Effect of Diabetes on Morbidity and Mortality in Patients With Acromegaly.

CONTEXT: Diabetes is a major risk factor for cardiovascular disease and death but its effect on outcomes in acromegaly is unknown. OBJECTIVE: This work aimed to study whether diabetes affects morbidity and mortality in patients with acromegaly. METHODS: A nationwide (Sweden), observational, matched-cohort study was conducted. Patients diagnosed with acromegaly between 1987 and 2020 were identified in the Swedish National Patient Registry and those with concomitant type 2 diabetes in the National Diabetes Registry and Drug Registry. The risk of overall mortality, and cardiovascular mortality and morbidity were estimated using Cox regression. RESULTS: The study included 254 patients with acromegaly and concomitant type 2 diabetes (ACRO-DM group) and 532 without diabetes (ACRO group). Mean (SD) age at baseline was 62.6 (11.4) and 60.0 (12.1) years (P = .004) and the mean (SD) duration of acromegaly was 6.8 (8.1) and 6.0 (6.2) years (P = .098) in the ACRO-DM and ACRO groups, respectively. Overall mean follow-up was 9.2 years. The unadjusted overall mortality rate per 1000 person-years was 35.1 (95% CI, 27.2-44.7) and 20.1 (95% CI, 16.5-24.3) in the respective groups. The hazard ratio (HR) for overall mortality adjusted for multiple confounders was 1.58 (95% CI, 1.12-2.23) in the ACRO-DM group compared with the ACRO group. Cardiovascular mortality (HR 2.11; 95% CI, 1.09-4.10) and morbidity (HR 1.49; 95% CI, 1.21-1.82) were also increased in the ACRO-DM group. CONCLUSION: The presence of diabetes in patients with acromegaly was associated with increased overall mortality as well as increased cardiovascular mortality and morbidity.

Impact of Socioeconomic Factors and Gender on Refill Adherence and Persistence to Lipid-Lowering Therapy in Type 1 Diabetes.

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.

Comparison between data-driven clusters and models based on clinical features to predict outcomes in type 2 diabetes: nationwide observational study.

AIMS/HYPOTHESIS: Research using data-driven cluster analysis has proposed five novel subgroups of diabetes based on six measured variables in individuals with newly diagnosed diabetes. Our aim was (1) to validate the existence of differing clusters within type 2 diabetes, and (2) to compare the cluster method with an alternative strategy based on traditional methods to predict diabetes outcomes. METHODS: We used data from the Swedish National Diabetes Register and included 114,231 individuals with newly diagnosed type 2 diabetes. k-means clustering was used to identify clusters based on nine continuous variables (age at diagnosis, HbA1c, BMI, systolic and diastolic BP, LDL- and HDL-cholesterol, triacylglycerol and eGFR). The elbow method was used to determine the optimal number of clusters and Cox regression models were used to evaluate mortality risk and risk of CVD events. The prediction models were compared using concordance statistics. RESULTS: The elbow plot, with values of k ranging from 1 to 10, showed a smooth curve without any clear cut-off points, making the optimal value of k unclear. The appearance of the plot was very similar to the elbow plot made from a simulated dataset consisting only of one cluster. In prediction models for mortality, concordance was 0.63 (95% CI 0.63, 0.64) for two clusters, 0.66 (95% CI 0.65, 0.66) for four clusters, 0.77 (95% CI 0.76, 0.77) for the ordinary Cox model and 0.78 (95% CI 0.77, 0.78) for the Cox model with smoothing splines. In prediction models for CVD events, the concordance was 0.64 (95% CI 0.63, 0.65) for two clusters, 0.66 (95% CI 0.65, 0.67) for four clusters, 0.77 (95% CI 0.77, 0.78) for the ordinary Cox model and 0.78 (95% CI 0.77, 0.78) for the Cox model with splines for all variables. CONCLUSIONS/INTERPRETATION: This nationwide observational study found no evidence supporting the existence of a specific number of distinct clusters within type 2 diabetes. The results from this study suggest that a prediction model approach using simple clinical features to predict risk of diabetes complications would be more useful than a cluster sub-stratification.

Diabetes mellitus was not associated with lower amputation-free survival after open revascularization for chronic limb-threatening ischemia - A nationwide propensity score adjusted analysis.

