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Background: Type 2 diabetes mellitus (T2DM) is considered a risk factor for fracture but the evidence regarding the impact of T2DM on fracture risk is conflicting. The objective of the study was to determine if patients with T2DM have increased fracture risk and if T2DM-related risk factors could be identified. Methods and findings: In this national cohort study in Sweden, we investigated the risk of fracture in 580,127 T2DM patients, identified through the national diabetes register including from both primary care and hospitals, and an equal number of population-based controls without diabetes matched for age, sex, and county from 2007 to 2017. The mean age at entry was 66.7 years and 43.6% were women. During a median follow-up time of 6.6 (interquartile range (IQR) 3.1 to 9.8) years, patients with T2DM had a marginally but significantly increased risk of major osteoporotic fracture (MOF) (hazard ratio (HR) 1.01 (95% confidence interval [CI] 1.00 to 1.03)) and hip fracture (HR 1.06 (95% CI 1.04 to 1.08)) compared to controls, associations that were only minimally affected (HR 1.05 (95% CI 1.03 to 1.06) and HR 1.11 (95% CI 1.09 to 1.14), respectively) by multivariable adjustment (age, sex, marital status, and an additional 20 variables related to general morbidity, cardiovascular status, risk of falls, and fracture). In a multivariable-adjusted Cox model, the proportion of the risk for all fracture outcomes (Heller's R2) explained by T2DM was below 0.1%. Among the T2DM patients, important risk factors for fracture were a low BMI (<25 kg/m2), long diabetes duration (≥15 years), insulin treatment, and low physical activity. In total, 55% of the T2DM patients had none of these risk factors and a significantly lower fracture risk than their respective controls. The relatively short mean duration of T2DM and lack of bone density data, constitute limitations of the analysis. Conclusion: In this study, we observed only a marginally increased fracture risk in T2DM, a condition that explained less than 0.1% of the fracture risk. Consideration of the herein identified T2DM-related risk factors could be used to stratify T2DM patients according to fracture risk. Kristian F. Axelsson and colleagues investigate fracture risk in patients with type 2 diabetes and seek to identify relevant risk factors. Author summary: Why was this study done?: Type 2 diabetes mellitus (T2DM) is considered a risk factor for fracture but the evidence regarding the impact of T2DM on fracture risk is conflicting. We sought to determine if patients with T2DM had increased fracture risk and if so, to identify T2DM-related risk factors. What did the researchers do and find?: We used a national register covering nearly all adult patients with T2DM in Sweden to compare the risk of fracture between T2DM patients (n = 580,127) and population controls (n = 580,127) without T2DM. In general, the risk of fracture was only marginally increased (by 1% for major osteoporotic fracture (MOF) and by 6% for hip fracture) for patients with T2DM compared to controls, but for patients with presence of risk factors, such as low BMI, long T2DM duration, insulin treatment, and/or low physical activity, the risk increase was more substantial (20% or higher) and potentially clinically relevant. What do these findings mean?: Our findings suggest that T2DM per se should not be considered an important risk factor for fracture. Special consideration of the T2DM-related risk factors can be used to identify T2DM patients with a clinically relevant increased fracture risk. Further studies are needed to develop fracture risk calculators for different settings and populations for T2DM patients specifically. [ABSTRACT FROM AUTHOR]

Aim: To assess the comparative cardiovascular and renal effectiveness of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors versus glucagon‐like peptide‐1 (GLP‐1) receptor agonists in routine clinical practice. Materials and Methods: A cohort study of nationwide registers from Sweden, Denmark, and Norway, including 87 525 new users of SGLT2 inhibitors and 63 921 new users of GLP‐1 receptor agonists, was conducted using data from 2013‐2018. Co‐primary outcomes, analysed using an intention‐to‐treat exposure definition, were major adverse cardiovascular events (MACE; myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure), and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Results: Use of SGLT2 inhibitors versus GLP‐1 receptor agonists was associated with a higher risk of MACE (adjusted incidence rate: 15.2 vs. 14.4 events per 1000 person‐years; HR 1.07 [95% CI 1.01‐1.15]), a similar risk of heart failure (6.0 vs. 6.0 events per 1000 person‐years; HR 1.02 [0.92‐1.12]), and a lower risk of serious renal events (2.9 vs. 4.0 events per 1000 person‐years; HR 0.76 [0.66‐0.87]). In as‐treated analyses, the HR (95% CI) was 1.11 (1.00‐1.24) for MACE, 0.88 (0.74‐1.04) for heart failure, and 0.60 (0.47‐0.77) for serious renal events. In secondary outcome analyses, use of SGLT2 inhibitors versus GLP‐1 receptor agonists was not associated with statistically significant differences for the risk of myocardial infarction (HR 1.09 [95% CI 1.00‐1.19]), cardiovascular death (HR 0.97 [95% CI 0.84‐1.12]), death from renal causes (HR 0.75 [95% CI 0.41‐1.35]), or any cause death (HR 1.01 [95% CI 0.94‐1.09]), while the risk of stroke was higher (HR 1.14 [95% CI 1.03‐1.26]), and the risk of renal replacement therapy (HR 0.74 [95% CI 0.56‐0.97]) and hospitalization for renal events (HR 0.75 [95% CI 0.65‐0.88]) were lower among users of SGLT2 inhibitors. Conclusions: Use of SGLT2 inhibitors versus GLP‐1 receptor agonists was associated with a similar risk of heart failure and a lower risk of serious renal events, while use of GLP‐1 receptor agonists versus SGLT2 inhibitors was associated with a slightly lower risk of MACE. In as‐treated analyses, the associations with MACE and serious renal events increased in magnitude, and the HR for heart failure tended towards a protective association for SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Introduction: Lipid-lowering therapy (LLT) reduces the risk of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, socioeconomic factors and gender may have an impact on the adherence to and non-persistence with LLT. Methods: This was a nationwide register-based cohort study that included 6192 individuals with T1D aged ≥ 18 years who were registered in the Swedish National Diabetes Register and had initiated novel use of LLT. Information on socioeconomic parameters (source: Statistics Sweden) and comorbidity (source: National Patient Register) was collected. The individuals were followed for 36 months, and adherence to LLT was analyzed according to age, socioeconomics and gender. The medication possession ratio (MPR; categorized into ≤ 80% and > 80%) and non-persistence (discontinuation) with medication was calculated after 18 and 36 months. Results: Individuals older than 53 years were more adherent to LLT (MPR > 80%) than those younger than 36 years (odds ratio [(OR] 1.30, p < 0.0001) at 36 months. Women were more adherent and less prone to discontinue LLT at 18 months (OR 1.05, p = 0.0005 and OR 0.95, p = 0.0004, respectively), but not at 36 months. Divorced individuals were less adherent than married ones (OR 0.93, p = 0.0005) and discontinued LLT more often than the latter (OR 1.06, p = 0.003). Education had no impact on adherence, but individuals with higher incomes discontinued LLT less frequently than those with lower incomes. Individuals with a country of origin other than Sweden discontinued LLT more often. Conclusion: Lower adherence to LLT in individuals with T1D was associated with male gender, younger age, marital status and country of birth. These factors should be considered when evaluating adherence to LLT in clinical practice, with the aim to help patients achieve full cardioprotective treatment. [ABSTRACT FROM AUTHOR]

Aim: To compare treatment persistence in patients with type 2 diabetes initiating the glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) dulaglutide, exenatide once‐weekly (QW), liraglutide or lixisenatide in routine clinical practice in Sweden and assess clinical outcomes. Materials and Methods: We performed a retrospective study using data from several nationwide Swedish health registries, including the National Diabetes Register and other mandatory and population‐based registries. Individual level data were collected from 17 361 patients who initiated GLP‐1 RA treatment from 23 May 2015 to 15 October 2017, up to 2.5 years postindex (treatment start date). Treatment persistence and modification, predictors of discontinuation, HbA1c and body weight were recorded. Non‐persistence was defined as a treatment gap of more than 45 days. Treatment modification included switching and augmentation. Confounding was addressed through the use of propensity scores. Results: Treatment persistence was higher and treatment modifications were lower in patients initiating dulaglutide compared with those on exenatide QW, liraglutide and lixisenatide. Patients who remained on the same treatment for 1‐year postindex experienced greater HbA1c reductions and a steadier decrease in body weight. Conclusions: Our study suggests that in clinical practice in Sweden there is a greater persistence of treatment among patients initiating dulaglutide compared with those on exenatide QW, liraglutide and lixisenatide. Persistence with the index GLP‐1 RA was closely correlated with positive clinical outcomes and thus should be considered a critical factor of patient‐centric treatment in Sweden. [ABSTRACT FROM AUTHOR]

