk equation for 5-year cardiovascular disease risk. Regarding calibration in the derivation data set, ratio predicted 5-year risk (mean 5.4 +/- 7.9%) to observed event rate was 1.0. Discrimination was sufficient, with C-statistic 0.83, sensitivity and specificity 72 and 77%, respectively, for the top quartile of predicted risk. Similarly, calibration and discrimination were adequate in the validation data set: ratio of predicted 4-year risk/observed rate 0.94, C-statistic 0.80, sensitivity and specificity 62 and 77%, respectively, for the top quartile.

    Conclusions: This 5-year cardiovascular disease risk model from a large observational study of patients with Type 1 diabetes in routine care showed adequate calibration and discrimination and can be useful for clinical practice. It should also be tested in patients with Type 1 diabetes from other countries.

  • 16.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Eeg-Olofsson, Katarina
    Eliasson, Björn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Nilsson, Peter M
    Gudbjörnsdottir, Soffia
    Risk prediction of cardiovascular disease in type 2 diabetes: A risk equation from the Swedish National Diabetes Register (NDR)2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 10, p. 2038-2043Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - Risk prediction models obtained in samples from the general population do mot perform well in type 2 diabetic patients. Recently, 5-year risk estimates were proposed as being more accurate than 10-year risk estimates. This study presents a diabetes-specific equation for estimation of the absolute 5-year risk of first incident fatal/nonfatal cardiovascular disease (CVD) in type 2 diabetic patients with the use of A1C and clinical characteristics.RESEARCH DESIGN AND METHODS - The study was based on 11,646 female and male patients, aged 18-70 years, from the Swedish National Diabetes Register with 1,482 first incident CVD events based on 58,342 person-years with mean follow-up) of 5.64 years.RESULTS - This risk equation incorporates A1C, as in the UK Prospective Diabetes Study risk engine, and several clinical characteristics: onset age of diabetes, diabetes duration, sex, BMI, smoking, systolic blood pressure, and antihypertensive and lipid-reducing drugs. All predictors included were associated with the Outcome (P < 0.0001, except for BMI P = 0.0016) with Cox regression analysis. Calibration was excellent when assessed by comparing observed and predicted risk. Discrimination was sufficient, with a receiver operator curve statistic of 0.70. Mean 5-year risk of CVD in all patients was 12.0 +/- 7.5%, whereas 54% of the patients had a 5-year risk >= 10%.CONCLUSIONS - This more simplified risk equation enables 5-year risk prediction of CVD based on easily available nonlaboratory predictors in clinical practice and A1C and was elaborated in a large observational study obtained from the normal patient population aged up to 70 years.

  • 17.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eliasson, Björn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eeg-Olofsson, Katarina
    Gudbjörnsdottir, Soffia
    Riskfaktorer för hjärt- kärlsjukdom: Resultat från Nationella diabetesregistret jämförs med internationella studier2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, no 17-18, p. 882-885Article, review/survey (Refereed)
    Abstract [sv]

    Observationsstudier från Nationella diabetesregistret visar att vid typ 1- och typ 2-diabetes ses en ökande risk för hjärt–kärl­sjukdom med stigande HbA1c-värden, men ingen ­förhöjd risk vid lägre HbA1c.

    Vid typ 2-diabetes ses påtagligt lägre risk för hjärt–kärlsjukdom vid blodtryck 130–135/75 mm Hg än vid 140/80 mm Hg eller högre.

    Lipidkvoten non-HDL-/HDL-­kolesterol är en starkare risk­faktor för ischemisk hjärtsjukdom än LDL-kolesterol. Lägre värden för kvoten ger lägre triglycerider och högre HDL-­kolesterol.

    Två verktyg för beräkning av 5-års­risken för hjärt–kärlsjukdom vid typ 1-och typ 2-diabetes presenteras.

  • 18.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Gudbjornsdottir, Soffia
    Eliasson, Björn
    Zethelius, Bjorn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eeg-Olofsson, Katarina
    Nilsson, Peter M.
    Blood pressure and risk of cardiovascular diseases in type 2 diabetes: further findings from the Swedish National Diabetes Register (NDR-BP II)2012In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 30, no 10, p. 2020-2030Article in journal (Refereed)
    Abstract [en]

    Objectives: Estimate risks of coronary heart disease (CHD), stroke and cardiovascular disease (CVD) with updated mean systolic (SBP) and diastolic (DBP) blood pressure in an observational study of patients with type 2 diabetes. Methods: Thirty-five thousand and forty-one patients treated with antihypertensive drugs, and 18 512 untreated patients, aged 30-75 years, without previous heart failure, followed for 6 years until 2009. Results: In treated patients, nonlinear splines for 6-year risk of fatal/nonfatal CHD, stroke and CVD by BP as a continuous variable showed a progressive increase with higher SBP from 140 mmHg and higher, and with DBP from 80 mmHg, with a J-shaped risk curve at lowest SBP levels, but not obviously at lowest DBP levels. Analysing intervals of SBP with 130-134 mmHg as reference at Cox regression, adjusted hazard ratios (HR) for fatal/nonfatal CHD, stroke and CVD with at least 140 mmHg were 1.22 [95% confidence interval (CI): 1.08-1.39], 1,43 (1.18-1.72), 1.26 (1.13-1.41), all P<0.001. HR with 115-129 and 135-139 mmHg were nonsignificant, whereas increased with 100-114 mmHg, 1.96 (P<0.001), 1.75 (P=0.02), 2.08 (P < 0.001), respectively. With DBP 75-79 mmHg as reference, adjusted HR for fatal/nonfatal CHD, stroke and CVD with DBP 80-84 mmHg were 1.42 (1.26-1.59), 1.46 (1.24-1.72), 1.39 (1.26-1.53), all P< 0.001. Corresponding HR with DBP at least 85 mmHg were 1.70 (1.50-1.92), 2.35 (1.99-2.77), 1..87 (1.69-2.07), all P < 0.001. Corresponding HR with DBP 60-69 and 70-74 mmHg were nonsignificant. The picture was similar in 7059 patients with previous CVD and in untreated patients. Conclusion: BP around 130-135/75-79 mmHg showed lower risks of cardiovascular diseases in patients with type 2 diabetes.

  • 19.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Gudbjörnsdottir, Soffia
    Eliasson, Björn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eeg-Olofsson, Katarina
    Nilsson, Peter M.
    Systolic blood pressure and risk of cardiovascular diseases in type 2 diabetes: an observational study from the Swedish national diabetes register2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, no 10, p. 2026-2035Article in journal (Refereed)
    Abstract [en]

    Objectives: To estimate risks of fatal/nonfatal coronary heart disease (CHD), stroke and cardiovascular disease (CVD) with SBP in an observational study of patients with type 2 diabetes.

