Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by De Block, C. E.M.
Right arrow Articles by Van Gaal, L. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by De Block, C. E.M.
Right arrow Articles by Van Gaal, L. F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes Care 25:912-917, 2002
© 2002 by the American Diabetes Association, Inc.

Pathophysiology/Complications
Original Article

Delayed Gastric Emptying and Gastric Autoimmunity in Type 1 Diabetes

Christophe E.M. De Block, MD 1, Ivo H. De Leeuw, MD, PHD1, Paul A. Pelckmans, MD, PHD2, Dirk Callens2, Emöke Máday, MSC, PHD 1 and Luc F. Van Gaal, MD, PHD1

1 Department of Endocrinology-Diabetology, Faculty of Medicine, University of Antwerp, University Hospital Antwerp, Edegem, Belgium
2 Department of Gastroenterology & Hepatology, Faculty of Medicine, University of Antwerp, University Hospital Antwerp, Edegem, Belgium


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
OBJECTIVE—Delayed gastric emptying and/or gastrointestinal symptoms occur in 30–50% of diabetic patients. Known contributing factors are autonomic neuropathy and acute hyperglycemia, but the role of gastric autoimmunity has never been investigated, although 15–20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA status, autonomic nerve function, HbA1c, thyroid-stimulating hormone (TSH), Helicobacter pylori (HP), acid production, and gastric histology.

RESEARCH DESIGN AND METHODS—Gastric emptying of solids and liquids (measured by 13C-octanoic acid and 13C-glycine breath tests, respectively) was tested in euglycemic conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age 40 ± 15 years; mean HbA1c 7.8 ± 0.9%). Gastrointestinal symptoms, autonomic nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric histology, and acid secretion (pentagastrin) were assessed.

RESULTS—Solid gastric emptying was delayed in 40% and liquid emptying in 36% of patients. Gastric motility did not correlate with symptoms. PCA status, gastric morphology, and acid secretion were similar in those with and without gastroparesis. HbA1c level (ß = 1.34, P = 0.011) was the only risk factor for delayed solid emptying in a logistic regression model testing HbA1c, autonomic nerve function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying time for liquids correlated with TSH level (r = 0.83, P < 0.0001) and autonomic neuropathy score (r = -0.79, P = 0.001).

CONCLUSIONS—We found that ~50% of type 1 diabetic patients studied had delayed gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. Metabolic control was worse in patients with delayed solid emptying.

Abbreviations: CAN, cardiovascular autonomic neuropathy • CV, coefficient of variation • fT4, free T4 • GEC, gastric emptying coefficient • HP, Helicobacter pylori • PCA, parietal cell antibody • t1/2, gastric half-emptying time • TSH, thyroid-stimulating hormone


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
As many as 30–50% of type 1 diabetic patients have evidence of delayed gastric emptying, a dysfunction that may be manifested in gastrointestinal symptoms and/or metabolic instability (1–4). Conversely, many patients with gastroparesis are asymptomatic, and subjects with symptoms may have normal gastric emptying (4,5). Diabetic gastroparesis comprises a decrease in fundic and antral motor activity (6–8), a reduction in or lack of the interdigestive migrating motor complex (8), gastric dysrhythmias (9), and "pylorospasms" (10). The etiology of diabetic gastroparesis is still not fully established, but important factors seem to be autonomic neuropathy (6,11–13), acute hyperglycemia (14,15), and abnormalities of gut hormones and neurotransmitters, such as motilin (16), gastrin (17), and nitric oxide (18). Thyroid function (19), gastric acid secretion (20,21), or Helicobacter pylori (HP) infection (22) may also modulate gastrointestinal motility. However, the role of gastric autoimmunity in diabetic gastroparesis has never been investigated, although 15–20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs) (23), which, by impairing acid secretion (24,25), may modify gastric motility. Because treatment is possible (1,2,26), diagnosing and identifying risk factors for gastroparesis is important for controlling symptoms and enhancing glucoregulation.

We examined the prevalence of delayed gastric emptying, under euglycemic conditions, in type 1 diabetic patients in relation to PCA status, cardiovascular autonomic function, HbA1c, HP status, thyroid function, acid production, gastrin levels, and gastric histology. The relationship between gastric emptying and gastrointestinal symptoms was also evaluated. We are one of the first to perform the 13C-octanoic acid breath test (13,27,28) and the first to use the 13C-glycine breath test for solid and liquid emptying, respectively, in diabetic patients.


