Gastroparesis and other types of gastric dysfunction result in substantial morbidity in diabetes patients. The pathophysiology of these disorders is incompletely understood. This article reviews techniques applicable to the assessment of gastric function in diabetes patients, including the measurement of emptying, accommodation, and contractility. Available treatment options are also reviewed, including novel yet unapproved serotonin 5-HT4 agonist pharmacological treatments, as well as the role of endoscopic, surgical, and device treatments of gastroparesis.
SoykanISivriBSarosiekIKiernanBMcCallumRW.Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. Dig Dis Sci.1998;43 (11): 2398–404.
2.
HoogerwerfWAPasrichaPJKallooANSchusterMM.Pain: the overlooked symptom in gastroparesis. Am J Gastroenterol.1999;94 (4): 1029–33.
3.
JonesKLRussoAStevensJEWishartJMBerryMKHorowitzM.Predictors of delayed gastric emptying in diabetes. Diabetes Care.2001;24 (7): 1264–9.
4.
Delgado-ArosSCamilleriMCastilloEJCremoniniFStephensDFerberIBaxterKBurtonDZinsmeisterAR.Effect of gastric volume or emptying on meal-related symptoms after liquid nutrients in obesity: a pharmacologic study. Clin Gastroenterol Hepatol.2005;3 (10): 997–1006.
5.
Delgado-ArosSCamilleriMCremoniniFFerberIStephensDBurtonDD.Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia. Gastroenterology.2004;127 (6): 1685–94.
6.
BredenoordAJChialHJCamilleriMMullanBPMurrayJA.Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptoms. Clin Gastroenterol Hepatol.2003;1 (4): 264–72.
7.
RaynerCKSamsomMJonesKLHorowitzM.Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care.2001;24 (2): 371–81.
8.
MalekiDLockeGR3rdCamilleriMZinsmeisterARYawnBPLeibsonCMeltonLJ3rd. Gastrointestinal tract symptoms among persons with diabetes mellitus in the community. Arch Intern Med.2000;160 (18): 2808–16.
9.
BytzerPTalleyNJLeemonMYoungLJJonesMPHorowitzM.Prevalence of gastrointestinal symptoms associated with diabetes mellitus: a population-based survey of 15,000 adults. Arch Intern Med.2001;161 (16): 1989–96.
10.
NowakTVJohnsonCPKalbfleischJHRozaAMWoodCMWeisbruchJPSoergelKH.Highly variable gastric emptying in patients with insulin dependent diabetes mellitus. Gut.1995;37 (1): 23–9.
11.
KongMFHorowitzMJonesKLWishartJMHardingPE.Natural history of diabetic gastroparesis. Diabetes Care.1999;22 (3): 503–7.
12.
CamilleriM.Clinical practice. Diabetic gastroparesis. N Engl J Med.2007;356 (8): 820–9.
13.
HyettBMartinezFJGillBMMehraSLemboAKellyCPLefflerDA.Delayed radionucleotide gastric emptying studies predict morbidity in diabetics with symptoms of gastroparesis. Gastroenterology.2009;137 (2)445–52.
14.
JungHKChoungRSLockeGR3rdSchleckCDZinsmeisterARSzarkaLAMullanBTalleyNJ.The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006. Gastroenterology.2009;136 (4): 1225–33.
15.
SzarkaLACamilleriM.Methods for measurement of gastric motility. Am J Physiol Gastrointest Liver Physiol.2009;296 (3): G461–75.
16.
CamilleriMHaslerWLParkmanHPQuigleyEMSofferE.Measurement of gastrointestinal motility in the GI laboratory. Gastroenterology.1998;115 (3): 747–62.
17.
AkkermansLMvan IsseltJW.Gastric motility and emptying studies with radionuclides in research and clinical settings. Dig Dis Sci.1994;39 (12 Suppl): 95S–6S.
18.
LooFDPalmerDWSoergelKHKalbfleischJHWoodCM.Gastric emptying in patients with diabetes mellitus. Gastroenterology.1984;86 (3): 485–94.
19.
AbellTLCamilleriMDonohoeKHaslerWLLinHCMaurerAHMcCallumRWNowakTNusynowitzMLParkmanHPShrevePSzarkaLASnapeWJJrZiessmanHA, American Neurogastroenterology and Motility Society, Society of Nuclear Medicine. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Am J Gastroenterol.2008;103 (3): 753–63.
20.
TougasGEakerEYAbellTLAbrahamssonHBoivinMChenJHockingMPQuigleyEMKochKLTokayerAZStanghelliniVChenYHuizingaJDRydénJBourgeoisIMcCallumRW.Assessment of gastric emptying using a low fat meal: establishment of international control values. Am J Gastroenterol.2000;95 (6): 1456–62.
