Jejunoileal side-to-side anastomosis as a promising option for type 2 diabetes

Abstract

In this editorial, I discuss the article by Wang et al, published in the World Journal of Diabetes, which explores jejunoileal side-to-side anastomosis as a novel surgical intervention for type 2 diabetes mellitus (T2DM). T2DM, often associated with obesity, remains a global health challenge, as sustained remission is difficult to achieve with conventional pharmacological therapy. Jejunoileal anastomosis offers a promising alternative, particularly for patients with normal or relatively high body mass index, and addresses the unique challenges posed by diverse patient populations. This procedure preserves gastric anatomy while simultaneously improving metabolic parameters, such as glycemic control, lipid profiles, and pancreatic β-cell function. Unlike traditional metabolic surgeries that involve permanent anatomical alterations, this approach provides advantages such as reversibility, shorter operative times, and minimal nutritional complications, making it appealing to patients for whom conventional bariatric surgery is unsuitable. Advances in gut hormone physiology and incretin modulation support these findings. This innovative approach represents a potential paradigm shift in T2DM treatment, offering insights into the evolving role of surgical interventions in metabolic regulation. While early findings show promising diabetes remission rates and metabolic improvements at six months post-surgery, further studies with longer follow-up periods and broader patient cohorts are required.

Key Words: Type 2 diabetes mellitus; Pancreatic function; Jejunoileal side-to-side anastomosis; Remission; Asian population

Core Tip: This editorial examines jejunoileal side-to-side anastomosis as a novel surgical approach for type 2 diabetes mellitus. It highlights the role of this surgical approach in modulating glucagon-like peptide-1, improving β-cell function, and preserving gastric anatomy, thereby offering a promising alternative for patients with type 2 diabetes mellitus and a relatively high body mass index.

INTRODUCTION

The global prevalence of diabetes continues to rise, currently affecting over 10% of adults worldwide, with a disproportionately larger number in low- and middle-income countries. Worse still, nearly half of all individuals with diabetes are unaware of their medical condition. The population with diabetes is expected to increase in the coming decades, with estimates indicating that nearly 1 in 8 adults will suffer from the condition by 2045[1]. This growing epidemic poses unprecedented challenges to healthcare systems, particularly in resource-limited developing nations. Asian countries face particularly unique challenges due to the earlier onset of type 2 diabetes mellitus (T2DM) in individuals with a lower body mass index (BMI) compared to Western populations, necessitating alternative treatment modalities tailored to these metabolic phenotypes. Although traditional pharmacological approaches remain the mainstay of T2DM management, their limitations, such as the requirement for lifelong medication, adherence issues, inconsistent efficacy, and poor durability, have prompted healthcare providers to explore alternative solutions, leading to a growing interest in surgical interventions.

INNOVATIONS IN METABOLIC SURGERY

Wang et al[2] proposed jejunoileal side-to-side anastomosis as a novel alternative to conventional metabolic and bariatric surgery (MBS), particularly for patients with normal or relatively high BMI. Over the past two decades, MBS has evolved significantly, with diabetes remission rates ranging from 30% to 70% following procedures such as the Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy. The outcomes of these procedures vary depending on the definition of remission, patient characteristics, surgical method, follow-up duration, and duration of preoperative diabetes[3,4]. However, these traditional procedures involve substantial risks and may be unsuitable for certain patient populations, especially in Asian countries where T2DM often manifests in individuals with a lower BMI[5]. The risks include irreversible anatomical alterations, nutritional deficiencies, and a higher prevalence of complications like the dumping syndrome[3,4,6]. These limitations highlight the need for safer and more adaptable approaches, particularly for populations with unique metabolic profiles.

The current study on the use of jejunoileal side-to-side anastomosis sought to bridge this gap in therapeutic management. Unlike RYGB or sleeve gastrectomy, both of which permanently alter gastric anatomy and can lead to significant nutritional challenges[6], jejunoileal side-to-side anastomosis preserves the physiological function of the stomach while modifying nutrient flow patterns. This innovative approach stimulates glucagon-like peptide-1 (GLP-1) secretion, enhancing glycemic control, promoting satiety, and improving β-cell function while minimizing the risk of nutritional deficiencies and other long-term complications, offering shorter operative times and maintaining the reversibility of the intervention. While weight loss was modest compared to RYGB, glycemic control was notably effective, with diabetes remission rates surpassing expectations[7]. This procedure could be particularly relevant for Asian populations, where traditional MBS may be less appropriate due to different body composition patterns and metabolic phenotypes[8].

