Pathophysiology of beta cell failure after prolonged remission of insulin-dependent diabetes mellitus (IDDM).
The pathophysiology of beta cell failure in IDDM has not been well documented. Islet cell responsiveness (C-peptide and glucagon) to oral glucose (OGTT), intravenous glucose (IVGTT), and arginine infusion was studied sequentially in a 24-yr-old nonobese patient with IDDM in prolonged remission interrupted by an episode of diabetic ketoacidosis and followed by a second transient (6 mo) partial recovery of beta cell function. The earliest abnormality in glucose tolerance was demonstrated with the IVGTT (K = 0.77) although OGTT (F, 101: 1/2 h, 177; 7 h, 211; 1 1 h, 144; and 2 h, 111 mg/dl) and glucagon responses to glucose and arginine were normal. With the development of abnormal OGTT, glucagon failed to suppress with hyperglycemia although basal levels were not elevated. With the development of frank clinical diabetes, C-peptide did not respond to oral or i.v. glucose although stimulation in response to arginine infusion was still possible. Basal glucagon concentrations were now elevated. Thus, the failing beta cell shows a progressive deterioration in its responsiveness to various secretagogues in a sequential manner (i.v. glucose followed by oral glucose and then i.v. arginine). Abnormalities in glucagon secretion can be demonstrated early in the development of abnormal oral glucose tolerance. With more precise elucidation of the etiology of diabetes, it may be possible to intervene therapeutically in diabetic individuals who experience a remission in order to prevent further deterioration in beta cell function.
D000328:Adult; D001120:Arginine; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D016883:Diabetic Ketoacidosis / Q000503:physiopathology; D005934:Glucagon / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male
D002096:C-Peptide; D005934:Glucagon; D001120:Arginine