Metabolic surgery for the treatment of type 2 diabetes in patients with BMI lower than 35 kg/m2: Why caution is still needed

Bariatric surgery has shifted from being a risky procedure to an evidence‐based one, with proven benefits on all‐cause mortality, cardiovascular disease, cancer, and diabetes control. The procedure has an overall positive result on type 2 diabetes mellitus (T2DM), with a substantial number of patients achieving disease remission. This has resulted in several studies assessing possible weight‐independent effects of bariatric surgery on glycemic improvement, in addition to recommendation of the procedure to patients with class 1 obesity and T2DM, for whom the procedure was classically not indicated, and adoption of a new term, “metabolic surgery,” to highlight the overall metabolic benefit of the procedure beyond weight loss. Recently, the Diabetes Surgery Summit (DSS) has included metabolic surgery in its T2DM treatment algorithm. Although the discussion brought by this consensus is highly relevant, the recommendation of metabolic surgery for patients with uncontrolled T2DM and a body mass index of 30 to 35 kg/m² still lacks enough evidence. This article provides an overall view of the metabolic benefits of bariatric/metabolic surgery in patients with class 1 obesity, compares the procedure against clinical treatment, and presents our rationale for defending caution on recommending the procedure to less obese individuals.     

Perioperative Glycemic Management of Patients Undergoing Bariatric Surgery

Bariatric surgery in patients with type 2 diabetes has been shown to improve glycemic control and reduce need for glucose-lowering medications. Some of these improvements occur in the early postoperative period prior to any weight loss. These early reductions in circulating glucose can be attributed to primarily perioperative caloric restriction and prolonged fasting. Inpatient glycemic targets for patients undergoing bariatric surgery are similar to those recommended for other surgical procedures as a way of minimizing risk for complications. There is evidence that achieving perioperative and postoperative glycemic targets can improve the ability to achieve remission of type 2 diabetes following gastric bypass surgery. This review provides recommendations regarding glycemic goals, strategies for achieving these goals with minimal risk for hypoglycemia, and an examination of the data suggesting an association between perioperative glycemic management and diabetes remission following bariatric surgery.     

Bariatric surgery and diabetes remission: Sleeve gastrectomy or mini-gastric bypass?

AIM:To investigate the weight loss and glycemic control status[blood glucose,hemoglobin A1c(HbA1c)and hypoglycaemic treatment].METHODS:The primary risk factor for type 2 diabetes is obesity,and 90%of all patients with type 2 diabetes are overweight or obese.Although a remarkable effect of bariatric surgery is the profound and durable resolution of type 2 diabetes clinical manifestations,little is known about the difference among various weight loss surgical procedures on diabetes remission.Data from patients referred during a 3-year period(from January2009 to December 2011)to the University of Naples"FedericoⅡ"diagnosed with obesity and diabetes were retrieved from a prospective database.The patients were split into two groups according to the surgical intervention performed[sleeve gastrectomy(SG)and mini-gastric bypass(MGB)].Weight loss and glycemic control status(blood glucose,HbA1c and hypoglycaemic treatment)were evaluated.RESULTS:A total of 53 subjects who underwent sleeve gastrectomy or mini-gastric bypass for obesity and diabetes were screened for the inclusion in this study.Of these,4 subjects were excluded because of surgical complications,7 subjects were omitted because young surgeons conducted the operations and 11 subjects were removed because of the lack of follow-up.Thirtyone obese patients were recruited for this study.A total of 15 subjects underwent SG(48.4%),and 16underwent MGB(51.6%).After adjusting for various clinical and demographic characteristics in a multivariate logistic regression analysis,high hemoglobin A1c was determined to be a negative predictor of diabetes remission at 12 mo(OR=0.366,95%CI:0.152-0.884).Using the same regression model,MGB showed a clear trend toward higher diabetes remission rates relative to SG(OR=3.780,95%CI:0.961-14.872).CONCLUSION:Although our results are encouraging regarding the effectiveness of mini-gastric bypass on diabetes remission,further studies are needed to provide definitive conclusions in selecting the ideal procedure for diabetes remission.     