Aims: To explore persistence with insulin degludec/liraglutide (IDegLira) treatment, clinical characteristics and concomitant medications in a large population of patients in clinical practice. Methods: This was an observational study in patients with type 2 diabetes (n = 2432) who initiated IDegLira between 26 May 2015 and 31 December 2017. Data were obtained from Swedish nationwide registers and linked on an individual level using unique Swedish personal identifiers. Dose calculations were made for patients with ≥ 180 days between the first and last collections of IDegLira prescription. Changes in clinical parameters were evaluated as change from the last observation during 12 months prior to the initiation date until ± 90 days from the last collection of IDegLira. Results: Pre-index regimens (index date being the date of filling the first prescription of IDegLira) included: multiple daily insulin injections (45.1%); insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) (19.7%); long-acting insulins (11.8%); non-injectable therapy only (11.4%); GLP-1 RA only (9.8%); and no collection of diabetes medication during the 6-month pre-index period (2.3%). The majority of patients (94 and 84%) were persistent with IDegLira at 6 and 12 months, respectively. The most commonly used concomitant medication was metformin (69.4%). Mean daily dose was 33 dose steps. Overall, there was a mean decrease in HbA1c (approx. 10 mmol/mol [1%]) and body weight (− 1.1 kg). Improvements in HbA1c were observed regardless of pre-index treatment. Conclusion: After 12 months, 84% of patients were persistent on IDegLira, with improved glycaemic control and reductions in body weight. [ABSTRACT FROM AUTHOR]

Objective: To develop a patient-level simulation model for predicting lifetime health outcomes of patients with type 1 diabetes and as a tool for economic evaluation of type 1 diabetes treatment based on data from a large, longitudinal cohort.Research Design and Methods: Data for model development were obtained from the Swedish National Diabetes Register. We derived parametric proportional hazards models predicting the absolute risk of diabetes complications and death based on a wide range of clinical variables and history of complications. We used linear regression models to predict risk factor progression. Internal validation was performed, estimates of life expectancies for different age-sex strata were computed, and the impact of key risk factors on life expectancy was assessed.Results: The study population consisted of 27,841 patients with type 1 diabetes with a mean duration of follow-up of 7 years. Internal validation showed good agreement between the predicted and observed cumulative incidence of death and 10 complications. Simulated life expectancy was ∼13 years lower than that of the sex- and age-matched general population, and patients with type 1 diabetes could expect to live with one or more complications for ∼40% of their remaining life. Sensitivity analysis showed the importance of preventing renal dysfunction, hypoglycemia, and hyperglycemia as well as lowering HbA1c in reducing the risk of complications and death.Conclusions: Our model was able to simulate risk factor progression and event histories that closely match the observed outcomes and to project events occurring over patients' lifetimes. The model can serve as a tool to estimate the impact of changing clinical risk factors on health outcomes to inform economic evaluations of interventions in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To assess the association between use of glucagon-like peptide 1 (GLP-1) receptor agonists and risk of serious renal events in routine clinical practice.Research Design and Methods: This was a cohort study using an active-comparator, new-user design and nationwide register data from Sweden, Denmark, and Norway during 2010-2016. The cohort included 38,731 new users of GLP-1 receptor agonists (liraglutide 92.5%, exenatide 6.2%, lixisenatide 0.7%, and dulaglutide 0.6%), matched 1:1 on age, sex, and propensity score to a new user of the active comparator, dipeptidyl peptidase 4 (DPP-4) inhibitors. The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospitalization for renal events. Secondary outcomes were the individual components of the main outcome. Hazard ratios (HRs) were estimated using Cox models and an intention-to-treat exposure definition. Mean (SD) follow-up time was 3.0 (1.7) years.Results: Mean (SD) age of the study population was 59 (10) years, and 18% had cardiovascular disease. A serious renal event occurred in 570 users of GLP-1 receptor agonists (incidence rate 4.8 events per 1,000 person-years) and in 722 users of DPP-4 inhibitors (6.3 events per 1,000 person-years, HR 0.76 [95% CI 0.68-0.85], absolute difference -1.5 events per 1,000 person-years [-2.1 to -0.9]). Use of GLP-1 receptor agonists was associated with a significantly lower risk of renal replacement therapy (HR 0.73 [0.62-0.87]) and hospitalization for renal events (HR 0.73 [0.65-0.83]) but not death from renal causes (HR 0.72 [0.48-1.10]). When we used an as-treated exposure definition in which patients were censored at treatment cessation or switch to the other study drug, the HR for the primary outcome was 0.60 (0.49-0.74).Conclusions: In this large cohort of patients seen in routine clinical practice in three countries, use of GLP-1 receptor agonists, as compared with DPP-4 inhibitors, was associated with a reduced risk of serious renal events. [ABSTRACT FROM AUTHOR]

Objective: We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study.Research Design and Methods: We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18-65 years, mean BMI >40 kg/m2, mean follow-up >4.5 years). The risks of postoperative outcomes were assessed with Cox regression models.Results: During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR <30 mL/min/1.73 m2.Conclusions: Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status. [ABSTRACT FROM AUTHOR]

Introduction: To date, only a few studies have addressed the long-term safety of basal insulins. We have therefore investigated the efficacy and safety of all available basal insulins used in the treatment of type 1 diabetes, using data from national databases in Sweden. Methods: We assessed patients with type 1 diabetes who were using insulin glargine 100 U/mL (IG100) and who either continued using IG100 or switched to insulin glargine 300 U/mL (IG300) or insulin degludec (ID) for differences in clinical characteristics at baseline (index date) and subsequent changes in glycated haemoglobin (HbA1c), weight and hospitalizations caused by hypoglycaemia, cardiovascular disease or death. Results: The mean follow-up time was 1.1 years for patients who switched to IG300 and ID and 1.6 years for those remaining on IG100. There were no marked differences in clinical characteristics between the groups, but patients on IG100 were slightly older and had used insulin pumps or continuous glucose monitors more seldom. The mean HbA1c levels were similar, and 4% of the patients had a history of cardiovascular disease. HbA1c decreased in all groups during follow-up, while the body mass index remained virtually unchanged. Rates of severe hypo- or hyperglycaemia were low and similar between the groups. Sixteen patients (0.7%) treated with IG300 and 13 patients (0.8%) treated with ID died during follow-up, while 221 patients (1.95%) on IG100 therapy died. All other severe adverse events were numerically more frequent in those patients receiving IG100, while there were no apparent differences between those receiving IG300 and those on ID. Conclusion: The long-term effects and safety of IG300 and ID appear to be very similar in adult patients with type 1 diabetes. The results of this study suggest that these basal insulin analogues may provide benefits compared with the established reference IG100. [ABSTRACT FROM AUTHOR]

Background: There is still a lack of knowledge on long-term effects of surgical and non-surgical weight-lowering treatments. BASUN is a prospective study with 10 years of follow-up that will observe the effects and consequences of surgical and medical treatment of obesity. The aims are to cover areas where data on long-term outcomes are lacking, e.g., nutritional deficiencies, substance abuse, psychiatric health, as well as patient-reported outcomes. Methods: BASUN is a cohort study that recruited study persons with obesity (BMI ≥ 35 kg/m2) referred to the Regional Obesity Centre of Region Västra Götaland. The interventions were Roux-en-Y gastric bypass (RYGB) or Sleeve gastrectomy (SG), or 12 months of structured, multi-professional medical treatment (MT), including very low energy diet, followed by diet and pharmaceutical treatment. The study is not randomized, but based on patients preferences and multidisciplinary assessments. The study persons are examined at baseline, 2, 5, and 10 years with blood tests, measurements and questionnaires. The recruitment period lasted from May 2015 to November 2017. Results: One thousand one hundred twenty-seven patients were included (74% female). Three hundred eighty-two patients were accepted for medical treatment, 589 for surgical treatment (388 RYGB and 201 SG) and 156 patients left the study without treatment, leaving a final study population of 971 patients. There were slight differences between the treatment groups with regards to age and BMI. Pharmaceutical treatments, level of education, smoking and marital status were not significantly different between the groups. Conclusion: This study will follow 971 obese subjects in clinical practice treated with the best surgical or medical methods currently available. It has the potential to evaluate outcomes usually not reported in short-term studies, and to assist in identifying factors that are of importance for the choices of treatment. The main limitations are non-randomization and differences in baseline characteristics. The large number of participants and the length of the prospective follow-up are major strengths of the study. BASUN is designed to identify both early and late benefits and adverse events of treatment of obesity. Trial registration: This trial was prospectively registered on March 03, 2015; NCT03152617. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate effects of person‐centred inpatient care on care processes in terms of satisfaction with care and person‐centred content in medical records, and to evaluate effects on self‐reported health and self‐efficacy. Background: Internal medicine inpatient care is complex, covering patients varying in age, medical conditions, health status, and other aspects. There has been limited research on the impact of person‐centred care (PCC) on satisfaction with care and health outcomes in internal medicine care environments regardless of diagnosis and care pathway. Design: A quasi‐experimental study with pre‐ and postmeasurements. Methods: Adult patients admitted to an internal medicine inpatient unit were consecutively included over 16 weeks in 2014 and 24 weeks in 2015–2016. Data were collected before a person‐centred inpatient care intervention (N = 204) and 12 months after the intervention was implemented (N = 177). Data on satisfaction with care and self‐reported health were collected at discharge and medical records were reviewed. The intervention included systematically applied person‐centred assessment, health plans, and persistent PCC. Results: After the intervention, patients rated higher satisfaction with care regarding essential components of PCC and more patients had received effective pain relief. There were no differences in information on self‐care or medications, self‐rated health, or self‐efficacy. Conclusion: Care focused on the foundations of person‐centredness seems to enhance both patients' perceptions of satisfaction and symptom management. Situational aspects such as care pathways should be considered when implementing person‐centred inpatient care. Trial registration: ClinicalTrials.gov, registration number: NCT03725813 [ABSTRACT FROM AUTHOR]

