19 results on '"Zethelius, Björn"'
Search Results
2. Exploring the association between use of gonadotropin releasing hormones agonists and prostate cancer diagnosis per se and diabetes control in men with type 2 diabetes mellitus: a nationwide, population-based cohort study.
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Lin, E., Garmo, Hans, Van Hemelrijck, Mieke, Adolfsson, Jan, Stattin, Pär, Zethelius, Björn, and Crawley, Danielle
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GONADOTROPIN releasing hormone ,PROSTATE cancer ,TYPE 2 diabetes ,CANCER diagnosis ,GLYCEMIC control ,DIAGNOSIS of diabetes ,DIABETES - Abstract
Background: Gonadotropin Releasing Hormones agonists (GnRH), which are first line treatment for metastatic prostate cancer (PCa), increase risk of type 2 diabetes mellitus (T2DM). This study aims to quantify the association of use of GnRH with diabetes control in PCa men with T2DM.Methods: Nationwide population-based cohort study in the Swedish National Diabetes Register and Prostate Cancer data Base Sweden 4.1, on the association between GnRH and diabetes control in T2DM men with PCa by comparing T2DM men with PCa vs. without PCa, as well as comparing T2DM men with PCa on or not on GnRH. The primary exposure was use of GnRH. Worsening diabetes control was the primary outcome, defined as: 1) HbA1c rose to 58 mmol/mol or higher; 2) HbA1c increase by 10 mmol/mol or more; 3) Start of antidiabetic drugs or switch to insulin. We also combined all above definitions. Cox proportional hazards regression was used to analyze the association.Results: There were 5714 T2DM men with PCa of whom 692 were on GnRH and 28,445 PCa-free men with T2DM with similar baseline characteristics. Diabetes control was worse in men with GnRH vs. PCa-free men (HR: 1.24, 95% CI: 1.13-1.34) as well as compared with PCa men without GnRH (HR:1.58, 95% CI: 1.39-1.80), when we defined the worsening control of diabetes by combining all definitions above.Conclusion: Use of GnRH in T2DM men with PCa was associated with worse glycemic control. The findings highlight the need to closely monitor diabetes control in men with T2DM and PCa starting GnRH. [ABSTRACT FROM AUTHOR]- Published
- 2021
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3. Association of type 2 diabetes mellitus and antidiabetic medication with risk of prostate cancer: a population-based case-control study.
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Lin, E., Garmo, Hans, Van Hemelrijck, Mieke, Adolfsson, Jan, Stattin, Pär, Zethelius, Björn, and Crawley, Danielle
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TYPE 2 diabetes ,PROSTATE cancer ,CASE-control method - Abstract
Background: Prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are prevalent conditions that often occur concomitantly. However, many aspects of the impact of T2DM, particularly the duration of T2DM and antidiabetic medications, on PCa risk are poorly understood.Methods: To assess the association of duration of T2DM and antidiabetic medication with PCa risk, we designed a matched case-control study, including 31,415 men with PCa and 154,812 PCa-free men in Prostate Cancer data Base Sweden (PCBaSe) 4.1.Results: Overall, a decreased risk of PCa was observed for men with T2DM (odds ratio (OR): 0.81, 95% confidence interval (CI): 0.78-0.84), as compared to men without T2DM. The decreased risk of PCa was consistently showed across duration of T2DM. With respect to use of antidiabetic drugs, this inverse association with duration was also found for all medications types, as compared to men without T2DM, including insulin, metformin and sulphonylurea (SU) (e.g. 3- < 5 yr insulin OR:0.69, 95%CI:0.60-0.80; 3- < 5 yr metformin OR: 0.82, 95%CI: 0.74-0.91; 3- < 5 yr SU OR: 0.72, 95%CI: 0.62-0.83). When stratifying by PCa risk categories, this decreased risk was most evident for diagnosis of low and intermediate-risk PCa (low-risk OR: 0.65, 95%CI: 0.66-0.70, intermediate-risk OR: 0.80, 95%CI: 0.75-0.85).Conclusions: The study showed an inverse association between pre-existing T2DM and PCa across different durations of T2DM and all types of T2DM medication received. This inverse association was most evident for low- and intermediate-risk PCa, suggesting that whilst T2DM and its medication may protect some men from developing PCa, the relationship warrants further study. [ABSTRACT FROM AUTHOR]- Published
- 2020
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4. SPISE and other fasting indexes of insulin resistance: risks of coronary heart disease or type 2 diabetes. Comparative cross-sectional and longitudinal aspects.
