Reviews

Bariatric surgery for type 2 diabetes: Weighing the impact for obese patients

Cleveland Clinic Journal of Medicine. 2010 July;77(7):468-476 | 10.3949/ccjm.77a.09135

References

DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 2004; 88:787–835.
Kashyap SR, Defronzo RA. The insulin resistance syndrome: physiological considerations. Diab Vasc Dis Res 2007; 4:13–19.
Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289:76–79.
Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003; 144:5159–5165.
Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 2002; 51:2005–2011.
Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393–403.
Look AHEAD Research Group; Pi-Sunyer X, Blackburn G, Brancati FL, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007; 30:1374–1383.
Look AHEAD Research Group; Wadden TA, West DS, Delahanty L, et al. The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obesity (Silver Spring) 2006; 14:737–752.
Nathan DM. Clinical practice. Initial management of glycemia in type 2 diabetes mellitus. N Engl J Med 2002; 347:1342–1349.
Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2008; 31:173–175.
Spann SJ, Nutting PA, Galliher JM, et al. Management of type 2 diabetes in the primary care setting: a practice-based research network study. Ann Fam Med 2006; 4:23–31.
Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009; 122:248–256.
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004; 292:1724–1737.
Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes. JAMA 2008; 299:316–323.
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; 222:339–350.
Kashyap SR, Daud S, Kelly KR, et al. Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes. Int J Obes (Lond) 2009; epub ahead of print
Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg 2003; 238:467–484.
Sjöström L, Lindroos AK, Peltonen M, et al; Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351:2683–2693.
Scopinaro N, Marinari GM, Camerini GB, Papadia FS, Adami GF. Specific effects of biliopancreatic diversion on the major components of metabolic syndrome: a long-term follow-up study. Diabetes Care 2005; 28:2406–2411.
Scopinaro N, Papadia F, Marinari G, Camerini G, Adami G. Long-term control of type 2 diabetes mellitus and the other major components of the metabolic syndrome after biliopancreatic diversion in patients with BMI < 35 kg/m2. Obes Surg 2007; 17:185–192.
Alexandrides TK, Skroubis G, Kalfarentzos F. Resolution of diabetes mellitus and metabolic syndrome following Roux-en-Y gastric bypass and a variant of biliopancreatic diversion in patients with morbid obesity. Obes Surg 2007; 17:176–184.
Chiellini C, Rubino F, Castagneto M, Nanni G, Mingrone G. The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI < 35 kg/m2. Diabetologia 2009; 52:1027–1030.
Consensus Development Conference Panel. NIH conference. Gastrointestinal surgery for severe obesity. Ann Intern Med 1991; 115:956–961.
Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab 2004; 89:2608–2615.
Cummings DE, Flum DR. Gastrointestinal surgery as a treatment for diabetes. JAMA 2008; 299:341–343.
Bikman BT, Zheng D, Pories WJ, et al. Mechanism for improved insulin sensitivity after gastric bypass surgery. J Clin Endocrinol Metab 2008; 93:4656–4663.
Guidone C, Manco M, Valera-Mora E, et al. Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes 2006; 55:2025–2031.
Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 2006; 244:741–749.
Vilsbøll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept 2003; 114:115–121.
Vollmer K, Holst JJ, Baller B, et al. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 2008; 57:678–687.
Laferrère B, Teixeira J, McGinty J, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab 2008; 93:2479–2485.
Korner J, Bessler M, Inabnet W, Taveras C, Holst JJ. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis 2007; 3:597–601.
le Roux CW, Aylwin SJ, Batterham RL, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 2006; 243:108–114.
Rubino F, Gagner M, Gentileschi P, et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg 2004; 240:236–242.
Salinari S, Bertuzzi A, Asnaghi S, Guidone C, Manco M, Mingrone G. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care 2009; 32:375–380.
Goldfine AB, Mun EC, Devine E, et al. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Metab 2007; 92:4678–4685.
Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346:1623–1630.
Chandarana K, Drew ME, Emmanuel J, et al. Subject standardization, acclimatization, and sample processing affect gut hormone levels and appetite in humans. Gastroenterology 2009; 136:2115–2126.
Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond) 2009; 33:786–795.
Boey D, Sainsbury A, Herzog H. The role of peptide YY in regulating glucose homeostasis. Peptides 2007; 28:390–395.
Hanusch-Enserer U, Ghatei MA, Cauza E, Bloom SR, Prager R, Roden M. Relation of fasting plasma peptide YY to glucose metabolism and cardiovascular risk factors after restrictive bariatric surgery. Wien Klin Wochenschr 2007; 119:291–296.
Laferrère B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care 2007; 30:1709–1716.
Tucker ON, Szomstein S, Rosenthal RJ. Nutritional consequences of weight-loss surgery. Med Clin North Am 2007; 91:499–514.
Davies DJ, Baxter JM, Baxter JN. Nutritional deficiencies after bariatric surgery. Obes Surg 2007; 17:1150–1158.
Angstadt JD, Bodziner RA. Peripheral polyneuropathy from thiamine deficiency following laparoscopic Roux-en-Y gastric bypass. Obes Surg 2005; 15:890–892.
Ritz P, Becouarn G, Douay O, Sallé A, Topart P, Rohmer V. Gastric bypass is not associated with protein malnutrition in morbidly obese patients. Obes Surg 2009; 19:840–844.
Service GJ, Thompson GB, Service FJ, Andrews JC, Collazo-Clavell ML, Lloyd RV. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med 2005; 353:249–254.
Sjöström L, Narbro K, Sjöström CD, et al;Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357:741–752.
Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007; 357:753–761.

