Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Diabetes Mellitus: HELP
Articles by Anna Norhammar
Based on 28 articles published since 2010
(Why 28 articles?)
||||

Between 2010 and 2020, A. Norhammar wrote the following 28 articles about Diabetes Mellitus.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Problems, Pitfalls and Encouraging Information on Patients with Diabetes and Heart Failure. 2016

Norhammar, Anna / Johansson, Isabelle / Rydén, Lars. ·Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. ·Cardiology · Pubmed #27120171.

ABSTRACT: -- No abstract --

2 Review Diabetes: Prevalence, prognosis and management of a potent cardiovascular risk factor. 2017

Norhammar, Anna / Mellbin, Linda / Cosentino, Francesco. ·1 Cardiology Unit, Department of Medicine Solna, Karolinska University Hospital, Stockholm, Sweden. · 2 Capio S:t Görans hospital, Sankt Göransplan, Stockholm, Sweden. ·Eur J Prev Cardiol · Pubmed #28618910.

ABSTRACT: This review highlights the increased risk of cardiovascular disease and the dismal prognosis after acute coronary events when diabetes is present. Although there have been improvements in this area, diabetes still confers an increased risk. In order to achieve successful outcomes in individuals with diabetes, extensive treatment of risk factors and the use of all available evidence-based therapies are needed. In this context, glucose-lowering therapies and antithrombotic and revascularisation strategies are detailed in this review. Emerging data indicate that novel glucose-lowering drugs may impact cardiovascular outcome with mechanisms that are beyond glucose control. In addition, this review addresses hidden diabetes and impaired glucose tolerance in patients with acute and stable coronary artery disease and how they influence future cardiovascular risk.

3 Article Elevated admission glucose is common and associated with high short-term complication burden after acute myocardial infarction: Insights from the VALIDATE-SWEDEHEART study. 2019

Ritsinger, Viveca / Jensen, Jens / Ohm, Daniel / Omerovic, Elmir / Koul, Sasha / Fröbert, Ole / Erlinge, David / James, Stefan / Lagerqvist, Bo / Norhammar, Anna. ·Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden. · Department of Research and Development, Region Kronoberg, Växjö, Sweden. · Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden. · Capio S:t Görans Hospital, Stockholm, Sweden. · Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden. · Departments of Cardiology and Clinical Sciences, Lund University, Lund, Sweden. · Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden. · Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. ·Diab Vasc Dis Res · Pubmed #31476896.

ABSTRACT: OBJECTIVE: To investigate the association between admission plasma glucose and cardiovascular events in patients with acute myocardial infarction treated with modern therapies including early percutaneous coronary intervention and modern stents. METHODS: Patients ( RESULTS: Mean age was 67 ± 11 years. Previously known diabetes was present in 21.2% ( CONCLUSION: In a well-treated contemporary population of acute myocardial infarction patients, 42% of those without diabetes had elevated admission plasma glucose levels with a greater risk for clinical events already within 180 days. Event rate increased with increasing admission plasma glucose levels. These findings highlight the importance of searching for undetected diabetes in the setting of acute myocardial infarction and that new treatment options are needed to improve outcome.

4 Article Copeptin and insulin-like growth factor binding protein-1 during follow-up after an acute myocardial infarction in patients with type 2 diabetes: A report from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction 2 cohort. 2019

Smáradóttir, Maria Isabel / Catrina, Sergiu-Bogdan / Brismar, Kerstin / Norhammar, Anna / Gyberg, Viveca / Mellbin, Linda G. ·1 Division of Cardiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. · 2 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. ·Diab Vasc Dis Res · Pubmed #30309264.

ABSTRACT: PURPOSE: Copeptin and insulin-like growth factor binding protein-1 analysed at admission for a myocardial infarction in patients with type 2 diabetes mellitus predicts cardiovascular events. The present aim was to study the association between copeptin and insulin-like growth factor binding protein-1, the development of the levels over time, and if the predictive value remained when measured at hospital discharge and 3 months thereafter. METHODS: Copeptin and insulin-like growth factor binding protein-1 were analysed in patients (median age = 70, male = 68%) with type 2 diabetes mellitus + myocardial infarction at admission (n = 393), discharge (n = 309) and 3 months later (n = 288). The primary endpoint was cardiovascular event (cardiovascular death/non-fatal myocardial infarction/stroke) with the three time points as separate baselines. RESULTS: The median copeptin levels were 21.8 pmol/L at admission, 8.5 pmol/L at discharge and 8.4 pmol/L after 3 months, while insulin-like growth factor binding protein-1 levels continued to increase. There were significant correlations between the biomarkers at all occasions. During an average follow-up of 2.5 years, copeptin, but not insulin-like growth factor binding protein-1, predicted cardiovascular event at all occasions in unadjusted analyses. Copeptin remained as a predictor at discharge and after 3 months in the final multiple model (including: heart failure/age/creatinine clearance). CONCLUSION: The relationship between copeptin and insulin-like growth factor binding protein-1 during the initial phase of a myocardial infarction persisted in a less-stressful situation, and copeptin remained as a prognostic indicator at discharge and 3 months later.

5 Article Type 2 diabetes and heart failure: Characteristics and prognosis in preserved, mid-range and reduced ventricular function. 2018

Johansson, Isabelle / Dahlström, Ulf / Edner, Magnus / Näsman, Per / Rydén, Lars / Norhammar, Anna. ·1 Karolinska University Hospital Solna and Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. · 2 Departments of Cardiology and Medical and Health Sciences, Linköping University, Linköping, Sweden. · 3 Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden. · 4 Capio St. Göran's Hospital, Stockholm, Sweden. ·Diab Vasc Dis Res · Pubmed #30176743.

