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Cederholm, Jan
Publications (10 of 66) Show all publications
Eeg-Olofsson, K., Zethelius, B., Gudbjornsdottir, S., Eliasson, B., Svensson, A.-M. & Cederholm, J. (2016). 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 Register. Diabetes & Vascular Disease Research, 13(4), 268-277.
Open this publication in new window or tab >>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 Register
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2016 (English)In: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 13, no 4, 268-277 p.Article in journal (Refereed) Published
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.

Keyword
Blood lipids, blood pressure, cardiovascular diseases, diabetes mellitus, HbA1c
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-298832 (URN)10.1177/1479164116637311 (DOI)000376973200003 ()27190080 (PubMedID)
Available from: 2016-07-11 Created: 2016-07-11 Last updated: 2017-11-28Bibliographically approved
Zethelius, B., Gudbjornsdottir, S., Eliasson, B., Eeg-Olofsson, K., Svensson, A.-M. & Cederholm, J. (2016). Electrical atrial vulnerability and renal complications in type 2 diabetes. Reply to Montaigne D, Coisne A, Sosner P et al [letter] [Letter to the editor]. Diabetologia, 59(4), 863-864.
Open this publication in new window or tab >>Electrical atrial vulnerability and renal complications in type 2 diabetes. Reply to Montaigne D, Coisne A, Sosner P et al [letter]
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2016 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 4, 863-864 p.Article in journal, Letter (Other academic) Published
Keyword
Albuminuria, Atrial fibrillation, Epidemiology, Longitudinal study design, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-296891 (URN)10.1007/s00125-016-3877-8 (DOI)000371802700026 ()26843077 (PubMedID)
Available from: 2016-07-05 Created: 2016-06-20 Last updated: 2017-11-28Bibliographically approved
Zethelius, B. & Cederholm, J. (2015). Comparison between indexes of insulin resistance for risk prediction of cardiovascular diseases or development of diabetes. Diabetes Research and Clinical Practice, 110(2), 183-192.
Open this publication in new window or tab >>Comparison between indexes of insulin resistance for risk prediction of cardiovascular diseases or development of diabetes
2015 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 110, no 2, 183-192 p.Article in journal (Refereed) Published
Abstract [en]

Aim: The predictive effect of various insulin resistance indexes for risk of cardiovascular diseases (CVD) or type 2 diabetes (T2DM) is still unclear. Methods: One thousand and forty-nine 71-years-old male subjects from the Swedish ULSAM study, mean follow-up 9 years. All subjects performed the euglycemic insulin clamp for M/I [glucose disposal/mean insulin], and 75-g oral glucose tolerance test for Ceder-IR: 1/glucose uptake rate/[mean glucose x log mean insulin]; Matsuda-IR: 1/10,000/square root [glucose0 x insulin0 x glucose120 x insulin120]; Belfiore-IR: 1/([glucose0 + glucose120]/normal mean glucose x [insulin0 + insulin120]/normal mean insulin)+1); and HOMA-IR: [glucose0 x insulin0]/22.5. Results: Bland-Altman plots showed best agreement between M/I versus Belfiore-IR and Ceder-IR with mean difference near zero, -0.21 to -0.46, while -0.68 to -0.77 for the other indexes. ISI-Ceder was the strongest predictor for incident nonfatal/fatal ischemic heart disease (CHD) or CVD at Cox regression in all subjects, and for incident T2DM at logistic regression in 1024 subjects with no baseline T2DM, with significantly higher hazard ratios or odds ratios than with all other indexes, also with best model fit, after adjusting for clinical characteristics and the traditional cardiovascular risk factors, including metabolic syndrome for CVD risk. Conclusion: Ceder-IR performed strongest as independent predictor for incidences of CHD/CVD and T2DM.

