Introduction

Diabetes mellitus (DM) accounts for about 1 in 11 adults worldwide [1], and 90% of whom have type 2 diabetes mellitus (T2DM), with Asia as the major area of the rapidly emerging DM global epidemic. Genetic predisposition, early developmental factors, unhealthy diet, and a sedentary lifestyle determine individual susceptibility to DM [2], with some risk factors potentially reversible [1]. Obesity has been long recognized to be associated with an increased risk of T2DM and a major contributing factor to cardiovascular disease (CVD) by the Global Burden of Disease group [3]. In obese individuals, adipose tissue releases non-esterified fatty acids, glycerol, pro-inflammatory cytokines, hormones, and other factors, which induce insulin resistance, cause dysfunction of pancreatic islet beta-cells, and finally lead to T2DM [4]. On the other hand, weight loss is effective in delaying the progression from prediabetes to T2DM and is highly beneficial in the treatment of T2DM for individuals who are overweight or obese [1, 5,6,7,8,9].

The major adverse cardiovascular events (MACE) are the leading cause of mortality in people with DM [10]. DM predisposes affected individuals to a significant spectrum of cardiovascular complications. Abnormalities in the cardiac metabolism, the mitochondrial compartment, and physiological and pathophysiological signaling, accompanied by oxidative stress, inflammation, neurohumoral mechanisms, and myocardial cell death pathways, are emphasized as potential contributing mechanisms to diabetic cardiomyopathy [11]. Thus, an effective and durable treatment of severe obesity in patients with DM, preventing and improving its comorbidities of MACE, may be crucial to decrease the cost and mortality. Lifestyle-based behavioral and pharmacological interventions for weight loss remain the major approaches to obesity prevention and management [12, 13] but with limited success. Metabolic and bariatric surgery (MBS) has become one of the most commonly performed operations in general surgery. The American Society for Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) estimated that long-term results of MBS consistently demonstrate safety and efficacy [14]. And total healthcare costs showed no difference between the surgery and conventional treatment groups for patients with diabetes [15].

Recently, MBS has been established as the most effective and safe method for producing long-term and sustained weight loss [16,17,18,19]. Weight loss after MBS may yield important health benefits for DM [20, 21], including similar benefits in patients with type 1 diabetes mellitus (T1DM) [22]. However, the results were debatable. In order to detect the overall effects from a quantitative synthesis of accumulated data from different studies, we carried out this meta-analysis to assess the risk of MACE among obese patients with diabetes after MBS.

Methods

Publication Search and Inclusion Criteria

We searched the databases including PubMed, Embase, Medline, and Web of Science for all cohort articles within a range of published years from 2000 to 2023 estimating major adverse cardiovascular events (MACE) among obese patients with diabetes after MBS (the last search was updated 20th February 2023). The following terms were used in this search: “MBS” or “gastric bypass” or “sleeve gastrectomy” and “cardiovascular” or “atrial fibrillation” or “heart failure” or “stroke” or “myocardial infarction” and “diabetes” and “cohort.” In order to identify the relevant publications, the references cited in the research papers were also scanned. The combined search resulted in 316 abstracts (Fig. 1). An additional 25 studies were identified through review articles and meta-analysis, thus a total of 341 studies were included.

Fig. 1
figure 1

Flowchart for identification of studies

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The exclusion criteria for individual study were: (1) reviews, books, or meeting/conference abstracts; (2) studies that contain duplicated data; (3) articles that are not written in English; (4) articles that are not prospective cohort studies; (5) paper that did not contain sufficient data to calculate the ORs and 95% CIs of any type of cardiovascular event after MBS; and (6) obese participants that did not suffer from diabetes.

Data Extraction

Two authors (Wenxing Yang and Mengjun Zhan) independently reviewed and extracted the data needed. Publications were read by both authors in order to check the original data extraction. Disagreements were resolved through discussion among the authors to achieve a consensus. The following information was recorded for each study if available: first author, year of publication, region, outcome, follow-up period, patients who underwent MBS, matched nonsurgical patients, age, BMI, observed duration of diabetes, level of hemoglobin A1c, and eGFR of both groups (all of the data are shown in Table 1).

Table 1 Characteristics of studies included in this meta-analysis
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Statistical Analysis

The odds ratio (OR) corresponding to the 95% confidence interval (95% CI) was used to assess the risk of MACE among patients with diabetes after MBS. In addition to the comparison among all subjects, we performed stratified analyses to assess the association between Roux-en-Y gastric bypass and the risk of MACE. We also performed subgroup analyses to assess the association between MBS and different cardiovascular outcomes. The statistical heterogeneity among studies was assessed by Q-test and I2 statistics [37]. If no obvious heterogeneity, the fixed-effects model (the Mantel–Haenszel method) was used to estimate the summary OR [38]; otherwise, the random-effects model (the DerSimonian and Laird method) was used [39]. Finally, random-effects models were used to calculate the overall OR estimates and 95% CIs. To explore sources of heterogeneity across studies, we did logistic meta-regression analyses and stratified analyses. Publication bias was evaluated with a funnel plot and Begg’s rank correlation method [40]. The statistical analyses were performed by STATA 12.0 software (Stata Corp., College Station, TX).

Results

Characteristics of Studies

A total of 341 abstracts were screened, in which 25 were retrieved for more detailed evaluation. Of the 10 excluded studies, six papers lack of sufficient data, four papers have duplicated data [41,42,43,44], and the updated data were included in the present analysis (shown in Fig. 1). Finally, 15 cohort studies [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36] met the inclusion criteria, involving 122,361 obese patients with diabetes. The details of the selected studies were listed in Table 1.

