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Prevalence of Gastrointestinal Symptoms Associated With Diabetes Mellitus
A Population-Based Survey of 15 000 Adults
Peter Bytzer, MD, PhD;
Nicholas J. Talley, MD, PhD;
Melanie Leemon, MDiet;
Lisa J. Young, BSc(Hons)(Psych);
Michael P. Jones, PhD;
Michael Horowitz, MD, PhD
Arch Intern Med. 2001;161:1989-1996.
ABSTRACT
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Background Gastrointestinal symptoms are reportedly common in diabetes, but a causal
link is controversial and adequate population control data are lacking.
Objective To determine whether gastrointestinal symptoms are more frequent in
persons with diabetes, particularly in those with poor glycemic control.
Methods Fifteen thousand adults were mailed a questionnaire (response rate,
60.0%) containing validated questions on the frequency of troublesome gastrointestinal
symptoms within the past 3 months, diabetic status, and self-reported glycemic
control. The prevalence of 16 symptoms and 5 symptom complexes, reported to
occur often or very often, was compared using logistic regression analysis,
adjusting for age and sex.
Results Overall, 8657 eligible subjects responded; 423 (4.9%) reported having
diabetes. Most (94.8%) had type 2 diabetes mellitus. Adjusting for age and
sex, all 16 symptoms and the 5 symptom complexes were significantly more frequent
in subjects with diabetes compared with controls. An increased prevalence
rate of symptoms was significantly associated with poorer levels of glycemic
control but not with duration of diabetes or type of diabetic treatment.
Conclusions Diabetes mellitus is associated with an increased prevalence of upper
and lower gastrointestinal symptoms. This effect may be linked to poor glycemic
control but not to duration of diabetes or type of treatment.
INTRODUCTION
GASTROINTESTINAL (GI) symptoms are reportedly common in diabetes mellitus
and are usually attributed to autonomic neuropathy.1-2
Although there is evidence that GI symptoms affect quality of life adversely3 and represent a substantial cause of morbidity in
patients with diabetes,4 the available epidemiological
data relating to the prevalence of GI symptoms in diabetes are conflicting
and can be challenged on methodological grounds.
Recently, Schvarcz et al5 evaluated the
prevalence of GI symptoms in a nonselected, population-based cohort of 110
young adult patients with long-standing type 1 diabetes mellitus, compared
with age- and sex-matched control subjects. In the patients with diabetes,
there was an increased prevalence of upper GI symptoms, such as anorexia and
vomiting, whereas there was no difference in the frequency of symptoms referable
to the lower GI tract. The prevalence of GI symptoms was significantly greater
in women than in men and in those subjects with the worst glycemic control,
as assessed by glycated hemoglobin concentrations. On the other hand, Janatuinen
et al6 found that the prevalence of upper GI
symptoms, abdominal pain, constipation, and diarrhea was similar in patients
with diabetes and controls. In that study, only middle-aged patients with
type 1 or type 2 diabetes mellitus who were treated with insulin or oral hypoglycemic
drugs were evaluated, and the questionnaire used to evaluate symptoms was
not a validated measure. A recent study from Hong Kong7
reported higher rates of all types of GI symptoms in 149 patients with type
2 diabetes mellitus who were referred to a university clinic, compared with
community controls. In this study, the duration of diabetes was the only factor
independently associated with GI symptoms. A German study8
of 333 diabetic patients referred to a diabetes research institute found that
only patients with type 2 diabetes mellitus had more upper and lower GI symptoms
than did community controls, the most common symptom being constipation. Finally,
a recent community-based study from the United States9
failed to detect differences in prevalence rates for GI tract symptoms in
persons with or without diabetes mellitus, except for a lower prevalence of
heartburn and an increased prevalence of constipation or laxative use in residents
with type 1 diabetes mellitus. The findings, however, are controversial because
the study did not include a single subject with diarrhea, and the controls
for type 1 diabetes mellitus (mean age, 44 years) reported more constipation
compared with the older group of controls for persons with type 2 diabetes
(mean age, 62 years). Furthermore, the authors reported no differences in
peripheral neuropathy and minor differences in autonomic neuropathy between
subjects with type 1 diabetes (mean disease duration, 23 years) and age-matched
controls.
Therefore, the literature relating to the prevalence and determinants
of GI symptoms in diabetes is conflicting and limited. The populations studied
mainly comprise patients attending diabetes clinics in tertiary hospitals,1, 7-8 who are unlikely to
be representative of the diabetic population in general, while other studies5-7 have focused only on
subgroups of patients with diabetes.
Because GI symptoms, particularly dyspepsia and symptoms compatible
with irritable bowel syndrome, occur frequently in the nondiabetic population,10-11 an appropriate control group is mandatory.
