Challenges in concurrent liver and pancreatic insufficiency: glucose control on a tight rope
Andrianni Karra1, Pei Chia Eng1, Maria Phylactou1, Manninder Gill2, Anna Pullen3, Lucy Fermor1, Sanjeev Mehta1, Nick Oliver4, Kevin Baynes1
1Department of diabetes and endocrinology, Ealing hospital
2Department of dietetics, Ealing hospital
3Department of clinical psychology, Ealing hospital
4Department of diabetes and endocrinology, Charing Cross Hospital
Introduction: Control of plasma glucose concentration requires flawless cooperation between the pancreas, liver and the intestine. In the event of diminished pancreatic function, impaired incretin secretion and loss of islet cell insulin and glucagon secretion contribute to brittle diabetes characterized by marked glycaemic lability.
Case and Investigations: We present a case of a 29-year old man who was diagnosed with pancreatic diabetes resulting from chronic alcohol misuse. He had significant weight loss and had extensive investigations for low body mass index. His computed tomography scans of his chest; abdomen and pelvis revealed gross chronic pancreatitis but did not suggest any evidence of malignancy. His tumour markers – CEA and CA19-9 were elevated at 6.6 and 251 suggesting chronic pancreatitis rather than malignancy. Further investigations including an oesophagoduodenoscopy and biopsy excluded gastrointestinal ulcer and malignancy. Hepatitis screen, liver autoantibodies, coeliac screen, alpha -1 antitrypsin, ceruloplasmin, copper and HIV serology have been negative. Despite being treated with a basal bolus regimen consisting of small doses of meal time novorapid and small doses of long acting basal insulin, his capillary blood glucose control had remained erratic ranging from 1 mmol/L to 47 mmol/L. Managing his hypoglycaemic episodes was challenging as these episodes were poorly responsive to glucagon therapy and could only be managed with intravenous dextrose. As he had repeated hypoglycaemic episodes, he developed impaired hypoglycaemic awareness and this eventually led to a severe hypoglycaemic event after which he sustained a basal ganglia infarction. Investigations for hypoglycaemia excluded endogenous insulin secretion as his paired plasma C-peptide, plasma insulin were appropriately suppressed at plasma glucose of 2mmol/L. IGF2 levels were within normal limits and urine sulphonylurea screen was negative. An early morning serum cortisol level is adequate at 819nmol/L.
Discussion: Control of hyperglycaemia and preventing hypoglycaemia remains the primary treatment target in pancreatic diabetes. There are no guidelines regarding the management of such patients. Abstaining from alcohol and smoking cessation reduce toxic insults to the pancreas. Pancreatic enzyme replacement aids fat digestion and provides incretin to maintain glucose tolerance during meal ingestion. Since the endocrine defect is insulin deficiency, most experts recommend multi dose basal bolus regimen including carbohydrate counting for flexible prandial coverage, with consideration of continuous subcutaneous insulin infusion or pump therapy. As the degree of beta cell impairment is seldom absolute, insulin dosing for such patients is challenging as the continued loss of glucagon secretion and replacement insulin doses may unpredictably predisposes to hypoglycemia. We would like to highlight the complexity in the management of this patient. Our patient has been referred to tertiary center and is being worked up for liver and pancreatic transplant.