type - gut.bmj.com · sulphur colloid and the 150 ml liquid com-ponent (dextrose 10%, 250 kj) was...

Gut 1997; 40: 641-646

Gastrointestinal motor mechanisms inhyperglycaemia induced delayed gastric emptyingin type I diabetes mellitus

M Samsom, L M A Akkermans, R J A Jebbink, H van Isselt, G P vanBerge-Henegouwen,A J P M Smout

AbstractBackground-Hyperglycaemia delays gas-tric emptying, both in healthy controls andin patients with diabetes mellitus. Theeffect ofhyperglycaemia on antroduodenalmotility in diabetes has not yet beenstudied.Aim-To investigate the gastrointestinalmotor mechanisms involved in the hyper-glycaemia induced retardation of gastricemptying in patients with type I diabetesmellitus and autonomic neuropathy. Ineight diabetic patients antroduodenalmanometry was performed simultaneouslywith scintigraphic measurement of emp-tying of a mixed solid-liquid meal, duringeuglycaemia (5-8 mmol/l glucose) andhyperglycaemia (16-19 mmol/l glucose),on separate days, in random order.Results-Hyperglycaemia decreased thecumulative antral motility index from 38-3(range 24.2-47.6) to 30-8 (range 17.3-38.1)(p=0.025) and reduced the number ofantral pressure waves propagated over.4-5 cm (p=0.04). Duodenal phase III-likeactivity was seen irrespective of theglycaemic state (in three patients duringeuglycaemia and in four patients duringhyperglycaemia). Hyperglycaemia signifi-candy affected gastric emptying of thesolid meal: it prolonged the lag phase from20-0 minutes to 28 5 minutes (p=0.02),increased the 50% emptying time from73'5 minutes to 104'5 minutes (p=0'03),and increased the percentage of isotoperemaining in the stomach after 120 min-utes from 33.5% to 46.5% (p=0.02). Thecumulative antral motility index wascorrelated with the 50% emptying time(r=0.75, p=002) during euglycaemia,but not during hyperglycaemia (r=0.28,p=0-31). Liquid emptying was not influ-enced by the blood glucose concentration.Conclusions-Hyperglycaemia reducespostprandial antral contractile activityand its organisation in patients with typeI diabetes and autonomic neuropathy.These changes in antroduodenal motilityare likely to constitute the mechanismthrough which gastric emptying of solidsis delayed during high blood glucoseconcentrations in these diabetic patients.(Gut 1997; 40: 641-646)

Keywords: diabetes mellitus, scintigraphic gastricemptying, antroduodenal motility, hyperglycaemia.

The prevalence of delayed gastric emptying inpatients with type I diabetes mellitus is about50%.'`3 Manometric studies performed withthe aim to elucidate the motor mechanismsresponsible for delayed gastric emptying in thisdisease have shown that postprandial motoractivity is often abnormal in diabetic patients.The abnormalities consist of antral hypo-motility, pyloric spasm, and pathologicalmotor patterns in the small intestine.6 Theseabnormalities in gastrointestinal motility maycause dyspeptic symptoms and may also affectglycaemic control.7"9Autonomic neuropathy is thought to be an

important causal factor in motility disordersin diabetes mellitus.' 10 However, the corre-lation between cardiovascular autonomicneuropathy tests and motility variables is poor.One of the reasons for this poor correlation isthat gastrointestinal motor activity is alsoinfluenced by the blood glucose concen-tration, as hyperglycaemia retards gastricemptying.11The effects of hyperglycaemia on antroduo-

denal motility have been studied in healthyvolunteers, and showed a decreased inter-digestive and postprandial antral motor activityand an increased number of isolated pyloricpressure waves during hyperglycaemia. 1214The underlying mechanism by which hyper-glycaemia affects upper gastrointestinal mo-tility is not known. However, the fact that highblood glucose concentrations have oppositeeffects on gastrointestinal motor function(inhibition of antral motility and stimulationof pyloric activity) in combination with thefinding that vagal-cholinergic activity is de-creased by hyperglycaemia make it very likelythat neuronal (vagal) control rather thansmooth muscle function itself is affected byhyperglycaemia. 15Whether the effects of hyperglycaemia on

antroduodenal motility are similar in diabeticpatients with vagal neuropathy as in healthyvolunteers has not yet been investigated. Theaim of the present study was, therefore, toinvestigate the gastrointestinal motor mechan-isms involved in the retardation of gastricemptying induced by hyperglycaemia inpatients with type I diabetes mellitus andautonomic neuropathy.Antroduodenal manometry was performed

simultaneously with scintigraphic measure-ment of gastric emptying of a mixed solid-liquid meal, during euglycaemia and hyper-glycaemia.

