Jejunoileal side-to-side anastomosis: New hope for patients with type 2 diabetes?

Abstract

In this article, we comment on an article by Wang et al published in the World Journal of Diabetes. Existing treatments with oral medications can partially mitigate the toxicity of elevated blood glucose levels in patients with type 2 diabetes mellitus. However, these patients often require lifelong, costly medications, and many struggle with poor compliance. To address the limitations of pharmacological treatments, laparoscopic jejunal-ileal lateral anastomosis has become increasingly common in clinical practice and generally yields favorable outcomes. This procedure stimulates the secretion of larger amounts of glucagon-like peptide-1 by intestinal L cells, which in turn promotes pancreatic islet cell proliferation, reduces insulin resistance, and effectively controls glucose and lipid metabolism disorders. Nonetheless, further research is needed to fully explore its indications, contraindications, the enhancement of patients' quality of life and patients’ satisfaction with the subjective experience of treatment and long-term effects.

Key Words: Type 2 diabetes; Jejunoileal side-to-side anastomosis; Glucagon-like peptide-1; Glycolipid metabolism; Islet function

Core Tip: Jejunoileal side-to-side anastomosis may offer new hope for patients with type 2 diabetes. It can stimulate the production of glucagon-like peptide 1 by the terminal L cells of the ileum to control blood sugar and improve the metabolism of patients. Research shows that the procedure showed significant improvements in patients' metabolic indicators such as body mass index, blood pressure, blood glucose, insulin resistance index, and cholesterol levels at 3 and 6 months post-surgery. Of course, further investigation is needed to fully explore its indications, contraindications, the enhancement of patients’ quality of life and patients’ satisfaction with the subjective experience of treatment and long-term effects.

TO THE EDITOR

Approximately 537 million adults have diabetes in the world, with the majority diagnosed with type 2 diabetes mellitus (T2DM). This number is projected to increase to around 783 million by 2045[1]. T2DM, traditionally defined by chronically elevated blood glucose levels, is now recognized as a complex cardio-renal-metabolic disease driven by chronic positive energy balance[2]. Over time, the disease leads to multiple metabolic and homeostatic disturbances, resulting in persistent disruptions in glucose and lipid metabolism. These metabolic imbalances severely compromise vascular integrity and function, contributing to organ dysfunction and death. T2DM significantly raises the risk of microvascular complications (such as retinopathy, neuropathy, and nephropathy) and macrovascular complications (including ischemic heart disease, cerebrovascular disease, and peripheral vascular disease)[3]. These complications impose a substantial socioeconomic burden and negatively impact patients' quality of life[4].

The significance of exploring new treatments for T2DM

The primary goal in diabetes management is to lower blood glucose levels to reduce the risk of microvascular and/or macrovascular complications[5]. Current treatments for T2DM include lifestyle modifications, pharmacotherapy (e.g., metformin, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sulfonylureas, meglitinides, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, and insulin), obesity management, sleep behavior adjustments, and maintaining mental well-being, all of which can help manage T2DM and its complications[3]. However, long-term effectiveness and patient adherence to these interventions is still significant challenges, especially in low- and middle-income regions[6-8]. Thus, exploring novel treatments for T2DM is crucial.

Continuous exploration of the surgical treatment of T2DM

The bariatric surgery was reported to be an effective treatment for T2DM due to its strong impact on reducing body weight, blood glucose levels, fasting insulin, and HbA1c[9]. Subsequent numerous studies have confirmed bariatric surgery efficacy in improving glucose homeostasis, reducing glucose-lowering medication need, and lowering both T2DM microvascular and macrovascular complications[10].

Traditional metabolic surgeries for T2DM involve Roux-en-Y Gastric Bypass (RYGB), Sleeve Gastrectomy (SG), Biliopancreatic Diversion, Adjustable Gastric Banding, and so on. Evidence shows that surgeries enhance the patient's glycolipid metabolic status[11]. However, these procedures are not devoid of risks, which include gastrointestinal motility disorders, postoperative dumping syndrome, intestinal herniations, Insulinoma, nutritional deficiency, and the potential for residual gastric malignancies[12,13].

In recent times, laparoscopic jejunoileal side-to-side anastomosis has surfaced as a promising surgical intervention. It is particularly appropriate for patients who are of normal weight or mildly overweight[14]. This surgical technique significantly lowers blood glucose, postpones the onset of complications, decreases the likelihood of requiring gastrectomy or open surgical approaches, and mitigates the symptoms. As previously mentioned, it shunts the jejunum and ileum. This facilitates the rapid transit of digestive secretions and undigested food components to the terminal ileum and colon. This stimulates GLP-1 secretion by L cells at the terminal ileum, ultimately aiding in blood sugar control and metabolic improvement.

We conducted a comparative analysis of three most commonly used surgical treatments: jejunoileal side-to-side anastomosis, RYGB, and SG, evaluating them based on targeting the crowd, effectiveness, safety, and cost-effectiveness. The findings are summarized in Table 1[14-18].