    Methods: Twelve thousand, six hundred and seventy-seven patients aged 30–75 years, treated with antihypertensive drugs, without previous congestive heart failure, followed for 5 years.

    Results: Risk curves of CHD and stroke increased progressively with higher baseline or updated mean SBP in a Cox model, in all participants, and in two subgroups without (n = 10 304) or with (n = 2373) a history of CVD, with no J-shaped risk curves at low SBP levels. Hazard ratios for CHD and stroke per 10-mmHg increase in updated mean SBP in all participants, adjusting for clinical characteristics and traditional risk factors, were 1.08 (1.04–1.13) and 1.20 (1.13–1.27), P < 0.001. With updated mean SBP of 110–129 mmHg as reference, SBP of at least 140 mmHg showed risk increases of 37% for CHD, 86% for stroke and 44% for CVD (P = 0.001 to <0.001), whereas SBP of 130–139 mmHg showed nonsignificant risk increases for these outcomes. With baseline SBP of 110–129 mmHg, CHD and CVD risks increased with further SBP reduction, hazard ratios were 1.77 and 1.73 (P = 0.002), but decreased considerably for CHD, stroke and CVD with higher baseline SBP.

    Conclusion: Risks of CHD and stroke increased progressively with higher SBP, with no J-shaped curves, although risk increase was significant only for SBP of at least 140 mmHg, but not comparing 130–139 and 110–129 mmHg. Additionally, baseline SBP of 110–129 mmHg showed increased CHD and CVD risk with further SBP reduction during follow-up, whereas baseline SBP of at least 130 showed benefits.

  • 20.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Nilsson, Peter M.
    Eliasson, Björn
    Eeg-Olofsson, Katarina
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjörnsdottir, Soffia
    Samband mellan riskfaktorer och komplikationer vid diabetes: samband mellan riskfaktorer och komplikationer vid diabetes [Connections between risk factors and complications in diabetes. A report after 13 years with the National Diabetes Registry (NDR)]2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 42, p. 2684-9Article in journal (Refereed)
  • 21.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eliasson, Bjorn
    Gudbjornsdottir, Soffia
    Nilsson, Peter M.
    Different methods to present the effect of blood pressure on cardiovascular diseases by Cox regression2012In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 30, no 1, p. 235-237Article in journal (Refereed)
  • 22.
    Cederholm, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nilsson, Peter M
    Eeg-Olofsson, Katarina
    Eliasson, Björn
    Gudbjörnsdottir, Soffia
    Effect of tight control of HbA1c and blood pressure on cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR)2009In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 86, no 1, p. 74-81Article in journal (Refereed)
    Abstract [en]

    AIM: To estimate hazard ratio (HR) of first incident fatal/non-fatal cardiovascular diseases (CVD) in female/male type 2 diabetic patients, with tight versus adverse control of HbA1c and blood pressure (BP) at baseline, age 30-70 years, no baseline CVD, followed for mean 5.7 years. METHODS: 2593 patients with tight control of HbA1c <7.5% and BP < or = 140/90 mmHg (median 6.5%/130/80 mmHg), and 2160 patients with adverse control 7.5-9.0%/141-190/91-110 mmHg (median 8.1%/155/85 mmHg). RESULTS: The hazard ratio (HR) for CVD with tight/adverse control was 0.67 (0.55-0.80; p<0.001), adjusting for age, sex, duration, hypoglycaemic treatment, smoking, BMI, lipid-lowering drugs, antihypertensive drugs, microalbuminuria. Adjusted HR for myocardial infarction, coronary heart disease, stroke and total mortality were 0.72 (0.56-0.92; p=0.01), 0.69 (0.55-0.86; p<0.001), 0.62 (0.45-0.84; p<0.001), 1.00 (0.72-1.39). The partial population-attributable risk percent for myocardial infarction, stroke and CVD was 23%, 33%, 29% if adverse HbA1c/BP control could be avoided, while 43%, 38%, 39% with overweight and smoking also avoided. Baseline lower BMI and absence of microalbuminuria were associated with tight control. CONCLUSION: Median difference of HbA1c/BP 1.6%/25/5 mmHg between tight and adverse control considerably reduced the risk of cardiovascular diseases. The findings call for a multi-factorial approach to improve HbA1c, BP, obesity, smoking, and microalbuminuria.

  • 23.
    Crawley, Danielle
    et al.
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Chamberlain, Florence
    Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Garmo, Hans
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Carroll, Paul
    Guys & St Thomas NHS Fdn Trust, Dept Diabet & Endocrinol, London, England.
    Van Hemelrijck, Mieke
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus2018In: ecancermedicalscience, ISSN 1754-6605, E-ISSN 1754-6605, Vol. 12, article id 802Article, review/survey (Refereed)
    Abstract [en]

    Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.

  • 24.
    Crawley, Danielle
    et al.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Garmo, Hans
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, London, England.; Kings Coll Londons, Comprehens Biomed Res Ctr, London, England. .
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Peri Operat Sci Urol & Androl, Umea, Sweden.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Uppsala, Sweden.
    Holmberg, Lars
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer.2018In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, no 2, p. 209-216Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

    SUBJECTS AND METHODS: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate- (T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

    RESULTS: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

    CONCLUSIONS: Men with T2DM were less likely to receive curative treatment for localized intermediate- and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under- nor overtreated.

  • 25.
    Dahlgren, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Variants of the TCF7L2 gene are associated with beta cell dysfunction and confer an increased risk of type 2 diabetes mellitus in the ULSAM cohort of Swedish elderly men2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 9, p. 1852-1857Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis:

    In a population-based cohort of elderly men with well-defined phenotypes and biochemical markers related to type 2 diabetes mellitus, we analysed two single nucleotide polymorphisms (SNPs), rs7903146 and rs12255372, in the transcription factor 7-like 2 gene (TCF7L2), which are associated with an increased risk of type 2 diabetes mellitus.

    Materials and methods:

    The 1,142 subjects were from the population-based Uppsala Longitudinal Study of Adult Men cohort study (see http://www.pubcare.uu.se/ULSAM/ , last accessed in May 2007). Insulin sensitivity was assessed using a euglycaemic-hyperinsulinaemic clamp; fasting intact and 32-33 split proinsulin, immunoreactive insulin and specific insulin were measured in plasma samples. The SNPs rs7903146 and rs12255372 were genotyped using a fluorescent homogeneous single base extension assay. The SNP genotypes were analysed against diabetes prevalence at age 70 using logistic regression and against quantitative biochemical measures using linear regression analysis.

