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.

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.

Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

BACKGROUND: Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated. METHODS: In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes. RESULTS: The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range. Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death. CONCLUSIONS: Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.).

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.

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.

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.

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.

Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

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.

Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes.

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.).

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.

Risk Factors for Severe Liver Disease in Patients With Type 2 Diabetes.

BACKGROUND & AIMS: Type 2 diabetes is a risk factor for development of cirrhosis and hepatocellular carcinoma. However, risk factors that identify persons with the highest risk for these outcomes are missing from unselected, population-based cohorts. METHODS: The National Diabetes Register contains data on about 90% of persons in Sweden with type 2 diabetes. In this cohort study, persons with type 2 diabetes listed in the National Diabetes Register were compared with 5 individuals from the general population (controls), matched for age, sex, and county. In total, 406 770 persons with type 2 diabetes and 2 033 850 controls were included and followed for 21 596 934 person-years. We used population-based registers to determine the incidence of severe liver disease, defined as a diagnosis of hepatocellular carcinoma, cirrhosis, decompensation, liver failure and/or death due to liver disease during follow up. Cox regression was performed to estimate the risk of severe liver disease and to examine risk factors in persons with type 2 diabetes. RESULTS: Risk for severe liver disease was increased in patients with type 2 diabetes compared to controls (hazard ratio, 2.28; 95% CI, 2.21-2.36). Risk factors associated with severe liver disease in persons with type 2 diabetes were higher age, male sex, hypertension, higher body mass index, lower glomerular filtration rate, microalbuminuria, and smoking. Statins were associated with a decreased risk of severe liver disease. CONCLUSIONS: Persons with type 2 diabetes have an increased risk for severe liver disease. Knowledge of risk factors can be helpful in identifying persons with type 2 diabetes who have a high risk for severe liver disease.

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.

Long-term Survival and Cardiovascular Morbidity after Elective Open Aortic Aneurysm Repair in Patients with and without Type 2 Diabetes: A Nationwide Propensity-Adjusted Analysis.

BACKGROUND: Epidemiological data indicate decreased risk for development and growth of abdominal aortic aneurysm (AAA) among patients with diabetes mellitus (DM), but DM also goes with increased cardiovascular (CV) morbidity and mortality. We evaluated the effects of DM on mortality and CV morbidity after elective open AAA repair. METHODS: This is a nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Register. Comparison of mortality and CV morbidity after elective open AAA repair in 397 patients with and 1709 without DM with propensity score-adjusted analysis, during median 4.51 years of follow-up for patients with DM and 4.59 years for those without. RESULTS: In adjusted analysis, diabetic patients showed higher rates of acute myocardial infarction (AMI) (relative risk [RR] 1.57, 95% confidence interval [CI] 1.04-2.36; P = 0.03) and major adverse cardiovascular events (MACEs, RR 1.28, CI 1.04-1.58; P = 0.02) during follow-up, whereas there were no differences in total (RR 0.98, CI 0.75-1.29; P = 0.91) or CV (RR 0.30, CI 0.07-1.26; P = 0.10) mortality or stroke (RR 1.06, CI 0.67-1.67; P = 0.80). Among diabetic patients, higher HbA1c was related to a higher risk for AMI during follow-up (RR 1.04, CI 1.01-1.08; P = 0.02). CONCLUSIONS: Patients with DM had higher rates of AMI and MACE after elective open AAA repair than those without DM, whereas neither total nor CV mortality differed between groups. Putative beneficial effects of DM on the aortic wall might not be relevant after open surgery including thrombus removal and aneurysmorrhaphy.

Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

BACKGROUND: Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population. METHODS: We included all patients ≥18 years of age with T1DM who were registered in the Swedish National Diabetes Register from January 1, 1998, through December 31, 2014, a total of 33 333 patients, each matched for age and sex with 5 controls without diabetes mellitus randomly selected from the population. Patients with T1DM were categorized according to number of risk factors not at target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial infarction, heart failure hospitalization, and stroke was examined in relation to the number of risk factors at target. RESULTS: The mean follow-up was 10.4 years in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for each additional risk factor not at target. Adjusted hazard ratios for patients achieving all risk factor targets compared with controls were 1.31 (95% confidence interval [CI], 0.93-1.85) for all-cause mortality, 1.82 (95% CI, 1.15-2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04-3.73) for heart failure hospitalization, and 1.17 (95% CI, 0.51-2.68) for stroke. The hazard ratio for patients versus controls with none of the risk factors meeting target was 7.33 (95% CI, 5.08-10.57) for all-cause mortality, 12.34 (95% CI, 7.91-19.48) for acute myocardial infarction, 15.09 (95% CI, 9.87-23.09) for heart failure hospitalization, and 12.02 (95% CI, 7.66-18.85) for stroke. CONCLUSIONS: A steep-graded association exists between decreasing number of cardiovascular risk factors at target and major adverse cardiovascular outcomes among patients with T1DM. However, risks for all outcomes were numerically higher for patients with T1DM compared with controls, even when all risk factors were at target, with risk for acute myocardial infarction and heart failure hospitalization statistically significantly higher.