Department ofGastroenterologyM SamsomRJ A JebbinkG P vanBerge-HenegouwenAJPMSmout

Department ofSurgeryLM A Akkermans

Department ofNuclearMedicine, UniversityHospital Utrecht,The NetherlandsH van IsseltCorrespondence to:Dr M Samsom,Department ofGastroenterology, UniversityHospital Utrecht, PO Box85500, 3508 GA Utrecht,The Netherlands.Accepted for publication31 October 1996

641

on May 2, 2020 by guest. P

rotected by copyright.http://gut.bm

j.com/

Gut: first published as 10.1136/gut.40.5.641 on 1 M

ay 1997. Dow

nloaded from

http://gut.bmj.com/

Samsom, Akkermans, _'ebbink, van Isselt, vanBerge-Henegouwen, Smout

Methods

PATIENTS

Eight patients with insulin dependent diabetesmellitus (six women, two men), mean age 49(range 43-67) years were studied. The patientswere randomly selected from outpatientsattending the endocrinology department of theUniversity Hospital at Utrecht and the Depart-ment of Internal Medicine of the CatharinaHospital at Eindhoven for management ofdiabetes mellitus. The median duration of theirdiabetes was 22 (range 15-44) years. Althoughpatients were not selected on the basis ofgastrointestinal symptoms, in all cases gastricoutlet obstruction was excluded by uppergastrointestinal endoscopy. The median gly-cylated haemoglobin concentration (HbAl)at the time of the study was 8 /5% (range8-11 7%, normal 4-7%). All patients had oneor more complications of diabetes mellitussuch as peripheral neuropathy, nephropathy,or retinopathy. Autonomic neuropathy wasevaluated using the cardiovascular autonomicneuropathy tests (maximum 5 points) accord-ing to Ewing and Clarke."6 In five patientsearly autonomic neuropathy (2,2,2,2, and 1 '2points) and in three patients definite auto-nomic neuropathy (2'2,3, and 3'2 points) werefound.The median creatinine concentration was

87-0 (range 67-371) mmolIl; the creatinineconcentration was abnormally high in onepatient. Any medication which could influencegastrointestinal motility (apart from insulin)was discontinued 48 hours before each study.

Written informed consent was obtained in allcases and the study was approved by the ethicscommittee of the University Hospital Utrecht.

PROTOCOLIn all patients gastric emptying and antroduo-denal motility were measured simultaneouslyduring euglycaemia (5-8 mmol/l) and hyper-glycaemia (16-19 mmol/l), on two separatedays at a one week interval and in randomorder.

Patients fasted from 2000 hours the pre-vious day and injected 50% of their normalinsulin dose on the morning of each study day.The antroduodenal catheter was introducedtransnasally and initially positioned underfluoroscopic control. Subsequently, the cath-eter position was monitored by measurementof antroduodenal transmucosal potentialdifference (TMPD).'7 After correct positioningof the catheter two cannulas were inserted intothe anticubital veins, one in each arm, one forinfusion of glucose and insulin and the otherfor blood sampling. The blood glucose concen-trations were measured every 10 minutes.Blood glucose concentrations were stabilised ineither the euglycaemic or hyperglycaemicrange. When blood glucose concentrations hadbeen stable for two hours a radioisotopicallylabelled test meal was given at about 13 30hours. Gastric emptying and antroduodenalmotility were recorded for 120 minutes afteringestion of the mixed liquid-solid meal.

