Long-term Diabetes Remission Rates After Bariatric Surgery

Surprisingly Low in Spite of Sustained Weight Loss

Mario Kratz

Disclosures

J Clin Endocrinol Metab. 2020;105(6) 

Bariatric surgeries, particularly Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), have become cornerstones in the treatment of severe obesity and type 2 diabetes (T2DM). Strong evidence indicates that a majority of patients with T2DM can expect at least partial remission within the first year after RYGB or VSG surgery.[1] Fewer data have been published comparing the efficacy of different types of bariatric surgery versus intensive lifestyle interventions on T2DM remission in the long term.

In a recent issue of the journal, Courcoulas and colleagues provide 5-year follow-up data from a randomized controlled trial, comparing 5-year diabetes remission rates in 61 patients with T2DM who underwent either RYGB, laparoscopic gastric banding (LAGB), or an intensive lifestyle modification.[2] The data presented could be read as a resounding success for bariatric surgery, particularly RYGB. As the authors state, "nearly 60% of those in the RYGB group and half of the LAGB group did not require any medications for T2DM treatment at 5 years." At the same time, it is noteworthy that while the weight loss in the RYGB group at year 5 (−25%) was very similar to that observed 1 year after surgery (−27%), prevalence rates of any T2DM remission were reduced from 60% at year 1 to 30% at year 5. Notably, complete remission (i.e., normal glucose tolerance) was achieved in only 1 out of 16 participants at year 5. In the group that had undergone LAGB, weight was still ~13% reduced from baseline at year 5; yet, no participant had normal glucose tolerance, and only 19% had partial T2DM remission. While the definition of diabetes remission differed between studies, 3 other trials have found fairly similar rates of partial or full T2DM remission 5 years following different types of bariatric surgery, including RYGB, VSG, LAGB, and biliopancreatic diversion, compared with an intensive lifestyle modification program.[3–5] For example, rates of partial T2DM remission, defined as glycated hemoglobin A1c (HbA1c) ≤ 6.5% without diabetes medications, ranged from 23% to 39% at 5 years following RYGB compared to 0% to 5% in the control groups in all 4 studies.[2–5] Full diabetes remission was defined slightly differently in all studies, and is therefore more difficult to compare. Courcoulas and colleagues applied the most stringent criteria (HBA1c < 5.7% and fasting glucose ≤ 100 mg/dL without diabetes medications), finding that 5% of participants were in full remission 5 years following RYGB, compared with 0% in the nonsurgery control group.[2] These figures were very similar in the study by Ikramuddin et al, at 7% vs 0%, using slightly less stringent criteria (HbA1c < 6.0% without diabetes medications).[4] Schauer and colleagues reported substantially higher diabetes remission, at 29% vs 5%, but they applied the least stringent criteria (HbA1c < 6.0% with or without diabetes medications).[3] While the data by Schauer et al are difficult to compare directly with those published by Ikramuddin et al and Courcoulas et al due to the different definitions used, they do not necessarily seem inconsistent with one another.

What these data cumulatively clearly show is that, whether we consider year 1 or year 5 data, bariatric surgery and specifically RYGB and VSG are still the best tools in the clinical toolshed to improve glycemic control in obese patients with T2DM. While these improvements are most impressive in the first year after surgery, even the remission rates 5 years from surgery are clinically highly significant, as are the longer-term reductions in the incidence of cardiovascular events as well as microvascular complications.[6] Similarly, it cannot be overlooked that in all studies the use of insulin and antidiabetic medications was substantially lower and glycemic control substantially better in individuals who had undergone bariatric surgery.[2–5] Still, the fact that glucose tolerance and glycemic control gradually worsen over time raises important questions.

First, why does glucose tolerance decline over time in spite of fairly stable weight loss? Could this potentially tell us something about the mechanisms through which bariatric surgeries improve glucose tolerance? It is as yet not conclusively known how certain types of bariatric surgery improve glucose tolerance so consistently and rapidly. The factors at play clearly include the substantial weight loss, albeit that is less of a factor in the short term. There is also good evidence for specific effects of different types of bariatric surgery on the gut microbiome, bile acid metabolism, incretin signaling, or measures of low-grade chronic systemic inflammation such as plasma C-reactive protein concentrations (summarized in[1]), all of which may improve glucose tolerance independent of weight loss. And lastly, the acute flip to a negative energy balance that occurs immediately following bariatric surgery has been proposed as a key driver of diabetes remission in the short term.[7] It seems plausible that physiologic benefits that manifest quickly as a result of drastically reduced calorie intake in the days and weeks following bariatric surgery, including reduced ectopic fat deposition in metabolically active organs such as the pancreas and the liver,[8] may help sustain improved glucose tolerance for several months or even 1 or 2 years. However, as the energy deficit shrinks over time, and eventually energy intake matches or even exceeds energy expenditure, these benefits would be expected to gradually disappear. The fact that glucose tolerance gradually declines in the years following bariatric surgery despite mostly sustained weight loss suggests that the acute calorie deficit plays at least an important contributing role in the manifestation of metabolic benefits following bariatric surgery. Similarly, weight stabilization and the absence of a caloric deficit between years 1 and 5 after bariatric surgery could quite plausibly explain the partial loss of glucose homeostasis–related benefits.

Second, clinically, these findings suggest that bariatric surgery is not the final answer to the twin epidemics of obesity and diabetes. When considering the new evidence of declining metabolic benefits of bariatric surgery over time, and when balanced against bariatric surgery–induced micronutrient deficiencies[9] and potentially increased risks of suicide[10] and—following some types of bariatric surgery—alcoholism,[11] the overall health benefits of bariatric surgery appear less impressive than the short-term effects seem to suggests. Thus, while bariatric surgery will remain a major option for obese patients with T2DM, the available evidence on the long-term metabolic and nonmetabolic health effects reinforces the importance of improving our ability to tackle obesity and T2DM also by nonsurgical means.

An important area that would benefit from intensified research efforts is our ability to help individuals adopt healthier lifestyles. The data by Courcoulas[2] and others[3–5] have made it very clear that current lifestyle modification programs are unable to reverse T2DM. Thus, research needs to focus on improving our understanding of how diet composition affects energy and glucose homeostasis, and how we can help individuals make more meaningful and lasting lifestyle changes to not just manage their T2DM, but to treat or even better, prevent it. At the same time, focusing on the individual will likely not be sufficient. We are living in an environment that constantly exposes us to calorically dense, highly seductive, unhealthy foods, and one in which the unhealthy choices are often the easier or cheaper ones, with regard to both diet and physical activity. Thus, if we are serious about addressing the global twin epidemics of obesity and T2DM in a way that is adequate given the scope of the problem, we need improvements in the food environment driven by changing policies for every level of society, affecting the access to healthy versus unhealthy foods, as well as their relative costs and the ways they are marketed. Improvements in our food environment, individual diet choices and physical activity habits, as well as more effective clinical lifestyle modification programs may help improve long-term T2DM remission rates after bariatric surgery further, and—more importantly—may reduce the need for most bariatric surgeries in the first place.

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