Bariatric surgery and type 2 diabetes: are there weight loss‐independent therapeutic effects of upper gastrointestinal bypass?

Type 2 diabetes (T2D) is a major worldwide public health concern. Despite a large armamentarium of T2D medications, a large proportion of patients fail to achieve recommended treatment goals for glycemic control. Weight loss has profound beneficial effects on the metabolic abnormalities involved in the pathogenesis of T2D. Accordingly, bariatric surgery, which is the most effective available weight loss therapy, is also the most effective therapy for treating patients with T2D. Surgical procedures that bypass the upper gastrointestinal (UGI) tract are particularly effective in achieving partial and even complete remission of T2D, suggesting that UGI bypass has weight loss‐independent effects on glycemic control. Although a number of hypotheses (e.g. a role for multiorgan insulin sensitivity, β‐cell function, incretin response, the gut microbiome, bile acid metabolism, intestinal glucose metabolism and browning of adipose tissue) have been proposed to explain the potential unique effects of UGI tract bypass surgery, none has yet been adequately evaluated to determine therapeutic importance in patients with T2D. Here, we review the efficacy of UGI bypass surgery in treating T2D and the mechanisms that have been proposed to explain its potential weight loss‐independent therapeutic effects.     

Effects of glucagon like peptide-1 to mediate glycemic effects of weight loss surgery

To date, weight loss surgeries are the most effective treatment for obesity and glycemic control in patients with type 2 diabetes. Roux-en-Y gastric bypass surgery (RYGB) and sleeve gastrectomy (SG), two widely used bariatric procedures for the treatment of obesity, induce diabetes remission independent of weight loss while glucose improvement after adjustable gastric banding (AGB) is proportional to the amount of weight loss. The immediate, weight-loss independent glycemic effect of gastric bypass has been attributed to postprandial hyperinsulinemia and an enhanced incretin effect. The rapid passage of nutrients into the intestine likely accounts for significantly enhanced glucagon like-peptide 1 (GLP-1) secretion, and postprandial hyperinsulinemia after GB is typically attributed to the combined effects of elevated glucose and GLP-1. For this review we focus on the beneficial effects of the three most commonly performed bariatric procedures, RYGB, SG, and AGB, on glucose metabolism and diabetes remission. Central to this discussion will be the extent to which the effects of surgery are mediated by GLP-1. Better understanding of these mechanisms could provide insight to development of novel therapeutic strategies for treatment of diabetes as well as refinement of surgical techniques.     

Serum levels of osteopontin predict diabetes remission after bariatric surgery

AimBariatric surgery has been shown to effectively improve glycaemic control in morbidly obese subjects. However, the molecular bases of this association are still elusive and may act independently of weight loss. Here, our retrospective study has investigated the inflammatory molecule osteopontin (OPN) as a potential predictor of type 2 diabetes mellitus (T2DM) remission.MethodsBaseline serum levels of OPN were analyzed in 41 T2DM patients who underwent bariatric surgery. Anthropometric measures and biochemical variables, including insulin sensitivity indices (HOMA2), were assessed at baseline and at 1 and 3 years after surgery.ResultsAt baseline, patients who experienced T2DM remission had increased waist circumference, body weight and BMI, and higher serum OPN, compared with non-remitters. Patients with and without T2DM remission improved their lipid and glucose profiles, although insulin resistance indices were only improved in the T2DM remission group. In the overall cohort of both T2DM remission and non-remission patients, baseline circulating levels of OPN significantly correlated with reductions of body weight and BMI over time, and insulin sensitivity improved as well. However, only the HOMA2-%S remained independently associated with serum OPN on multivariate linear regression analysis (B: 0.227, 95% CI: 0.067–0.387, β = 0.831; P = 0.010). Baseline values of OPN predicted 3-year T2DM remission independently of body weight loss, lower BMI and duration of diabetes (OR: 1.046, 95% CI: 1.004–1.090; P = 0.033).ConclusionAlthough larger studies are still needed to confirm our preliminary results, pre-operative OPN serum levels might be useful for predicting 3-year T2DM remission independently of weight loss in patients undergoing bariatric surgery.     

