Diabetes-related risk factors and survival among individuals with type 2 diabetes and breast, lung, colorectal, or prostate cancer.

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.

Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study.

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.

Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data.

The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals. ASSET (AI for Sustainable Prevention of Autoimmunity in the Society; www.asset.healthcare ) is a public/private consortium that was established to contribute to research around screening for type 1 diabetes and particularly to how AI can drive the implementation of a precision medicine approach to disease prevention. ASSET will additionally focus on issues pertaining to operational implementation of screening. The authors of this article, researchers and clinicians active in the field of type 1 diabetes, met in an open forum to independently debate key issues around screening for type 1 diabetes and to advise ASSET. The potential use of AI in the analysis of longitudinal data from observational cohort studies to inform the design of improved, more individualised screening programmes was also discussed. A key issue was whether AI would allow the research community and industry to capitalise on large publicly available data repositories to design screening programmes that allow the early detection of individuals at high risk and enable clinical evaluation of preventive therapies. Overall, AI has the potential to revolutionise type 1 diabetes screening, in particular to help identify individuals who are at increased risk of disease and aid in the design of appropriate follow-up plans. We hope that this initiative will stimulate further research on this very timely topic.

Risk Factors for and Risk of Peripheral Artery Disease in Swedish Individuals With Type 2 Diabetes: A Nationwide Register-Based Study.

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.

Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A Scandinavian cohort study.

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.

The correlation between small papillary thyroid cancers and gamma radionuclides Cs-137, Th-232, U-238 and K-40 using spatially-explicit, register-based methods.

A steep increase of small papillary thyroid cancers (sPTCs) has been observed globally. A major risk factor for developing PTC is ionizing radiation. The aim of this study is to investigate the spatial distribution of sPTC in Sweden and the extent to which prevalence is correlated to gamma radiation levels (Caesium-137 (Cs-137), Thorium-232 (Th-232), Uranium-238 (U-238) and Potassium-40 (K-40)) using multiple geospatial and geostatistical methods. The prevalence of metastatic sPTC was associated with significantly higher levels of Gamma radiation from Th-232, U-238 and K-40. The association is, however, inconsistent and the prevalence is higher in densely populated areas. The results clearly indicate that sPTC has causative factors that are neither evenly distributed among the population, nor geographically, calling for further studies with bigger cohorts. Environmental factors are believed to play a major role in the pathogenesis of the disease.

Educational Outcomes in Children and Adolescents With Type 1 Diabetes and Psychiatric Disorders.

Importance: Research shows that children and adolescents with type 1 diabetes (T1D), compared with their peers without diabetes, have a greater risk of psychiatric disorders. However, no study has comprehensively examined whether having psychiatric disorders is associated with educational outcomes in children and adolescents with T1D. Objective: To investigate educational outcomes in children and adolescents with T1D with and without psychiatric disorders. Design, Setting, and Participants: This cohort study used data from multiple Swedish registers. The main study cohort included individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed up from birth through December 31, 2013. Data analyses were conducted from March 1 to June 30, 2022. Exposures: Type 1 diabetes and psychiatric disorders (including neurodevelopmental disorders, depression, anxiety disorders, eating disorders, bipolar disorder, psychotic disorder, and substance misuse) diagnosed before 16 years of age. Main Outcomes and Measures: Achieving educational milestones (completing compulsory school [primary and lower secondary education], being eligible to and finishing upper secondary school, and starting and finishing university) and compulsory school performances. Results: Of 2 454 862 individuals (51.3% male), 13 294 (0.5%; 53.9% male) were diagnosed with T1D (median [IQR] age at diagnosis, 9.5 [6.0-12.5] years), among whom 1012 (7.6%) also had at least 1 psychiatric disorder. Compared with healthy individuals (without T1D and psychiatric disorders), individuals with T1D alone had slightly lower odds of achieving the examined educational milestones. However, those with both T1D and any psychiatric disorder had much lower odds of achieving milestones, including completing compulsory school (odds ratio [OR], 0.17; 95% CI, 0.13-0.21), being eligible for (OR, 0.25; 95% CI, 0.21-0.30) and finishing (OR, 0.19; 95% CI, 0.14-0.26) upper secondary school, and starting (OR, 0.36; 95% CI, 0.29-0.46) and finishing (OR, 0.30; 95% CI, 0.20-0.47) university. They also showed lower grade point averages for compulsory school subjects. These findings remained similar in sibling comparison analyses, suggesting independence from familial confounding. Conclusions and Relevance: In this cohort study of Swedish-born children and adolescents, those with T1D alone had minor difficulties with their educational outcomes, whereas those with both T1D and psychiatric disorders had universal long-term educational underachievement. These findings highlight the importance of identifying psychiatric disorders in pediatric patients with T1D and the need for targeted educational intervention and support to minimize the education gap between the affected children and their peers.