21.
DegenLPPhillipsSF.Variability of gastrointestinal transit in healthy women and men. Gut.1996;39 (2): 299–305.
22.
TalleyNJLockeGR3rdLahrBDZinsmeisterARTougasGLigozioGRojavinMATackJ.Functional dyspepsia, delayed gastric emptying, and impaired quality of life. Gut.2006;55 (7): 933–9.
23.
ViramontesBEKimDYCamilleriMLeeJSStephensDBurtonDDThomfordeGMKleinPDZinsmeisterAR.Validation of a stable isotope gastric emptying test for normal accelerated or delayed gastric emptying. Neurogastroenterol Motil.2001;13 (6): 567–74.
24.
SzarkaLACamilleriMVellaABurtonDBaxterKSimonsonJZinsmeisterAR.A stable isotope breath test with a standard meal for abnormal gastric emptying of solids in the clinic and in research. Clin Gastroenterol Hepatol.2008;6 (6): 635–43.
25.
Van de CasteeleMLuypaertsAGeypensBFeveryJGhoosYNevensF.Oxidative breakdown of octanoic acid is maintained in patients with cirrhosis despite advanced disease. Neurogastroenterol Motil.2003;15 (2): 113–20.
26.
KuoBMcCallumRWKochKLSitrinMDWoJMCheyWDHaslerWLLacknerJMKatzLASemlerJRWildingGEParkmanHP.Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther.2008;27 (2): 186–96.
27.
CassillyDKantorSKnightLCMaurerAHFisherRSSemlerJParkmanHP.Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil.2008;20 (4): 311–9.
28.
SchwizerWFraserRMaeckeHSieboldKFunckRFriedM.Gd-DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI. Magn Reson Med.1994;31 (4): 388–93.
29.
KunzPCrelierGRSchwizerWBorovickaJKreissCFriedMBoesigerP.Gastric emptying and motility: assessment with MR imaging—preliminary observations. Radiology.1998;207 (1): 33–40.
30.
BorovickaJLehmannRKunzPFraserRKreissCCrelierGBoesigerPSpinasGAFriedMSchwizerW.Evaluation of gastric emptying and motility in diabetic gastroparesis with magnetic resonance imaging: effects of cisapride. Am J Gastroenterol.1999;94 (10): 2866–73.
31.
LauensteinTCVogtFMHerbornCUDeGreiffADebatinJFHoltmannG.Time-resolved three-dimensional MR imaging of gastric emptying modified by IV administration of erythromycin. Am J Roentgenol.2003;180 (5): 1305–10.
32.
BilecenDSchefflerKSeifritzEBongartzGSteinbrichW.Hydro-MRI for the visualization of gastric wall motility using RARE magnetic resonance imaging sequences. Abdom Imaging.2000;25 (1): 30–4.
33.
FidlerJBharuchaAECamilleriMCampJBurtonDGrimmRRiedererSJRobbRAZinsmeisterAR.Application of magnetic resonance imaging to measure fasting and postprandial volumes in humans. Neurogastroenterol Motil.2009;21 (1): 42–51.
34.
BourasEPDelgado-ArosSCamilleriMCastilloEJBurtonDDThomfordeGMChialHJ.SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication. Single photon emission computed tomography. Gut.2002;51 (6): 781–6.
35.
Delgado-ArosSBurtonDDBrinkmannBHCamilleriM.Reliability of a semi-automated analysis to measure gastric accommodation using SPECT in humans. Gastroenterology.2001;120: A287.
36.
De SchepperHCamilleriMCremoniniFFoxx-OrensteinABurtonD.Comparison of gastric volumes in response to isocaloric liquid and mixed meals in humans. Neurogastroenterol Motil.2004;16 (5): 567–73.
37.
GiljaOHHauskenTOdegaardSBerstadA.Monitoring postprandial size of the proximal stomach by ultrasonography. J Ultrasound Med.1995;14 (2): 81–9.
38.
LiaoDGregersenHHauskenTGiljaOHMundtMKassabG.Analysis of surface geometry of the human stomach using real-time 3-D ultrasonography in vivo. Neurogastroenterol Motil.2004;16 (3): 315–24.
39.
ManiniMLBurtonDDMeixnerDDEckertDJCallstromMSchmitGEl-YoussefMCamilleriM.Feasibility and application of 3-dimensional ultrasound for measurement of gastric volumes in healthy adults and adolescents. J Pediatr Gastroenterol Nutr.2009;48 (3): 287–93.
40.
AzpirozFMalageladaJR.Gastric tone measured by an electronic barostat in health and postsurgical gastroparesis. Gastroenterology.1987;92 (4): 934–43.
41.