    Results:

    We replicated the association with type 2 diabetes mellitus for both SNPs in this cohort of elderly males. The highest significant odds ratio (2.15, 95% CI 1.20-3.85) was found for SNP rs7903146. The odds ratio for SNP rs12255372 was 1.69 (95% CI 1.20-2.39). Both TCF7L2 SNPs were found to be significantly associated with plasma proinsulin when adjusting for insulin sensitivity, both in the whole cohort and when the diabetic subjects were excluded. Analysis for fasting plasma insulin or insulin sensitivity did not give significant results.

    Conclusions/interpretation:

    The association between the risk alleles of the two SNPs studied and levels of proinsulin in plasma, identified when adjusting for insulin sensitivity using euglycaemic-hyperinsulinaemic clamp measurements in this study, is an important novel finding.

  • 26.
    Dunder, Kristina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, Lars
    Department of Medical Sciences.
    Lagerqvist, Bo
    Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Vessby, Bengt
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lithell, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Cardiovascular risk factors for stable angina pectoris versus unheralded myocardial infarction.2004In: Am Heart J, ISSN 1097-6744, Vol. 147, no 3, p. 502-8Article in journal (Refereed)
  • 27.
    Dunder, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lithell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Evaluation of a scoring scheme, including proinsulin and the apolipoprotein B/apolipoprotein A1 ratio, for the risk of acute coronary events in middle-aged men: Uppsala Longitudinal Study of Adult Men (ULSAM)2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 148, no 4, p. 596-601Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In recent years, the importance of circulating levels of proinsulin and apolipoproteins as risk factors for myocardial infarction (MI) has been highlighted. The aims of the current study were to investigate whether introduction of these new markers of coronary risk could improve the performance of a risk prediction score and to compare this new score with traditional scoring schemes, such as the Framingham Study and the Prospective Cardiovascular Munster (PROCAM) Study schemes.

    METHODS: From 1970 to 1973 all 50-year-old men in Uppsala, Sweden, were invited to participate in a health survey aimed at identifying risk factors for cardiovascular disease (the Uppsala Longitudinal Study of Adult Men [ULSAM] cohort). The current study investigated metabolic characteristics at baseline and the incidence of fatal and nonfatal MI (n = 251) during 28.7 years of follow-up in 1108 men who were free of coronary heart disease at baseline.

    RESULTS: The risk prediction score was derived from one half of the population sample from the ULSAM cohort and included systolic blood pressure, smoking, family history of MI, serum proinsulin, and the ratio between apolipoprotein B and apolipoprotein A1. The score was highly predictive for future MI (hazard ratio, 1.77 for a 1 SD increase; 95% CI, 1.49 to 2.10, P <.0001) in the other half of the population that was not used for generating the score. The ULSAM score performed slightly better than the Framingham and PROCAM scores (evaluated as areas under the receiver operating curves; Framingham, 61%; PROCAM, 63%; ULSAM, 66%; P =.08).

    CONCLUSIONS: A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was highly predictive for future fatal and nonfatal MI and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.

  • 28.
    Dunder, Kristina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Department of Public Health and Caring Sciences. Akut- och internmedicin.
    Lind, Lars
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Zethelius, Björn
    Department of Public Health and Caring Sciences.
    Berglund, Lars
    Department of Public Health and Caring Sciences.
    Lithell, Hans
    Department of Public Health and Caring Sciences.
    Increase in blood glucose concentration during antihypertensive treatment as a predictor of myocardial infarction: population based cohort study.2003In: BMJ, ISSN 1468-5833, Vol. 326, no 7391, p. 681-Article in journal (Refereed)
  • 29.
    Dunder, Kristina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lind, Lars
    Department of Medical Sciences.
    Zethelius, Björn
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lithell, Hans
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Public Health and Caring Sciences.
    A new Q/QS pattern on the resting electrocardiogram is associated with impaired insulin secretion and a poor prognosis in elderly men independently of history of myocardial infarction.2004In: J Intern Med, ISSN 0954-6820, Vol. 255, no 2, p. 221-8Article in journal (Refereed)
  • 30. Eeg-Olofsson, K
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Nilsson, P M
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nunez, L
    Gudbjörnsdóttir, S
    Eliasson, B
    Risk of cardiovascular disease and mortality in overweight and obese patients with type 2 diabetes: an observational study in 13,087 patients2009In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no 1, p. 65-73Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The aim of this study of type 2 diabetic patients in the Swedish National Diabetes Register was to study the associations of BMI, overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI >or= 30 kg/m(2)) with cardiovascular disease in type 2 diabetes, as these associations have not previously been clarified. METHODS: Patients aged 30-74 years with no previous CHD or stroke (N = 13,087) were followed for a mean of 5.6 years until 2003 for fatal or non-fatal CHD, stroke, cardiovascular disease (CHD or stroke) and total mortality. In total, 1,922 cardiovascular-disease events occurred, based on 64,864 person-years. RESULTS: The relative risks of CHD, stroke, cardiovascular disease and total mortality for a 5 unit increase in BMI at baseline were 15%, 11%, 13% and 27%, respectively, using Cox regression analysis, after adjusting for age, sex, diabetes duration, hypoglycaemic treatment and smoking (model 1), and were 9%, 4% (not significant), 7% and 20%, respectively, when adjusting also for HbA(1c), blood pressure, antihypertensive drugs, lipid-reducing drugs and microalbuminuria (model 2). Adjusted hazard ratios (model 1) for CHD, cardiovascular disease and total mortality with overweight were 1.27 (95% CI 1.09-1.48), 1.24 (1.09-1.41) and 1.16 (0.94-1.45), respectively, and 1.49 (1.27-1.76), 1.44 (1.26-1.64) and 1.71 (1.36-2.14) with obesity, as compared with normal weight. Significant hazard ratios were attenuated when adjusted according to model 2. For a 1 unit increase in BMI during follow-up, the relative risk of CHD (model 2) was 1.13 (1.04-1.23; p = 0.005). CONCLUSIONS/INTERPRETATION: Both overweight and obesity independently increased the risk of CHD and cardiovascular disease in patients with type 2 diabetes. The CHD risk was higher with increasing BMI than with stable or decreasing BMI during the study.

  • 31. Eeg-Olofsson, K
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Nilsson, P M
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Svensson, A-M
    Gudbjörnsdóttir, S
    Eliasson, B
    New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR).2010In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 268, no 5, p. 471-482Article in journal (Refereed)
    Abstract [en]

    AIMS

    To analyse the association between glycosylated haemoglobin A1c (HbA1c) and cardiovascular disease (CVD) in patients with type 2 diabetes in the Swedish National Diabetes Register (NDR).