   RESEARCH DESIGN AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
Patients
We studied 42 euthyroidic type 1 diabetic patients, comprising 15 PCA+ and 27 PCA- subjects (male/female 29/13; mean age 40 ± 15 years; mean diabetes duration 18 ± 9 years; mean HbA1c 7.8 ± 0.9%). The patients were consecutively recruited, regardless of gastrointestinal symptoms, from 69 PCA+ and 100 PCA- patients attending the Antwerp University Diabetes Clinic, and fulfilled criteria for type 1 diabetes (29). Patients with a history of gastric surgery or gastric outlet obstruction or who were taking motility-altering drugs, anti-inflammatory drugs, antacids, or proton pump inhibitors were excluded. Smoking, drinking beverages containing alcohol or caffeine, and strenuous exercise were prohibited in the 24 h before the gastric emptying tests. The local ethics committee approved the study, and each patient gave written informed consent.

Methods
PCAs were assayed by indirect immunofluorescence (Medical Diagnostics California, Carlsbad, CA; Nl <1/20 dilution) (23). Gastrin was measured by radioimmunoassay (Euro-Diagnostics, Malmö, Sweden; Nl <110 ng/l). Thyroid peroxidase antibodies were assayed by radiobinding assay (Henningtest, Brahms, Germany; Nl <100 units/ml). Thyroid function was estimated by assay of thyroid-stimulating hormone (TSH) (Nl 0.47–4.7 mU/l) and free T4 levels (fT4) (Nl 10.8–21.9 pmol/l) (Vitros; Ortho Clinical Diagnostics, Amersham, Amersham, U.K.).

Gastrointestinal symptoms.
Gastrointestinal symptoms were assessed by questionnaire. Anorexia, nausea, early satiety, abdominal bloating/fullness, vomiting, abdominal pain, dysphagia, heartburn, and acid regurgitation were graded as 0 = none, 1 = mild (the symptom could be ignored), 2 = moderate (the symptom could not be ignored, but did not influence daily activities), and 3 = severe (the symptom influenced daily activities) (3). Reproducibility of this questionnaire was measured by a test-retest procedure, and validity was documented by comparing questionnaire data with an independent interview. The reproducibility and validity were high in this study (coefficients of variation [CVs] 4.8 and 9.5%, respectively).

Autonomic nerve function.
Autonomic nerve function was documented by standardized cardiovascular reflex tests (30). Parasympathetic function was evaluated by the variation of heart rate (R-R interval) during deep breathing and the immediate heart rate response to standing (30:15 ratio) and the Valsalva maneuver. Sympathetic function was assessed by the fall in systolic blood pressure in response to standing. The results were classified as follows: 0 = normal; 1 = borderline cardiovascular autonomic neuropathy (CAN; one abnormal heart rate test), 2 = definite CAN (>=2 abnormal heart rate tests), and 3 = severe CAN (all abnormal heart rate and blood pressure tests). The reproducibility, expressed as the CV for autonomic neuropathy test, was 2.4% for heart rate variability, 9.5% for the deep breathing test and Valsalva maneuver, and 7.1% for the heart rate response to standing and for the postural blood pressure test.

Helicobacter pylori.
HP IgG antibodies were assayed by enzyme-linked immunosorbent assay (Roche Diagnostics, Brussels, Belgium). Urea breath tests, using 75 g 13C-urea, were performed after a 12-h overnight fast (31). Antrum, corpus, and fundus biopsies were examined for HP colonization by a modified Giemsa stain and/or immunostaining. HP infection was diagnosed if any test was positive. The period between the urea breath test and gastroscopy was <=14 days.

At upper gastrointestinal endoscopy (Olympus Videoscope GIF/Q140; Melville, NY), at least two biopsies from fundus, corpus, antrum, and descending duodenum were taken. Then, two investigators evaluated 5-µm sections, unaware of the patient’s clinical and laboratory findings. The visual analog scale of the updated Sydney system was used to evaluate inflammation, activity, atrophy, intestinal metaplasia, and HP colonization (32). HP immunostaining was performed by standard procedures using a polyclonal rabbit HP IgG antibody (Dako B0471; Dako, Glostrup, Denmark; dilution 1/200).

