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  • 1. Afghahi, H
    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.
    Eliasson, B
    Nilsson, PM
    Eeg-Olofsson, K
    Gudbjornsdottir, S
    Svensson, MK
    Different sets of risk factors for the development of albuminuria and renal impairment in type 2 diabetes: the Swedish National Diabetes register (NDR)2009In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no Suppl 1, S25-S25 p.Article in journal (Refereed)
  • 2. Afghahi, H
    et al.
    Hadimeri, H
    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
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjornsdottir, S
    Svensson, MK
    The majority of type 2 diabetic patients with renal impairment have non-albuminuric renal disease: the Swedish National Diabetes register (NDR)2010In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 53, no Suppl 1, 110- p.Article in journal (Refereed)
  • 3.
    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, 1236-1243 p.Article 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.

  • 4.
    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, 1213-1220 p.Article 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.

  • 5.
    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, 2038-2043 p.Article 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.

  • 6.
    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.
    Eliasson, B.
    Nilsson, P.M.
    Weiss, L.
    Gudbjörnsdottir, S.
    Microalbuminuria and risk factors in type 1 and type 2 diabetic patients2005In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 67, no 3, 258-66 p.Article in journal (Refereed)
    Abstract [en]

    A prospective study of normoalbuminuric diabetic patients was performed between 1997 and 2002 on 4097 type 1 and 6513 type 2 diabetic patients from the Swedish National Diabetes Register (NDR); mean study period, 4.6 years. The strongest independent baseline risk factors for the development of microalbuminuria (20–200μg/min) were elevated HbA1c and diabetes duration in both types 1 and 2 diabetic patients. Other risk factors were high BMI, elevated systolic and diastolic BP in type 2 patients, and antihypertensive therapy in type 1 patients.

    A subsequent larger cross-sectional study in 2002 showed that established microalbuminuria was independently associated with HbA1c, diabetes duration, systolic BP, BMI, smoking and triglycerides in types 1 and 2 diabetic patients, and also with HDL-cholesterol in type 2 patients. Relatively few types 1 and 2 patients with microalbuminuria achieved treatment targets of HbA1c < 6.5% (21–48%), BP < 130/85mmHg (33–13%), cholesterol < 5mmol/l (48–46%), triglycerides < 1.7mmol/l (83–48%) and BMI < 25kg/m2 (50–18%), respectively.

    In conclusion, high HbA1c, BP and BMI were independent risk factors for the development of microalbuminuria in types 1 and 2 diabetic patients. These risk factors as well as triglycerides, HDL-cholesterol and smoking were independently associated with established microalbuminuria. Treatment targets were achieved by a relatively few patients with microalbuminuria.

  • 7.
    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, 882-885 p.Article, 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.

  • 8.
    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, 2020-2030 p.Article 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.

  • 9.
    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, 2026-2035 p.Article 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.

  • 10.
    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.
    Korpela, Mirja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Diagnosredovisning för läkarbesök år 1998 vid vårdcentralen i Tierp.Enligt Klassifikation av sjukdomar och hälsoproblem 1997 (ICD-10), Primärvård2000Other (Other academic)
  • 11.
    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.
    Nilsson, Peter M
    A review of risk factors and cardiovascular disease in diabetes care - 20112011In: European journal of cardiovascular medicine, ISSN 2042-4884, Vol. 1, no 3Article, review/survey (Refereed)
  • 12.
    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, 2684-9 p.Article in journal (Refereed)
  • 13.
    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, PM
    Anderberg, CP
    Fröberg, L
    Petersson, U
    Blood pressure and other cardiovascular risk factors among treated hypertensives in Swedish primary health care2002In: Scandinavian Journal of Primary Health Care, ISSN 0281-3432, E-ISSN 1502-7724, Vol. 20, no 4, 224-229 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate antihypertensive treatment and other cardiovascular risk factors in primary health care.

    DESIGN: Cross-sectional survey of consecutive patients with treated hypertension in 1999.

    SETTING: 17 primary care centres in Sweden.

    SUBJECTS: 512 patients (mean age 67; SD 11 years).

    MAIN OUTCOME MEASURES: Antihypertensive treatment, cardiovascular risk factors.

    RESULTS: Patients with high diastolic BP (> or = 100 mmHg) and systolic BP (> 180 mmHg) values were few. The proportions with diastolic BP < 90, BP < 160/95 and < 140/90 mmHg were 64%, 54% and 15%. Mono-therapy was given in 51%, and > or = 3 drugs in 13%. Hypertensives with hyperlipidaemia were 42%, and only 26% of them were given lipid-lowering drugs, mainly statins, 21%. Smokers were 10%, 23% had diabetes, and many had overweight BMI = 25 kg/m2, 72%.

    CONCLUSION: Although two-thirds had diastolic BP < 90 mmHg, few had BP below the current treatment target < 140/90 mmHg. More than half of the hypertensives had at least one additional cardiovascular risk factor, and these hypertensives also had low proportions within several current treatment targets of hypertension and hyperlipidaemia, implying a need for intensified multiple risk factor intervention.