The risk of major amputation is higher after urgently planned endovascular therapy for chronic limb-threatening ischemia (CLTI) in patients with diabetes mellitus (DM). The aim of this nationwide cohort study was to compare outcomes between patients with and without DM following urgently planned open revascularization for CLTI from 2010 to 2014. Out of 1537 individuals registered in the Swedish Vascular Registry, 569 were registered in the National Diabetes Register. A propensity score adjusted Cox regression analysis was conducted to compare outcome between the groups with and without DM. Median follow-up was 4.3 years and 4.5 years for patients with and without DM, respectively. Patients with DM more often had foot ulcers (p = 0.034) and had undergone more previous amputations (p = 0.001) at baseline. No differences in mortality, cardiovascular death, major adverse cardiovascular events (MACE), or major amputation were observed between groups. The incidence rate of stroke was 70% higher (95% CI: 1.11-2.59; p = 0.0137) and the incidence rate of acute myocardial infarction (AMI) 39% higher (95% CI: 1.00-1.92; p = 0.0472) among patients with DM in comparison to those without. Open vascular surgery remains a first-line option for a substantial number of patients with CLTI, especially for limb salvage in patients with DM. The higher incidence rates of stroke and AMI among patients with DM following open vascular surgery for infrainguinal CLTI require specific consideration preoperatively with the aim of optimizing medical treatment to improve cardiovascular outcome postoperatively.

Effect of flash glucose monitoring in adults with type 1 diabetes: a nationwide, longitudinal observational study of 14,372 flash users compared with 7691 glucose sensor naive controls.

AIMS/HYPOTHESIS: The aim of this work was to evaluate changes in glycaemic control (HbA1c) and rates of severe hypoglycaemia over a 2 year period after initiation of flash glucose monitoring (FM) in type 1 diabetes. METHODS: Using data from the Swedish National Diabetes Registry, 14,372 adults with type 1 diabetes with a new registration of FM during 2016-2017 and with continued FM for two consecutive years thereafter, and 7691 control individuals using conventional self-monitoring of blood glucose (SMBG) during the same observation period, were included in a cohort study. Propensity sores and inverse probability of treatment weighting (IPTW) were used to balance FM users with SMBG users. Changes in HbA1c and events of severe hypoglycaemia were compared. RESULTS: After the start of FM, the difference in IPTW change in HbA1c was slightly greater in FM users compared with the control group during the follow-up period, with an estimated mean absolute difference of -1.2 mmol/mol (-0.11%) (95% CI -1.64 [-0.15], -0.75 [-0.07]; p < 0.0001) after 15-24 months. The change in HbA1c was greatest in those with baseline HbA1c ≥70 mmol/mol (8.5%), with the estimated mean absolute difference being -2.5 mmol/mol (-0.23%) (95% CI -3.84 [-0.35], -1.18 [-0.11]; p = 0.0002) 15-24 months post index. The change was also significant in the subgroups with initial HbA1c ≤52 mmol/mol (6.9%) and 53-69 mmol/mol (7.0-8.5%). Risk of severe hypoglycaemic episodes was reduced by 21% for FM users compared with control individuals using SMBG (OR 0.79 [95% CI 0.69, 0.91]; p = 0.0014)]. CONCLUSIONS/INTERPRETATION: In this large cohort, the use of FM was associated with a small and sustained improvement in HbA1c, most evident in those with higher baseline HbA1c levels. In addition, FM users experienced lower rates of severe hypoglycaemic events compared with control individuals using SMBG for self-management of glucose control.

Potential Effects of Bariatric Surgery on the Incidence of Heart Failure and Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus and Obesity and on Mortality in Patients With Preexisting Heart Failure: A Nationwide, Matched, Observational Cohort Study.

Background Obesity and diabetes mellitus are strongly associated with heart failure (HF) and atrial fibrillation (AF). The benefits of bariatric surgery on cardiovascular outcomes are known in people with or without diabetes mellitus. Surgical treatment of obesity might also reduce the incidence of HF and AF in individuals with obesity and type 2 diabetes mellitus (T2DM). Methods and Results In this register-based nationwide cohort study we compared individuals with T2DM and obesity who underwent Roux-en-Y gastric bypass surgery with matched individuals not treated with surgery. The main outcome measures were hospitalization for HF and/or AF and mortality in patients with preexisting HF. We identified 5321 individuals with T2DM and obesity who had undergone Roux-en-Y gastric bypass surgery between January 2007 and December 2013 and 5321 matched controls. The individuals included were 18 to 65 years old and had a body mass index >27.5 kg/m2. The follow-up time for hospitalization was until the end of 2015 (mean 4.5 years) and the end of 2016 for death. Our results show a 73% lower risk for HF (hazard ratio [HR], 0.27; CI, 0.19-0.38), 41% for AF (HR, 0.59; CI, 0.44-0.78), and 77% for concomitant AF and HF (HR, 0.23; CI, 0.12-0.46) in the surgically treated group. In patients with preexisting HF we observed significantly lower mortality in the group who underwent surgery (HR, 0.23; 95% CI, 0.12-0.43). Conclusions Bariatric surgery may reduce risk for HF and AF in patients with T2DM and obesity, speculatively via positive cardiovascular and renal effects. Obesity treatment with surgery may also be a valuable alternative in selected patients with T2DM and HF.

