Metabolic surgery in diabetes
Bariatric surgery versus intensive medical therapy for diabetes: 5-year outcomes
Here, the 5-year results from a randomized study comparing intensive medical therapy alone or with either Roux-en-Y gastric bypass or sleeve gastrectomy are presented, showing the effects of these two surgeries to be durable and significantly better than medical therapy alone.
| Summary points |
- The Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial was a three-group randomized controlled trial involving 150 obese patients with type 2 diabetes mellitus who were randomized to intensive medical therapy alone or with either gastric bypass or sleeve gastrectomy.
- Of the 134 patients who completed the 5-year follow up, a glycated hemoglobin level of ≤6% (primary study endpoint) at 5 years was achieved in 2 of 38 patients receiving medical therapy, compared with 14/49 for gastric bypass and 11/47 for sleeve gastrectomy.
- At 5 years, both surgical procedures were superior to intensive medical therapy for achieving glycated hemoglobin of ≤6% without use of diabetes medication (remission), ≤6.5% without use of diabetes medication and ≤7% with use of diabetes medication.
- The reductions in glycated hemoglobin levels and body mass index (BMI) in the surgical groups were similar among patients with a BMI of <35 kg/m2 and those with a BMI of 35 kg/m2 or more.
- At 5 years, cardiovascular and glucose-lowering medication use was reduced from baseline in the two surgical groups, and reductions in body weight, BMI, waist circumference and waist-to-hip ratio, as well as in triglyceride levels, were greater after surgery than after intensive medical therapy, as were increases in high-density lipoprotein.
- Changes in quality of life measures were significantly better in both the gastric bypass and sleeve gastrectomy groups than in the intensive medical therapy group at 5 years.
- The results of this 5-year follow-up show that the beneficial effects of bariatric surgery on glycemic control are durable, even among patients with mild obesity.
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Schauer PR et al. N Engl J Med 2017; 376: 641–651. doi: 10.1056/NEJMoa1600869
Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5-year follow-up of an open-label, single-center, randomized controlled trial
Five-year results of a randomized controlled trial comparing metabolic surgery and conventional medical treatment in obese patients with type 2 diabetes mellitus (T2DM) are presented here, with results supporting the addition of surgery to the treatment algorithm for T2DM.
| Summary points |
- Sixty patients with type 2 diabetes mellitus (T2DM) and a body mass index of at least 35 kg/m2 were randomized to receive medical treatment, Roux-en-Y gastric bypass or biliopancreatic diversion; 53 patients completed 5 years’ follow-up.
- The primary endpoint was rate of diabetes remission (fasting glucose concentration of ≤5.6 mmol/L and HbA1c of ≤6.5% without active pharmacological treatment for at least 1 year) at 2 years.
- At 5 years, 0/15 patients in the medical treatment group and 19 (50%) of the 38 patients in the surgery group (7/19 in the gastric bypass and 12/19 in the biliopancreatic diversion group) had achieved diabetes remission.
- Hyperglycemia relapsed in 15/34 (44%) surgery patients who achieved 2-year diabetes remission, but these patients maintained a mean HbA1c of 6·7% at 5 years with diet and either metformin or no medication; overall, 31/38 surgical patients maintained HbA1c <7% with little or no glucose-lowering medication.
- At 5 years, surgically treated patients had significantly lower plasma total cholesterol, LDL cholesterol and triglyceride concentrations than medically treated patients, with surgically treated patients also having better scores on quality of life measures than medically treated patients.
- In summary, surgery was shown to be more effective than medical treatment for long-term control of T2DM among obese patients, supporting consideration of surgery in the treatment algorithm for T2DM.
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Mingrone G et al. Lancet 2015; 386: 964–973. doi: 10.1016/S0140-6736(15)00075-6
Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: The CROSSROADS randomized controlled trial
This paper presents the results of the randomized CROSSROADS study, demonstrating that gastric bypass surgery is superior to intensive medical and lifestyle intervention in patients with type 2 diabetes with mild-to-moderate obesity.
| Summary points |
- In the prospective randomized controlled CROSSROADS (Calorie Reduction Or Surgery: Seeking to Reduce Obesity And Diabetes Study) trial, a population-based recruitment strategy was used to enroll patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 30–45 kg/m2, to compare Roux-en-Y (RYGB) surgery to an intensive lifestyle and medical intervention (ILMI).