Use of incretin-based drugs and risk of cholangiocarcinoma: Scandinavian cohort study.

AIMS/HYPOTHESIS: Concerns have been raised regarding a potential association of use of the incretin-based drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1)-receptor agonists with risk of cholangiocarcinoma. We examined this association in nationwide data from three countries. METHODS: We used data from nationwide registers in Sweden, Denmark and Norway, 2007-2018, to conduct two cohort studies, one for DPP4 inhibitors and one for GLP-1-receptor agonists, to investigate the risk of incident cholangiocarcinoma compared with an active-comparator drug class (sulfonylureas). The cohorts included patients initiating treatment episodes with DPP4 inhibitors vs sulfonylureas, and GLP-1-receptor agonists vs sulfonylureas. We used Cox regression models, adjusted for potential confounders, to estimate hazard ratios from day 366 after treatment initiation to account for cancer latency. RESULTS: The main analyses of DPP4 inhibitors included 1,414,144 person-years of follow-up from 222,577 patients receiving DPP4 inhibitors (median [IQR] follow-up time, 4.5 [2.6-7.0] years) and 123,908 patients receiving sulfonylureas (median [IQR] follow-up time, 5.1 [2.9-7.8] years) during which 350 cholangiocarcinoma events occurred. Use of DPP4 inhibitors, compared with sulfonylureas, was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.15 [95% CI 0.90, 1.46]; absolute rate difference 3 [95% CI -3, 10] events per 100,000 person-years). The main analyses of GLP-1-receptor agonists included 1,036,587 person-years of follow-up from 96,813 patients receiving GLP-1-receptor agonists (median [IQR] follow-up time, 4.4 [2.4-6.9] years) and 142,578 patients receiving sulfonylureas (median [IQR] follow-up time, 5.5 [3.2-8.1] years) during which 249 cholangiocarcinoma events occurred. Use of GLP-1-receptor agonists was not associated with a statistically significant increase in risk of cholangiocarcinoma (incidence rate 26 vs 23 per 100,000 person-years; adjusted HR, 1.25 [95% CI 0.89, 1.76]; absolute rate difference 3 [95% CI -5, 13] events per 100,000 patient-years). CONCLUSIONS/INTERPRETATION: In this analysis using nationwide data from three countries, use of DPP4 inhibitors and GLP-1-receptor agonists, compared with sulfonylureas, was not associated with a significantly increased risk of cholangiocarcinoma.

A national observation study of cancer incidence and mortality risks in type 2 diabetes compared to the background population over time.

We examined changing patterns in cancer incidence and deaths in diabetes compared to the background population. A total of 457,473 patients with type 2 diabetes, included between 1998 and 2014, were matched on age, sex, and county to five controls from the population. Incidence, trends in incidence and post-cancer mortality for cancer were estimated with Cox regression and standardised incidence rates. Causes of death were estimated using logistic regression. Relative importance of risk factors was estimated using Heller's relative importance model. Type 2 diabetes had a higher risk for all cancer, HR 1.10 (95% CI 1.09-1.12), with highest HRs for liver (3.31), pancreas (2.19) and uterine cancer (1.78). There were lesser increases in risk for breast (1.05) and colorectal cancers (1.20). Type 2 diabetes patients experienced a higher HR 1.23 (1.21-1.25) of overall post-cancer mortality and mortality from prostate, breast, and colorectal cancers. By the year 2030 cancer could become the most common cause of death in type 2 diabetes. Persons with type 2 diabetes are at greater risk of developing cancer and lower chance of surviving it. Notably, hazards for specific cancers (e.g. liver, pancreas) in type 2 patients cannot be explained by obesity alone.