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Cederholm, Jan and Zethelius, Björn
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TYPE 2 diabetes , *INSULIN resistance , *CORONARY disease , *HEART diseases , *RANK correlation (Statistics) - Abstract
Background: Fasting insulin resistance indexes are used extensively nowadays. We intended to analyze a new recently presented fasting index, SPISE (sensitivity formula: 600 × HDL-cholesterol0.185/triglycerides0.2/BMI1.338), in comparison with three previously known fasting indexes, regarding correlation with the insulin clamp index, and for the predictive effects of future long-term risks of coronary heart disease (CHD) or manifest type 2 diabetes. Methods: A total of 1049 71-year-old male subjects from the Swedish ULSAM study, median follow-up 8 years, were included. All subjects performed the euglycemic insulin clamp, and analyses of four fasting insulin resistance indexes: SPISE-IR (= 10/SPISE), QUICKI-IR, Log HOMA-IR, and Revised QUICKI-IR. Results: Spearman correlation coefficients with the insulin clamp were 0.60–0.62 for all indexes. Area under curve at ROC analysis was 0.80 for SPISE-IR, and 0.84 for QUICKI-IR, Log HOMA-IR, and Rev QUICKI-IR. Adjusted hazard ratios per 1 SD index increase for long-term risk CHD were similar in all patients: 1.20–1.24 (p = 0.02–0.03). However, comparing the highest quartile (recommended to define insulin resistance) with the lower quartiles, SPISE-IR was the strongest and the only statistically significant insulin resistance index: HR 1.53 (p = 0.02). Adjusted odds ratios per 1 SD index increase for long-term risk of type 2 diabetes were fairly similar (p < 0.001) in all patients: 1.62 for SPISE-IR, 1.97 for QUICKI-IR and Log HOMA-IR, and 2.04 for Rev QUICKI-IR, and also when comparing the highest versus the lower quartiles: 2.8–3.1 (p < 0.001). Conclusion: SPISE, easily applicable, performed equally well as other fasting insulin indexes previously recommended for clinical use, regarding correlation with the insulin clamp, and as predictor for future long-term risks of CHD or type 2 diabetes. [ABSTRACT FROM AUTHOR]
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- 2019
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5. A new model for 5-year risk of cardiovascular disease in type 2 diabetes, from the Swedish National Diabetes Register (NDR)
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Zethelius, Björn, Eliasson, Björn, Eeg-Olofsson, Katarina, Svensson, Ann-Marie, Gudbjörnsdottir, Soffia, Cederholm, Jan, Zethelius, Björn, Eliasson, Björn, Gudbjörnsdottir, Soffia, and NDR
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CARDIOVASCULAR diseases , *TYPE 2 diabetes , *EPIDEMIOLOGY , *CEREBROVASCULAR disease , *MORTALITY , *MYOCARDIAL infarction , *CHOLESTEROL - Abstract
Aim: We assessed the association between risk factors and cardiovascular disease (CVD) in an observational study of type 2 diabetes patients from the Swedish National Diabetes Register.Methods: A derivation sample of 24,288 patients, aged 30-74 years, 15.3% with previous CVD, baseline 2002, 2488 CVD events when followed for 5 years until 2007. A separate validation data set of 4906 patients, baseline 2003, 522 CVD events when followed for 4 years.Results: Adjusted hazard ratios at Cox regression for fatal/nonfatal CVD were: onset-age 1.59, diabetes duration 1.55, total-cholesterol-to-HDL-cholesterol ratio 1.20, HbA1c 1.12, systolic BP 1.09, BMI 1.07 (1 SD increase in natural log continuous variables); males 1.41, smoker 1.35, microalbuminuria 1.27, macroalbuminuria 1.53, atrial fibrillation 1.50, previous CVD 1.98 (all p<0.001 except BMI p=0.0018). All 12 variables were used to elaborate an equation for 5-year CVD risk in the derivation dataset: mean 5-year risk 11.9±8.4%. Calibration in the validation dataset was adequate: ratio predicted 4-year risk/observed rate 0.97. Discrimination was sufficient: C statistic 0.72, sensitivity 51% and specificity 78% for top quartile.Conclusion: This CVD risk model from a large observational study of patients in routine care showed adequate calibration and discrimination, and can be useful for clinical practice. [ABSTRACT FROM AUTHOR]- Published
- 2011
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6. Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register.