  • 14.
    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, 235-237 p.Article in journal (Refereed)
  • 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 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, 74-81 p.Article 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.

  • 16. 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, 65-73 p.Article 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.

  • 17. 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, 471-482 p.Article 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.

  • 18. 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, S185-S186 p.Article in journal (Other academic)
  • 19. 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, S493-S493 p.Article in journal (Other academic)
  • 20. 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, 1640-1646 p.Article 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.

  • 21.
    Eeg-Olofsson, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    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.
    Gudbjörnsdottir, S.
    Eliasson, B.
    Glycemic and risk factor control in type 1 diabetes: results from 13,612 patients in a national diabetes register2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 3, 496-502 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - This study was designed to investigate the clinical characteristics of a large type 1 diabetic population and to evaluate the degree of fulfillment of recently updated treatment goals. RESEARCH DESIGN AND METHODS - The Swedish National Diabetes Register was initiated in 1996 as a tool for quality assurance in diabetes care. AlC levels, treatment, and risk factors were analyzed in two cross-sectional samples of 9,424 patients in 1997 and 13,612 patients in 2004 and in a smaller longitudinal sample from 1997 to 2004. RESULTS - Mean AlC decreased from 8.2 ± 1.3% in 1997 to 8.0 ± 1.2% in 2004 (P < 0.001). The proportion of patients reachingAlC <7.0% increased from 17.4 to 21.2% in 2004. A slow but significant improvement in blood pressure levels was seen, but only 61.3% reached the blood pressure goal of <130/80 mmHg in 2004. Lipid control improved, and the use of lipid-lowering drugs increased. Among patients treated with lipid-lowering agents, 38% reached the goal of total cholesterol <4.5 mmol/l, and 48% reached the goal of LDL cholesterol <2.5 mmol/l. Successful long-term glycemic and blood pressure control were both independently predicted by low BMI and the absence of microalbuminuria in 1997. CONCLUSIONS - In this large cohort of type 1 diabetic patients, there was a slow improvement in glycemic and risk factor control from 1997 to 2004, although the gap between the clinical results and current Swedish and American treatment goals is still unsatisfactory. It is crucial that additional measures be taken to improve risk factor control in type 1 diabetic patients.

  • 22. 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, 136-144 p.Article 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.

  • 23.
    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, 268-277 p.Article 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.

  • 24. 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, S91-S92 p.Article in journal (Other academic)
  • 25. 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, 717-726 p.Article 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.

  • 26. Ekström, Nils
    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.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eliasson, Björn
    Fhärm, Eva
    Rolandsson, Olov
    Miftaraj, Mervete
    Svensson, Ann-Marie
    Gudbjörnsdottir, Soffia
    Aspirin treatment and risk of first incident cardiovascular diseases in patients with type 2 diabetes: an observational study from the Swedish National Diabetes Register.2013In: BMJ open, ISSN 2044-6055, Vol. 3, no 4Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the benefits and risks associated with aspirin treatment in patients with type 2 diabetes and no previous cardiovascular disease (CVD) in clinical practice.

    DESIGN: Population-based cohort study between 2005 and 2009, mean follow-up 3.9 years.

    SETTING: Hospital outpatient clinics and primary care in Sweden.

    PARTICIPANTS: Men and women with type 2 diabetes, free from CVD, including atrial fibrillation and congestive heart failure, at baseline, registered in the Swedish National Diabetes Register, with continuous low-dose aspirin treatment (n=4608) or no aspirin treatment (n=14 038).

    MAIN OUTCOME MEASURES: Risks of CVD, coronary heart disease (CHD), stroke, mortality and bleedings, associated with aspirin compared with no aspirin, were analysed in all patients and in subgroups by gender and estimated cardiovascular risk. Propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression, and the effect of unknown covariates was evaluated in a sensitivity analysis.

    RESULTS: There was no association between aspirin use and beneficial effects on risks of CVD or death. Rather, there was an increased risk of non-fatal/fatal CHD associated with aspirin; HR 1.19 (95% CI 1.01 to 1.41), p=0.04. The increased risk of cardiovascular outcomes associated with aspirin was seen when analysing women separately; HR 1.41 (95% CI 1.07 to 1.87), p=0.02, and HR 1.28 (95% CI 1.01 to 1.61), p=0.04, for CHD and CVD, respectively, but not for men separately. There was a trend towards increased risk of a composite of bleedings associated with aspirin, n=157; HR 1.41 (95% CI 0.99 to 1.99).

    CONCLUSIONS: The results support the trend towards more restrictive use of aspirin in patients with type 2 diabetes and no previous CVD. More research is needed to explore the differences in aspirin's effects in women and men.

  • 27. 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, e001076- p.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.

  • 28. 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, 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.

