Dear Dr Emmanuel,
Thank you for seeing this 74-year-old diabetic lady under the two-week cancer rule. She has noticed a change in bowel habit over the last four months, with diarrhoea on most days and often at night. There has been no blood or weight loss, and examination is normal.
We did consider the possibility that her metformin was to blame, as the dose had been increased around the time her symptoms developed, but temporary discontinuation did not improve matters.
She is currently on metformin 500mg bd, gliclazide 80mg per day, simvastatin 40mg per day and co-codamol 8/500 prn.
She is keen to attribute her symptoms to irritable bowel syndrome, which runs in the family, but I feel further investigation is mandatory here.
Many thanks for your referral. Mrs A has had a diagnosis of type 2 diabetes for 22 years, and has a six-month history of diarrhoea. This was a notable change from her background tendency towards constipation for many years. Significantly, she had to wake up on most nights to open her bowels.
A bowel diary she maintained over two weeks showed watery stools on almost all occasions, interspersed with days of no bowel opening. There is no blood or mucus loss.
On direct questioning, there has been a loss of appetite with early satiety, but no vomiting.
Weight has fluctuated over these six months, and she has lost 2kg overall. Abdominal pain and bloating are frequent, but not related to bowel habit, thereby excluding IBS. She has retinopathy and sensory loss in her toes. Her diet is unremarkable – she uses sweeteners and drinks a lot of diet fizzy drinks.
Of note, she has had two children, both born vaginally and one with forceps extraction. She reports marked faecal urgency and on several occasions has been faecally incontinent. She needs to wear a pad at nights and now sleeps on her own because of this symptom. Her medication is as you describe – importantly, there is no temporal relationship between metformin administration and loose stools.
Examination revealed a postural blood pressure drop of 25mmHg and prominent tachycardia during a Valsalva manoeuvre. Digital rectal examination revealed normal anal tone at rest, but reduced squeeze pressure – the rectum was empty, excluding impaction and overflow. She has a BMI of 26.
In view of the symptoms and weight loss she underwent the following investigations:
1 Upper GI endoscopy and duodenal biopsies – despite an eight-hour fast there was food residue in the stomach (likely gastroparesis) and biopsies excluded coeliac disease, which is a known associated comorbidity of diabetes.
2 Colonoscopy and biopsies – excluded malignancy, diverticular disease (an unlikely cause of diarrhoea) and microscopic colitis (a known associated comorbidity of diabetes).
3 She underwent endoanal ultrasound, which showed an obstetric defect in the external sphincter – this sphincter defect is likely to be contributing to her symptoms.
4 A hydrogen breath test with glucose substrate was positive within 30 minutes, suggestive of small intestinal bacterial overgrowth (another consequence of diabetes).
In essence, this woman has diabetic autonomic neuropathy, in keeping with her other diabetic complications – retinopathy, neuropathy and gastroparesis – with secondary bacterial overgrowth and chronic sphincter injury.
A one-week course of doxycycline 100mg bd improved some aspects of diarrhoea and more significantly bloating. She has started pelvic floor biofeedback and titrated loperamide (in syrup formulation to fine tune and avoid constipating side-effects) to improve her incontinence. Metformin and statins may be contributing in small part, but cannot be changed in light of her diabetes and BMI. She was asked to stop her sweeteners and fizzy drinks since they are a significant cause of osmotic diarrhoea.
Dr Anton Emmanuel
1. Diabetic autonomic neuropathy is present in as many as one-third of type 2 diabetes patients.
2. Diabetic autonomic neuropathy is more prevalent with duration of diabetes and presence of other diabetes complications and symptoms, such as postural hypotension. Formal autonomic testing is intrusive and not mandated for what can be a clinical diagnosis.
3. Small intestinal bacterial overgrowth can be diagnosed with a non-invasive breath test and can be treated with simple antibiotics. Symptom recurrence is common, however, due to the immune paresis associated with diabetes.
4. The absence of a temporal relationship between pain and diarrhoea makes IBS unlikely. Similarly, nocturnal diarrhoea is not seen in IBS, and should raise the probability of an organic cause.
5. Faecal incontinence is common, and often needs direct questioning to elicit this stigmatising symptom. Simple treatment is beneficial in most situations, without need for intrusive and expensive therapies.
Dr Anton Emmanuel is a consultant gastroenterologist at University College London Hospitals