Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years - PubMed (original) (raw)

Review

Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years

Purna Kashyap et al. Gut. 2010 Dec.

Abstract

Diabetic gastroparesis is a disorder that occurs in both type 1 and type 2 diabetes. It is associated with considerable morbidity among these patients and with the resultant economic burden on the health system. It is primarily a disease seen in middle-aged women, although the increased predisposition in women still remains unexplained. Patients often present with nausea, vomiting, bloating, early satiety and abdominal pain. The pathogenesis of this complex disorder is still not well understood but involves abnormalities in multiple interacting cell types including the extrinsic nervous system, enteric nervous system, interstitial cells of Cajal (ICCs), smooth muscles and immune cells. The primary diagnostic test remains gastric scintigraphy, although other modalities such as breath test, capsule, ultrasound, MRI and single photon emission CT imaging show promise as alternative diagnostic modalities. The mainstay of treatment for diabetic gastroparesis has been antiemetics, prokinetics, nutritional support and pain control. In recent years, gastric stimulation has been used in refractory cases with nausea and vomiting. As we better understand the pathophysiology, newer treatment modalities are emerging with the aim of correcting the underlying defect. In this review, what has been learned about diabetic gastroparesis in the past 5 years is highlighted. The epidemiology, pathogenesis, diagnosis and treatment of diabetic gastroparesis are reviewed, focusing on the areas that are still controversial and those that require more studies. There is also a focus on advances in our understanding of the cellular changes that underlie development of diabetic gastroparesis, highlighting new opportunities for targeted treatment.

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Conflict of interest statement

Competing interests: none to declare

Figures

Figure 1

Figure 1

Figure 1A: Anatomy of the human stomach as it relates to normal gastric physiology in the postprandial state Normal gastric function requires interplay of several cell types including extrinsic nerves, enteric nervous system, immune cells, interstitial cells of Cajal (ICC) and smooth muscle. The fundus is the receptive organ in the stomach and accommodates a meal without increasing intragastric pressure. Vagal efferents through release of NO and other neurotransmitters are primarily responsible for receptive relaxation of the fundus. ICC generate slow waves which are rapidly propagated to smooth muscle circumferentially and slowly propagated longitudinally resulting in circumferential contractions that sweep the body and antrum. Smooth muscle cells secrete insulin like growth factor (IGF-1) which exerts protective effects on ICC. Macrophages are normally resident in the stomach. In conditions associated with increased oxidative stress, a subclass of macrophages express antioxidant enzymes such as heme oxygenase-1. Heme oxygenase-1 protects against the deleterious effects of increased oxidative stress through generation of products such as carbon monoxide (CO). Antral contractions triturate the food particles against a closed pylorus till they reach a size <3mm at which point they pass through the pylorus into the duodenum. Gastric emptying is also regulated by feedback form the duodenum through enterogastric reflexes and release of hormones such as cholecystokinin. Figure 1B - Pathophysiological changes in diabetic gastroparesis Autonomic neuropathy leads to disordered motility and function of the stomach and may underlie the pain experienced by patients. In diabetes, advanced glycation products formed due to increased reactive oxygen species can lead to loss of nNOS, impaired neurotransmission and delayed gastric emptying. Increased oxidative stress seen in diabetes is usually offset by upregulation of anti-oxidant enzymes in macrophages such as heme oxygenase-1. Loss of upregulation leads to damage and loss of ICC resulting in delayed gastric emptying. In addition smooth muscle atrophy leads to loss of IGF-1, a survival factor for ICC.

Figure 1

Figure 1

Figure 1A: Anatomy of the human stomach as it relates to normal gastric physiology in the postprandial state Normal gastric function requires interplay of several cell types including extrinsic nerves, enteric nervous system, immune cells, interstitial cells of Cajal (ICC) and smooth muscle. The fundus is the receptive organ in the stomach and accommodates a meal without increasing intragastric pressure. Vagal efferents through release of NO and other neurotransmitters are primarily responsible for receptive relaxation of the fundus. ICC generate slow waves which are rapidly propagated to smooth muscle circumferentially and slowly propagated longitudinally resulting in circumferential contractions that sweep the body and antrum. Smooth muscle cells secrete insulin like growth factor (IGF-1) which exerts protective effects on ICC. Macrophages are normally resident in the stomach. In conditions associated with increased oxidative stress, a subclass of macrophages express antioxidant enzymes such as heme oxygenase-1. Heme oxygenase-1 protects against the deleterious effects of increased oxidative stress through generation of products such as carbon monoxide (CO). Antral contractions triturate the food particles against a closed pylorus till they reach a size <3mm at which point they pass through the pylorus into the duodenum. Gastric emptying is also regulated by feedback form the duodenum through enterogastric reflexes and release of hormones such as cholecystokinin. Figure 1B - Pathophysiological changes in diabetic gastroparesis Autonomic neuropathy leads to disordered motility and function of the stomach and may underlie the pain experienced by patients. In diabetes, advanced glycation products formed due to increased reactive oxygen species can lead to loss of nNOS, impaired neurotransmission and delayed gastric emptying. Increased oxidative stress seen in diabetes is usually offset by upregulation of anti-oxidant enzymes in macrophages such as heme oxygenase-1. Loss of upregulation leads to damage and loss of ICC resulting in delayed gastric emptying. In addition smooth muscle atrophy leads to loss of IGF-1, a survival factor for ICC.

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