Bariatric surgery can significantly improve glycaemic control and even alleviate diabetes in people with T2DM, so can it also benefit people with T1DM?

The International Federation for the Surgery of Obesity and Metabolic Disorders stated in 2016 that bariatric surgery not only treats obesity-related diseases but also improves insulin resistance and reduces insulin requirements, so obese T1DM can be used as a therapeutic indication for bariatric surgery[32]. Studies have shown that bariatric surgery leads to significant improvements in weight and cardiometabolic variables and modest improvements in blood glucose with few reported adverse events in cohorts of patients with obesity and T1DM[33]. The study by Vilarrasa et al[34] described the long-term outcomes of bariatric surgery in a cohort of patients with T1DM: Bariatric surgery provided some benefits in terms of weight loss, insulin requirements, obesity comorbidities and diabetic complications in patients with T1DM, but the long-term impact on glycaemic control was likely to be small. The study by Landau et al[35] demonstrated the same point; in people with obesity and T1DM, weight loss after bariatric surgery was successful without significant im-provement in glycaemic control. A meta-analysis involving 9 studies with a total of 78 patients showed that glycated hemoglobin (HbA1c), insulin dose, and body mass index (BMI) improved after surgery, although the improvement in HbA1c did not reach statistical significance (P = 0.40)[36]. It is worth noting that the postoperative risks of diabetic ketoacidosis and severe hypoglycemic episodes should also be considered when performing bariatric surgery in the T1DM population[35].

In summary, bariatric surgery has brought new hope to the treatment of obese T1DM and, apart from its controversial effect on blood glucose, it has played a significant role in reducing BMI, improving obesity-related diseases, improving insulin sensitivity, and alleviating or even reversing diabetic complications. As a result of these positive results, more and more patients with T1DM are willing to undergo bariatric surgery.

More than 10 years ago, some animal studies have successively confirmed that bariatric surgery has certain effects on non-obese DM[37,38]. Bariatric surgery was performed in 69 patients with T2DM and a BMI of 21-29 kg/m², with a mean follow-up of 21.7 months, resulting in satisfactory glycaemic control in 95.7% of patients[39]. The study of Zhang et al[40] showed that Billroth II gastrojejunostomy for the treatment of non-obese patients with T2DM had similar short- and medium-term glycaemic control effects as Roux-en-Y gastric bypass (RYGB) surgery for the treatment of obese patients with T2DM. Malapan et al[41] included 29 non-obese (BMI < 27 kg/m²) T2DM patients who underwent laparoscopic RYGB and showed a significant reduction in mean body weight, mean BMI, and mean waist circumference, as well as mean systolic and diastolic blood pressure over a one-year prospective follow-up; and other biochemical variables, including blood glucose, HbA1c, C-peptide, insulin, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and homeostatic model assessment insulin resistance were significantly improved. More surprisingly, ten patients with T2DM and a BMI < 24.0 kg/m² (mean BMI 23.8 kg/m² ± 1.2 kg/m²) were reported to have undergone duodenojejunal bypass, with resolution of T2DM in one patient and significant reductions in fasting glucose, 2-hour postprandial glucose and HbA1c at all postoperative time points, without significant weight loss[42]. However, the sample sizes of these clinical trials are small, and further large, multicentre, prospective, randomized controlled trials are needed to confirm the role of bariatric surgery in mildly obese or normal-weight patients with T2DM.

For obese and diabetic patients, bariatric surgery can provide relief from both conditions. But can bariatric surgery benefit non-diabetic patients? Bariatric surgery has been shown to restore visual cortical plasticity in non-diabetic obese patients[43]. Luo et al[44] reported on the effects of bariatric surgery in diabetic and non-diabetic patients who were followed for five years, and final subgroup analyses showed a linear increase in the percentage of non-diabetic patients from the worst clinical outcome to successful weight loss, and even more unexpectedly, non-diabetics lost a higher percentage of excess weight than diabetics over all five years. In addition, the Michigan Bariatric Surgery Collaborative reported that patients without DM were more likely to achieve a post-operative BMI of less than 30 kg/m² within one year[45]. It is well known that the obese population is at an increased risk of microvascular complications, and the risk is even greater in patients with T2DM. Bashir et al[46] evaluated the effects of bariatric surgery on microvascular complications in diabetic and non-diabetic patients, and they concluded that obese patients with or without DM benefit from the improvement in microvascular complications with bariatric surgery.