    METHODS

    An observational study of 18 334 patients (age 30-79 years, previous CVD in 18%, baseline HbA1c 5.0-10.9%) who were followed for 6 years (mean 5.6 years) from 1997/1998 until 2003.

    RESULTS

    Hazard ratios per 1% unit increase in baseline or updated mean HbA1c for fatal/nonfatal coronary heart disease (CHD), CVD and total mortality were 1.11-1.13, 1.10-1.11 and 1.09-1.10, respectively (all P < 0.001), adjusted for several risk factors and clinical characteristics in Cox regression. Adjusted 6-year event rates increased with higher baseline or updated mean HbA1c with no J-shaped risk curves, in all patients and also when subgrouping by shorter (mean 3 years) or longer (mean 14 years) diabetes duration, by presence or absence of previous CVD, or by treatment with oral hypoglycaemic agents (OHAs) or insulin. Risk reductions of 20% for CHD and 16% for CVD (P < 0.001) were found in patients with a baseline mean HbA1c of 6.5%, compared to those with a mean level of 7.5%. Compared to OHA-treated patients, insulin-treated patients had an increased risk of total mortality, due almost exclusively to an increased risk of non-CVD mortality, and due less to a weakly significant increased risk of fatal CVD. HbA1c was not associated with non-CVD mortality.

    CONCLUSIONS

    This observational study showed progressively increasing risks of CHD, CVD and total mortality with higher HbA1c, and no risk increase at low HbA1c levels even with longer diabetes duration, previous CVD or treatment with either insulin or OHAs. Patients achieving HbA1c <7% showed benefits for risk reduction.

  • 32. Eeg-Olofsson, K.
    et al.
    Gudbjornsdottir, S.
    Eliasson, B.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    The triglycerides-to-HDL-cholesterol ratio and cardiovascular disease risk in obese patients with type 2 diabetes: a report from the Swedish national diabetes register2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, p. S185-S186Article in journal (Other academic)
  • 33. Eeg-Olofsson, K.
    et al.
    Gudbjornsdottir, S.
    Eliasson, B.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Svensson, A. -M
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Multifactorial risk factor control in clinical practice and risk of cardiovascular disease in type 2 diabetes: report from the Swedish national diabetes register2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no S1, p. S493-S493Article in journal (Other academic)
  • 34. Eeg-Olofsson, Katarina
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Nilsson, Peter M
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Svensson, Ann-Marie
    Gudbjörnsdóttir, Soffia
    Eliasson, Björn
    Glycemic control and cardiovascular disease in 7,454 patients with type 1 diabetes: an observational study from the Swedish National Diabetes Register (NDR).2010In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 33, no 7, p. 1640-1646Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    We assessed the association between A1C and cardiovascular diseases (CVDs) in an observational study of patients with type 1 diabetes followed for 5 years.

    RESEARCH DESIGN AND METHODS

    A total of 7,454 patients were studied from the Swedish National Diabetes Register (aged 20-65 years, diabetes duration 1-35 years, followed from 2002 to 2007).

    RESULTS

    Hazard ratios (HRs) for fatal/nonfatal coronary heart disease (CHD) per 1% unit increase in baseline or updated mean A1C at Cox regression analysis were 1.31 and 1.34 and 1.26 and 1.32, respectively, for fatal/nonfatal CVD (all P < 0.001 after adjustment for age, sex, diabetes duration, blood pressure, total and LDL cholesterol, triglycerides, BMI, smoking, and history of CVD). HRs were only slightly lower for CHD (P = 0.002) and CVD (P = 0.002-0.007) after also adjusting for albuminuria. Adjusted 5-year event rates of CHD and CVD increased progressively with higher A1C, ranging from 5 to 12%, as well as when subgrouped by shorter (1-20 years) or longer (21-35 years) duration of diabetes. A group of 4,186 patients with A1C 5-7.9% (mean 7.2) at baseline showed risk reductions of 41% (95% confidence intervals: 15-60) (P = 0.005) for fatal/nonfatal CHD and 37% (12-55) (P = 0.008) for CVD, compared with 3,268 patients with A1C 8-11.9% (mean 9.0), fully adjusted also for albuminuria.

    CONCLUSIONS

    This observational study of patients in modern everyday clinical practice demonstrates progressively increasing risks for CHD and CVD with higher A1C, independently of traditional risk factors, with no J-shaped risk curves. A baseline mean A1C of 7.2% showed considerably reduced risks of CHD and CVD compared with A1C 9.0%, emphasizing A1C as a strong independent risk factor in type 1 diabetes.

  • 35. Eeg-Olofsson, Katarina
    et al.
    Gudbjornsdottir, Soffia
    Eliasson, Bjorn
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    The triglycerides-to-HDL-cholesterol ratio and cardiovascular disease risk in obese patients with type 2 diabetes: An observational study from the Swedish National Diabetes Register (NDR)2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 106, no 1, p. 136-144Article in journal (Refereed)
    Abstract [en]

    Aims: Assessing the association between BMI and risk of coronary heart disease (CHD), cardiovascular disease (CVD) and mortality in patients with type 2 diabetes, also with regard to higher or lower levels of the ratio triglycerides-to-HDL-cholesterol (TG:HDL). Methods: 54,061 patients with BMI >= 18.5 kg/m(2), mean age and duration 61.5 +/- 8 and 6.9 +/- 6 years, 59% males, 14% with CVD history, from the Swedish National Diabetes Register, followed for mean 4.8 years. Results: Adjusting at Cox regression for non-BMI-linked (age, sex, smoking, CVD history) and BMI-linked (blood lipids, blood pressure, HbA1c, albuminuria) covariates, hazard ratios (HR) for fatal/nonfatal CHD and CVD were mainly increased with prominent obesity (BMI >= 35 kg/m(2)), 1.19 (p = 0.01) and 1.17 (p = 0.009), compared to normal weight (BMI 18.5-24.9 kg/m(2)), although increased also with obesity (BMI 30-34.9 kg/m(2)), 1.34 and 1.30 (p < 0.001), when adjusting only for non-BMI-linked covariates. Stratifying by 75th percentile of TG: HDL, with normal weight and TG: HDL < 1.9 as reference, obese and prominently obese with TG: HDL >= 1.9 had considerably increased HR around 1.7 for fatal/nonfatal CHD and 1.6 for CVD (p < 0.001), while obese and prominently obese with TG: HDL < 1.9 only had HR 1.2-1.3 for CHD and CVD (p 0.003-<0.01). Conclusion: Obese T2D patients with high TG: HDL, associated with increased insulin resistance, had considerably increased risk of CHD and CVD.