Introduction: Were the participants of the EMPA-REG OUTCOME trial representative of patients receiving empagliflozin in clinical practice? The aim of the present study was to examine the prevalence of cardiovascular disease (CVD) in type 2 diabetes patients starting empagliflozin treatment in routine clinical practice in Sweden. Methods: We used nationwide data from the Swedish National Diabetes Register (NDR), the Swedish Prescribed Drug Register, and the Swedish National Patient Register to provide clinical characteristics and ongoing treatments. Results: The total study cohort included 460,558 patients, of whom 130,508 (28.3%) had a history of CVD. The number of patients starting empagliflozin during the study period was 16,985. Among these, 1952 (11.5%) had a history of CVD. The patients starting empagliflozin were younger than the total cohort and were more likely to have retinopathy despite having a similar duration of diabetes to the overall cohort. They also exhibited higher BMI, HbA1c, and eGFR, and were more likely to be treated with insulin and lipid-lowering and blood-pressure-lowering medications. The patients with CVD who were starting empagliflozin were slightly older and had been diabetic for slightly longer than the patients without CVD who were starting empagliflozin, but they also had lower eGFR. Among the patients with CVD who were starting empagliflozin, 87% had coronary heart disease, 8% had suffered a stroke, 13% had peripheral artery disease, 16% had atrial fibrillation, and 20% had congestive heart failure. Conclusion: The prevalence of CVD in patients with type 2 diabetes in clinical practice in Sweden was 28.3% during the study period, and it was 11.5% in the patients starting empagliflozin treatment. Patients of the latter cohort were, however, younger, more obese, and more likely to have unsatisfactory glycemic control, requiring additional treatment. Overall, a large proportion of type 2 diabetes patients should be considered at high cardiovascular risk. Funding: Boehringer Ingelheim AB, Sweden. [ABSTRACT FROM AUTHOR]

Aims: To compare the resource allocation and organisational features in Swedish primary diabetes care for patients with type 2 diabetes mellitus (T2DM) between 2006 and 2013.Methods: Using a repeated cross-sectional study design, questionnaires covering personnel resources and organisational features for patients with T2DM in 2006 and 2013 were sent to all Swedish primary health care centres (PHCCs) during the following year. In total, 684 (74.3%) PHCCs responded in 2006 and 880 (76.4%) in 2013.Results: Compared with 2006, the median list size had decreased in 2013 (p<0.001), whereas the median number of listed patients with T2DM had increased (p<0.001). Time devoted to patients with T2DM and diabetes-specific education levels for registered nurses (RNs) had increased, and more PHCCs had in-house psychologists (all p<0.001). The use of follow-up systems and medical check-ups had increased (all p<0.05). Individual counselling was more often based on patients' needs, while arrangement of group-based education remained low. Patient participation in setting treatment targets mainly remained low.Conclusions: Even though the diabetes-specific educational level among RNs increased, the arrangement of group-based education and patient participation in setting treatment targets remained low. These results are of concern and should be prioritised as key features in the care of patients with T2DM. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of lipid-lowering therapy (LLT) in primary prevention on cardiovascular disease (CVD) and death in type 1 diabetes.Research Design and Methods: We used the Swedish National Diabetes Register (NDR) to perform a propensity score-based study. Propensity scores for treatment with LLT were calculated from 32 baseline clinical and socioeconomic variables. The propensity score was used to estimate the effect of LLT in the overall cohort (by stratification). We estimated risk of acute myocardial infarction, stroke, coronary heart disease, and cardiovascular and all-cause mortality in individuals with and without LLT using Cox regression. A total of 24,230 individuals included in 2006-2008 NDR with type 1 diabetes without a history of CVD were followed until 31 December 2012; 18,843 were untreated and 5,387 treated with LLT (97% statins). The mean follow-up was 6.0 years.Results: The propensity score allowed balancing of all 32 covariates, with no differences between treated and untreated after accounting for propensity score. Hazard ratios (HRs) for treated versus untreated were as follows: cardiovascular death 0.60 (95% CI 0.50-0.72), all-cause death 0.56 (0.48-0.64), fatal/nonfatal stroke 0.56 (0.46-0.70), fatal/nonfatal acute myocardial infarction 0.78 (0.66-0.92), fatal/nonfatal coronary heart disease 0.85 (0.74-0.97), and fatal/nonfatal CVD 0.77 (0.69-0.87).Conclusions: This observational study shows that LLT is associated with 22-44% reduction in the risk of CVD and cardiovascular death among individuals with type 1 diabetes without history of CVD and underlines the importance of primary prevention with LLT to reduce cardiovascular risk in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To compare the performance of the recently developed Swedish experience-based time trade-off (TTO) valuation of the EuroQol-5D-3L (EQ-5D-3L) against the hypothetical-based TTO valuations from UK, US, Germany and Denmark. Methods: Type 2 diabetes patients from the Swedish National Diabetes Register (N = 1 757) responded to EQ-5D-3L questionnaire in 2008. Health utilities were compared using a range of parametric and nonparametric tests. Absolute agreement and consistency were investigated using intra-class correlations coefficients (ICCs) and Bland- Altman plots. Differences in health utilities between known-groups were evaluated. Transition scores for pairs of observed EQ-5D-3L health states were calculated and compared. Results: The Swedish tariff (SWT) resulted in substantially higher health utilities and differences were more profound for more severe health problems. ICC ranged 0.6 to 0.8 and Bland-Altman plots showed wide limits of agreement. While all tariffs discriminate between known-groups, the effect sizes were generally small. The SWT had higher (lower) knowngroup validity for macrovascular (microvascular) complications. The SWT and UK tariff were associated with the lowest and the highest mean absolute transition scores, respectively, for 2775 observed pairs of the EQ-5D-3L health states. Conclusion: There were systematic differences between the SWT and tariffs from other countries meaning that the choice of tariff might have substantial impact on funding decisions. The Swedish experienced-based TTO valuation will give higher priority to life-extending interventions than those which improve quality of life. We suggest that economic evaluations in Sweden include both Swedish experience-based and non-Swedish hypothetical-based valuations through a sensitivity analysis. [ABSTRACT FROM AUTHOR]

The aim of the current study was to provide updated time-path equations for risk factors of type-2-diabetes-related cardiovascular complications for application in risk calculators and health economic models. Observational data from the Swedish National Diabetes Register were analysed using Generalized Method of Moments estimation for dynamic panel models (N = 5, 043, aged 25-70 years at diagnosis in 2001-2004). Validation was performed using persons diagnosed in 2005 (n = 414). Results were compared with the UKPDS outcome model. The value of the risk factor in the previous year was the main predictor of the current value of the risk factor. People with high (low) values of risk factor in the year of diagnosis experienced a decreasing (increasing) trend over time. BMI was associated with elevations in all risk factors, while older age at diagnosis and being female generally corresponded to lower levels of risk factors. Updated time-path equations predicted risk factors more precisely than UKPDS outcome model equations in a Swedish population. Findings indicate new time paths for cardiovascular risk factors in the post-UKPDS era. The validation analysis confirmed the importance of updating the equations as new data become available; otherwise, the results of health economic analyses may be biased. [ABSTRACT FROM AUTHOR]

Objectives: To describe the use and evaluate the effectiveness of different lipid lowering therapies in unselected patients with type 1 and type 2 diabetes in clinical practice. Design: Observational population-based study using the personal identification number to link information from the National Diabetes Register, the Prescribed Drug Register and the Patient register in Sweden. All patients in the NDR aged 18-75 years with diabetes more than one year were eligible, but only patients starting any lipid lowering treatment with at least three prescriptions 1 July 2006-30 June 2007 were included (n = 37182). The mean blood lipid levels in 2008 and reductions in LDL cholesterol were examined. Results: Blood lipid levels were similar in patients treated with simvastatin, atorvastatin and rosuvastatin, showing similar lipid lowering effect as currently used. Users of pravastatin, fluvastatin, ezetimib and fibrate more seldom reach treatment goals. Moderate daily doses of the statins were used, with 76% of simvastatin users taking 20 mg or less, 48% of atorvastatin users taking 10 mg, 55% of pravastatin users taking 20 mg, and 76% of rosuvastatin users taking 5 or 10 mg. Conclusions: This observational study shows that the LDL-C levels in patients taking simvastatin, atorvastatin or rosuvastatin are very similar as currently used, as well as their LDL-C lowering abilities. There is potential to intensify lipid lowering treatment to reduce the remaining high residual risk and achieve better fulfilment of treatment goals, since the commonly used doses are only low to moderate. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register.Methods. Three thousand and six hundred sixty-seven patients with T2D aged 30–74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m2 according to MDRD) were followed up for 5 years (2002–2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m2 by MDRD or eCrCl > 60 mL/min by Cockgroft–Gault (C–G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes.Results. Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6–7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C–G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD).Conclusions. Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C–G) had an impact on interpretation of data, especially with regard to body composition and gender [ABSTRACT FROM AUTHOR]