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.

Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study.

OBJECTIVE: To assess the association between use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and risk of serious renal events in data from routine clinical practice. DESIGN: Cohort study using an active comparator, new user design and nationwide register data. SETTING: Sweden, Denmark, and Norway, 2013-18. PARTICIPANTS: Cohort of 29 887 new users of SGLT2 inhibitors (follow-up time: dapagliflozin 66.1%; empagliflozin 32.6%; canagliflozin 1.3%) and 29 887 new users of an active comparator, dipeptidyl peptidase-4 inhibitors, matched 1:1 on the basis of a propensity score with 57 variables. Mean follow-up time was 1.7 (SD 1.0) years. EXPOSURES: SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors, defined by filled prescriptions and analysed according to intention to treat. MAIN OUTCOME MEASURES: The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospital admission for renal events. Secondary outcomes were the individual components of the main outcome. RESULTS: The mean age of the study population was 61.3 (SD 10.5) years; 11 108 (19%) had cardiovascular disease, and 1974 (3%) had chronic kidney disease. Use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a reduced risk of serious renal events (2.6 events per 1000 person years versus 6.2 events per 1000 person years; hazard ratio 0.42 (95% confidence interval 0.34 to 0.53); absolute difference -3.6 (-4.4 to -2.8) events per 1000 person years). In secondary outcome analyses, the hazard ratio for use of SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors was 0.32 (0.22 to 0.47) for renal replacement therapy, 0.41 (0.32 to 0.52) for hospital admission for renal events, and 0.77 (0.26 to 2.23) for death from renal causes. In sensitivity analyses in each of the Swedish and Danish parts of the cohort, the model was further adjusted for glycated haemoglobin and estimated glomerular filtration rate (Sweden and Denmark) and for blood pressure, body mass index, and smoking (Sweden only); in these analyses, the hazard ratio moved from 0.41 (0.26 to 0.66) to 0.50 (0.31 to 0.81) in Sweden and from 0.42 (0.32 to 0.56) to 0.55 (0.41 to 0.74) in Denmark. CONCLUSIONS: In this analysis using nationwide data from three countries, use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a significantly reduced risk of serious renal events.

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.

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.

Pros and cons of gastric bypass surgery in individuals with obesity and type 2 diabetes: nationwide, matched, observational cohort study.

OBJECTIVES: Long-term effects of gastric bypass (GBP) surgery have been presented in observational and randomised studies, but there are only limited data for persons with obesity and type 2 diabetes mellitus (T2DM) regarding postoperative complications. DESIGN: This is a nationwide observational study based on two quality registers in Sweden (National Diabetes Register, NDR and Scandinavian Obesity Surgery Register, SOReg) and other national databases. SETTING: After merging the data, we matched individuals with T2DM who had undergone GBP with those not surgically treated for obesity on propensity score, based on sex, age, body mass index (BMI) and calendar time. The risks of postoperative outcomes (rehospitalisations) were assessed using Cox regression models. PARTICIPANTS: We identified 5321 patients with T2DM in the SOReg and 5321 matched controls in the NDR, aged 18-65 years, with BMI >27.5 kg/m² and followed for up to 9 years. PRIMARY AND SECONDARY OUTCOME MEASURES: We assessed risks for all-cause mortality and hospitalisations for cardiovascular disease, severe kidney disease, along with surgical and other medical conditions. RESULTS: The results agree with the previously suggested lower risks of all-cause mortality (49%) and cardiovascular disease (34%), and we also found positive effects for severe kidney disease but significantly increased risks (twofold to ninefold) of several short-term complications after GBP, such as abdominal pain and gastrointestinal conditions, frequently requiring surgical procedures, apart from reconstructive plastic surgery. Long-term, the risk of anaemia was 92% higher, malnutrition developed approximately three times as often, psychiatric diagnoses were 33% more frequent and alcohol abuse was three times as great as in the control group. CONCLUSIONS: This nationwide study confirms the benefits and describes the panorama of adverse events after bariatric surgery in persons with obesity and T2DM. Long-term postoperative monitoring and support, as better selection of patients by appropriate specialists in interdisciplinary settings, should be provided to optimise the outcomes.