MEASUREMENT OF ANTRODUODENALPRESSURESAntroduodenal manometry was performedwith a nine channel perfused catheter (outsidediameter 4-7 mm, internal diameter 0 74 mm).The catheter was stiffened with a guidewirethrough the central lumen (1 fi33 mm) to facili-tate its introduction. Pressure sensors werelocated at 5, 15, 25, 40, 45, 46-5, 48-0, and49-5 cm from the tip. The four proximal sideholes were positioned in the antrum. The sideholes located at 40 cm and 45 cm were usedto measure the antroduodenal TMPD. Mano-metric channels were perfused with degassedliquid at a rate of 0 3 ml/min with a lowcompliance pneumohydraulic pump. Theantral and duodenal TMPD channels wereperfused with saline from separate reservoirsand all other channels were perfused withdistilled water. Pressures were measured byexternal transducers (DPT-200, Medisize,Hillegom, The Netherlands). The pressuresignals from the six proximal side holes (fourantral, two duodenal) and the TMPD wererecorded on a portable data logger (MedicalMeasurement Systems, Enschede, the Nether-lands). Whereas the storage capacity of the datalogger is 1 MB, maximum data compressionallowed storage of 1-9 MB. The samplefrequency was 4 Hz. A stationary MS-DOScomputer served as an on line display andretrieval system. Pressure recordings wereanalysed only when the antral TMPD was .-20mV and the duodenal TMPD was .-15 mVwith a difference between the two of at least 15mV, indicating a correct catheter position.'7The manometric data were analysed both

visually and automatically. Using commerciallyavailable software (Medical MeasurementSystems, Enschede, The Netherlands) thenumber (n) of pressure waves of amplitude.1-4 kPa (10 mm Hg), and their meanamplitude (MA) were calculated after elim-ination of the artefacts such as abdominalpressure peaks, respiration, and drift of thepressure transducers.'8

In addition, the motility index (MI) wascalculated, defined as MI=ln(n X E amplitudes+ 1). Phase III in the antrum or duodenum wasdefined as contractile activity at the maximumfrequency for at least one minute in the antrum(three contractions/min) and for at least twominutes in the duodenum (10-12 contractions/min), which was propagated over at least tworecording sites and was followed by motorquiescence.'9 When pressure waves with maxi-mum frequency were only seen in the mostdistal duodenal channel or if they were notfollowed by motor quiescence, the pattern wascalled phase III-like activity. Short bursts weredefined as contractile activity in the duodenumat maximum frequency 0-5-1-0 minutes induration without distal propagation.4 Antralpressure waves were considered to be "propa-gated" if the onset of the antral pressure waveat one recording site occurred within fiveseconds of the onset of an antral pressure waverecorded at an adjacent site.20 The number ofantral pressure waves propagated over adistance .4.5 cm was calculated.

642



j.com/


ay 1997. Dow

nloaded from

http://gut.bmj.com/

Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus

MEASUREMENT OF GASTRIC EMPTYING

Gastric emptying was measured using a doubleisotope technique.2" Each study was performedwith the patient seated in front of thescintillation camera. The solid component ofthe meal (pancake; 1240 kJ; 14% protein, 15%fat, 71% carbohydrate) was labelled with 99mTcsulphur colloid and the 150 ml liquid com-ponent (dextrose 10%, 250 kJ) was labelledwith 1l3mIn-DPTA. Data were collected in oneminute frames and were corrected for move-ment, Compton scatter, y ray attenuation, andradionuclide decay.2' For the solid and liquidcomponents, the time for 50% gastric emp-tying and the percentage isotope remaining inthe stomach after 120 minutes were calculated.When the 50% emptying time (T5") was longerthan the 120 minutes ofthe study period, it wascalculated by extrapolating the linear emptyingcurve of the solid meal. Figure 3 (see later)shows the normal range (mean (2SD)) of the50% emptying time determined in 16 healthyvolunteers. These data were obtained fromgastric emptying studies performed in non-intubated healthy volunteers. As it has beenshown that duodenal intubation does not altergastric emptying, these data could be used forcomparison with the gastric emptying dataobtained in this study.22 The lag phase for thesolid meal, the time interval between ingestionof the meal, and the appearance of the firstradioactivity in the duodenum, were deter-mined visually.

STABILISATION OF BLOOD GLUCOSE

CONCENTRATIONS

Euglycaemia and hyperglycaemia were in-duced by infusion of 20% glucose and insulinintravenously (Actrapid, Novo Nordisk FarmaBV, Zoeterwoude, The Netherlands).23 Therate of 20% glucose infusion was adjusted tomaintain the blood glucose concentration at5-8 mmol/l or 16-19 mmol/l. Blood sampleswere drawn from the cannula that was notused for glucose and insulin infusion, for themeasurement of glucose concentrations after10 minutes using Glukotest 1-44R strips(Boehringer Mannheim, Germany) and a port-able glucose meter (Reflolux S, BoehringerMannheim, Germany).The blood glucose concentrations (mean

(SEM)) measured during euglycaemia were7*54 (0.23) mmolI and 18-05 (0.23) mmolIduring hyperglycaemia. The glucose concen-tration at t=0 minutes was 4-6 (0 7) mmolIl andthis had increased to 8-4 (2-3) mmol/l at t=60minutes. In seven of 104 blood samples takenin the postprandial period the blood glucoseconcentration was between 10 and 12-5 mmoll.