ABSTRACT: OBJECTIVE: To study the characteristics and prognostic implications of type 2 diabetes in different heart failure entities from a nationwide perspective. METHODS: This observational study comprised 30,696 heart failure patients prospectively included in the Swedish Heart Failure Registry (SwedeHF) 2003-2011 from specialist care, with mortality information available until December 2014. Patients were categorized into three heart failure entities by their left ventricular ejection fraction (heart failure with preserved ejection fraction: ⩾50%, heart failure with mid-range ejection fraction: 40%-49% and heart failure with reduced ejection fraction: <40%). All-cause mortality stratified by type 2 diabetes and heart failure entity was studied by Cox regression. RESULTS: Among the patients, 22% had heart failure with preserved ejection fraction, 21% had heart failure with mid-range ejection fraction and 57% had heart failure with reduced ejection fraction. The proportion of type 2 diabetes was similar, ≈25% in each heart failure entity. Patients with type 2 diabetes and heart failure with preserved ejection fraction were older, more often female and burdened with hypertension and renal impairment compared with heart failure with mid-range ejection fraction and heart failure with reduced ejection fraction patients among whom ischaemic heart disease was more common. Type 2 diabetes remained an independent mortality predictor across all heart failure entities after multivariable adjustment, somewhat stronger in heart failure with left ventricular ejection fraction below 50% (hazard ratio, 95% confidence interval; heart failure with preserved ejection fraction: 1.32 [1.22-1.43], heart failure with mid-range ejection fraction: 1.51 [1.39-1.65], heart failure with reduced ejection fraction: 1.46 [1.39-1.54]; p-value for interaction, p = 0.0049). CONCLUSION: Type 2 diabetes is an independent mortality predictor across all heart failure entities increasing mortality risk by 30%-50%. In type 2 diabetes, the heart failure with mid-range ejection fraction entity resembles heart failure with reduced ejection fraction in clinical characteristics, risk factor pattern and prognosis.

6 Article Diabetes and cardiovascular mortality: the impact of sex. 2018

Norhammar, Anna. ·Cardiology Research Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden; Capio Saint Gõrans Hospital, Stockholm, Sweden. Electronic address: anna.norhammar@ki.se. ·Lancet Diabetes Endocrinol · Pubmed #29752193.

ABSTRACT: -- No abstract --

7 Article Severe Periodontitis Is Associated with Myocardial Infarction in Females. 2018

Nordendahl, E / Gustafsson, A / Norhammar, A / Näsman, P / Rydén, L / Kjellström, B / Anonymous10630941. ·1 Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden. · 2 Department of Medicine, Karolinska Institutet, Stockholm, Sweden. · 3 Capio S:t Görans Hospital, Stockholm, Sweden. · 4 Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden. ·J Dent Res · Pubmed #29596754.

ABSTRACT: The aim of the present study was to test the hypothesis that there is a sex difference in the association between periodontitis (PD) and a first myocardial infarction (MI). The analysis in the case-control study was based on 785 patients (147 females and 638 males) with a first MI and 792 matched controls (147 females and 645 males), screened for cardiovascular risk factors and subjected to a panoramic dental X-ray. Periodontal status was defined by alveolar bone loss and diagnosed as no PD (≥80% remaining alveolar bone), mild to moderate PD (66% to 79%), or severe PD (<66%). Logistic regression was used when analyzing PD as a risk factor for MI, adjusting for age, smoking, diabetes, education, and marital status. The mean age was 64 ± 7 y for females and 62 ± 8 y for males. Severe PD was more common in female patients than female controls (14 vs. 4%, P = 0.005), with an increased risk for severe PD among female patients with a first MI (odds ratio [OR] = 3.92, 95% confidence interval [CI] =1.53 to 10.00, P = 0.005), which remained (OR = 3.72, 95% CI = 1.24 to 11.16, P = 0.005) after adjustments. Male patients had more severe PD (7% vs. 4%; P = 0.005) than male controls and an increased risk for severe PD (OR = 1.88, 95% CI = 1.14 to 3.11, P = 0.005), but this association did not remain following adjustment (OR = 1.67, 95% CI = 0.97 to 2.84, NS). Severe PD was associated with MI in both females and males. After adjustments for relevant confounders, this association did, however, remain only in females. These data underline the importance of considering poor dental health when evaluating cardiovascular risk, especially in females.

8 Article Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: Results from the CVD-REAL study. 2018

Kosiborod, Mikhail / Birkeland, Kåre I / Cavender, Matthew A / Fu, Alex Z / Wilding, John P / Khunti, Kamlesh / Holl, Reinhard W / Norhammar, Anna / Jørgensen, Marit E / Wittbrodt, Eric T / Thuresson, Marcus / Bodegård, Johan / Hammar, Niklas / Fenici, Peter / Anonymous7010940. ·Department of Cardiovascular Diseases, Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City, Kansas City, Missouri. · University of Oslo and Oslo University Hospital, Oslo, Norway. · Department of Medicine, University of North Carolina, Chapel Hill, North Carolina. · Georgetown University Medical Center, Washington, District of Columbia. · Obesity and Endocrinology Research Group, University of Liverpool, Liverpool, UK. · Leicester Diabetes Centre, University of Leicester, Leicester, UK. · Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany. · Karolinska Institutet, Stockholm, Sweden. · Capio S:t Görans Hospital, Stockholm, Sweden. · Steno Diabetes Center, Copenhagen, Denmark. · National Institute of Public Health, Southern Denmark University, Odense, Denmark. · Health Economics and Outcomes Research, AstraZeneca, Wilmington, Delaware. · Statisticon AB, Uppsala, Sweden. · AstraZeneca Nordic-Baltic, Oslo, Norway. · AstraZeneca R&D, Gothenburg, Sweden. · Global Medicines Development, AstraZeneca, Cambridge, UK. ·Diabetes Obes Metab · Pubmed #29569378.

ABSTRACT: The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs other glucose-lowering drugs (oGLDs). This sub-analysis of the CVD-REAL study sought to determine the association between initiation of SGLT-2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non-parsimonious propensity score was developed within each country to predict initiation of SGLT-2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent-to-treat analysis, over 188 551 and 188 678 person-years of follow-up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT-2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72-1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71-0.97; P = .02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT-2i, specifically as it relates to ischaemic events.

9 Article Characteristics and Prognosis in Women and Men With Type 1 Diabetes Undergoing Coronary Angiography: A Nationwide Registry Report. 2018

Ritsinger, Viveca / Hero, Christel / Svensson, Ann-Marie / Saleh, Nawzad / Lagerqvist, Bo / Eeg-Olofsson, Katarina / Norhammar, Anna. ·Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden viveca.ritsinger@ki.se. · Department of Research and Development, Region Kronoberg, Växjö, Sweden. · Department of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden. · National Diabetes Register, Centre of Registers, Region Västra Götaland, Gothenburg, Sweden. · Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden. · Department of Cardiology, Uppsala University Hospital, Uppsala, Sweden. · Capio S:t Göran's Hospital, Stockholm, Sweden. ·Diabetes Care · Pubmed #29463579.