AbellTLBernsteinRKCuttsTFarrugiaGForsterJHaslerWLMcCallumRWOldenKWParkmanHPParrishCRPasrichaPJPratherCMSofferEETwillmanRVinikAI.Treatment of gastroparesis: a multidisciplinary clinical review. Neurogastroenterol Motil.2006;18 (4): 263–83.
42.
FiorettoPSteffesMWSutherlandDEGoetzFCMauerM.Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med.1998;339 (2): 69–75.
43.
KendallDMRooneyDPSmetsYFBoldingL SalazarRobertsonRP.Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes and autonomic neuropathy. Diabetes.1997;46 (2): 249–57.
44.
SoldersGTydenGPerssonAGrothCG.Improvement of nerve conduction in diabetic neuropathy. A follow-up study 4 yr after combined pancreatic and renal transplantation. Diabetes.1992;41 (8): 946–51.
45.
CashionAKHolmesSLHathawayDKGaberAO.Gastroparesis following kidney/pancreas transplant. Clin Transplant.2004;18 (3): 306–11.
46.
SalehiMAulingerBAD'AlessioDA.Targeting beta-cell mass in type 2 diabetes: promise and limitations of new drugs based on incretins. Endocr Rev.2008;29 (3): 367–79.
47.
VellaABockGGieslerPDBurtonDBSerraDBSaylanMLDunningBEFoleyJERizzaRACamilleriM.Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes.2007;56 (5): 1475–80.
48.
PasrichaPJPehlivanovNSugumarAJankovicJ.Drug insight: from disturbed motility to disordered movement—a review of the clinical benefits and medicolegal risks of metoclopramide. Nat Clin Pract Gastroenterol Hepatol.2006;3 (3): 138–48.
49.
KenneyCHunterCDavidsonAJankovicJ.Metoclopramide, an increasingly recognized cause of tardive dyskinesia. J Clin Pharmacol.2008;48 (3): 379–84.
50.
McCallumRWRicciDARakatanskyHBeharJRhodesJBSalenGDerenJIppolitiAOlsenHWFalchukK.A multicenter placebo-controlled clinical trial of oral metoclopramide in diabetic gastroparesis. Diabetes Care.1983;6 (5): 463–7.
51.
PattersonDAbellTRothsteinRKochKBarnettJ.A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. Am J Gastroenterol.1999;94 (5): 1230–4.
52.
SoykanISarosiekIMcCallumRW.The effect of chronic oral domperidone therapy on gastrointestinal symptoms, gastric emptying, and quality of life in patients with gastroparesis. Am J Gastroenterol.1997;92 (6): 976–80.
53.
JanssensJPeetersTLVantrappenGTackJUrbainJLDe RooMMulsEBouillonR.Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies. N Engl J Med.1990;322 (15): 1028–31.
54.
ChenCCLinCSKoYPHungYCLaoHCHsuYW.Premedication with mirtazapine reduces preoperative anxiety and postoperative nausea and vomiting. Anesth Analg.2008;106 (1): 109–13.
55.
KastREFoleyKF.Cancer chemotherapy and cachexia: mirtazapine and olanzapine are 5-HT3 antagonists with good antinausea effects. Eur J Cancer Care.2007;16 (4): 351–4.
56.
TalleySJBytzerPHammerJYoungLJonesMHorowitzM.Psychological distress is linked to gastrointestinal symptoms in diabetes mellitus. Am J Gastroenterol.2001;96 (4): 1033–8.
57.
KimSWShinISKimJMKangHCMunJUYangSJYoonJS.Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment. Psychosomatics.2006;47 (5): 440–2.
58.
De MaeyerJHLefebvreRASchuurkesJA.5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil.2008;20 (2): 99–112.
59.
BourasEPCamilleriMBurtonDDThomfordeGMcKinzieSZinsmeisterAR.Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology.2001;120 (2): 354–60.
60.
CamilleriM.Functional dyspepsia: mechanisms of symptom generation and appropriate management of patients. Gastroenterol Clin North Am.2007;36 (3): 649–64.
61.
PerkelMSMooreCHershTDavidsonED.Metoclopramide therapy in patients with delayed gastric emptying: a randomized, double-blind study. Dig Dis Sci.1979;24 (9): 662–6.
62.
McCallumRWRicciDARakatanskyHBeharJRhodesJBSalenGDerenJIppolitiAOlsenHWFalchukK.A multicenter placebo-controlled clinical trial of oral metoclopramide in diabetic gastroparesis. Diabetes Care.1983;6 (5): 463–7.
63.
ChampionMCGulenchynKO'LearyTIrvinePEdwardsABraatenJGayJ.Domperidone (motilium) improves symptoms and solid phase gastric emptying in diabetic gastroparesis. Am J Gastroenterol.1987;82: 975–80.
64.