- Of 1808 screened candidates, 43 were randomized, 23 to surgery and 20 to the ILMI, with 32 participants included in analyses (five surgery participants and six ILMI participants had a baseline BMI of <35 kg/m2).
- The primary outcome, percentage of participants in each group who achieved diabetes remission at 1 year (HbA1c <6.0% off all diabetes medications) was met in 60% of participants after RYGB vs 5.9% with ILMI, with an odds ratio for diabetes remission at 1 year after RYGB compared with ILMI of 19.8 (95% confidence interval 2.0, 194.6).
- Diabetes remission was not predicted by baseline BMI, age or sex, or amount of weight lost during 1 year, and there was no correlation between change in body weight and change in HbA1c at 6 or 12 months among those who underwent RYGB.
- Overall, at 1 year, surgery was superior to the ILMI for diabetes remission, glycemic control, reductions in body weight, adiposity, systolic blood pressure, estimated insulin resistance, use of diabetes medications and hypertension, and overall health state.
- There were 64 adverse events in the ILMI group and 31 in the RYGB group, with more hypoglycemic events with ILMI (n=43) than RYGB (n=16).
- Of note, RYGB was shown to be both safe and effective regardless of BMI, with no greater risk among people with a BMI of <35 kg/m2, the currently accepted threshold for bariatric surgery, calling into question the practice of using strict BMI cutoffs as the primary criteria for surgical selection in patients with T2DM.
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Cummings DE et al. Diabetologia 2016; 59: 945–953. doi: 10.1007/s00125-016-3903-x
Longer-term physiological and metabolic effects of gastric bypass surgery
This review summarizes the metabolic and physiological effects of Roux-en-Y gastric bypass surgery on pancreatic function, peripheral insulin sensitivity and gastrointestinal remodeling.
| Summary points |
- The acute metabolic response to gastric bypass surgery is thought to occur via mechanisms such as improved incretin response, elevated insulin secretion, β-cell protection and proliferation, and increased gut glucose utilization.
- Diabetes reversal after Roux-en-Y gastric bypass (RYGB) surgery may occur via preservation of β-cell function and mass, with two emerging hypotheses for this response:
- The foregut hypothesis – nutrients entering the duodenum stimulate release of an unknown hormone, an anti-incretin. Bypassing this section of the gut inhibits release of this anti-incretin, allowing normal glycemic control.
- The hindgut hypothesis – food entering the lower gut stimulates incretin hormone release (glucagon-like peptide 1), acting on the pancreas to amplify glucose-induced insulin secretion and thus regulation of blood glucose concentrations.
- Improved glycemic control following surgery is associated with acute improvement in β-cell function and survival, leading to compensation of insulin resistance via elevated insulin secretion – the more persistent response in the RYGB group may be due to decreased accumulation of truncal fat and elevated β-cell function.
- Many of the long-term metabolic improvements that occur following bariatric surgery may be explained by the significant weight loss that occurs.
- Gastric bypass surgery has a profound metabolic effect on the liver, skeletal muscle and adipose tissue, with evidence of significant long-term changes in expression and sensitivity of proteins in the insulin-signaling pathway in skeletal muscle.
- Several studies support long-term remodeling of the gastrointestinal mucosa after bariatric surgery, with data suggesting that gastric bypass surgery may improve glycemic control by stimulating intestinal hypertrophy and glucose utilization.
- Bariatric surgery alters exposure of nutrients to bile acids, with the bile acids increasingly recognized as signaling molecules playing a crucial role in lipid and glucose homeostasis.
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Mosinski JD, Kirwan JP. Curr Diab Rep 2016; 16: 50. doi: 10.1007/s11892-016-0747-1
Glycemic control and reduction of cardiovascular risk following bariatric surgery
This chapter examines the effects of the currently used bariatric procedures on cardiovascular risk factors.
| Summary points |
- The four most common bariatric procedures, Roux-en-Y gastric bypass (RYGB), adjustable gastric banding (AGB), vertical sleeve gastrectomy (VSG) and biliopancreatic diversion (BDP) are all associated with significant improvements in cardiovascular risk factors, but specific effects differ.
- The extent of weight loss following bariatric surgery varies by procedure, with the greatest losses occurring with BDP, followed by RYGB and VSG, all of which are associated with rapid loss, followed by AGB, which is associated with more gradual loss.