Cardiorenal and other diabetes related outcomes with SGLT-2 inhibitors compared to GLP-1 receptor agonists in type 2 diabetes: nationwide observational study.

BACKGROUND: Major prospective randomized clinical safety trials have demonstrated beneficial effects of treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in people with type 2 diabetes and elevated cardiovascular risk, and recent clinical treatment guidelines therefore promote early use of these classes of pharmacological agents. In this Swedish nationwide observational study, we compared cardiorenal outcomes and safety of new treatment with GLP-1RA and SGLT-2i in people with type 2 diabetes. METHODS: We linked data from national Swedish databases to capture patient characteristics and outcomes and used propensity-score based matching to account for differences between the two groups. The treatments were compared using Cox regression models. RESULTS: We identified 9648 participants starting GLP-1RA and 12,097 starting SGLT-2i with median follow-up times 1.7 and 1.1 years, respectively. The proportion of patients with a history of MACE were 15.8%, and 17.0% in patients treated with GLP-1RA and SGLT-2i, respectively. The mean age was 61 years with 7.6 years duration of diabetes. Mean HbA1c were 8.3% (67.6 mmol/mol) and 8.3% (67.2 mmol/mol), and mean BMI 33.3 and 32.5 kg/m2 in patients treated with GLP-1RA or SGLT-2i, respectively. The cumulative mortality risk was non-significantly lower in the group treated with SGLT-2i, HR 0.78 (95% CI 0.61-1.01), as were incident heart failure outcomes, but the risks of cardiovascular or renal outcomes did not differ. The risks of stroke and peripheral artery disease were higher in the SGLT-2i group relative to GLP-1RA, with HR 1.44 (95% CI 0.99-2.08) and 1.68 (95% CI 1.04-2.72), respectively. CONCLUSIONS: This observational study suggests that treatment with GLP-1RA and SGLT-2i result in very similar cardiorenal outcomes. In the short term, treatment with GLP-1RA seem to be associated with lower risks of stroke and peripheral artery disease, whereas SGLT-2i seem to be nominally associated with lower risk of heart failure and total mortality.

The impact of diabetes mellitus on major amputation among patients with chronic limb threatening ischemia undergoing elective endovascular therapy- a nationwide propensity score adjusted analysis.

AIM: To investigate the risk of major amputation after elective endovascular therapy in patients with chronic limb threatening ischemia (CLTI) comparing patients with and without diabetes mellitus (DM). METHODS: In this nationwide cohort study, all patients registered in the Swedish Vascular Register after elective endovascular therapy for CLTI caused by infra-inguinal arterial disease from 2010 to 2014 were included. Among 4578 individuals, 2251 had DM and were registered in the National Diabetes Register between 2009 and 2014. A propensity score adjusted Cox regression analysis was conducted to compare outcomes between groups. Median follow-up was 4.0 and 3.6 years for patients with DM and without DM, respectively. RESULTS: The incidence rates of major amputation and acute myocardial infarction (AMI) were 43% (95% CI 1.23-1.67) and 37% (95% CI 1.13-1.67) higher, respectively, among patients with DM compared to patients without DM. There was no difference in mortality (HR 1.04, 95% CI 0.95-1.14). CONCLUSIONS: Patients with DM had a higher risk of major amputation and AMI compared to those without DM after elective endovascular therapy for CLTI. Prevention of DM with CLTI is of utmost importance to reduce the risk of adverse limb and cardiovascular outcomes.

Higher long-term cardiovascular morbidity after open surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes - a nationwide observational cohort study.