  • 29. Eliasson, B.
    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.
    Gudbjörnsdóttir, S.
    The gap between guidelines and reality: Type 2 diabetes in a National Diabetes Register 1996-20032005In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 22, no 10, 1420-6 p.Article in journal (Refereed)
    Abstract [en]

    Guidelines for the treatment of risk factors in diabetes care have been updated recently, due to indisputable results from clinical end-point trials. This study evaluates risk factor control compared with current national and international targets during the period 1996–2003 in Type 2 diabetes (DM2). Patients were registered in primary-care and hospital outpatient clinics using computer software, or via the Internet. The clinical characteristics of the patients, treatment, HbA1c, and risk factors were reported after screening by local methods. The numbers of cases of DM2 reported were 17547 in 1996 and 57119 in 2003. The mean HbA1c decreased from 7.8 to 7.2%, while blood pressure decreased from 150/82 to 143/78 mmHg during the same period. Longitudinal analysis of results was performed in 5356 patients repeatedly reported, showing slightly lower effects. The new European treatment targets of HbA1c≤ 6.1%, blood pressure < 130/80 mmHg and total cholesterol < 4.5 mmol/l were attained by 16, 13 and 28% of the patients in 2003, respectively. The prevalence of the metabolic syndrome in 2003 was 77%. Aspirin was prescribed in 36% of cases. Lipid-lowering, anti-hypertensive drugs, and treatment with oral hypoglycaemic agents in combination with insulin were increasingly employed during the period studied. Risk factor control in DM2 reported to the National Diabetes Register (NDR) is slowly improving, although multiple risk factors and the metabolic syndrome are found in most patients. The majority of subjects do not achieve current target levels for HbA1c, blood pressure and blood lipids. Thus, giving up smoking and increased use of aspirin are called for, as well as more aggressive treatment of hyperglycaemia, elevated blood pressure and blood lipid levels, in accordance with updated international guidelines.

  • 30. Eliasson, B
    et al.
    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 Clinical Epidemiology.
    Nilsson, P M
    Gudbjörnsdóttir, S
    Antihyperglycaemic treatment of type 2 diabetes: results from a national diabetes register2007In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 33, no 4, 269-276 p.Article in journal (Refereed)
    Abstract [en]

    Aim

    To describe clinical characteristics and antihyperglycaemic treatment patterns in patients with varying duration of diabetes.

    Methods

    We performed a cross-sectional survey of 61 890 type 2 diabetic (DM2) patients from the Swedish National Diabetes Register (NDR) in 2004. We also analysed the effect of types of treatment and risk factors on glycaemic control in a longitudinal cohort study from 1996 to 2004. HbA1c, risk factors and treatments were determined locally in primary care as well as hospital outpatient clinics.

    Results

    Insulin was frequently used in DM2 patients with long duration of diabetes, although the mean HbA1c increased and only a few in this group reached HbA1c < 7.0%. Patients showing long-term improvement in HbA1c (> 1%) from 1996 to 2004 were more often treated with insulin than with oral hypoglycaemic agents (OHA). During this period, the HbA1c levels leading to additional treatment decreased. A low BMI, decreasing BMI and not smoking were predictors of good long-term metabolic control. Hypertension and hyperlipidaemia were frequent in both newly diagnosed DM2 patients and in patients with a long duration of diabetes.

    Conclusions

    Insulin treatment was frequently used, particularly in patients with a long duration of DM2. The glycaemic control, which usually deteriorates over time, did not reach the recommended goal, despite the fact that complementary treatment was added at lower HbA1c levels in 2003 than in 1996. High frequencies of hypertension, hyperlipidaemia and high 10-year risks of coronary heart disease necessitate intensified risk factor control in the future.

  • 31. Eliasson, B
    et al.
    Gudbjörnsdottir, S
    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.
    Liang, Y
    Vercruysse, F
    Smith, U
    Weight loss and metabolic effects of topiramate in overweight and obese type 2 diabetic patients: randomized double-blind placebo-controlled trial2007In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 31, no 7, 1140-1147 p.Article in journal (Refereed)
    Abstract [en]

    Objective:

    To examine the metabolic effects and body composition changes after topiramate treatment of obese type 2 diabetic patients (DM2) for 11 months.

    Design and subjects:

    Thirty-eight DM2 on diet or sulfonylurea treatment participated in this randomized double-blind placebo-controlled trial. Thirteen placebo-treated and nine topiramate-treated patients completed the trial. Patients were randomized to treatment with topiramate 96 mg b.i.d. or placebo (6-week run-in phase, 2-months titration phase, 9-months maintenance phase).

    Measurements:

    Insulin sensitivity was measured with euglycaemic hyperinsulinemic clamps. Weight, HbA1c, fasting glucose, blood lipids and safety variables were measured at regular intervals. Body composition was determined with computerized tomography. Meal tests were performed to evaluate postprandial glucose and insulin levels. Three-day diet recalls were carried out to evaluate energy ingestion.

    Results:

    The mean age was 58.67.1 years, body weight 98.116.1 kg, BMI 33.04.5 kg/m2, and glycosylated hemoglobin (HbA1c) 7.30.9%. In topiramate-treated patients, there were significant reductions in HbA1c (1.10.9%), fasting plasma glucose, body weight (-6.63.3%), as well as body fat, lean body mass, postprandial glucose and free fatty acid levels but there were no significant changes in insulin sensitivity. The daily average energy intake decreased more in the topiramate group than in the placebo group. Paresthesia and central nervous system-related side effects were the main causes for the dropout rate.