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[sub 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[sub 1c] and BP values were registered during the 4-year study period for both type 1 (HbA[sub 1c] 7.5-7.3% and BP 130/75-130/74 mmHg) and type 2 diabetic patients (HbA[sub 1c] 7.0- 6.7 % and BP 151/82-147/80 mmHg). Treatment aims of HbA[sub 1c] and BP levels were also achieved in increasing proportions for type 1 (HbA[sub 1c] <7.5%: 50-58% and BP ≤140/85 mmHg: 77-79%), and type 2 diabetic patients (HbA[sub 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[sub 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[sub 1c] and BP levels and the wider use of lipidlowering 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... [ABSTRACT FROM AUTHOR]

This open study examined the effect of smoking reduction and smoking cessation on established cardiovascular risk factors. Fifty-eight healthy adult smokers (smoking ≥15 cigarettes/day for at least 3 years) were provided with nicotine nasal spray (to be used ad libitum) and asked to stop smoking. The primary goal during the first 8 weeks, however, was to reduce their daily smoking by at least 50%. Subjects were then followed for another 8 weeks; at this point, 33 participants had successfully stopped smoking. Cardiovascular risk factors including fibrinogen, hemoglobin, hematocrit, triglycerides, and cholesterol were measured at baseline and at 9 and 17 weeks. After 8 weeks of smoking reduction, the mean number of cigarettes smoked per day had decreased from 21.5 ± 0.6 (baseline) to 10.8 ± 0.6 (p < 0.001). This was accompanied by significant improvements in fibrinogen (from 2.9 ± 0.1 g/l at baseline to 2.6 ± 0.1 g/l, p = 0.011), white blood cells (from 7.0 ± 0.4 to 6.2 ± 0.3 × 10[sup 9]/l, p = 0.005) and the high-density/low-density lipoprotein (HDL/LDL) ratio (0.33 ± 0.03 to 0.37 ± 0.03, p < 0.005). Following 8 weeks of abstinence from smoking, the mean white blood cell count was further reduced (to 6.1 ± 0.3 × 10[sup 9]/l, p = 0.026 vs. baseline) and there were also significant improvements in HDL (from 1.16 ± 0.06 mmol/l at baseline to 1.32 ± 0.06, p < 0.001) and LDL (from 3.78 ± 0.16 mmol/l at baseline to 3.52 ± 0.17, p = 0.015). In conclusion, 8 weeks of smoking reduction resulted in clinically significant improvements in established cardiovascular risk factors. These improvements were even greater after an additional period of abstinence from smoking. [ABSTRACT FROM AUTHOR]

The impact of glycemic control in the risk of stent failure in subjects with type 2 diabetes (T2D) is currently unknown. This study sought to study whether poor glycemic control is associated with a higher risk of stent failure in subjects with T2D. This observational study included all patients in Sweden with T2D who underwent implantation of second-generation drug-eluting stents (DES) during 2010 to 2020. The exposure variable was the updated mean of glycated hemoglobin (HbA 1c). Individuals were stratified by glycemic control, with HbA 1c 6.1% to 7.0% (43-53 mmol/mol) as the reference group. The primary endpoint was the occurrence of stent failure (in-stent restenosis and stent thrombosis). The main result was analyzed in a complete cases model. Sensitivity analyses were performed for missing data and a model with death as a competing risk. The study population consisted of 52,457 individuals (70,453 DES). The number of complete cases was 24,411 (29,029 DES). The median follow-up was 6.4 years. The fully adjusted HR was 1.10 (95% CI: 0.80-1.52) for HbA 1c of ≤5.5% (≤37 mmol/mol), 1.02 (95% CI: 0.85-1.23) for HbA 1c of 5.6% to 6.0% (38-42 mmol/mol), 1.25 (95% CI: 1.11-1.41) for HbA 1c of 7.1% to 8.0% (54-64 mmol/mol), 1.30 (95% CI: 1.13-1.51) for HbA 1c of 8.1% to 9.0% (65-75 mmol/mol), 1.46 (95% CI: 1.21-1.76) for HbA 1c of 9.1% to 10.0% (76-86 mmol/mol), and 1.33 (95% CI: 1.06-1.66) for HbA 1c of ≥10.1% (≥87 mmol/mol). Sensitivity analyses did not change the main result. We found a significant association between poor glycemic control and a higher risk of stent failure driven by in-stent restenosis. [Display omitted] [ABSTRACT FROM AUTHOR]

The National Diabetes Register (NDR) of Sweden was initiated in response to The Saint Vincent Declaration (published 1990), to provide a tool for continuous quality assurance in diabetes care. The original purpose, to monitor the results of health centres from year to year and to compare these with national and regional means, is still the most important one, while continuous follow-up of guidelines, treatments and complications are as important on a national level. The data reported contain basal clinical characteristics of the patients, as well as measures of risk-factor control and the presence of diabetes complications. Many clinics use templates within the medical record systems to verify that all information relevant to good quality assurance in diabetes care is complete, and thereafter export data to NDR. In order to create extra value, the NDR web interface, online at ndr.nu, offers functions to use when interacting with the individual patient, such as reports of all information reported to NDR, including medications and risk-factor control. The clinical results are thus reported back to the health centres (printed and instantaneously online), but are also used for scientific analyses. Such are required by the funding bodies to develop the analytical methods by quality registers, and to widely spread information, including publishing in scientific journals. Ongoing studies address, e.g., the effects of different glucose-lowering therapies, the role of ethnicity and migration, patient-reported outcomes and risks of morbidity and mortality in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background Patients with diabetes mellitus (DM) have an increased risk of adverse outcomes after coronary artery bypass grafting (CABG). Previous studies have reported prognosis in relation to treatment with or without insulin, and not to the type of diabetes. Objectives This study investigated long-term survival in patients with type 1 DM (T1DM) and type 2 DM (T2DM) following CABG. Methods We included all patients from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register who underwent primary isolated CABG in Sweden during 2003 through 2013. We identified patients with T1DM or T2DM in the Swedish National Diabetes Register. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause mortality in patients with T1DM or T2DM. Results In total, 39,235 patients were included, of whom 725 (1.8%) had T1DM and 8,208 (21%) had T2DM. Patients with TDM1 were younger (59 vs. 67 years), had reduced kidney function (31% vs. 24%), and had peripheral vascular disease (21% vs. 11%) more often than patients with TDM2 or no diabetes. During a mean follow-up of 5.9 ± 3.2 years (230,085 person-years), 6,765 (17%) patients died. Among patients with T1DM, 152 (21%) died, and among patients with T2DM, 1,549 (19%) died. Adjusted hazard ratio (95% confidence interval) for death in patients with T1DM and T2DM, compared with patients without diabetes, were 2.04 (1.72 to 2.42), and 1.11 (1.05 to 1.18), respectively. Conclusions Patients with T1DM had more than double the long-term risk of death after CABG compared with patients without diabetes. The long-term risk of death in patients with T2DM was only slightly increased. [ABSTRACT FROM AUTHOR]

Aims Assessing the association between BMI and risk of coronary heart disease (CHD), cardiovascular disease (CVD) and mortality in patients with type 2 diabetes, also with regard to higher or lower levels of the ratio triglycerides-to-HDL-cholesterol (TG:HDL). Methods 54,061 patients with BMI ≥ 18.5 kg/m 2 , mean age and duration 61.5 ± 8 and 6.9 ± 6 years, 59% males, 14% with CVD history, from the Swedish National Diabetes Register, followed for mean 4.8 years. Results Adjusting at Cox regression for non-BMI-linked (age, sex, smoking, CVD history) and BMI-linked (blood lipids, blood pressure, HbA1c, albuminuria) covariates, hazard ratios (HR) for fatal/nonfatal CHD and CVD were mainly increased with prominent obesity (BMI ≥ 35 kg/m 2 ), 1.19 ( p = 0.01) and 1.17 ( p = 0.009), compared to normal weight (BMI 18.5–24.9 kg/m 2 ), although increased also with obesity (BMI 30–34.9 kg/m 2 ), 1.34 and 1.30 ( p < 0.001), when adjusting only for non-BMI-linked covariates. Stratifying by 75th percentile of TG:HDL, with normal weight and TG:HDL < 1.9 as reference, obese and prominently obese with TG:HDL ≥ 1.9 had considerably increased HR around 1.7 for fatal/nonfatal CHD and 1.6 for CVD ( p < 0.001), while obese and prominently obese with TG:HDL < 1.9 only had HR 1.2–1.3 for CHD and CVD ( p 0.003–<0.01). Conclusion Obese T2D patients with high TG:HDL, associated with increased insulin resistance, had considerably increased risk of CHD and CVD. [ABSTRACT FROM AUTHOR]

To identify physical activity trajectories, explore the factors associated with them and assess their relationship with all-cause mortality. This was a population-based longitudinal cohort study, with data from all specialist care units for type 1 diabetes in Sweden. A total of 48.921 adult patients were included, each with at least 3 registrations of physical activity, and a maximum follow-up of 14 years. The main outcomes were the longitudinal physical activity trajectories and all-cause mortality. Of 48.921 patients, 55.9% were males and mean (SD) age was 39.7(16.7). Four physical activity trajectories were identified: Steady Low (10.8%), Decreaser (12.7%), Increaser (20.7%) and Steady High (55.8%). Female sex, higher education, higher income, normal BMI, fewer comorbidities and foot free from diabetic disease were significantly associated with sustained high physical activity. Compared to the steady low group, the decreaser, increaser, and steady high physical activity groups exhibited lower adjusted risk of all-cause mortality (53–73% reduction). Consistently low physical activity is associated with higher all-cause mortality. This study underscores the importance of identifying patients at risk of low physical activity and tailoring personalized approaches to promote sustained physical activity in type 1 diabetes, ultimately improving outcomes. [ABSTRACT FROM AUTHOR]