Gastric acid secretion.
Gastric acid secretion was studied in euglycemic conditions after a 12-h overnight fast using pentagastrin-stimulated acid output (6 µg/kg body wt., s.c.) (Pentagastrin Injection BP; Cambridge Laboratories, Newcastle Upon Tyne, UK). Gastric juice was collected for 1 h before and 1 h after pentagastrin administration in 15-min aliquots. Hypochlorhydria was defined as a maximal acid output <15 mmol H+/h.

Gastric emptying
To eliminate the effect of acute hyperglycemia on gastric emptying, patients’ blood glucose levels were stabilized in the euglycemic range. Patients received their standard morning insulin dose at least 30 min before the test meal. At 15-min intervals, glycemia was tested by fingerstick (One Touch blood glucose meter; Lifescan, Milpitas, CA) to maintain glycemia at 4.5–6 mmol/l for at least 30 min before and at 4.5–8 mmol/l after the test meal. One intravenous cannula was inserted into antecubital vein for infusion of glucose 5% buffered with 10 units short-acting insulin at 50 ml/h (Human Actrapid; Novo Nordisk, Copenhagen, Denmark) to maintain euglycemia. If glycemia exceeded >= 7 mmol/l, intravenous short-acting insulin was given: 1 unit for glycemia >=7 mmol/l, 2 units for glycemia >=8 mmol/l, and 3 units for glycemia >=9 mmol/l. If glycemia was <3.5 mmol/l, 20% glucose in 10-ml aliquots was given to normalize levels: 1 ampulla of 10 ml glucose 20% for glycemia <3.5 mmol/l and 2 ampullae for glycemia <2.5 mmol/l. To avoid 14C, we used two 13C breath tests, which were performed within an 8- to 24-day period.

13C octanoic acid breath test (solids)
The test was performed after a 12-h overnight fast. Patients avoided 13C-rich meals 48 h before the breath test to increase its accuracy. Baseline breath 13CO2 before eating the test meal was measured. The test meal consisted of a beaten egg with the yolk doped with 100 mg of 13C-octanoic acid (Isotec, Miamisburg, OH), two slices of white bread, and 5 g margarine (33,34). The yolk was baked separately from the egg white to ensure firm labeling. The meal, with a caloric value of 250 kcal (42% carbohydrates, 18% protein, and 40% fat), was ingested in 10 min, and patients were allowed to drink 150 ml water in this period. Breath samples were collected over a 4-h period at 15-min intervals. 13CO2 measurements were performed with an isotope ratio mass spectrometer (Finnigan MAT-250; Finnigan, Bremen, Germany). Mathematical analysis of the excretion rate of 13CO2 allowed the definition of the gastric-emptying coefficient (GEC) and the gastric half-emptying time (t1/2). With a cutoff value for t1/2breathsolids of 75 min and a cutoff value for GECbreathsolids of 3.1 min, excellent sensitivity, specificity, and positive and negative predictive values were obtained to separate normal subjects from patients with delayed gastric emptying (33,34).

13C-glycine breath test (liquids)
We chose 100 mg of 13C-glycine as the marker of the liquid phase because it is easily solubilized in water and is rapidly absorbed and converted into 13CO2 after it enters the small intestine. Cutoff values for the GECbreathliquids and t1/2breathliquids were 3 and 55', respectively (34).

Good-to-excellent correlations between the GEC and the scintigraphic half-emptying time (r = 0.74 for liquids, r = 0.88 for solids) and between the t1/2 determined by breath test and scintigraphy (r = 0.91 for liquids, r = 0.92 for solids) have been previously described (33,34).

Statistical analysis
Results were statistically analyzed using SPSS software (SPSS, Chicago, IL). The unpaired t test or Mann-Whitney U test was used to determine differences between groups. Differences in distributions of categorical data were investigated by {chi}2 or Fisher’s exact test. The Pearson or Spearman rank correlation test was used. Stepwise forward logistic regression analysis was used to assess the strength and independence of associations. A two-tailed P < 0.05 was considered significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
Gastrointestinal symptoms were reported by 43% of patients, but the majority of patients had no or only mild symptoms, with a median symptom score of 4. Early satiety and abdominal bloating were present in 17 patients (33%), nausea and/or vomiting in 7 patients (17%), abdominal pain in 6 patients, and regurgitation and/or heartburn in 5 patients. No associations were noted between presence or score of symptoms and indexes of solid and liquid emptying (GEC and t1/2). Autonomic neuropathy was present in seven patients (three severe, two definite, and two borderline).