SoykanISarosiekIMcCallumRW.The effect of chronic oral domperidone therapy on gastrointestinal symptoms, gastric emptying, and quality of life in patients with gastroparesis. Am J Gastroenterol.1997;92 (6): 976–80.
65.
SilversDKipnesMBroadstoneVPattersonDQuigleyEMMcCallumRLeidyNKFarupCLiuYJoslynA, DOM-USA-5 Study Group. Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. Clin Ther.1998;20 (3): 438–53.
66.
FranzeseABorrelliOCorradoGReaPDi NardoGGrandinettiALDitoLCucchiaraS.Domperidone is more effective than cisapride in children with diabetic gastroparesis. Aliment Pharmacol Ther.2002;16 (5): 951–7.
67.
CamilleriMKerstensRBeyensGRobinsonPVandeplasscheL.A double-blind, placebo-controlled trial to evaluate the safety and tolerability of prucalopride oral solution in constipated elderly patients living in a nursing facility. Gastroenterology.2009;136 (Suppl 1): 240.
68.
CamilleriMVazquez-RoqueMIBurtonDFordTMcKinzieSZinsmeisterARDruzgalaP.Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans. Neurogastroenterol Motil.2007;19 (1): 30–8.
69.
SmithJABeattieDTMarquessDShawJPVickeryRGHumphreyPP.The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol.2008;378 (1): 125–37.
70.
BeattieDTArmstrongSRShawJPMarquessDSandlundCSmithJATaylorJAHumphreyPP.The in vivo gastrointestinal activity of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol.2008;378 (1): 139–47.
71.
ManiniMLCamilleriMGoldbergMSweetserSMcKinzieSBurtonDWongSKittMMLiYPZinsmeisterAR.Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation. Neurogastroenterol Motil.2009. [Epub ahead of print.].
72.
CamilleriMPapathanasopoulosAOdunsiST.Actions and therapeutic pathways of ghrelin for gastrointestinal disorders. Nat Rev Gastroenterol Hepatol.2009;6 (6): 343–52.
73.
FriedenbergFKPalitAParkmanHPHanlonANelsonDB.Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol.2008;103 (2): 416–23.
74.
JonesMPMagantiK.A systematic review of surgical therapy for gastroparesis. Am J Gastroenterol.2003;98 (10): 2122–9.
75.
KimCHNelsonDK.Venting percutaneous gastrostomy in the treatment of refractory idiopathic gastroparesis. Gastrointest Endosc.1998;47 (1): 67–70.
76.
MichaudLGuimberDCarpentierBSfeirRLambilliotteAMazingueFGottrandFTurckD.Gastrostomy as a decompression technique in children with chronic gastrointestinal obstruction. J Pediatr Gastroenterol Nutr.2001;32 (1): 82–5.
77.
MapleJTPetersenBTBaronTHHarewoodGCJohnsonCDSchmitGD.Abdominal CT as a predictor of outcome before attempted direct percutaneous endoscopic jejunostomy. Gastrointest Endosc.2006;63 (3): 424–30.
78.
LinZSarosiekIForsterJMcCallumRW.Symptom responses, long-term outcomes and adverse events beyond 3 years of high-frequency gastric electrical stimulation for gastroparesis. Neurogastroenterol Motil.2006;18 (1): 18–27.
79.
LinZMcElhinneyCSarosiekIForsterJMcCallumR.Chronic gastric electrical stimulation for gastroparesis reduces the use of prokinetic and/or antiemetic medications and the need for hospitalizations. Dig Dis Sci.2005;50 (7): 1328–34.
80.
AbellTMcCallumRHockingMKochKAbrahamssonHLeblancILindbergGKonturekJNowakTQuigleyEMTougasGStarkebaumW.Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology.2003;125 (2): 421–8.
81.
McCallumRBrodyFJParkmanHPWoJMNowakTVSnapeWJLerewDRRuehlowLSarosiekI.Enterra® gastric electrical stimulation for diabetic gastroparesis: results from a multicenter randomized study. Gastroenterology.2009;136 (Suppl 1): 376.
82.
XingJBrodyFRosenMChenJDSofferE.The effect of gastric electrical stimulation on canine gastric slow waves. Am J Physiol Gastrointest Liver Physiol.2003;284 (6): G956–62.
83.
LinZForsterJSarosiekIMcCallumR.Efficiency of two-channel gastric electrical pacing for entrainment of gastric slow waves. Gastroenterology.2009;136 (Suppl 1): W2042.
84.
JonesMPMagantiK.A systematic review of surgical therapy for gastroparesis. Am J Gastroenterol.2003;98 (10): 2122–9.
85.
CamilleriM.The stomach in diabetes: from villain to ally. Clin Gastroenterol Hepatol.2009;7 (3): 285–7.