Despite this, a control group was either lacking or poorly defined in some
previous studies.1, 7
Although several studies5, 7-8
agree that GI symptoms are more common in patients with diabetes compared
with nondiabetic controls, the pathogenesis of symptoms remains poorly defined.
It has been suggested that symptoms reflect abnormal GI motility as a manifestation
of irreversible autonomic neuropathy.1, 8
Evidence for this concept, however, is limited.5, 7, 9, 12
Ko et al7 found that rates of GI symptoms in
patients with diabetes with and without peripheral neuropathy were similar,
while Clouse and Lustman,12 in their study
of 114 subjects with type 1 and type 2 diabetes mellitus, found that GI symptoms
were poorly correlated with neuropathic complications once the coexistence
of psychiatric illness was considered in the analysis. Other studies have
implicated duration of diabetes,7 type of diabetes
treatment,13 or an increased perception of
distension14 as risk factors for GI symptoms.
Several studies15-20
have shown that acute change in blood glucose concentration has a major effect
on motor function throughout the GI tract in healthy subjects and in patients
with diabetes mellitus. Variations in blood glucose concentration also have
the potential to affect symptoms arising from the GI tract.15, 18-19,21
For example, in healthy subjects, nausea and fullness, produced by distension
of the proximal stomach or duodenum, have been observed to be more intense
during hyperglycemia than during euglycemia.22-23
In patients with type 1 diabetes mellitus, the perception of fullness, both
before and after a meal, is related to blood glucose concentration.21 These observations support the concept that GI symptoms
in patients with diabetes may be related to glycemic control.5
Only one other study9 has estimated the
frequency and severity of GI symptoms as it affects a nonselected population
of subjects with diabetes across all ages and grades of severity. We devised
an epidemiological survey using a standard questionnaire, and we hypothesized
that troublesome GI symptoms would be more prevalent in patients with diabetes
compared with community controls, after adjusting for age and sex. Furthermore,
we hypothesized that GI symptoms would be associated with poor glycemic control.
MATERIALS AND METHODS
SURVEY METHOD
In Australia, all adults aged 18 years and older are required by law
to be registered on the electoral rolls. Fifteen thousand subjects on the
electoral rolls for Penrith and the Blue Mountains areas west of Sydney, Australia,
were randomly selected for the study. This area has a population of 155 000,
which is demographically similar to the general Australian population, according
to the 1996 census data, except that it is slightly younger and of slightly
higher socioeconomic status.11
The survey was conducted from August 1, 1999, to September 15, 1999,
and the study was closed at the end of November 1999. The list of selected
subjects was divided into 5 batches of 3000 subjects each, and mailings were
begun at intervals approximately 1 week apart. A letter outlining the study
and requesting their participation was sent to all eligible subjects. A $2.00
lottery ticket was included to enhance the response rate.24
Subjects were given the option of refusing to participate. Two reminder letters
were sent at 3-week intervals. Ethical approval was obtained from the Wentworth
Area Health Service Research and Ethics Committee of Nepean Hospital, Penrith.
ASSESSMENT OF SYMPTOMS
The 2-page questionnaire was based on elements from questionnaires that
have previously been validated.11, 25-26
Individual questions were taken from the Bowel Disease Questionnaire,25 and the period was adapted from the validated questionnaire
by Agréus et al.27 The questionnaire
contained 16 questions on the frequency of GI symptoms that had been troublesome
in the preceding 3 months. The frequency of each symptom was rated on a 5-point
Likert scale and coded as not at all, rarely, sometimes, often, or very often.
For the purposes of this analysis, a positive answer was recorded when the
troublesome symptom was reported to occur often or very often.
All symptoms that were not completely self-explanatory were accompanied
by a standard description, consistent with the Rome II criteria28: early satiety (feeling full soon after starting to eat,
rendering the person unable to finish a normal meal); postprandial
fullness (an unpleasant feeling of food staying in the stomach after
a normal meal); bloating (a feeling as if the stomach
or abdomen were swollen); heartburn (a burning pain
or discomfort behind the breastbone rising up toward the throat); dysphagia (difficulty in swallowing, in which solid food or liquids
stick on the way down); anal blockage (a feeling
of blockage in the anus or back passage that made it difficult to pass bowel
movements); and urgency (a need to have a bowel movement
that made the person rush to the toilet).
Subjects were classified into the following 5 symptom complexes based
on their symptoms reported to occur often or very often: esophageal symptoms (heartburn, dysphagia, or both); upper dysmotility symptoms (any of the symptoms of early satiety, postprandial
fullness, bloating, nausea, or vomiting); any bowel symptom (any of the symptoms of self-reported diarrhea or constipation, loose
or watery stools, >3 bowel movements per day, urgency, fecal incontinence,
<3 bowel movements per week, lumpy or hard stools, or anal blockage); diarrhea symptoms (any of the symptoms of >3 bowel movements
per day, loose or watery stools, or urgency); and constipation
symptoms (any of the symptoms of <3 bowel movements per week, lumpy
or hard stools, or anal blockage).
