Metabolic surgery in the treatment of type 2 diabetes mellitus

Faced with the dual pandemics of obesity and type 2 diabetes mellitus, heath care providers require a broad array of treatment options. Diet, exercise, and medications remain the cornerstones of type 2 diabetes therapy, but long-term results with lifestyle modifications can be disappointing, and, despite an ever-increasing armamentarium of pharmacotherapeutics, adequate glycaemic control often remains elusive. Moreover, most diabetes medications promote weight gain, and using them to achieve tight glycaemic control introduces a proportionate risk of hypoglycaemia. In cases where behavioural/pharmacological strategies prove insufficient, gastrointestinal surgery offers powerful alternatives for obesity and type 2 diabetes treatment (Fig. 13.4.5.1). Among severely obese patients, bariatric operations cause profound, sustained weight loss, ameliorating obesity-related comorbidities and reducing long-term mortality (1–4). Operations involving intestinal bypasses exert particularly dramatic antidiabetes effects. For example, approximately 84% of obese patients with type 2 diabetes experience diabetes remission after a Roux-en-Y gastric bypass (RYGB), maintaining euglycaemia off diabetes medications for at least 14 years (1, 5–8). Mounting evidence indicates that these effects result not only from weight loss, but also from weight-independent antidiabetic mechanisms (9). Whereas diabetes is traditionally viewed as a relentless disease in which delay of end-organ complications is the major treatment goal, gastrointestinal surgery offers a novel endpoint: complete disease remission. Consequently, conventional bariatric procedures and experimental gastrointestinal manipulations are being used worldwide to treat type 2 diabetes in association with obesity, and, increasingly, among less obese or merely overweight patients (8). Gastrointestinal surgery also offers valuable research opportunities to improve knowledge of diabetes pathogenesis and help develop less invasive procedures and novel pharmaceuticals. This chapter discusses the effects of gastrointestinal operations on type 2 diabetes, and focuses on potential antidiabetic mechanisms that mediate those effects.