  • 36.
    Eeg-Olofsson, Katarina
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Uppsala, Sweden..
    Gudbjornsdottir, Soffia
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Eliasson, Bjorn
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Svensson, Ann-Marie
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Considerably decreased risk of cardiovascular disease with combined reductions in HbA1c, blood pressure and blood lipids in type 2 diabetes: Report from the Swedish National Diabetes Register2016In: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 13, no 4, p. 268-277Article in journal (Refereed)
    Abstract [en]

    Objectives: Assess the effect of risk factors changes on risk for cardiovascular disease and mortality in patients with type 2 diabetes selected from the Swedish National Diabetes Register. Methods: Observational study of 13,477 females and males aged 30-75years, with baseline HbA1c 41-67mmol/mol, systolic blood pressure 122-154mmHg and ratio non-HDL:HDL 1.7-4.1, followed for mean 6.5years until 2012. Four groups were created: a reference group (n=6757) with increasing final versus baseline HbA1c, systolic blood pressure and non-HDL:HDL cholesterol during the study period, and three groups with decreasing HbA1c (n=1925), HbA1c and systolic blood pressure (n=2050) or HbA1c and systolic blood pressure and non-HDL:HDL (n=2745). Results: Relative risk reduction for fatal/nonfatal cardiovascular disease was 35% with decrease in HbA1c only (mean 6 to final 49mmol/mol), 56% with decrease in HbA1c and systolic blood pressure (mean 12 to final 128mmHg) and 75% with combined decreases in HbA1c, systolic blood pressure and non-HDL:HDL (mean 0.8 to final 2.1), all p<0.001 adjusting for clinical characteristics, other risk factors, treatments and previous cardiovascular disease. Similar risk reductions were found for fatal/nonfatal coronary heart disease, fatal cardiovascular disease, all-cause mortality and also in a subgroup of 3038 patients with albuminuria. Conclusion: Considerable risk reductions for cardiovascular disease and mortality were seen with combined long-term risk factor improvement.

  • 37.
    Eggers, Kai M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Al-Shakarchi, Jinan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    High-sensitive cardiac troponin T and its relations to cardiovascular risk factors, morbidity, and mortality in elderly men2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 541-+Article in journal (Refereed)
    Abstract [en]

    Background Cardiac troponin is emerging as risk indicator in community-dwelling populations. In this study, we investigated the associations of cardiac troponin T (cTnT) to cardiovascular (CV) disease and outcome in elderly men. Methods Cardiac troponin T was measured using a high-sensitive assay in 940 men aged 71 years participating in the Uppsala Longitudinal Study of Adult Men. We assessed both the cross-sectional associations of cTnT to CV risk factors and morbidities including cancer and the longitudinal associations to outcomes over 10 years of follow-up. Results Cardiac troponin T levels were measurable in 872 subjects (92.8%). In the cross-sectional analyses, cTnT was associated to CV risk factors (diabetes, smoking, and obesity), renal dysfunction, CV disease including atrial fibrillation and coronary artery disease, and biomarkers of inflammation and left ventricular dysfunction. In the longitudinal analyses, cTnT independently predicted total mortality and CV events including stroke. The standardized adjusted hazard ratio regarding the composite CV end point was 1.5 (95% CI 1.3-1.8), P < .001, for men with prevalent CV disease and 1.2 (95% CI 1.0-1.4), P = .02, for men without. Cardiac troponin T improved discrimination metrics for all outcomes in the total population. This was mainly driven by the prognostic value of cTnT in subjects with prevalent CV disease. Conclusions In community-dwelling men, cTnT levels are associated to CV risk factors and morbidities and predict both fatal and nonfatal CV events. The relations to outcome are mainly seen in men with prevalent CV disease indicating that the prognostic value of cTnT in subjects free from CV disease is limited.

  • 38. Ekstrom, N.
    et al.
    Miftaraj, M.
    Svensson, A. -M
    Sundell, K. Andersson
    Eeg-Olofsson, K.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjornsdottir, S.
    Eliasson, B.
    Durability of oral hypoglycaemic agents in drug naive patients with type 2 diabetes: observational study from the Swedish National Diabetes Register (NDR)2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, p. S91-S92Article in journal (Other academic)
  • 39. Ekström, N.
    et al.
    Miftaraj, M.
    Svensson, A. -M
    Sundell, K. Andersson
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjörnsdottir, S.
    Eliasson, B.
    Glucose-lowering treatment and clinical results in 163 121 patients with type 2 diabetes: an observational study from the Swedish national diabetes register2012In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 14, no 8, p. 717-726Article in journal (Refereed)
    Abstract [en]

    Aims: To analyse clinical characteristics and treatment results in unselected type 2 diabetes mellitus (T2DM) patients, with non-pharmacological treatment as well as the most commonly used pharmacological glucose-lowering treatment regimens, in everyday clinical practice. Methods: In this population-based cross-sectional study, information was linked from the Swedish National Diabetes Register, Prescribed Drug Register and Patient Register. T2DM patients with non-pharmacological treatment and T2DM patients continuously using the 12 most common pharmacological treatment regimens were included in the study (n = 163121). Results: There were statistically significant differences in clinical characteristics between the groups. Patients with insulin-based treatment regimens had the longest duration of diabetes and more cardiovascular risk factors than the T2DM-population in general. The proportion of patients reaching HbA1c =7% varied between 70.1% (metformin) and 25.0% [premixed insulin (PMI) + SU) in patients with pharmacological treatment. 84.8% of the patients with non-pharmacological treatment reached target. Compared to patients on metformin, patients on other pharmacological treatments had a lower likelihood, with hazard ratios ranging from 0.58; 95% confidence interval (CI), 0.540.63 to 0.97;0.940.99, of having HbA1c =7% (adjusted for covariates). Patients on insulin-based treatments had the lowest likelihood, while non-pharmacological treatment was associated with an increased likelihood of having HbA1c =7%. Conclusion: This nation-wide study shows insufficiently reached treatment goals for haemoglobin A1c (HbA1c) in all treatment groups. Patients on insulin-based treatment regimens had the longest duration of diabetes, more cardiovascular risk factors and the highest proportions of patients not reaching HbA1c target.

  • 40. Ekström, Nils
    et al.
    Schiöler, Linus
    Svensson, Ann-Marie
    Eeg-Olofsson, Katarina
    Miao Jonasson, Junmei
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eliasson, Björn
    Gudbjörnsdottir, Soffia
    Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 4, p. e001076-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    To evaluate the effectiveness and safety of metformin use in clinical practice in a large sample of pharmacologically treated patients with type 2 diabetes and different levels of renal function.