Parietal cell antibody findings
Sex, age, diabetes duration, HbA1c, and presence and severity of gastrointestinal symptoms were similar in PCA+ and PCA- diabetic subjects (Table 1). PCA+ patients were more prone to having hypochlorhydria (odds ratio 12.1 [2.7–54.3], P = 0.0008) and higher gastrin levels (P = 0.003) than PCA- subjects. However, no differences were found in the prevalence of autonomic neuropathy, gastrointestinal complaints, HP infection, or delayed solid and liquid gastric emptying between PCA+ and PCA- subjects (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1— Clinical characteristics of PCA+ and PCA– type 1 diabetic patients.

 
Solid gastric emptying
Solid gastric emptying was delayed (GECbreathsolids <3.1, t1/2breathsolids >75') in 40% of type 1 diabetic patients. The mean glycemia during solid emptying was 119 ± 37 mg/dl. In this range, glycemia did not correlate with indexes of solid emptying (GEC and t1/2). However, patients with delayed solid emptying had higher HbA1c levels than those with normal solid emptying (P = 0.005) (Table 2). Autonomic neuropathy was equally common in both groups, and no association was observed between CAN score and rate of solid emptying. No differences were found in gastric histology (i.e., absence/presence of autoimmune gastritis), acid secretion parameters (basal, maximal, or peak acid output), or gastrin levels between those with and without gastroparesis. HbA1c level (ß = 1.34;P = 0.011) was the only independent risk factor for delayed solid gastric emptying in a logistic regression model testing HbA1c, autonomic nerve function, PCA, HP status, gastrin, TSH, age, sex, and diabetes duration. The t1/2breathsolid correlated strongly with GECbreathsolid (r = -0.81, P < 0.0001). Patients with delayed solid emptying tended to have a delay in liquid emptying (P = 0.1); furthermore, a correlation between t1/2breathsolid and t1/2breathliquid (r = 0.44, P = 0.037) was found. Solid and/or liquid emptying was delayed in 23 patients (55%).


View this table:
[in this window]
[in a new window]
  		Table 2— Clinical characteristics of type 1 diabetic patients with and without delayed solid gastric emptying

 
Liquid gastric emptying
Liquid gastric emptying was delayed (GECbreathliquids <3, t1/2breathliquids >55') in 36% of type 1 diabetic patients. The mean glycemia during liquid emptying was 129 ± 34 mg/dl. No correlations were observed between the level of glycemia and indexes of liquid emptying (GEC and t1/2). Although each subject was euthyroidic, patients with delayed liquid emptying had higher TSH levels (P = 0.02) than those with normal liquid emptying (Table 3). Further, a strong correlation was noted between t1/2breathliquid on one hand and TSH levels (r = 0.83, P < 0.0001), fT4 levels (r = -0.65, P = 0.021), and CAN score (r = -0.79, P = 0.001) on the other. However, logistic regression analysis could not identify a single independent risk factor for liquid gastric emptying when HbA1c, autonomic nerve function, PCA and HP infection status, gastrin and TSH levels, age, sex, and duration of diabetes were tested.


View this table:
[in this window]
[in a new window]
  		Table 3— Clinical characteristics of type 1 diabetic patients with and without delayed liquid gastric emptying

 

