Severe islet amyloidosis in congenital generalized lipodystrophy

• Published in: Diabetes care Vol. 19; no. 1; pp. 28 - 31
• Main Authors: GARG, A, CHANDALIA, M, VUITCH, F
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.1996
• Subjects: Adult; Amyloidosis - blood; Amyloidosis - complications; Amyloidosis - pathology; Associated diseases and complications; Biological and medical sciences; Blood Glucose - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Glucose Tolerance Test; Humans; Insulin - blood; Islets of Langerhans - pathology; Lipodystrophy - blood; Lipodystrophy - complications; Lipodystrophy - pathology; Medical sciences; Pancreatic Diseases - blood; Pancreatic Diseases - complications; Pancreatic Diseases - pathology; Human; Pancreatic hormone; Skin disease; Congenital; Langerhans islet; Metabolic diseases; Enzymopathy; Generalized; Insulin; Proteins; Protein hormone; Target tissue resistance; B-Cell; Atrophia; Lipodystrophy; Amyloidosis; Adipose tissue disorders; Endocrine pancreatic diseases
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.19.1.28

Severe islet amyloidosis in congenital generalized lipodystrophy. A Garg , M Chandalia and F Vuitch Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235-9052, USA. garg@crcvax.swmed.edu Abstract OBJECTIVE: Islet amyloidosis may be one mechanism for pancreatic islet beta-cell loss that is associated with the development of NIDDM. However, the question remains whether chronic overstimulation of insulin and islet amyloid polypeptide (IAPP) secretion in states of insulin resistance 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 resistance that may provide some clues. RESEARCH DESIGN AND METHODS: Our patient was a 24-year-old African-American woman with congenital generalized lipodystrophy. Severe acanthosis nigricans was noted in her since age 6. At ages 12 and 16, normal and impaired glucose tolerances, respectively, were noted on oral glucose tolerance tests but were accompanied by extreme fasting and post-prandial hyperinsulnemia. Overt diabetes developed at age 18 and she required approximately 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 methods and immunohistochemical techniques. RESULTS: Some scarring of the pancreas as a result of previous episodes of acute pancreatitis was observed. Severe amyloidosis was noted in 89% of the islets, sparing those that were rich in pancreatic polypeptide-secreting cells. Amyloid deposits stained intensely on immunostaining with antibodies against amylin. Marked paucity of beta-cells was evident. The ratio of beta- to alpha-cells was reduced to 1:1 (normal ratio approximately 4:1). CONCLUSIONS: These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as beta-cell atrophy.