* Assit. prof., *** Prof. & Head of deptt., Deptt. of Surgery, MGIMS ** Asstt prof Deptt. of Medicine. REVIEW ARTICLE

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1 REVIEW ARTICLE TYPE 2 DIABETES MELLITUS - EXPLORING THE AVENUE OF BARIATRIC SURGERY. S RAO*, JAIN VV**, GUPTA DO***. Diabetes is a growing public health problem world-wide and especially in India which pronounced as the capital of diabetes by WHO. Rapid urbanization is giving rise to a multitude of life style changes which adversely affect the metabolic processes, leading to an epidemic of diseases associated with such life style changes. It is predicted that by the year 2025, the maximum prevalence of diabetes would be in India and every 4 th diabetic in the world would be an Indian. 1,2,3. The socioeconomic burden posed by this disease is enormous due its spectrum of complications ranging from peripheral vascular disease (PVD) to coronary artery disease (CAD), chronic kidney disease (CKD), blindness etc. Obesity is an independent risk factor for development of diabetes. In United sates more than 50% patients diagnosed with type 2 DM are obese with a BMI > 30kg/m2 and about 9% are morbidly obese with a BMI > 40kg/m25. this epidemic of obesity has become widespread in the developed world and is spreading rapidly in the developing world 4. Obesity predisposes to type 2 diabetes mellitus (T2DM) through various mechanisms like insulin resistance, impaired glucose tolerance and pancreatic beta cell failure. The adipocyte which is also an endocrine organ releases an array of humoral factors which are responsible for insulin resistance as well as a chronic proinflammatory state. Even a moderate weight loss of 10kgs can cause 30-50% fall in fasting blood glucose (FBG) and 15% fall in glycated hemoglobin (HbA1c) in diabetic patients 5. * Assit. prof., *** Prof. & Head of deptt., Deptt. of Surgery, MGIMS ** Asstt prof Deptt. of Medicine.

2 It is thus not entirely hypothetical to think that weight reduction may offer mortality benefits in association with other factors to maintain euglycemia. Modern medicine offers a concoction of various Insulins and oral hypoglycemic agents targeted to obtain euglycemia. Some of them help in weight reduction but many cause weight gain which further compounds the situation. Lifestyle intervention programs with diet therapy, behavior modification, exercise programs, and pharmacotherapy are widely used in various combinations for obese T2DM patients. Unfortunately with extremely rare exceptions, clinically significant weight loss is generally very modest and transient, particularly in patients with severe obesity 6. Naturally with the commonest options for weight loss like diet and exercise taking a toss, the more lucrative option is Bariatric surgery. Obese diabetes undergoing bariatric surgery show a phenomenal improvement in their glycemic control within days of bariatric surgery and has also been mentioned as "cure for diabetes". It is prudent to say that Bariatric surgery is that ray of hope for those obese and morbidly obese individuals in whom life style interventions are not showing appropriate results. Bariatric surgery includes a spectrum of surgical procedures which can be performed in obese individuals depending upon their varied indications. As per the latest guidelines indications for bariatric surgery include either a BMI >= 40kg/m2 or a BMI of >= 35 kg/m2 with other co morbidities like diabetes mellitus, hypertension or cardiovascular disease 7. In a recently published study, 80 adults with mild to moderate obesity (BMI kg/m2) were randomized to nonsurgical intervention (very-low calorie diet, Orlistat, and lifestyle change) or to surgical intervention (Gastric banding). Surgical treatment was significantly more effective than nonsurgical therapy in reducing weight, resolving the metabolic syndrome, and improving quality of life during a 24-month treatment program. At 2 years, the surgical group had greater weight loss, with a mean of 21.6% of initial weight loss and 87.2% of excess weight loss, whereas the nonsurgical group had a loss of 5.5% of initial weight and 21.8% of excess weight (P _0.001) 8. In a series of 165 patients of diabetes and impaired glucose tolerance Pories et al found a long lasting resolution of diabetes, normalization of HbA1c in 83% of diabetics and 99% of patients with IGT at year following GPB surgery 9.