Medical and surgical management of obesity and diabetes: what's new?

We conducted a narrative review of the medical and surgical management of people with obesity and diabetes. Results of this review showed that a 5–10% loss in body weight can be achieved with a change in lifestyle, diet and behaviour and with approved pharmacological therapies in people with obesity and diabetes. New targeted therapies are now available for patients with previously untreatable genetic causes of obesity. Compared to medical treatment, metabolic and bariatric surgery is associated with significantly higher rates of remission from type 2 diabetes and lower rates of incident macrovascular and microvascular complications and mortality. The National Institute for Health and Care Excellence and the American Diabetes Association endorse metabolic and bariatric surgery in obese adults with type 2 diabetes and there may also be a role for this in obese individuals with type 1 diabetes. The paediatric committee of the American Society for Metabolic and Bariatric Surgery have recommended metabolic and bariatric surgery in obese adolescents with type 2 diabetes. Earlier and more aggressive treatment with metabolic and bariatric surgery in obese or overweight people with diabetes can improve morbidity and mortality.     

Role of bariatric-metabolic surgery in the treatment of obese type 2 diabetes with body mass index <35 kg/m2: a literature review

Bariatric surgery has been used to treat type 2 diabetes mellitus (T2DM); however, its efficacy is still debatable. This literature review analyzed articles that evaluated the effects of bariatric surgery in treatment of T2DM in obese patients with a body mass index (BMI) of <35?kg/m(2). A paired t test was applied for the analysis of pre- and postintervention mean BMI, fasting plasma glucose (FPG), and glycosylated hemoglobin (A1c) values. A significant (P<0.001) reduction in BMI (from 29.95±0.51?kg/m(2) to 24.83±0.44?kg/m(2)), FPG (from 207.86±8.51?mg/dL to 113.54±4.93?mg/dL), and A1c (from 8.89±0.15% to 6.35±0.18%) was observed in 29 articles (n=675). T2DM resolution (A1c <7% without antidiabetes medication) was achieved in 84.0% (n=567) of the subjects. T2DM remission, control, and improvement were observed in 55.41%, 28.59%, and 14.37%, respectively. Only 1.63% (n=11) of the subjects presented similar or worse glycemic control after the surgery. T2DM remission (A1c <6% without antidiabetes medication) was higher after mini-gastric bypass (72.22%) and laparoscopic/Roux-en-Y gastric bypass (70.43%). According to the Foregut and Hindgut Hypotheses, T2DM results from the imbalance between the incretins and diabetogenic signals. The procedures that remove the proximal intestine and do ileal transposition contribute to the increase of glucagon-like peptide-1 levels and improvement of insulin sensitivity. These findings provide preliminary evidence of the benefits of bariatric-metabolic surgery on glycemic control of T2DM obese subjects with a BMI of <35?kg/m(2). However, more clinical trials are needed to investigate the metabolic effects of bariatric surgery in T2DM remission on pre-obese and obese class I patients.     

Application of the International Diabetes Federation and American Diabetes Association criteria in the assessment of metabolic control after bariatric surgery

The International Diabetes Federation (IDF) and the American Diabetes Association (ADA) have introduced specific criteria to define the ‘optimization’ of the metabolic state and glycaemic ‘remission’ of type 2 diabetes mellitus (T2DM) after bariatric surgery, respectively. Our objective was to assess the percentage of patients achieving these criteria. Data were collected for body mass index, glycaemic markers, lipids, blood pressure, hypoglycaemia and medication usage from 396 morbidly obese T2DM patients who underwent bariatric surgery in two centres and followed up for 2 years. At year 1, 14% of patients achieved the IDF criteria and 38% the ADA criteria, whereas at 2 years 8 and 9% satisfied these criteria, respectively. A relatively low proportion of patients achieved optimization of the metabolic state and T2DM remission. These patients may potentially benefit from the combination of bariatric surgery and adjuvant medical therapy to achieve optimal metabolic outcomes.     