Background: The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied.Methods: In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses. In addition, we examined optimal cut point levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. Patients with type 1 diabetes mellitus were followed up until death or study end on December 31, 2013. The primary outcomes were death resulting from all causes, fatal/nonfatal acute myocardial infarction, fatal/nonfatal stroke, and hospitalization for heart failure.Results: Of 32 611 patients with type 1 diabetes mellitus, 1809 (5.5%) died during follow-up over 10.4 years. The strongest predictors for death and cardiovascular outcomes were glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol. Glycohemoglobin displayed ≈2% higher risk for each 1-mmol/mol increase (equating to ≈22% per 1% glycohemoglobin difference), whereas low-density lipoprotein cholesterol was associated with 35% to 50% greater risk for each 1-mmol/L increase. Microalbuminuria or macroalbuminuria was associated with 2 to 4 times greater risk for cardiovascular complications and death. Glycohemoglobin <53 mmol/mol (7.0%), systolic blood pressure <140 mm Hg, and low-density lipoprotein cholesterol <2.5 mmol/L were associated with significantly lower risk for outcomes observed.Conclusions: Glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol appear to be the most important predictors for mortality and cardiovascular outcomes in patients with type 1 diabetes mellitus. Lower levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than contemporary guideline target levels appear to be associated with significantly lower risk for outcomes. [ABSTRACT FROM AUTHOR]

Background: People with type 1 diabetes are at elevated risk of mortality and cardiovascular disease, yet current guidelines do not consider age of onset as an important risk stratifier. We aimed to examine how age at diagnosis of type 1 diabetes relates to excess mortality and cardiovascular risk.Methods: We did a nationwide, register-based cohort study of individuals with type 1 diabetes in the Swedish National Diabetes Register and matched controls from the general population. We included patients with at least one registration between Jan 1, 1998, and Dec 31, 2012. Using Cox regression, and with adjustment for diabetes duration, we estimated the excess risk of all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, acute myocardial infarction, stroke, cardiovascular disease (a composite of acute myocardial infarction and stroke), coronary heart disease, heart failure, and atrial fibrillation. Individuals with type 1 diabetes were categorised into five groups, according to age at diagnosis: 0-10 years, 11-15 years, 16-20 years, 21-25 years, and 26-30 years.Findings: 27 195 individuals with type 1 diabetes and 135 178 matched controls were selected for this study. 959 individuals with type 1 diabetes and 1501 controls died during follow-up (median follow-up was 10 years). Patients who developed type 1 diabetes at 0-10 years of age had hazard ratios of 4·11 (95% CI 3·24-5·22) for all-cause mortality, 7·38 (3·65-14·94) for cardiovascular mortality, 3·96 (3·06-5·11) for non-cardiovascular mortality, 11·44 (7·95-16·44) for cardiovascular disease, 30·50 (19·98-46·57) for coronary heart disease, 30·95 (17·59-54·45) for acute myocardial infarction, 6·45 (4·04-10·31) for stroke, 12·90 (7·39-22·51) for heart failure, and 1·17 (0·62-2·20) for atrial fibrillation. Corresponding hazard ratios for individuals who developed type 1 diabetes aged 26-30 years were 2·83 (95% CI 2·38-3·37) for all-cause mortality, 3·64 (2·34-5·66) for cardiovascular mortality, 2·78 (2·29-3·38) for non-cardiovascular mortality, 3·85 (3·05-4·87) for cardiovascular disease, 6·08 (4·71-7·84) for coronary heart disease, 5·77 (4·08-8·16) for acute myocardial infarction, 3·22 (2·35-4·42) for stroke, 5·07 (3·55-7·22) for heart failure, and 1·18 (0·79-1·77) for atrial fibrillation; hence the excess risk differed by up to five times across the diagnosis age groups. The highest overall incidence rate, noted for all-cause mortality, was 1·9 (95% CI 1·71-2·11) per 100 000 person-years for people with type 1 diabetes. Development of type 1 diabetes before 10 years of age resulted in a loss of 17·7 life-years (95% CI 14·5-20·4) for women and 14·2 life-years (12·1-18·2) for men.Interpretation: Age at onset of type 1 diabetes is an important determinant of survival, as well as all cardiovascular outcomes, with highest excess risk in women. Greater focus on cardioprotection might be warranted in people with early-onset type 1 diabetes.Funding: Swedish Heart and Lung Foundation. [ABSTRACT FROM AUTHOR]

Background: It is unknown if coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) may offer a survival benefit in patients with type 1 diabetes (T1D) in need of multivessel revascularization.Objectives: This study sought to determine if patients with T1D and multivessel disease may benefit from CABG compared with PCI.Methods: In an observational cohort study, the authors included all patients with T1D who underwent a first multivessel revascularization in Sweden from 1995 to 2013. The authors used the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) register, the Swedish National Diabetes Register, and the Swedish National Patient Register to retrieve information about patient characteristics and outcomes. They estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) for all-cause and coronary heart disease mortality, myocardial infarction, repeat revascularization, stroke, and heart failure using inverse probability of treatment weighting based on propensity scores.Results: In total, 683 patients who underwent CABG and 1,863 patients who underwent PCI were included. During a mean follow-up of 10.6 years, 53% of patients in the CABG group and 45% in the PCI group died. PCI, compared with CABG, was associated with a similar risk of all-cause mortality (HR: 1.14; 95% CI: 0.99 to 1.32), but higher risks of death from coronary heart disease (HR: 1.45; 95% CI: 1.21 to 1.74), myocardial infarction (HR: 1.47; 95% CI: 1.23 to 1.78), and repeat revascularization (HR: 5.64; 95% CI: 4.67 to 6.82). No differences in risks of stroke or heart failure were found.Conclusions: Notwithstanding the inclusion of patients with T1D who might not have been able to undergo CABG in the PCI group we found that PCI, compared with CABG, was associated with higher rates and risks of coronary heart disease mortality, myocardial infarction, and repeat revascularizations. Our findings indicate that CABG may be the preferred strategy in patients with T1D in need of multivessel revascularization. [ABSTRACT FROM AUTHOR]

Background: Long-term trends in excess risk of death and cardiovascular outcomes have not been extensively studied in persons with type 1 diabetes or type 2 diabetes.Methods: We included patients registered in the Swedish National Diabetes Register from 1998 through 2012 and followed them through 2014. Trends in deaths and cardiovascular events were estimated with Cox regression and standardized incidence rates. For each patient, controls who were matched for age, sex, and county were randomly selected from the general population.Results: Among patients with type 1 diabetes, absolute changes during the study period in the incidence rates of sentinel outcomes per 10,000 person-years were as follows: death from any cause, -31.4 (95% confidence interval [CI], -56.1 to -6.7); death from cardiovascular disease, -26.0 (95% CI, -42.6 to -9.4); death from coronary heart disease, -21.7 (95% CI, -37.1 to -6.4); and hospitalization for cardiovascular disease, -45.7 (95% CI, -71.4 to -20.1). Absolute changes per 10,000 person-years among patients with type 2 diabetes were as follows: death from any cause, -69.6 (95% CI, -95.9 to -43.2); death from cardiovascular disease, -110.0 (95% CI, -128.9 to -91.1); death from coronary heart disease, -91.9 (95% CI, -108.9 to -75.0); and hospitalization for cardiovascular disease, -203.6 (95% CI, -230.9 to -176.3). Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls.Conclusions: In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. (Funded by the Swedish Association of Local Authorities and Regions and others.). [ABSTRACT FROM AUTHOR]

Importance: Concerns have been raised regarding a link between use of glucagon-like peptide-1 (GLP-1) receptor agonists and increased risk of suicidality and self-harm., Objective: To assess the association between use of GLP-1 receptor agonists and the risk of suicide death in routine clinical practice., Design, Setting, and Participants: This active-comparator new-user cohort study used nationwide register data from Sweden and Denmark from 2013 to 2021. Adults 18 to 84 years old who initiated treatment with GLP-1 receptor agonists or the comparator sodium-glucose cotransporter-2 (SGLT2) inhibitors were included. Data were analyzed from March to June 2024., Exposure: Initiation of treatment with a GLP-1 receptor agonist or SGLT2 inhibitor., Main Outcomes and Measures: The primary outcome was suicide death recorded in the cause of death registers. Secondary outcomes were the composite of suicide death and nonfatal self-harm and the composite of incident depression and anxiety-related disorders. Using propensity score weighting, hazard ratios (HRs) with 95% CIs were calculated separately in the 2 countries and pooled in a meta-analysis., Results: In total, 124 517 adults initiated a GLP-1 receptor agonist and 174 036 initiated an SGLT2 inhibitor; among GLP-1 receptor agonist users, the mean (SD) age was 60 (13) years, and 45% were women. During a mean (SD) follow-up of 2.5 (1.7) years, 77 suicide deaths occurred among users of GLP-1 receptor agonists and 71 suicide deaths occurred among users of SGLT2 inhibitors: weighted incidences were 0.23 vs 0.18 events per 1000 person-years (HR, 1.25; 95% CI, 0.83-1.88), with an absolute difference of 0.05 (95% CI, -0.03 to 0.16) events per 1000 person-years. The HR was 0.83 (95% CI, 0.70-0.97) for suicide death and nonfatal self-harm, and the HR was 1.01 (95% CI, 0.97-1.06) for incident depression and anxiety-related disorders., Conclusions and Relevance: This cohort study, including mostly patients with type 2 diabetes, does not show an association between use of GLP-1 receptor agonists and an increased risk of suicide death, self-harm, or incident depression and anxiety-related disorders. Suicide death among GLP-1 receptor agonist users was rare, and the upper limit of the confidence interval was compatible with an absolute risk increase of no more than 0.16 events per 1000 person-years.

