Weight-reducing surgery

Bariatric surgery (weight loss surgery) was pioneered to treat intractable severe obesity, and was initially associated with high morbidity and mortality. With greater experience it has become a relatively safe and highly effective means of achieving weight loss, and it is also a highly effective means of reversing type 2 diabetes. Bariatric surgery is often able to restore euglycaemia, allowing medication to be withdrawn. These benefits emerge rapidly following surgery, and appear to be due both to calorie restriction and to changes in gut physiology. Controlled trials confirm that bariatric surgery has advantages over medical diabetes treatment in the short term, but medium-to-long term relapse rates indicate that it is often not “curative”. By-pass surgery, although very effective in producing weight loss, also results in permanent loss of gut tissue and absorptive capacity, with a permanent requirement for dietary supplements and a range of possible undesirable consequences. It is however a cost-effective option and undoubtedly effective when all other strategies have failed. Bariatric surgery now has an important place in the management of diabetes, but there is ongoing debate as to the extent to which it suitable or desirable for larger numbers of people with diabetes.

Introduction

Although bariatric surgery now has an established place in the management of diabetes, many questions remain. Should it, for example, be restricted to the overweight? Enthusiasts point to benefits in non-obese people with diabetes, but the place of “metabolic surgery” in the non-obese is hotly debated. Patient and professional perspectives may differ concerning surgical intervention, which is often welcomed by the intractably obese but may seem less attractive by those with diabetes and lesser degree of obesity.

At an operational level, procedures that bypass or accelerate transit through the foregut appear more effective than restrictive procedures, and emerging endoscopic therapies may provide less invasive alternatives to surgery. The choice here is between less invasive and potentially reversible restrictive or endoscopic techniques as against more effective but irreversible bypass procedures.

Last but not least, there is great interest in the mechanisms by which bariatric surgery achieves its glucose-lowering effects, well in advance of weight reduction. Better understanding of these mechanisms could lead to alternative approaches to medical management.

Observational studies

In a provocatively titled paper, “Who’d have thought it? An operation proves to be the most effective therapy for adult onset diabetes mellitus”, Pories reported that 83% of patients with T2D undergoing the roux-en-Y gastric bypass (RYGB) appeared to maintain euglycaemia during follow-up of up to 14 years [1]. Although this was an uncontrolled study, and there was little description of the methods used to diagnose and monitor the patients, the results showed that bariatric surgery can radically alter the natural history of T2D, and the need for clinical trials to evaluate the potential of bariatric surgery in the management of patients with T2D was clearly demonstrated[2]. Subsequent meta-analysis of mainly uncontrolled observational studies suggested an overall short term diabetes remission rate of 78% [3]. However, other reports indicate medium to long relapse of diabetes following bariatric surgery in around 40% or more of patients [4][5].

Controlled studies

Controlled studies confirm the findings from observational studies. The Swedish Obese Subjects (SOS) study confirmed that recurrence of T2D was significantly reduced following bariatric surgery compared with non-surgically treated subjects [6], although the difference in remission narrowed to 23% at 10 years. The limitation of the SOS study was that patients with diabetes were not intentionally recruited and there was no medical diabetes treatment arm. Dixon et al. undertook the first small RCT, comparing gastric banding versus medical treatment for T2D, and demonstrated superiority of surgical treatment at 2 years [7]. In the RCT of Schauer and colleagues, at 3 years diabetes remission was achieved by 5% in the medical group, 38% in the gastric bypass group and 24% in the sleeve gastrectomy group [8]. In the RCT of Mingrone et al superior diabetes remission rates were found at 5 years after gastric bypass (37%) and biliopancreatic diversion (63%) compared with medical therapy. Although hyperglycaemia recurred in around 50% by 5 years, the majority of patients maintained low levels of HbA1c [9]. A recently published study comparing the effects of gastric bypass or gastric banding added to medical therapy demonstrated broadly similar results at 3 years [10].

New concept of metabolic surgery

Rubino has also suggested that bariatric surgery, when used as a diabetes treatment, might better be called metabolic surgery [11]. A series of studies including small numbers of patients at lower BMI levels suggests that the glycaemic and metabolic benefits of bariatric surgery are not restricted to patients with T2D and BMI>35 kg/m2, and these data have been presented as a call to abandon all consideration of BMI [12]. There would be considerable commercial, academic and practical implications of such a step, and the current evidence seems at best poor.