Current status of bariatric surgery in the treatment of type 2 diabetes

Bariatric surgery (from the Greek words baros meaning ‘weight’ and iatrikos‘the art of healing’) is a rapidly evolving branch of surgical science. The aim is to induce major weight loss in those whose obesity places them at high risk of serious health problems. In an attempt to balance the risks of surgery against the benefits of weight loss, bariatric operations are currently performed only in the morbidly obese, or those with a body mass index (BMI) > 35 kgm^?2 who already have developed comorbidity such as type 2 diabetes. Although weight loss is beneficial for obese patients with diabetes, current medical treatment for obesity is difficult. In contrast, observational studies show a major impact of bariatric surgery on diabetes, raising the question whether this approach should be used more widely to treat diabetes in obese patients? If bariatric surgery were shown to be the best way to treat diabetes in obese subjects the implications for health services would be wide‐ranging. Bariatric surgery leads to withdrawal of diabetic treatment in about 60% or more of patients, and reductions of therapy for many others. Although data on bariatric surgery in subjects with diabetes are provocative, most studies have been uncontrolled or flawed in other ways. Most importantly, bariatric surgery has not yet been compared against standard medical treatment for diabetes in randomized controlled trials with diabetes‐specific endpoints in all relevant patient groups. Potential indications for bariatric surgery are discussed, and the unanswered questions that need to be addressed by clinical trials are summarized. Although small numbers of patients may be interested in bariatric surgery for type 2 diabetes, current data are insufficient to endorse its wide scale use for this indication. Until essential studies are undertaken the role and economics of bariatric surgery in the diabetic clinic will remain uncertain.     

Role of gut microbiota,bile acids and their cross‐talk in the effects of bariatric surgery on obesity and type 2 diabetes

Type 2 diabetes mellitus is becoming increasingly prevalent worldwide, and has become one of the greatest threats to global health. Bariatric surgery was initially designed to achieve weight loss, and subsequently was noted to induce improvements or remission of type 2 diabetes. Currently, these bariatric operations, such as Roux‐en‐Y gastric bypass and sleeve gastrectomy, are the most effective procedures for the treatment of obesity and type 2 diabetes mellitus worldwide. However, the specific mechanism mediating the beneficial effects of metabolic surgery has remained largely unknown. Those mechanical explanations, such as restriction and malabsorption, are challenged by accumulating evidence from human and animal models of these procedures, which points to the weight‐independent factors, such as hormones, bile acids, gut microbiota, nervous system and other potential underlying mechanisms. A growing body of evidence suggests that gut microbiota are associated with the development of several metabolic disorders, and bile acids and FXR signaling are important for the metabolic benefits of bariatric surgery. Given the close relationship between bacteria and bile acids, it is reasonable to propose that microbiota–bile acid interactions play a role in the mechanisms underlying the effects of metabolic surgery.     

Role of the incretin system in the remission of type 2 diabetes following bariatric surgery

AimsIt has been observed, as a collateral outcome of bariatric surgery, that morbidly obese patients with frank type 2 diabetes mellitus or impaired glucose tolerance undergone Roux-en-Y Gastric Bypass (RYGB) or bilio-pancreatic diversion (BPD) became and remained euglycemic since surgery. But, most interestingly, the conversion to euglycemia happened within few days from the operation, long before a significant weight loss could intervene.The purpose of this viewpoint is to try to elucidate the mechanisms involved in the resolution/remission of diabetes after bariatric surgery, in particular highlighting the role played by the modifications in incretin secretion.Data synthesisThe effect of purely restrictive procedures in improving glucose control is directly proportional to the degree of weight loss. In contrast, either RYGB or BPD, the first a mainly restrictive and the second a quite purely malabsorptive bariatric technique, operate through a different mechanism, as a probable consequence of the small intestine bypass. The bypass of different intestinal portions covers a central role in the mechanisms of action of these two surgical procedures. In fact, while RYGB does not affect insulin resistance but increases insulin secretion via the stimulation of nutrient-mediated incretin secretion, BPD induces a full normalization of insulin resistance and, consequently, a significant reduction of insulin secretion. The insulin resistance reversion is only partially explained by the incretin level changes after BPD.ConclusionA role of incretins in type 2 diabetes improvement or resolution is ascertained although it is possible that other, not yet identified, hormone(s) can cooperate with them.     