Aims: To develop and externally validate the LIFE-T1D model for the estimation of lifetime and 10-year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes., Materials and Methods: A sex-specific competing risk-adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non-high-density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank., Results: During a median follow-up of 11.8 years (interquartile interval 6.1-17.1 years), 4608 CVD events and 1316 non-CVD deaths were observed in the NDR (n = 39 756). The internal validation c-statistic was 0.85 (95% confidence interval [CI] 0.84-0.85) and the external validation c-statistics were 0.77 (95% CI 0.74-0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70-0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts., Conclusions: The LIFE-T1D model can estimate lifetime risk of CVD and CVD-free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background & Aims: Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction., Methods: Using data from nationwide registers in Sweden, Denmark, and Norway, 2013-2021, we conducted 2 cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 [SGLT2] inhibitors)., Results: Among 19,0321 new users of DPP4 inhibitors (median (interquartile range [IQR]) follow-up time, 1.3 [0.6-2.6] years) and 139,315 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.7] years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 2.0 vs 1.8 per 1000 person-years; hazard ratio, 1.13; 95% confidence interval, 0.96-1.34). Among 121,254 new users of GLP-1 receptor agonists (median [standard deviation] follow-up time, 0.9 [0.4-1.9] years) and 185,027 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.8] years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 1.3 vs 1.6 per 1000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.69-1.01)., Conclusions: In this analysis of nationwide data from 3 countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Clinical trials suggest that glucagon-like peptide-1 (GLP-1) receptor agonists may have beneficial effects on NAFLD, but the impact on hard hepatic end points is unknown. We assessed the association between the use of GLP-1 receptor agonists and the risk of serious liver events in routine clinical practice., Approach and Results: Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, 2007-2020, including 91,479 initiators of GLP-1 receptor agonists and 244,004 initiators of the active comparator, dipeptidyl peptidase-4 inhibitors, without a history of chronic liver disease other than NAFLD/NASH. The primary outcome was serious liver events: a composite of incident compensated and decompensated cirrhosis and HCC. Secondary outcomes were the individual components of the primary outcome. Cox regression was used to estimate HRs, using propensity score weighting to control for confounding. Users of GLP-1 receptor agonists had 608 serious liver events (adjusted incidence rate: 16.9 events per 10,000 person-years), compared with 1770 events among users of dipeptidyl peptidase-4 inhibitors (19.2 events per 10,000 person-years). The adjusted HR was 0.85 (95% CI: 0.75 to 0.97), and the rate difference was -2.1 (-4.4 to 0.1) events per 10,000 person-years. In secondary outcome analyses, the adjusted HR was 0.85 (0.75 to 0.97) for compensated and decompensated cirrhosis and 1.05 (0.80 to 1.39) for HCC., Conclusions: The use of GLP-1 receptor agonists was associated with a significantly reduced risk of serious liver events, driven by a reduction of compensated and decompensated cirrhosis., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Premature death in diabetes is increasingly caused by cancer. The objectives were to estimate the excess mortality when individuals with type 2 diabetes(T2D) were diagnosed with cancer, and to examine the impact of modifiable diabetes-related risk factors. This longitudinal nationwide cohort study included individuals with T2D registered in the Swedish National Diabetes Register between 1998-2019. Poisson models were used to estimate mortality as a function of time-updated risk-factors, adjusted for sex, age, diabetes duration, marital status, country of birth, BMI, blood pressure, lipids, albuminuria, smoking, and physical activity. We included 690,539 individuals with T2D and during 4,787,326 person-years of follow-up 179,627 individuals died. Overall, the all-cause mortality rate ratio was 3.75 [95%confidence interval(CI):3.69-3.81] for individuals with T2D and cancer compared to those remaining free of cancer. The most marked risk factors associated to mortality among individuals with T2D and cancer were low physical activity, 1.59 (1.57-1.61) and smoking, 2.15 (2.08-2.22), whereas HbA1c, lipids, hypertension, and BMI had no/weak associations with survival. In a future with more patients with comorbid T2D and cancer diagnoses, these results suggest that smoking and physical activity might be the two most salient modifiable risk factors for mortality in people with type 2 diabetes and cancer., (© 2024. The Author(s).)

Objective: To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer., Design: Scandinavian cohort study., Setting: Denmark, Norway, and Sweden, 2007-21., Participants: Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment., Main Outcome Measures: Thyroid cancer identified from nationwide cancer registers. An active-comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting., Results: The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference -0.13, 95% confidence interval -0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05)., Conclusions: In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from Swedish Cancer Society, Swedish Research Council, Karolinska Institutet, Novo Nordisk Foundation, Lundbeck Foundation, Independent Research Foundation Denmark, Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, and Danish Cancer Society for the submitted work; CJ is an employee of NordicRWE; BE reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Mundipharma, Navamedic, Novo Nordisk, and Sanofi outside the submitted work; HS is a former employee of IQVIA; AH is a scientific advisory board member of VAC4EU; the other authors declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims/hypothesis: This register-based study aimed to describe autoimmune comorbidity in children and young adults from type 1 diabetes onset, and to investigate whether such comorbidity was associated with a difference in HbA 1c or mortality risk compared with children/young adults with type 1 diabetes without autoimmune comorbidity., Methods: A total of 15,188 individuals from the Swedish National Diabetes Register, registered with type 1 diabetes before 18 years of age between 2000 and 2019, were included. Five randomly selected control individuals from the Swedish population (Statistics Sweden) were matched to each individual with type 1 diabetes (n=74,210 [346 individuals with type 1 diabetes were not found in the Statistics Sweden register at the date of type 1 diabetes diagnosis, so could not be matched to control individuals]). The National Patient Register was used to attain ICD-10 codes on autoimmune diseases and the Cause of Death Register was used to identify deceased individuals., Results: In the total type 1 diabetes cohort, mean±SD age at onset of type 1 diabetes was 9.5±4.4 years and mean disease duration at end of follow-up was 8.8±5.7 years. Of the individuals with type 1 diabetes, 19.2% were diagnosed with at least one autoimmune disease vs 4.0% of the control group. The HRs for comorbidities within 19 years from onset of type 1 diabetes were 11.6 (95% CI 10.6, 12.6) for coeliac disease, 10.6 (95% CI 9.6, 11.8) for thyroid disease, 1.3 (95% CI 1.1, 1.6) for psoriasis, 4.1 (95% CI 3.2, 5.3) for vitiligo, 1.7 (95% CI 1.4, 2.2) for rheumatic joint disease, 1.0 (95% CI 0.8, 1.3) for inflammatory bowel disease, 1.0 (95% CI 0.7, 1.2) for systemic connective tissue disorder, 1.4 (95% CI 1.1, 1.9) for uveitis, 18.3 (95% CI 8.4, 40.0) for Addison's disease, 1.8 (95% CI 0.9, 3.6) for multiple sclerosis, 3.7 (95% CI 1.6, 8.7) for inflammatory liver disease and 19.6 (95% CI 4.2, 92.3) for atrophic gastritis. Autoimmune disease in addition to type 1 diabetes had no statistically significant effect on HbA 1c or mortality risk., Conclusions/interpretation: To our knowledge, this is the first comprehensive study where young individuals with type 1 diabetes were followed regarding development of a wide spectrum of autoimmune diseases, from onset of type 1 diabetes. In this nationwide and population-based study, there was already a high prevalence of autoimmune diseases in childhood, especially coeliac and thyroid disease. The presence of autoimmune comorbidity did not have a statistically significant effect on metabolic control or mortality risk., (© 2024. The Author(s).)

Objective: To investigate to what extent having control of peripheral artery disease (PAD) risk factors is associated with the risk of incident PAD in individuals with type 2 diabetes., Research Design and Methods: A total of 148,096 individuals with type 2 diabetes in the Swedish National Diabetes Register between 2005 and 2009 were included and matched with 320,066 control subjects on the basis of age, sex, and county. A few control subjects who developed type 2 diabetes after recruitment, during wash-in (<0.2%), were not censored but instead matched with two new control subjects. Individuals with type 2 diabetes were evaluated according to the number of PAD risk factors beyond recommended guideline levels at baseline, including LDL cholesterol, blood pressure, smoking, glycated hemoglobin, and estimated glomerular filtration rate. Incident PAD events were ascertained from 2006 to 2019., Results: A graded association was observed between the number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes. The adjusted hazard ratio for PAD was 1.41 (95% CI 1.23-1.63) for those with type 2 diabetes with all PAD risk factors within target compared with control subjects matched for sex, age, and county but not risk factor status, in contrast with 9.28 (95% CI 3.62-23.79) for those with all five PAD risk factors not at target., Conclusions: A graded association was observed between increasing number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes., (© 2023 by the American Diabetes Association.)