ABSTRACT: OBJECTIVE: To describe sex aspects on extent of coronary artery disease (CAD) and prognosis in a contemporary population with type 1 diabetes. RESEARCH DESIGN AND METHODS: All patients undergoing coronary angiography, 2001-2013, included in the Swedish Coronary Angiography and Angioplasty Registry and the Swedish National Diabetes Register as type 1 diabetes were followed for mortality until 31 December 2013. The coronary angiogram was classified into normal, one-vessel disease, two-vessel disease, three-vessel disease, and left main stem disease. RESULTS: In all, 2,776 patients (42% women) with mean age 58 years (SD 11) were followed for 7.2 years (SD 2.2). Diabetes duration was longer in women (37 ± 14 vs. 34 ± 14 years in men; CONCLUSIONS: In patients with type 1 diabetes admitted for coronary angiography, the extent of CAD was almost similar in women and men, and total long-term mortality did not differ. Type 1 diabetes was associated with higher mortality risk in women than in men when compared with the general population. These data support that type 1 diabetes attenuates the cardiovascular risk difference seen in men and women in the general population.

10 Article High overall cardiovascular risk and mortality in patients with atrial fibrillation and diabetes: A nationwide report. 2018

Karayiannides, Stelios / Lundman, Pia / Friberg, Leif / Norhammar, Anna. ·1 Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden. · 2 Department of Internal Medicine, Danderyd University Hospital, Stockholm, Sweden. · 3 Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden. · 4 Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · 5 Department of Clinical Physiology, Capio St Görans Hospital, Stockholm, Sweden. ·Diab Vasc Dis Res · Pubmed #29052435.

ABSTRACT: AIM: To describe nationwide complication patterns in patients with atrial fibrillation and diabetes mellitus. METHODS: All ( n = 326,832) patients in Sweden with non-valvular atrial fibrillation during 2006-2012 were identified, and information on events, comorbidities and pharmacological therapy was extracted using nationwide mandatory registers. Patients were followed until 31 December 2013 and the mean follow-up time was 3.7 years (0.9-8 years). RESULTS: Diabetes was present in 17.7%. The most frequent events in those with and without diabetes were mortality (48.8% vs 36.4%; p < 0.001), heart failure (21.4% vs 13.1%; p < 0.001), ischaemic stroke (8.2% vs 6.8%; p < 0.001), myocardial infarction (7.3% vs 4.3%; p < 0.001) and any bleeding (6.3% vs 5.2%; p < 0.001), respectively. Diabetes predicted mortality (hazard ratio = 1.28; 95% confidence interval = 1.25-1.31), combined event (first of mortality, heart failure, ischaemic stroke or myocardial infarction; hazard ratio = 1.22; 95% confidence interval = 1.20-1.25), single events and bleeding (hazard ratio = 1.12; 95% confidence interval = 1.06-1.19). The standardised mortality ratio for patients with atrial fibrillation and diabetes compared to the general population was 2.06 (95% confidence interval = 2.00-2.12) and for patients with atrial fibrillation without diabetes was 1.33 (95% confidence interval = 1.31-1.35). CONCLUSION: In this real-world setting, patients with atrial fibrillation and diabetes have a high cardiovascular risk, with mortality and heart failure rates exceeding those for stroke.

11 Article Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: A multinational observational study. 2018

Persson, Frederik / Nyström, Thomas / Jørgensen, Marit E / Carstensen, Bendix / Gulseth, Hanne L / Thuresson, Marcus / Fenici, Peter / Nathanson, David / Eriksson, Jan W / Norhammar, Anna / Bodegard, Johan / Birkeland, Kåre I. ·Steno Diabetes Centre, Copenhagen, Denmark. · Karolinska Institutet, Södersjukhuset, Stockholm, Sweden. · Oslo University Hospital, Oslo, Norway. · Statisticon AB, Uppsala, Sweden. · AstraZeneca, Cambridge, UK. · Uppsala University, Uppsala, Sweden. · Karolinska Institutet, Stockholm, Sweden. · Capio S:t Görans Hospital, Stockholm, Sweden. · AstraZeneca Nordic-Baltic, Oslo, Norway. · University of Oslo, Oslo, Norway. ·Diabetes Obes Metab · Pubmed #28771923.

ABSTRACT: AIMS: To compare the sodium-glucose-cotransporter-2 (SGLT-2) inhibitor dapagliflozin with dipeptidyl peptidase-4 (DPP-4) inhibitors with regard to risk associations with major adverse cardiovascular (CV) events (MACE; non-fatal myocardial infarction, non-fatal stroke or cardiovascular mortality), hospitalization for heart failure (HHF), atrial fibrillation and severe hypoglycaemia in patients with type 2 diabetes (T2D) in a real-world setting. METHODS: All patients with T2D prescribed glucose-lowering drugs (GLDs) during 2012 to 2015 were identified in nationwide registries in Denmark, Norway and Sweden. Patients were divided into two groups: new users of dapagliflozin and new users of DPP-4 inhibitors, matched 1:3 by propensity score, calculated by patient characteristics, comorbidities and drug treatment. Cox survival models were used to estimate hazard ratio (HR) per country separately, and a weighted average was calculated. RESULTS: After matching, a total of 40 908 patients with T2D were identified as new users of dapagliflozin (n = 10 227) or a DPP-4 inhibitor (n = 30 681). The groups were well balanced at baseline; their mean age was 61 years and 23% had CV disease. The mean follow-up time was 0.95 years, with a total of 38 760 patient-years. Dapagliflozin was associated with a lower risk of MACE, HHF and all-cause mortality compared with DPP-4 inhibitors: HRs 0.79 (95% confidence interval [CI] 0.67-0.94), 0.62 (95% CI 0.50-0.77), and 0.59 (95% CI 0.49-0.72), respectively. Numerically lower, but non-significant HRs were observed for myocardial infarction (0.91 [95% CI 0.72-1.16]), stroke (0.79 [95% CI 0.61-1.03]) and CV mortality (0.76 [95% CI 0.53-1.08]) Neutral associations with atrial fibrillation and severe hypoglycaemia were observed. CONCLUSIONS: Dapagliflozin was associated with lower risks of CV events and all-cause mortality compared with DPP-4 inhibitors in a real-world clinical setting and a broad T2D population.