A systematic review and meta-analysis of recent short term studies confirmed the idea that bariatric surgery can be beneficial at lower BMI levels but rightly emphasises the need for longer term data [13]. At the time of writing, NICE in the UK, not without controversy, endorsed metabolic surgery as an appropriate option to consider for people with T2D and grade 1 obesity in people of European origin, or at BMI 27.5 kg/m2 in other ethnic groups [14]. It remains to be seen whether patients and their physicians will wish to take advantage of this opportunity. In contrast, the American Diabetes Association, in its clinical practice recommendations of 2015, continued to regard the evidence as insufficient to warrant this recommendation [15]. Treatment efficacy, judged by short term biochemical or clinical endpoints, and long term acceptability to patients are entirely separate matters. Patients’ perceptions of long term safety and nutritional implications will influence the uptake of invasive treatments.

Which operation?

There has been much debate whether any one operation is more likely to achieve remission of T2D. In recent RCTs, glycaemic and metabolic improvements were superior with gastric bypass and biliopancreatic diversion compared with medical therapy [9] and with gastric bypass and sleeve gastrectomy compared with medical therapy [8]. In general, more invasive procedures seem more effective, but are also more likely to have unwanted consequences, so that the relative risks of each surgical option need to be considered carefully by well informed patients. The invasive nature of surgery has led to attempts to develop less invasive procedures that replicate the effects of bariatric surgery. Duodeno-jejunal bypass liner (DJBL) is one such approach. Short term studies suggest significant improvements in glycaemic control and insulin resistance [16]. If endoscopic therapies can perform as well as bariatric surgery this could broaden the appeal of interventional therapies for T2D.

Mechanisms of diabetes remission

The mechanism of diabetes remission following bariatric surgery has attracted great interest. Pories observed that glycaemic improvement occurred within a few days of gastric bypass, well in advance of weight loss [1] – an observation that has been interpreted as showing that non weight loss-related mechanisms improve insulin sensitivity and insulin secretion. Reduced caloric intake is likely to be one factor. There is also evidence for involvement of GLP-1 [17] in the glycaemic improvement following bariatric surgery, and there is recent interest in mechanisms including altered gut microflora and serum bile acids. The identification of the exact mechanisms of diabetes remission is an important research goal, because this could point the way to new and less invasive therapies.

Health economics

The observation of diabetes remission following bariatric surgery raises the possibility that bariatric surgery may be more cost effective than medical therapy in terms of reduced diabetes medication and complication rates. Keating reported that gastric banding was slightly more cost effective than medical therapy for diabetes in long term modelling [18]. However, costs of running bariatric surgery programmes, postoperative care, late surgical complications, cosmetic and metabolic side effects and occasional legal costs are often underestimated.

Although diabetes medications may be reduced or withdrawn, high long term relapse rates in some studies [4][5][9]suggest that patients should remain under long-term observation. Further, reduced diabetes treatment is offset by the need for nutritional monitoring and the occasional need for surgical intervention. There is therefore some uncertainty as to whether bariatric surgery is more cost effective than medical diabetes treatment, and it is distinctly possible that the true costs of surgical intervention have been underestimated. It appears more appropriate to consider surgery as an adjunct to continued medical therapy, for selected patients, rather than as an alternative choice.

The patient perspective

Ultimately, patient choice will decide the extent of bariatric surgery as a treatment for diabetes, especially in grade 1 obese and non-obese patients, and the patient perspective has so far received insufficient attention. Bariatric surgery was developed as a treatment for severe obesity, and the surgical risks and dietary restrictions involved are frequently acceptable to this group. The perception of acceptable risks for metabolic surgery is another matter. Several studies have investigated the attitude of people with T2D to bariatric surgery as treatment for T2D. In a study of patients in a research database in the USA, there was a low level of response to the questionnaire and low interest in bariatric surgery [19]. Summers et al interviewed patients with T2D identified from primary care in the UK. This study also encountered low levels of interest in bariatric surgery as a diabetes treatment [20]. These results seem unsurprising from a medical perspective.

One likely reason is that bariatric surgery is essentially irreversible and carries small, yet nonetheless important surgical risks that the patients would not otherwise have to worry about. Bariatric surgery is seen by patients as a very challenging treatment, and these reservations presumably also apply when the intent of the surgery is metabolic rather than bariatric. This important area has received scant attention. The surgical debate has too often focused upon the selection of the most effective operation, rather than the most acceptable procedure, or the one that produces the best long-term outcome. By-pass surgery, although very effective in producing weight loss, also results in permanent loss of gut tissue and absorptive capacity, with a permanent requirement for dietary supplements and a range of possible undesirable consequences.