Background: The goal of this work was to investigate trends (2001-2019) for cardiovascular events and cardiometabolic risk factor levels in individuals with type 2 diabetes (T2D) and matched control subjects., Methods: This study included 679 072 individuals with T2D from the Swedish National Diabetes Register and 2 643  800 matched control subjects. Incident outcomes comprised coronary artery disease, acute myocardial infarction, cerebrovascular disease, and heart failure (HF). Trends in time to first event for each outcome were analyzed with Cox regression and standardized incidence rates. In the group with T2D, Cox regression was also used to assess risk factor levels beyond target and outcomes, as well as the relative importance of each risk factor to each model., Results: Among individuals with T2D, incidence rates per 10 000 person-years in 2001 and 2019 were as follows: acute myocardial infarction, 73.9 (95% CI, 65.4-86.8) and 41.0 (95% CI, 39.5-42.6); coronary artery disease, 205.1 (95% CI, 186.8-227.5) and 80.2 (95% CI, 78.2-82.3); cerebrovascular disease, 83.9 (95% CI, 73.6-98.5) and 46.2 (95% CI, 44.9-47.6); and HF, 98.3 (95% CI, 89.4-112.0) and 75.9 (95% CI, 74.4-77.5). The incidence for HF plateaued around 2013, a trend that then persisted. In individuals with T2D, glycated hemoglobin, systolic blood pressure, estimated glomerular filtration rate, and lipids were independently associated with outcomes. Body mass index alone potentially explained >30% of HF risk in T2D. For those with T2D with no risk factor beyond target, there was no excess cardiovascular risk compared with control subjects except for HF, with increased hazard with T2D even when no risk factor was above target (hazard ratio, 1.50 [95% CI, 1.35-1.67]). Risk for coronary artery disease and cerebrovascular disease increased in a stepwise fashion for each risk factor not within target. Glycated hemoglobin was most prognostically important for incident atherosclerotic events, as was body mass index for incident of HF., Conclusions: Risk and rates for atherosclerotic complications and HF are generally decreasing among individuals with T2D, although HF incidence has notably plateaued in recent years. Modifiable risk factors within target levels were associated with lower risks for outcomes. This was particularly notable for systolic blood pressure and glycated hemoglobin for atherosclerotic outcomes and body mass index for heart failure., Competing Interests: Disclosures Dr Bhatt discloses the following relationships: advisory boards for Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; boards of directors for Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; chair/inaugural chair of the American Heart Association Quality Oversight Committee; consultant for Broadview Ventures and Hims; data monitoring committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT Trial); honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair of the ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI Clinical Trial Steering Committee funded by Boehringer Ingelheim; AEGIS-II executive committee, funded by CSL Behring), Belvoir Publications (editor in chief of Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief of the Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (co-chair for interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director of Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national coleader, funded by Bayer), Slack Publications (chief medical editor of Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees), Wiley (steering committee); other: clinical cardiology (deputy editor), NCDR-ACTION Registry steering committee (chair), and VA CART Research and Publications Committee (chair); named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital (assigned to Lexicon; neither Dr Bhatt nor Brigham and Women’s Hospital receives any income from this patent); research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties from Elsevier (editor of Braunwald’s Heart Disease); site co- investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee of the American College of Cardiology; and unfunded research from FlowCo and Takeda. Dr McGuire reports receiving executive committee fees and consulting fees from Boehringer Ingelheim, Sanofi US, and AstraZeneca; data monitoring committee fees from CSL Behring; executive committee fees, consulting fees, and advisory board fees from Lilly USA and Novo Nordisk; executive committee fees from Lexicon and Eisai; steering committee fees from Esperion; consulting fees from Metavant, Applied Therapeutics, Bayer, and Afimmune; and advisory board fees from Pfizer, Merck Sharp, and Dohme. Dr Sattar has consulted for Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi, MSD, Novartis, Novo Nordisk, Pfizer, and Sanofi, and received grant support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. The other authors report no conflicts.

Aims: The 2021 European Society of Cardiology (ESC) guidelines recommend that patients with type 2 diabetes (T2D) with a very high cardiovascular disease (CVD) risk receive cardiovascular (CV)-protective glucose-lowering medication (glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter-2 inhibitors). This analysis compared previous prescribing practices with the ESC recommendations., Methods and Results: Patients in the Swedish National Diabetes Register (NDR) with T2D, aged 18-90 years, not receiving CV-protective glucose-lowering medication in 2017 were identified, and the ESC criteria for very high CVD risk were applied. The composite outcome of major adverse CV events (MACEs; defined as CV death, non-fatal stroke or non-fatal myocardial infarction) during 2017 was calculated, and the number of MACE avoided with semaglutide, an example of a CV-protective glucose-lowering medication, was estimated for patients with a certain CV risk score. Of the 320 028 patients in the NDR with T2D who were not receiving CV-protective glucose-lowering medication, 129 512 patients had a very high CVD risk. Patients with a very high CVD risk had a high incidence of MACE (75.4 events/1000 person-years), which was higher in those with atherosclerotic CVD (ASCVD) with and without elevated glycated haemoglobin (>9%; 136.5 and 90.8 events/1000 person-years, respectively). If patients with a very high CVD risk, according to the ESC, and ASCVD received semaglutide, 803 MACE may have been avoided in 2017., Conclusions: This analysis highlights differences between previous prescribing practices in Sweden and the 2021 ESC guidelines and offers strategies to prioritize CV-protective glucose-lowering medication for patients who would benefit most., Competing Interests: Conflict of interest: B.E. has received personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mundipharma, Navamedic, Novo Nordisk, and RLS Global, and grants and personal fees from Sanofi. C.N.H. is an employee of Novo Nordisk Scandinavia AB. M.L.W. and K.S.M. are employees of Novo Nordisk A/S. S.J. reports no personal conflicts of interest. Their institution has received research from Amgen, AstraZeneca, Bayer, Janssen, Novartis, and Novo Nordisk., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: SMARTEST is a register-based randomized clinical trial (RRCT) that compares dapagliflozin to metformin in early-stage type 2 diabetes. The primary outcome includes progression of microvascular complications based on data from the Swedish National Diabetes Register (NDR). In this sub-study, the aim was to validate microvascular complication variables in the NDR against electronic health records (EHRs)., Methods: Data were extracted from EHRs of 276 SMARTEST participants with a median observation period of 3 years in the Uppsala, Örebro and Sörmland counties and compared with NDR data. Agreement was determined for all corresponding data entries as well as for progression of microvascular complications after randomization., Results: The agreement for all corresponding data entries was 98.9% (Intraclass Correlation Coefficient 0.999) for creatinine and eGFR, 95.1% for albuminuria, 91.6% for foot-at-risk and 98.2% for retinopathy status (Kappa 0.67-0.91). The agreement for progression of microvascular complications was 98.0% for CKD stage, 98.9% for albuminuria grade, 96.3% for foot-at-risk grade and 99.6% for retinopathy grade progression (Gwet's AC 1 0.96-1.00)., Conclusion: Microvascular complication variables in the NDR show good agreement with EHR data. The use of a well-established national health care registry, exemplified by the NDR, for endpoint collection in RRCTs such as SMARTEST is supported by this study.

Aims: To investigate the association between glycemic control and outcome in people with type 2 diabetes (T2D) after carotid intervention due to carotid stenosis., Methods: Observational nationwide population-based cohort study using inverse probability treatment weighting (IPTW) and Cox regressions with covariates, that is, 4 stepwise models, investigating the relationship between terciles of glycated hemoglobin (HbA1c) levels and stroke or death., Results: 1115 subjects with T2D undergoing carotid intervention were included during Jan 1st 2009 to Dec 31st 2015. Divided into terciles, with a mean HbA1c level of 44 (tercile 1), 53 (tercile 2), and 72 (tercile 3) mmol/mol. By using IPTW and Cox regression, each model was stepwise introduced for the investigating of relative risks, that is, hazard ratios (HRs) with associated 95% confidence intervals (CI). There was a significant increased risk for stroke or death, in every model observed for tercile 3, compared to tercile 1: HR for model 4: 1.35 (95% CI 1.02-1.78). No difference for stroke or death within 30 days was observed between the groups., Conclusion: Poor glycemic control in people with T2D after carotid intervention is associated with an increased long-term risk for stroke or death.

Context: Obesity is considered to have a detrimental impact on health-related quality of life (HRQoL)., Objective: To compare HRQoL in a well-defined group of people with obesity with a population-based control group from the general public., Design: Observational cross-sectional cohort study with a reference population., Setting: The Regional Obesity Center at the Department of Medicine at Sahlgrenska University Hospital, Gothenburg, Sweden., Participants: People with obesity (n = 1122) eligible for surgical and non-surgical obesity treatment in routine care were included consecutively between 2015 and 2017 into the BASUN study. Men and women from the WHO-MONICA-GOT project were used as a reference population (n = 414)., Main Outcome Measures: HRQoL was measured with the RAND-36/Short Form-36 questionnaire (SF-36) and a Visual Analogue Scale (VAS) for self-related health (SRH). Prescription drugs for hypertension, diabetes mellitus, depression, and anxiety were taken as a proxy for these conditions., Results: People with obesity rated their overall HRQoL lower than the reference population according to the SRH-VAS. Lower scores were reported on physical and social functioning, vitality, general and mental health after adjustment for age and use of prescription drugs (considered a proxy for burden of disease, or comorbidities) using the RAND-36/SF-36 questionnaire. Use of some psychopharmacological agents was more common in patients with obesity., Conclusion: People with obesity seeking help with weight reduction are more likely to have lower physical and mental self-reported HRQoL than the general population., Competing Interests: The authors have declared that no competing interests exist.