12 Article Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis. 2017

Birkeland, Kåre I / Jørgensen, Marit E / Carstensen, Bendix / Persson, Frederik / Gulseth, Hanne L / Thuresson, Marcus / Fenici, Peter / Nathanson, David / Nyström, Thomas / Eriksson, Jan W / Bodegård, Johan / Norhammar, Anna. ·Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway. · Steno Diabetes Center Copenhagen, Gentofte, Denmark; National Institute of Public Health, Southern Denmark University, Copenhagen, Denmark. · Steno Diabetes Center Copenhagen, Gentofte, Denmark. · Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. · Statisticon AB, Uppsala, Sweden. · AstraZeneca, Cambridge, UK. · Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden. · Department of Medical Sciences, Uppsala University, Uppsala, Sweden. · Medical Department, AstraZeneca Nordic-Baltic, Oslo, Norway. Electronic address: johan.bodegard@astrazeneca.com. · Department of Medicine, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Capio St Görans Hospital, Stockholm, Sweden. ·Lancet Diabetes Endocrinol · Pubmed #28781064.

ABSTRACT: BACKGROUND: In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. METHODS: CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. FINDINGS: Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0·9 (SD 4·1) years (80 669 patient-years) and mean age of 61 (12·0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0·53 [95% CI 0·40-0·71]), major adverse cardiovascular events (0·78 [0·69-0·87]), and hospital events for heart failure (0·70 [0·61-0·81]; p<0·0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0·76 [0·65-0·90]; p=0·001). For cardiovascular mortality, the differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0·60 [0·42-0·85] vs 0·55 [0·34-0·90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0·70 (0·59-0·83) versus 0·90 (0·76-1·07) in the group without. INTERPRETATION: In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs-a finding consistent with the results of clinical trials in patients at high cardiovascular risk. FUNDING: AstraZeneca.

13 Article Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors). 2017

Kosiborod, Mikhail / Cavender, Matthew A / Fu, Alex Z / Wilding, John P / Khunti, Kamlesh / Holl, Reinhard W / Norhammar, Anna / Birkeland, Kåre I / Jørgensen, Marit Eika / Thuresson, Marcus / Arya, Niki / Bodegård, Johan / Hammar, Niklas / Fenici, Peter / Anonymous6640906. ·From Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City (M.K.) · University of North Carolina, Chapel Hill (M.A.C.) · Georgetown University Medical Center, Washington, DC (A.Z.F.) · University of Liverpool, United Kingdom (J.P.W.) · University of Leicester, United Kingdom (K.K.) · University of Ulm, Germany (R.W.H.) · Karolinska Institutet, Stockholm, Sweden (A.N., N.H.) · University of Oslo, Norway (K.I.B.) · Oslo University Hospital, Norway (K.I.B.) · Steno Diabetes Center, Copenhagen, Gentofte, Denmark (M.E.J.) · National Institute of Public Health, Southern Denmark University, Copenhagen (M.E.J.) · Statisticon AB, Uppsala, Sweden (M.T.) · AstraZeneca, Gaithersburg, MD (N.A.) · AstraZeneca, Oslo, Norway (J.B.) · AstraZeneca Gothenburg, Sweden (N.H.) · and AstraZeneca, Cambridge, United Kingdom (P.F.). ·Circulation · Pubmed #28522450.

ABSTRACT: BACKGROUND: Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class. METHODS: Data were collected via medical claims, primary care/hospital records, and national registries from the United States, Norway, Denmark, Sweden, Germany, and the United Kingdom. Propensity score for SGLT-2i initiation was used to match treatment groups. Hazard ratios for HHF, death, and their combination were estimated by country and pooled to determine weighted effect size. Death data were not available for Germany. RESULTS: After propensity matching, there were 309 056 patients newly initiated on either SGLT-2i or other glucose-lowering drugs (154 528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42%, and 5% of the total exposure time in the SGLT-2i class, respectively. Baseline characteristics were balanced between the 2 groups. There were 961 HHF cases during 190 164 person-years follow-up (incidence rate, 0.51/100 person-years). Of 215 622 patients in the United States, Norway, Denmark, Sweden, and the United Kingdom, death occurred in 1334 (incidence rate, 0.87/100 person-years), and HHF or death in 1983 (incidence rate, 1.38/100 person-years). Use of SGLT-2i, versus other glucose-lowering drugs, was associated with lower rates of HHF (hazard ratio, 0.61; 95% confidence interval, 0.51-0.73; CONCLUSIONS: In this large multinational study, treatment with SGLT-2i versus other glucose-lowering drugs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of patients with type 2 diabetes mellitus in real-world practice. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02993614.

14 Article Copeptin in patients with acute myocardial infarction and newly detected glucose abnormalities - A marker of increased stress susceptibility? A report from the Glucose in Acute Myocardial Infarction cohort. 2017

Smaradottir, Maria Isabel / Ritsinger, Viveca / Gyberg, Viveca / Norhammar, Anna / Näsman, Per / Mellbin, Linda G. ·1 Cardiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden. · 2 Department of Research and Development, Region Kronoberg, Växjö, Sweden. · 3 Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden. · 4 Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden. ·Diab Vasc Dis Res · Pubmed #28118730.

ABSTRACT: OBJECTIVE: To characterize copeptin levels and to explore its prognostic importance in patients with acute myocardial infarction with newly detected glucose abnormalities. METHODS: Copeptin was measured in 166 patients with acute myocardial infarction without known diabetes and in 168 age- and gender-matched controls. Participants were classified as having normal glucose tolerance or abnormal glucose tolerance (impaired glucose tolerance + type 2 diabetes mellitus) by oral glucose tolerance test. Study participants were followed over a decade for major cardiovascular event (acute myocardial infarction/stroke/congestive heart failure/cardiovascular death), cardiovascular and total death. RESULTS: Median copeptin level was higher in patients (10.5 pmol/L) than controls (5.9 pmol/L; p < 0.01). Patients with abnormal glucose tolerance had higher copeptin (12.2 pmol/L) than those with normal glucose tolerance (7.9 pmol/L; p < 0.01) but levels of copeptin did not differ in controls with abnormal glucose tolerance or normal glucose tolerance. Copeptin predicted major cardiovascular events [ n = 64; hazard ratio = 1.15 (1.01-1.32; p = 0.04)], cardiovascular mortality [ n = 29; hazard ratio = 1.24 (1.06-1.46; p = 0.01)] and total death [ n = 51; hazard ratio = 1.21 (1.05-1.40; p = 0.01)] in unadjusted Cox regression analyses in the patient cohort. In controls, copeptin predicted major cardiovascular events [ n = 26; hazard ratio = 1.17 (1.01-1.36; p = 0.03)]. CONCLUSION: Copeptin levels are highest among acute myocardial infarction patients with glucose disturbances and predict an adverse prognosis in unadjusted analyses. These findings imply that raised copeptin reflects stress rather than acting as a pathogenic factor for glucose abnormalities.

