Author(s): Sony S Thazhath 1 , Karen L Jones 1 , Michael Horowitz 1 , Christopher K Rayner [*] 2
diabetic gastroparesis; heme oxygenase-1; interstitial cells of Cajal; neuronal nitric oxide synthase; postprandial glycemia; Type 1 diabetes; Type 2 diabetes
Reports of gastric motor dysfunction in patients with diabetes have existed in the literature since at least 1925  , and in 1958, Kassander used the term 'gastroparesis diabeticorum' to describe abnormally increased gastric retention in these patients  . Diabetic gastroparesis is increasingly recognized as an important clinical disorder, probably reflecting both greater awareness and advances in diagnostic techniques. The American Gastroenterological Association and American Nuclear Medicine Society define gastroparesis as a syndrome characterized by delayed gastric emptying in the absence of mechanical obstruction  , although in defining 'diabetic gastroparesis', other important criteria include: (i) exclusion of transient effects of hyperglycemia (blood glucose >12 mmol/l [220 mg/dl]) or other potential etiologies  , and (ii) association with upper gastrointestinal symptoms such as early satiation, fullness, abdominal pain or bloating, or postprandial hypoglycemia (in insulin-treated patients). The disorder can range from being mildly symptomatic to having severe symptoms leading to malnutrition, electrolyte imbalances and impaired glycemic control  . This review discuses the pathophysiology and management of diabetic gastroparesis, focusing particularly on recent insights.
As the correlation between symptoms and the magnitude of the delay in gastric emptying is poor, it is difficult to make an accurate assessment of the incidence or prevalence of diabetic gastroparesis  . Existing estimates are highly dependent on the definition of gastroparesis chosen by the investigators, and whether the measurements were conducted in the euglycemic state, but delayed gastric emptying per se has a reported prevalence among patients with long-standing Type 1 or Type 2 diabetes ranging from approximately 5% to as high as 65% [5-7] . Although the prevalence of gastroparesis is thought to be greater among Type 1 compared with Type 2 diabetic patients, the absolute number is probably higher in the latter group, given their larger number overall  . Moreover, a 158% rise in hospitalizations for gastroparesis was recorded in the USA between 1995 and 2004  . Female sex and symptoms of abdominal bloating and fullness have been shown to have some predictive value for the presence of delayed gastric emptying of both solids and liquids in Type 1 and Type 2 diabetes  .
Physiology of normal gastric motility
The GI tract is innervated by extrinsic autonomic nerves providing a connection with the CNS, and by the enteric nervous system consisting of the myenteric (Auerbach's) plexus between the longitudinal and circular muscle layers of the muscularis externa, and the submucosal (Meissner's) plexus that is involved in the regulation of absorption, secretion and mucosal blood flow. Interstitial cells of Cajal (ICC), which are non-neural cells with pacemaker properties, function at the interface between the enteric nervous system and the smooth muscle.
The gastric pacemaker is located in the greater curvature of the mid to upper corpus  . ICCs generate electrical slow waves from this region, at a rate of 3 per...