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Ekström, Nils, Svensson, Ann‐Marie, Miftaraj, Mervete, Franzén, Stefan, Zethelius, Björn, Eliasson, Björn, and Gudbjörnsdottir, Soffia
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HYPOGLYCEMIC agents ,TREATMENT of diabetes ,CARBOHYDRATE intolerance ,DIABETES insipidus ,GLYCEMIC control - Abstract
Aim To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. Research design and methods Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios ( HRs) with 95% confidence intervals ( CIs) of mortality, cardiovascular disease ( CVD), coronary heart disease ( CHD), stroke and congestive heart failure ( CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. Results Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea ( SU), 21% basal insulin, 12% thiazolidinedione ( TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 ( DPP-4) inhibitor, 1% glucagon-like peptide-1 ( GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [ HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. Conclusions This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Reducing the noise in signal detection of adverse drug reactions by standardizing the background: a pilot study on analyses of proportional reporting ratios-by-therapeutic area.
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Grundmark, Birgitta, Holmberg, Lars, Garmo, Hans, and Zethelius, Björn
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CONFIDENCE intervals ,DATABASES ,DIAGNOSTIC errors ,DRUG side effects ,TYPE 2 diabetes ,PROSTATE diseases ,PILOT projects ,DATA analysis software ,STATISTICAL models - Abstract
Purpose: Disproportionality screening analysis is acknowledged as a tool for performing signal detection in databases of adverse drug reactions (ADRs), e.g., in the European Union (EU) Drug Authority setting. The purpose of this study was to explore the possibility of decreasing false-positive signals of disproportionate reporting (SDR) by calculating the proportional reporting ratio (PRR)-by-therapeutic area (TA), while still maintaining the ability to detect relevant SDRs. Methods: In the EudraVigilance (EV) Database, output from PRR calculated with a restricted TA comparator background was compared in detail to output from conventional authority-setting PRR calculations for four drugs: bicalutamide, abiraterone, metformin, and vildagliptin, within the TAs of prostate gland disease and type 2 diabetes mellitus. Results: ADR reports per investigated drug ranged from 2,400 to 50,000. The PRR-TA's ability to detect true-positive SDRs (as acknowledged in approved labeling) was increased compared to the conventional PRR, and performed 8-31 % better than a recently proposed stricter EU-SDR definition. The PRR-TA removed false SDRs confounded by disease or disease spill-over by up to 63 %, while retaining/increasing the number of unclassified SDRs relevant for manual validation, and thereby improving the ratio between confounded SDRs (i.e., noise) and unclassified SDRs for all investigated drugs (possible signals). Conclusions: The performance of the PRR was improved by background restriction with the PRR-TA method; the number of false-positive SDRs decreased, and the ability to detect true-positive SDRs increased, improving the signal-to-noise ratio. Further development and validation of the method is needed within other TAs and databases, and for disproportionality analysis methods. [ABSTRACT FROM AUTHOR]
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- 2014
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8. Albuminuria and renal function as predictors of cardiovascular events and mortality in a general population of patients with type 2 diabetes: A nationwide observational study from the Swedish National Diabetes Register.
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Svensson, Maria K, Cederholm, Jan, Eliasson, Björn, Zethelius, Björn, and Gudbjörnsdottir, Soffia
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- 2013
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9. HbA1C and Cancer Risk in Patients with Type 2 Diabetes - A Nationwide Population-Based Prospective Cohort Study in Sweden.
