Gastroparesis is defined by objective delaying of gastric emptying without any evidence of mechanical obstruction. Diabetic gastroparesis is a potential complication that occurs in the setting of poorly controlled diabetes, resulting from dysfunction in the coordination and function of the autonomic nervous system, neurons and specialized pacemaker cells (interstitial cells of Cajal, ICC) of the stomach and intestine, and the smooth muscle cells of the gastrointestinal tract.
Hyperglycemia (blood glucose greater than 200 mg/dL), commonly seen in the setting of poorly controlled diabetes, has been associated with diabetic gastroparesis that occurs as a result of neuropathy in the setting of chronic hyperglycemia and does not resolve with improved glycemic control. Acute hyperglycemia, on the other hand, though it can also result in delayed gastric emptying, is often reversible with improved glycemic control.
Gastric emptying requires coordination of fundal tone and antral phasic contraction with simultaneous inhibition of pyloric and duodenal contractions. This coordination also requires interactions between the enteric and autonomic nervous systems, smooth muscle cells, and the specialized pacemaker cells (ICC) of the stomach. The gastric motor dysfunction that is encountered in the setting of diabetes may occur as a result of autonomic neuropathy (both sympathetic and parasympathetic), enteric neuropathy (both excitatory and inhibitory neurons), ICC abnormalities (intrinsic neuropathy), acute blood glucose fluctuations, use of incretin-based medications, or psychosomatic factors. As a result, most diabetic patients tend to have dysfunction at multiple points in the process of gastric emptying. This includes abnormal postprandial proximal gastric accommodation and contraction, as well as abnormalities in antral motor function.
Although idiopathic gastroparesis is the most common form of gastroparesis, diabetes is the most common disease associated with the condition. Upper gastrointestinal symptoms are reported in 11% to 18% of diabetic patients, the majority of which are associated with delayed gastric emptying. Gastroparesis is seen in approximately 4.8% of individuals with type 1 diabetes, 1% of those with type 2 diabetes, and 0.1% of those without diabetes. Although there is a stronger association between type 1 diabetes and gastroparesis, the incidence of type 2 diabetes is much greater, and therefore, gastroparesis associated with type 2 diabetes is seen more frequently. Additionally, incretin mimetics are used to treat type 2 diabetic patients, and these medications pose an additional risk factor for developing gastroparesis.
Signs and symptoms of delayed gastric emptying are seen more frequently in individuals with type 1 versus type 2 diabetes, and typically in those patients who have had the disorder for at least five years. It has been observed that gastroparesis typically occurs in patients with a diagnosis of diabetes of at least ten years, and therefore seen more commonly in older individuals (with type 2 diabetes).
Diabetic gastroparesis occurs as a result of dysfunction in the autonomic and enteric nervous systems. Chronically high levels of blood glucose (or inefficient glucose uptake) leads to neuronal damage resulting in abnormal myenteric neurotransmission (e.g., vagus nerve), impaired inhibitory (nitric oxide) neuronal function, and dysfunctional smooth muscle and pacemaker (interstitial cells of Cajal) cells. Altogether, this dysfunction results in a combination of fewer contractions of the antrum, uncoordinated antro-duodenal contractions, and pyloric spasms ultimately resulting in delayed gastric emptying (gastroparesis).
Delayed gastric emptying in diabetic patients, particularly of solids, may also occur in the setting of abnormal small bowel motility which is thought to occur by a similar mechanism as that which is described in the stomach. Some diabetic patients may additionally experience changes in gastric compliance, both increased or decreased, which may also contribute to delayed gastric emptying.
In addition to this, serum (postprandial) glucose levels have a direct relationship with gastric emptying. In the setting of diabetic autonomic neuropathy, acute hyperglycemia stimulates gastric electrical activity. In diabetic patients (without neuropathy) and healthy controls, acute hyperglycemia will instead relax the proximal stomach, and suppress gastric electrical activity (e.g., reduced the frequency, propagation, and contraction of the antrum) in both fasting and post-prandial conditions, thereby slowing gastric emptying.
Acute hyperglycemia has also been associated with increased sensitivity in the gastrointestinal tract. This may be responsible for the postprandial dyspepsia (e.g., early satiety, nausea, vomiting, heartburn, bloating and pain) frequently experienced by patients with diabetic gastroparesis.
