Bariatric Surgery and T2DM: Long-term Boon or Bust?

Bariatric surgery holds promise as a means to induce remission in type 2 diabetes mellitus (T2DM), but does it really work in the long term?

One recent randomized controlled trial conducted at the University of Pittsburgh says yes. The analysis included 52 patients and found that 40% of patients who received roux-en-Y gastric bypass and 29% who received laparoscopic gastric banding were still in remission 3 years after surgery, while no patients assigned to an intensive lifestyle weight loss intervention achieved remission (P=0.004).¹

On the other hand, another recent study conducted in Israel raises some questions.² The single-center, retrospective study found significant weight regain and decreased T2DM remission rates over time in 443 patients who received laparoscopic sleeve gastrectomy by the same team. One-year remission rates were 50.7%, and these declined to 38.2% at 3 years and 20.0% at 5 years.

These results come at about the same time that the FDA approved two less invasive systems for weight loss. On July 28, 2015, the Reshape Dual Balloon system gained approval. It consists of two attached balloons inserted through the mouth using minimally invasive endoscopy. The balloons, filled with saline and methylene blue dye, occupy space in the stomach. Intended as temporary, they can stay in place for up to six months. Clinical trial results have shown that patients who received the device (n=187) lost 14.3 pounds or 25.1% of excess weight, while those who did not (n=139) lost about 7.2 pounds, or 11.3% of excess body weight.³   

On August 5, 2015 the FDA also approved the Orbera^TM Intragastric Balloon System. Orbera utilizes a single balloon also placed into the stomach through the mouth with minimally invasive endoscopy. It is also intended to be temporary, up to 6 months. The balloon can be filled with varying amounts of saline, depending on the patient’s body habitus. A clinical study in 255 patients showed that patients who received Orbera lost about 22 pounds (10.2% of their body weight) 6 months after balloon placement. Three months after removing the device, patients maintained 19.8 pounds of weight loss, while patients who did not receive Orbera lost about 7 pounds (3.3% of their body weight).⁴

Whether or not these devices can result in maintenance of weight loss over time or improve diabetes remission remains an open question. 

The relationship between weight loss and diabetes remission may be complex, as suggested by recent results from an Italian study.⁵  The study is noteworthy in reporting for the first time long-term 5-year results from an open-label RCT comparing bariatric surgery to antidiabetes medications. Results showed that 50% of patients who received Roux-en-Y gastric bypass or biliopancreatic diversion were still in diabetes remission at 5 years, but no patients treated with medical therapy achieved remission. Interestingly, post-surgical weight changes did not predict remission.

In fact, there may be more going on than just weight loss. Surgical effects independent of weight loss, duration of diabetes, and remaining beta cell function may also play a role.⁶

Aside from gastric effects and decreased food intake, bariatric surgery may also have an impact on mechanisms in the small bowel involved in glycemic control. Studies have suggested that increasing the rate of food transit in the gut increases secretion of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic (GIP), peptide-YY (PYY), and oxyntmodulin (OXM), all of which affect glucose metabolism. Lower ghrelin levels, which decrease appetite, have been shown after bariatric surgery. Human and animal studies have also suggested proliferation of the beta cell mass after surgery. Moreover, improved hepatic insulin sensitivity has been reported within a few days of surgery and before any significant weight loss can happen. Improvements in plasma bile acids, lipid metabolism, and gut microbiota may also improve glycemic and lipid control, though the mechanisms remain unclear.⁷

Taking things a step further, results from the prospective Swedish Obese Subjects (SOS) study have suggested prioritization of patients with obesity and recent-onset diabetes because they may stand to benefit the most from bariatric surgery. The study included over 2000 patients in Sweden, and found that after 15 years of follow up, patients who had recent onset diabetes and received bariatric surgery had lower long-term health costs, compared to those who received conventional diabetes treatment. To identify obese patients who might benefit most from bariatric surgery, the authors recommended a measure of glucose impairment rather than BMI, as recommended by the US National Institutes of Health.⁸

Given evidence suggesting that bariatric surgery should be performed earlier rather than later in the course of diabetes, there may indeed be a strong need for guidelines that take into account uncontrolled diabetes rather than just BMI. Whether that will help clear up some of the mystery about long-term outcomes and remission of T2DM after bariatric surgery remains to be seen.⁹

Take-home Points

• Long-term results suggest that bariatric surgery can improve rates of diabetes remission, but these rates may decline over time.

• Weight loss, weight-loss independent surgical effects, duration of diabetes, and remaining beta cell function may also play a role in diabetes remission after bariatric surgery.

• Obese patients with recent onset diabetes may benefit most from bariatric surgery, and may need prioritization.

References:

1. Courcoulas AP, et al. Three-year outcomes of bariatric surgery vs lifestyle intervention for type 2 diabetes mellitus treatment: a randomized clinical trial. JAMA Surg. 2015 Jul 1. [Epub ahead of print]

2. Golomb I, et al. Long-term metabolic effects of laparoscopic sleeve gastrectomy. JAMA Surg. 2015 Aug 5. [Epub ahead of print]

3. Food and Drug Administration. ReShape Integrated Dual Balloon System- P140012. Accessed September 17, 2015 at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm456293.htm

4. Food and Drug Administration. Orbera^TM Intragastric Balloon System- P14008. Accessed September 17, 2015 at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm457416.htm

5. Mingrone G, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet. 2015 Sep 5;386(9997):964-973.

6. Adams TD, et al. Long-term mortality after gastric bypass surgery. New ENgl J Med 2007;357:56-61.

7. Pappachan JM, Viswanath AK. Metabolic surgery: a paradigm shift in type 2 diabetes management. World J Diabetes. 2015 Jul 25;6(8):990-998.

8. Keating C, et al. Healthcare costs over 15 years after bariatric surgery for patients with different baseline glucose status: results from the Swedish Obese Subjects study. Lancet Diabetes Endocrinol. Published online September 17, 2015.

9. Cohen R. Bariatric surgery: time to move beyond clinical outcomes. Lancet Diabetes Endocrinol. Published online Sept 17, 2015.