Dataset Information

Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity.

ABSTRACT:

Importance

Although metabolic surgery (defined as procedures that influence metabolism by inducing weight loss and altering gastrointestinal physiology) significantly improves cardiometabolic risk factors, the effect on cardiovascular outcomes has been less well characterized.

Objective

To investigate the relationship between metabolic surgery and incident major adverse cardiovascular events (MACE) in patients with type 2 diabetes and obesity.

Design, setting, and participants

Of 287 438 adult patients with diabetes in the Cleveland Clinic Health System in the United States between 1998 and 2017, 2287 patients underwent metabolic surgery. In this retrospective cohort study, these patients were matched 1:5 to nonsurgical patients with diabetes and obesity (body mass index [BMI] ≥30), resulting in 11 435 control patients, with follow-up through December 2018.

Exposures

Metabolic gastrointestinal surgical procedures vs usual care for type 2 diabetes and obesity.

Main outcomes and measures

The primary outcome was the incidence of extended MACE (composite of 6 outcomes), defined as first occurrence of all-cause mortality, coronary artery events, cerebrovascular events, heart failure, nephropathy, and atrial fibrillation. Secondary end points included 3-component MACE (myocardial infarction, ischemic stroke, and mortality) and the 6 individual components of the primary end point.

Results

Among the 13 722 study participants, the distribution of baseline covariates was balanced between the surgical group and the nonsurgical group, including female sex (65.5% vs 64.2%), median age (52.5 vs 54.8 years), BMI (45.1 vs 42.6), and glycated hemoglobin level (7.1% vs 7.1%). The overall median follow-up duration was 3.9 years (interquartile range, 1.9-6.1 years). At the end of the study period, 385 patients in the surgical group and 3243 patients in the nonsurgical group experienced a primary end point (cumulative incidence at 8-years, 30.8% [95% CI, 27.6%-34.0%] in the surgical group and 47.7% [95% CI, 46.1%-49.2%] in the nonsurgical group [P < .001]; absolute 8-year risk difference [ARD], 16.9% [95% CI, 13.1%-20.4%]; adjusted hazard ratio [HR], 0.61 [95% CI, 0.55-0.69]). All 7 prespecified secondary outcomes showed statistically significant differences in favor of metabolic surgery, including mortality. All-cause mortality occurred in 112 patients in the metabolic surgery group and 1111 patients in the nonsurgical group (cumulative incidence at 8 years, 10.0% [95% CI, 7.8%-12.2%] and 17.8% [95% CI, 16.6%-19.0%]; ARD, 7.8% [95% CI, 5.1%-10.2%]; adjusted HR, 0.59 [95% CI, 0.48-0.72]).

Conclusions and relevance

Among patients with type 2 diabetes and obesity, metabolic surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident MACE. The findings from this observational study must be confirmed in randomized clinical trials.

Trial registration

ClinicalTrials.gov Identifier: NCT03955952.

SUBMITTER: Aminian A

PROVIDER: S-EPMC6724187 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThere are high-quality randomized clinical trial data demonstrating the effect of bariatric surgery on type 2 diabetes remission, but these studies are not powered to study mortality in this patient group. Large observational studies are warranted to study the association of bariatric surgery with mortality in patients with type 2 diabetes.ObjectiveTo determine the association between bariatric surgery and all-cause mortality among patients with type 2 diabetes and severe obesity.Design, setting, and participantsThis retrospective, population-based matched cohort study included patients with type 2 diabetes and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) 35 or greater who underwent bariatric surgery from January 2010 to December 2016 in Ontario, Canada. Multiple linked administrative databases were used to define confounders, including age, baseline BMI, sex, comorbidities, duration of diabetes diagnosis, health care utilization, socioeconomic status, smoking status, substance abuse, cancer screening, and psychiatric history. Potential controls were identified from a primary care electronic medical record database. Data were analyzed in 2020.ExposureBariatric surgery (gastric bypass and sleeve gastrectomy) and nonsurgical management of obesity provided by the primary care physician.Main outcomes and measuresThe primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality and nonfatal morbidities. Groups were compared through a multivariable Cox proportional Hazards model.ResultsA total of 6910 patients (mean [SD] age at baseline, 52.04 [9.45] years; 4950 [71.6%] women) were included, with 3455 patients who underwent bariatric surgery and 3455 match controls and a median (interquartile range) follow-up time of 4.6 (3.22-6.35) years. In the surgery group, 83 patients (2.4%) died, compared with 178 individuals (5.2%) in the control group (hazard ratio [HR] 0.53 [95% CI, 0.41-0.69]; P < .001). Bariatric surgery was associated with a 68% lower cardiovascular mortality (HR, 0.32 [95% CI, 0.15-0.66]; P = .002) and a 34% lower rate of composite cardiac events (HR, 0.68 [95% CI, 0.55-0.85]; P < .001). Risk of nonfatal renal events was also 42% lower in the surgical group compared with the control group (HR, 0.58 [95% CI, 0.35-0.95], P = .03). Of the groups that had the highest absolute benefit associated with bariatric surgery, men had an absolute risk reduction (ARR) of 3.7% (95% CI, 1.7%-5.7%), individuals with more than 15 years of diabetes had an ARR of 4.3% (95% CI, 0.8%-7.8%), and individuals aged 55 years or older had an ARR of 4.7% (95% CI, 3.0%-6.4%).Conclusions and relevanceThese findings suggest that bariatric surgery was associated with reduced all-cause mortality and diabetes-specific cardiac and renal outcomes in patients with type 2 diabetes and severe obesity.