Carbohydrate absorption is highly dependent on the speed of gastric emptying through the release of peptides such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in which slower gastric emptying results in higher level of carbohydrate absorption. Therefore, a higher serum glucose level as a result of delayed gastric emptying can itself lead to worsening of gastroparesis.
The most common symptoms associated with gastroparesis include nausea, vomiting of undigested food, early satiety, bloating of the abdomen, and abdominal pain. In some cases, gastroparesis may also be associated with heartburn, and in severe cases, weight loss.
Factors that may trigger an exacerbation of diabetic gastroparesis include uncontrolled blood glucose levels, medication noncompliance or intolerance, adrenal insufficiency, or infection.
Diabetic gastroparesis is usually suspected based on clinical signs and symptoms, once other potential causes of symptoms have been excluded. Diagnostic evaluation involves scintigraphy (e.g., measuring the rate of emptying of solids) showing delayed gastric emptying, with obstruction (e.g., in the stomach or small intestine) ruled out by endoscopy or imaging (e.g., computed tomography or magnetic resonance imaging).
Treatment of diabetic gastroparesis is aimed at alleviating the associated symptoms and replenishing electrolytes, nutrition, and hydration.  Modalities typically include correction of blood glucose levels (in other words, improved glycemic control), treatment with antiemetics or prokinetics, and modifications to diet. If a patient is on a regimen of incretin-based diabetic therapy (for example, pramlintide or GLP-1 analogs). These medications should be discontinued as they are also known to slow gastric emptying.
Frequently used medications include erythromycin (macrolide antibiotic associated with increased gastrointestinal motility) and metoclopramide (antiemetic and prokinetic). Miralax (polyethylene glycol 3350) may additionally be used to provide relief from severe constipation. Pain relief should be achieved through the use of non-narcotic medications, as narcotics are also known to delay gastric emptying.
Patients who continue to experience symptoms of gastroparesis despite medical therapy may be candidates for gastric electrical stimulation (GES) wherein an electrical device is implanted into the abdomen. It functions to deliver electrical impulses to both the smooth muscles and the neurons innervating the lower stomach. Gastric electrical stimulation has been shown to decrease symptoms of nausea and vomiting in patients with a history of gastroparesis.
Management of diabetic gastroparesis is extremely challenging and is best done with a multidisciplinary team that includes an internist, endocrinologist, diabetic nurse, primary care provider and a gastroenterologist.
Treatment of diabetic gastroparesis is aimed at alleviating the associated symptoms and replenishing electrolytes, nutrition, and hydration.
Frequently used medications include erythromycin (macrolide antibiotic associated with increased gastrointestinal motility) and metoclopramide (antiemetic and prokinetic) and Miralax (polyethylene glycol 3350) may additionally be used to provide relief from severe constipation.
Patients who continue to experience symptoms of gastroparesis despite medical therapy may be candidates for gastric electrical stimulation (GES) wherein an electrical device is implanted into the abdomen.