Quantitative Synthesis

The evaluation of the risk of primary MACE among patients with diabetes after MBS was shown in Table 2, and Figs. 2 and 3. Overall, there was statistical evidence of significantly decreased morbidity, and mortality of MACE was found to be associated with MBS (OR = 0.65, 95% CI = 0.59–0.72, I2 = 62.8% for morbidity, OR = 0.49, 95% CI = 0.36–0.67, I2 = 68.7% for mortality). In subgroup analysis, MBS was significantly associated with decreased cerebrovascular disease risk (OR = 0.65, 95% CI = 0.48–0.87, I2 = 0.0%), coronary artery disease risk (OR = 0.67, 95% CI = 0.50–0.92, I2 = 83.2%), atrial fibrillation risk (OR = 0.80, 95% CI = 0.71–0.90, I2 = 0.0%), heart failure risk (OR = 0.46, 95% CI = 0.38–0.56, I2 = 44.8%), myocardial infarction risk (OR = 0.61, 95% CI = 0.47–0.79, I2 = 0.0%), and stroke risk (OR = 0.62, 95% CI = 0.42–0.93, I2 = 26.5%). As shown in Table 2 and Fig. 4, in terms of stratified analyses, Roux-en-Y gastric bypass was significant with decreased MACE risk (OR = 0.55, 95% CI = 0.49–0.63, I2 = 1.4%).

Table 2 Associations between MBS and risk of major adverse cardiovascular events
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Fig. 2
figure 2

Forest plot for primary outcome of MACE morbidity and mortality after metabolic surgery

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Fig. 3
figure 3

Forest plot for secondary outcome of MACE after metabolic surgery

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Fig. 4
figure 4

Forest plot for MACE after Roux-en-Y gastric bypass

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Evaluation of Heterogeneity

There was heterogeneity among studies in overall comparisons (Pheterogeneity = 0.001, I2 = 62.8%, Tau2 = 0.017). To explore sources of heterogeneity across studies, we performed stratified analyses; heterogeneity among studies decreased when performed by different cardiovascular outcomes.

Sensitivity Analysis

The influence of a single study on the overall meta-analysis estimate was investigated by omitting one study at a time, and the omission of any study made no significant difference, indicating that our results were statistically reliable.

Publication Bias

Begg’s test was performed to evaluate the publication bias of selected literature. Figure 5 displays a funnel plot that examined MBS and MACE risk included in the meta-analysis. No evidence of publication bias in our study was observed (P = 0.101).

Fig. 5
figure 5

Begg’s funnel plot for publication bias test. Each point represents a separate study for the indicated association. s.e.: standardized effect

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Discussion

Obesity and DM are increasing together rapidly. Approximately a quarter of morbidly obese individuals have DM [3, 45], and the obesity-associated mortality is largely attributed to diabetes and cardiovascular dysfunction.

In patients with obesity and DM, weight loss interventions, including intensive lifestyle modification, pharmacotherapy, and MBS, can compensate MACE risk factors [46,47,48]. The efficacy of lifestyle modification and pharmacotherapy is highly variable as it relies on persistent patient motivation and engagement [25, 26] and has relatively modest effects on mortality [49,50,51]. In comparison, MBS controls glycemic level better [52, 53], leads to greater DM remission, which is usually defined as a glycated hemoglobin A1c level at or below 6.0% to 6.5% without the use of diabetes medications [54], and results in remission of comorbidities in 50% to 70% patients [55,56,57].

MACE is one of the leading causes of morbidity and mortality for obese patients with DM. Clinical guidelines for the management of DMs emphasize lowering MACE risk factors by optimizing glycemic control, blood pressure, and serum lipid levels [58, 59]. However, most patients with intensive lifestyle modification and pharmacotherapy did not achieve these recommended treatment goals, resulting in continued morbidity and costs [60]. In the present study, we carried out this meta-analysis to assess the risk of MACE among obese patients with diabetes after MBS. Our results indicate that significantly decreased morbidity and mortality of MACE are associated with MBS. In subgroup analysis, we found that MBS is significantly associated with decreased cerebrovascular disease, coronary artery disease, atrial fibrillation, heart failure, myocardial infarction, and stroke risk.

A constellation of factors mediate postoperative glycemic improvement after MBS. Multiorgan insulin sensitivity, bile acid metabolism, intestinal glucose metabolism, β-cell function, incretin response, the gut microbiome, and browning of adipose tissue have been proposed to explain the potential unique effects of MBS [61, 62]. Anatomical changes in the gastrointestinal tract inducing beneficial metabolic and neurohormonal changes are factors partially independent of weight loss [63]. Thus, ASMBS and IFSO define the long-term results of MBS to be safe and efficacious and recommend MBS in patients with T2D and BMI ≥ 30kg/m2 [14].

However, people who undergo MBS may also be at increased risk for substance abuse, worsening or new-onset depression and anxiety disorders, and suicidal ideation [64,65,66]. Thus, candidates for MBS should be assessed after consultation with a multidisciplinary team to help manage the patient’s modifiable risk factors with the goal of reducing the risk of perioperative complications and improving outcomes [14, 65, 67].

A few limitations of our study should be considered. Although we did observe significant decreased risk of MACE among obese patients with diabetes after MBS, we failed to analyze the effect in patients with diverse BMI, age, or other biochemical index due to insufficient data. Moreover, adjusted ORs and 95% CIs were used for analysis, which may ignore potential adjusted risk factors.

In conclusion, our meta-analysis indicated that MBS for obese patients with diabetes will be beneficial to decreasing MACE risk. Moreover, further studies estimating the functional effect may eventually provide a better and comprehensive understanding of the effect on different populations.