Although the risks of obesity in people with human immunodeficiency virus (HIV) are unclear, the incidence of DM and cardiovascular disease is increased in HIV-infected people, whether they are obese or not[47]. Many of those treating obese HIV patients are concerned that weight loss is unsafe for these patients. Flancbaum et al[48] reported on the first cohort of HIV-infected patients to undergo bariatric surgery, including six morbidly obese patients with obesity-related comorbidities who had asymptomatic, stable HIV infection. In their study, none of the patients showed a clinically significant deterioration in CD4 count or immune status, or progression of acquired immunodeficiency syndrome, and all of the patients’ comorbidities improved or resolved. Fazylov et al[49] reported two cases of morbidly obese, asymp-tomatic HIV-infected patients who underwent laparoscopic RYGB, both patients successfully lost weight and maintained their weight loss at the last follow-up. Yang et al[50] evaluated the efficacy and safety of bariatric surgery in three HIV-infected patients. In their three cases, bariatric surgery resulted in stable CD4 counts and undetectable viral loads. A growing body of data suggests that bariatric surgery can be safely performed in HIV-infected patients without progression to acquired immunodeficiency syndrome.

Obesity is a major risk factor for cancer morbidity and mortality[51,52]. Whether the anatomical, physiological, and microbiome changes induced by bariatric surgery in the gastrointestinal tract result in an increased risk of cancer in this area remains an open question. Numerous studies have shown that bariatric surgery is beneficial in reducing morbidity and mortality from all cancers[53-55], particularly breast[56-58] and endometrial cancers[59,60]. In addition to the effects on cancer development, some studies have suggested that bariatric surgery improves cancer prognosis in severely obese patients[61,62]. However, esophagogastric cancers have been reported to be induced after bariatric surgery[63], but epidemiological studies have not shown a higher incidence of these cancers in patients undergoing bariatric surgery compared with the general population[64]. Equally distressing is the conflicting evidence regarding the risk of colorectal cancer after bariatric surgery, with several studies showing a reduced risk of colorectal cancer in patients who have undergone bariatric surgery[65,66], while Aravani et al[67] showed that bariatric surgery was not associated with an increased risk of colorectal cancer, and others even suggest that patients who have undergone bariatric surgery are at an increased risk of colorectal cancer[68,69]. There are still some unanswered questions about the possible effects of bariatric surgery on cancer risk in patients with obesity, and there is a need for prospective, randomized controlled, and longer studies in populations undergoing bariatric surgery.

In addition to the special populations mentioned above, it is also important to consider what to do when pregnancy and bariatric surgery conflict, with the best evidence to date coming from expert opinion[70,71] that either pregnancy should be postponed during the bariatric surgery phase or bariatric surgery should be postponed during pregnancy. More high-quality randomized controlled trials are needed to explore the relationship between bariatric surgery and pregnancy in more detail.

Although a large proportion of patients with T2DM who have undergone bariatric surgery initially experience remission, some patients later relapse. It is estimated that around half of patients regain 5% of their body weight within two years of bariatric surgery[72]. An observational study of 300 patients undergoing RYGB showed that 37% of patients regained ≥ 25% of their maximum weight loss after a mean follow-up of 7 years[73]. The incidence of weight regain ranges from 9% to 91%, depending on the definition used[74]. Similarly, patients are at risk of developing a new onset DM after bariatric surgery[75]. In an analysis of data from a non-randomized, prospective, controlled trial, Carlsson et al[76] found that the incidence of new-onset T2DM after bariatric surgery was 6.8 cases per 1000 patient-years during a 15-year follow-up period. In a single-center retrospective study, Nor Hanipah et al[77] investigated the incidence of new-onset DM over 17 years after bariatric surgery, and they found that the incidence of new-onset DM was 0.4%; weight regain was common among patients with new-onset DM (> 50%).

Many studies have tried to explore the best biological and clinical predictors of T2DM recurrence after surgery[78-81]. Unfortunately, it is still difficult to predict which patients will experience postoperative weight regain or new-onset DM. A prospective study of 175 patients with RYGB T2DM and a 5-year follow-up found that several baseline factors (duration of DM, number of DM medications, HbA1c) and status at 1 year (fasting blood glucose, number of DM medications, remission status, percentage total weight loss) predicted the rate of DM remission and recurrence at 5 years[82]. A growing number of studies have shown that shorter duration of T2DM, better preoperative glycaemic control, lower baseline HbA1c and waist circumference, and greater postoperative weight loss are associated with higher rates of T2DM remission and lower risk of recurrence[83-85]. In addition, it has been suggested that gender is also an important factor in T2DM recurrence, with men having a lower risk of T2DM recurrence[86,87].

