Showa Univ J Med Sci 15(1), 21•`26, March 2003

Original

Pathophysiology in Diabetic Patients with

Makoto WATANABE 1) Aklra TSUNODA 1) Goichi KAMIYAMA 1) Tsutomu HIRANo 2) and Mitsuo KUSANO 1)

Abstract : The aim of this study was to investigate the pathophysiology of fecal incontinence in patients with mellitus. Methods. Two groups of diabetic patients were studied. Group A consisted of 7 subjects (48 to 76 years, mean age 53.5 years) with fecal incontinence and Group B consisted of 9 subjects (38 to 79 years, mean age 62.1 years) without fecal incontinence. A third group of 10 healthy volunteers (Group C) were included as control subjects. All subjects underwent anorectal manometry and rectal sensitivity tests, and pudendal nerve terminal motor latency ( PNTML) . Results. Anal resting pressure was significantly lower in Group A (38 cm H20) compared to Group B (60 cm H20) and Group C (59 cm H20). Maximum squeeze pressure was significantly lower in Group A (98 cm H20) and Group B (160 cm H20) compared to Group C (240 cm H20). Initial sensation volume was significantly higher in Group A (80 cm H20) compared to Group C (30 cm H20). Pudendal nerve terminal motor latency was significantly higher in Group A (3.15 msec) compared to Group B (2.45 msec) and Group C (2.03 msec). There was no significant difference in the length of the high-pressure zone, urgency, or maximum tolerable volume between the three groups. Conclusion. Our results demonstrate that autonomic neuropathy causes internal sphincter or initial rectal sensation damage, and that somatic neuropathy, such as pudendal neuropathy, may play an important role in fecal incontinence in diabetic patients.

Key words : , fecal incontinence, anorectal manometry, (PNTML)

Introduction

Abnormalities of gastrointestinal function are common in patients with diabetes mellitus 1). Fecal incontinence is one such complication and contributes to a reduced quality of life of these patients 2). Martin reported that 18% of patients with peripheral diabetic neuropathy suffered from fecal incontinence 3), and Wald and Tunuguntla reported that 4 % of diabetic patients, from a survey of 160 patients, suffered from fecal incontinence 4). Although fecal incontinence as a complication of diabetes mellitus is not uncommon, investigations into the underlying pathophysiology of diabetic patients with fecal incontinence are rare. Further- more, there has been no adequate study of the incidence and prevalence of fecal

) Second Department of Surgery, Showa University school of Medicine, 1-5-8 Hatanodai Shinagawaku, Tokyo, 142- 8666, Japan. 2)First Department of Internal Medicine, Showa University School of Medicine

1 22 Makoto WATANABE, et al

Table 1. Characteristics of the three groups of subjects

Group A : Diabetic patients with fecal incontinence (n = 7 ) Group B : Diabetic patients without fecal incontinence (n = 9 ) Group C : Healthy volunteers (n =10 ) incontinence in diabetic patients. The aim of this study was to investigate the pathophysiology of fecal incontinence in patients with diabetes mellitus.

Patients and Methods

Patients Of 214 diabetic patients who had been treated at Showa University Hospital between April 1998 and April 2000, 7 had experienced fecal incontinence (Group A). A total of 9 diabetic patients without fecal incontinence (Group B) were included in the study as a comparison control, and 10 healthy volunteers (Group C) were included as normal control subjects. No subjects had anorectal disease, gynecological disease, neurological disease, or a history of previous surgery. Table 1 shows characteristics of the three groups of subjects. There were no significant differences in age or sex among the three groups. During the evaluation and follow-up periods, diabetic control by medical treatment was stable in all diabetic patients. In Group A, two patients were incontinent for formed stool during the daytime only; the remaining five were incontinent for liquid stools during the night only. All patients in Group A were able to sense stools in the rectum during the day, and three patients were not able to discriminate between stool and flatus. In addition to fecal incontinence, diabetic retinopathy was present in 2 patients, in 6, and nocturnal in 2. In Group B, 2 patients had diabetic retinopathy, 6 had peripheral neuropathy, and 3 had diarrhea. Informed consent was obtained in all cases, and all subjects underwent the following examinations.

Anorectal manometry Anorectal manometry was performed with subjects lying in the left lateral position, using a catheter-tip pressure transducer (Gaeltec U-228). The following parameters were evaluated : a) length of high pressure zone, b) anal resting pressure, c) maximum anal squeeze pressure, and d) anorectal inhibitory reflex. Rectal sensation (initial sensation volume, urgency, maximum tolerable volume) was performed using a 50-mm-long cylindrical balloon connected to a 12-F catheter placed in the rectum and inflated with air Fecal Incontinence in Diabetes Mellitus 23 at the rate of approximately 25 ml / s5). The volume required to elicit an •gonset of sensation,•h a •gcall to stool,•h and •gurgency of defecation•h was recorded.