SUBJECTS WITH DIABETES
Persons with diabetes were defined as individuals
who responded yes to the question "Have you ever been diagnosed with diabetes
by a doctor?" Subjects with diabetes were asked to provide information about
their diabetic treatment (insulin only, insulin and oral hypoglycemic tablets,
oral hypoglycemic tablets only, or diet only) and the duration of diabetes
(in years and months). Finally, they were asked to rate control of their blood
glucose levels in general on a 5-point Likert scale. The scale included the
following options: very good control, good control, average control, poor
control, or very poor control. To investigate the relationship between self-reported
glycemic control and symptoms, the grades "very good control" and "good control"
were combined into one grade ("good control"), and the grades "very poor control"
and "poor control" into a single grade ("poor control"), because few subjects
rated their glycemic control in the extreme grades.
Subjects were classified as having type 1 diabetes mellitus if their
age at diagnosis was younger than 30 years and they currently used insulin.29-30 All other subjects with diabetes
were classified as having type 2 diabetes mellitus. Those who reported diabetes
only during pregnancy were excluded from further analysis.
STATISTICAL ANALYSIS
The aim of the study was to compare the prevalence of several GI symptoms
in subjects with and without diabetes. The prevalence of symptoms in the general
community was expected to range from approximately 2% to 15%. An elevation
among subjects with diabetes of 10% was deemed to be the least that would
be of clinical significance. To achieve a statistical power of 0.9 at the P<.05 level of statistical significance, 120 subjects
would be required per study group for symptoms with a prevalence in the community
of 2%, while 335 would be required per study group for symptoms with a prevalence
of 15%. To determine how many subjects would need to be surveyed by mail to
obtain 335 subjects with diabetes with usable data, it was assumed that the
prevalence of known diabetes in the community was 4%31
and that a response rate of 70% would be achieved.24
The calculations suggested that a mailing of approximately 12 000 would
be required. This was increased to 15 000, because resources allowed
for it and in case the response rate was lower than expected.
The association between diabetes and the proportion of subjects with
and without a particular symptom or symptom group was assessed based on logistic
regression analysis, adjusting for age and sex. Results are reported as odds
ratios (ORs) with 95% confidence intervals (CIs). Differences in the number
of symptoms reported between groups were tested using Mann-Whitney tests.
To compare the accuracy of diabetic symptoms in discriminating between
subjects with or without poor glycemic control, logistic regression models
were developed. A forward stepwise analysis was used to identify which symptoms
or symptom groups independently differentiated the groups, after adjusting
for confounding factors.
RESULTS
Of 15 000 questionnaires mailed, 429 were returned because the
address was unknown or incorrect. Another 99 persons did not receive their
questionnaires; this group consisted mostly of people who had died recently
or who were overseas. Six hundred twenty-three people refused to participate
and returned the questionnaire blank. Of the 14 472 that were delivered,
8657 questionnaires were completed and returned, for a response rate of 60.0%.
The mean ± SD age of the respondents was 45.3 ± 15.8 years (range,
18-101 years), and the proportion of respondents who were 40 years and older
was similar to that of the Australian adult population in general (61.8% vs
61.0%). The proportion of women in the responding sample was slightly higher
compared with that of the Australian population (53.5% vs 51.4%).
Four hundred seventy-two subjects (5.4%) reported having diabetes. Of
these, 49 women reported diabetes in pregnancy only, leaving 423 subjects
with diabetes (4.9%) for further analysis.
Subjects with diabetes were older than controls (59.5 ± 14.1
years vs 44.6 ± 15.6 years, P<.001) and
more likely to be men (229/423 [54.1%] vs 3793/8185 [46.3%], P<.002). Three hundred sixty-two subjects (85.6%) with diabetes
were 45 years and older. Therefore, these differences were adjusted for in
the logistic regression analyses.
Table 1 summarizes characteristics
of the subjects with diabetes. The mean duration of known diabetes was 5.0
years (interquartile [IQ] range, 2.2-11.0 years). Most (94.8%) of the patients
had type 2 diabetes mellitus and were receiving oral hypoglycemic therapy.
There was no sex variation in type of diabetes, levels of self-reported glycemic
control, or duration of disease. There was a trend for more women to be treated
with insulin compared with men (23.4% vs 15.7%, P
= .08).
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Table 1. Characteristics of 423 Diabetic Subjects*
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Patients with diabetes reported significantly more symptoms per individual
than control subjects (1.39, IQ range, 0-2 vs 0.96, IQ range, 0-1; P<.001). No symptoms and 6 or more symptoms, respectively, were
reported by 59.6% and 9.7% of subjects with diabetes; the corresponding figures
for controls were 66.5% and 4.6%. There was a marked sex difference, with
women reporting more symptoms per individual compared with men, among subjects
with diabetes (1.77 vs 1.07, P<.002) and controls
(1.17 vs 0.72, P<.001).
