Deficiency of total and nonglycosylated amylin in plasma characterizes subjects with impaired glucose tolerance and type 2 diabetes

This study was undertaken to characterize first and second phase secretory profiles of total and nonglycosylated amylin and insulin and to determine w hether excessive glycosylation of amylin or hyperamylinemia is a feature of abnormal glucose tolerance in humans. Plasma concentrations of total and n onglycosylated amylin and serum immunoreactive insulin were measured under identical hyperglycemic conditions using the hyperglycemic clamp technique in subjects with type 2 diabetes, impaired and normal glucose tolerance. Bo th amylin and insulin concentrations followed a biphasic pattern in subject s with normal and impaired glucose tolerance. In the subjects with normal:a nd impaired glucose tolerance, the second phase amylin concentrations marke dly exceeded those of the first phase, whereas the reverse was true for ins ulin. The first phase concentrations of both peptides were significantly lo wer in impaired than the normal glucose tolerance subjects. In patients wit h type 2 diabetes no first phase peak for either amylin or insulin could be identified, and the second phases of both amylin and insulin were signific antly lower compared to subjects with normal or impaired glucose tolerance. Nonglycosylated amylin concentrations accounted for 25-45% of total amylin , regardless of glucose tolerance, and mimicked the pattern of total amylin concentrations. In summary: 1) glucose-induced increases in the magnitude of the first and second phase amylin plasma concentrations differed from th ose of insulin; 2) subjects with impaired glucose tolerance and more striki ngly those with type 2 diabetes have impaired amylin responses; and 3) the ratio of nonglycosylated to total amylin is normal irrespective of glucose tolerance. These data imply, in view of many reports describing accumulatio n of amyloid in the pancreas, that circulating levels of amylin decrease as amyloid deposits accumulate and beta -cell function deteriorates and that the amount of glycosylated amylin in plasma is not increased in patients wi th type 2 diabetes.