Table 1 Comparison of three most commonly used surgical treatments.

	Jejunoileal side-to-side anastomosis	Roux-en-Y gastric bypass	sleeve gastrectomy
Targeting the crowd	It is mainly targeted at T2DM patients with normal or relatively high BMI and comorbidities	It is primarily targeted at T2DM patients with high BMI and comorbidities	It is primarily targeted at T2DM patients with high BMI and with or without comorbidities
Effectiveness	Effectively alleviates T2DM and related comorbidities	Significant weight loss and effective reduction of T2DM and related comorbidities	The weight loss outcomes were substantial; however, the improvement in comorbidities was less pronounced compared to Roux-en-Y gastric bypass
Safety	It may cause long-term nutrient absorption problems due to intestinal reconstruction, but there are few clinical studies and no obvious data support	Early complications include: Anastomotic leak, hemorrhage obstruction Venous thrombo-embolic disease. Infections: Late complications include: Internal herniation (most common). Stricture. Micronutrient deficiency. Hyperoxaluria. Gallstone formation. Dumping syndrome. Marginal ulcers. Gastrogastric fistula. Failed weight loss maintenance. Roux-en-Y Gastric Bypass has a higher mortality rate of about 0.2% than sleeve gastrectomy	The complication rate is low but there may be problems with gastroesophageal reflux
Cost-effectiveness	Surgery is shorter and hospital stays less, so initial costs are lower, but costs for long-term nutritional management may increase	Although surgery costs are high, medical expenses may be reduced in the long term due to diabetes remission	In between

T2DM: Type 2 diabetes mellitus; BMI: Body mass index.

Improvement and significance of relevant indexes after jejunal side-to-side anastomosis

T2DM pathophysiological studies indicate that obesity is a significant risk factor for its development. Hepatic metabolic dysfunction, cardiocerebrovascular disease, dyslipidemia, and hyperuricemia are increasingly recognized in many patients with T2D[19].

This article[14] presents a retrospective analysis involving 78 individuals who have undergone laparoscopic jejunoileal side-to-side anastomosis at their medical facility. They aimed to assess the effects of the surgical intervention on various metabolic parameters by measuring preoperative and postoperative levels of glucose, lipids, and purines. They discovered a notable decrease in body mass index, blood pressure and indicators associated with blood glucose metabolism at 3/6 months post-surgery.

No statistically significant differences in pancreatic islet function were observed at 3 months post-surgery compared to preoperative values. However, at 6 months post-surgery, significant improvements were noted. As the function of pancreas improved, there were concurrent enhancements in metabolic indicators, with concurrent reductions in insulin resistance and secretion abnormalities.

The authors evaluated and contrasted the levels of transaminases before and after surgery within their study group. They found no significant differences, which they attributed to the mean BMI of their patients being less than 25 kg/m². They discovered that lateral jejunoileal anastomosis surgery improves blood lipid profiles within 3 months and demonstrates more significant enhancements in lipid profiles and uric acid levels 6 months following the surgical procedure. The authors speculated that these changes were likely related to the elevated secretion of GLP-1, stimulated by the surgical diversion of the ileum, which enhances the production of GLP-1 by L cells[14]. The role of GLP-1 in human metabolism is well-documented in the literature[3,5,19].

Laparoscopic jejunoileal anastomosis promoted the metabolisms of glucose, lipid, and purine, along with other related parameters in T2DM patients. Beyond lowering blood glucose levels, this procedure appears to offer broader benefits, including improved metabolism of lipids and purines, as well as better control of weight and blood pressure. Through the augmentation of endogenous GLP-1, this surgery addresses the underlying mechanisms of insulin resistance and insufficient insulin secretion, potentially reducing the postoperative complications typically seen with traditional weight-loss surgeries.

CONCLUSION

The sample size of this study is relatively small, with only 78 cases included. Each surgery has specific indications and contraindications, and compared to pharmacological treatments, fewer patients may be suitable for this procedure. This study primarily reviews the relevant indicators at 3 and 6 months post-surgery, which limits our ability to assess the long-term effects of the surgery on T2DM complications. Furthermore, the study did not adequately address the enhancement of patients' quality of life and their satisfaction with the subjective experience of treatment. Nonetheless, the study provides a valuable new perspective on the treatment of T2DM. Jejunoileal side-to-side anastomosis may offer new hope for patients with T2DM. Further in-depth and longer-term retrospective studies are needed to fully evaluate its long-term efficacy and impact.

ACKNOWLEDGEMENTS

We thank Dr. Zhao J, department of endocrinology, the First Affiliated Hospital of Yunnan University of Chinese Medicine, for the answer to the operation and specific benefit mechanism of this surgery. We are thankful to Professor Zhang PY of the Second Clinical College of Yunnan University of Chinese Medicine for the guidance of the revised comments.