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The Effect of Acarbose on the Colonic Transit Time of Elderly Long-term Care Patients With Type 2 Diabetes Mellitus

^a Department of Gastroenterology, Wolfson Hospital, Holon, Israel
^b Diabetes Unit, Wolfson Hospital, Holon, Israel
^c Geriatric Medical Center, Shmuel Harofe Hospital, Beer Yaakov, Israel

Refael Segal, Geriatric Medical Center, Shmuel Harofe Hospital, Post Office Box 2, Beer Yaakov, Israel E-mail: Shmuelh{at}netvision.net.il.

	Abstract

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Background. Constipation is common in elderly patients with diabetes mellitus (DM); its prevalence is estimated as up to 60% among patients with diabetic neuropathy. Acarbose, an -glucosidase inhibitor, has a beneficial role in controlling DM, although one of its side effects is diarrhea. This study evaluates the efficacy of acarbose in improving constipation using transit time (TT) studies in elderly long-term care (LTC) patients.

Methods. Twenty-eight patients with type 2 DM and constipation were recruited for the study. TT was measured by radiopaque markers and was calculated separately for the four segments of the colon (ascending, transverse, descending, and rectosigmoid) and for the total colonic transit time (CTT). Segmental TT and CTT were evaluated in each patient before and after 1 week, and again after 4 weeks of treatment with acarbose.

Results. The mean baseline CTT measured in patients was 202 ± 136 hours. After 1 and 4 weeks of acarbose treatment, the baseline CTT significantly decreased to 149 ± 107 hours and 161 ± 97 hours, respectively (p < .002). For each segment studied, the TT was shortened, but it reached significance for the ascending and transverse colon only (p < .02 and p < .03, respectively). The effect of diet composition was examined. The amount of fiber consumed correlated with shortened CTT, while fat tended to be in negative correlation with TT.

Conclusions. Acarbose therapy reduced the extremely prolonged CTT in LTC diabetic persons with constipation. The drug could be useful in relieving constipation in these patients, in addition to its beneficial effect in the control of diabetes.

CONSTIPATION is highly prevalent in long-term care (LTC) patients and is reported for up to 73% of the residents ⁽¹⁾⁽²⁾. It is probably more severe in those suffering concomitantly from diabetes mellitus (DM), because of the contributing effects of neuropathy and impaired anorectal function ⁽³⁾⁽⁴⁾.

In the last decade, acarbose, an -glucosidase inhibitor, was introduced to the therapy of DM. Its mode of action is through delaying carbohydrate absorption in the small bowel, thereby lowering postprandial glucose levels ⁽⁵⁾⁽⁶⁾. Its main side effects are gastrointestinal, especially flatulence and diarrhea. These phenomena tend to occur soon after initiation of therapy and are attributed to colonic bacterial fermentation of the unabsorbed carbohydrates ⁽⁷⁾. With continuation of therapy, these symptoms tend to subside.

One of the best ways to assess objectively "true" constipation is transit time (TT) measurements using radiopaque markers or radioisotopes. In most studies, the reported colonic transit time (CTT) in a normal population was 30 to 50 hours ⁽⁸⁾⁽⁹⁾. TT studies in elderly patients are scarce and highly variable, ranging from 1 day in ambulant elderly persons to up to 3 weeks in bedridden patients ^{(8)(9)(10)(11)(12)(13)(14)}. Age, by itself, does not significantly prolong the TT ^(8)(9)(14).

In a preliminary study, we assessed the CTT in LTC patients in our institution and found an extremely prolonged TT in both diabetic (around 200 hours [h]) and nondiabetic (around 150 h) patients (unpublished data).

Since most of our bedridden LTC elderly patients suffer from constipation and some have uncontrolled DM, we hypothesized that adding acarbose to their treatment might improve not only glycemic control but also constipation. This study evaluates the efficacy of acarbose in shortening the CTT and in relieving constipation in frail elderly patients with type 2 DM.

	Methods

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Subjects
Frail elderly patients with type 2 DM and constipation were enrolled for an open trial. Because Rome 2 criteria for definition of constipation are inapplicable for most of our LTC patients, the inclusion criteria for this study were as follows: less than two spontaneous bowel movements per week, a need for a planned evacuation program, or chronic laxative use. Nearly 20% of our patients, those having spontaneous daily bowel movements, were excluded. Patients who had had major abdominal operations were excluded as well.