Project description:BackgroundWith the increasing prevalence of obesity and type 2 diabetes, the availability of different treatment options remains essential. Studies comparing the outcomes of glucagon-like peptide 1 receptor agonists with those of metabolic bariatric surgery in patients with type 2 diabetes and obesity are lacking.MethodsUsing propensity score matching, based on data from several nationwide clinical registries, patients who underwent primary metabolic bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) were matched with patients who received glucagon-like peptide 1 receptor agonists. Outcome measures included the occurrence of major cardiovascular events, microvascular complications, and potential side effects (alcohol/substance abuse, self-harm, and fractures).ResultsOver a mean follow-up of 7 years, major cardiovascular events occurred in 191 of 2039 patients (cumulative incidence 14.5%) in the surgery group compared with 247 of 2039 patients (19.6%) in the glucagon-like peptide 1 receptor agonist group (HR 0.75 (95% c.i. 0.62 to 0.91), P = 0.003). Patients in the surgery group had lower haemoglobin A1c values 5 years after treatment (mean difference 9.82 (95% c.i. 8.51 to 11.14) mmol/mol, P < 0.001) and fewer microvascular complications (retinopathy HR 0.88 (95% c.i. 0.79 to 0.99), P = 0.039; nephropathy HR 0.72 (95% c.i. 0.66 to 0.80), P < 0.001; and neuropathy or leg ulcers HR 0.82 (95% c.i. 0.74 to 0.92), P < 0.001), but a higher risk of alcohol/substance abuse (HR 2.56 (95% c.i. 1.87 to 3.50), P < 0.001), self-harm (HR 1.41 (95% c.i. 1.17 to 1.71), P < 0.001), and fractures (HR 1.86 (95% c.i. 1.11 to 3.12), P = 0.019).ConclusionCompared with glucagon-like peptide 1 receptor agonist treatment, metabolic bariatric surgery is associated with superior metabolic outcomes and a lower risk of major cardiovascular events in patients with type 2 diabetes and obesity, but a higher risk of alcohol/substance abuse, self-harm, and fractures.

Project description:ImportanceNo therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH).ObjectiveTo investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis.Design, setting, and participantsIn the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021.ExposuresBariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care.Main outcomes and measuresThe primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework.ResultsA total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2).Conclusions and relevanceAmong patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.

Project description:BackgroundThe triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM.MethodsThis post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients' (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed.ResultsOver a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17-2.16), 1.97 (95% CI 1.19-3.26), and 1.66 (95% CI 1.02-2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value.ConclusionsIn patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs. Trial registration URL: http://www.Clinicaltrialsgov . Unique identifier: NCT00000620.

Project description:BackgroundAlthough recent guidelines advocate for HbA1c target individualization, a comprehensive criterion for patient categorization remains absent. This study aimed to categorize HbA1c variability levels and explore the relationship between glycemic control, cardiovascular outcomes, and mortality across different degrees of variability.MethodsAction to Control Cardiovascular Risk in Diabetes study data were used. HbA1c variability was measured using the HbA1c variability score (HVS) and standard deviation (SD). K-means and K-medians clustering were used to combine the HVS and SD.ResultsK-means clustering was the most stable algorithm with the lowest clustering similarities. In the low variability group, intensive glucose-lowering treatment significantly reduced the risk of adverse cardiovascular outcomes (HR: 0·78 [95% CI: 0·63, 0·97]) without increasing mortality risk (HR: 1·07 [0.81, 1·42]); the risk of adverse cardiovascular events (HR: 1·33 [1·14, 1·56]) and all-cause mortality (HR: 1·23 [1·01,1·51]) increased with increasing mean HbA1c. In the high variability group, treatment increased the risk of cardiovascular events (HR: 2.00 [1·54, 2·60]) and mortality (HR: 2·20 [1·66, 2·92]); a higher mean HbA1c (7·86%, [7·66%, 8·06%]) had the lowest mortality risk, when the mean HbA1c was < 7·86%, a higher mean HbA1c was associated with a lower mortality risk (HR: 0·63 [0·42, 0·95]). In the medium variability group, a mean HbA1c around 7·5% was associated with the lowest risk.ConclusionsHbA1c variability can guide glycemic control targets for patients with type 2 diabetes. For patients with low variability, the lower the HbA1c, the lower the risk. For those with medium variability, controlling HbA1c at 7·5% provides the maximum benefit. For patients with high variability, a mean HbA1c of around 7·8% presents the lowest risk of all-cause mortality, a lower HbA1c did not provide cardiovascular benefits but instead increased the mortality risk. Further studies, especially those with patients that reflect the general population with type 2 diabetes undergoing the latest therapeutic approaches, are essential to validate the conclusions of this study.