Background: Diabetes mellitus (DM) is a risk factor for peripheral arterial disease (PAD). Indications for open surgery in infrainguinal intermittent claudication (IC) are limited, and reports are lacking regarding outcomes in DM patients. Study aims were to compare short and long-term effects on major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, major amputation, and mortality after infrainguinal open surgery for IC in patients with and without DM, and to evaluate relationships between glycaemic control and outcomes. Methods: Nationwide observational cohort study of all patients registered in the Swedish Vascular Registry after planned infrainguinal open surgery for IC from January 1st 2010 to December 31st 2014. Patients registered in the National Diabetes Registry were compared with patients without diabetes by propensity score adjusted comparison of MACE, AMI, stroke, major amputation, and mortality. Results: After 30 days, there were no differences in MACE, AMI, stroke, major amputation, or mortality between patients with (n = 323, mean age 70.5 [SD 7.4] years, 92 [28.5%] females) and without (n = 679, mean age 69.7 years [SD 11.2], 234 [34.5%] females) DM. At last follow-up after median 5.2 years, patients with DM showed higher rates of MACE (Hazard ratio [HR] 1.33, confidence interval [CI] 1.08-1.62; p < 0.01), and AMI (HR 2.21, CI 1.46-3.35; p < 0.01) than patients without diabetes. Among DM patients, higher glycated haemoglobin (HbA1c) was associated with higher rates of MACE (HR 1.02, CI 1.00-1.03; p = 0.02), stroke (HR 1.05, CI 1.00-1.11; p = 0.04), and total mortality (HR 1.03, CI 1.01-1.06; p < 0.01), during follow-up, whereas duration of diabetes was associated with higher rate of major amputation (HR 1.08, CI 1.02-1.15; p < 0.01). Conclusions: DM patients showed higher rates of MACE and AMI in propensity score adjusted analysis five years after planned infrainguinal open surgery for IC. Higher HbA1c was associated with MACE, stroke, and total mortality in patients with DM, whereas longer duration of DM was associated with major amputation.

Treatment persistence in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists in clinical practice in Sweden.

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.

Worse cardiovascular prognosis after endovascular surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes.

BACKGROUND: Diabetes mellitus (DM) is an established risk factor for intermittent claudication (IC) and other manifestations of atherosclerotic peripheral arterial disease. Indications for surgery in infrainguinal IC are debated, and there are conflicting reports regarding its outcomes in patients with DM. Aims of this study were to compare both short- and long-term effects on total- and cardiovascular (CV) mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), stroke, and major amputation following infrainguinal endovascular surgery for IC in patients with and without DM. We also evaluated potential relationships between diabetic control and outcomes in patients with DM. METHODS: Nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Registry. Propensity score adjusted comparison of total and CV mortality, MACE, AMI, stroke, and major amputation after elective infrainguinal endovascular surgery for IC in 626 patients with and 1112 without DM at 30 postoperative days and after median 5.2 [interquartile range (IQR) 4.2-6.3] years of follow-up for patients with DM, and 5.4 (IQR 4.3-6.5) years for those without. RESULTS: In propensity score adjusted Cox regression after 30 postoperative days, there were no differences between groups in morbidity or mortality. At last follow-up, patients with DM showed higher rates of MACE [hazard ratio (HR) 1.26, confidence interval (CI) 1.07-1.48; p < 0.01], AMI (HR 1.48, CI 1.09-2.00; p = 0.01), and major amputation (HR 2.31, CI 1.24-4.32; p < 0.01). Among patients with DM, higher HbA1c was associated with higher total mortality during follow-up (HR 1.01, CI 1.00-1.03; p = 0.045). CONCLUSION: Patients with DM have higher rates of MACE, AMI, and major amputation in propensity score adjusted analysis during 5 years of follow-up after infrainguinal endovascular surgery for IC. Furthermore, HbA1c is associated with total mortality in patients with DM. Prevention and treatment of DM is important to improve cardiovascular and limb outcomes.

Potential Benefits and Harms of Gastric Bypass Surgery in Obese Individuals With Type 1 Diabetes: A Nationwide, Matched, Observational Cohort Study.