Table 2 shows the crude
prevalence rates and the age- and sex-adjusted ORs for symptoms and symptom
groups in subjects with diabetes and in controls. All GI symptoms and each
of the 5 symptom groups had a significantly higher prevalence among persons
with diabetes compared with control subjects, after adjusting for age and
sex. The strongest associations were found for fecal incontinence (OR, 2.74;
95% CI, 1.40-5.37), dysphagia (OR, 2.71; 95% CI, 1.69-4.36), and vomiting
(OR, 2.51; 95% CI, 1.12-5.66).
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Table 2. Prevalence Rates of Gastrointestinal Symptoms in Patients
With Diabetes and Control Subjects*
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Fecal incontinence was reported by 54 (12.8%) of 423 subjects with diabetes
at least sometimes, compared with only 3.8% of the controls (P<.001). Most patients (61.1%) with fecal incontinence at least
sometimes did not report any diarrhea symptoms, a rate similar to that of
control subjects (54.1%).
GLYCEMIC CONTROL
Overall, 37 subjects with diabetes rated their glycemic control as poor
or very poor, compared with 229 subjects who rated their control as good or
very good; 143 subjects rated their glycemic control as average (Table 1). There was a dose-response relationship
between the quality of self-reported glycemic control and the prevalence rates
of all symptoms (except for early satiety and fecal incontinence), with higher
prevalence rates associated with poorer levels of glycemic control (Table 3). After adjusting for age and sex,
there was an association between poor glycemic control and the 5 symptom complexes,
and a moderate to strong association with 12 of the 16 symptoms (Table 3). For 4 of the symptoms (early
satiety, vomiting, <3 bowel movements per week, and loose or watery stools),
the association failed to reach statistical significance, but there was a
clear trend in the direction of self-reported poor control (Table 3).
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Table 3. Association Between Gastrointestinal Symptoms and Self-reported
Glycemic Control*
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Adjusting for the confounding factors of age and sex, the symptoms lumpy
or hard stools (OR, 3.75; 95% CI, 1.72-8.17) and urgency (OR, 3.12; 95% CI,
1.55-6.26) and the symptom complex upper dysmotility symptoms (OR, 1.97; 95%
CI, 1.16-3.37) were independently associated with self-reported poor glycemic
control.
Patients with diabetes who reported poor glycemic control had significantly
more symptoms per individual than patients with average glycemic control (3.49,
IQ range, 0-6 vs 1.38, IQ range, 0-2; P<.001)
or patients with good glycemic control (3.49, IQ range, 0-6 vs 0.89, IQ range,
0-1; P<.001). Of 37 patients with poor control,
11 (29.7%) reported no symptoms and 7 (18.9%) reported 6 or more symptoms.
The corresponding figures for 143 patients with average glycemic control were
77 (53.8%) and 13 (9.1%). Of 141 patients with good glycemic control, 96 (68.1%)
did not report any symptoms and only 6 (4.3%) reported 6 or more symptoms.
DURATION OF DIABETES
Duration of diabetes was not significantly associated with the prevalence
of GI symptoms. After adjusting for age, sex, and self-reported glycemic control,
only the symptom complex constipation (OR, 2.46; 95% CI, 1.32-4.56) and the
symptoms anal blockage (OR, 2.28; 95% CI, 1.12-4.67) and lumpy or hard stools
(OR, 2.45; 95% CI, 1.14-5.27) were significantly associated with long-standing
diabetes. In a median regression analysis, patients with constipation reported
a disease duration on average 2.1 years longer (95% CI, 0.17-5.33; P<.04) than patients without that symptom complex.
TYPE OF DIABETES
Patients with type 1 diabetes mellitus tended to have fewer GI symptoms
than those with type 2 diabetes, after adjusting for age, sex, and self-reported
glycemic control. However, only the symptom complex any bowel symptom was
significantly more common in subjects with type 2 diabetes in an adjusted
model (OR, 8.33; 95% CI, 1.39-50.0).
TYPE OF DIABETES TREATMENT
We undertook 3 different analyses to explore any association between
types of diabetes treatment and prevalence of GI symptoms. In these analyses,
adjustments were made for age, sex, and self-reported glycemic control. In
the first analysis, 77 patients who were insulin users were compared with
323 non–insulin users. We found no significant differences in the prevalence
of any symptom or symptom complex. In the second analysis, 198 users of oral
hypoglycemic drugs were compared with 170 patients who did not use these drugs.