3 There are various types of procedure in bariatric surgery and are classified as Restrictive, Malabsorptive or Combined. Restrictive procedures include laparoscopic adjustable gastric banding (LABG) and vertical banded gastroplasty (VBG) which primarily reduce the volume of the stomach which decrease the food intake and give early satiety. Malabsorptive procedures like biliopancreatic diversion (BPD) decrease the length of the small intestine and decrease the absorption of nutrients from small gut. Combined procedures include the Roux-en-Y gastric bypass (RYGB) which is the gold standard of treatment for obesity 7. Both the Malabsorptive and combined procedures alter the secretion of orexigenic and anorexigenic gut peptides which interact with the appetite centres in the arcuate nucleus of the hypothalamus and cause decrease in the appetite. It is postulated that the sudden glycemic control within days of surgery in diabetic obese individuals is probably due to caloric restriction and alteration in hormonal levels controlling insulin secretion. These bariatric procedures affect the enteroinsular axis and alter the levels of Incretins (increase in GLP- 1, glucagon like pepetide-1 and reduction in GIP, glucose dependent insulinotropic peptide) as well as cause decreased secretion of ghrelins. The bariatric literature has consistently demonstrated a significant effect of bariatric surgery in T2DM remission in patients with BMI 35kg/m2. T2DM resolution or remission has usually been defined as HbA1C values ranging from <6% to <7% in the absence of antidiabetic medications. The prospective, controlled Swedish Obese Subjects Study by Sjöström et al 10 reported a significant difference in the prevalence of diabetes between the surgery group and the conventional treatment group (2 years: 1% versus 8%, P <.001; 10 years: 7% versus 24%, P <.001). Participants who underwent surgery were more likely to recover from diabetes (2 years: 72% versus 21%, P <.001; 10 years: 36% versus 13%, P <.001). A systematic review and meta-analysis of bariatric surgery by Buchwald et al 11 included 136 studies for a total of 22,094 patients; mean baseline BMI was 46.9 kg/m2 ( ). The studies that reported resolution of T2DM included a total of 1846 patients. Diabetes resolution rates were 98.9% after biliopancreatic diversion (BPD), 83.7% after RYGB and 47.9% after AGB. Another systematic review by Levy et al11 confirmed that bariatric surgery was highly effective in obtaining weight reduction in morbidly obese patients of up to 60% of the excess weight, along with resolution of preoperative diabetes in more than 75% of the cases.

4 Gill RS et al 12 did a systematic review on the effects of laparoscopic sleeve gastrectomy (LSG) in weight loss and the remission of type 2 DM. A total of 27 studies and 673 patients were analyzed. The baseline mean body mass index for the 673 patients was 47.4 kg/m2 (range ). The mean percentage of excess weight loss was 47.3% (range %), with a mean follow-up of 13.1 months (range 3-36). DM had resolved in 66.2% of the patients, improved in 26.9%, and remained stable in 13.1%. The mean decrease in blood glucose and hemoglobin A1c after sleeve gastrectomy was mg/dl and -1.7%, respectively. They concluded that. LSG might play an important role as a metabolic therapy for patients with type 2 DM. Trends in mortality in bariatric surgery were reported by Buchwald et al 11. This systematic review and meta-analysis included 360 studies for a total of 85,000 patients with a mean BMI of 47.4 kg/m2. In contrast to the popular belief that bariatric surgery is a drastic measure to treat obesity because of its associated risks, this study demonstrates that mortality from laparoscopic RYGB (LRYGB) is comparable to mortality from laparoscopic cholecystectomy, which is considered to be a safe operation by the general public. Mortality rates from LRYGB in this study were 0.16% within 30 days and 0.09% from 30 days to 2 years. Gastric bypass surgery has been associated with decreased long-term total mortality in severely obese patients, as demonstrated by Adams et al. This retrospective cohort study compared the long-term mortality of 7925 patients who underwent gastric bypass surgery matched for age, sex, and BMI to severely obese control subjects who applied for driver's licenses, using the National Death Index11. During a mean follow up of 7.1 years, adjusted long-term mortality from any cause in the surgery group decreased by 40%, as compared with that in the control group (37.6 versus 57.1 deaths per 10,000 person-years, P <.001); cause-specific mortality in the surgery group decreased by 56% for coronary artery disease (2.6 versus 5.9 per 10,000 person-years, P =.006), by 92% for diabetes (0.4 versus 3.4 per 10,000 person-years, P =.005) and by 60% for cancer (5.5 versus 13.3 per 10,000 person-years, P <.001) However, rates of death not caused by disease, such as accidents and suicide, were 58% higher in the surgery group than in the control group (11.1 versus 6.4 per 10,000 person-years, P =.04). After bariatric surgery, weight loss usually reaches a maximum between 18 and 24 months postoperatively. Mean percent excess weight loss at five years ranged from 48 to 74 % after gastric bypass and from 50 to 60% after vertical banded gastroplasty. In a study of over 600 patients