Prescription of lipid-lowering medications for patients with type 2 diabetes mellitus and risk-associated LDL cholesterol: a nationwide study of guideline adherence from the Swedish National Diabetes Register.

BACKGROUND: Management of type 2 diabetes mellitus (T2DM) encompasses intensive glycaemic control, along with treatment of comorbidities and complications to handle the increased risk of cardiovascular disease (CVD). Improved control of LDL-cholesterol (LDL-C) with lipid-lowering medications is associated with reduced CVD risk in T2DM patients. Thus, treatment guidelines recommend lipid-lowering medications for T2DM patients with LDL-C above risk-associated thresholds. This study aimed to assess healthcare provider adherence to guidelines regarding lipid-lowering medication prescription among T2DM patients and to analyse factors associated with lipid-lowering medication prescription. METHODS: Observations in 2007 - 2014 for T2DM patients age ≥ 18 were collected from the Swedish National Diabetes Register. Observations were excluded if they lacked information about LDL-C, lipid-lowering medication prescription or CVD. Observations with established CVD were attributed to secondary prevention; remaining observations were attributed to primary prevention. The analyses included primary and secondary prevention observations with LDL-C above risk-associated thresholds (LDL-C ≥ 2.5 mmol/l and LDL-C ≥ 1.8 mmol/l respectively). Guideline adherence was analysed as the probability of prescribing lipid-lowering medications using mixed-effect model regression adjusted for potential confounders. Factors associated with prescribing lipid-lowering medications were analysed for patient and healthcare provider characteristics using mixed-effect model regression and odds ratio. RESULTS: A total of 1,204,376 observations from 322,046 patients reported by 1352 healthcare providers were included. Primary prevention accounted for 63%; 52% were men, mean age was 64 and mean LDL-C was 3.4 mmol/l. For secondary prevention, 60% were men, mean age was 72 and mean LDL-C was 2.7 mmol/l. During 2007-2014, guideline adherence ranged from 36 to 47% for primary prevention and 59 to 69% for secondary prevention. In general, concomitant prescription of diabetes medications, antiplatelets and antihypertensives along with smoking and specialised care were associated with higher prescription of lipid-lowering medications. Patients age ≥ 80 were associated with lower prescription of lipid-lowering medications. Higher prescription was associated with longer diabetes duration in primary prevention and men in secondary prevention. CONCLUSIONS: Adherence to treatment guidelines levelled off after an initial increase in both prevention groups. Lipid-lowering medication prescription was based on individualised CVD risk.

Refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes: A nation-wide register-based study.

PURPOSE: This study aimed to describe and compare refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes by previous cardiovascular disease (CVD). METHODS: We followed 97 595 patients (58% men; 23% with previous CVD) who were 18 years of age or older when initiating lipid-lowering medicines in 2007-2010 until first fill of multi-dose dispensed medicines, death, or 3 years. Using personal identity numbers, we linked individuals' data from the Swedish Prescribed Drug Register, the Swedish National Diabetes Register, the National Patient Register, the Cause of Death Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. We assessed refill adherence using the medication possession ratio (MPR) and the maximum gap method, and measured persistence from initiation to discontinuation of treatment or until 3 years after initiation. We analyzed differences in refill adherence and persistence by previous CVD in multiple regression models, adjusted for socioeconomic status, concurrent medicines, and clinical characteristics. RESULTS: The mean age of the study population was 64 years, 80% were born in Sweden, and 56% filled prescriptions for diabetes medicines. Mean MPR was 71%, 39% were adherent according to the maximum gap method, and mean persistence was 758 days. Patients with previous CVD showed higher MPR (3%) and lower risk for discontinuing treatment (12%) compared with patients without previous CVD (P < 0.0001). CONCLUSIONS: Patients with previous CVD were more likely to be adherent to treatment and had lower risk for discontinuation compared with patients without previous CVD.

Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register.

AIM: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. RESULTS: Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. CONCLUSIONS: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality.

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.

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.

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.