Keyword
Myocardial infarction, Cardiovascular diseases, Diabetes mellitus, Insulin resistance, Insulin clamp test
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-272301 (URN)10.1016/j.diabres.2015.09.003 (DOI)000366317100010 ()
Available from: 2016-01-14 Created: 2016-01-13 Last updated: 2017-11-30Bibliographically approved
Ekström, N., Svensson, A.-M., Miftaraj, M., Andersson Sundell, K., Cederholm, J., Zethelius, B., . . . Gudbjörnsdottir, S. (2015). Durability of oral hypoglycemic agents in drug naïve patients with type 2 diabetes: report from the Swedish National Diabetes Register (NDR). BMJ open diabetes research & care, 3, Article ID e000059.
Open this publication in new window or tab >>Durability of oral hypoglycemic agents in drug naïve patients with type 2 diabetes: report from the Swedish National Diabetes Register (NDR)
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2015 (English)In: BMJ open diabetes research & care, ISSN 2052-4897, Vol. 3, e000059Article in journal (Refereed) Published
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.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-268229 (URN)10.1136/bmjdrc-2014-000059 (DOI)25815205 (PubMedID)
Available from: 2015-12-03 Created: 2015-12-03 Last updated: 2015-12-04Bibliographically approved
Steineck, I., Cederholm, J., Eliasson, B., Rawshani, A., Eeg-Olofsson, K., Svensson, A.-M., . . . Gudbjornsdottir, S. (2015). Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study. BMJ-BRITISH MEDICAL JOURNAL, 350, Article ID h3234.
Open this publication in new window or tab >>Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study
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2015 (English)In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 350, h3234Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes. Design Observational study. SETTING Swedish National Diabetes Register, Sweden 2005-12. PARTICIPANTS 18 168 people with type 1 diabetes, 2441 using insulin pump therapy and 15 727 using multiple daily insulin injections. MAIN OUTCOME MEASURES Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases. RESULTS Follow-up was for a mean of 6.8 years until December 2012, with 114 135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in > 80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association. CONCLUSION Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-258768 (URN)10.1136/bmj.h3234 (DOI)000357158600005 ()26100640 (PubMedID)
Available from: 2015-07-20 Created: 2015-07-20 Last updated: 2015-07-20Bibliographically approved
Zethelius, B., Gudbjornsdottir, S., Eliasson, B., Eeg-Olofsson, K., Svensson, A.-M. & Cederholm, J. (2015). Risk factors for atrial fibrillation in type 2 diabetes: report from the Swedish National Diabetes Register (NDR). Diabetologia, 58(10), 2259-2268.
Open this publication in new window or tab >>Risk factors for atrial fibrillation in type 2 diabetes: report from the Swedish National Diabetes Register (NDR)
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2015 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no 10, 2259-2268 p.Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Atrial fibrillation (AF) is more frequent in patients with diabetes than in the general population. However, characteristics contributing to AF risk in diabetes remain speculative. Methods Observational study of 83,162 patients with type 2 diabetes, aged 30-79 years, with no baseline AF, 17% had history of cardiovascular disease (CVD) and 3.3% history of congestive heart failure (CHF), followed up for development of AF during mean 6.8 years from 2005-2007 to 2012. A subgroup of 67,780 patients without history of CVD or CHF was also analysed. Results Using Cox regression, cardiovascular risk factors associated with risk for AF were updated mean BMI (HR 1.31 per 5 kg/m(2)) or obesity (HR 1.51), updated mean systolic BP (SBP; HR 1.13 per 10 mmHg) or hypertension (HR 1.71), and cumulative microalbuminuria (HR 1.21), p < 0.001 for all analyses. Male sex, increasing age and height were also significant predictors. HRs were 1.76 for a history of CHF and 2.56 for in-study CHF, while 1.32 for history of CVD and 1.38 for in-study CHD (p < 0.001). Among patients without history of CVD or CHF, significant predictors were similarly BMI, SBP, and cumulative microalbuminuria and CHF. The risk of AF differed in the subgroups achieving or not achieving a target BP < 140/85 mmHg. The HRs for AF were (per 10 mmHg increase) 0.88 and 1.24, respectively. Conclusions/interpretation The modifiable risk factors high BP, high BMI and albuminuria were strongly associated with AF in type 2 diabetes. CVD, advancing age and height were also associated with AF in type 2 diabetes.

Keyword
Atrial fibrillation, Cardiovascular diseases, Diabetes mellitus, Myocardial infarction, Registry
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-264820 (URN)10.1007/s00125-015-3666-9 (DOI)000361538600008 ()26088442 (PubMedID)
Funder
Swedish Association of Local Authorities and Regions
Available from: 2015-10-29 Created: 2015-10-19 Last updated: 2017-12-01Bibliographically approved
Jonasson, J. M., Cederholm, J. & Gudbjornsdottir, S. (2014). Excess Body Weight and Cancer Risk in Patients with Type 2 Diabetes Who Were Registered in Swedish National Diabetes Register: Register-Based Cohort Study in Sweden. PLoS ONE, 9(9), e105868.
Open this publication in new window or tab >>Excess Body Weight and Cancer Risk in Patients with Type 2 Diabetes Who Were Registered in Swedish National Diabetes Register: Register-Based Cohort Study in Sweden
2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, e105868- p.Article in journal (Refereed) Published
Abstract [en]

