High prevalence of pancreatic islet amyloid in patients with end-stage renal failure on dialysis treatment.
Islet amyloid polypeptide (IAPP) is the main proteinaceous component of pancreatic islet amyloid, which is a characteristic feature of type 2 diabetes. The factors responsible for amyloid deposition are unclear. Patients with end-stage renal failure (ESRF) on dialysis treatment have increased insulin resistance which is associated with hypersecretion of beta-cell products. Furthermore, elevated concentrations of circulating IAPP are found in these patients due to reduced renal clearance of IAPP. To determine the prevalence of islet amyloid in this group of patients, pancreas was examined from 23 non-diabetic [aged 62 (29-79) years, median and range] and four type 2 diabetic [aged 67 (56-72) years] patients with ESRF on dialysis treatment. Pancreatic specimens from 30 non-diabetic control subjects [aged 67.5 (56-86) years] and 14 type 2 diabetic subjects without renal disease [aged 69 (48-86) years] were used as control groups. Islet amyloid was present in all type 2 diabetic patients with ESRF and in 12 out of 14 type 2 diabetic control subjects (86 per cent). Amyloid deposits were found in 8 out of 23 non-diabetic patients with ESRF (35 per cent), which was a higher prevalence than that found in non-diabetic control subjects (3 per cent) (P < 0.01). This may be related to undiagnosed (pre)diabetes. Elevated secretion rates of IAPP due to insulin resistance and high circulating IAPP concentrations as a result of severely reduced renal clearance of IAPP will cause high pericellular concentrations of IAPP. This condition is likely to enhance amyloid fibril formation in pancreatic islets similar to that observed in type 2 diabetes.
de Koning
E J
EJ
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, U.K.
Fleming
K A
KA
Gray
D W
DW
Clark
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000032:analysis*; D000686:Amyloidosis / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000737:chemistry*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010182:Pancreatic Diseases / Q000209:etiology; D006435:Renal Dialysis
D000682:Amyloid; D058228:Islet Amyloid Polypeptide