OBJECTIVE: To study the potential long-term benefits and possible complications of bariatric surgery in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In this register-based nationwide cohort study, we compared individuals with T1D and obesity who underwent Roux-en-Y gastric bypass (RYGB) surgery with patients with T1D and obesity matched for age, sex, BMI, and calendar time that did not undergo surgery. By linking the Swedish National Diabetes Register and Scandinavian Obesity Surgery Registry study individuals were included between 2007 and 2013. Outcomes examined included all-cause mortality, cardiovascular disease, stroke, heart failure, and hospitalization for serious hypo- or hyperglycemic events, amputation, psychiatric disorders, changes in kidney function, and substance abuse. RESULTS: We identified 387 individuals who had undergone RYGB and 387 control patients. Follow-up for hospitalization was up to 9 years. Analysis showed lower risk for cardiovascular disease (hazard ratio [HR] 0.43; 95% CI 0.20-0.9), cardiovascular death (HR 0.15; 95% CI 0.03-0.68), hospitalization for heart failure (HR 0.32; 95% CI 0.15-0.67), and stroke (HR 0.18; 95% CI 0.04-0.82) for the RYGB group. There was a higher risk for serious hyperglycemic events (HR 1.99; 95% CI 1.07-3.72) and substance abuse (HR 3.71; 95% CI 1.03-3.29) after surgery. CONCLUSIONS: This observational study suggests bariatric surgery may yield similar benefits on risk for cardiovascular outcomes and mortality in patients with T1D and obesity as for patients with type 2 diabetes. However, some potential serious adverse effects suggest need for careful monitoring of such patients after surgery.

Persistence with IDegLira in Patients in Clinical Practice: A Nationwide Observational Study in Sweden.

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.

Renal and Cardiovascular Outcomes After Weight Loss From Gastric Bypass Surgery in Type 2 Diabetes: Cardiorenal Risk Reductions Exceed Atherosclerotic Benefits.

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.

Efficacy and Safety of Treatment with New Basal Insulin Analogues in Type 1 Diabetes: Nation-Wide Survey.

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.

Adherence to lipid-lowering therapy and risk for cardiovascular disease and death in type 1 diabetes mellitus: a population-based study from the Swedish National Diabetes Register.

AIMS/HYPOTHESIS: Dyslipidemia is an important modifiable risk factor and lipid-lowering treatment (LLT) is essential to reduce the risk of cardiovascular disease (CVD). Studies in type 2 diabetes indicate that low adherence to statin therapy is a barrier to reach full protective potential, and less is known in type 1 diabetes (T1D). The aim was to assess risk of CVD by adherence and nonpersistence to LLT in T1D.  METHOD: A population-based study with a retrospective longitudinal design was conducted between 2006 and 2010, with follow-up until December 2013. In total, 6192 adult individuals with T1D, initiating LLT between 2006 and 2010, were included. Information on LLT, socioeconomic characteristics, comorbidities and cardiovascular events were collected. After 18 months, refill adherence was estimated by calculating medication possession ratio (MPR). Nonpersistence was defined as being without medicines on hand for at least 180 days. Individuals were thereafter followed until CVD, death or end of follow-up in December 2013. Cox regression analyses were performed to assess adherence level and nonpersistence of LLT as predictor of CVD. Analyses were adjusted for cardiovascular risk factors and socioeconomic status.   RESULTS: Mean MPR was 72%, 52% of the participants had an MPR above 80% and 27% discontinued LLT. There were 637 nonfatal and 58 fatal CVD events, mean follow-up 3.6 and 3.9 years, respectively. MPR above 80% was associated with reduced risk for nonfatal CVD compared with lower MPR, HR 0.78 (95% CI 0.65 to 0.93)). For fatal CVD, results indicated a negative effect of high adherence but the association did not reach statistical significance, HR 1.96 (0.96 to 4.01). Individuals discontinuing LLT had higher risk of nonfatal CVD, HR 1.43 (95% CI 1.18 to 1.73).  CONCLUSIONS/INTERPRETATION: In T1D, the risk for nonfatal CVD was lower among individuals with high adherence and higher among those discontinuing LLT within 18 months. It is important to evaluate and emphasize adherence to prescribed LLT at clinical visits to achieve treatment goals and reduce the risk of CVD.

Nationwide comparison of long-term survival and cardiovascular morbidity after acute aortic aneurysm repair in patients with and without type 2 diabetes.