Aim: To assess the association between excess body weight and cancer risk in patients with type 2 diabetes (T2D) who were registered in the Swedish National Diabetes Register (NDR). Methods: This is a cohort study based on 25,268 patients with T2D and baseline BMI >= 18.5 kg/m(2) from NDR 1997-1999. Subjects were grouped according to BMI into normal weight (18.5 to 24.9), overweight (25 to 29.9) or obesity (30 or more). All subjects were followed until the first occurrence of cancer, or death, or the end of follow-up (December 31, 2009). Adjusted hazard ratios (HRs) and 95% confidence interval (CI) for cancer risks were estimated by Cox regression. Results: In men with T2D, overweight was associated with increased risks of all cancer [1.13 (1.02-1.27)], gastrointestinal cancer [1.34 (1.07-1.72)] and colorectal cancer [1.59 (1.18-2.13)]; obesity was related to higher risks of all cancer [1.17 (1.04-1.33)], gastrointestinal cancer [1.40 (1.08-1.82)] and colorectal cancer [1.62 (1.17-2.24)]. In women with T2D, obesity was associated with increased risk of all cancer [1.30 (1.12-1.51)], gastrointestinal cancer [1.40 (1.03-1.91)] and postmenopausal breast cancer [1.39 (1.00-1.91)]. Conclusions: Excess body weight was associated with increased risks of all cancer, gastrointestinal cancer and colorectal cancer in men with T2D. Obesity was related with elevated risks of all cancer, gestational cancer and postmenopausal breast cancer in women with T2D.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-235067 (URN)10.1371/journal.pone.0105868 (DOI)000341304700019 ()25198347 (PubMedID)
Available from: 2014-10-29 Created: 2014-10-28 Last updated: 2017-12-05Bibliographically approved
Eliasson, B., Gudbjörnsdottir, S., Zethelius, B., Eeg-Olofsson, K. & Cederholm, J. (2014). LDL-cholesterol versus non-HDL-to-HDL-cholesterol ratio and risk for coronary heart disease in type 2 diabetes. European Journal of Preventive Cardiology, 21(11), 1420-1428.
Open this publication in new window or tab >>LDL-cholesterol versus non-HDL-to-HDL-cholesterol ratio and risk for coronary heart disease in type 2 diabetes
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2014 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 21, no 11, 1420-1428 p.Article in journal (Refereed) Published
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.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-219079 (URN)10.1177/2047487313494292 (DOI)000343901800013 ()23774274 (PubMedID)
Available from: 2014-02-21 Created: 2014-02-21 Last updated: 2017-12-05Bibliographically approved
Zethelius, B., Gudbjörnsdottir, S., Eliasson, B., Eeg-Olofsson, K. & Cederholm, J. (2014). Level of physical activity associated with risk of cardiovascular diseases and mortality in patients with type-2 diabetes: report from the Swedish National Diabetes Register.. European Journal of Preventive Cardiology, 21(2), 244-251.
Open this publication in new window or tab >>Level of physical activity associated with risk of cardiovascular diseases and mortality in patients with type-2 diabetes: report from the Swedish National Diabetes Register.
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2014 (English)In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 21, no 2, 244-251 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Sage Publications, 2014
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-219598 (URN)10.1177/2047487313510893 (DOI)000337979200012 ()
Available from: 2014-03-04 Created: 2014-03-04 Last updated: 2017-12-05Bibliographically approved
Eeg-Olofsson, K., Gudbjornsdottir, S., Eliasson, B., Zethelius, B., Svensson, A.-M. -. & Cederholm, J. (2014). Multifactorial risk factor control in clinical practice and risk of cardiovascular disease in type 2 diabetes: report from the Swedish national diabetes register. Paper presented at 50th EASD Annual Meeting, 15–19 September 2014, Vienna, Austria. Diabetologia, 57(S1), S493-S493.
Open this publication in new window or tab >>Multifactorial risk factor control in clinical practice and risk of cardiovascular disease in type 2 diabetes: report from the Swedish national diabetes register
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2014 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no S1, S493-S493 p.Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-242454 (URN)000344386102471 ()
Conference
50th EASD Annual Meeting, 15–19 September 2014, Vienna, Austria
Available from: 2015-01-28 Created: 2015-01-26 Last updated: 2017-12-05Bibliographically approved
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