    Conclusions:

    Topiramate treatment of overweight DM2 reduced body weight and body fat, and was associated with a marked improvement in glycaemic control whereas no significant improvement in insulin-stimulated glucose uptake was demonstrated. Further studies are required to clarify whether this effect might occur through changes in insulin sensitivity in the liver and/or pancreatic insulin secretion.

  • 32. 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, 1420-1428 p.Article 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.

  • 33. Eliasson, B.
    et al.
    Moeller-Goede, D.
    Eeg-Olofsson, K.
    Wilson, C.
    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.
    Fleck, P.
    Diamant, M.
    Taskinen, M. -R
    Smith, U.
    Lowering of postprandial lipids in individuals with type 2 diabetes treated with alogliptin and/or pioglitazone: a randomised double-blind placebo-controlled study2012In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 4, 915-925 p.Article in journal (Refereed)
    Abstract [en]

    Pharmacological augmentation of glucagon-like peptide 1 receptor signalling by dipeptidyl peptidase 4 (DPP-4) inhibition reduced intestinal lipoprotein secretion in experimental studies, suggesting that DPP-4 inhibitors may ameliorate dyslipidaemia and thus reduce cardiovascular risk in patients with type 2 diabetes. We assessed the effects of alogliptin (Alo) and Alo co-administered with pioglitazone (Pio) vs placebo (Pbo) on triacylglycerol (TG)-rich lipoproteins in type 2 diabetes before and following a high-fat meal. Seventy-one patients (age 18-70 years), who did not reach HbA(1c) 6.5% (48 mmol/mol) with lifestyle and/or metformin, sulfonylurea or glinide therapy, participated in this 16 week, double-centre (university hospitals) Pbo-controlled parallel-group study. All participants, people doing measurements or examinations, and people assessing the outcomes were blinded to group assignment. Fasting TG 1.7-5.0 mmol/l was among the entry criteria. Patients received a high-fat mixed meal before and 4 and 16 weeks after randomisation (allocation by central office) to Alo (n = 25), Alo/Pio (n = 22) or Pbo (n = 24). Blood was sampled at pre-specified intervals, starting at 15 min before and ending 8 h after meal ingestion. At week 16, Alo (n = 25) and Alo/Pio (n = 21) vs Pbo (n = 24) produced similar significant reductions in total postprandial TG response (incremental AUC [iAUC]; p < 0.001), as well as in chylomicron TG (p < 0.001) and VLDL1 TG iAUCs (p < 0.001 and p = 0.012, respectively). Postprandial chylomicron apolipoprotein B-48 iAUC showed a significant decrease after Alo treatment (p = 0.028), and a non-significant trend towards a decrease with Alo/Pio (p = 0.213). The incidence of adverse events was low and consistent with previous studies. Treatment with Alo and Alo/Pio produced significant reductions in postprandial TG and TG-rich lipoproteins, contributing to an improved overall cardiometabolic risk profile in type 2 diabetes. The data support the concept that incretins not only modulate glucose metabolism but also influence chylomicron metabolism in intestinal cells.

  • 34. 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, 2095-2100 p.Article 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.

  • 35. Eliasson, Björn
    et al.
    Goede-Möller, D
    Eeg-Olofsson, K
    Wilson, C
    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.
    Fleck, P
    Diamant, M
    Taskinen, MR
    Smith, U
    The DPP-4 inhibitor alogliptin reduces postprandial TG and TG-rich lipoproteins in type 2 diabetes2011In: 47th European Association for the study of Diabetes 2011: Lissabon, Portugal, 2011Conference paper (Other academic)
  • 36. 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, 97-105 p.Article 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.

  • 37. Fhärm, E
    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.
    Eliasson, B
    Gudbjörnsdottir, S
    Rolandsson, O
    Time trends in absolute and modifiable coronary heart disease risk in patients with Type 2 diabetes in the Swedish National Diabetes Register (NDR) 2003-20082012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 2, 198-206 p.Article in journal (Refereed)
    Abstract [en]

    Aims: 

    The aim was to evaluate treatment goal achievements early in the course of Type 2 diabetes, and their effect on 10-year risk of coronary heart disease in patients receiving usual care.

    Methods: 

    Assessment of risk factor control 3 years after diagnosis in patients with Type 2 diabetes with no previous coronary heart disease included from the Swedish National Diabetes Register; a total of 19 382 patients (mean age 58 years) in cross-sectional surveys from 2003 to 2008, and a subgroup of 4293 patients followed individually from year of diagnosis to follow-up after a mean 2.6 years. Estimation of absolute 10-year risk of coronary heart disease using the UK Prospective Diabetes Study risk engine, and modifiable 10-year risk defined as percentage excess risk above patients with 'normal' risk factor values.

    Results: 

    Treatment goals for HbA(1c) , blood pressure, total and LDL cholesterol were achieved in 78.4, 65.5, 55.6% and 61.0%, respectively, in the cross-sectional survey in 2008, following a trend of generally improved control. In the individually followed patients in the subgroup, mean absolute 10-year coronary heart disease risk increased from 13.7% (men/women 16.9/9.5%) to 14.2 (men/women 17.6/9.6%) (P < 0.001) from year of diagnosis to follow-up after 2.6 years, while mean modifiable risk decreased from 37.7% (men/women 28.6/49.9%) to 19.1% (13.2/26.9%) (P < 0.001 in all).

    Conclusions:

    A high achievement of treatment goals and a low mean modifiable 10-year coronary heart disease risk was found at the 3-year follow-up, both in the cross-sectional survey in 2008 and in patients individually followed since diagnosis. This indicates the feasibility and significance of early multifactorial risk factor treatment.

  • 38. Gudbjörnsdottir, S
    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
    Eliasson, B
    The National Diabetes Register in Sweden: an implementation of the St. Vincent Declaration for Quality Improvement in Diabetes Care2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 4, 1270-1276 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:To monitor glycemic control, treatable risk factors, and treatment profile for quality assessment of diabetes care on a national scale.

    RESEARCH DESIGN AND METHODS:Four samples of 23,546, 32,903, 30,311, and 29,769 patients with diabetes (1996-1999) were studied based on a repeated national screening and quality assessment of diabetes care by the National Diabetes Register, Sweden, with participation of both hospitals and primary health care. Clinical characteristics included were age, sex, diabetes duration and treatment, glycemic control (HbA(1c)), office blood pressure (BP), BMI, smoking habits, and use of lipid-lowering drugs in patients with type 1 or type 2 diabetes.

    RESULTS:Favorable decreases of mean HbA(1c) and BP values were registered during the 4-year study period for both type 1 (HbA(1c) 7.5-7.3% and BP 130/75-130/74 mmHg) and type 2 diabetic patients (HbA(1c) 7.0-6.7% and BP 151/82-147/80 mmHg). Treatment aims of HbA(1c) and BP levels were also achieved in increasing proportions for type 1 (HbA(1c) <7.5%: 50-58% and BP </=140/85 mmHg: 77-79%), and type 2 diabetic patients (HbA(1c) <7.5%: 66-73% and BP </=140/85 mmHg: 32-42%). The use of lipid-lowering drugs increased for type 1 (4-11%) and type 2 diabetic patients (10-22%). In type 2 diabetic patients, treatment with oral agents alone decreased, but combination therapy (insulin and oral agents) increased during the study period. Mean BMI increased during 1996-1999 in type 2 diabetic patients. High HbA(1c) and BP values in 1999 were predicted by high BMI values 1996 and by high increase of BMI during the period, independent of diabetes duration, age, and sex.

    CONCLUSIONS:Decreasing mean HbA(1c) and BP levels and the wider use of lipid-lowering drugs during the late 1990s in patients with diabetes in a national sample from Sweden should translate into clinical benefits regarding micro- and macrovascular complications as well as diabetes-related mortality.

  • 39. Gudbjörnsdottir, S
    et al.
    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 Clinical Epidemiology.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Eliasson, B
    Nilsson, P. M.
    Risk factor control in patients with Type 2 diabetes and coronary heart disease: findings from the Swedish National Diabetes Register (NDR)2009In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 26, no 1, 53-60 p.Article in journal (Refereed)
    Abstract [en]

    AIMS: Patients with Type 2 diabetes and coronary heart disease (CHD) are infrequently treated to risk factor targets in current guidelines. We aimed to examine risk factor management and control levels in a large sample of patients with Type 2 diabetes with CHD. METHODS: This was an observational study of 1612 patients with first incidence of CHD before 2002, and of 4570 patients with first incidence of CHD before 2005, from the Swedish National Diabetes Register (NDR). RESULTS: In patients with CHD 1-2 years before follow-up, the achievement of cardiovascular risk factor targets (follow-up 2002/follow-up 2005) was: HbA(1c) < 7%, 47%/54% (P < 0.01); blood pressure < or = 130/80 mmHg, 31%/40% (P < 0.001); total cholesterol < 4.5 mmol/l, 47%/60% (P < 0.001); and low-density lipoprotein-cholesterol < 2.5 mmol/l, 49%/65% (P < 0.001). Use of medication: antihypertensives, 90%/94% (P < 0.01); lipid-lowering drugs, 75%/86% (P < 0.001); and aspirin, 85%/89% (P < 0.05). A high prevalence of adverse lifestyle characteristics prevailed (2002/2005): overweight [body mass index (BMI) > or = 25 kg/m(2)], 86%/85%; obesity (BMI > or = 30 kg/m(2)), 41%/42%; smokers in age group < 65 years, 16-23%/18-19%; as well as waist circumference > or = 102 cm (men) or > or = 88 cm (women), 68% in 2005. CONCLUSIONS: Patients with a combination of Type 2 diabetes and CHD showed an increased use of lipid-lowering drugs over time, corresponding to improving blood lipid levels. A discrepancy existed between the prevalent use of antihypertensive drugs and the low proportion reaching blood pressure targets. Regretfully, a high prevalence of adverse lifestyle characteristics prevailed. Evidence-based therapy with professional lifestyle intervention and drugs seems urgent for improved quality of secondary prevention in these patients.