Gastrointestinal Surgery: Cardiovascular Risk Reduction and Improved Long-Term Survival in Patients with Obesity and Diabetes

Whereas the initial focus of bariatric surgery primarily focused on weight loss and was considered by many clinicians and the public as a cosmetic-driven procedure, this surgical therapy is now recognized as a successful approach to reducing cardiovascular disease risk and the only substantial and sustainable weight loss treatment for most severely obese patients. In addition, as a result of the multiple metabolic-related benefits associated with bariatric surgery, efforts to understand physiologic and biochemical mechanisms have led to a dramatic increase in scientific discovery. This review focuses on bariatric research conducted during the past two decades in relation to cardiovascular disease risk and the effects of this surgical therapy on diabetes. Cardiovascular and diabetes mortality and morbidity associated with bariatric surgery are reviewed. The opportunity for bariatric (and/or metabolic) surgery to provide a preventive strategy for cardiovascular disease and diabetes as well as treatment therapy is presented for clinical consideration.     

Obesity, bariatric surgery and type 2 diabetes--a systematic review

Obesity is endemic in the United States and is closely linked to the development of type 2 diabetes. Both obesity and diabetes are responsible for significant morbidity and mortality. Likewise, both conditions are resistant to treatment. Recent studies have evaluated prevention of type 2 diabetes through intensive lifestyle intervention, while others are examining the impact of bariatric surgery on type 2 diabetes. This article presents an overview of the impact of bariatric surgical and lifestyle interventions on the prevention and treatment of type 2 diabetes. Although studies using a variety of bariatric surgical techniques are included, the focus is on two interventions in particular: the Roux-en-Y gastric bypass and the laparoscopic silicone gastric banding procedure. Outcomes of these procedures are further contrasted with recent lifestyle intervention studies, in particular, the Diabetes Prevention Program study. Gastric bypass studies have been associated with a 99 to 100% prevention of diabetes in patients with IGT and an 80 to 90% clinical resolution of diagnosed early type 2 diabetes. Gastric banding procedures are associated with a lower median (50-60%) clinical remission of type 2 diabetes. Lifestyle intervention studies of obese and glucose-intolerant patients have achieved a 50% reduction in the progression of IGT to diabetes over the short term, with no reported resolution of the disease. Weight loss by any means in the obese patient appears to prevent progression to type 2 diabetes, at least in the short term. Furthermore, sustained weight loss through bariatric surgical intervention is associated both with prevention of progression of IGT and with clinical remission of early type 2 diabetes.     

Recent advances in the modification of taste and food preferences following bariatric surgery

There is a large body of evidence indicating that bariatric surgery provides durable weight loss and health benefits to patients who are obese and have comorbidities such as type 2 diabetes (T2D). However, there are still many questions related to mechanisms of metabolic improvement, predictors of success/failure, and long term consequences, which need to be answered. More recently, there has been a particular interest in the modulation of taste and food preferences that occurs after bariatric surgery and how this affects weight loss in different individuals. Animal models as well as human studies have shed some light on the role of taste in changing food preferences and how these changes may affect weight loss after surgery. The goal of this review is to discuss the physiological and behavioral consequences of bariatric surgery as a treatment for obesity and T2D, with particular emphasis on recent studies describing bariatric surgery-induced modifications in taste perception and food preferences.     

Bariatric Surgery: Effects on the Metabolic Complications of Obesity

Bariatric surgery is increasing at an enormous rate in all countries but the indications for the operation on the basis of metabolic derangements are not clear, as only one controlled randomized trial specifically for a comorbidity has been performed. Thus, it is not clear if bariatric surgery should be offered to all obese patients with long standing type 2 diabetes or poorly controlled hypertension or hypertriglyceridemia, even though these conditions clearly respond in most patients to bariatric surgery and weight loss. It would appear that patients with early type 2 diabetes with reasonable control and a greater body mass index gain more benefit from the operation. More randomized trials are required.     

