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Metabolic surgery for treating type 2 diabetes mellitus: Now supported by the world's leading diabetes organizations

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ABSTRACT

The term metabolic surgery describes bariatric surgical procedures used primarily to treat type 2 diabetes and related metabolic conditions. Originally, bariatric surgery was used as an alternative weight-loss therapy for patients with severe obesity, but clinical data revealed its metabolic benefits in patients with type 2 diabetes. Metabolic surgery is more effective than lifestyle or medical management in achieving glycemic control, sustained weight loss, and reducing diabetes comorbidities. Perioperative adverse events are similar to other gastrointestinal surgeries. New guidelines for type 2 diabetes expand use of metabolic surgery to patients with a lower body mass index.

KEY POINTS

  • Randomized clinical trials have shown that metabolic surgery is statistically superior to medical treatment in achieving targeted glycemic levels along with improvements in weight loss, remission of metabolic syndrome, reduction in medications, and improvements in lipid levels.
  • The safety of metabolic and bariatric surgery has significantly improved with the advent of laparoscopic surgery, resulting in complication profiles similar to those of cholecystectomy and appendectomy.
  • Metabolic surgery is now recommended as standard treatment option for type 2 diabetes in patients with body mass index levels as low as 30 kg/m2.


 

References

Relative distribution of body mass index of patients with diabetes Data from Bays et al.1

Figure 1. Relative distribution of body mass index of patients with diabetes. SHIELD = Study to Help Improve Early Evaluation and Management of Risk Factors Leading to Diabetes (2004); 4,266 of 127,420 survey respondents with diabetes (type 1 = 368; type 2 = 3,898). NHANES = National Health and Nutrition Examination Survey (1999–2002); 998 of 11,441 survey repondents with diabetes (type 1 and 2).

Type 2 diabetes mellitus (DM) and obesity are chronic diseases that often coexist. Combined, they account for tremendous morbidity and mortality. Approximately 85% of all patients with type 2 DM have a body mass index (BMI) cate­gorizing them as overweight (BMI 25.0–29.9 kg/m2) or obese (BMI > 30.0 kg/m2) (Figure 1).1 Obesity is strongly associated with diabetes and is a major cause of insulin resistance that leads to the cascade of hyperglycemia, glucotoxicity, and beta-cell failure, which ultimately leads to the development of microvascular (neuropathy, nephropathy, retinopathy) and macrovascular (myocardial infarction, stroke) complications. Treatment guidelines emphasize that both diabetes and obesity should be treated to optimize long-term outcomes.2–5 Metabolic surgery is the only diabetes treatment proven to result in long-term remission in 23% to 60% of patients depending upon preoperative duration of diabetes and disease severity. This review presents the evidence supporting use of metabolic surgery as a primary treatment for type 2 DM, potential mechanisms for its effects, associated complications, and recommendations for its use in expanded patient populations.

LIMITATIONS OF LIFESTYLE MANAGEMENT AND MEDICATIONS

First-line therapy with lifestyle management and second-line therapy with medications, including oral agents and insulin, are the mainstays of type 2 DM therapy. Although these approaches have reduced hyperglycemia and cardiovascular mortality, many patients have poor glycemic control and develop severe diabetes-related complications. A study using data from the National Health and Nutrition Examination Survey (N = 4,926) to evaluate success rates of lifestyle management plus drug therapy found that just 53% of patients with type 2 DM maintained a hemoglobin A1c (HbA1c) below 7%.6 Similarly, only 51% of those patients achieved a systolic and diastolic blood pressure less than 130/80 mm Hg, and only 56% achieved a low-density lipoprotein cholesterol level less than 100 mg/dL. Altogether, only 19% of the study cohort achieved all 3 therapy targets. Documented limitations of lifestyle counseling and drug therapy include behavior maladaptation, limitations in drug potency, nonadherence to medications, adverse effects, and economic deterrents.7

METABOLIC SURGERY FOR TYPE 2 DM

For patients with obesity and type 2 DM in whom lifestyle management and medications do not achieve desired treatment goals, bariatric surgery has emerged as the most effective treatment for attaining significant and durable weight loss. These gastrointestinal (GI) procedures, which reduce gastric volume with or without rerouting nutrient flow through the small intestine, were developed to yield long-term weight loss in patients with severe obesity. It is now known that they also cause dramatic improvement or remission of obesity-related comorbidities, especially type 2 DM. Research has shown that these effects are not only secondary to weight loss but also depend on neuroendocrine mechanisms secondary to changes in GI physiology. For these reasons, bariatric surgery is increasingly used with the primary intent to treat type 2 DM or metabolic disease, a practice referred to as metabolic surgery.

Most common metabolic surgical procedures.

Figure 2. Most common metabolic surgical procedures.

Between 150,000 and 200,000 bariatric procedures are performed annually in the United States, and nearly 500,000 worldwide.8 The most common procedures are sleeve gastrectomy (SG, 49%), Roux-en-Y gastric bypass (RYGB, 43%), laparoscopic adjustable gastric banding (LAGB, 6%), and bilio­pancreatic diversion with duodenal switch (BPD-DS, 2%) (Figure 2).9,10 The development of laparoscopic, minimally invasive approaches to these procedures, starting in the mid-1990s, has significantly reduced rates of perioperative morbidity and mortality.

For more than 2 decades, indications for metabolic surgery reflected guidelines from a 1991 National Institutes of Health (NIH) consensus conference, which suggested considering surgery only in patients with a BMI of 40 kg/m2 or greater or a BMI of 35 kg/m2 or greater and significant obesity-related comorbidities.11 Guidelines published in 2013 expanded the recommendations to include adults with a BMI of at least 35 kg/m2 and an obesity-related comorbidity, such as diabetes, who are motivated to lose weight.4 These recommendations were primarily designed to guide the use of surgery as a weight-loss intervention for severe obesity. However, guidelines published in 2016 support use of metabolic surgery as a specific treatment for type 2 DM.5

Potential mechanisms resolving type 2 DM: More than weight loss

Bariatric surgery has been shown to have profound glucoregulatory effects. These include rapid improvement in hyperglycemia and reduction in exogenous insulin requirements that occur early after surgery and before the patient has any significant weight loss.12,13 Additionally, experiments in rodents showed that changes to GI anatomy can directly influence glucose homeostasis, independently of weight loss and caloric restriction.14

Although the exact molecular mechanisms underlying the effects of metabolic surgery on diabetes are not fully understood, many factors appear to play a role, including changes in bile acid metabolism, GI tract nutrient sensing, glucose utilization, insulin resistance, and intestinal microbiomes.15 These changes, acting through peripheral or central pathways, or perhaps both, lead to reduced hepatic glucose production, increased tissue glucose uptake, improved insulin sensitivity, and enhanced beta-cell function. A constellation of gut-derived neuro­endocrine changes, rather than a single overarching mechanism, is the likely mediator of postoperative glycemic improvement, with the contributing factors varying according to the surgical procedure.

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