Gastric Bypass Induces Diabetes Remission in Mildly Obese



Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m2 or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m2."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."


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