Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations

doi:10.1016/j.soard.2016.05.018

Surgery for Obesity and Related Diseases

Volume 12, Issue 6, July 2016, Pages 1144-1162

https://doi.org/10.1016/j.soard.2016.05.018 Get rights and content

Abstract

Background

Despite growing evidence that bariatric/metabolic surgery powerfully improves type 2 diabetes (T2D), existing diabetes treatment algorithms do not include surgical options.

Aim

The 2nd Diabetes Surgery Summit (DSS-II), an international consensus conference, was convened in collaboration with leading diabetes organizations to develop global guidelines to inform clinicians and policymakers about benefits and limitations of metabolic surgery for T2D.

Methods

A multidisciplinary group of 48 international clinicians/scholars (75% nonsurgeons), including representatives of leading diabetes organizations, participated in DSS-II. After evidence appraisal (MEDLINE [1 January 2005–30 September 2015]), three rounds of Delphi-like questionnaires were used to measure consensus for 32 data-based conclusions. These drafts were presented at the combined DSS-II and 3rd World Congress on Interventional Therapies for Type 2 Diabetes (London, U.K., 28–30 September 2015), where they were open to public comment by other professionals and amended face-to-face by the Expert Committee.

Results

Given its role in metabolic regulation, the gastrointestinal tract constitutes a meaningful target to manage T2D. Numerous randomized clinical trials, albeit mostly short/midterm, demonstrate that metabolic surgery achieves excellent glycemic control and reduces cardiovascular risk factors. On the basis of such evidence, metabolic surgery should be recommended to treat T2D in patients with class III obesity (BMI≥40 kg/m²) and in those with class II obesity (BMI 35.0–39.9 kg/m²) when hyperglycemia is inadequately controlled by lifestyle and optimal medical therapy. Surgery should also be considered for patients with T2D and BMI 30.0–34.9 kg/m² if hyperglycemia is inadequately controlled despite optimal treatment with either oral or injectable medications. These BMI thresholds should be reduced by 2.5 kg/m² for Asian patients.

Conclusions

Although additional studies are needed to further demonstrate long-term benefits, there is sufficient clinical and mechanistic evidence to support inclusion of metabolic surgery among antidiabetes interventions for people with T2D and obesity. To date, the DSS-II guidelines have been formally endorsed by 45 worldwide medical and scientific societies. Health care regulators should introduce appropriate reimbursement policies.

Section snippets

Executive Summary

T2D is associated with complex metabolic dysfunctions, leading to increased morbidity, mortality, and cost. Although population-based efforts through lifestyle interventions are essential to prevent obesity and diabetes, people who develop this disease should have access to all effective treatment options.

Given its role in metabolic regulation, the GI tract constitutes a clinically and biologically meaningful target for the management of T2D.

A substantial body of evidence has accumulated,

DSS-II Partners and Selection of Voting Delegates

The DSS-II organizing committee and the partner diabetes organizations tasked a multidisciplinary group of 48 international authorities to develop a set of evidence-based recommendations. This DSS-II Expert Committee included scholars representing diabetology, endocrinology, internal medicine, cardiology, gastroenterology, primary care, nutrition, and surgery, including official representatives of partner diabetes organizations (Table 2). To ensure maximum scholarship, voting delegates were

Evidence Supporting Surgical Treatment of T2D

The GI tract is an important contributor to normal glucose homeostasis [35], and mounting evidence, especially over the past decade, has demonstrated benefits of bariatric/metabolic surgery to treat and prevent T2D [3], [5], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [51], [52], [53]. Beyond inducing weight loss–related metabolic improvements, some operations engage mechanisms that improve glucose homeostasis independent of weight loss [6],

Statements and Recommendations

(See Table 3.)