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Jonasson, Junmei Miao, Cederholm, Jan, Eliasson, Björn, Zethelius, Björn, Eeg-Olofsson, Katarina, and Gudbjörnsdottir, Soffia
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DIABETIC acidosis ,CANCER patients ,RENAL cancer ,TYPE 2 diabetes ,GENITOURINARY organs ,CARDIOPULMONARY system - Abstract
Background: Diabetes is associated with increased cancer risk. The underlying mechanisms remain unclear. Hyperglycemia might be one risk factor. HbA1c is an indicator of the blood glucose level over the latest 1 to 3 months. This study aimed to investigate association between HbA1c level and cancer risks in patients with type 2 diabetes based on real life situations. Methods: This is a cohort study on 25,476 patients with type 2 diabetes registered in the Swedish National Diabetes Register from 1997-1999 and followed until 2009. Follow-up for cancer was accomplished through register linkage. We calculated incidences of and hazard ratios (HR) for cancer in groups categorized by HbA1c ≤58 mmol/mol (7.5%) versus >58 mmol/mol, by quartiles of HbA1c, and by HbA1c continuously at Cox regression, with covariance adjustment for age, sex, diabetes duration, smoking and insulin treatment, or adjusting with a propensity score. Results: Comparing HbA1c >58 mmol/mol with ≤58 mmol/mol, adjusted HR for all cancer was 1.02 [95% CI 0.95-1.10] using baseline HbA1c, and 1.04 [95% CI 0.97-1.12] using updated mean HbA1c, and HRs were all non-significant for specific cancers of gastrointestinal, kidney and urinary organs, respiratory organs, female genital organs, breast or prostate. Similarly, no increased risks of all cancer or the specific types of cancer were found with higher quartiles of baseline or updated mean HbA1c, compared to the lowest quartile. HR for all cancer was 1.01 [0.98-1.04] per 1%-unit increase in HbA1c used as a continuous variable, with non-significant HRs also for the specific types of cancer per unit increase in HbA1c. Conclusions: In this study there were no associations between HbA1c and risks for all cancers or specific types of cancer in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]
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- 2012
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10. Trends in blood pressure control in patients with type 2 diabetes - Data from the Swedish National Diabetes Register (NDR).
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Nilsson, Peter M., Cederholm, Jan, Zethelius, Björn, Eliasson, Björn, Eeg-Olofsson, Katarina, and Gudbjörnsdottir, Soffia
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BLOOD pressure ,TYPE 2 diabetes ,PEOPLE with diabetes ,HYPERTENSION ,CARDIOVASCULAR diseases - Abstract
We assessed blood pressure (BP) trends in patients with type 2 diabetes from a national diabetes register using three cross-sectional samples (aged 30-85 years) in 2005, 2007 and 2009, and in patients from 2005 followed individually until 2009. The prevalence of hypertension was 87% among all 180 369 patients in 2009, although lower in subgroups with ages 30-39, 40-49 and 50-59 years: 40%, 60% and 77%. In the three cross-sectional surveys, mean BP decreased (141/77-136/76 mmHg), uncontrolled BP≥ 140/90 mmHg decreased (58-46%), and antihypertensive drug treatment (AHT) increased (73-81%). Comparatively in 79 185 patients followed individually for 5 years, mean BP decreased (141/77-137/75 mmHg), uncontrolled BP ≥140/90 mmHg decreased (58-47%) and AHT increased (73-82%). Independent predictors of BP decrease were BMI decrease (stronger) and increase in AHT. AHT occurred among 81% of all patients in 2009. In 57 645 patients on AHT followed individually, mean BP decreased (143/77-138/75 mmHg) and uncontrolled BP ≥140/90 mmHg decreased (63-50%). Among 5164 patients with nephropathy on AHT followed individually, BP <130/80 mmHg increased (12-21%). In conclusion, BP control improved from 2005 to 2009, relative to BMI decrease and AHT increase, although still about half had BP ≥140/90 mmHg. [ABSTRACT FROM AUTHOR]
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- 2011
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11. Clinical Usefulness of Different Lipid Measures for Prediction of Coronary Heart Disease in Type 2 Diabetes.