15 Article Novel oral glucose-lowering drugs are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes. 2017

Nyström, Thomas / Bodegard, Johan / Nathanson, David / Thuresson, Marcus / Norhammar, Anna / Eriksson, Jan W. ·Unit for Diabetes Research, Division of Internal Medicine, Department of Clinical Science and Education, Karolinska Institute, Södersjukhuset, Stockholm, Sweden. · AstraZeneca Nordic-Baltic, Södertälje, Sweden. · Cardiology Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden. · Capio S:t Görans Hospital, Stockholm, Sweden. · Statisticon AB, Uppsala, Sweden. · Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden. ·Diabetes Obes Metab · Pubmed #28116795.

ABSTRACT: AIMS: To investigate the association of novel oral glucose-lowering drugs (GLDs), compared with that of insulin, with risk of all-cause mortality, cardiovascular disease (CVD) and severe hypoglycaemia. METHODS: During 2013 to 2014 all patients with type 2 diabetes in Sweden identified as new users of novel oral GLDs, either dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT2) inhibitors (only dapagliflozin available in Sweden during the study period), with those initiating insulin as a comparison group, in the Prescribed Drug Register were included and followed in the Patient and Cause of Death Registers. The novel GLD group and insulin group were matched 1:1 using propensity score. Cox regression models were used to estimate risks. RESULTS: Of 37 603 patients, 21 758 were matched 1:1 to novel GLD vs insulin groups, with median follow-up times of 1.51 years (16 304 patient-years) and 1.53 years (16 306 patient-years), respectively. Treatment with novel GLDs was associated with a 44% (hazard ratio [HR] 0.56 [95% confidence interval {CI} 0.49-0.64]), 15% (HR 0.85 [95% CI 0.73-0.99]) and 74% (0.26 [95% CI 0.12-0.57]) lower risk of all-cause mortality, CVD and hypoglycaemia, respectively, compared with insulin treatment. In separate analyses for the two novel GLDs, dapagliflozin was associated with lower risks of all-cause mortality and CVD (56% [HR 0.44, 95% CI 0.28-0.70] and 49% [HR 0.51, 95% CI 0.30-0.86], respectively), while DPP-4 inhibitor treatment was associated with lower risk of all-cause mortality (41% [HR 0.59, 95% CI 0.51-0.67]), but not with CVD (HR 0.87, 95% CI 0.75-1.01). CONCLUSIONS: Novel oral GLD treatment was associated with lower risk of all-cause mortality, CVD and severe hypoglycaemia compared with insulin treatment. Dapagliflozin was associated with a lower risk of both all-cause mortality and CVD, whereas DPP-4 inhibitor treatment was only associated with lower risk of all-cause mortality.

16 Article Mortality and extent of coronary artery disease in 2776 patients with type 1 diabetes undergoing coronary angiography: A nationwide study. 2017

Ritsinger, V / Hero, C / Svensson, A M / Saleh, N / Lagerqvist, B / Eeg-Olofsson, K / Norhammar, A. ·1 Unit of Cardiology, Department of Medicine, Solna, Karolinska Institutet & Karolinska University Hospital, Stockholm, Sweden. · 2 Department of Research and Development, Region Kronoberg, Sweden. · 3 Department of Medicine, University of Gothenburg, Sweden. · 4 The National Diabetes Register, Sweden. · 5 Department of Medical Sciences, Uppsala University, Sweden. · 6 Capio St Göran's Hospital, Stockholm, Sweden. ·Eur J Prev Cardiol · Pubmed #28084092.

ABSTRACT: Background In a modern perspective there is limited information on mortality by affected coronary vessels assessed by coronary angiography in patients with type 1 diabetes. The aim of the present study was to characterise distribution of coronary artery disease and impact on long-term mortality in patients with type 1 diabetes undergoing coronary angiography. Design The design of this research was a nationwide population-based cohort study. Methods Individuals ( n = 2776) with type 1 diabetes undergoing coronary angiography 2001-2013 included in the Swedish National Diabetes Registry and Swedish Coronary Angiography and Angioplasty Registry were followed for mortality until 31 December 2013 (mean 7.1 years). In 79% the indication was stable or acute coronary artery disease. Coronary artery disease was categorised into normal (21%), one- (23%), two- (18%), three- (29%) and left main-vessel disease (8%). Results Mean age was 57 years and 58% were male. Mean diabetes duration was 35 years, glycated haemoglobin was 67 mmol/mol and 44% had normal or one-vessel disease. In multivariate Cox proportional analyses hazard ratio for mortality compared with normal findings was 1.09 (95% confidence interval 0.80-1.48) for one, 1.43 (1.05-1.94) for two, 1.47 (1.10-1.96) for three and 1.90 (1.35-2.68) for left main-vessel disease. Renal failure 2.29 (1.77-2.96) and previous heart failure 1.76 (1.46-2.13) were highly associated with mortality. Standard mortality ratio the first year was 5.55 (4.65-6.56) and decreased to 2.80 (2.18-3.54) after five years. Conclusions In patients with type 1 diabetes referred for coronary angiography mortality is influenced by numbers of affected coronary vessels. The overall mortality rate was higher compared with the general population. These results support early intensive prevention of coronary artery disease in this population.

17 Article Second line initiation of insulin compared with DPP-4 inhibitors after metformin monotherapy is associated with increased risk of all-cause mortality, cardiovascular events, and severe hypoglycemia. 2017

Nyström, Thomas / Bodegard, Johan / Nathanson, David / Thuresson, Marcus / Norhammar, Anna / Eriksson, Jan W. ·Department of Clinical Science and Education, Division of Internal Medicine, Unit for Diabetes Research, Karolinska Institute, Södersjukhuset, Stockholm, Sweden. · AstraZeneca Nordic-Baltic, Södertälje, Sweden. Electronic address: johan.bodegard@astrazeneca.com. · Statisticon AB, Uppsala, Sweden. · Cardiology Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden; Capio S:t Görans Hospital, Stockholm, Sweden. · Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden. ·Diabetes Res Clin Pract · Pubmed #28056431.