- Bariatric surgery is also associated with significant improvements in glycemic control, although the magnitude varies by procedure, with the greatest effects again seen with BPD, followed by RYGB and VSG, with a substantially lesser effect with AGB.
- Bariatric surgery is associated with diabetes remission in a high proportion of patients, although over 10 years, many patients experience relapse.
- Alterations in lipid metabolism also occur following bariatric surgery, particularly with BPD, followed by RYGB and VSG.
- Current evidence suggests that all four procedures lead to initial improvements in blood pressure but significant, sustained changes are only seen with RYGB and BPG.
- Bariatric surgery has also been shown to attenuate systemic inflammation, which with RYGB, VSG and BPD may be due to the anti-inflammatory effects of glucagon-like peptide 1.
- There is also evidence to suggest that bariatric surgery may prevent, halt and even reverse progression of renal impairment associated with type 2 diabetes mellitus and obesity.
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Elliott JA, le Roux CW. In: Obesity, bariatric and metabolic surgery: A practical guide. Edited by Agrawal S. Springer International Publishing, 2015. doi: 10.1007/978-3-319-04343-2_55
Clinical outcomes of metabolic surgery: Microvascular and macrovascular complications
In this article, the authors review background information, clinical findings to date and current research regarding microvascular and macrovascular outcomes following bariatric surgery.
| Summary points |
- Data on the impact of bariatric surgery on microvascular outcomes (complications related to renal disease and diabetes-related eye disease and neuropathy) and macrovascular outcomes (coronary artery, cerebrovascular and peripheral vascular diseases), including cardiovascular death, are scarce.
- Tight glycemic control reduces microvascular complications, but macrovascular complications and cardiovascular mortality remain difficult to address.
- While there is substantial evidence for glycemia-lowering effects of bariatric surgery in patients with type 2 diabetes mellitus, remission after surgery is not durable in all patients, with many relapsing at some point.
- Current evidence suggests that the amount of time spent in each of three intermediate health states (unremitted diabetes, durable diabetes remission and diabetes remission followed by relapse) may significantly affect the incidence of micro- and macrovascular complications.
- Nonsurgical treatment modalities have demonstrated a consistent reduction in risk of microvascular disease, and a number of small studies have also reported favorable outcomes in renal function markers following bariatric surgery.
- Studies available to date have shown important reductions in risk of both microvascular and macrovascular outcomes following bariatric surgery, including reductions in risk of all-cause mortality and cardiovascular mortality, cardiovascular events and incidence of albuminuria.
- High-quality randomized controlled trials are needed to define the impact of bariatric surgery on long-term micro- and macrovascular outcomes.
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Adams TD et al. Diabetes Care 2016; 39: 912–923. doi: 10.2337/dc16-0157
Healthcare costs during 15 years after bariatric surgery for patients with different baseline glucose status
In this study, Keating et al. assessed 15-year healthcare costs associated with bariatric surgery compared with conventional medical therapy in obese patients with various baseline glucose states.
| Summary points |
- Healthcare costs were assessed over 15 years in 2010 obese patients who chose to undergo bariatric surgery and compared with a contemporaneously matched obese control group of 2037 patients using Swedish healthcare registers.
- In the surgery group, 13% underwent gastric bypass, 19% underwent gastric banding and 68% underwent vertical-banded gastroplasty.
- Fifteen-year drug costs did not differ between surgery and control groups in euglycemic patients but lower 15-year drug costs were observed in the surgery than the control group in patients with prediabetes and in patients with diabetes. Greater 15-year inpatient costs were observed in the surgery group for all glucose subgroups.
- Total healthcare costs were higher in surgery patients in the euglycemic and prediabetes subgroups, while no difference was detected between treatment groups in patients with diabetes.
- In this study, in which surgery was performed between 1987 and 2001, the rate of laparoscopic surgery was only 11%, compared with 97% in 2012 in Sweden, with such surgery associated with significantly lower costs than open surgery. Additionally, the majority of patients underwent gastric banding and later had re-operations to convert to gastric bypass.
- Overall, for obese patients with type 2 diabetes mellitus, the upfront costs of bariatric surgery appear to be offset by the prevention of further healthcare and drug use.
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Keating C et al. Lancet Diabetes Endo 2015; 3: 855–865. doi: 10.1016/S2213-8587(15)00290-9