Only anal blockage was significantly less common in oral hypoglycemic drug
users (OR, 0.38; 95% CI, 0.16-0.88). In the final analysis, 125 patients who
were treated with diet only were compared with 275 users of insulin, oral
hypoglycemic drugs, or both. Postprandial fullness (OR, 2.29; 95% CI, 1.10-4.77),
anal blockage (OR, 2.84; 95% CI, 1.29-6.24), and the symptom complex constipation
(OR, 2.09; 95% CI, 1.07-4.08) were significantly more common in patients treated
with diet only.
COMMENT
The present findings expand our understanding of GI symptoms in diabetes
in 2 important ways. Unlike most previous studies, our study was performed
in a community setting and incorporated an adequate control group and a representative
population of subjects with diabetes of all ages and grades of severity. We
found that all GI symptoms occur more frequently in subjects with diabetes
compared with community controls, after adjusting for the potential confounding
factors of age and sex. Furthermore, we found evidence of an association between
self-reported glycemic control and GI symptoms, with more symptoms in subjects
with diabetes who reported poor glycemic control.
The present study had important methodological strengths. We designed
the survey to have sufficient power to detect differences in prevalence rates
of 10% or more. We used a standard questionnaire and applied well-accepted
criteria to diagnose diabetes mellitus in community subjects. Compared with
data reported from a population-based US study,30
using the same criteria for diagnosis and type of diabetes, we found nearly
identical prevalence rates of subjects with known diabetes in the community
(4.4% vs 4.9%), proportion of type 1 diabetes mellitus (7% vs 5.2%), and proportion
of subjects with diabetes aged 45 years and older (83% vs 86%). The prevalence
of diabetes, including gestational diabetes, was only slightly higher in our
study (5.4%) compared with the estimates given in a recent health survey in
our area31 of 4.2% in men and 4.5% in women.
Therefore, the study sample seems representative of subjects with known diabetes
in the community. Although we cannot exclude the possibility that persons
with diabetes may have been more likely to return the questionnaire than nondiabetic
subjects, it is unlikely that any response bias would have seriously affected
the results of the study. It is also unlikely that subjects with undiagnosed
diabetes mellitus among the control subjects would have skewed the results,
because, according to epidemiological data, the prevalence of undiagnosed
diabetes in adults in Australia is only around 2%.32
We observed the same preponderance of GI symptoms in women, in subjects
with and without diabetes, as has been described in other epidemiological
studies.5, 11, 33 This
difference is probably related to a higher prevalence of functional GI disorders
in women. Sex differences in levels of psychosocial distress experienced may
also play a role. For example, it has recently been shown that women report
a more negative effect of diabetes on daily life compared with men.34
The pathogenesis of GI symptoms in diabetes has not been clearly elucidated.
It has been suggested that neurological impairment, especially autonomic neuropathy,
is an important factor.1, 8 Our
study does not discount a role for autonomic neuropathy in the pathogenesis
of GI symptoms. However, other investigators have observed a poor correlation
between GI symptoms and autonomic neuropathy,9
although in most studies the latter has been evaluated using standardized
cardiovascular reflexes, rather than a specific test of GI autonomic function.35-36 Furthermore, patients with diabetes
without demonstrable neuropathy also experience GI symptoms,7, 9, 12
and it has been suggested that factors such as poor glycemic control,5 psychiatric disorders,12
or other metabolic derangements secondary to diabetes4
may affect GI function in these patients. The present study suggests that
irreversible autonomic nerve dysfunction is unlikely to be the only factor
that explains the observed higher prevalence of GI symptoms in patients with
diabetes. If long-term diabetic complications, such as autonomic neuropathy,
played a major role, we would expect an association with duration of known
diabetes. This was tested in the cohort with diabetes in the present study;
only symptoms compatible with constipation were associated with long-standing
diabetes. Our results are in contrast to the findings of a recent study7 in which duration of diabetes was the only independent
risk factor for GI symptoms. However, in that study, only younger persons
(mean age, 47 years) with type 2 diabetes mellitus recruited from a tertiary
referral center were included. Furthermore, the clinical significance of the
association is questionable, as it was based on the reporting of mild symptoms
that did not affect daily activity.
The higher prevalence of GI symptoms in persons with diabetes appears
not to be explained by diabetes treatment per se. Notably, after adjusting
for potential confounding factors, including age, sex, and self-reported glycemic
control, we found no differences in symptom prevalence related to insulin
treatment and only sporadic evidence of an association with treatment using
hypoglycemic drugs and diet. Investigators37
have recently reported that troublesome GI symptoms in patients with diabetes
do not appear to be caused by use of oral hypoglycemic medications or other
drugs, except for diarrhea and fecal incontinence, which are strongly and
independently associated with metformin use. These results are consistent
with those of 2 other studies13, 38
in which diarrhea was reported to be associated with metformin treatment,
but not with diet control, insulin use, or treatment with other types of oral
hypoglycemic drugs. In this study, we did not obtain information on specific
types of oral hypoglycemic drugs used.