  • 40. Gudbjörnsdottir, S
    et al.
    Eliasson, B
    Eeg-Olofsson, K
    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.
    Additive effects of glycaemia and dyslipidaemia on risk of cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 10, 2544-2551 p.Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS:

    The study aimed to assess the relative importance of the control of HbA(1c) and total cholesterol/HDL-cholesterol ratio (TC/HDL) on risk of cardiovascular disease (CVD).

    METHODS:

    In 22,135 participants with type 2 diabetes (age 30-75 years, 15% with previous CVD) followed for 5 years, baseline and annually updated mean HbA(1c) and TC/HDL were analysed and also categorised in combinations of quartiles. Outcomes were fatal/non-fatal CHD, stroke, CVD and total mortality.

    RESULTS:

    In all participants, HRs per 1 SD increase in updated mean HbA(1c) or TC/HDL using Cox regression analysis were 1.13 (95% CI 1.07, 1.19) and 1.31 (1.25, 1.37) for CHD, 1.15 (1.06, 1.24) and 1.25 (1.17, 1.34) for stroke, 1.13 (1.08, 1.18) and 1.29 (1.24, 1.34) for CVD (all p < 0.001), and 1.07 (1.02, 1-13; p = 0.01) and 1.18 (1.12, 1.24; p < 0.001) for total mortality, respectively, adjusted for clinical characteristics and traditional risk factors. The p value for the interaction between HbA(1c) and TC/HDL was 0.02 for CHD, 0.6 for stroke and 0.1 for CVD. Adjusted mean 5-year event rates in a Cox model, in combinations of quartiles of updated mean TC/HDL and HbA(1c) (lowest <3.1 mmol/l and 5.0-6.4% [31-46 mmol/mol]; <3.1 mmol/l and ≥7.8% [≥62 mmol/mol]; ≥4.6 mmol/l and 5.0-6.4% 31-46 mmol/mol; and highest ≥4.6 mmol/l and ≥7.8% [≥62 mmol/mol]), were 4.8%, 7.0%, 9.1% and 14.5% for CHD, and 7.1%, 9.9%, 12.8% and 19.4% for CVD, respectively. Adjusted HRs for highest vs lowest combinations were 2.24 (1.58-3.18) for CHD and 2.43 (1.79-3.29) for CVD (p < 0.001).

    CONCLUSIONS/INTERPRETATION:

    Hyperglycaemia and hyperlipidaemia were less than additive for CHD and additive for other endpoints, with the lowest risk at lowest combination levels and a considerable increase in absolute risk at high combination levels.

  • 41. Gudbjörnsdottir, Soffia
    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
    Eliasson, Björn
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Adamson, Ulf
    Nationella diabetesregistret 1996-2003: Kvalitetsvärdering visar att diabetesvården har förbättrats2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 47, 3790-3797 p.Article in journal (Other academic)
    Abstract [en]

    The Swedish National Diabetes Register presents results during the period 1996- 2003. Quality of care data from more than 75,000 diabetic patients (2003) treated at medical departments and primary health care centres are evaluated concerning national goals of HbA1c <6,5% and BP <140/85 mm Hg, the prevalence of lipid treatment, smoking etc. The national goals of HbA1c and BP were reached with increasing degree in cross-sectional analysis during the period, and were achieved by 33% and 71% at medical departments, and by 61% and 48% in primary health care in 2003. A similar tendency was also seen in longitudinal analysis of subgroups 1996-2003. The use of antihypertensive and lipid-lowering drugs was also considerably increased. This should imply a reduction of the risk for diabetic complications. As the national goals are still difficult to reach, individual goals should be set for the treatment.

  • 42. Jonasson, Junmei Miao
    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.
    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
    HbA1C and Cancer Risk in Patients with Type 2 Diabetes: A Nationwide Population-Based Prospective Cohort Study in Sweden2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 6, e38784- p.Article in journal (Refereed)
    Abstract [en]

    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.

  • 43. Jonasson, Junmei Miao
    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.
    Gudbjornsdottir, Soffia
    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 Sweden2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, e105868- p.Article in journal (Refereed)
    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.

  • 44. Kelly, P. J.
    et al.
    Clarke, P. M.
    Hayes, A. J.
    Gerdtham, U. -G
    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.
    Nilsson, P.
    Eliasson, B.
    Gudbjornsdottir, S.
    Predicting mortality in people with Type 2 diabetes mellitus after major complications: a study using Swedish National Diabetes Register data2014In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 31, no 8, 954-962 p.Article in journal (Refereed)
    Abstract [en]