At 2 years, the rate of remission (defined as hemoglobin A _1c < 6.2% and a normal fasting glucose level) was 13% in the medical treatment group vs 73% in the surgery group ( P < .001). Patients receiving medical treatment had lost a mean of 1.7% of their body weight, vs 20.7% in the surgical patients ( P < .001). Weight loss was strongly associated with remission of type 2 diabetes after surgery.

This study was controversial in that the medical intervention in this trial was not as aggressive as in the Diabetes Prevention Project and Look AHEAD trials.

INDICATIONS FOR BARIATRIC SURGERY IN PATIENTS WITH DIABETES

According to guidelines from the National Institutes of Health, ²³ the current indications for bariatric surgery include a BMI of 40 kg/m ² or higher, or a BMI between 35 and 40 kg/m ² with at least two obesity-related comorbidities. Diabetes is considered a key comorbidity that justifies the risk of surgery. The guidelines suggest that bariatric surgery be discussed with all severely obese patients (BMI > 35 kg/m ²) with type 2 diabetes who have not been able to lose weight with other weight-control approaches.

Since type 2 diabetes mellitus is a progressive disease characterized by relentless deterioration of beta-cell function, many endocrinologists favor aggressive weight-loss approaches early in the course of the disease. We believe that bariatric surgery should be considered early, as it may help preserve pancreatic betacell function and slow the progression of microvascular and macrovascular complications.

HOW DOES BARIATRIC SURGERY IMPROVE TYPE 2 DIABETES?

Three major mechanisms have been proposed to explain how bariatric surgery reverses diabetes. ^24,25 Table 2 summarizes the effects of the different procedures on factors involved.

Hypothesis 1: Weight loss increases insulin sensitivity

The enforced caloric restriction, negative energy balance, and weight loss after bariatric surgery reduce insulin resistance. Consequently, the beta cells can rest because they don’t need to produce as much insulin. These effects have been observed after both gastric restrictive procedures and gastric bypass procedures.

Hypothesis 2: Less lipotoxicity, inflammation

Another theory is that bariatric surgery lessens insulin resistance by reducing “lipotoxicity,” a condition related to dysregulated fatty acid flux, lipid metabolites in tissues, and direct and indirect effects of hormones secreted by adipocytes.

The strongest evidence for this theory comes from Bikman et al, ²⁶ who found that insulin sensitivity increased after Roux-en-Y surgery more than expected from weight loss alone. One year after surgery, even though they remained anthropometrically obese (BMI > 30 kg/m ²), the patients had insulin sensitivity levels similar to those in a control group of lean people (BMI < 25 kg/m ²).

Insulin sensitivity begins to improve within 1 week of intestinal bypass procedures, ^15,27 suggesting that these procedures are doing something more than simply forcing weight loss via caloric restriction, as gastric restrictive procedures do.

Hypothesis 3: An effect on gut hormones

Figure 1.

The third theory is likely the most relevant and relates to various hormones secreted by the gut in response to food ( Figure 1

