| 1. |
- Cederholm, Jan, et al.
(författare)
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Blood pressure and risk of cardiovascular diseases in type 2 diabetes : further findings from the Swedish National Diabetes Register (NDR-BP II)
- 2012
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 30:10, s. 2020-2030
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Franzon, Kristin, et al.
(författare)
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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 Cohort
- 2015
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 63:5, s. 877-885
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Ingelsson, Erik, et al.
(författare)
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Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans
- 2010
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Konferensbidrag (refereegranskat)abstract
- OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS-The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS-Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. Diabetes 59:1266-1275, 2010
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| 4. |
- Rawshani, Aidin, et al.
(författare)
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Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus
- 2019
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 139:16, s. 1900-1912
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied. METHODS: In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses. In addition, we examined optimal cut point levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. Patients with type 1 diabetes mellitus were followed up until death or study end on December 31, 2013. The primary outcomes were death resulting from all causes, fatal/nonfatal acute myocardial infarction, fatal/nonfatal stroke, and hospitalization for heart failure. RESULTS: Of 32 611 patients with type 1 diabetes mellitus, 1809 (5.5%) died during follow-up over 10.4 years. The strongest predictors for death and cardiovascular outcomes were glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol. Glycohemoglobin displayed approximate to 2% higher risk for each 1-mmol/mol increase (equating to approximate to 22% per 1% glycohemoglobin difference), whereas low-density lipoprotein cholesterol was associated with 35% to 50% greater risk for each 1-mmol/L increase. Microalbuminuria or macroalbuminuria was associated with 2 to 4 times greater risk for cardiovascular complications and death. Glycohemoglobin <53 mmol/mol (7.0%), systolic blood pressure <140 mm Hg, and low-density lipoprotein cholesterol <2.5 mmol/L were associated with significantly lower risk for outcomes observed. CONCLUSIONS: Glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol appear to be the most important predictors for mortality and cardiovascular outcomes in patients with type 1 diabetes mellitus. Lower levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than contemporary guideline target levels appear to be associated with significantly lower risk for outcomes.
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| 5. |
- Wallentin, Lars, et al.
(författare)
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GDF-15 for Prognostication of Cardiovascular and Cancer Morbidity and Mortality in Men
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e78797-
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to evaluate the hypothesis that growth-differentiation factor 15 (GDF-15) is an independent marker of the long-term risk for both cardiovascular disease and cancer morbidity beyond clinical and biochemical risk factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity data were obtained from public registries. At baseline there were independent associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin-C) and inflammatory activity (C-reactive protein), and previous cardiovascular disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115 and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561) cohort. After adjustment for conventional cardiovascular risk factors, one SD increase in log GDF-15 were, in the respective total and non-CVD populations, associated with 48% (95%CI 26 to 73%, p<0.001) and 67% (95%CI 28 to 217%, p<0.001) incremental risk of cardiovascular mortality, 48% (95%CI 33 to 67%, p<0.001) and 61% (95%CI 38 to 89%, p<0.001) of total mortality and 36% (95%CI 19 to 56%, p<0.001) and 44% (95%CI 17 to 76%, p<0.001) of coronary heart disease morbidity and mortality. The corresponding incremental increase for cancer mortality in the respective total and non-cancer disease (n=882) population was 46% (95%CI 21 to 77%, p<0.001) and 38% (95%CI 12 to 70%, p<0.001) and for cancer morbidity and mortality in patients without previous cancer disease 30% (95%CI 12 to 51%, p<0.001). In conclusion, in elderly men, GDF-15 improves prognostication of both cardiovascular, cancer mortality and morbidity beyond established risk factors and biomarkers of cardiac, renal dysfunction and inflammation.
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