   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
This study investigated the putative role of PCA, present in 15–20% of type 1 diabetic patients (23), in the etiology of diabetic gastroparesis, using breath tests for liquid and solid emptying in euglycemic conditions. More than half of our type 1 diabetic patients (55%) had delayed gastric emptying (solids in 40% and liquids in 36%), in line with previous data (1–3). HbA1c level was identified as a risk factor for delayed solid emptying. Autonomic nerve function, PCA or HP status, gastric histology, acid secretion, or gastrin or TSH level did not seem to affect solid emptying. On the other hand, TSH level and autonomic neuropathy score correlated with t1/2breathliquid. Age, sex, and diabetes duration did not correlate with gastric emptying rate, supporting results from other studies (13,35,36). Breath tests have several advantages over scintigraphy, with which they correlate very well (see RESEARCH DESIGN AND METHODS). They are easy to perform, noninvasive, have good reproducibility, and avoid radiation burden, thereby facilitating emptying studies in fertile women and children (13,27,28,33,34). Moreover, many tests can be done simultaneously because 13CO2 can be analyzed overnight. Unlike a number of studies, ours controlled for many variables that may affect gastrointestinal symptoms and emptying: glucose level at the time of gastric emptying, gastric mucosal status, HP status, and autonomic nerve function.

Most patients had no or only minor complaints, reflecting the fact that they were not selected on the basis of symptoms. We observed no association between gastric motility and symptoms, confirming some (7,37), but opposing other reports (4,13,38). In line with recent data (38), bloating was the most common symptom. Abnormalities in visceral sensation (39) or a variable degree of vagal afferent and efferent dysfunction (1) might explain the poor link between symptoms and gastric motility. Glycemic control may also influence the prevalence or perception of gastrointestinal symptoms (15,40), although this was not supported by our results.

Gastric neuromuscular dysfunction may account for poor metabolic control, resulting from the dyssynchrony of insulin administration and emptying of nutrients (2,3). All our patients had good metabolic control. Nevertheless, we found that HbA1c levels were associated with delayed solid emptying, contrary to findings in other studies (12,13). It is not clear whether worse metabolic control determines or is determined by delayed gastric emptying. Prospective follow-up studies designed to see whether improving HbA1c would also improve gastric motility may help to clarify this interesting finding. Acute hyperglycemia may slow down gastric emptying (14,15) by evoking pyloric contractions (41) or suppressing antral contractions (42). In contrast, others found no link between glycemia and gastric motility (4,6). In euglycemic conditions, we did not see an effect of glucose levels on gastric emptying.

Autonomic neuropathy with loss of vagal tone and increased sympathetic nervous system activity has been associated with gastric dysrhythmias (5,43). Years ago, Kassander (5) noted the similarity between clinical and radiographic findings of gastroparesis and gastric atony observed after surgical vagotomy. In addition, some (44), but not all (45), researchers have found histologic abnormalities in vagal nerve tissue of diabetic patients. We did not observe a link between CAN scores and rates of solid emptying, confirming results from some studies (4,27,37), but opposing results from other studies, describing a weak association (6,12,13). However, a good correlation was found with t1/2breathliquid. Perhaps these conflicting results are caused by differences in neuropathic involvement in solid and liquid emptying (4) or by differences in accuracy between classical CAN tests and the new ones using spectral and vector analysis (46). Our approach in which breath tests were performed on 2 days to avoid the use of 14C could also have introduced a source of variability. However, all tests were done in euglycemic conditions using standard procedures. Despite the poor relationship between emptying of solids and liquids (6,13), suggesting that predictors of delayed solid emptying differ from those of liquid emptying (38), we observed a weak correlation between t1/2breathsolid and t1/2breathliquid; in addition, patients with delayed solid emptying tended to have a delay in liquid emptying.

Cyclic variation in gastric acid secretion, synchronous with the various phases of the migrating motor complex, have been shown in duodenal ulcer disease (21). Moreover, one group observed a delay in gastric emptying in patients with chronic atrophic gastritis and hypo- or achlorhydria (20). However, others have reported that interdigestive antroduodenal motility in achlorhydria is not different from that in normal acid-secreting control subjects (21). Our results support the observation that acid secretion is not essential in the regulation of gastric motility (47). Moreover, we did not observe a link between gastric motility and PCA positivity, the latter being associated with hypochlorhydria, or gastric histology. Furthermore, HP infection did not influence gastric emptying or the presence or severity of gastrointestinal symptoms (22). This is an important observation, because abnormal gastric emptying could affect urea breath test results. We and others have found no association between urea breath test and gastric emptying breath test results (22).

Despite the fact that all patients were euthyroidic, we observed a strong correlation between t1/2breathliquid and TSH levels. Thus subclinical hypothyroidism may affect gastric motor activity, as does overt hypothyroidism (19). The pathogenesis of gastric motor hypoactivity is not precisely known. Autonomic neuropathy, disturbance of impulse conduction at the myoneural junction, changes in gastrointestinal peptide hormone metabolism, and autoimmune factors might explain this dysfunction.