STATISTICAL ANALYSISData were evaluated with the Wilcoxon test(paired). Relations between antroduodenalpressures and gastric emptying were evaluatedwith Pearson's correlation coefficient. Data areshown as median and range, unless statedotherwise. A p value <0 05 was consideredsignificant.

ResultsThe nasogastric intubation was well toleratedin all patients. The catheter position wascorrect during 94% of the recording time.

ANTRODUODENAL PRESSURESThe numbers of antral pressure waves andtheir amplitude recorded from the individualside holes were not significantly decreased byhyperglycaemia (Table). However, the numberof antral pressure waves propagated over adistance .4-5 cm was lower during hypergly-caemia (Fig 1). Hyperglycaemia significantlydecreased the cumulative motility index,from 38-3 (24-2-47-6) to 30-8 (17.3-38.1)(p=0025; Fig 2).At the level of the duodenum the number of

pressure waves at the proximal duodenalrecording site (p=0 04; Table) and the motilityindex (13-8 v 11-8, p=0.02) were lower duringhyperglycaemia. Abnormal duodenal motilitypatterns consisted of short bursts in five patientsduring euglycaemia and in three patients duringhyperglycaemia, comprising 6.44% and 2-27%of the total recording time during euglycaemiaand hyperglycaemia respectively (p=0-34).

207

E

E

A

cn

Caen

0.1CDal)QL

16 F

12 F

8

4

Euglycaemia Hyperglycaemia

Figure 1: Individual values ofthe number ofantral pressurewaves propagated over a distance .4-5 cm.Hyperglycaemia reduced the number ofpropagated antralpressure waves in the period after the meal (p<004).

Number ofpressure waves and amplitude (median, range) observed in the first two hours after ingestion of a meal

Pressure PressureRecording waves during waves during Amplitude during Amplitude dunngsite euglycaemia hyperglycaemia p Value euglycaemia hyperglycaemia p Value

Antrum 1 36 (12-191) 10 (1-215) 0-06 3-19 (0-01-5-79) 3-34 (1-405-29) 0-87Antrum 2 82 (20-236) 24 (2-146) 0-09 3-03 (0-10-6-48) 2-71 (0-95-5 84) 0-83Antrum 3 68 (8-148) 27 (5-129) 0-30 2-31 (0-10-4-23) 2-83 (1-58-5-20) 0-77Antrum 4 80 (19-228) 67 (22-146) 0-14 4-49 (2-55-10-14) 4-08 (2-50-10-29) 0-48Duodenum 1 397 (138-545) 186 (86-369) 0-04 4-74 (3-61-7-04) 4 07 (3-065-71) 0-17Duodenum 2 612 (245-494) 319 (156-558) 0 09 4-32 (3-13-6-88) 4-10 (2.73-5 29) 0 77

u

643



j.com/


ay 1997. Dow

nloaded from

http://gut.bmj.com/

Samsom, Akkermans, Jebbink, van Isselt, vanBerge-Henegouwen, Smout

0

03

*~I.I0

0


Figure 2: Individual values of the cumulative antralmotility index after the meal, showing a decrease in thecumulative antral motility index during hyperglycaemia(*p<0-025).

prolonged (20-0 (2-28) v 28-5 (9-43) minutes;p=002). Figure 3 shows that the 50% empty-ing time was longer during hyperglycaemia(73 5 (46-178) minutes v 104-5 (range28-185) minutes; p=0 03). The percentage ofisotope in the stomach after 120 minutes wasalso increased by hyperglycaemia (from 33-5(5-65)% to 46.5 (4-85)%; p=002). In onepatient gastric emptying was accelerated duringhyperglycaemia. This patient had a 50% empty-ing time of 42 minutes during euglycaemia and28 minutes during hyperglycaemia.During euglycaemia the cumulative antral

motility index was correlated with the 50%emptying time (rf=0 75, p=002), but duringhyperglycaemia no correlation was found(r=0-28, p=0-31). The number of antral con-tractions and number of antral contractionspropagated more than 4-5 cm and the emptyingvariables were not related.