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ELIASSON, BJÖRN, CEDERHOLM, JAN, EEG-OLOFSSON, KATARINA, SVENSSON, ANNE-MARIE, ZETHELIUS, BJÖRN, and GUDBJÖRNSDOTTIR, SOFFIA
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BLOOD lipids ,LIPIDS ,CORONARY disease ,DIAGNOSIS ,TYPE 2 diabetes ,DIABETES - Abstract
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 ≤ 1.8 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. [ABSTRACT FROM AUTHOR]
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- 2011
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12. Risk factors for the development of albuminuria and renal impairment in type 2 diabetes—the Swedish National Diabetes Register (NDR).
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Afghahi, Henri, Cederholm, Jan, Eliasson, Björn, Zethelius, Björn, Gudbjörnsdottir, Soffia, Hadimeri, Henrik, and Svensson, Maria K.
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ALBUMINURIA ,KIDNEY diseases ,FOLLOW-up studies (Medicine) ,REGRESSION analysis ,BODY mass index ,TRIGLYCERIDES - Abstract
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 m2 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 m2 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 [ABSTRACT FROM AUTHOR]
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- 2011
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13. Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans.
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Ingelsson, Erik, Langenberg, Claudia, Hivert, Marie-France, Prokopenko, Inga, Lyssenko, Valeriya, Dupuis, Josée, Mägi, Reedik, Sharp, Stephen, Jackson, Anne U., Assimes, Themistocles L., Shrader, Peter, Knowles, Joshua W., Zethelius, Björn, Abbasi, Fahim A., Bergman, Richard N., Bergmann, Antje, Berne, Christian, Boehnke, Michael, Bonnycastle, Lori L., and Bornstein, Stefan R.
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INSULIN ,GLUCOSE ,TYPE 2 diabetes ,DIABETIC acidosis ,MONOSACCHARIDES ,HYPOGLYCEMIC agents ,DIABETES - 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 pro-insulin, 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 [ABSTRACT FROM AUTHOR]- Published
- 2010
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14. 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)
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Cederholm, Jan, Zethelius, Björn, Nilsson, Peter M., Eeg-Olofsson, Katarina, Eliasson, Björn, and Gudbjörnsdottir, Soffia
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GLYCOSYLATED hemoglobin , *BLOOD pressure , *CARDIOVASCULAR diseases risk factors , *TYPE 2 diabetes , *SCIENTIFIC observation , *ANTILIPEMIC agents , *MYOCARDIAL infarction , *CEREBROVASCULAR disease - Abstract
Abstract: 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 ≤140/90mmHg (median 6.5%/130/80mmHg), and 2160 patients with adverse control 7.5–9.0%/141–190/91–110mmHg (median 8.1%/155/85mmHg). 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%/25/5mmHg 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. [Copyright &y& Elsevier]
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- 2009
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15. Risk Prediction of Cardiovascular Disease in Type 2 Diabetes.
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Cederholm, Jan, Eeg-Olofsson, Katarina, Eliasson, Björn, Zethelius, Björn, Nilsson, Peter M., and Gudbjörnsdottir, Soffia
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CARDIOVASCULAR diseases ,TYPE 2 diabetes ,DISEASE risk factors ,DIABETES complications ,BLOOD pressure ,ANTIHYPERTENSIVE agents - Abstract
OBJECTIVE -- Risk prediction models obtained in samples from the general population do not 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 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 ail 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. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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16. The Interaction between Impaired Acute Insulin Response and Insulin Resistance Predicts Type 2 Diabetes and Impairment of Fasting Glucose.