ABSTRACT: AIMS: The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: All patients with T2D in Sweden who initiated second-line treatment with insulin or DPP-4i after metformin monotherapy during 2007-2014 identified in the Swedish Prescribed Drug Register were followed for outcome in the Cause of Death and National Patient Registers. Insulin and DPP-4i patients were matched 1:1 using propensity-score matching. Comparisons between groups were performed using unadjusted Cox regression models. Additionally, multivariate adjusted survival models were used to test the results using the full population without matching. RESULTS: Of 27,767 mono-metformin-treated patients, 55.7% started insulin and 44.3% a DPP-4i, and after matching both groups had 9278 patients each. Median follow-up (patients years) times were 3.84 (37,578) and 3.93 (37,983) for insulin and DPP-4i-groups, respectively. Insulin compared with DPP-4i was associated with higher risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia; adjusted HR (95% CI): 1.69 (1.45-1.96); 1.39 (1.21-1.61); and 4.35 (2.26-8.35), respectively. When performing multivariate adjusted analyses on the full population similar results were found. CONCLUSIONS: Initiation of insulin, compared with DPP-4i treatment, was associated with an increased risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia. Results from randomized trials will be important to elucidate causal relationships.

18 Article Prognostic Implications of Type 2 Diabetes Mellitus in Ischemic and Nonischemic Heart Failure. 2016

Johansson, Isabelle / Dahlström, Ulf / Edner, Magnus / Näsman, Per / Rydén, Lars / Norhammar, Anna. ·Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. Electronic address: isabelle.johansson@ki.se. · Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. · Cardiology Unit, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. · Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden. ·J Am Coll Cardiol · Pubmed #27659462.

ABSTRACT: BACKGROUND: Heart failure (HF) is a common and serious complication in type 2 diabetes mellitus (T2DM). The prognosis of ischemic HF and impact of revascularization in such patients have not been investigated fully in a patient population representing everyday practice. OBJECTIVES: This study examined the impact of ischemic versus nonischemic HF and previous revascularization on long-term prognosis in an unselected population of patients with and without T2DM. METHODS: Patients stratified by diabetes status and ischemic or nonischemic HF and history of revascularization in the Swedish Heart Failure Registry (SwedeHF) from 2003 to 2011 were followed up for mortality predictors and longevity. A propensity score analysis was applied to evaluate the impact of previous revascularization. RESULTS: Among 35,163 HF patients, those with T2DM were younger, and 90% had 1 or more associated comorbidities. Ischemic heart disease (IHD) occurred in 62% of patients with T2DM and 47% of those without T2DM, of whom 53% and 48%, respectively, had previously undergone revascularization. T2DM predicted mortality regardless of the presence of IHD, with adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.40 (1.33 to 1.46) and 1.30 (1.22 to 1.39) in those with and without IHD, respectively. Patients with both T2DM and IHD had the highest mortality, which was further accentuated by the absence of previous revascularization (adjusted HR: 0.82 in favor of such treatment; 95% CI: 0.75 to 0.91). Propensity score adjustment did not change these results (HR: 0.87; 95% CI: 0.78 to 0.96). Revascularization did not abolish the impact of T2DM, which predicted mortality in those with (HR: 1.36; 95% CI: 1.24 to 1.48) and without (HR: 1.45; 95% CI: 1.33 to 1.56) a history of revascularization. CONCLUSIONS: Ninety percent of HF patients with T2DM have preventable comorbidities. IHD in patients with T2DM had an especially negative influence on mortality, an impact that was beneficially influenced by previous revascularization.

19 Article Sulphonylurea compared to DPP-4 inhibitors in combination with metformin carries increased risk of severe hypoglycemia, cardiovascular events, and all-cause mortality. 2016

Eriksson, Jan W / Bodegard, Johan / Nathanson, David / Thuresson, Marcus / Nyström, Thomas / Norhammar, Anna. ·Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden. · AstraZeneca Nordic-Baltic, Södertälje, Sweden. · Department of Clinical Science and Education, Division of Internal Medicine, Unit for Diabetes Research, Karolinska Institute, Södersjukhuset, Stockholm, Sweden. · Statisticon AB, Uppsala, Sweden. · Cardiology Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden. ·Diabetes Res Clin Pract · Pubmed #27329021.

ABSTRACT: AIMS: There are safety concerns related to sulphonylurea treatment. The objective of this nationwide study was to compare the risk of cardiovascular disease (CVD), all-cause mortality and severe hypoglycemia in patients with type 2 diabetes (T2D) starting second-line treatment with either metformin+sulphonylurea or metformin+dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: All patients with T2D in Sweden who initiated second-line treatment with metformin+sulphonylurea or metformin+DPP-4i during 2006-2013 (n=40,736 and 12,024, respectively) were identified in this nationwide study. The Swedish Prescribed Drug Register and the Cause of Death and National Patient Registers were used, and Cox survival models adjusted for age, sex, fragility, prior CVD, and CVD-preventing drugs were applied to estimate risks of events. Propensity score adjustments and matching methods were used to test the results. RESULTS: Of 52,760 patients; 77% started metformin+SU and 23% metformin+DPP-4i. Crude incidences for severe hypoglycemia, CVD, and all-cause mortality in the SU cohort were 2.0, 19.6, and 24.6 per 1000 patient-years and in the DPP-4i cohort were 0.8, 7.6, and 14.9 per 1000 patient-years, respectively. Sulphonylurea compared with DPP4i was associated with higher risk of subsequent severe hypoglycemia, fatal and nonfatal CVD, and all-cause mortality; adjusted HR (95% CI): 2.07 (1.11-3.86); 1.17 (1.01-1.37); and 1.25 (1.02-1.54), respectively. Results were confirmed by additional propensity-adjusted and matched analyses. Among the SU drugs, glibenclamide had the highest risks. CONCLUSIONS: Metformin+SU treatment was associated with an increased risk of subsequent severe hypoglycemia, cardiovascular events, and all-cause mortality compared with metformin+DPP4i. Results from randomized trials will be important to elucidate causal relationships.

20 Article Copeptin, insulin-like growth factor binding protein-1 and sitagliptin: A report from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction study. 2016

Arnetz, Lisa / Hage, Camilla / Brismar, Kerstin / Catrina, Sergiu-Bogdan / Norhammar, Anna / Lundman, Pia / Wallander, Märit / Ryden, Lars / Mellbin, Linda. ·Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden lisa.arnetz@karolinska.se. · Department of Medicine, Cardiology Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden. · Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden. · Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden. ·Diab Vasc Dis Res · Pubmed #27190088.