Our results demonstrate that self-reported poor glycemic control is
strongly associated with presence of GI symptoms. We found a dose-response
relationship between the level of self-reported glycemic control and the prevalence
rates of the 5 symptom complexes and 12 of the 16 symptoms, with higher prevalence
rates associated with poorer glycemic control. The plausibility of the results
is supported by the findings of several physiological studies15, 22-23,39-41
in healthy controls and in patients with diabetes that have established that
acute hyperglycemia affects GI motor function and the perception of sensations
arising from the GI tract. For example, the perception of nausea, occurring
as a result of proximal gastric distension, is greater during hyperglycemia.14 Acute hyperglycemia also slows gastric emptying in
persons with diabetes,42 reduces lower esophageal
sphincter pressure and the velocity of esophageal peristalsis,39
and alters motility in the small bowel and gallbladder.41
The gastrocolic and ascending components of the colonic peristaltic reflex
are inhibited during hyperglycemia in healthy subjects,15
but colonic tone, compliance, and motor patterns were not affected in another
study.43
Although a direct measure of glycemic control would have been preferable,
this was not possible in our epidemiological study. However, investigators
have recently shown that self-reported glycemic control, using a 5-point scale
similar to ours, was significantly correlated with objective measures of glycemic
control, including glycated hemoglobin (P<.001)
and plasma glucose (P = .005) levels in 166 subjects
with diabetes (N.J.T., Johann Hammer, MD, M.P.J., and M.H., unpublished data,
February 1999). No specific guidelines were offered to the patients in the
present study about which category average blood glucose level would correspond
to among the various categories of self-reported glycemic control. It is therefore
possible that many patients overestimated their level of good glycemic control.
However, this bias toward optimism would tend to strengthen the present observations.
Unfortunately, the direction of the association between poor glycemic
control and GI symptoms could not be addressed by the methods used in this
study. Symptoms of upper GI dysmotility, including nausea, vomiting, and early
satiety, may lead to loss of glycemic control as a result of unpredictable
delivery of nutrients to the small intestine. Therefore, we cannot exclude
the possibility that upper GI symptoms, secondary in part to autonomic neuropathy,
have led to poor glycemic control. However, this hypothesis would not explain
the increased prevalence of symptoms related to bowel dysfunction, such as
constipation, diarrhea, urgency, and fecal incontinence. A logical extension
of this work will be to undertake longitudinal studies to establish the direction
of these associations and to differentiate causes from effects. However, as
previously stated, several pathophysiological studies15, 39-41
suggest that poor glycemic control in itself promotes symptoms arising from
all parts of the GI tract.
We were also unable to measure other risk factors that may be important
in the pathogenesis of GI symptoms in diabetes, such as diabetic complications,
psychosocial distress or psychiatric comorbidity, alcohol ingestion, obesity,
and the use of medications other than insulin and oral hypoglycemic agents.
Patients with type 2 diabetes mellitus are characteristically obese, and obesity
is a risk factor for dyspepsia (broadly defined) in women,44
but a role for obesity in other GI symptoms remains uncertain. The relative
importance of the type of diabetes could not be evaluated definitively because
only 22 subjects had established type 1 diabetes mellitus.
In summary, this population-based study provides evidence that troublesome
GI symptoms are more prevalent in subjects with diabetes compared with controls,
especially in those who report poor glycemic control. Our findings suggest
that this effect may be explained, at least in part, by poor glycemic control
and is not associated with duration of diabetes or type of diabetic treatment.
AUTHOR INFORMATION
Accepted for publication January 9, 2001.
This work was supported by grants from Diabetes Australia, Sydney, and
the National Health and Medical Research Council of Australia, Canberra (grant
980080).
Corresponding author and reprints: Nicholas J. Talley, MD, PhD, Department
of Medicine, University of Sydney, Nepean Hospital, Clinical Sciences Building,
PO Box 63, Penrith, New South Wales 2751, Australia (e-mail: ntalley{at}blackburn.med.usyd.edu.au).
From the Department of Medicine, University of Sydney, Nepean Hospital,
Penrith, Australia (Drs Bytzer, Talley, and Jones and Mss Leemon and Young);
and Department of Medicine, University of Adelaide, Royal Adelaide Hospital,
Adelaide, Australia (Dr Horowitz).
REFERENCES
| |
1. Feldman M, Schiller LR. Disorders of gastrointestinal motility associated with diabetes mellitus. Ann Intern Med. 1983;98:378-384.
2. Weber JR, Ryan JC. Effects on the gut of systemic disease and other extraintestinal conditions. In: Feldman M, Scharschmidt BF, Sleisinger MH, eds. Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa: WB Saunders
Co; 1998:413-416.