METABOLIC MECHANISMS AND IMPROVEMENTS

Recent advances in research on incretin physiology provide an important context for understanding the metabolic benefits observed in this study. The reductions in blood pressure, postprandial blood glucose, and glycated hemoglobin levels at three months post-jejunoileal side-to-side anastomosis, with further enhancements at six months, are consistent with current research on the role of gut hormones in metabolic regulation[9]. The study also demonstrated improvements in pancreatic function markers, including elevated post-prandial C-peptide, insulin, and homeostasis model assessment of β-cell function levels, suggesting potential β-cell recovery. This is consistent with research indicating that reduction in glucotoxicity and lipotoxicity, a process facilitated by the procedure’s ability to improve ectopic fat deposition in the liver and pancreas, can partially restore β-cell insulin secretion dynamics and systemic insulin sensitivity, even in long-standing diabetes[10,11]. Additionally, reductions in systemic inflammation markers, such as C-reactive protein, may enhance insulin sensitivity and β-cell preservation, underscoring the procedure’s anti-inflammatory effects. Interestingly, the observed improvements in lipid profile, particularly reductions in triglycerides and low-density lipoprotein cholesterol, suggest additional pathways of metabolic regulation. Enhanced bile acid reabsorption and modulation of gut microbiota composition post-surgery may further contribute to these outcomes, supporting broader systemic benefits.

Weight loss, whether achieved through surgical or nonsurgical means, plays a critical role in the remission of T2DM. By reducing ectopic fat deposits in the liver and pancreas, weight loss improves hepatic and pancreatic insulin sensitivity[12,13]. This reduction in glucotoxicity and lipotoxicity facilitates the recovery of pancreatic β-cell function, restoring the insulin secretion dynamics critical for glucose homeostasis[14]. Additionally, the physiological effects of weight loss extend beyond glycemic control, influencing systemic inflammation, lipid metabolism, and cardiovascular health[15-17]. The secretion of GLP-1 is enhanced with weight loss, further promoting satiety, improved insulin sensitivity, and β-cell preservation[18].

Beyond glycemic regulation, the observed improvements in lipid profiles and reductions in uric acid levels highlight the broader benefits of jejunoileal side-to-side anastomosis for a multisystem disorder such as T2DM. These findings illuminate the complex interplay between glucose homeostasis, lipid metabolism, and cardiovascular health, advancing our understanding of how targeted surgical interventions can address the systemic nature of T2DM[19,20].

LIMITATIONS AND FUTURE DIRECTION

Despite promising results, the relatively short six-month follow-up period of this study is a limitation, as metabolic improvements may decline over time[3,21,22]. Long-term studies are needed to evaluate the durability of metabolic improvements and monitor potential late complications. Moreover, patient selection criteria, particularly the requirement for specific C-peptide thresholds, suggest that only a subset of T2DM patients may benefit optimally from this procedure. This suggests that the broader applicability of jejunoileal anastomosis across diverse populations needs further exploration, as highlighted by the recent consensus guidelines[23,24]. Nevertheless, the incorporation of detailed mechanistic insights into incretin modulation, bile acid signaling, and gut microbiota dynamics in the study underscores the potential of the procedure to influence the broader landscape of metabolic surgery.

While increased GLP-1 secretion likely plays a central role in metabolic improvements[25], earlier studies indicate that bile acid signaling[26] and gut microbiome changes[27] also play key roles in post-surgical metabolic regulation through a complex interplay of mechanisms. These findings underscore the innovative nature of the procedure, which integrates multiple metabolic pathways and highlights the need for advanced research to optimize its application and understand its full therapeutic potential. Future studies should incorporate advanced omics technologies, including metabolomics and microbiome profiling, to uncover these intricate interactions and their contribution to long-term efficacy.

CONCLUSION

This study contributes to the research on the role of metabolic surgery for T2DM by demonstrating the potential of less invasive techniques to achieve significant metabolic improvements. By delving into multifaceted mechanisms, including gut-pancreas signaling, lipid metabolism, and bile acid pathways, the study highlights a paradigm shift in the surgical management of diabetes. Given the exponentially rising burden of diabetes globally, future research should include large-scale randomized controlled trials with long-term follow-ups to establish the role of this procedure in T2DM management and expand treatment options.