    Aim To predict mortality risk and life expectancy for patients with Type 2 diabetes after a major diabetes-related complication. Methods The study sample, taken from the Swedish National Diabetes Register, consisted of 20 836 people with Type 2 diabetes who had their first major complication (myocardial infarction, stroke, heart failure, amputation or renal failure) between January 2001 and December 2007. A Gompertz proportional hazards model was derived which determined significant risk factors associated with mortality and was used to estimate life expectancies. Results Risk of death changed over time according to type of complication, with myocardial infarction initally having the highest initial risk of death, but after the first month, the risk was higher for heart failure, renal failure and amputation. Other factors that increased the risk of death were male gender (hazard ratio 1.06, 95% CI 1.02-1.12), longer duration of diabetes (hazard ratio 1.07 per 10 years, 95% CI 1.04-1.10), smoking (hazard ratio 1.51, 95% CI 1.40-1.63) and macroalbuminuria (hazard ratio 1.14, 95% CI 1.06-1.22). Low BMI, low systolic blood pressure and low estimated GFR also increased mortality risk. Life expectancy was highest after a stroke, myocardial infarction or heart failure, lower after amputation and lowest after renal failure. Smoking and poor renal function were the risk factors which had the largest impact on reducing life expectancy. Conclusions Risk of death and life expectancy differs substantially among the major complications of diabetes, and factors significantly increasing risk included smoking, low estimated GFR and albuminuria.

  • 45. Nilsson, P.
    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.
    Eliasson, B.
    Eeg-Olofsson, K.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjornsdottir, S.
    SYSTOLIC BLOOD PRESSURE AND RISK OF CARDIOVASCULAR DISEASE IN TYPE 2 DIABETIC PATIENTS, ON ANTIHYPERTENSIVE TREATMENT OR NOT: NATIONAL DATA2010In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 28, E220-E220 p.Article in journal (Other academic)
  • 46. Nilsson, P M
    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.
    Eeg-Olofsson, K
    Eliasson, B
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gudbjörnsdóttir, S
    Pulse pressure strongly predicts cardiovascular disease risk in patients with type 2 diabetes from the Swedish National Diabetes Register (NDR)2009In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 35, no 6, 439-446 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To analyze pulse pressure (PP) as a risk predictor for coronary heart disease (CHD), stroke and cardiovascular disease (CVD; CHD and/or stroke) in type 2 diabetic patients. METHODS: A total of 11,128 female and male type 2 diabetic patients with known baseline PP values and no CVD, aged 50-74 years, were followed for a mean duration of 5.6 years (1998-2003). A subgroup of 5521 patients with known mean PP values (mean values at baseline and at the end of the study) was also included. RESULTS: Hazard ratios (HRs) with 95% CI for fatal/nonfatal CHD with baseline or mean PP>or=75mmHg, compared to <75mmHg, were 1.23 (1.07-1.40; P=0.003) and 1.32 (1.07-1.62; P=0.009), respectively, after adjusting for mean blood pressure (MBP), age, gender, diabetes duration, HbA(1c), body mass index (BMI), lipid-reducing drugs, microalbuminuria > 20microg/min, antihypertensive drugs and hypoglycaemic treatment, using Cox regression analyses. Fully-adjusted respective HRs for stroke were 1.17 (0.98-1.39) and 1.21 (0.90-1.61) and, for CVD, 1.23 (1.10-1.37; P<0.001) and 1.28 (1.07-1.52; P=0.007). Fully-adjusted HRs for baseline PP increased per quartile and, CHD, stroke or CVD, were 1.09 (1.03-1.16; P=0.004), 1.14 (1.05-1.23; P=0.002) and 1.11 (1.05-1.17; P<0.001), respectively. The data suggest that, if a mean PP>or=75mmHg were to be avoided, then 15% and 17% of CHD and or CVD, cases, respectively, in such a cohort might be prevented after multivariable adjustments, with a further 10% of cases avoided if also adjusted for MBP and age. Increasing baseline MBP, age and microalbuminuria were independently and significantly associated (P<0.001) with increasing baseline or mean PP. CONCLUSION: Increased PP is a powerful independent risk predictor of CVD in type 2 diabetic patients, and lowering PP can lead to a marked reduction in risk.

  • 47. Nilsson, P M
    et al.
    Gudbjörnsdottir, S
    Eliasson, B
    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.
    Hypertension in diabetes: trends in clinical control in repeated large-scale national surveys from Sweden2003In: Journal of Human Hypertension, ISSN 0950-9240, E-ISSN 1476-5527, Vol. 17, no 1, 37-44 p.Article in journal (Refereed)
    Abstract [en]

    Hypertension in diabetes is an important and treatable cardiovascular risk factor. Treatment targets from guidelines cannot always be achieved in everyday clinical practice. It is therefore of great importance to monitor trends in hypertension control in defined populations. Patients with type I diabetes (range 6685-10100; treated hypertension 21-29%) or with type II diabetes (range 15935-22605; treated hypertension 47-56%) were included in four national samples between 1996 and 1999. This screening was part of the procedures for the National Diabetes Register in Sweden, which monitors trends in clinical practice and risk factors for patients with diabetes, recruited both in primary health care and at the hospital level. A favourable trend in mean and median blood pressure levels was noticed during the 4-year study period, based either on data from repeated surveys or on repeated measures in the same individual, both for type I diabetes (mean: -2/-2 mmHg; P < 0.01) and for type II diabetes (mean: -5/-3 mmHg; P < 0.001). Correspondingly, the proportion of hypertensive patients in acceptable control of blood pressure (less than or equal to140/ 85 mmHg) increased (P < 0.001) both in type I diabetes (52.0-57.9%) and in type 11 diabetes (22.4-33.3%). It was concluded that hypertension is a widespread cardiovascular risk factor in patients with diabetes, especially systolic hypertension. A trend for a better systolic blood pressure control during the late 1990s in hypertensive patients with type II diabetes in Sweden could translate into substantial (estimated) clinical benefits in cardiovascular and diabetes-related morbidity. The National Diabetes Register makes a quality assessment of the hypertension treatment possible.