In conclusion, more than half of type 1 diabetic patients studied had a delay in gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. HbA1c level was the only independent risk factor for delayed solid emptying. Autonomic nerve function, PCA or HP infection status, age, sex, diabetes duration, gastric histology, gastrin levels, and acid secretion did not seem to affect solid emptying. On the other hand, TSH level and autonomic neuropathy score were correlated with t1/2breathliquid. It is important to report the lack of contribution of gastric autoimmunity to delayed gastric emptying and to propose an etiological role of HbA1c and subclinical hypothyroidism. It is hoped this work will stimulate new hypotheses and encourage the use of breath tests.


   Acknowledgments
 
This study was supported by a grant from the European Foundation for the Study of Diabetes.

The technique of the breath tests was introduced to the Department of Gastroenterology by Prof. Dr. Y. Ghoos and Dr. B. Geypens (Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium).

We gratefully acknowledge Dr. K. Van Acker and Dr. F. Peiffer (Department of Endocrinology-Diabetology) for their help in patient recruitment, Dr. C. Van Campenhout and K. Van Cotthem (Laboratory of Immunology and Protein Chemistry), Prof. Dr. E. Van Marck and Prof. Dr. J. Bogers (Department of Pathology), Prof. Dr. V. Van Hoof (Laboratory of Biochemistry), Apr. M. Martin (Laboratory of Hormonology), Prof. Dr. M. Ieven (Laboratory of Microbiology), B. Raeymaeckers and R. Borrie (Department of Gastroenterology), and Dr. B. Manuel y Keenoy, J. Vertommen, P. Aerts, S. Schrans, and M. Vinckx (Laboratory of Endocrinology-Diabetology) of the University of Antwerp.

Parts of this study were presented at the 61st Scientific Sessions of the American Diabetes Association, Philadelphia, PA, June 2001.


   Footnotes
 
Address correspondence and reprint requests to Christophe De Block, MD, Department of Endocrinology-Diabetology, Faculty of Medicine, University of Antwerp, University Hospital Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium. E-mail: cdeblock{at}uia.ua.ac.be.

Received for publication 2 August 2001 and accepted in revised form 7 February 2002.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.