ABSTRACT: PURPOSE: To investigate whether sitagliptin affects copeptin and osmolality, suggesting arginine vasopressin activation and a potential for fluid retention, compared with placebo, in patients with a recent acute coronary syndrome and newly discovered type 2 diabetes or impaired glucose tolerance. A second aim was to confirm whether copeptin correlated with insulin-like growth factor binding protein-1. METHODS: Fasting blood samples were used from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction trial, in which patients recently hospitalized due to acute coronary syndrome and with newly detected abnormal glucose tolerance were randomized to sitagliptin 100 mg once daily (n = 34) or placebo (n = 37). Copeptin, osmolality and insulin-like growth factor binding protein-1 were analysed at baseline and after 12 weeks. RESULTS: Copeptin and osmolality were unaffected by sitagliptin. There was no correlation between copeptin and insulin-like growth factor binding protein-1. CONCLUSION: Sitagliptin therapy does not appear to be related to activation of the arginine vasopressin system.

21 Article Incidence, prevalence and mortality of type 2 diabetes requiring glucose-lowering treatment, and associated risks of cardiovascular complications: a nationwide study in Sweden, 2006-2013. 2016

Norhammar, Anna / Bodegård, Johan / Nyström, Thomas / Thuresson, Marcus / Eriksson, Jan W / Nathanson, David. ·Cardiology Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden. anna.norhammar@ki.se. · Capio St Görans Hospital, Stockholm, Sweden. anna.norhammar@ki.se. · Astra Zeneca Nordic-Baltic, Södertälje, Sweden. · Department of Clinical Science and Education, Division of Internal Medicine, Unit for Diabetes Research, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden. · Statisticon AB, Uppsala, Sweden. · Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden. ·Diabetologia · Pubmed #27189067.

ABSTRACT: AIMS/HYPOTHESIS: The global diabetes epidemic affects countries differently. We aimed to describe trends in the incidence and prevalence of type 2 diabetes mellitus requiring glucose-lowering treatment, together with associated life expectancy and risks of significant clinical complications. METHODS: Data on patients with type 2 diabetes who filled a prescription for any glucose-lowering drug (GLD) during the period 2006-2013 were extracted from the Swedish Prescribed Drug Register, Cause of Death Register and Swedish National Patient Register. RESULTS: In 2013, the prevalence of GLD-treated type 2 diabetes was 4.4% (n = 352,436) and the incidence was 399 per 100,000 population (n = 30,620). During 2006-2013, the prevalence increased by 61% while the incidence remained relatively stable; the prevalence of cardiovascular disease (CVD, 34% in 2013) and microvascular disease (16% in 2013) was also stable. Insulin use increased by 29% while sulfonylurea use declined by 55%. Compared with the general population, patients with type 2 diabetes had increased risk of myocardial infarction, stroke and all-cause mortality, with age-standardised risks of ∼1.7-, 1.5- and 1.3-fold, respectively. These risks declined over time. Life-years lost due to diabetes was most pronounced at younger ages and improved in women over time from 2006 to 2013. CONCLUSIONS/INTERPRETATION: The prevalence of type 2 diabetes requiring GLD treatment in Sweden increased substantially in recent years, while the incidence remained stable. Use of sulfonylurea declined while insulin use increased. The high prevalence of diabetes-related comorbidities, increased risk of complications and life-years lost highlights the need for optimised and new preventive strategies in patients with type 2 diabetes.

22 Article Improved glycemic control due to sitagliptin is not related to cortisol or the surrogate marker IGFBP-1 for hepatic insulin sensitivity. 2015

Arnetz, Lisa / Hage, Camilla / Ekberg, Neda Rajamand / Alvarsson, Michael / Brismar, Kerstin / Norhammar, Anna / Mellbin, Linda. ·Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: Lisa.Arnetz@karolinska.se. · Cardiology Unit, Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address: camilla.hage@karolinska.se. · Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: neda.ekberg@ki.se. · Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: michael.alvarsson@karolinska.se. · Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, 17176 Stockholm, Sweden; Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital Solna, 17176 Stockholm, Sweden. Electronic address: kerstin.brismar@ki.se. · Cardiology Unit, Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address: anna.norhammar@karolinska.se. · Cardiology Unit, Department of Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address: linda.mellbin@karolinska.se. ·Growth Horm IGF Res · Pubmed #26283275.

ABSTRACT: IMPORTANCE: Elevated cortisol levels and dysregulated insulin-like growth factor binding protein-1 (IGFBP-1; a marker of hepatic insulin sensitivity) are both related to insulin resistance and glucose abnormalities. It is unknown whether improvement in these parameters is related to improved glucose metabolism during treatment with sitagliptin. OBJECTIVE: To determine whether improved insulin sensitivity and beta-cell function during treatment with sitagliptin is related to lower cortisol levels and/or improved regulation of IGFBP-1 in patients with recent acute coronary syndrome (ACS) and newly discovered glucose abnormalities. DESIGN: Samples were taken from The BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction (BEGAMI) trial, a double-blinded, placebo-controlled randomized clinical trial on the efficacy and safety of sitagliptin for patients with ACS and newly discovered glucose abnormalities. SETTING: Cardiology departments (cardiac ICU and outpatient clinic) in two hospitals in Stockholm, Sweden. PARTICIPANTS: Subjects hospitalized (or recently hospitalized) for ACS, in whom an oral glucose tolerance test revealed previously unknown glucose abnormalities. INTERVENTIONS: Subjects were randomized to sitagliptin 100mg once daily (n=34) or placebo (n=37) for twelve weeks. Oral glucose tolerance test (OGTT) and randomization occurred after stabilization median 7 days after ACS. MAIN OUTCOMES AND MEASURES: Fasting serum cortisol and IGFBP-1 were analyzed before OGTT, around 8a.m., and after at 10a.m. The latter time point was chosen as the spread in cortisol levels around is small then, allowing improved chances to detect differences between groups. RESULTS: Glucose tolerance and insulin sensitivity improved in both groups, while HbA1c and indices of β-cell function improved only in the sitagliptin group as reported previously. Both groups displayed decreased cortisol levels around 10a.m. (from 338±21 to 278±14 nmol/L, p=0.038, in the sitagliptin group; from 343±17 to 302±15 nmol/L, p=0.017, in the placebo group), and improved correlation between fasting log-IGFBP-1 and insulin. CONCLUSIONS AND RELEVANCE: These findings suggest that a stress-related elevation in cortisol may have negative impact on glucose tolerance in patients with recent ACS. However, improved glycemic control with sitagliptin does not appear to be related to changes in cortisol levels or hepatic insulin sensitivity as assessed by IGFBP-1.