OBJECTIVE: Epidemiologic data indicate decreased risk for development, growth, and rupture of abdominal aortic aneurysm (AAA) among patients with type 2 diabetes mellitus (DM). We therefore evaluated mortality and cardiovascular morbidity after acute repair of AAA in diabetic and nondiabetic patients. METHODS: In this nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Register, we compared mortality and morbidity after acute open (n = 1357 [61%]) or endovascular (n = 860 [39%]) repair of ruptured (n = 1469 [66%]) or otherwise symptomatic (n = 748 [34%]) AAAs in 363 patients with and 1854 patients without DM with propensity score-adjusted analysis. RESULTS: Follow-up was 3.91 years for patients with DM and 3.18 years for those without. In propensity-adjusted analysis, diabetic patients showed lower total mortality (relative risk [RR], 0.75; 95% confidence interval [CI], 0.59-0.95; P = .016) and cardiovascular mortality (RR, 0.17; 95% CI, 0.06-0.50; P = .01) than those without DM, whereas there were no differences in rates of major adverse cardiovascular events (RR, 1.10; 95% CI, 0.87-1.42; P = .42), acute myocardial infarction (RR, 1.36; 95% CI, 0.70-2.63; P = .37), or stroke (RR, 1.31; 95% CI, 0.84-2.03; P = .23). CONCLUSIONS: Patients with type 2 DM had lower rates of both total and cardiovascular mortality after acute AAA repair than those without DM, whereas rates of cardiovascular events, acute myocardial infarction, and stroke did not differ between groups. This might be explained by putative protective effects of DM on the aortic wall.

Survival, cardiovascular morbidity, and reinterventions after elective endovascular aortic aneurysm repair in patients with and without diabetes: A nationwide propensity-adjusted analysis.

Epidemiological data indicate decreased risk for development and growth of abdominal aortic aneurysm (AAA) among patients with diabetes mellitus (DM). On the other hand, DM adds to increased cardiovascular (CV) morbidity and mortality. In a nationwide observational cohort study of patients registered in the Swedish Vascular Register and the Swedish National Diabetes Register, we evaluated potential effects of DM on total mortality, CV morbidity, and the need for reintervention after elective endovascular aneurysm repair (EVAR) for AAA. We compared 748 patients with and 2630 without DM with propensity score-adjusted analysis, during a median 4.22 years of follow-up for patients with DM, and 4.05 years for those without. In adjusted analysis, diabetic patients showed higher rates of acute myocardial infarction (AMI) during follow-up (relative risk (RR) 1.44, 95% CI 1.06-1.95; p = 0.02), but lower need for reintervention (RR 0.12, CI 0.02-0.91; p = 0.04). There were no differences in total (RR 0.88, CI 0.74-1.05; p = 0.15) or CV (RR 1.58, CI 0.87-2.86; p = 0.13) mortality, or stroke (RR 0.95, CI 0.68-1.32; p = 0.75) during follow-up. In conclusion, patients with DM had higher rates of AMI and lower need for reintervention after elective EVAR than those without DM, whereas neither total nor CV mortality differed between groups. The putative protective effects of DM towards further AAA enlargement and late sac rupture may help explain the lower need for reintervention and absence of excess mortality.

Risk of cardiovascular event and mortality in relation to refill and guideline adherence to lipid-lowering medications among patients with type 2 diabetes mellitus in Sweden.

Objective: To analyze the risk of cardiovascular (CV) events and mortality in relation to adherence to lipid-lowering medications by healthcare centers and patients with type 2 diabetes mellitus (T2DM). Research design and methods: We included 121 914 patients (12% secondary prevention) with T2DM reported by 1363 healthcare centers. Patients initiated lipid-lowering medications between July 2006 and December 2012 and were followed from cessation of the first filled supply until multidose dispensed medications, migration, CV events, death or December 2016. The study period was divided into 4-month intervals through 2014, followed by annual intervals through 2016. Adherence measures were assessed for each interval. Patients' (refill) adherence was measured using the medication possession ratio (MPR). Healthcare centers' (guideline) adherence represented the prescription prevalence of lipid-lowering medications according to guidelines. The risk of CV events and mortality was analyzed for each interval using Cox proportional hazard regression and Kaplan-Meier. Results: Compared with high-adherent patients (MPR >80%), low-adherent primary prevention patients (MPR ≤80%) showed higher risk of all outcomes: 44%-51 % for CV events, doubled for all-cause mortality and 79%-90% for CV mortality. Corresponding risks for low-adherent secondary prevention patients were 17%-19% for CV events, 88%-97% for all-cause and 66%-79% for CV mortality. Primary prevention patients treated by low-adherent healthcare centers (guideline adherence <48%) had a higher risk of CV events and CV mortality. Otherwise, no difference in the risk of CV events or mortality was observed by guideline adherence level. Conclusions: Our results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.

Cardiovascular Disease in Patients with Type 2 Diabetes and in Patients Starting Empagliflozin Treatment: Nationwide Survey.

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.