|||Fehnel S,Fiedorek FT,Nelson L,DiBenedetti D,Spence S,Carson RT, Development and psychometric evaluation of the Diabetic Gastroparesis Symptom Severity Diary. Clinical and experimental gastroenterology. 2019; [PubMed PMID: 30863134]|
|||Chedid V,Halawi H,Brandler J,Burton D,Camilleri M, Gastric accommodation measurements by single photon emission computed tomography and two-dimensional scintigraphy in diabetic patients with upper gastrointestinal symptoms. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2019 Mar 13; [PubMed PMID: 30868676]|
|||Parkman HP,Wilson LA,Hasler WL,McCallum RW,Sarosiek I,Koch KL,Abell TL,Schey R,Kuo B,Snape WJ,Nguyen L,Farrugia G,Grover M,Clarke J,Miriel L,Tonascia J,Hamilton F,Pasricha PJ, Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life. Digestive diseases and sciences. 2019 Mar 9; [PubMed PMID: 30852767]|
|||Liang GG,Zhang QK,Zhang GX,Liu MC, Therapeutic effect of a temporary transpyloric stent in refractory post-surgical gastroparesis: a case report. BMC surgery. 2019 Feb 27; [PubMed PMID: 30813940]|
|||Revicki DA,Speck RM,Lavoie S,Puelles J,Kuo B,Camilleri M,Almansa C,Parkman HP, The American neurogastroenterology and motility society gastroparesis cardinal symptom index-daily diary (ANMS GCSI-DD): Psychometric evaluation in patients with idiopathic or diabetic gastroparesis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2019 Apr; [PubMed PMID: 30734412]|
|||Abell TL,Kedar A,Stocker A,Beatty K,McElmurray L,Hughes M,Rashed H,Kennedy W,Wendelschafer-Crabb G,Yang X,Fraig M,Omer E,Miller E,Griswold M,Pinkston C, Gastroparesis syndromes: Response to electrical stimulation. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2019 Mar; [PubMed PMID: 30706646]|
|||Gulati R,Khalid S,Tafoya MA,McCarthy D, Nausea and Vomiting in a Diabetic Patient with Delayed Gastric Emptying: Do not Delay Diagnosis. Digestive diseases and sciences. 2019 Mar; [PubMed PMID: 30673987]|
|||Moshiree B,Potter M,Talley NJ, Epidemiology and Pathophysiology of Gastroparesis. Gastrointestinal endoscopy clinics of North America. 2019 Jan; [PubMed PMID: 30396519]|
|||Izzy M,Lee M,Johns-Keating K,Kargoli F,Beckoff S,Chun K,Tokayer A, Glycosylated hemoglobin level may predict the severity of gastroparesis in diabetic patients. Diabetes research and clinical practice. 2018 Jan; [PubMed PMID: 29111279]|
|||Burlen J,Runnels M,Mehta M,Andersson S,Ducrotte P,Gourcerol G,Lindberg G,Fullarton G,Abrahamsson H,Al-Juburi A,Lahr C,Rashed H,Abell T, Efficacy of Gastric Electrical Stimulation for Gastroparesis: US/European Comparison. Gastroenterology research. 2018 Oct; [PubMed PMID: 30344806]|
|||Krishnasamy S,Abell TL, Diabetic Gastroparesis: Principles and Current Trends in Management. Diabetes therapy : research, treatment and education of diabetes and related disorders. 2018 Jul; [PubMed PMID: 29934758]|
|||Camilleri M, Clinical practice. Diabetic gastroparesis. The New England journal of medicine. 2007 Feb 22; [PubMed PMID: 17314341]|
|||Koch TR,Shope TR,Camilleri M, Current and future impact of clinical gastrointestinal research on patient care in diabetes mellitus. World journal of diabetes. 2018 Nov 15; [PubMed PMID: 30479683]|
|||Parkman HP,Yamada G,Van Natta ML,Yates K,Hasler WL,Sarosiek I,Grover M,Schey R,Abell TL,Koch KL,Kuo B,Clarke J,Farrugia G,Nguyen L,Snape WJ,Miriel L,Tonascia J,Hamilton F,Pasricha PJ,McCallum RW, Ethnic, Racial, and Sex Differences in Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients With Gastroparesis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018 Nov 4; [PubMed PMID: 30404035]|
|||Harberson J,Thomas RM,Harbison SP,Parkman HP, Gastric neuromuscular pathology in gastroparesis: analysis of full-thickness antral biopsies. Digestive diseases and sciences. 2010 Feb; [PubMed PMID: 19997975]|
|||Grover M,Bernard CE,Pasricha PJ,Lurken MS,Faussone-Pellegrini MS,Smyrk TC,Parkman HP,Abell TL,Snape WJ,Hasler WL,McCallum RW,Nguyen L,Koch KL,Calles J,Lee L,Tonascia J,Ünalp-Arida A,Hamilton FA,Farrugia G, Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2012 Jun; [PubMed PMID: 22339929]|
|||Heckert J,Thomas RM,Parkman HP, Gastric neuromuscular histology in patients with refractory gastroparesis: Relationships to etiology, gastric emptying, and response to gastric electric stimulation. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2017 Aug; [PubMed PMID: 28374487]|
|||Neshatian L,Gibbons SJ,Farrugia G, Macrophages in diabetic gastroparesis--the missing link? Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2015 Jan; [PubMed PMID: 25168158]|
|||Moore JG,Christian PE,Coleman RE, Gastric emptying of varying meal weight and composition in man. Evaluation by dual liquid- and solid-phase isotopic method. Digestive diseases and sciences. 1981 Jan; [PubMed PMID: 7460704]|
|||Bujanda L, The effects of alcohol consumption upon the gastrointestinal tract. The American journal of gastroenterology. 2000 Dec; [PubMed PMID: 11151864]|
|||Miller G,Palmer KR,Smith B,Ferrington C,Merrick MV, Smoking delays gastric emptying of solids. Gut. 1989 Jan; [PubMed PMID: 2920927]|
|||Parkman HP,Hasler WL,Fisher RS, American Gastroenterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology. 2004 Nov; [PubMed PMID: 15521026]|
|||Lata PF,Pigarelli DL, Chronic metoclopramide therapy for diabetic gastroparesis. The Annals of pharmacotherapy. 2003 Jan; [PubMed PMID: 12503946]|
|||Peeters TL, Erythromycin and other macrolides as prokinetic agents. Gastroenterology. 1993 Dec; [PubMed PMID: 8253365]|
|||Feighner SD,Tan CP,McKee KK,Palyha OC,Hreniuk DL,Pong SS,Austin CP,Figueroa D,MacNeil D,Cascieri MA,Nargund R,Bakshi R,Abramovitz M,Stocco R,Kargman S,O'Neill G,Van Der Ploeg LH,Evans J,Patchett AA,Smith RG,Howard AD, Receptor for motilin identified in the human gastrointestinal system. Science (New York, N.Y.). 1999 Jun 25; [PubMed PMID: 10381885]|
|||Silvers D,Kipnes M,Broadstone V,Patterson D,Quigley EM,McCallum R,Leidy NK,Farup C,Liu Y,Joslyn A, Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. DOM-USA-5 Study Group. Clinical therapeutics. 1998 May-Jun; [PubMed PMID: 9663360]|
|||Davis RH,Clench MH,Mathias JR, Effects of domperidone in patients with chronic unexplained upper gastrointestinal symptoms: a double-blind, placebo-controlled study. Digestive diseases and sciences. 1988 Dec; [PubMed PMID: 3058442]|
|||Horowitz M,Harding PE,Chatterton BE,Collins PJ,Shearman DJ, Acute and chronic effects of domperidone on gastric emptying in diabetic autonomic neuropathy. Digestive diseases and sciences. 1985 Jan; [PubMed PMID: 3965269]|
|||Jones MP,Maganti K, A systematic review of surgical therapy for gastroparesis. The American journal of gastroenterology. 2003 Oct; [PubMed PMID: 14572555]|
|||Fontana RJ,Barnett JL, Jejunostomy tube placement in refractory diabetic gastroparesis: a retrospective review. The American journal of gastroenterology. 1996 Oct; [PubMed PMID: 8855743]|
|||Jacober SJ,Narayan A,Strodel WE,Vinik AI, Jejunostomy feeding in the management of gastroparesis diabeticorum. Diabetes care. 1986 Mar-Apr; [PubMed PMID: 3084186]|
|||Parkman HP,Harris AD,Krevsky B,Urbain JL,Maurer AH,Fisher RS, Gastroduodenal motility and dysmotility: an update on techniques available for evaluation. The American journal of gastroenterology. 1995 Jun; [PubMed PMID: 7771415]|
|||Guo JP,Maurer AH,Fisher RS,Parkman HP, Extending gastric emptying scintigraphy from two to four hours detects more patients with gastroparesis. Digestive diseases and sciences. 2001 Jan; [PubMed PMID: 11270790]|
|||Abell TL,Camilleri M,Donohoe K,Hasler WL,Lin HC,Maurer AH,McCallum RW,Nowak T,Nusynowitz ML,Parkman HP,Shreve P,Szarka LA,Snape WJ Jr,Ziessman HA, Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Journal of nuclear medicine technology. 2008 Mar; [PubMed PMID: 18287197]|
|||Hoogerwerf WA,Pasricha PJ,Kalloo AN,Schuster MM, Pain: the overlooked symptom in gastroparesis. The American journal of gastroenterology. 1999 Apr; [PubMed PMID: 10201478]|