Publication of a new, albeit retrospective, study has shown that almost a third of obese patients with type 2 diabetes undergoing gastric bypass were effectively "cured" of their diabetes, being in complete remission as per the strictest definition possible that was maintained for 6 years after the surgery.
The researchers also found that patients undergoing such surgery significantly reduced their cardiovascular risk factors according to the Framingham Risk Score and that diabetic nephropathy either improved or was completely resolved; the latter is "remarkable," said the surgeon who led the study, Stacy A. Brethauer, MD, from the Cleveland Clinic, Ohio.
Of the patients, "27% had complete remission maintained for 5 years, and that is the operational definition of a 'cure' by [American Diabetes Association] ADA standards. Hopefully this will help people understand that the effects we see after these procedures are durable. Even in the patients who had some of their diabetes come back, the disease came back milder; we have changed the trajectory," he told Medscape Medical News
Dr. Brethauer first reported the results of the study at the American Surgical Association meeting in Indianapolis in April, and they have been published online today in the Annals of Surgery. His colleague, Philip Schauer, MD, also from the Cleveland Clinic, presented the findings at the Prediabetes and the Metabolic Syndrome 2013 Congress in Vienna, Austria around the same time.
At the time of the presentation at the surgery meeting, the study generated many comments and questions, which are included, together with Dr. Brethauer's responses, in the article.
One noted that this study adds to the findings of STAMPEDE, a randomized controlled trial also carried out at the Cleveland Clinic: "Today's paper adds even more proof. Not only does it work, but it works 5 years later. It is not totally new. We reported good results at 10 years. The Swedish colleagues reported at 20 years. But your paper was far more elegant and far more detailed," observed Walter J. Pories, MD, from East Carolina University, Greenville, North Carolina. Why, then, he wonders, are there still "cries for more evidence, more evidence?"
Dr. Brethauer replies that the surgical community must continue "to provide data to support the concept that this is a surgically treated disease. It is a major paradigm shift for our endocrinology colleagues to accept. And I think it is going to require time and a new generation of endocrinologists before they fully embrace this."
Talking of Cure is "Controversial and Provocative"
Dr. Brethauer explained to Medscape Medical News that while his study is not unique in reporting longer-term outcomes, it is one of the few to have used the strictest definition of remission, as per ADA criteria, "that a patient has to have HbA1c of 6% or less, normal fasting blood glucose [<100 mg/dL], and be completely off diabetes medications for one year."
In their study, the Cleveland Clinic researchers went back and examined the clinical outcomes of 217 patients with type 2 diabetes who underwent bariatric surgery between 2004 and 2007 and had at least 5 years of follow-up. The majority of patients (n = 162) underwent Roux-en-Y gastric bypass (RYGB), with the remainder undergoing gastric banding (n = 32) or sleeve gastrectomy (n = 23).
At a median follow-up of 6 years (range, 5–9 years), a mean excess weight loss of 55% was associated with mean reductions in HbA1c from 7.5% to 6.5% (P < .001) and fasting blood glucose (FBG) from 155.9 mg/dL to 114.8 mg/dL (P < .001).
Long-term complete remission, as per the ADA criteria, occurred in 24% of patients, and partial remission (HbA1c 6%–6.4%, FBG of 100–125 mg/dL for 1 year in the absence of antidiabetic medications) was observed in 26% of patients. In addition, a further 34% of patients improved their long-term diabetes control compared with presurgery status. There were 16% of patients who remained unchanged.
When only the RYGB patients were considered, 31% of patients achieved complete remission; 27% of bypass patients continuously sustained this for more than 5 years, the ADA definition of a "cure," the researchers note, although Dr. Brethauer observed that the use of this term with respect to type 2 diabetes "is still quite controversial and somewhat provocative."
Realistic Expectations; Diabetes Recurs but Legacy Effect
Dr. Brethauer and colleagues go on to say that it's now obvious that the remission rates first seen in short-term studies of bariatric surgery, approaching 80%, are not sustained long term. For example, the 2-year diabetes remission rate seen in the Swedish Obese Subjects (SOS) study of 72% declined to a 36% remission rate after 10 years.
However, what must be appreciated, they say, is that despite recurrences — and "some would consider the recurrence of type 2 diabetes as a failure" — "our data and others must be measured against the known risks of poorly controlled diabetes in patients who do not undergo bariatric surgery."
Even experiencing remission for a few years or simply an improvement in diabetes should yield significant reductions in terms of micro- and macrovascular end points, a "legacy effect," similar to that seen with tight glycemic control in type 2 diabetes in the United Kingdom Prospective Diabetes Study (UKPDS) or with type 1 diabetes in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), they note.
For example, in the subgroup of patients with diabetic nephropathy at baseline in the current study, the condition "either improved or was completely resolved," noted Dr. Brethauer, with 53% of patients seeing regression, 47% remaining stable, and no cases of progression.
And long-term control of cardiovascular risk factors in the study exceeded that of the general population, he points out, with 62% meeting blood-pressure goals after surgery and 72% meeting LDL-cholesterol goals (compared with figures of 51% and 56% in the National Health and Nutrition Examination Survey [NHANES]), for example.
SOS has already demonstrated a reduction in all-cause mortality, cardiovascular deaths, and first-time cardiovascular events after bariatric surgery, he noted, and among those with type 2 diabetes in that trial, "there was a significant reduction in the number of myocardial infarctions at 13 years in the surgery group compared with the standard-treatment group."
Predictors of Remission; Gastric Bypass the Best Tool
His team also found, consistent with other studies, that shorter duration of type 2 diabetes is associated with a higher rate of remission after surgery, as is greater long-term weight loss. But it did not show that poor preoperative glycemic control and insulin use were predictors of remission, as has other research. However, this was probably because relatively few participants had very poor glycemic control in this study, he noted.
All said, the findings indicate that gastric bypass "should be considered as an earlier treatment option for patients with uncontrolled type 2 diabetes," he urged.
And the current results also support prior findings that "gastric bypass is the best metabolic and diabetes operation we can offer," giving the best chance of diabetes remission, he concluded.