Funding and Duality of Interest

The DSS-II and WCITD 2015 were supported by the International Diabetes Surgery Task Force (a nonprofit organization), King’s College London, King’s College Hospital, Johnson & Johnson, Medtronic, Novo Nordisk, Fractyl, DIAMOND MetaCure, Gore, MedImmune, and NGM Biopharmaceuticals. These sponsors played no role in the selection of voting delegates, the Delphi process, the DSS-II and WCITD 2015 programs, or the writing of this article. None of the DSS-II codirectors, members of the organizing

Author Contributions

F.R. and D.E.C. chaired the writing committee for this article and spearheaded its development. D.M.N., R.H.E., P.R.S., K.G.M.M.A., P.Z.Z., S.D.P., L.J., S.M.S., W.H.H., S.A.A., L.M.K., and G.T.-O. contributed to the preparation of this report. The 48 voting delegates listed in Table 2 participated in a 4-monthlong Delphi-like process to craft the 32 consensus statements, culminating in the DSS-II conference in London, U.K. F.R., D.E.C., P.R.S., and L.M.K. served as codirectors of DSS-II.

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After bariatric surgery, patients with obesity achieve sustainable weight loss, gain in mobility, quality of life and life expectancy. Bariatric surgery can lead to remission of type 2 diabetes or to long term glycaemic control for patients with type 2 diabetes, while medical treatment has a preventive efficacy on micro and macrovascular complications. This has led to the concept of metabolic surgery to treat type 2 diabetes. Despite the benefits, only a small proportion of eligible patients undergo bariatric/metabolic surgery.
Powerful antidiabetic medications, self-estimated lack of knowledge by medical professionals and fear of surgical complications are some of the arguments to prefer medical treatment of type 2 diabetes obesity versus metabolic surgery. We have reviewed in this paper the barriers which explain the low referral rate to metabolic surgery. With the point of view of the diabetologist, the general practitioner and the patient, we have addressed them to help clinicians and patients model an evidenced-based patient-oriented medical plan.
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  Metabolic and bariatric surgery (MBS) is recommended for individuals with a body mass index (BMI) ≥35 kg/m², regardless of presence, absence, or severity of co-morbidities.
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  MBS should be considered for individuals with metabolic disease and BMI of 30-34.9 kg/m².
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  BMI thresholds should be adjusted in the Asian population such that a BMI ≥25 kg/m² suggests clinical obesity, and individuals with BMI ≥27.5 kg/m² should be offered MBS.
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  Long-term results of MBS consistently demonstrate safety and efficacy.
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  Appropriately selected children and adolescents should be considered for MBS.
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While clinical findings demonstrate a superior benefit of cardiovascular (CV) risk reduction in obese patients with type 2 diabetes mellitus (T2D) receiving bariatric surgery over non-T2D patients, the mechanism is unclear. This study aimed to investigate the changes in the CV risk score and five CV-associated biomarkers after gastric bypass surgery.
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The T2D group was significantly older and had a higher CV risk score than the non-T2D group, but body mass index (BMI) was similar between the groups. Preoperative biomarker levels were similar in both the T2D and the non-T2D groups. One year after surgery, the percentage of total weight loss (%TWL) was similar between the two groups (32.2 ± 19.5% versus 34.1% ± 8.8%, p = 0.611). Complete T2D remission (hemoglobin A1c (HbA1c) < 6.0%) was achieved in 29 patients (72.5%). The 10-year CV risk scores by the UKPDS risk engine reduced significantly in both the T2D and the non-T2D groups, but more in the T2D group. Three of five biomarkers changed significantly after surgery: the FGF-19 increased from 195.6 ± 249.1 pg/mL to 283.2 ± 211.8 pg/mL, corin increased from 3.3 ± 2.3 ng/mL to 4.6 ± 3.7 ng/mL, and ox-LDL decreased from 148.5 ± 71.7–107.9 U/L; the P values were 0.002, 0.002 and < 0.001, respectively. The T2D group showed a significantly different change in FGF-19 increase and FGF-21 decrease compared to the non-T2D group. The changes in corin and ox-LDL levels were not different between the T2D and non-T2D groups.
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With an increasing prevalence of obesity, there is a need for new therapies to improve body weight management and metabolic health. Multireceptor agonists in development may provide approaches to fulfill this unmet medical need. LY3437943 is a novel triple agonist peptide at the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R). In vitro, LY3437943 shows balanced GCGR and GLP-1R activity but more GIPR activity. In obese mice, administration of LY3437943 decreased body weight and improved glycemic control. Body weight loss was augmented by the addition of GCGR-mediated increases in energy expenditure to GIPR- and GLP-1R-driven calorie intake reduction. In a phase 1 single ascending dose study, LY3437943 showed a safety and tolerability profile similar to other incretins. Its pharmacokinetic profile supported once-weekly dosing, and a reduction in body weight persisted up to day 43 after a single dose. These findings warrant further clinical assessment of LY3437943.