3. Farup CE, Leidy NK, Murray M, Williams GR, Helbers L, Quigley EMM. Effect of domperidone on the health-related quality of life of patients
with symptoms of diabetic gastroparesis. Diabetes Care. 1998;21:1699-1706.
ABSTRACT
4. Verne GN, Sninsky CA. Diabetes and the gastrointestinal tract. Gastroenterol Clin North Am. 1998;27:861-874.
FULL TEXT
| PUBMED
5. Schvarcz E, Palmér M, Ingberg CM, Åman J, Berne C. Increased prevalence of upper gastrointestinal symptoms in long-term
type 1 diabetes mellitus. Diabet Med. 1996;13:478-481.
FULL TEXT
|
ISI
| PUBMED
6. Janatuinen E, Pikkarainen P, Laakso M, Pyörälä K. Gastrointestinal symptoms in middle-aged diabetic patients. Scand J Gastroenterol. 1993;28:427-432.
ISI
| PUBMED
7. Ko GT, Chan WB, Chan JC, Tsang LW, Cockram CS. Gastrointestinal symptoms in Chinese patients with type 2 diabetes
mellitus. Diabet Med. 1999;16:670-674.
PUBMED
8. Enck P, Rathmann W, Spiekermann M, et al. Prevalence of gastrointestinal symptoms in diabetic patients and non-diabetic
subjects. Z Gastroenterol. 1994;32:637-641.
ISI
| PUBMED
9. Maleki D, Locke III GR, Camilleri M, et al. Gastrointestinal tract symptoms among persons with diabetes mellitus
in the community. Arch Intern Med. 2000;160:2808-2816.
FREE FULL TEXT
10. Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ. Dyspepsia and dyspepsia subgroups: a population-based study. Gastroenterology. 1992;102:1259-1268.
ISI
| PUBMED
11. Talley NJ, Boyce P, Jones M. Identification of distinct upper and lower gastrointestinal symptom
groupings in an urban population. Gut. 1998;42:690-695.
FREE FULL TEXT
12. Clouse RE, Lustman PJ. Gastrointestinal symptoms in diabetic patients: lack of association
with neuropathy. Am J Gastroenterol. 1989;84:868-872.
ISI
| PUBMED
13. Dandona P, Fonseca V, Mier A, Beckett AG. Diarrhea and metformin in a diabetic clinic. Diabetes Care. 1983;6:472-474.
ABSTRACT
14. Rayner CK, Verhagen MAMT, Hebbard GS, DiMatteo AC, Doran SM, Horowitz M. Proximal gastric compliance and perception of distension in type 1
diabetes mellitus: effects of hyperglycemia. Am J Gastroenterol. 2000;95:1175-1183.
FULL TEXT
| PUBMED
15. Chey WD, Kim M, Hasler WL, Owyang C. Hyperglycemia alters perception of rectal distension and blunts the
rectoanal inhibitory reflex in healthy volunteers. Gastroenterology. 1995;108:1700-1708.
FULL TEXT
|
ISI
| PUBMED
16. Horowitz M, Fraser R. Disordered gastric motility in diabetes mellitus. Diabetologia. 1994;37:543-551.
ISI
| PUBMED
17. de Boer SY, Masclee AAM, Lam WF, Schipper J, Jansen JBMJ, Lamers CBHW. Hyperglycemia modulates gallbladder motility and small intestinal transit
time in man. Dig Dis Sci. 1993;38:2228-2235.
FULL TEXT
|
ISI
| PUBMED
18. Russo A, Sun WM, Sattawatthamrong Y, et al. Acute hyperglycaemia affects anorectal motor and sensory functions
in normal subjects. Gut. 1997;41:494-499.
FREE FULL TEXT
19. Rayner CK, Smout AJPM, Sun WM, et al. Effects of hyperglycemia on cortical response to esophageal distension
in normal subjects. Dig Dis Sci. 1999;44:279-285.
FULL TEXT
|
ISI
| PUBMED
20. Samsom M, Akkermans LMA, Jebbink RJA, van Isselt H, vanBerge-Henegouwen GP, Smout AJPM. Gastrointestinal motor mechanisms in hyperglycaemia induced delayed
gastric emptying in type I diabetes mellitus. Gut. 1997;40:641-646.
FREE FULL TEXT
21. Jones KL, Horowitz M, Berry M, Wishart JM, Guha S. The blood glucose concentration influences postprandial fullness in
IDDM. Diabetes Care. 1997;20:1141-1146.
ABSTRACT
22. Lingenfelser T, Sun WM, Hebbard GS, Dent J, Horowitz M. Effects of duodenal distension on antropyloroduodenal pressures and
perception are modified by hyperglycemia. Am J Physiol. 1999;276:G711-G718.