Background: Obesity is a growing health issue. This study estimated the costs of obesity among people aged 25-84 years in Sweden using disease and non-disease specific attributable fractions from published data. A prognosis of costs of obesity in 2030 is presented., Methods and Materials: Diseases related to obesity and their respective risks and population attributable fraction were retrieved by literature review. Longitudinal data on age and sex related prevalence of obesity was used to construct three scenarios for costs of obesity in 2030., Results: Nearly 4% of all deaths among people 25-84 years in 2016 (n = 3,400) were attributed to obesity. Obesity cost EUR 2.7 billion in 2016, or EUR 377 per inhabitant aged ≥25 years. Non-health care costs were dominant and represented 80% of total societal costs. Main drivers were premature mortality (28%) and permanent sick leave (37%). If the proportion of obese remain at 2016 level, costs will increase 9% by 2030, but with continued linear growth, costs will increase by 66%., Conclusions: The responsibility, costs and treatment fall on several actors with a considerable burden falling on the individual and the society at large. New health promoting interventions and policy programs are needed and must be evaluated in terms of resource use and expected return., (Copyright © 2022. Published by Elsevier B.V.)

Background: HbA1c variability has emerged as risk factor for cardiovascular diseases in diabetes. However, the impact of HbA1c variability on cardiovascular diseases in subjects within the recommended HbA1c target has been relatively unexplored., Methods: Using data from a large database, we studied 101,533 people with type 2 diabetes without cardiovascular diseases. HbA1c variability was expressed as quartiles of the standard deviation of HbA1c during three years (exposure phase). The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, all-cause mortality and was assessed during five years following the first three years of exposure to HbA1c variability (longitudinal phase). An expanded composite outcome including non-fatal myocardial infarction, non-fatal stroke, coronary revascularization/reperfusion procedures, peripheral revascularization procedures, and all-cause mortality was also considered, as well as a series of specific cardiovascular complications. Cox models were adjusted for a large range of risk factors and results were expressed as adjusted hazard ratios., Results: An association between HbA1c variability and all the outcomes considered was found. The correlation between HbA1c variability and cardiovascular complications development was confirmed in both the subgroups of subjects with a mean HbA1c ≤ 53 mmol/mol (recommended HbA1c target) or > 53 mmol/mol during the exposure phase. The risk related to HbA1c variability was higher in people with mean HbA1c ≤ 53 mmol/mol for the primary outcome (p for interaction 0.004), for the expanded secondary outcome (p for interaction 0.001) and for the stroke (p for interaction 0.001), even though HbA1c remained at the target during the follow-up., Conclusions: These findings suggest that HbA1c variability may provide additional information for an optimized management of diabetes, particularly in people within the target of HbA1c., (© 2022. The Author(s).)

Background and Aims: Insulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D., Materials and Methods: Nationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4-6, 6-8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R 2 (± SE) values calculating the explainable log-likelihoods in the Cox regression., Results: A total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4-6, 6-8 and > 8 were: 0.77 (0.69-0.87), 0.68 (0.58-0.80) and 0.60 (0.48-0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70-0.94), 0.75 (0.64-0.88) and 0.68 (0.53-0.89). The attributed relative risk R 2 (± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively., Conclusion: A low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension., (© 2021. The Author(s).)

Aims/hypothesis: Tables reporting life expectancies by common risk factors are available for individuals with type 2 diabetes; however, there is currently no published equivalent for individuals with type 1 diabetes. We aimed to develop a life expectancy table using a recently published simulation model for individuals with type 1 diabetes., Methods: The simulation model was developed using data from a real-world population of patients with type 1 diabetes selected from the Swedish National Diabetes Register. The following six important risk factors were included in the life table: sex; age; current smoking status; BMI; eGFR; and HbA 1c . For each of 1024 cells in the life expectancy table, a synthetic cohort containing 1000 individuals was created, with other risk factors assigned values representative of the real-world population. The simulations were executed for all synthetic cohorts and life expectancy for each cell was calculated as mean survival time of the individuals in the respective cohort., Results: There was a substantial variation in life expectancy across patients with different risk factor levels. Life expectancy of 20-year-old men varied from 29.3 years to 50.6 years, constituting a gap of 21.3 years between those with worst and best risk factor levels. In 20-year-old women, this gap was 18.9 years (life expectancy range 35.0-53.9 years). The variation in life expectancy was a function of the combination of risk factor values, with HbA 1c and eGFR consistently showing a negative and positive correlation, respectively, with life expectancy at any level combination of other risk factors. Individuals with the lowest level (20 kg/m 2 ) and highest level of BMI (35 kg/m 2 ) had a lower life expectancy compared with those with a BMI of 25 kg/m 2 . Non-smokers and women had a higher life expectancy than smokers and men, respectively, with the difference in life expectancy ranging from 0.4 years to 2.7 years between non-smokers and smokers, and from 1.9 years to 5.9 years between women and men, depending on levels of other risk factors., Conclusions/interpretation: The life expectancy table generated in this study shows a substantial variation in life expectancy across individuals with different modifiable risk factors. The table allows for rapid communications of risk in an easily understood format between healthcare professionals, health economists, researchers, policy makers and patients. Particularly, it supports clinicians in their discussion with patients about the benefits of improving risk factors., (© 2021. The Author(s).)

Background: The development of obesity is most likely due to a combination of biological and environmental factors some of which might still be unidentified. We used a machine learning technique to examine the relative importance of more than 100 clinical variables as predictors for BMI., Methods: BASUN is a prospective non-randomized cohort study of 971 individuals that received medical or surgical treatment (treatment choice was based on patient's preferences and clinical criteria, not randomization) for obesity in the Västra Götaland county in Sweden between 2015 and 2017 with planned follow-up for 10 years. This study includes demographic data, BMI, blood tests, and questionnaires before obesity treatment that cover three main areas: gastrointestinal symptoms and eating habits, physical activity and quality of life, and psychological health. We used random forest, with conditional variable importance, to study the relative importance of roughly 100 predictors of BMI, covering 15 domains. We quantified the predictive value of each individual predictor, as well as each domain., Results: The participants received medical (n = 382) or surgical treatment for obesity (Roux-en-Y gastric bypass, n = 388; sleeve gastrectomy, n = 201). There were minor differences between these groups before treatment with regard to anthropometrics, laboratory measures and results from questionnaires. The 10 individual variables with the strongest predictive value, in order of decreasing strength, were country of birth, marital status, sex, calcium levels, age, levels of TSH and HbA1c, AUDIT score, BE tendencies according to QEWPR, and TG levels. The strongest domains predicting BMI were: Socioeconomic status, Demographics, Biomarkers (notably TSH), Lifestyle/habits, Biomarkers for cardiovascular disease and diabetes, and Potential anxiety and depression., Conclusions: Lifestyle, habits, age, sex and socioeconomic status are some of the strongest predictors for BMI levels. Potential anxiety and / or depression and other characteristics captured using questionnaires have strong predictive value. These results confirm previously suggested associations and advocate prospective studies to examine the value of better characterization of patients eligible for obesity treatment, and consequently to evaluate the treatment effects in groups of patients., Trial Registration: March 03, 2015; NCT03152617 ., (© 2021. The Author(s).)

Background: There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes., Methods: Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability., Results: After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39-1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality)., Conclusions: High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations., (© 2021. The Author(s).)

Objectives: To investigate early and long-term outcomes after treatment of carotid artery stenosis in patients with type 2 diabetes (T2D) compared to patients without T2D., Design/method: This observational nationwide population-based retrospective cohort study investigated all T2D patients treated for carotid stenosis registered in the National Swedish Vascular Surgery and the National Diabetes Registries. Data was collected prospectively for all patients after carotid intervention, during 2009-2015. We estimated crude early (within 30-days) hazard ratios (HRs) risk of stroke and death, and long-term HRs risk, adjusted for confounders with 95% confidence intervals (CIs), for stroke and death and major adverse cardiovascular events (MACE) by using inverse probability of treatment weighting matching., Results: A total of 1341 patients with T2D and 4162 patients without T2D were included; 89% treated for symptomatic carotid stenosis, 96% with carotid endarterectomy. There was an increased early risk, HRs (95% CI), for stroke in T2D patients 1.65 (1.17-2.32), whereas risk for early death 1.00 (0.49-2.04) was similar in both groups. During a median follow-up of 4.3 (T2D) and 4.6 (without T2D), with a maximum of 8.0 years; after propensity score matching there was an increased HRs (95% CI) of stroke 1.27 (1.05-1.54) and death 1.27 (1.10-1.47) in T2D patients compared to patients without T2D. Corresponding numbers for MACE were 1.21 (1.08-1.35)., Conclusions: Patients with T2D run an increased risk for stroke, death, and MACE after carotid intervention. They also have an increased perioperative risk for stroke, but not for death.