  • 48. Nilsson, P M
    et al.
    Gudbjörnsdottir, S
    Eliasson, B
    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.
    Smoking is associated with increased HbA1c values and microalbuminuria in patients with diabetes: data from the National Diabetes Register in Sweden2004In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 30, no 3, 261-268 p.Article in journal (Other academic)
    Abstract [en]

    OBJECTIVES:

    The aim was to examine trends in the proportion of smoking in diabetes patients, and to study associations between smoking, glycaemic control, and microalbuminuria.

    METHODS:

    Smoking habits were reported to the Swedish National Diabetes Register (NDR), with data from hospitals and primary health care. Patient characteristics included were age, gender, type of treatment, diabetes duration, HbA1c, BMI, blood pressure, antihypertensive and lipid-lowering drugs, and microalbuminuria.

    RESULTS:

    The proportion of smokers in type 1 diabetes was 12-15% during 1996-2001, it was high in females<30 years (12-16%), and was higher in the age group 30-59 years (13-17%) than in older (6-9%) patients. The corresponding proportion of smoking in type 2 diabetes was 10-12%, higher in those less than 60 years of age (17-22%) than in older (7-9%) patients. Smoking type 1 and type 2 patients in 2001 had higher mean HbA1c but lower mean BMI values than non-smokers. Smokers also had higher frequencies of microalbuminuria, in both type 1 (18 vs 14%) and type 2 (20% vs 13%) diabetes. Multiple logistic regression analyses disclosed that smoking was independently associated with elevated HbA1c levels (p<0.001) and microalbuminuria (p<0.001), but negatively with BMI (p<0.001), in both type 1 and type 2 diabetes.

    CONCLUSIONS:

    Smoking in patients with diabetes was widespread, especially in young female type 1, and in middle-aged type 1 and type 2 diabetes patients, and should be the target for smoking cessation campaigns. Smoking was associated with both poor glycaemic control and microalbuminuria, independently of other study characteristics.

  • 49. Nilsson, Peter M.
    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.
    Diabetes, Hypertension, and Outcome Studies: Overview 20102011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, S109-S113 p.Article in journal (Refereed)
  • 50. Nilsson, Peter M
    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.
    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.
    Fagard, Robert
    Gudbjörnsdóttir, Soffia
    Smoking as an independent risk factor for myocardial infarction or stroke in type 2 diabetes: a report from the Swedish National Diabetes Register2009In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, no 4, 506-512 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Few earlier studies have analysed smoking as a risk factor for myocardial infarction (MI) or stroke in type 2 diabetic patients. DESIGN AND METHODS: A longitudinal study involved 13 087 female and male patients with type 2 diabetes from the Swedish National Diabetes Register with no previous MI or stroke at baseline, aged 30-74 years, and with data available for all analysed variables, followed up for mean 5.7 years. RESULTS: Adjusted hazard ratios (HRs) for smoking and first-incident fatal/nonfatal MI, stroke and total mortality were 1.7 [95% confidence interval (CI): 1.4-2.0; P<0.001], 1.3 (95% CI: 1.1-1.6; P = 0.006) and 1.8 (95% CI: 1.5-2.2; P<0.001), respectively, by Cox regression analysis, adjusted for age, sex, diabetes duration, hypoglycaemic treatment, haemoglobin A1c, blood pressure, body mass index, microalbuminuria, antihypertensive and lipid-lowering drugs. Adjusted HR was higher for fatal MI, 2.1 (95% CI: 1.7-2.7; P<0.001), than for nonfatal MI, 1.4 (95% CI: 1.2-1.7; P<0.001). The highest HRs were observed in more frequently smoking (22%), middle-aged patients (age <60 years) for fatal/nonfatal MI, 2.3 (95% CI: 1.8-3.1; P<0.001) and for total mortality, 2.5 (95% CI: 1.6-3.8, P<0.001), whereas lower HRs were observed in older and less smoking patients. With predicted cessation of smoking in patients aged below 60 years, 24% (95% CI: 15-33%) of cases of fatal/nonfatal MI and 24% (11-37%) of cases of total mortality may have been prevented. CONCLUSION: The risk for MI and total mortality associated with smoking is high in type 2 diabetes, especially in more frequently smoking, middle-aged patients, and was higher for MI than for stroke, and also higher for fatal than for nonfatal events. Smoking cessation would strongly affect risk reduction.

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