A 71 year old gentleman presented with polydipsia, polyuria and nocturia for two weeks and weight loss of 10.5 Kg over the preceding two years. He had hypertension controlled with valsartan, hydrochlorthiazide, amlodipine and doxazosin. His average alcohol intake was 55 units per week. His brother had diabetes of uncertain aetiology. Examination was unremarkable apart from mild dehydration. His body mass index was 28 kg/m2 and there were no clinical signs suggestive of insulin resistance or lipodystrophy. Investigations showed venous glucose of 43.9 mmol/L, plasma ketones of 1.0 mm, HbA1c of 116 mmol/mol (12.8%), normal pH and renal function. He was initially managed with intravenous fluids and variable rate insulin infusion with smooth transition towards basal bolus insulin regimen. Due to excess alcohol intake and weight loss, a CT abdomen was undertaken which showed features suggestive of chronic calcifying pancreatitis and no evidence of malignancy. A diagnosis of secondary diabetes due to chronic pancreatitis (type 3c diabetes) was made and the patient was counselled for alcohol intake. Islet cell antibodies were negative but anti-GAD antibody was strongly positive at 1961 u/ml (reference range 15), challenging the diagnosis of secondary diabetes.
Acute pancreatitis has been reported to increase anti-GAD antibody levels by damaging GAD65 antigen, leading to transient or permanent insulin dependent diabetes. In contrast, islet autoantibodies were negative in a study of patients with chronic pancreatitis, even in the presence of a diabetogenic HLA haplotype. This case is unusual as GAD antibody titres usually tend to be lower in autoimmune diabetes (less than 100 U/mL). We propose that pancreatitis led to elevation in anti-GAD antibody levels causing autoimmune damage to islet cells leading to insulinopaenia. This case highlights the importance of keeping a broad differential when assessing a patient with diabetes.