Project description:ImportanceMacrovascular disease is a leading cause of morbidity and mortality for patients with type 2 diabetes, and medical management, including lifestyle changes, may not be successful at lowering risk.ObjectiveTo investigate the relationship between bariatric surgery and incident macrovascular (coronary artery disease and cerebrovascular diseases) events in patients with severe obesity and type 2 diabetes.Design, setting, and participantsIn this retrospective, matched cohort study, patients with severe obesity (body mass index ≥35) aged 19 to 79 years with diabetes who underwent bariatric surgery from 2005 to 2011 in 4 integrated health systems in the United States (n = 5301) were matched to 14 934 control patients on site, age, sex, body mass index, hemoglobin A1c, insulin use, observed diabetes duration, and prior health care utilization, with follow-up through September 2015.ExposuresBariatric procedures (76% Roux-en-Y gastric bypass, 17% sleeve gastrectomy, and 7% adjustable gastric banding) were compared with usual care for diabetes.Main outcomes and measuresMultivariable-adjusted Cox regression analysis investigated time to incident macrovascular disease (defined as first occurrence of coronary artery disease [acute myocardial infarction, unstable angina, percutaneous coronary intervention, or coronary artery bypass grafting] or cerebrovascular events [ischemic stroke, hemorrhagic stroke, carotid stenting, or carotid endarterectomy]). Secondary outcomes included coronary artery disease and cerebrovascular outcomes separately.ResultsAmong a combined 20 235 surgical and nonsurgical patients, the mean (SD) age was 50 (10) years; 76% of the surgical and 75% of the nonsurgical patients were female; and the baseline mean (SD) body mass index was 44.7 (6.9) and 43.8 (6.7) in the surgical and nonsurgical groups, respectively. At the end of the study period, there were 106 macrovascular events in surgical patients (including 37 cerebrovascular and 78 coronary artery events over a median of 4.7 years; interquartile range, 3.2-6.2 years) and 596 events in the matched control patients (including 227 cerebrovascular and 398 coronary artery events over a median of 4.6 years; interquartile range, 3.1-6.1 years). Bariatric surgery was associated with a lower composite incidence of macrovascular events at 5 years (2.1% in the surgical group vs 4.3% in the nonsurgical group; hazard ratio, 0.60 [95% CI, 0.42-0.86]), as well as a lower incidence of coronary artery disease (1.6% in the surgical group vs 2.8% in the nonsurgical group; hazard ratio, 0.64 [95% CI, 0.42-0.99]). The incidence of cerebrovascular disease was not significantly different between groups at 5 years (0.7% in the surgical group vs 1.7% in the nonsurgical group; hazard ratio, 0.69 [95% CI, 0.38-1.25]).Conclusions and relevanceIn this observational study of patients with type 2 diabetes and severe obesity who underwent surgery, compared with those who did not undergo surgery, bariatric surgery was associated with a lower risk of macrovascular outcomes. The findings require confirmation in randomized clinical trials. Health care professionals should engage patients with severe obesity and type 2 diabetes in a shared decision making conversation about the potential role of bariatric surgery in the prevention of macrovascular events.

