CHAPTER 27 GASTROINTESTINAL MANIFESTATIONS OF Adil E. Bharucha, MD, G. Richard Locke, MD, and Joseph A. Murray, MD

Dr. Adil E. Bharucha is Professor of Medicine and Dr. G. Richard Locke is Professor of Medicine, and both are consultants in the Division of and and the Clinical Enteric Neuroscience Translational and Epidemiological Research Program, and Dr. Joseph A. Murray is Professor of Medicine and a consultant in the Division of Gastroenterology and Hepatology, Gastroenterology Research Unit and Department of Immunology, Mayo Clinic, Rochester, MN.

SUMMARY

Although most attention has traditionally focused on the , diabetes can affect the entire gastrointestinal (GI) tract, as implied by the term diabetic . This chapter details the epidemiology and summarizes the salient features of the pathophysiology, clinical features, and management of diabetic enteropathy.

Diabetic enteropathy may be asymptomatic or manifest with upper (i.e., , dysphagia, dyspepsia, gastroparesis) or lower GI symptoms (i.e., , , and fecal incontinence). GI symptoms are not uncommon ( experienced in 7.6%, in 1.7%) in patients with diabetes presenting for care. However, in community studies, the prevalence of GI symptoms is, for the most part, either not different or only slightly higher in type 1 and than in people without diabetes. For example, 17% of persons with and 14% of those without diabetes had constipation in one study.

Limited data are available on the epidemiology, particularly risk factors, and natural history of these specific GI manifestations among patients with diabetes in the community. For example, the risk of developing gastroparesis over 10 years was 5% in type 1 diabetes and 1% in type 2 diabetes versus <1% in persons without diabetes. GI dysmotility in diabetes is multifactorial: extrinsic and intrinsic (i.e., enteric) neural dysfunction, , and hormonal disturbances have been implicated. Delayed gastric emptying in diabetes is often asymptomatic and is associated with impaired glycemic control.

Approaches to manage diabetic enteropathy primarily focus on correcting the motor disturbance, symptom relief, managing compli- cations, and improving glycemic control. However, there is no evidence that improving glycemic control is beneficial in diabetic enteropathy. From a public health perspective, further studies to better understand the risk factors for diabetic enteropathy and the relationship between diabetic enteropathy and impaired glycemic control and to develop novel approaches to managing diabetic enteropathy are critical.

Type 1 diabetes is associated with gluten-sensitive enteropathy (also known as celiac disease [CD]). CD is very common (approximately 5%) in patients with type 1 diabetes, is often overlooked clinically, and may be asymptomatic while patients accrue health consequences, including growth retardation, bone demineralization, and eventually, symptoms. CD is readily detectable, and at the very least, those looking after patients with type 1 diabetes should have a very low threshold for testing. Screening at initial diabetes diagnosis and yearly for at least 5 years later should be considered in children and at least once in adults. Conversely, there is also a twofold increase in type 1 diabetes in patients with a prior diagnosis of CD (hazard ratio 2.4, 95% conf