The exacerbation of pancreatic endocrine dysfunction by potent pancreatic exocrine supplements in patients with chronic pancreatitis.

BACKGROUND

Chronic pancreatitis often culminates in maldigestion and diabetes. Clinical management is complex as the correction of maldigestion often disturbs diabetic control.

METHODS

In the following study, we examined the effects of a potent new commercial pancreatic enzyme on food absorption and blood glucose control. Enzymes were manufactured in enteric-coated mini-microsphere form (0.7--1.6 mm), designed to prevent gastric acid degradation and facilitate co-migration with food, and given in quantities calculated to cover normal digestion requirements (four capsules with meals, two with snacks; content/capsule: lipase 10,000 USP units, protease 37,500 units, amylase 33,200 units). Forty patients with chronic pancreatitis were screened during a run-in nonenzyme-supplemented phase; only those with stool fat excretion rates over 10 g/d (n = 29) were advanced to a 14-day parallel randomized placebo versus enzyme supplement group comparison.

RESULTS

Of these, 62% were diabetic (50% insulin-dependent) and 52% were malnourished (body mass index less than 20 kg/m(2) ). After enzyme supplementation, stool fat and nitrogen excretion decreased, whereas fat absorption increased from 54.0 +/- 9.7% to 80.8 +/- 3.8% per day (p = 0.002) and protein from 80.5 +/- 3.4% to 86.8 +/- 2.2% per day (p = 0.004). Changing treatment from active enzyme supplementation to placebo (and vice versa) resulted in major problems with glucose control; blood glucose levels became abnormal in 28 of 29 patients, one patient required hospitalization for symptomatic hypoglycemia (0.9 mmol/L) during placebo treatment, and one developed diabetic ketoacidosis after recommencing active enzyme supplementation.

CONCLUSIONS

In conclusion, high-dose pancreatin mini-microspheres improved, but did not normalize, fat absorption, possibly because of the residual influence of diabetes and malnutrition on absorptive function. In view of the brittle nature of blood glucose control in malnourished insulin-dependent patients, enzyme adjustment should be carefully supervised in-hospital.