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Zethelius, Björn, Berglund, Lars, Hänni, Arvo, and Berne, Christian
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REGRESSION analysis , *INSULIN resistance , *DIABETES complications , *TYPE 2 diabetes , *BLOOD sugar - Abstract
Background: Impaired acute insulin response (AIR) and insulin resistance (IR) are characteristics of Type 2 diabetes (T2DM). The aim was to develop risk models for T2DM and impaired fasting glucose (IFG), reflecting estimates both of AIR and IR, and of their interaction, as predictors over 20 years of follow-up. Methods: We developed predictive models using hierarchic multiple regression analyses in a population-based cohort of 1227 men with normal fasting blood glucose at baseline (1970-73) and were reinvestigated after 10 and after 20 years. Using IVGTT-variables correlated either to AIR or to IR, separate models were developed. Combined models were also estimated from which prediction scores, representing individual risk, were calculated. Results: In combined models, interaction between prediction scores reflecting AIR and IR predicted T2DM and IFG. Lowest tertile of AIR and the highest tertile of IR showed a relative risk (RR) of 15.3 (95%-CI=5.58-41.84) for T2DM compared to the contrast group (high AIR and low IR). Corresponding RR for IFG was 13.23 (95%-CI=6.53-26.78). C-statistic increased from 0.76 to 0.79 (p=0.018) for T2DM and from 0.77 to 0.80 for IFG (p=0.062) taking interaction into account. Main effects of lowest tertile of AIR and highest tertile of IR versus best were: RR for T2DM, 8.80 (95%-CI=4.25-18.21) and 6.31 (95%-CI=3.26-12.21); for IFG, 9.07, (95%-CI=5.38-15.29) and 4.49 (95%-CI=2.98-6-76). Conclusion:. The interaction between low AIR and high IR revealed a high relative risk for T2DM or IFG reflecting the interplay between these factors over long time on worsening glucose tolerance and development of manifest disease. [ABSTRACT FROM AUTHOR]
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- 2008
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17. A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus.
- Author
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Crawley, Danielle, Chamberlain, Florence, Garmo, Hans, Rudman, Sarah, Zethelius, Björn, Holmberg, Lars, Adolfsson, Jan, Stattin, Par, Carroll, Paul, and Van Hemelrijck, Mieke
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PROSTATE cancer , *TYPE 2 diabetes , *SYSTEMATIC reviews - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2018
- Full Text
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18. 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).
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Eeg-Olofsson, Katarina, Gudbjörnsdottir, Soffia, Eliasson, Björn, Zethelius, Björn, and Cederholm, Jan
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CARDIOVASCULAR diseases risk factors , *TYPE 2 diabetes , *TRIGLYCERIDES , *HIGH density lipoproteins , *CHOLESTEROL , *OBESITY - Abstract
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. [ABSTRACT FROM AUTHOR]
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- 2014
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19. Early insulin response and insulin sensitivity are equally important as predictors of glucose tolerance after correction for measurement errors
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Berglund, Lars, Berne, Christian, Svärdsudd, Kurt, Garmo, Hans, and Zethelius, Björn
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INSULIN , *GLUCOSE tolerance tests , *MEASUREMENT errors , *TYPE 2 diabetes , *CALIBRATION , *REGRESSION analysis - Abstract
Abstract: Aims: : We estimated measurement error (ME) corrected effects of insulin sensitivity (M/I), from euglycaemic insulin clamp, and insulin secretion, measured as early insulin response (EIR) from oral glucose tolerance test (OGTT), on fasting plasma glucose, HbA1c and type 2 diabetes longitudinally and cross-sectional. Methods: : In a population-based study (n =1128 men) 17 men made replicate measurements to estimate ME at age 71 years. Effect of 1 SD decrease of predictors M/I and EIR on longitudinal response variables fasting plasma glucose (FPG) and HbA1c at follow-ups up to 11 years, were estimated using uncorrected and ME-corrected (with the regression calibration method) regression models. Results: : Uncorrected effect on FPG at age 77 years was larger for M/I than for EIR (effect difference 0.10mmol/l, 95% CI 0.00;0.21), while ME-corrected effects were similar (0.02mmol/l, 95% CI −0.13;0.15mmol/l). EIR had greater ME-corrected impact than M/I on HbA1c at age 82 years (−0.11%, −0.28; −0.01%). Conclusions: : Due to higher ME effect of EIR on glycaemia is underestimated as compared with M/I. By correcting for ME valid estimates of relative contributions of insulin secretion and insulin sensitivity on glycaemia are obtained. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
- View/download PDF
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