Duodenal phase III or phase III-like activityoccurred in the two hour period after the mealduring euglycaemia in three patients and infour patients during hyperglycaemia. Duringeuglycaemia, phase III or phase III-like activitywas found three times, 105, 23, and 87 minutesafter the meal. At this time the percentage of thesolid meal in the stomach was 46%, 80%, and70% respectively. During hyperglycaemia phaseIII or phase III-like activity was found eighttimes in four patients. In these patients the firstphase III or phase III-like activity occurred 104,70, 55, and 93 minutes after the meal. Thepercentage of the solid meal remaining in thestomach at this time was 42%, 68%, 20%, and78% respectively.

SCINTIGRAPHIC DATA

Solid emptyingEmptying of the solid meal was slower duringhyperglycaemia than during euglycaemia.During hyperglycaemia the lag phase was

*

200

180

160c

140(DE 120

c 100

a 80E

0 600

A

20

20_


Figure 3: Individual values for gastric emptying, showingan increased 50% emptying time during hyperglycaemia(p<0.03). Shaded area shows normal range (mean(2SD)) obtainedfrom 16 healthy volunteers.

Liquid emptyingHyperglycaemia did not affect gastric emptyingof the 10% dextrose solution. The 50%/emptying time was 32 (16-88) minutes duringeuglycaemia and 31 (18-73) minutes duringhyperglycaemia (p=0 73). After 120 minutes 10(0-35)% of the drink was still in the stomachduring euglycaemia and 21 (5-34)% duringhyperglycaemia (p=0 34). The 50% emptyingtime of the drink showed no relation with the50% emptying time of the solid meal.Furthermore, no relation was seen between theliquid emptying data and the motility data at30, 60, and 120 minutes.

DiscussionThis study has shown that hyperglycaemiadelays gastric emptying of solids by prolongingthe lag phase and by decreasing the postlagemptying rate. These results are consistentwith the findings made in an earlier studyshowing that high blood glucose concentrationdelayed gastric emptying of solids in patientswith type I diabetes." In the present studygastric emptying of the solid meal was normalin six of eight patients during euglycaemiaand in only three of eight patients duringhyperglycaemia. These data underline theimportance of stabilising the blood glucoseconcentrations within the euglycemic range indiabetic patients during scintigraphic gastricemptying studies.

In our study gastric emptying of the 10%dextrose drink was not affected by the bloodglucose concentration. This is by contrast witha study of Fraser et al, who found a delay ofliquid emptying using the same nutrientdrink." Although the decrease was significant,it was very small, 50% emptying time changingfrom 35 minutes to 41 minutes. However, theeffect ofhyperglycaemia on gastric emptying ofliquid might have been more prominent whena high caloric drink was used,24 instead of therelative low caloric drink used in the study ofFraser et al" and our study.

In the present study blood glucose concen-tration in the euglycaemic arm of the study

60 r-

50 [-

40K

30 F

20 K

x4)

c

0E

iE-a

10 -

o

644

a4U r-



j.com/


ay 1997. Dow

nloaded from

http://gut.bmj.com/

Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus

increased after 60 minutes from 4-6 (0 7) mmol/to 8-4 (2.3) mmol/l. This modest increase inblood glucose concentration may have reducedthe frequency of antral pressure waves slightly,as it has been shown that even modest changesin blood glucose concentrations affect antralmotility in healthy volunteers. 14The motor mechanisms responsible for the

retardation of the solid emptying are complex.The present study shows that hyperglycaemiachanged the antral as well as proximal duo-denal contractile activity. Hyperglycaemiaaffected the cumulative motility index and theorganisation of the antral pressure waves at thelevel of the antrum.Although proximal duodenal contractile

activity was decreased by hyperglycaemia, theoccurrence of abnormal duodenal motilitypatterns was not influenced by blood glucoseconcentration. Phase III (like activity) wasnoted within two hours after the meal in threeof eight patients during euglycaemia and fourof eight patients during hyperglycaemia. Innone of these patients was gastric emptyingcompleted at the time the phase III (likeactivity) occurred. Experiments with a similarstudy design performed in healthy subjects didnot show the occurrence of phase III activityduring gastric emptying of solids.25 26 There-fore, the early phase III observed in the diabeticpatients is likely to be a pathological motorpattern. The mechanism underlying this motorabnormality is unknown, but our findingsindicate that it is related to abnormal neuronalcontrol rather than to hyperglycaemia.Autonomic neuropathy, especially of the