References

DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 2004; 88:787–835.
Kashyap SR, Defronzo RA. The insulin resistance syndrome: physiological considerations. Diab Vasc Dis Res 2007; 4:13–19.
Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289:76–79.
Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003; 144:5159–5165.
Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 2002; 51:2005–2011.
Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393–403.
Look AHEAD Research Group; Pi-Sunyer X, Blackburn G, Brancati FL, et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007; 30:1374–1383.
Look AHEAD Research Group; Wadden TA, West DS, Delahanty L, et al. The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obesity (Silver Spring) 2006; 14:737–752.
Nathan DM. Clinical practice. Initial management of glycemia in type 2 diabetes mellitus. N Engl J Med 2002; 347:1342–1349.
Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2008; 31:173–175.
Spann SJ, Nutting PA, Galliher JM, et al. Management of type 2 diabetes in the primary care setting: a practice-based research network study. Ann Fam Med 2006; 4:23–31.
Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med 2009; 122:248–256.
Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004; 292:1724–1737.
Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes. JAMA 2008; 299:316–323.
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; 222:339–350.
Kashyap SR, Daud S, Kelly KR, et al. Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell function and insulinotropic hormones in severely obese patients with type 2 diabetes. Int J Obes (Lond) 2009; epub ahead of print
Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus. Ann Surg 2003; 238:467–484.
Sjöström L, Lindroos AK, Peltonen M, et al; Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351:2683–2693.
Scopinaro N, Marinari GM, Camerini GB, Papadia FS, Adami GF. Specific effects of biliopancreatic diversion on the major components of metabolic syndrome: a long-term follow-up study. Diabetes Care 2005; 28:2406–2411.
Scopinaro N, Papadia F, Marinari G, Camerini G, Adami G. Long-term control of type 2 diabetes mellitus and the other major components of the metabolic syndrome after biliopancreatic diversion in patients with BMI < 35 kg/m2. Obes Surg 2007; 17:185–192.
Alexandrides TK, Skroubis G, Kalfarentzos F. Resolution of diabetes mellitus and metabolic syndrome following Roux-en-Y gastric bypass and a variant of biliopancreatic diversion in patients with morbid obesity. Obes Surg 2007; 17:176–184.
Chiellini C, Rubino F, Castagneto M, Nanni G, Mingrone G. The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI < 35 kg/m2. Diabetologia 2009; 52:1027–1030.
Consensus Development Conference Panel. NIH conference. Gastrointestinal surgery for severe obesity. Ann Intern Med 1991; 115:956–961.
Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab 2004; 89:2608–2615.
Cummings DE, Flum DR. Gastrointestinal surgery as a treatment for diabetes. JAMA 2008; 299:341–343.
Bikman BT, Zheng D, Pories WJ, et al. Mechanism for improved insulin sensitivity after gastric bypass surgery. J Clin Endocrinol Metab 2008; 93:4656–4663.
Guidone C, Manco M, Valera-Mora E, et al. Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes 2006; 55:2025–2031.
Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg 2006; 244:741–749.
Vilsbøll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept 2003; 114:115–121.
Vollmer K, Holst JJ, Baller B, et al. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes 2008; 57:678–687.
Laferrère B, Teixeira J, McGinty J, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab 2008; 93:2479–2485.
Korner J, Bessler M, Inabnet W, Taveras C, Holst JJ. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis 2007; 3:597–601.
le Roux CW, Aylwin SJ, Batterham RL, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 2006; 243:108–114.
Rubino F, Gagner M, Gentileschi P, et al. The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism. Ann Surg 2004; 240:236–242.
Salinari S, Bertuzzi A, Asnaghi S, Guidone C, Manco M, Mingrone G. First-phase insulin secretion restoration and differential response to glucose load depending on the route of administration in type 2 diabetic subjects after bariatric surgery. Diabetes Care 2009; 32:375–380.
Goldfine AB, Mun EC, Devine E, et al. Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. J Clin Endocrinol Metab 2007; 92:4678–4685.
Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346:1623–1630.
Chandarana K, Drew ME, Emmanuel J, et al. Subject standardization, acclimatization, and sample processing affect gut hormone levels and appetite in humans. Gastroenterology 2009; 136:2115–2126.
Korner J, Inabnet W, Febres G, et al. Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond) 2009; 33:786–795.
Boey D, Sainsbury A, Herzog H. The role of peptide YY in regulating glucose homeostasis. Peptides 2007; 28:390–395.
Hanusch-Enserer U, Ghatei MA, Cauza E, Bloom SR, Prager R, Roden M. Relation of fasting plasma peptide YY to glucose metabolism and cardiovascular risk factors after restrictive bariatric surgery. Wien Klin Wochenschr 2007; 119:291–296.
Laferrère B, Heshka S, Wang K, et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care 2007; 30:1709–1716.
Tucker ON, Szomstein S, Rosenthal RJ. Nutritional consequences of weight-loss surgery. Med Clin North Am 2007; 91:499–514.
Davies DJ, Baxter JM, Baxter JN. Nutritional deficiencies after bariatric surgery. Obes Surg 2007; 17:1150–1158.
Angstadt JD, Bodziner RA. Peripheral polyneuropathy from thiamine deficiency following laparoscopic Roux-en-Y gastric bypass. Obes Surg 2005; 15:890–892.
Ritz P, Becouarn G, Douay O, Sallé A, Topart P, Rohmer V. Gastric bypass is not associated with protein malnutrition in morbidly obese patients. Obes Surg 2009; 19:840–844.
Service GJ, Thompson GB, Service FJ, Andrews JC, Collazo-Clavell ML, Lloyd RV. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med 2005; 353:249–254.
Sjöström L, Narbro K, Sjöström CD, et al;Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357:741–752.
Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007; 357:753–761.

Bariatric surgery for type 2 diabetes: Weighing the impact for obese patients

References

Hypothesis 1: Weight loss increases insulin sensitivity

Hypothesis 2: Less lipotoxicity, inflammation

Hypothesis 3: An effect on gut hormones

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