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: This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc16-0236/-/DC1.

: F.R. and D.E.C. chaired the writing committee for this report.

: This article is reprinted with permission of the American Diabetes Association, Inc., Copyright 2016. The version of record appears in Diabetes Care 2016;39:861–877; doi: 10.2337/dc16-0236.

^⁎⁎: The 2nd Diabetes Surgery Summit voting delegates are listed in Table 2.

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Diabetes special issueMetabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations

Abstract

Background

Aim

Methods

Results

Conclusions

Section snippets

Executive Summary

DSS-II Partners and Selection of Voting Delegates

Evidence Supporting Surgical Treatment of T2D

Statements and Recommendations

Funding and Duality of Interest

Author Contributions

Lancet

Lancet Diabetes Endocrinol

Diabetes Res Clin Pract

Lancet Diabetes Endocrinol

Lancet

Lancet Diabetes Endocrinol

Lancet Diabetes Endocrinol

Cell Metab

Lancet Diabetes Endocrinol

Lancet

J Am Coll Cardiol

J Health Econ

Surg Obes Relat Dis

Lancet Oncol

J Am Coll Surg

J Gastrointest Surg

Surg Obes Relat Dis

Lancet Diabetes Endocrinol

The amelioration of diabetes mellitus following subtotal gastrectomy

Surg Gynecol Obstet

Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery

N Engl J Med

Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus

Ann Surg

Metabolic surgery to treat type 2 diabetes: clinical outcomes and mechanisms of action

Annu Rev Med

Effect of duodenaljejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease

Ann Surg

Potential of surgery for curing type 2 diabetes mellitus

Ann Surg

The Diabetes Surgery Summit consensus conference: recommendations for the evaluation and use of gastrointestinal surgery to treat type 2 diabetes mellitus

Ann Surg

Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial

JAMA

Bariatric surgery versus conventional medical therapy for type 2 diabetes

N Engl J Med

Bariatric surgery versus intensive medical therapy in obese patients with diabetes

N Engl J Med

Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: the Diabetes Surgery Study randomized clinical trial

JAMA

Surgical vs medical treatments for type 2 diabetes mellitus: a randomized clinical trial

JAMA Surg

Roux-en-Y gastric bypass surgery or lifestyle with intensive medical management in patients with type 2 diabetes: feasibility and 1-year results of a randomized clinical trial

JAMA Surg

Randomized pilot trial of bariatric surgery versus intensive medical weight management on diabetes remission in type 2 diabetic patients who do NOT meet NIH criteria for surgery and the role of soluble RAGE as a novel biomarker of success

Ann Surg

Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes

N Engl J Med

Adjustable gastric band surgery or medical management in patients with type 2 diabetes: a randomized clinical trial

J Clin Endocrinol Metab

Gastric bypass surgery vs intensive lifestyle and medical intervention for type 2 diabetes: the CROSSROADS randomised controlled trial

Diabetologia

Three-year outcomes of bariatric surgery vs lifestyle intervention for type 2 diabetes mellitus treatment: a randomized clinical trial

JAMA Surg

Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials

BMJ

Minireview: hormonal and metabolic mechanisms of diabetes remission after gastrointestinal surgery

Endocrinology

Gastric bypass alters both glucose-dependent and glucose-independent regulation of islet hormone secretion

Obesity (Silver Spring)

Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass

Diabetologia

Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes

Nat Med

FXR is a molecular target for the effects of vertical sleeve gastrectomy

Nature

Diabetes special issue
Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations