PANCREATIC PATHOLOGY IN NON-INSULIN-DEPENDENT DIABETES (NIDDM)

NIDDM is a heterogeneous disease and subgroups of NIDDM include MODY ( Maturity Onset Diabetes of the Young), Malnutrition-related diabetes ( MRDM) and Fibrocalculus pancreatic diabetes (FCPD). Endocrine cell pop ulation is relatively unchanged in NIDDM: B-cells are reduced by up to 30% and A-cells increased by 10%. Islet amyloid is found in 96% of su bjects occupying up to 80% of the islet associated with a reduction in B-cells. Amyloid formation is unlikely to cause diabetes but progress ive accumulation increases the severity of the disease. Islet amyloid is formed from the islet amyloid polypeptide (LAPP), a normal constitu ent of B-cells, co-secreted with insulin. The causal factors for IAPP fibrillogenesis are unknown but abnormal synthesis or overproduction c ould be involved: stimulation of B-cell secretion in NIDDM by obesity, hyperglycaemia or suphonylurea therapy may promote amyloidosis and fu rther aggravate islet pathology. A mutation of the glucokinase gene in MODY leads to diminished B-cell secretion but not amyloid formation. Diabetes and mutations of mitochondrial DNA is associated with poorly developed islet structure. Exocrine pancreatic size is reduced and the re is evidence of sub-clinical chronic pancreatitis in NIDDM. In MRDM and FCPD, chronic pancreatitis and exocrine necrosis is associated wit h reduced insulin secretion. Unlike cystic fibrosis where islet amyloi d is present in diabetic individuals, amyloid is absent from subjects with FCPD. Pathological changes in the exocrine and endocrine pancreas in NIDDM results from and contributes to the pathophysiology of insul in secretion in NIDDM.