   References
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

  1. Koch KL: Diabetic gastropathy. Gastric neuromuscular dysfunction in diabetes mellitus: a review of symptoms, pathophysiology, and treatment. Dig Dis Sci 44:1061–1075, 1999[Medline]
  2. Nilsson P: Diabetic gastroparesis: a review. J Diabetes Complications 10:113–122, 1996[Medline]
  3. Kong MF, Horowitz M, Jones KL, Wishart JM, Harding PE: Natural history of diabetic gastroparesis. Diabetes Care 22:503–507, 1999[Abstract]
  4. Jebbink HJA, Bravenboer B, Akkermans LMA, van Berge-Henegouwen GP, Smout AJPM: Relationships between dyspeptic symptoms and gastrointestinal motility in patients with type 1 (insulin dependent) diabetes mellitus. Diabetologia 36:948–954, 1993[Medline]
  5. Kassander P: Asymptomatic gastric retention in diabetics (gastroparesis diabeticorum). Ann Intern Med 48:797–812, 1958
  6. Keshavarian A, Iber FL, Vaeth J: Gastric emptying in patients with insulin requiring diabetes mellitus. Am J Gastroenterol 82:29–35, 1987[Medline]
  7. Urbain JLC, Vekemans MC, Bouillon R, Van Cauteren J, Bex M, Mayeur SM, Van den Maegdenbergh V, Bataille G, Charkes ND, Malmud LS, De Roo M: Characterization of gastric antral motility disturbances in diabetes using a scintigraphic technique. J Nucl Med 34:576–581, 1993[Abstract/Free Full Text]
  8. Fox S, Behar J: Pathogenesis of diabetic gastroparesis: a pharmacologic study. Gastroenterology 78:757–763, 1980[Medline]
  9. Koch KL, Stern RM, Stewart WR, Vasey MW: Gastric emptying and gastric myoelectrical activity in patients with diabetic gastroparesis: effect of domperidone treatment. Am J Gastroenterol 84:1069–1075, 1989[Medline]
  10. Mearin F, Camilleri M, Malagelada JR: Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology 90:1919–1925, 1986[Medline]
  11. Enck P, Frieling T: Pathophysiology of diabetic gastroparesis. Diabetes 46(Suppl. 2):S77–S81, 1997
  12. Merio R, Festa A, Bergmann H, Eder T, Eibl N, Stacher-Janotta G, Weber U, Budka C, Heckenberg A, Bauer P, Francesconi M, Schernthaner G, Stacher G: Slow gastric emptying in type 1 diabetes: relation to autonomic and peripheral neuropathy, blood glucose, and glycemic control. Diabetes Care 20:419–423, 1997[Abstract]
  13. Ziegler D, Schadewaldt P, Pour Mirza A, Piolot R, Schommartz B, Reinhardt M, Vosberg H, Brosicke H, Gries FA: [13C] Octanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients: validation and relationship to gastric symptoms and cardiovascular autonomic function. Diabetologia 39:823–830, 1996[Medline]
  14. Schvarcz E, Palmér M, Aman J, Horowitz M, Stridsberg M, Berne C: Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus. Gastroenterology 113:60–66, 1997[Medline]
  15. Rayner CK, Samsom M, Jones KL, Horowitz M: Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care 24:371–381, 2001[Abstract/Free Full Text]
  16. Achem-Karam SR, Funakoshi A, Vinik AJ, Chung O: Plasma motilin concentration and interdigestive migrating motor complex in diabetic gastroparesis: effect of metoclopramide. Gastroenterology 88:492–499, 1985[Medline]
  17. Feldman M, Corbett D, Ramsey E, Walsh J, Richardson CT: Abnormal gastric function in longstanding insulin-dependent diabetic patients. Gastroenterology 77:12–17, 1979[Medline]
  18. Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, Herman AG: Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 345:346–347, 1990[Medline]
  19. Holdsworth DC, Besser GM: Influence of gastric emptying rates and insulin response on oral glucose tolerance in thyroid disease. Lancet ii:700–702, 1968
  20. Davies WT, Kirkpatrick JR, Owen GM, Shield R: Gastric emptying in atrophic gastritis and carcinoma of the stomach. Scand J Gastroenterol 6:297–301, 1971[Medline]
  21. Bortolotti M, Barbara L: Interdigestive gastroduodenal motor activity in subjects with increased gastric acid secretion. Digestion 41:156–160, 1988[Medline]
  22. Perri F, Ghoos YF, Maes BD, Geypens BJ, Ectors N, Geboes K, Hiele MI, Rutgeerts PJ: Gastric emptying and Helicobacter pylori infection in duodenal ulcer disease. Dig Dis Sci 41:462–468, 1996[Medline]
  23. De Block CEM, Van Gaal LF, De Leeuw IH, Belgian Diabetes Registry: High prevalence of manifestations of gastric autoimmunity in parietal cell-antibody positive type 1 (insulin dependent) diabetic patients. J Clin Endocrinol Metab 84:4062–4067, 1999[Abstract/Free Full Text]
  24. Wolfe MM, Soll AH: The physiology of gastric acid secretion. N Engl J Med 319:1707–1715, 1988[Medline]