vagal nerves, is regarded as one of the majorfactors in the pathogenesis of abnormal gastro-intestinal motility in diabetes mellitus.1 10Previous manometric studies performed inpatients with type I diabetes showed post-prandial antral hypomotility, pyloric spasm,and intestinal dysmotility.6 In most of thesestudies the blood glucose concentrations werenot monitored, let alone stabilised. Therefore,many of the gastrointestinal motor abnormali-ties reported in diabetic patients may havebeen influenced by raised blood glucoseconcentration in combination with irreversibleautonomic neuropathy.

Several studies in healthy volunteers havereported a relation between the cumulativeantral motility index, the number of propa-gated antropyloroduodenal pressure waves,and gastric emptying of solids.25 26 In ourstudy, there was a relation between thecumulative antral motility index and the timefor 50% emptying of the solid meal duringeuglycaemia. The fact that such a relation wasnot apparent during hyperglycaemia suggestsinvolvement of other parts of the uppergastrointestinal tract. Earlier scintigraphic datashowed that the percentage of solid mealremaining in the proximal stomach was directlycorrelated with the duration of the lag phase."Thus the increase in duration of lag phasefound in our study suggests changes in thegastric tone. Data concerning the function ofthe proximal stomach in diabetic patientsduring hyperglycaemia are not yet available,

but studies performed in healthy volunteers inthe fasting period showed an increase in gastriccompliance during hyperglycaemia.27The finding that gastrointestinal motility in

patients with type I diabetes with autonomicneuropathy is influenced by the blood glu-cose concentration has several implications.Because most previous studies did not takethe blood glucose concentration into account,the percentage of diabetic patients with abnor-mal gastrointestinal motor function due toirreversible vagal damage, especially antralhypomotility, may have been overestimated.Therefore, the actual prevalence of delayedgastric emptying and abnormal antroduodenalmotor function is not known. In the future,motility tests in diabetic patients should beperformed with blood glucose concentrationswithin the euglycaemic range, preferably usinga modified glucose clamp technique.23 Fur-thermore, as glucose concentrations influencegastrointestinal motility and hence gastricemptying, high blood glucose concentrationsmay cause further dysregulation of glucosehomeostasis in diabetic patients.

In conclusion, this study has shown thathyperglycaemia reduces postprandial antralcontractile activity and the propagation ofantral pressure waves and decreases duodenalmotility in type I diabetic patients with auto-nomic neuropathy. The changes in antroduo-denal motility are likely to constitute themechanism through which gastric emptying ofsolids is delayed during high blood glucoseconcentrations in these diabetic patients.

This study was supported by a grant from the Diabetes FondsNederland.

1 Kassander P. Asymptomatic gastric retention in diabetics(gastroparesis diabeticorum). Ann Int Med 1958; 48:797-812.

2 Horowitz M, Harding M, Maddox A, et al. Gastric andesophageal emptying in insulin-dependent diabetesmellitus. J Gastroenterol Hepatol 1986; 1: 97-113.

3 Keshavarzian A, Iber FL, Vaeth J. Gastric emptying inpatients with insuline-requiring diabetes mellitus. Am JGastroenterol 1986; 82: 29-35.

4 Camilleri M, Malagelada J-R. Abnormal intestinal motilityin diabetes with gastroparesis syndrome. Eur3t Clin Invest1984; 14: 420-7.

5 Jebbink HJA, Bravenboer B, Akkermans LMA, van Berge-Henegouwen GP, Smout AJPM. Relationship betweendyspeptic symptoms and gastrointestinal motility inpatients with type I (insulin-dependent) diabetes mellitus.Diabetologia 1993; 36: 948-54.

6 Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunctionin diabetics with recurrent nausea and vomiting.Gastroenterology 1986; 90: 1919-25.

7 Feldman M, Schiller LR. Disorders of gastrointestinalmotility associated with diabetes mellitus. Ann Int Med1983;98: 378-84.

8 Parkman HP, Schwartz SS. Esophagitis and gastroduodenaldisorders associated with diabetes mellitus. Arch InternMed 1987; 147: 1477-80.

9 Horowitz M, Edelbroek M, Fraser R, Maddox A, Wishart J.Disordered gastric motor function in diabetes mellitus.Recent insights into prevalence, pathophysiology, clinicalrelevance and treatment. Scand Jr Gastroenterol 1991; 26:673-84.