    DESIGN

    Observational study between July 2004 and December 2010, mean follow-up 3.9 years.

    SETTING

    Hospital outpatient clinics and primary care in Sweden.

    PARTICIPANTS

    51 675 men and women with type 2 diabetes, registered in the Swedish National Diabetes Register, and on continuous glucose-lowering treatment with oral hypoglycaemic agents (OHAs) or insulin.

    MAIN OUTCOME MEASURES

    Risks of cardiovascular disease (CVD), all-cause mortality and acidosis/serious infection, associated with each treatment regimens, were analysed in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. Covariance adjustment and propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression.

    RESULTS

    Compared with metformin in monotherapy, HRs for fatal/non-fatal CVD and all-cause mortality with all other OHAs combined (approximately 80% sulphonylureas) in monotherapy were 1.02 (95% CI 0.93 to 1.12) and 1.13 (1.01 to 1.27), while 1.18 (1.07 to 1.29) and 1.34 (1.19 to 1.50) with insulin in monotherapy, adjusting using propensity scores. Metformin, compared with any other treatment, showed reduced risks of acidosis/serious infection (adjusted HR 0.85, 95% CI 0.74 to 0.97) and all-cause mortality (HR 0.87, 95% CI 0.77 to 0.99), in patients with eGFR 45-60 ml/min/1.73 m(2), and no increased risks of all-cause mortality, acidosis/serious infection or CVD were found in patients with eGFR 30-45 ml/min/1.73 m(2).

    CONCLUSIONS

    Metformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects.

  • 41. Ekström, Nils
    et al.
    Svensson, Ann-Marie
    Miftaraj, Mervete
    Andersson Sundell, Karolina
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eliasson, Björn
    Gudbjörnsdottir, Soffia
    Durability of oral hypoglycemic agents in drug naïve patients with type 2 diabetes: report from the Swedish National Diabetes Register (NDR)2015In: BMJ open diabetes research & care, ISSN 2052-4897, Vol. 3, article id e000059Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyze the durability of monotherapy with different classes of oral hypoglycemic agents (OHAs) in drug naïve patients with type 2 diabetes mellitus (T2DM) in real life.

    METHODS: Men and women with T2DM, who were new users of OHA monotherapy and registered in the Swedish National Diabetes Register July 2005-December 2011, were available (n=17 309) and followed for up to 5.5 years. Time to monotherapy failure, defined as discontinuation of continuous use with the initial agent, switch to a new agent, or add-on treatment of a second agent, was analyzed as a measure of durability. Baseline characteristics were balanced by propensity score matching 1:5 between groups of sulfonylurea (SU) versus metformin (n=4303) and meglitinide versus metformin (n=1308). HRs with 95% CIs were calculated using Cox regression models.

    RESULTS: SU and meglitinide, as compared with metformin, were associated with increased risk of monotherapy failure (HR 1.74; 95% CI 1.56 to 1.94 and 1.66; 1.37 to 2.00 for SU and meglitinide, respectively). When broken down by type of monotherapy failure, SU and meglitinide were associated with an increased risk of add-on treatment of a second agent (HR 3.14; 95% CI 2.66 to 3.69 and 2.52; 1.89 to 3.37 for SU and meglitinide, respectively) and of switch to a new agent (HR 2.81; 95% CI 2.01 to 3.92 and 3.78; 2.25 to 6.32 for SU and meglitinide, respectively). The risk of discontinuation did not differ significantly between the groups.

    CONCLUSIONS: In this nationwide observational study reflecting clinical practice, SU and meglitinide showed substantially increased risk of switch to a new agent or add on of a second agent compared with metformin. These results indicate superior glycemic durability with metformin compared with SU and also meglitinide in real life.

  • 42. Eliasson, B
    et al.
    Gudbjornsdottir, S
    Eeg-Olofsson, K
    Svensson, AM
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    LDL-cholesterol is not the best blood lipid predictor of CHD risk in type 2 diabetes2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, no Suppl 1Article in journal (Refereed)
  • 43. Eliasson, B
    et al.
    Gudbjörnsdottir, S
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eeg-Olofsson, K
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    LDL-cholesterol versus non-HDL-to-HDL-cholesterol ratio and risk for coronary heart disease in type 2 diabetes2014In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 21, no 11, p. 1420-1428Article in journal (Refereed)
    Abstract [en]

    AIMS: We assessed the association between different blood lipid measures and risk of fatal/nonfatal coronary heart disease (CHD), which has been less analysed previously in type 2 diabetes.

    DESIGN, METHODS: Observational study of 46,786 patients with type 2 diabetes, aged 30-70 years, from the Swedish National Diabetes Register, followed for a mean of 5.8 years until 2009. Baseline and updated mean low-density lipoprotein (LDL)-, high-density lipoprotein (HDL)-, non-HDL-cholesterol, and non-HDL-to-HDL-cholesterol ratio were measured.

    RESULTS: Hazard ratios (HR) for CHD with quartiles 2-4 of baseline lipid measures, with lowest quartile 1 as reference: 1.03-1.29-1.63 for LDL; 1.23-1.41-1.95 for non-HDL; 1.29-1.39-1.57 for HDL; and 1.31-1.67-2.01 for non-HDL:HDL, all p < 0.001 except for quartile 2 of LDL, when adjusted for clinical characteristics and nonlipid risk factors. A similar picture was seen with updated mean values. Splines with absolute 6-year CHD rates in a Cox model showed decreasing rates only down to around 3 mmol/l for LDL, with linearly decreasing rates to the lowest level of non-HDL:HDL.Non-HDL and HDL were independent additive risk factors for CHD risk. HRs per 1 SD continuous decrease in baseline or updated mean HDL were 1.14-1.17 when fully adjusted as above, and 1.08-1.13 when also adjusted for non-HDL (p < 0.001). HRs were 1.13-1.16 adjusted for LDL, and 1.22-1.26 adjusted for total cholesterol and triglycerides (p < 0.001). Splines showed progressively increasing 6-year CHD rates with lower HDL down to 0.5 mmol/l.

    CONCLUSIONS: This study suggests that lower levels of non-HDL:HDL are a better risk marker for CHD than LDL-cholesterol below 3 mmol/l.

  • 44. Eliasson, Björn
    et al.
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eeg-Olofsson, Katarina
    Svensson, Anne-Marie
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjörnsdottir, Soffia
    Clinical Usefulness of Different Lipid Measures for Prediction of Coronary Heart Disease in Type 2 Diabetes: A report from the Swedish National Diabetes Register2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 9, p. 2095-2100Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We assessed the association between different blood lipid measures and risk of fatal/nonfatal coronary heart disease (CHD).