  25. De Block C, De Leeuw I, Van Gaal L, Van Acker K, Peiffer F, Máday E, Van Hoof V, Pelckmans P: Gastric acid secretion and autoimmune gastropathy in type 1 diabetes (Abstract). Diabetes 50(Suppl. 1):A259, 2001
  26. Sturm A, Holtmann G, Goebell H, Gerken G: Prokinetics in patients with gastroparesis: a systematic analysis. Digestion 60:422–427, 1999[Medline]
  27. Pfaffenbach B, Wegener M, Adamek RJ, Wissuwa H, Schaffstein J, Aygen S, Hennemann O: Nicht-invasiver 13C-Oktansäureatemtest zur messung der magen-entleerung einer festen testmahlzeit: korrelation mit der szintigraphie bei diabetikern und reproduzierbarkeit bie gesunden probanden. Z Gastroenterol 33:141–145, 1995[Medline]
  28. Lee JS, Camilleri M, Zinsmeister AR, Burton DD, Choi MG, Nair KS, Verlinden M: Toward office-based measurement of gastric emptying in symptomatic diabetics using [13C]octanoic acid breath test. Am J Gastroenterol 95:2751–2761, 2000[Medline]
  29. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183–1197, 1997[Medline]
  30. Ewing DJ, Clarke BF: Diagnosis and management of diabetic autonomic neuropathy. Br Med J 285:916–918, 1982
  31. Peeters M, Ghoos Y, Geypens B, Rutgeerts P: Breath tests in Helicobacter pylori infection: methodological aspects. J Physiol Pharmacol 48(Suppl. 4):67–73, 1997
  32. Dixon MF, Genta RM, Yardley JH, Correa P: Classification and grading of gastritis: the updated Sydney system. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol20:1161–1181, 1996
  33. Ghoos YF, Maes BD, Geypens BJ, Mys G, Hiele MI, Rutgeerts PJ, Vantrappen G: Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test. Gastroenterology 104:1640–1647, 1993[Medline]
  34. Maes BD, Ghoos YF, Geypens BJ, Mys G, Hiele MI, Rutgeerts PJ, Vantrappen G: Combined carbon-13-glycine/carbon-14-octanoic acid breath test to monitor gastric emptying rates of liquids and solids. J Nucl Med 35:824–831, 1994[Abstract/Free Full Text]
  35. Horowitz M, Maddern GJ, Chatterton BE, Collins PJ, Harding PE, Shearman DJC: Changes in gastric emptying rates with age. Clin Sci 67:213–218, 1984[Medline]
  36. Datz FL, Christian PE, Moore J: Gender-related differences in gastric emptying. J Nucl Med 28:1204–1207, 1987[Abstract/Free Full Text]
  37. Jebbink HJA, Bruijs PPM, Bravenboer B, Akkermans LMA, van Berge-Henegouwen, Smout AJPM: Gastric myoelectrical activity in patients with type I diabetes and autonomic neuropathy. Dig Dis Sci 39:2376–2383, 1994[Medline]
  38. Jones KL, Russo A, Stevens JE, Wishart JM, Berry MK, Horowitz M: Predictors of delayed gastric emptying in diabetes. Diabetes Care 24:1264–1269, 2001[Abstract/Free Full Text]
  39. Rathmann W, Enck P, Frieling T, Gries FA: Visceral afferent neuropathy in diabetic gastroparesis. Diabetes Care 14:1086–1089, 1991[Abstract]
  40. Schvarcz E, Palmer M, Ingberg CM, Aman J, Berne C: Increased prevalence of upper gastrointestinal symptoms in long-term type 1 diabetes mellitus. Diabet Med 13:478–481, 1996[Medline]
  41. Fraser R, Horowitz M, Dent J: Hyperglycaemia stimulates pyloric motility in normal subjects. Gut 32:475–478, 1991[Abstract/Free Full Text]
  42. Hasler WL, Soudah HC, Dulai G, Owyang C: Mediation of hyperglycemia-evoked gastric slow-wave dysrhythmias by endogenous prostaglandins. Gastroenterology 108:727–736, 1995[Medline]
  43. Koch KL, Stern RM, Vasey MW, Seaton JF, Demers LM, Harrison TS: Neuroendocrine and gastric myoelectrical responses to illusory self-motion in humans. Am J Physiol 258:E304–E310, 1990[Abstract/Free Full Text]
  44. Duchen LW, Anjorin A, Watkins PJ, Mackay JD: Pathology of autonomic neuropathy in diabetes mellitus. Ann Intern Med 92:301–303, 1980
  45. Yoshida MM, Shuffler MD, Sumi SM: There are no morphologic abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis. Gastroenterology 94:907–914, 1988[Medline]
  46. Ziegler D, Laux G, Dannehl K, Spüler M, Mühlen H, Mayer P, Gries FA: Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med 9:166–175, 1992[Medline]
  47. Gielkens HA, Niewenhuizen A, Biemond I, Lamers C, Masclee A: Interdigestive antro-duodenal motility and gastric acid secretion. Aliment Pharmacol Ther 12:27–33, 1998[Medline]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by De Block, C. E.M.
Right arrow Articles by Van Gaal, L. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by De Block, C. E.M.
Right arrow Articles by Van Gaal, L. F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum