14th March 2018, Dr Chee L Khoo
Bariatric/metabolic surgery is an effective strategy to attain diabetes remission in obese patients. Significant and rapid weight loss by any means will improve insulin sensitivity, the internal glucotoxicity and lipotoxicity. Bariatric surgery, in particular, is thought to also lead to changes in gut incretins and neurotransmitters, improvement of hepatic and peripheral insulin sensitivity, altered bile acid metabolism and gut microbiota that are independent of weight loss. All that should lead to improvement in plasma glucose (and lipids).
It would be helpful if there are guidelines that tell us what to do with the anti-diabetic medications after bariatric surgery but there are none. We can get some guide on the long term management of type 2 diabetes (T2D) by looking at studies that informs us on what happens to these patients after bariatric surgery. That’s not hard to do but the literature provides heterogenous remission/recurrence criteria. Some studies will accept remission if metformin is used. It’s a bit hard to compare studies when the criteria are not consistent.
Nonetheless, in a five year retrospective observational study conducted in a population of patients with BMI >35 kg/m2, 165 patients underwent bariatric surgery ((32.7% underwent laparoscopic adjustable band gastroplasty, 56.4% Roux-en-Y gastric bypass, and 10.9% sleeve gastrectomy) between 2010-2012. 110 of them remained compliant for follow up. They used the ADA T2D diagnostic criteria of fasting glucose of >7mmol/L, 2 hour postprandial glucose of >11.0 mmol/L or HbA1c ≥ 6.5%. They define complete remission as HbA1c < 6.0% and on no anti-diabetic medications and partial remission as HbA1c <6.5 and on no anti-diabetic medications.
The mean age of the population was 49.5 +/- 9.02 years. The average BMI was 43.9 +/- 5.93 kg/m2. 95.5% were on at least one anti-diabetic medication. 93.3% were on metformin and 10.5% were on insulin therapy. Maximal weight loss was achieved in the first year. Further weight loss slowed down after that. Significant reduction in HbA1c ((5.72 ± 0.64; p < 0.001) was achieved in the first year and the reduction was maintained till 5th year.
Remission rate
Complete remission (i.e. HbA1c < 6.0% without metformin) was reached by 47.3% of the patients at the end of the first year. If we include patients on metformin, an additional 22% achieve remission. Remission rate remained stable for the 5 years. Interestingly, in patients who were on insulin before surgery, only 1 attained complete remission at year 1 and at year 5, none were in remission.
Recurrence rate
T2DM recurrence criteria was documented in 10 out of the 63 patients (15.9%) who ever attained complete remission. Recurrence happened 20.4 ± 9.88 months after achieving remission. However, HbA1c levels at the end of the follow-up period were still significantly lower than preoperative ones (mean difference of 1.02 ± 0.41%; p < 0.05) in these patients.
Medical management post surgery
Anti-diabetic medication was fully withdrawn in 54 patients (51.4%) during Y1. Younger patients (p < 0.01), those with lower pre-operative fasting glucose (p < 0.05) and HbA1c (p = 0.001) and greater excess body weight loss (EBWL) (p < 0.01) had higher chances of seeing their T2DM medication discontinued. Among patients on insulin therapy before the bariatric procedure (n = 11), seven discontinued it in the first post-operative year (mean HbA1c at Y1 of 6.29 ± 0.70%) but only three were free of any kind of T2DM-targeted therapy. None of them attainted a HbA1c = 6.5% at Y5, probably a sign of a poorer beta cell function in insulin-treated patients.
After year 1, a further 16% of patients’ medications were also stopped. However, medications were restarted in 15% of patients subsequently. The average HbA1c when medications were withdrawn was 5.7%. Insulin therapy was discontinued in three additional patients with no need to be reintroduced in any of the total 10 individuals that withdrew it in the 5-year follow-up period.
Metformin after surgery
Among patients who achieve complete remission, the relapse rate did not differ whether metformin was continued or not. The results were similar over the subsequent 4 years. There were also no difference in their HbA1c whether metformin was continued or not. Higher HbA1c levels at year 1 and greater weight regain were the main predictors of HbA1c levels during the follow-up period of these individuals.
Large clinical trials like the 10-year follow-up of United Kingdom Prospective Diabetes Study (UKPDS) and Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) proved a “legacy effect” showing long-term benefits despite the loss of glycaemic differences after the conclusion of the studies.
T2DM recurrence should not be seen as a surgical failure given that transient remission can potentially bring lifelong benefits. In other words, does a significant improvement in HbA1c control for some period of time later in the T2D disease count towards reduction in microvascular disease? One study focused on this issue in a bariatric cohort and proved that among patients who experienced T2DM relapse the length of time spent in remission was inversely related to the risk of incident microvascular disease (2)
Obesity is closely related to the development of type 2 diabetes (T2D). The ADA/EASD Consensus Statement specifically recommend that all overweight and obese patients with diabetes should be advised of the health benefits of weight loss and encouraged to engage in a program of intensive lifestyle management, which may include food substitution and bariatric surgery
References:
- Pedro Souteiro, Sandra Belo, Daniela Magalhães et al. Long-term diabetes outcomes after bariatric surgery—managing medication withdrawl. International Journal of Obesity https://doi.org/10.1038/s41366-019-0320-5
- Coleman KJ, Haneuse S, Johnson E, Bogart A, Fisher D, O’Connor PJ, et al. Long-term microvascular disease outcomes in patients with type 2 diabetes after bariatric surgery: evidence for the legacy effect of surgery. Diabetes Care. 2016;39:1400–7.