All patients had resided permanently in the LTC departments of the Geriatric Medical Center "Shmuel Harofe" for at least 3 months. All were wheelchair bound. This study was approved by the local ethics committee, and each patient signed an informed consent. If the patient was incoherent, informed consent was obtained from a guardian.

CTT Study Design
According to the method described by Metcalf and colleagues ⁽⁸⁾, three different types of radiopaque markers were used (rods, small rings, and large rings). Twenty markers were stored within each gelatin capsule (weight, 6 mg or 15 mg; specific gravity, 1.63; Dunn Nutrition Centre, Cambridge, United Kingdom). Subjects ingested a capsule at 8:00 AM on 3 consecutive days. The three types of markers were always ingested in the same sequence. Abdominal x-rays were obtained using a high-kilovoltage fast-film technique to reduce the amount of radiation exposure. Films were taken every 4 days until the expulsion of at least 80% of the markers. TT was calculated for each of the four segments of the colon (ascending, transverse, descending, or rectosigmoid), and total TT (CTT) was the sum of all four segments. The calculation of segmental TT was done using the formula developed by Metcalf and colleagues ⁽⁸⁾, which was based on a previous work by Arhan and colleagues ⁽⁹⁾. Each patient participated in three colonic TT studies. The first study was performed before acarbose therapy; the second and third studies commenced after 1 and 4 weeks, respectively, on the maximal dose of acarbose therapy. Acarbose was started at a dose of 50 mg t.i.d. for 3 days and followed at a dose of 100 mg t.i.d. on Weeks 2 to 18. Patients were maintained on a controlled diabetic diet throughout the study period; their various medications (except antidiabetics), including laxatives, remained unchanged as well. Total caloric intake and the consumption of specific ingredients were calculated by a dietary consultant. Fasting and postprandial blood glucose was obtained 2 to 3 times weekly. Glycosylated hemoglobin and fructoseamine levels were obtained before and after 1 and 3 months of acarbose therapy. The drug was administered orally under medical staff surveillance, either as a whole tablet or smashed and dissolved in a small amount of water for those with swallowing difficulties. Special attention was paid to possible side effects such as nausea, vomiting, abdominal cramps, or flatulence in the patients with cognitive disorders that inhibit them from complaining. A maintained appetite was the main monitoring sign in this subgroup.

Statistical Analysis
TT was calculated according to the Metcalf formula ⁽⁸⁾. The changes in TT were evaluated by paired t test or multivariate analysis of variance (MANOVA). Correlation studies were performed using the Pearson or biserial correlation coefficient.

	Results

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Twenty-eight LTC elderly patients with diabetes, all suffering from constipation, entered the study. Six patients withdrew after 1 week of acarbose therapy (3 refused to continue, 2 were discharged from the hospital, and 1 had pneumonia and was excluded). Twenty-two patients finished all three phases of the study. Patients' characteristics, including comorbid conditions, medications, and anticonstipation therapy, are given in Table 1 and Table 2 . Most patients had required 1 to 2 manual or enema disimpactions during the month preceding the acarbose study. Diet and drug regimes were not changed during the study period.

View larger version (34K): [in this window] [in a new window]   Figure 1. The effect of acarbose on total and segmental transit times in constipated frail elderly patients. The results are expressed in hours, pretherapy and after 1 and 4 weeks of acarbose therapy. *p < .03; **p < .02; ***p < .002.

Although we could not observe a significant change in bowel movements during acarbose therapy, none of the patients required either a manual or sodium phosphate enema for disimpaction during the study period, and there were no cases of diarrhea.

In evaluating the different factors that might cause constipation and affect TT, we could not find any association between the patients' age, duration of diabetes and its complications (neuropathy, nephropathy, retinopathy, or peripheral vascular disease), and the basal measured TT. Neither could we find any correlation of TT with other medical conditions, such as central nervous system involvement (cerebrovascular accident, dementia, and Parkinson's disease).

In evaluating the impact of diet on TT, we found that the amount of fiber was in negative correlation with total TT (r = -.49, p = .023), while fat was in positive correlation of borderline significance (r = .385, p = .076). No correlation was found between the total caloric consumption, dietary protein, or carbohydrates and basal TT. None of the dietary components had any effect on the segmental TTs. Evaluation of different relevant medications taken by the patients, such as Ca⁺⁺ channel blockers, hypnotics, antidepressants, or laxatives, showed that neither group had any effect on the basal TT in our patients.

Glycosylated hemoglobin levels before (7.38% ± 1.4%) and after (7.44% ± 1.6%) 3 months of therapy did not change significantly. Similarly, fructoseamine levels (282 ± 87 mmol/l vs 301 ± 96 mmol/l) remained unchanged following acarbose therapy. However, a positive effect on diabetes balance was shown with the reduction of oral hypoglycemic drugs and insulin dosage in half of the patients; therefore, basal and postprandial blood glucose were not significantly different after 1 month of acarbose therapy. Fasting levels were 160 ± 73 mg/dl versus 145 ± 95 mg/dl; postprandial levels were 232 ± 160 mg/dl versus 195 ± 124 mg/dl for the basal measurements and after 1 month on acarbose therapy, respectively. No significant side effects were observed in any patient during acarbose therapy. None of the treated patients complained of abdominal cramps or flatulence, and no exceptional eating difficulties occurred during the study period.

	Discussion

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Frail elderly, immobile patients often suffer from constipation that can often complicate into fecal impaction ^(2)(15)(16). DM is a known aggravating factor in these patients.

We have shown in this study that adding acarbose to antidiabetic treatment significantly improved CTT and alleviated constipation in these bedridden and frail elderly, immobile people.

Ours is the first study that uses radiopaque markers and also calculates the segmental TT in frail elderly patients using the method described by Metcalf and colleagues ⁽⁸⁾.

We found in this patient group that the mean TT was 202 hours (8.4 days), which is two- to threefold longer than the reported values in mobile elderly patients ^(8)(9)(13).

The main purpose of this study was to examine the effect of acarbose on CTT. The idea underlying this work was to use the main side effect of acarbose, diarrhea, to accelerate the TT of constipated diabetic patients. Indeed, we found a significant reduction of 30% in the TT after 1 week of therapy (p = .03), and this trend was maintained after 1 month on acarbose (p = .02; Fig. 1). Although acarbose shortened the TT in all colonic segments, these changes were statistically significant only for the ascending (p < .02) and transverse (p < .03) segments. These segments are the site of bacterial degradation of carbohydrates and, in this sense, the acarbose mechanism of action is similar to that of lactulose ⁽¹⁷⁾. In a previous study, Ladas and colleagues ⁽¹⁸⁾ tested the effects of acarbose on orocecal TT and attributed its beneficial effect to reduced small-bowel TT. Our study shows that acarbose improves the CTT, which is clinically a more significant indicator of constipation.

Clinical evaluation of defecation habits is hard to quantify in this population of LTC patients. However, during the study period, none of the patients required fecal disimpaction, which is highly beneficial in itself, in view of the high prevalence of fecal impaction in nursing homes ⁽¹⁾⁽²⁾.

It may be argued that the beneficial effects of acarbose could be transitory. This effect could disappear later on as there have been reports that diarrhea subsides with continuing acarbose therapy, an effect attributed to distal ileal induction of -glucosidase ⁽¹⁹⁾. In our study group, we found that the effect of acarbose on TT lasts over 1 month of therapy. We may speculate that the distal ileal induction of -glucosidase could be slower or nonexistent in this unique geriatric population.

We could not find any correlation between the baseline TT and clinical parameters such as comorbid state; diabetic complications, mainly neuropathy; or relevant medications. This could be explained by the small size and clinical diversity of our study population. We also suggest that the impact of immobilization is more dominant than any other clinical factor on constipation.

The improvement in glycemic control following the addition of acarbose to our study group was reflected by the dosage reduction of oral hypoglycemics or insulin in half of our patients. However, we did not observe the beneficial decline in glycosylated hemoglobin or fructoseamine levels. This could be due to the reduction of other hypoglycemic drugs and the short duration of this study. No hypoglycemia or any other side effects were observed during acarbose therapy.

In conclusion, we found that CTT is extremely prolonged in elderly LTC patients with diabetes and inclusion of acarbose to the treatment caused a significant reduction in the CTT. Its use should be considered for the treatment of constipated, LTC patients with diabetes.

	Acknowledgments

 
We thank the Department of Radiology of the Geriatric Medical Center "Shmuel Harofe," Mr. Alon Noiman, and Mrs. Dikla Geva, MSc for statistical analysis.

Received March 5, 2001

Accepted May 17, 2001

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