Pudendal nerve terminal motor latency (PNTML) PNTML was measured as previously described 6). In short, pudendal nerve stimulation was performed transanally using a St. Mark's disposable electrode (Dantec, 13L40, Skovlunde, Denmark) in the left lateral position for both the right and left pudendal nerves. The electrode consists of a stimulating electrode at the tip and two surface recording electrodes at the base at the level of the anal sphincter. With the electrode mounted on the examiners gloved index finger, the pudendal nerve is stimulated over the ischial spine, which is easily palpated. Stimulation was performed with an EMG machine (Counterpoint MK2, Dantec, Skovlunde, Denmark) using square wave stimuli of 0.1 millisecond (msec). The recording electrodes were connected to the computerized EMG machine, which calculated and displayed the conduction latency from stimulation of the recording electrode.

Statistical analysis Values were expressed as mean •} SD ; a p value < 0.05 was regarded as statistically significant. The statistical analysis was performed using the software Stat View 5.0 for

Windows (SAS Institute Inc., Copyright(C)). The Mann-Whitney U test was used to assess the significance of the differences between the groups.

Results

Anorectal manometry (anal sphincter function)

Anal resting pressure was significantly lower in Group A (38 •} 11 cm H20) compared to

Group B (60 •} 13 cm H20) or Group C (66 •} 24 cm H20) (p<0.01), but there was no significant difference in the pressure between Groups B and C. Maximum squeeze pressure was significantly higher in Group C (232 •} 61 cm H20) compared to Group A (112 •} 53 cm

H20) or Group B (163 •} 95 cm H20) (p< 0.01), but there was no significant difference in the pressure between Groups A and B. There was no significant difference in the length of the high-pressure zone among the three groups (Table 2).

Anorectal manometry (rectal sensation, tolerated volume)

The initial sensation volume was significantly higher in Group A (77 •} 37 ml) compared to Group C (35 •} 15 ml) (p< 0.05), but there was no significant differences in initial

Table 2. Anorectal manometry

Values are expressed as mean •} SD (range) *p < 0 .01 vs Group A ; tp < 0.01 vs Group C 24 Makoto WATANABE, et al

Table 3. Rectal sensation

Values are expressed as mean •} SD (range) *p<0 .05 vs Group A

Fig, 1. Pudendal nerve terminal motor latency (PNTML) in three groups of subjects. bar, mean ; *p<0.05 vs Group A or Group B sensation volume between Groups A and B, or between Groups B and C. There was no significant difference in urgency or maximum tolerable volume between the three groups (Table 3).

PNTML

PNTML was significantly higher in Group A (3.3 •} 0.9 msec) than in Group B (2.5 •} 0.4 msec) or Group C (2.1 •} 0.2 msec) (p< 0.05; Fig. 1).

Discussion

Wald and Tunuguntla reported that 4 % of diabetic patients suffered from fecal incontinence 4). In the present investigation, 7 out of 214 surveyed diabetic patients suffered from fecal incontinence, this is a rate of 3.3%. The underlying pathophysiology of anorectal function in diabetic patients with fecal incontinence is not well understood. It has been suggested that internal anal sphincter dysfunction causes fecal incontinence in diabetic patients 7,8). In contrast, Rogers et al 9) reported that external anal sphincter dysfunction may Fecal Incontinence in Diabetes Mellitus 25

Fig. 2. Schematic representation of the innervation of the distal colon and anal canal (taken from Caviezel et al 13)).

be important. Other reports suggested that both the internal and external anal sphincter might be involved 10,11)By comparison, Erckenbrecht et al 11) reported that there was no significant correlation between neuropathy and the presence of fecal incontinence. Epanomeritakis et al 12) reported that the diabetes disease period and anorectal function were negatively correlated. In the present study, the diabetic disease period was comparable in all diabetic patients with or without fecal incontinence, and diabetic control was stable in all patients. A schematic representation of the innervation of the distal colon and anal canal is taken from Caviezel's et a113 (Fig. 2). The lumbar sympathetic innervation inhibits the colon and provides motor stimulation to the internal anal sphincter. The pudendal nerves, on the other hand, are somatic nerves that innervate the external anal sphincter. It was reported that pudendal neuropathy, which extends the nerve conduction time, causes soiling and incontinence 13). Delay of nerve conduction time slows the external anal sphincter response, and this is thought to cause fecal incontinence 14). Diabetic pudendal neuropathy leads to the delay of PNTML, causing external sphincter damage, and may result in fecal incontinence. Diabetic autonomic neuropathy, involving lumbar sympathetic innervation, may cause internal sphincter damage, resulting in fecal incontinence. In our findings, there were significant differences in anal resting pressure, maximum squeeze pressure, initial sensation volume, and PNTML between diabetic patients with fecal incontinence and normal control subjects. Anal resting pressure involves an autonomic nerve, while initial sensation volume, maximum squeeze pressure, and PNTML involve somatic nerves. Therefore, our results suggest that somatic neuropathy plays an important role in fecal incontinence in diabetic patients, combined with sensation threshold impairment as a feature of an autonomic involvement. 26 Makoto WATANABE, et al

