Severe islet amyloidosis in congenital generalized lipodystrophy

Abhimanyu Garg, Manisha Chandalia, Frank Vuitch

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

OBJECTIVE - Islet amyloidosis may be one mechanism for pancreatic islet β-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 women with congenital generalized lipodystrophy. Severe acanthosis nigrans 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 postprandial hyperinsulinemia. Overt diabetes developed at age 18 and she required ~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 β-cells was evident. The ratio of β- to α-cells was reduced to 1:1 (normal ratio - 4:1). CONCLUSIONS - These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as β-cell atrophy.

Original languageEnglish (US)
Pages (from-to)28-31
Number of pages4
JournalDiabetes Care
Volume19
Issue number1
StatePublished - Jan 1996

Fingerprint

Congenital Generalized Lipodystrophy
Amyloidosis
Islets of Langerhans
Islet Amyloid Polypeptide
Insulin Resistance
Type 2 Diabetes Mellitus
Pancreatic Polypeptide-Secreting Cells
Insulin
Glucose Intolerance
Amyloid Plaques
Hyperinsulinism
Glucose Tolerance Test
Pancreatitis
African Americans
Atrophy
Cicatrix
Pancreas
Autopsy
Fasting
Histology

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Severe islet amyloidosis in congenital generalized lipodystrophy. / Garg, Abhimanyu; Chandalia, Manisha; Vuitch, Frank.

In: Diabetes Care, Vol. 19, No. 1, 01.1996, p. 28-31.

Research output: Contribution to journalArticle

Garg, A, Chandalia, M & Vuitch, F 1996, 'Severe islet amyloidosis in congenital generalized lipodystrophy', Diabetes Care, vol. 19, no. 1, pp. 28-31.
Garg, Abhimanyu ; Chandalia, Manisha ; Vuitch, Frank. / Severe islet amyloidosis in congenital generalized lipodystrophy. In: Diabetes Care. 1996 ; Vol. 19, No. 1. pp. 28-31.
@article{401d23e6a003484d86648fcb749054bc,
title = "Severe islet amyloidosis in congenital generalized lipodystrophy",
abstract = "OBJECTIVE - Islet amyloidosis may be one mechanism for pancreatic islet β-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 women with congenital generalized lipodystrophy. Severe acanthosis nigrans 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 postprandial hyperinsulinemia. Overt diabetes developed at age 18 and she required ~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 β-cells was evident. The ratio of β- to α-cells was reduced to 1:1 (normal ratio - 4:1). CONCLUSIONS - These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as β-cell atrophy.",
author = "Abhimanyu Garg and Manisha Chandalia and Frank Vuitch",
year = "1996",
month = "1",
language = "English (US)",
volume = "19",
pages = "28--31",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "1",

}

TY - JOUR

T1 - Severe islet amyloidosis in congenital generalized lipodystrophy

AU - Garg, Abhimanyu

AU - Chandalia, Manisha

AU - Vuitch, Frank

PY - 1996/1

Y1 - 1996/1

N2 - OBJECTIVE - Islet amyloidosis may be one mechanism for pancreatic islet β-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 women with congenital generalized lipodystrophy. Severe acanthosis nigrans 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 postprandial hyperinsulinemia. Overt diabetes developed at age 18 and she required ~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 β-cells was evident. The ratio of β- to α-cells was reduced to 1:1 (normal ratio - 4:1). CONCLUSIONS - These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as β-cell atrophy.

AB - OBJECTIVE - Islet amyloidosis may be one mechanism for pancreatic islet β-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 women with congenital generalized lipodystrophy. Severe acanthosis nigrans 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 postprandial hyperinsulinemia. Overt diabetes developed at age 18 and she required ~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 β-cells was evident. The ratio of β- to α-cells was reduced to 1:1 (normal ratio - 4:1). CONCLUSIONS - These observations suggest that chronic presence of extreme insulin resistance may induce premature and severe islet amyloidosis as well as β-cell atrophy.

UR - http://www.scopus.com/inward/record.url?scp=0030042475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030042475&partnerID=8YFLogxK

M3 - Article

VL - 19

SP - 28

EP - 31

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 1

ER -