5 following gastric bypass, with 96% follow-up, mean percent excess weight loss still exceeds 50% fourteen years13. Gastric restrictive surgery in the motivated, cooperative patient, who has been educated in the nutritional requirements to maintain adequate protein/calorie/mineral/vitamin intake, routinely results in a smooth post-operative course, with some protein deficit in the first 3 postoperative months, which is completely restored 18 months after surgery, by which time the patient will have re-established a lean body mass appropriate to the total body weight. Pure gastric restrictive procedures such as vertical banded gastroplasty (VBG), silicone ring vertical gastroplasty (SRG), adjustable silicone gastric banding (ASGB) all achieve weight loss vertical gastroplasty (SRG), adjustable silicone gastric banding (ASGB) all achieve weight loss by restricting volume of intake. Intake becomes a function of the patients' motivation to chew well and eat slowly. Failure to do so may result in repeated vomiting and isolated cases of protein and vitamin deficiency have been reported in these circumstances. Careful patient follow up is therefore mandatory, with particular emphasis on the first three postoperative months. Gastric bypass with Roux-y results in ingested food bypassing the gastric fundus, body, antrum, duodenum and a variable length of proximal jejunum. In consequence, these patients are at risk to develop iron deficiency secondary to lack of contact of food iron with gastric acid and consequent reduced conversion of iron from the relatively insoluble ferrous to the more absorbable ferric form. In addition, vitamin B12 deficiency may result in consequence of food no longer coming in contact with gastric intrinsic factor. Vitamin D and calcium absorption may also be reduced since the duodenum and proximal jejunum, which are the preferential sites of absorption, are bypassed by this procedure. Lifelong supplements of multivitamins, vitamin B12 and calcium are mandatory following this procedure. In spite of the failure of medical therapy by drugs, diet, behavior modification and exercise to achieve documented long term weight loss in the morbidly obese, it is accepted practice to require that the potential candidate for surgical treatment have made good faith attempts to achieve weight loss by dietary means. Although the segment of the morbidly obese population able to lose significant weight by non-surgical means is miniscule, candidates for surgery must be given the opportunity

6 to try, a proposition which justifies insistence on at least one attempt at dietary weight loss prior to acceptance into a bariatric surgery program. References : 1. King H, Aubert RE, Herman WH. Global burden of diabetes ;prevalence,numerical estimates, and projection. Diabetes care 1998; 21: Ramchandran A, Snehlata C, Kapur A, Vijay V, et al for diabetes epidemiology study group in India. High prevalence of diabetes and impaired glucose tolerance in India: National urban diabetes survey. Diabetologia 2001; 44: Ramchandran A, Snehlata C, et al. Impacts of urbanization on the lifestyle and on the prevalence of diabetes in native Asian Indian population. Diabetes Res Clin Pract 1999; 44: Ogden CL, Carroll MD, Curtin LR, Mc- Dowell MA, Tabak CJ, Flegal KM: Prevalence of overweight and obesity in the United States JAMA 2006; 295: Pinkey JH, Sjorstorm CD, Gale EAM. Should surgeons treat diabetes in severely obese people? Lancet 2001; 357: Anderson JW, Grant L, Gotthelf L, Stifler LT: Weight loss and long-term follow-up of severely obese individuals treated with an intense behavioral program. Int J Obes 31: , Marion L. Vetter,Serena Cardillo, Michael R. Rickels, Nayyar Iqbal. Narrative Review: Effect of Bariatric Surgery on Type 2 Diabetes Mellitus. Annals of Internal Medicine 2006 ;150: O'Brien PE, Dixon JB, Laurie C, Skinner S, Proietto J, McNeil J, Strauss B, Marks S, Schachter L, Chapman L, Anderson M:Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial. Ann Intern Med 144: , Pories WJ. Bariatric surgery: risks and rewards. J clin Endocrinol metab.2008;93: Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H et al. effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med Aug 23;357(8):

7 11. Nestor Villamizar,Aurora D. Pryor.. Safety, Effectiveness, and Cost Effectiveness of Metabolic Surgery in the Treatment of Type 2 Diabetes Mellitus. J Obes Gill RS, Birch DW, Shi X, Sharma AM, Karmali S. Sleeve gastrectomy and type 2 diabetes mellitus: a systematic review. Surg Obes Relat Dis Nov-Dec;6(6): Pories WJ, Swanson MS, MacDonald KG, 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(3):339-50; discussion