Bariatric Surgery Halves Microvascular Risk in Type 2 Diabetes

Bariatric surgery is associated with a lower risk for microvascular disease in people with type 2 diabetes, new research suggests.

The findings, from a retrospective analysis of data from four US integrated healthcare systems, were published online August 7 in Annals of Internal Medicine by Rebecca O'Brien, MD, of Kaiser Permanente Medical Group, Oakland, California, and colleagues.

Among more than 4000 patients who underwent bariatric surgery, the 5-year incidence of microvascular disease — including neuropathy, nephropathy, and retinopathy — was nearly 60% lower than that of 11,000 matched nonsurgical control patients receiving usual diabetes care.

"What's new here is that, with a very large sample size, we found a difference in hard endpoints. Very few studies have done this," senior investigator David Arterburn, MD, MPH, and internist at Kaiser Permanente Washington Health Research Institute, Seattle, told Medscape Medical News.

The study is also notable for including a greater proportion of patients who underwent the more contemporary bariatric procedures, Roux-en-Y gastric bypass and sleeve gastrectomy. Prior studies tended to include a number of patients who underwent older procedures that are now falling out of favor.

Arterburn said that at the very least, the option of bariatric surgery should be discussed with patients who have type 2 diabetes and a body mass index (BMI) of 35 kg/m² or greater.

"It deserves consideration even though the uptake is still very small relative to medical therapy and will remain small, but it should be part of the conversation."

In an accompanying editorial, Carel W. le Roux, MBChB, PhD, professor of experimental pathology at the Diabetes Complications Research Centre, University College Dublin, Ireland, and Philip R. Schauer, MD, professor of surgery at Cleveland Clinic Lerner College of Medicine, Ohio, write, "The healthcare policy implication of these findings is that bariatric surgery should now be considered as an effective [type 2 diabetes] treatment not only to improve hyperglycemia but also to prevent the complications which account for the morbidity and mortality of the disease."

Schauer and le Roux note that although bariatric surgery is traditionally limited to patients with type 2 diabetes who have severe obesity with the aim of reducing the obesity, "with these new data...we can now consider surgery as a treatment for diabetes beyond glycemia."

"Bariatric surgery can now be intended to prevent complications...Surgery should not be a last resort, but instead should be used earlier, as prevention is definitely better than cure."

Asked to comment, endocrinologist Janet B. McGill, MD, professor of medicine at Washington University School of Medicine, St. Louis, Missouri, said, "While the major study limitation is the retrospective design, the findings are important nonetheless."

But, she also pointed out, "Lack of follow-up HbA_1c and other risk factor data make it impossible to determine whether the success of bariatric procedures was simply due to the reduction or resolution of hyperglycemia, or whether other factors such as reduction in hypertension contributed."

"Weight loss should be a focus of treatment for overweight patients with type 2 diabetes, and implementation of weight loss strategies early in the course of diabetes is likely to produce the best results in preventing microvascular disease."

"Remarkable" Decrease in Microvascular Complications

The study included 4024 adults with type 2 diabetes and BMI ≥ 35 kg/m² who underwent bariatric surgery between 2005 and 2011, matched with 11,059 nonsurgical patients with type 2 diabetes and similar BMI and other baseline characteristics, such as age, sex, HbA_1c, insulin use, and diabetes duration.

The bariatric procedures performed were 76% gastric bypass, 17% sleeve gastrectomy, and 7% adjustable gastric banding.

Median follow-up was 4.3 years in both groups.

The rates of incident combined microvascular disease at 1, 3, 5, and 7 years were 6.0%, 11.8%, 16.9%, and 22.5%, respectively, after bariatric surgery, compared with 11.2%, 24.3%, 34.7%, and 44.2% after usual care.

The difference was primarily driven by the incidence of neuropathy, with 5-year rates of 7.2% versus 21.4%.

At 5 years, the risk for incident microvascular disease was significantly lower in surgical patients than in the matched nonsurgical patients, with a hazard ratio of 0.41. The results were significant for each individual complication, with hazard ratios of 0.37 for diabetic neuropathy, 0.41 for nephropathy, and 0.55 for retinopathy.

"Such a remarkable decrease in microvascular complications has rarely been demonstrated by any form of diabetes therapy," le Roux and Schauer write.

Randomized Controlled Trial Still Needed

Despite the successful results, the editorialists say a randomized, controlled trial is necessary as the retrospective design of the current study leaves open the possibility of nonrandomized selection bias; that is, the possibility that patients who choose to have surgery might have unrecognized outcome advantages compared with controls.

The editorialists also point out that the reduced nephropathy findings should be interpreted with caution because the biomarker used to determine kidney function was serum creatinine.

"Substantial weight loss will reduce serum creatinine even if kidney function remains stable or slightly declines, because serum creatinine is also dependent on muscle mass. Thus, as weight declines, so does muscle mass and subsequently serum creatinine," they explain.

However, they add, "That being said, it is reassuring that markers of kidney function didn't deteriorate after surgery and putting all the evidence together it is likely that bariatric surgery does prevent nephropathy."

McGill pointed out that the benefits of bariatric surgery compared with medical treatment stem from "greater weight loss and greater chance that diabetes will remit altogether if done soon enough," but she also stressed that if surgery is performed "later, it might not have the same effect."

The authors conclude, "The findings from this study should help patients and providers to better understand the potential trade-offs of bariatric surgery as treatment of [type 2 diabetes] and help them to make more informed decisions about care."

O'Brien has reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Arterburn has reported receiving grants from the Patient-Centered Outcomes Research Institute, and grants from the National Institutes of Health outside the submitted work. He also has reported receiving personal fees and nonfinancial support from the Michigan Bariatric Surgery Collaborative outside the submitted work. le Roux has reported receiving grants from Science Foundation Ireland and Health Research Board during the conduct of the study, and Novo Nordisk and GI Dynamics. He has reported receiving grants and/or personal fees from Eli Lilly, Johnson & Johnson, Sanofi Aventis, AstraZeneca, Janssen, Bristol-Myers Squibb, Boehringer Ingelheim. Schauer has reported receiving grants and/or personal fees from Ethicon, Medtronic, Pacira, Novo Nordisk, The Medicines Company, Neurotronic, AMAG. McGill has reported receiving research support from the National Institutes of Health, AstraZeneca, Jaeb, Medtronic, Dexcom, Sanofi, and Novartis, serving as a consultant for Boehringer Ingelheim, Novo Nordisk, and Bayer, and participating in speaker's bureaus for Aegerion Pharmaceuticals, MannKind, and Janssen.

Ann Intern Med. Published online August 7, 2018. Abstract

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