Surgical treatment of type 2 diabetes: the surgeon perspective

Type 2 diabetes mellitus (T2DM) is a major health priority globally, having achieved pandemic status in the twenty-first century. Several gastrointestinal procedures that were primarily designed to treat morbid obesity result in dramatic remission of diabetes. Studies in experimental rodent models and humans have shown that the glycemic benefits of surgery are at least in part weight-independent and extend to non-morbidly obese subjects with T2DM. Bariatric procedures differ in their ability to ameliorate type 2 diabetes, with intestinal bypass procedures being more effective than purely restrictive procedures. Several studies have demonstrated that the benefits of bariatric surgery extend beyond amelioration of hyperglycemia and include improvement in other cardiovascular risk factors such as dyslipidemia and hypertension. The safety and cost-effectiveness of bariatric surgery are also well established by several studies. In this paper, the authors present the surgeon perspective on the management of type 2 diabetes focusing on the efficacy, safety and cost-effectiveness of metabolic surgery. The available evidence warrants the inclusion of metabolic surgery in the treatment algorithm of type 2 diabetes.     

Gastrointestinal Surgery for Obesity and Diabetes: Weight Loss and Control of Hyperglycemia

Obesity is associated with a variety of weight-related metabolic comorbidities. Bariatric surgery (metabolic/gastrointestinal surgery) not only achieves significant and sustainable weight loss, but also induces extraordinary effects on nearly all obesity-related comorbidities, particularly remission of type 2 diabetes mellitus (T2DM). The mechanisms underlying such effects are slowly being elucidated, and it appears that the metabolic benefits of bariatric surgery are not only attributable to weight loss, but there are also weight independent mechanisms at play. This article outlines the metabolic effects of the most commonly performed bariatric procedures, with a particular emphasis on how they affect glucose metabolism and T2DM.     

Bariatric Surgery and Type 2 Diabetes Mellitus: Surgically Induced Remission

The relationship between obesity and type 2 diabetes mellitus (T2DM) is well known. Morbidly obese patients with T2DM who undergo bariatric surgery have improvement or remission of their diabetes. Different types of bariatric operations offer varying degrees of T2DM remission. These operations are classified as restrictive, malabsorptive, or a combination of both. The gold-standard operation, known as the Roux-en-Y gastric bypass, is a combination operation.Most often, improvement of the diabetes is seen within days of the operation. Various theories to explain this rapid change include calorie restriction and hormonal changes from exclusion of the upper gastrointestinal tract. Weight loss accounts for the sustained improvements in glucose control. The patients who benefit the most are those who are early in their disease course.Having a single treatment for both obesity and T2DM is ideal. As bariatric surgery has become a safe operation when performed by experienced surgeons, it should be considered a treatment for these diseases. The impact it can have on the lives of individual patients and society as a whole is tremendous.     

Cardiovascular benefits of bariatric surgery in morbidly obese patients

Morbid obesity is associated with increased morbidity and represents a major healthcare problem with increasing incidence worldwide. Bariatric surgery is considered an effective option for the management of morbid obesity. We searched MEDLINE, Current Contents and the Cochrane Library for papers published on bariatric surgery in English from 1 January 1990 to 20 July 2010. We also manually checked the references of retrieved articles for any pertinent material. Bariatric surgery results in resolution of major comorbidities including type 2 diabetes mellitus, hypertension, dyslipidemia, metabolic syndrome, non‐alcoholic fatty liver disease, nephropathy, left ventricular hypertrophy and obstructive sleep apnea in the majority of morbidly obese patients. Through these effects and possibly other independent mechanisms bariatric surgery appears to reduce cardiovascular morbidity and mortality. Laparoscopic Roux‐en‐Y gastric bypass (LRYGB) appears to be more effective than laparoscopic adjustable gastric banding (LAGB) in terms of weight loss and resolution of comorbidities. Operation‐associated mortality rates after bariatric surgery are low and LAGB is safer than LRYGB. In morbidly obese patients bariatric surgery is safe and appears to reduce cardiovascular morbidity and mortality.