10 Rundles RW. Diabetic neuropathy; general review withreports of 125 cases. Medicine 1945; 24: 111-60.

11 Fraser RJ, Horowitz M, Maddox AF, Harding PE,Chatterton BE, Dent J. Hyperglycaemia slows gastricemptying in type 1 (insulin-dependent) diabetes mellitus.Diabetologia 1990; 33: 675-80.

12 Fraser RJ, Horowitz M, Dent J. Hyperglycemia stimulatespyloric motility in normal subjects. Gut 1990; 32: 475-8.

13 Bamett JL, Owyang C. Serum glucose concentration as amodulator of interdigestive gastric motility. Gastroenter-ology 1988; 94: 739-44.

14 Hasler WL, Soudah HC, Dulai G, Owyang C. Mediationof hyperglycemia-evoked gastric slow-wave dysrhythmiasby endogenous prostaglandins. Gastroenterology 1995;108: 727-36.

645



j.com/


ay 1997. Dow

nloaded from

http://gut.bmj.com/

Samsom, Akkermans, J7ebbink, van Isselt, vanBerge-Henegouwen, Smout

15 Lam WF, De Boer SY, Masclee AAM, Lamers CBHW.Hyperglycemia reduces gastric secretory and plasmapancreatic polypeptide responses to modified shamfeeding. Digestion 1993; 54: 48-53.

16 Ewing DJ, Clarke BF. Diagnosis and management ofdiabetic autonomic neuropathy. BMJ3 1982; 285: 916-8.

17 Heddle R, Fone D, Dent J, Horowitz M. Stimulation ofpyloric motility by intraduodenal dextrose in normalsubjects. Gut 1988; 29: 1349-57.

18 Samsom M, Jebbink HJA, Akkermans LMA, van Berge-Henegouwen GP, Smout AJPM. Abnormalities ofantroduodenal motility in type I (insulin-dependent)diabetes mellitus. Diabetes Care 1996; 19: 21-7.

19 Smout AJPM, Bogaard JW, van Hattum J, AkkermansLMA. Effects of cimetidine and ranitidine on inter-digestive and postprandial lower esophageal sphincterpressure and plasma gastrin levels in normal subjects.Gastroenterology 1985; 88: 557-63.

20 Fraser R, Horowitz M, Maddox M, Dent J. Organizationof antral, pyloric and duodenal motility in patients withgastroparesis. Gastrointest Motil 1993; 5: 167-75.

21 Collins PJ, Horowitz M, Cook DJ, Harding PE,Shearman DJC. Gastric emptying in normal subjects. Areproducible technique using a single scintillation camera.Gut 1983;24: 1117-25.

22 Fone DR, Horowitz M, Heddle R, Maddox AF, Collins PJ,Read NW, Dent J. Comparative effects of duodenal andileal intubation on gastric emptying and postprandialantral, pyloric and duodenal motility. Scand Gastro-enterol 1991; 26: 16-22.

23 DeFronzo RA, Tobin JD, Andres R. Glucoseclamp technique: a method for quantifying insulinsecretion and resistance. Am I Physiol 1979; 237:E214-23.

24 MacGregor, Gueller R, Watts HD, Meyer JH. The effect ofacute hyperglycemia on gastric emptying in man.Gastroenterology 1976; 70: 190-6.

25 Camilleri M, Malagelada JR, Brown ML, Becker G,Zinsmeister AR. Relation between antral motility andgastric emptying of solids and liquids in humans. Am .7

Physiol 1985; 249: G580-5.26 Houghton LA, Read NW, Heddle R, Horowitz M,

Collins PJ, Chatterton B, Dent J. Relationship of themotor activity of the antrum, pylorus and duodenum togastric emptying of a solid-liquid mixed meal.Gastroenterology 1988; 94: 1285-91.

27 Hebbard G, Samsom M, Sun WM, Dent J, Horowitz M.Hyperglycemia affects proximal gastric motor and sensoryfunction during small intestinal nutrient infusion.Gastroenterology 1996; 110: A676.

646



j.com/


ay 1997. Dow

nloaded from

http://gut.bmj.com/

type - gut.bmj.com · sulphur colloid and the 150 ml liquid com-ponent (dextrose 10%, 250 kj) was...

Documents