Project description:ImportanceType 2 diabetes is associated with increased cardiovascular risk. In placebo-controlled cardiovascular safety trials, the dipeptidyl peptidase-4 inhibitor linagliptin demonstrated noninferiority, but it has not been tested against an active comparator.ObjectiveThis trial assessed cardiovascular outcomes of linagliptin vs glimepiride (sulfonylurea) in patients with relatively early type 2 diabetes and risk factors for or established atherosclerotic cardiovascular disease.Design, setting, and participantsRandomized, double-blind, active-controlled, noninferiority trial, with participant screening from November 2010 to December 2012, conducted at 607 hospital and primary care sites in 43 countries involving 6042 participants. Adults with type 2 diabetes, glycated hemoglobin of 6.5% to 8.5%, and elevated cardiovascular risk were eligible for inclusion. Elevated cardiovascular risk was defined as documented atherosclerotic cardiovascular disease, multiple cardiovascular risk factors, aged at least 70 years, and evidence of microvascular complications. Follow-up ended in August 2018.InterventionsPatients were randomized to receive 5 mg of linagliptin once daily (n = 3023) or 1 to 4 mg of glimepiride once daily (n = 3010) in addition to usual care. Investigators were encouraged to intensify glycemic treatment, primarily by adding or adjusting metformin, α-glucosidase inhibitors, thiazolidinediones, or insulin, according to clinical need.Main outcomes and measuresThe primary outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke with the aim to establish noninferiority of linagliptin vs glimepiride, defined by the upper limit of the 2-sided 95.47% CI for the hazard ratio (HR) of linagliptin relative to glimepiride of less than 1.3.ResultsOf 6042 participants randomized, 6033 (mean age, 64.0 years; 2414 [39.9%] women; mean glycated hemoglobin, 7.2%; median duration of diabetes, 6.3 years; 42% with macrovascular disease; 59% had undergone metformin monotherapy) were treated and analyzed. The median duration of follow-up was 6.3 years. The primary outcome occurred in 356 of 3023 participants (11.8%) in the linagliptin group and 362 of 3010 (12.0%) in the glimepiride group (HR, 0.98 [95.47% CI, 0.84-1.14]; P < .001 for noninferiority), meeting the noninferiority criterion but not superiority (P = .76). Adverse events occurred in 2822 participants (93.4%) in the linagliptin group and 2856 (94.9%) in the glimepiride group, with 15 participants (0.5%) in the linagliptin group vs 16 (0.5%) in the glimepiride group with adjudicated-confirmed acute pancreatitis. At least 1 episode of hypoglycemic adverse events occurred in 320 (10.6%) participants in the linagliptin group and 1132 (37.7%) in the glimepiride group (HR, 0.23 [95% CI, 0.21-0.26]).Conclusions and relevanceAmong adults with relatively early type 2 diabetes and elevated cardiovascular risk, the use of linagliptin compared with glimepiride over a median 6.3 years resulted in a noninferior risk of a composite cardiovascular outcome.Trial registrationClinicalTrials.gov Identifier: NCT01243424.

Project description:ImportanceHanding over the care of a patient from one anesthesiologist to another occurs during some surgeries and might increase the risk of adverse outcomes.ObjectiveTo assess whether complete handover of intraoperative anesthesia care is associated with higher likelihood of mortality or major complications compared with no handover of care.Design, setting, and participantsA retrospective population-based cohort study (April 1, 2009-March 31, 2015 set in the Canadian province of Ontario) of adult patients aged 18 years and older undergoing major surgeries expected to last at least 2 hours and requiring a hospital stay of at least 1 night.ExposureComplete intraoperative handover of anesthesia care from one physician anesthesiologist to another compared with no handover of anesthesia care.Main outcomes and measuresThe primary outcome was a composite of all-cause death, hospital readmission, or major postoperative complications, all within 30 postoperative days. Secondary outcomes were the individual components of the primary outcome. Inverse probability of exposure weighting based on the propensity score was used to estimate adjusted exposure effects.ResultsOf the 313 066 patients in the cohort, 56% were women; the mean (SD) age was 60 (16) years; 49% of surgeries were performed in academic centers; 72% of surgeries were elective; and the median duration of surgery was 182 minutes (interquartile [IQR] range, 124-255). A total of 5941 (1.9%) patients underwent surgery with complete handover of anesthesia care. The percentage of patients undergoing surgery with a handover of anesthesiology care progressively increased each year of the study, reaching 2.9% in 2015. In the unweighted sample, the primary outcome occurred in 44% of the complete handover group compared with 29% of the no handover group. After adjustment, complete handovers were statistically significantly associated with an increased risk of the primary outcome (adjusted risk difference [aRD], 6.8% [95% CI, 4.5% to 9.1%]; P < .001), all-cause death (aRD, 1.2% [95% CI, 0.5% to 2%]; P = .002), and major complications (aRD, 5.8% [95% CI, 3.6% to 7.9%]; P < .001), but not with hospital readmission within 30 days of surgery (aRD, 1.2% [95% CI, -0.3% to 2.7%]; P = .11).Conclusions and relevanceAmong adults undergoing major surgery, complete handover of intraoperative anesthesia care compared with no handover was associated with a higher risk of adverse postoperative outcomes. These ﬁndings may support limiting complete anesthesia handovers.