Another neglected fact is that modern medical treatment for T2D can proved highly effective and acceptable. It appears unnecessary to strive for full biochemical “remission” of T2D through surgery in order to mitigate most of the macrovascular disease risks. Finally, bariatric surgery substantially limits patients’ dietary freedom, and loss of dietary freedom ranks high among the concerns of patients with T2D [21]. Therefore, from the patient perspective, it is by no means a foregone conclusion that people with T2D in large numbers will embrace the suggested opportunity for metabolic surgery.

Conclusions

Bariatric surgery is an appropriate treatment option to consider for selected obese people with T2D, and offers the best current opportunity to significantly alter the natural history of T2D, at least for a period of time. Although the benefits appear to extend to those with grade 1 obesity, and perhaps some non-obese subjects, the evidence in these groups is far less and long term data are lacking. Therefore the wisdom of extending bariatric surgery to these groups, especially the latter, is seen by many physicians as highly questionable. The reporting of surgical studies has focused on glycaemic endpoints, which are less important than macrovascular disease risk, and the latter is also reduced highly effectively by non-surgical therapies. There are also significant surgical risks, the need for major dietary adaptation, and substantial medium-long term risks of diabetes relapse. It appears appropriate to see bariatric surgery as an additional treatment option for selected patients, and not an intervention that obviates the need for continuing medical management of T2D in the paradigm of a life long chronic condition.

References

  1. ^ Pories WJ et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995; 222:339-350; discussion 350-332.

  2. ^ Pinkney JH, Sjostrom CD, Gale EA. Should surgeons treat diabetes in severely obese people? Lancet 2001; 357:1357-1359.

  3. ^ Buchwald H et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009; 122:248-256 e245.

  4. ^ Chikunguwo SM et al. Analysis of factors associated with durable remission of diabetes after Roux-en-Y gastric bypass. Surg Obes Relat Dis 2010; 6:254-259.

  5. ^ DiGiorgi M et al. Re-emergence of diabetes after gastric bypass in patients with mid- to long-term follow-up. Surg Obes Relat Dis 2010; 6:249-253.

  6. ^ Sjostrom L et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351:2683-2693.

  7. ^ Dixon JB et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA 2008; 299:316-323.

  8. ^ Schauer PR et al. Bariatric surgery versus intensive medical therapy for diabetes--3-year outcomes. N Engl J Med 2014; 370:2002-2013.

  9. ^ Mingrone G et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 2015; 386:964-973.

  10. ^ Courcoulas AP et al. Three-Year Outcomes of Bariatric Surgery vs Lifestyle Intervention for Type 2 Diabetes Mellitus Treatment: A Randomized Clinical Trial. JAMA Surg 2015.

  11. ^ Rubino F et al. Bariatric, metabolic, and diabetes surgery: what's in a name? Ann Surg 2013; 259:117-122.

  12. ^ Cummings DE, Cohen RV. Beyond BMI: the need for new guidelines governing the use of bariatric and metabolic surgery. Lancet Diabetes Endocrinol 2014; 2:175-181.

  13. ^ Muller-Stich BP et al. Surgical versus medical treatment of type 2 diabetes mellitus in nonseverely obese patients: a systematic review and meta-analysis. Ann Surg 2015; 261:421-429.

  14. ^ National Institute for Health and Care Excellence. Obesity: identification, assessment and management of overweight and obesity in children, young people and adults

  15. ^ American Diabetes Association. Standards of medical care in diabetes - 2015. Diabetes Care 2015; 18:S8-S16.

  16. ^ de Moura EG et al. Improvement of insulin resistance and reduction of cardiovascular risk among obese patients with type 2 diabetes with the duodenojejunal bypass liner. Obes Surg 2011; 21:941-947.

  17. ^ Manning S, Pucci A, Batterham RL. GLP-1: a mediator of the beneficial metabolic effects of bariatric surgery? Physiology (Bethesda) 2015; 30:50-62.

  18. ^ Keating CL et al. Cost-effectiveness of surgically induced weight loss for the management of type 2 diabetes: modeled lifetime analysis. Diabetes Care 2009; 32:567-574.

  19. ^ Sarwer DB et al. Attitudes about the safety and efficacy of bariatric surgery among patients with type 2 diabetes and a body mass index of 30-40 kg/m2. Surg Obes Relat Dis 2013; 9:630-635.

  20. ^ Summers RH et al. Weight loss surgery for non-morbidly obese populations with type 2 diabetes: is this an acceptable option for patients? Prim Health Care Res Dev 2013; 15:277-286.

  21. ^ Speight J, Bradley, C. Patient perceptions of diabetes and diabetes therapy: assessing quality of life. Diabetes Metab Res Rev 2002; 18:S64-S69.

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