While biofeedback therapy is reported to be effective for diabetic patients with fecal incontinence 15), there is no established therapy regime. Aldose reductase inhibitors (ARI) have recently been shown to be effective for painful diabetic . Jaspan et al 17) reported that ARI had an effect on both autonomic and somatic nerves. Nakamura at al 18) reported the effectiveness of ARI in the treatment of in cases with diabetic gastroenteropathy. If diabetic fecal incontinence originates as a result of diabetic neuropathy, ARI may be an effective treatment. Further investigations are required to ascertain the clinical effectiveness of ARI for fecal incontinence in diabetic patients. In conclusion, our results demonstrate that that autonomic neuropathy causes internal sphincter or initial rectal sensation damage, and that somatic neuropathy, such as pudendal neuropathy, may also play an important role in fecal incontinence in diabetic patients

References 1) Feldman M and Schiller LR : Disorder of the gastrointestinal motility associated with diabetes mellitus. Ann Intern Med 98:378-384 (1983) 2) Talley NJ, Young L, Bytzer P, Hammer J, Leemon M, Jones M and Horowitz M : Impact of chronic gastrointestinal symptoms in diabetes mellitus on health-related quality of life. Am J Gastroenterol96 : 71-76 (2001) 3) Martin MM : Diabetic neuropathy: a clinical study of 150 cases. Brain 75 : 594-624 (1958) 4) Wald A and Tunuguntla AK : Anorectal sensonmotor dysfunction in fecal incontinence and diabetes mellitus. N Engl J Med 310 :1282-1287 (1984) 5) Farthing MJ and Lennard-Jones JE : Sensibilityof the rectum to distention and the ano-rectal distention reflex in ulcerative colitis. Gut 19 : 64-69 (1978) 6) Swash M and Snooks SJ : Motor nerve conduction studies of the pelvic floor innervation. In :. Coloproctology and the pelvic floor. Henry MM, Swash M (Eds) pp. 196-207, London, Butterwarth-Heinemann,(1992) 7) Schiller LR, Santa Ana CA, Schmulen C, Hendler RS, Harford WV and Fordtran JS : Pathogenesis of fecal incontinence in diabetes mellitus: evidence for internal anal sphincter dysfunction. N Engl J Med 307 :1666- 1671 (1982) 8) Sun WM, Katsinelos P, Horowitz M and Read NW : Disturbances in anorectal function in patients with diabetes mellitus and faecal incontinence.Eur J GastroenterolHepatol 8 : 1007-1012 (1996) 9) Rogers J, Levy DM, Henry MM and Misiewicz JJ : Pelvic floor neuropathy: a comparative study of diabetes mellitus and idiopathic faecal incontinence. Gut 29 : 756-761 (1988) 10) Pintor MP, Zara GP, Falletto E, Monge L, Demattei M, Carta Q and Masenti E : Pudendal neuropathy in diabetic patients with faecal incontinence.Int J ColorectalDis 9 :105-109 (1994) 11) Erckenbrecht JF, Winter HJ, Cicmir I and Wienbeck M : Faecal incontinence in diabetes mellitus: is it correlated to diabetic autonomic or peripheral neuropathy ? Z Gastroenterol12 : 731-736 (1988) 12) EpanomeritakisE, Koutsoumbi P, Tsiaoussis I, Ganotakis E, Vlata M, Vassilakis JS and Xynos E : Impairment of anorectal function on diabetes mellitus duration of disease. Dis Colon Rectum 42: 1394-1400 (1999) 13) Caviezel F, Bossi A, Baresi A and Salvini A : Ano-rectal manometry as an evaluating test for impaired ano-rectal function in diabetes mellitus. Acta Diabetol Lat 23: 331-338 (1986) 14) Kiff ES and Swash M : Slowed conduction in the pudendal nerves in idiopathic (neurogenic) faecal incontinence.Br J Surg 71: 614-616 (1984) 15) Tomita R, Ikeda T, Fujisaki S, Park E, Tanjoh K and Fukuzawa M : Pathophysiological study on terminal motor latency on the pudendal nerve for ulcerative colitis after ileal J pouch-anal anastomosis with or without soiling. Jpn J GastroenterolSurg 34: 1582-1586 (2001) (In Japanese) 16) Wald A : Incontinenceand anorectal dysfunction in patients with diabetes mellitus. Eur J GastroenterolHepatol 7:737-739 (1995) 17) Jaspan J, Maselli R, Heroid K and Bartkus C : Treatment of severely painful diabetic neuropathy with an aldose reductase inhibitor: Relief of pain and improvedsomatic and autonomic nerve function. Lancet 2 : 758-762 (1983) 18. Nakamura T, Okano R, Uchiyama H, Seo Y and Okada S : Effectiveness of aldose reductase inhibitors for diabetic gastroenteropathywith constipation. Intern Med 36 : 479-483 (1997)

[Received October 28, 2002 : Accepted December 12, 2002]