23. Hebbard GS, Samsom M, Sun WM, Dent J, Horowitz M. Hyperglycemia affects proximal gastric motor and sensory function during
small intestinal triglyceride infusion. Am J Physiol. 1996;271:G814-G819.
24. Kalantar JS, Talley NJ. The effects of lottery incentive and length of questionnaire on health
survey response rates: a randomized study. J Clin Epidemiol. 1999;52:1117-1122.
FULL TEXT
|
ISI
| PUBMED
25. Talley NJ, Phillips SF, Melton LJI, Wiltgen C, Zinsmeister AR. A patient questionnaire to identify bowel disease. Ann Intern Med. 1989;111:671-674.
26. Talley NJ, Boyce P, Owen BK, Newman P, Paterson K. Initial validation of a bowel symptom questionnaire and measurement
of chronic gastrointestinal symptoms in Australians. Aust N Z J Med. 1995;25:302-308.
ISI
| PUBMED
27. Agréus L, Svärdsudd K, Nyrén O, Tibblin G. Reproducibility and validity of a postal questionnaire: the Abdominal
Symptom Study. Scand J Prim Health Care. 1993;11:252-262.
PUBMED
28. Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR, Tytgat GNJ. Functional gastroduodenal disorders. Gut. 1999;45(suppl 2):II37-II42.
29. World Health Organization Study Group. Prevention of Diabetes. Geneva, Switzerland: World Health Organization; 1994:13.
30. Beckles GLA, Engelau MM, Narayan KMV, Herman WH, Aubert RE, Williamson DF. Population-based assessment of the level of care among adults with
diabetes in the U.S. Diabetes Care. 1998;21:1432-1438.
ABSTRACT
31. New South Wales Health Department. Report of the NSW Chief Health Officer. Sydney, Australia: New South Wales Health Dept; 1997.
32. Welborn TA, Glatthaar C, Whittall D, Bennett S. An estimate of diabetes prevalence from a national population sample:
a male excess. Med J Aust. 1989;150:78-81.
PUBMED
33. Talley NJ, Zinsmeister AR, van Dyke C, Melton LJI. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology. 1991;101:927-934.
ISI
| PUBMED
34. Wredling R, Stalhammer J, Berne C, Larsson Y, Östman J. Well-being and treatment satisfaction in adults with diabetes: a Swedish
population-based study. Qual Life Res. 1995;4:515-522.
FULL TEXT
|
ISI
| PUBMED
35. Jebbink HJ, Bravenboer B, Akkermans LM. Relationships between dyspeptic symptoms and gastrointestinal motility
in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1993;36:948-954.
PUBMED
36. Horowitz M, Harding P, Maddox A. Gastric and oesophageal emptying in insulin-dependent diabetes mellitus. J Gastroenterol Hepatol. 1986;1:97-113.
37. Bytzer P, Talley NJ, Jones MP, Horowitz M. Oral hypoglycaemic drugs and gastrointestinal symptoms in diabetes
mellitus. Aliment Pharmacol Ther. 2001;15:137-142.
PUBMED
38. Lysy J, Israeli E, Goldin E. The prevalence of chronic diarrhea among diabetic patients. Am J Gastroenterol. 1999;94:2165-2170.
FULL TEXT
|
ISI
| PUBMED
39. de Boer SY, Masclee AAM, Lam WF, Lamers CBHW. Effect of acute hyperglycemia on esophageal motility and lower esophageal
sphincter pressure in humans. Gastroenterology. 1992;103:775-780.
ISI
| PUBMED
40. Fraser R, Horowitz M, Maddox A, Chatterton BE, Harding P, Dent J. Hyperglycaemia slows gastric emptying in type 1 diabetes mellitus. Diabetologia. 1990;33:675-680.
FULL TEXT
|
ISI
| PUBMED
41. de Boer SY, Masclee AAM, Lamers CBHW. Effect of hyperglycaemia on gastrointestinal and gallbladder motility. Scand J Gastroenterol. 1992;27(suppl 194):13-18.
42. Horowitz M, Harding PE, Maddox AF, et al. Gastric and oesophageal emptying in patients with type 2 (non-insulin-dependent)
diabetes mellitus. Diabetologia. 1989;32:151-159.
FULL TEXT
|
ISI
| PUBMED
43. Maleki D, Camilleri M, Zinsmeister AR, Rizza RA. Effect of acute hyperglycemia on colorectal motor and sensory function
in humans. Am J Physiol. 1997;273:G859-G864.
44. Woodward M, Morrison CE, McColl KEL. The prevalence of dyspepsia and use of antisecretory medication in
North Glasgow: role of Helicobacter pylori vs. lifestyle
factors. Aliment Pharmacol Ther. 1999;13:1505-1509.
FULL TEXT
| PUBMED
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