    RESEARCH DESIGN AND METHODS: We conducted an observational study of patients with type 2 diabetes from the Swedish National Diabetes Register. Baseline LDL cholesterol, non-HDL cholesterol, ratio of non-HDL to HDL cholesterol (non-HDL:HDL), and ratio of triacylglycerol to HDL cholesterol (TG:HDL) was measured in 18,673 patients aged 30-70 years, followed for a mean of 4.8 years from 2003 to 2007.

    RESULTS: Hazard ratios (HRs) for CHD per 1-SD increment in lipid measures were 1.23 with non-HDL:HDL, 1.20 with non-HDL cholesterol, 1.17 with LDL cholesterol, and 1.15 with TG: HDL (all P < 0.001 when adjusted for clinical characteristics and nonlipid risk factors). The best global model fit was found with non-HDL:HDL. When patients within the lowest tertile of a lipid measure were compared with those with all lipid measures within the highest tertile, the adjusted HR for CHD was 0.62 with non-HDL:HDL <3.5 mmol/L, 0.65 with non-HDL cholesterol <3.3 mmol/L, and 0.70 with LDL cholesterol <2.5 mmol/L (all P < 0.001). The lowest tertile of LDL and non-HDL cholesterol corresponded with treatment targets according to U.S. and European guidelines. HRs for CHD were 0.52, 0.62, and 0.66 with the lowest deciles of non-HDL:HDL, non-HDL cholesterol, and LDL cholesterol mmol/L (all P < 0.001). Mean TG:HDL was considerably lower in patients within the lowest tertile of non-HDL:HDL, 0.82 +/- 0.47, than in those within the lowest tertile of LDL cholesterol (<2.5 mmol/L), 1.49 +/- 1.03.

    CONCLUSIONS: Non-HDL:HDL had a stronger effect on CHD risk than LDL cholesterol, and low TG:HDL values were more often seen within the lowest non-HDL:HDL tertile than within the lowest LDL cholesterol tertile. LDL cholesterol was not the best predictor of CHD risk in type 2 diabetes.

  • 45. Eriksson, Mats
    et al.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eeg-Olofsson, Katarina
    Nilsson, Peter M.
    Gudbjörnsdottir, Soffia
    Cederholm, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eliasson, Björn
    Blood lipids in 75,048 type 2 diabetic patients: a population-based survey from the Swedish National diabetes register2011In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 18, no 1, p. 97-105Article in journal (Refereed)
    Abstract [en]

    Background: Type 2 diabetes and diabetic dyslipidemia are high-risk conditions for cardiovascular disease. However, the description of the distribution of blood lipids in diabetic patients has not been based on population-based surveys. The aim of this study was to describe diabetic dyslipidemia in a large unselected sample of patients from the Swedish National Diabetes Register. Methods: Blood lipid profiles and clinical characteristics in 75,048 type 2 diabetic patients (57% men) were studied. Results: Pronounced hypertriglyceridemia (triglycerides >4.0mmol/l) was seen in 3.4% of the patients. Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and non-HDL-C were generally higher, and LDL-C/HDL-C and Non-HDL-C/HDL-C ratios were lower in women. Mean TC, LDL-C as well as HDL-C values were lower in patients treated with lipid-lowering agents, whereas triglycerides was higher than in the untreated patients. In patients not treated with lipid-lowering agents all blood lipids increased in women and decreased in men (except HDL-C) at higher ages. Patients with LDL-C/HDL-C ratio >= 3 were slightly younger, less frequently used lipid-lowering drugs and had not so often a history of coronary heart disease or stroke. Conclusion: The distribution of blood lipids in this large sample of unselected type 2 diabetic patients challenges the previous conception of diabetic dyslipidemia, and calls for new studies to explain the roles of LDL-C and HDL-C as strong cardiovascular risk factors in type 2 diabetes.

  • 46. Fall, Katja
    et al.
    Garmo, Hans
    Gudbjornsdottir, Soffia
    Stattin, Par
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Diabetes Mellitus and Prostate Cancer Risk; A Nationwide Case-Control Study within PCBaSe Sweden2013In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 22, no 6, p. 1102-1109Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes mellitus (DM) increases the risk for cancer at almost all sites, but data on the association with prostate cancer are inconsistent. Methods: We assessed the risk of a prostate cancer diagnosis among men with type 2 (T2)DM in a nationwide population-based case-control study including 44,352 men with prostate cancer identified through the Prostate Cancer data Base Sweden (PCBaSe) between 2002 and 2006 and 221,495 age-matched men from the general population. Results: Overall, the risk of prostate cancer among men with T2DM was lower than among men without T2DM [OR, 0.80; 95% confidence interval (CI), 0.76-0.85]. The risk decreased with longer disease duration and was observed across all tumor risk categories, although most clearly among men with low risk tumors (OR, 0.71; 95% CI, 0.64-0.80). The risk for prostate cancer was reduced among diabetic men on dietary treatment only (OR, 0.89; 95% CI, 0.80-0.99) but more markedly among men on oral hypoglycemic agents (OR, 0.80; 95% CI, 0.74-0.87) and insulin (OR, 0.72; 95% CI, 0.69-0.81). Obese diabetic men (BMI > 30 kg/m(2)) showed a reduced risk (OR, 0.72; 95% CI, 0.65-0.80) compared with men without diabetes. There was a trend of decreasing risk with increasing levels of HbA1c (P < 0.05). Conclusions: This nationwide study confirmed a reduced risk of being diagnosed with prostate cancer among men with T2DM, especially for low-risk tumors. An altered hormonal milieu is a plausible explanation, although the possibility of decreased prostate cancer detection among diabetic men cannot be ruled out. Impact: This is the largest study to examine the association between T2DM and prostate cancer accounting for tumor risk group and diabetes treatment.

  • 47.
    Franzon, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Uppsala, Sweden.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in Octogenarian Men2017In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, no 9, p. 1953-1960Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To examine the longitudinal associations between aging with preserved functionality, i.e. independent aging and survival, and lifestyle variables, dietary pattern and cardiovascular risk factors.

    DESIGN: Cohort study.

    SETTING: Uppsala Longitudinal Study of Adult Men, Sweden.

    PARTICIPANTS: Swedish men (n = 1,104) at a mean age of 71 (range 69.4-74.1) were investigated, 369 of whom were evaluated for independent aging 16 years later, at a mean age of 87 (range 84.8-88.9).