23 Article Risk factors, treatment and prognosis in men and women with heart failure with and without diabetes. 2015

Johansson, Isabelle / Dahlström, Ulf / Edner, Magnus / Näsman, Per / Rydén, Lars / Norhammar, Anna. ·Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm. · Department of Cardiology and Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden. · Center for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden. ·Heart · Pubmed #26034118.

ABSTRACT: OBJECTIVE: To test the hypothesis that risk factor pattern, treatment and prognosis differ between men and women with heart failure (HF) with and without diabetes in the Swedish Heart Failure Registry. METHODS: Patients with (n=8809) and without (n=27 465) type 2 diabetes (T2DM) included in the Swedish Heart Failure Registry (2003-2011) were followed for mortality during a median follow-up of 1.9 years (range 0-8.7 years). All-cause mortality, differences in background and HF characteristics were analysed in women and men with and without T2DM and with a special regard to different age groups. RESULTS: Of 36 274 patients, 24% had T2DM and 39% were women. In patients with T2DM, women were older than men (78 years vs 73 years), more frequently had hypertension, renal dysfunction and preserved ventricular function. Regardless of T2DM status, women with reduced ventricular function, compared with their male counterparts, were less frequently offered, for example, ACE inhibitors/angiotensin receptor II blockers (ARB). Absolute mortality was 48% in women with T2DM, 40% in women without; corresponding male mortality rates were 43% and 35%, respectively. Kaplan-Meier curves revealed shorter longevity in women with T2DM but female sex did not remain a significant mortality predictor following adjustment (OR 95% CI 0.90; 0.79 to 1.03). In those without T2DM, women compared with men lived longer; this pattern remained after adjustment (OR 0.72; 0.66 to 0.78). T2DM was a stronger predictor of mortality in women (OR 1.72; 1.53 to 1.94) than in men (OR 1.47; 1.34 to 1.61). CONCLUSIONS: T2DM is a strong mortality predictor in men and women with HF, somewhat stronger in women. The shorter survival time in women with T2DM and HF related to comorbidities rather than sex per se. Evidence-based management was less prevalent in women. Mechanisms behind these findings remain incompletely understood and need further attention.

24 Article High event rate after a first percutaneous coronary intervention in patients with diabetes mellitus: results from the Swedish coronary angiography and angioplasty registry. 2015

Ritsinger, Viveca / Saleh, Nawsad / Lagerqvist, Bo / Norhammar, Anna. ·From the Karolinska Institute, Department of Medicine, Cardiology Unit, Karolinska University Hospital, Stockholm, Sweden (V.R., N.S., A.N.) · Department of Research and Development, Region Kronoberg, Sweden (V.R.) · and Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden (B.L.). ·Circ Cardiovasc Interv · Pubmed #26025219.

ABSTRACT: BACKGROUND: Patients with diabetes mellitus have reduced longevity after acute coronary syndromes and revascularization. However, knowledge of the long-term complication rates and patterns from an everyday life setting is lacking. METHODS AND RESULTS: Consecutive patients undergoing percutaneous coronary intervention included in the Swedish Coronary Angiography Angioplasty Registry (SCAAR) between 2006 and 2010 and with no previous revascularization were prospectively followed up for combined cardiovascular events (first of all-cause mortality, myocardial infarction, stroke, and heart failure) until December 31, 2010. The mean follow-up period was 920 days (SD, 530 days). Differences in background and procedural characteristics were adjusted for in a multivariate Cox regression model. Of 58 891 patients, mean age 67 years, 19% had diabetes mellitus; 27% of them were on diet treatment, 33% on oral glucose lowering, and 40% on insulin treatment. At admission, cardiovascular risk factors, multiple coronary vessel, and left main stem disease were more frequent in patients with diabetes mellitus and their revascularization was less often complete. The adjusted risk for combined cardiovascular events was higher in patients on insulin (hazard ratio [95% confidence interval], 1.63 [1.55-1.72]), on oral treatment (1.23 [1.15-1.31]), and on diet alone (1.21 [1.12-1.29]) compared with patients without diabetes mellitus. Insulin-treated patients ran an increased risk of restenosis (1.54 [1.39-1.71]) and stent thrombosis (1.56 [1.25-1.96]). CONCLUSIONS: The prognosis after a first percutaneous coronary intervention is more severe in patients with diabetes mellitus, in particular, in patients treated with insulin, with higher rates of mortality, cardiovascular events, and stent thrombosis over the following 5 years.

25 Article Sustained prognostic implications of newly detected glucose abnormalities in patients with acute myocardial infarction: long-term follow-up of the Glucose Tolerance in Patients with Acute Myocardial Infarction cohort. 2015

Ritsinger, Viveca / Tanoglidi, Eleni / Malmberg, Klas / Näsman, Per / Rydén, Lars / Tenerz, Åke / Norhammar, Anna. ·Cardiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden Unit for Research and Development Kronoberg County Council, Växjö, Sweden viveca.ritsinger@ki.se. · Department of Medicine and Centre for Clinical Research, Central Hospital Västerås, Västerås, Sweden. · Cardiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. · Centre for Safety Research, KTH Royal Institute of Technology, Stockholm, Sweden. ·Diab Vasc Dis Res · Pubmed #25311248.

ABSTRACT: OBJECTIVE: To investigate long-term prognostic importance of newly discovered glucose disturbances in patients with acute myocardial infarction (AMI). METHODS: During 1998-2001, consecutive patients with AMI (n = 167) and healthy controls (n = 184) with no previously known diabetes were investigated with an oral glucose tolerance test (OGTT). Patients and controls were separately followed up for cardiovascular events (first of cardiovascular mortality/AMI/stroke/heart failure) during a decade. RESULTS: In all, 68% of the patients and 35% of the controls had newly detected abnormal glucose tolerance (AGT). Cardiovascular event (n = 72, p = 0.0019) and cardiovascular mortality (n = 31, p = 0.031) were more frequent in patients with newly detected AGT. Regarding patients, a Cox proportional-hazard regression analysis identified AGT (hazard ratio (HR): 2.30; 95% confidence interval (CI): 1.24-4.25; p = 0.008) and previous AMI (HR: 2.39; CI: 1.31-4.35; p = 0.004) as prognostically important. CONCLUSION: An OGTT at discharge after AMI disclosed a high proportion of patients with previously unknown AGT which had a significant and independent association with long-term prognosis.

Next