SEVERE ISLET AMYLOIDOSIS IN CONGENITAL GENERALIZED LIPODYSTROPHY

OBJECTIVE - Islet amyloidosis may be one mechanism for pancreatic isle t beta-cell loss that is associated with the development of NIDDM. How ever, the question remains whether chronic overstimulation of insulin and islet amyloid polypeptide (LAPP) secretion in states of insulin re sistance could lead to formation of islet amyloidosis and hence NIDDM in some patients. We studied pancreatic islet pathology in congenital generalized lipodystrophy, a genetic syndrome of extreme insulin resis tance that may provide some clues. RESEARCH DESIGN AND METHODS - Our p atient was a 24-year-old African-American woman with congenital genera lized lipodystrophy. Severe acanthosis nigricans was noted in her sinc e age 6. At ages 12 and 16, normal and impaired glucose tolerances, re spectively, were noted on oral glucose tolerance rests but were accomp anied by extreme fasting and postprandial hyperinsulinemia. Overt diab etes developed at age 18 and she required similar to 180 U of insulin daily. Immediately after an accidental death at age 24, an autopsy was performed. Pancreatic histology was studied in detail using routine m ethods and immunohistochemical techniques. RESULTS - Some scarring of the pancreas as a result of previous episodes of acute pancreatitis wa s observed. Severe amyloidosis was noted in 89% of the islets, sparing those that were rich in pancreatic polypeptide-secreting cells. Amylo id deposits stained intensely on immuno-staining with antibodies again st amylin. Marked paucity of beta-cells was evident. The ratio of beta - to alpha-cells was reduced to 1:1 (normal ratio similar to 4:1). CON CLUSIONS - These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as beta-cell atrophy.