Prediction of individual life-years gained without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with Type 2 diabetes mellitus.

AIMS: Although group-level effectiveness of lipid, blood pressure, glucose, and aspirin treatment for prevention of cardiovascular disease (CVD) has been proven by trials, important differences in absolute effectiveness exist between individuals. We aim to develop and validate a prediction tool for individualizing lifelong CVD prevention in people with Type 2 diabetes mellitus (T2DM) predicting life-years gained without myocardial infarction or stroke. METHODS AND RESULTS: We developed and validated the Diabetes Lifetime-perspective prediction (DIAL) model, consisting of two complementary competing risk adjusted Cox proportional hazards functions using data from people with T2DM registered in the Swedish National Diabetes Registry (n = 389 366). Competing outcomes were (i) CVD events (vascular mortality, myocardial infarction, or stroke) and (ii) non-vascular mortality. Predictors were age, sex, smoking, systolic blood pressure, body mass index, haemoglobin A1c, estimated glomerular filtration rate, non- high-density lipoprotein cholesterol, albuminuria, T2DM duration, insulin treatment, and history of CVD. External validation was performed using data from the ADVANCE, ACCORD, ASCOT and ALLHAT-LLT-trials, the SMART and EPIC-NL cohorts, and the Scottish diabetes register (total n = 197 785). Predicted and observed CVD-free survival showed good agreement in all validation sets. C-statistics for prediction of CVD were 0.83 (95% confidence interval: 0.83-0.84) and 0.64-0.65 for internal and external validation, respectively. We provide an interactive calculator at www.U-Prevent.com that combines model predictions with relative treatment effects from trials to predict individual benefit from preventive treatment. CONCLUSION: Cardiovascular disease-free life expectancy and effects of lifelong prevention in terms of CVD-free life-years gained can be estimated for people with T2DM using readily available clinical characteristics. Predictions of individual-level treatment effects facilitate translation of trial results to individual patients.

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.).

PCI Versus CABG in Patients With Type 1 Diabetes and Multivessel Disease.

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.

Changes in risk factors and their contribution to reduction of mortality risk following gastric bypass surgery among obese individuals with type 2 diabetes: a nationwide, matched, observational cohort study.

OBJECTIVE: We recently showed that Roux-en-Y gastric bypass (RYGB) reduces risks of mortality, cardiovascular death and myocardial infarction in obese individuals compared with matched patients with diabetes mellitus (DM). We have examined changes in risk factors after RYGB, with the aim of explaining these effects. RESEARCH DESIGN AND METHODS: We matched (1:1) 6132 RYGB patients with DM reported to the Scandinavian Obesity Surgery Register with patients who had not undergone RYGB, based on sex, age, body mass index (BMI) and time, and assessed effects 2007-2014. We used causal mediation analysis to study effects mediated through changes to BMI and risk factors at 1 year based on Cox proportional hazards models. RESULTS: Baseline BMI was 42 kg/m2. Following RYGB, the lowest BMI was observed after 2 years (mean 31.9 kg/m2), and hemoglobin A1c (HbA1c) after 1 year (mean 6.32% (45.6 mmol/mol)). Maximum high-density lipoprotein (HDL) cholesterol was observed after 3-5 years (mean 1.46 mmol/L). Differences in BMI, HbA1c and HDL between the groups were statistically significant up to 6 years, and 2-3 years for low-density lipoprotein (LDL) and blood pressure, despite fewer glucose-lowering, hypertensive and lipid-lowering treatments. The causal mediation analysis suggested that RYGB has a positive effect on mortality risk, mainly by means of weight reduction (as opposed to changes to the risk factors analyzed). CONCLUSIONS: Improvements in risk factors might contribute to the reduction of mortality risk after RYGB in obese individuals with type 2 diabetes, but the main effect seems to be mediated through a decrease in BMI, which could serve as a proxy for several mechanisms.