Despite the risk of weight regain or a new onset of DM, surgery still has the potential to have beneficial metabolic effects in the long term. Therefore, a higher risk of recurrence should not be a reason for exclusion from surgery. Careful preoperative patient selection and preoperative optimization appear to be important. Patients with postoperative recurrence, either weight regain or diabetic recurrence, are usually re-operated. Previous studies have shown that early surgery reduces the risk of recurrence[85,86]. Therefore, patients with obesity and T2DM should prioritize metabolic surgery at an early stage. Of course, it seems equally important to optimize lifestyle changes in patients after bariatric surgery[88]. In addition, the use of anti-obesity medications may provide more options for patients and healthcare providers[89].

PBSH typically presents with palpitations, sweating, weakness, and dizziness one to three hours after a meal, and some patients experience severe and potentially life-threatening symptoms of hypoglycemia, including seizures, coma, or loss of consciousness. Repeated hypoglycemic events lead to reduced quality of life for patients[104] and are associated with increased all-cause mortality[105], risk of dementia[106], and risk of motor vehicle accidents[107], and severe hypo-glycemia increases morbidity and mortality in patients with T2DM[108].

The true incidence of PBSH remains uncertain, with previous reports ranging from 0.1% to 50.0%[109-111]. However, as there are cases where hypoglycemia goes undiagnosed due to undetected hypoglycemia[103], it is clear that the true incidence is likely to be underestimated. The incidence of hypoglycemia based on continuous glucose monitoring data has been reported to be as high as 75% in postoperative RYGB patients[112].

The pathogenesis of PBSH is controversial and involves rather complex mechanisms that can be divided into insulin-dependent and non-insulin-dependent mechanisms. Insulin-dependent mechanisms include excessive insulin secretion by pancreatic beta cells, decreased insulin clearance, and increased insulin sensitivity. Non-insulin-dependent mechanisms include functional and structural adaptations in the gut after bariatric surgery that affect gastric emptying rate, glucose absorption, glucagon-like peptide-1 (GLP-1) levels, bile acid levels, gut microbiota, and counter-regulatory mechanisms to prevent hypoglycemia[113-118].

The management of PBSH is equally challenging and requires a multidisciplinary approach that includes dietary, pharmacological, and surgical interventions. The first line of treatment for PBSH is dietary modification, particularly restriction of carbohydrate intake and avoidance of simple carbohydrates[119,120]. If dietary changes do not adequately control the patient's symptoms, pharmacological treatment with GLP-1 agonists, acarbose, growth inhibitor analogues, and calcium channel blockers may be considered[121-123]. Avexitide and glucagon pumps are two newer therapeutic options that have recently been tested[124,125]. Recent studies have shown that the acute effects of exercise training on glycaemic homeostasis after bariatric surgery can be used as a non-pharmacological adjunctive therapy[126]. Surgery is the last option when all other treatments have failed [127,128].

In a prospective controlled Swedish study of patients treated with bariatric surgery for up to 31 years, male gender, older age, and higher HbA1c levels were associated with hypoglycemia-related events[129]. Previous studies have found that preoperative HbA1c, lower BMI, and greater postoperative weight loss are predictors of PBSH[109,130]. A study by Nielsen et al[131] showed that younger age and lower postoperative BMI were strong predictors of PBSH, while a study by Belligoli et al[132] demonstrated that the incidence of hypoglycemia was higher in younger patients with lower fasting blood glucose levels and higher triglyceride levels before laparoscopic sleeve gastrectomy. It has also been shown that the longer the duration of surgery, the higher the risk of hypoglycemia[109,133].

Much remains to be learned about the causes, diagnosis, and treatment of PBSH, and it will be necessary in the future to reach a consensus on the definition and diagnostic criteria for PBSH and to adopt a more scientifically intelligent diagnostic paradigm for the long-term monitoring of bariatric surgery patients in order to detect and reduce the risk of PBSH promptly. In conclusion, despite the risk of serious adverse events from reactive hypoglycemia, it is not sufficient to be a contraindication to bariatric surgery.

As the prevalence of obesity continues to rise, medical technology improves, and health awareness increases, more and more people with DM will benefit from bariatric surgery. With further basic and clinical research, we believe that the challenges we face today will become clearer in the future. Looking ahead, if one day we discover the mechanism for treating diabetes surgically, looking back, bariatric surgery may be just one step in the treatment of diabetes; we even look forward to the day when a genetic means of curing diabetes in the truest sense of the word will be found, by increasing or eliminating a particular segment of a gene, or by increasing or suppressing the expression of a particular factor.

This review also has some limitations. Firstly, most of the studies had a short follow-up period, and the advantages and disadvantages of bariatric surgery for specific populations require longer follow-ups to obtain more stable and reliable results. Secondly, we did not adequately discuss the effects of bariatric surgery on pregnancy and gender.