    MEASUREMENTS: A questionnaire was used to obtain information on lifestyle, including education, living conditions, and physical activity. Adherence to a Mediterranean-like diet was assessed according to a modified Mediterranean Diet Score derived from 7-day food records. Cardiovascular risk factors were measured. Independent aging at a mean age of 87 was defined as lack of diagnosed dementia, a Mini-Mental State Examination score of 25 or greater, not institutionalized, independence in personal activities of daily living, and ability to walk outdoors alone. Complete survival data at age 85 were obtained from the Swedish Cause of Death Register.

    RESULTS: Fifty-seven percent of the men survived to age 85, and 75% of the participants at a mean age of 87 displayed independent aging. Independent aging was associated with never smoking (vs current) (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.05-4.60) and high (vs low) adherence to a Mediterranean-like diet (OR = 2.69, 95% CI = 1.14-6.80). Normal weight or overweight and waist circumference of 102 cm or less were also associated with independent aging. Similar associations were observed with survival.

    CONCLUSION: Lifestyle factors such as never smoking, maintaining a healthy diet, and not being obese at age 71 were associated with survival and independent aging at age 85 and older in men.

  • 48.
    Franzon, Kristin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Zethelius, Bjorn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Modifiable Midlife Risk Factors, Independent Aging, and Survival in Older Men: Report on Long-Term Follow-Up of the Uppsala Longitudinal Study of Adult Men Cohort2015In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 63, no 5, p. 877-885Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo examine relationships between modifiable midlife factors, aging, and physical and cognitive function (independent aging) and survival in very old age. DesignProspective cohort. SettingUppsala Longitudinal Study of Adult Men, Uppsala, Sweden. ParticipantsSwedish men investigated in 1970-74 (aged 48.6-51.1) and followed up for four decades (N=2,293). MeasurementsConventional cardiovascular risk factors, body mass index (BMI), and dietary biomarkers were measured, and a questionnaire was used to gather information on lifestyle variables at age 50. Four hundred seventy-two men were reinvestigated in 2008-09 (aged 84.8-88.9). Independent aging was defined as survival to age 85, Mini-Mental State Examination score of 25 or greater, not living in an institution, independent in personal care and hygiene, able to walk outdoors without personal help, and no diagnosis of dementia. The National Swedish Death Registry provided survival data. ResultsThirty-eight percent of the cohort survived to age 85. Seventy-four percent of the participants in 2008-09 were aging independently. In univariable analyses, high leisure-time physical activity predicted survival but not independent aging. Low work-time physical activity was associated more strongly with independent aging (odds ratio (OR)=1.84, 95% confidence interval (CI)=1.18-2.88) than with survival (OR=1.27, 95% CI=1.05-1.52). In multivariable analyses, midlife BMI was negatively associated (OR=0.80/SD, 95% CI=0.65-0.99/SD), and never or former smoking was positively associated (OR=1.66, 95% CI=1.07-2.59), with independent aging. As expected, conventional cardiovascular and lifestyle risk factors were associated with mortality. ConclusionA normal midlife BMI and not smoking were associated with independent aging close to four decades later, indicating that normal weight at midlife has the potential not only to increase survival, but also to preserve independence with aging.

  • 49. Frystyk, Jan
    et al.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Flyvbjerg, Allan
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum adiponectin is a predictor of coronary heart disease: a population-based 10-year follow-up study in elderly men2007In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 92, no 2, p. 571-576Article in journal (Refereed)
    Abstract [en]

    Context: Cross-sectional and nested case-control studies indicate a relationship between adiponectin, obesity, and coronary heart disease (CHD). Objective: Our objective was to investigate whether adiponectin could predict CHD in a population-based cohort of elderly men. Design and Setting: From 1991-1995 a baseline investigation was carried out in 832 healthy men aged 70 yr in the Uppsala Longitudinal Study of Adult Men (ULSAM study). They were followed up to 10.4 yr using Swedish national registry data. The baseline investigation included anthropometry, blood pressure, smoking, serum lipids, a euglycemic insulin clamp, and fasting serum adiponectin. Main Outcome Measures: Main outcome measures were defined as death or first-time hospitalization for CHD (n = 116), recorded in the Cause of Death Registry or in the Hospital-Discharge Registry of the National Board of Health and Welfare, Sweden. Associations were analyzed using Cox's proportional hazards regression, presented as hazard ratios (HR) with 95% confidence intervals (CI) for 1 SD increase in the predictor variable. Results: In a multivariable analysis including total cholesterol (HR, 1.24; CI, 1.02-1.50), high-density lipoprotein cholesterol (HR, 0.72; CI, 0.58-0.89), smoking (HR, 1.39; CI, 0.91-2.14), and systolic blood pressure (HR, 1.26; CI, 1.05-1.52), serum adiponectin was associated with lower risk for CHD (HR, 0.81; CI, 0.66-0.99). The association was independent of BMI and remained significant after adjustment for insulin sensitivity index. Conclusions: In this population-based cohort of healthy men, elevated serum levels of adiponectin were associated with a lower risk for CHD. Importantly, the association between adiponectin and CHD was independent of other well-known risk factors.

  • 50. Gao, He
    et al.
    Fall, Tove
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
    van Dam, Rob M
    Flyvbjerg, Allan
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
    Hägg, Sara
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
    Evidence of a Causal Relationship Between Adiponectin Levels and Insulin Sensitivity: A Mendelian Randomization Study2013In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 62, no 4, p. 1338-1344Article in journal (Refereed)
    Abstract [en]

    The adipocyte-secreted protein adiponectin is associated with insulin sensitivity in observational studies. We aimed to evaluate whether this relationship is causal using a Mendelian randomization approach. In a sample of Swedish men aged 71 years (n = 942) from the Uppsala Longitudinal Study of Adult Men (ULSAM), insulin sensitivity (M/I ratio) was measured by the euglycemic insulin clamp. We used three genetic variants in the ADIPOQ locus as instrumental variables (IVs) to estimate the potential causal effect of adiponectin on insulin sensitivity and compared these with results from conventional linear regression. The three ADIPOQ variants, rs17300539, rs3774261, and rs6444175, were strongly associated with serum adiponectin levels (all P ≤ 5.3 × 10−9) and were also significantly associated with M/I ratio in the expected direction (all P ≤ 0.022). IV analysis confirmed that genetically determined adiponectin increased insulin sensitivity (β = 0.47–0.81, all P ≤ 0.014) comparable with observational estimates (β = 0.50, all Pdifference ≥ 0.136). Adjustment for BMI and waist circumference partly explained the association of both genetically determined and observed adiponectin levels with insulin sensitivity. The observed association between higher adiponectin levels and increased insulin sensitivity is likely to represent a causal relationship partly mediated by reduced adiposity.

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