LETTERS
Perturbation of Glucose Metabolism in Fam&al Amyloidotic Polyneuropathy Yukio Ando, MD," Shigehiro Yi, MD," Masayasu Inoue, MD, PhD,t Shinichi Ikegawa, MD, PhD," Akira Miyazaki, MD,+ and Shukuro Araki, MD, PhD" Recent studies reveal that replacement of Val-30 of prealbumin by methionine is a prerequisite to the formation of amyloid deposit in type I familial amyloidotic polyneuropathy (FAP) [l, 2}. Many serious complaints of patients with FAP reflect disordered autonomic function, such as alternating diarrhea and constipation, orthostatic hypotension, faintness, syncope, and urinary retention {33. The major treatment for FAP patients with faintness and syncope is administration of ~-threo-3,4-dihydroxyphenylserine (L-threoDOPS) for orthostatic hypotension [4} and pacemaker implantation for cardiac arrhythmias caused by amyloid deposition. In 6 of 13 FAP patients, however, complaints of faintness and syncope persisted after medication with L-threoDOPS and pacemaker implantation. We noticed that FAP patients often complain of faintness before or after meals, suggesting that symptoms might result from hypoglycemia. Histochemical analysis reveals that amyloid deposition occurs in pancreatic stroma and visceral nerves although Langerhans islets remain intact. Thus, pancreatic regulation of insulin or glucagon secretion might be affected in FAP patients through a mechanism of denervation hypersensitivity. To investigate the possibility of perturbed glucose metabolism in the pathogenesis of faintness in FAP patients, changes in plasma levels of glucose and related hormones were examined in 12 fasted FAP patients without obesity (35-56 Kg body weight, 23-73 years old) by administering 75 gm oral glucose (OG'IT) to them after they received their usual diet for at least three days prior to study. N o subject had a family history of diabetes. Fasting plasma levels of glucose and insulin were within normal range. However, following OGTT plasma levels of glucose, insulin and glucagon changed abnormally in all 12 FAP patients. Although plasma insulin levels of control individuals during OGTT were 12 to 5 5 U/ml, 4 FAP patients showed marked hyperinsulinemia (>110 U/ml) followed by hypoglycemia (
Perturbation of Glucose Metabolism in Fam&al Amyloidotic Polyneuropathy Yukio Ando, MD," Shigehiro Yi, MD," Masayasu Inoue, MD, PhD,t Shinichi Ikegawa, MD, PhD," Akira Miyazaki, MD,+ and Shukuro Araki, MD, PhD" Recent studies reveal that replacement of Val-30 of prealbumin by methionine is a prerequisite to the formation of amyloid deposit in type I familial amyloidotic polyneuropathy (FAP) [l, 2}. Many serious complaints of patients with FAP reflect disordered autonomic function, such as alternating diarrhea and constipation, orthostatic hypotension, faintness, syncope, and urinary retention {33. The major treatment for FAP patients with faintness and syncope is administration of ~-threo-3,4-dihydroxyphenylserine (L-threoDOPS) for orthostatic hypotension [4} and pacemaker implantation for cardiac arrhythmias caused by amyloid deposition. In 6 of 13 FAP patients, however, complaints of faintness and syncope persisted after medication with L-threoDOPS and pacemaker implantation. We noticed that FAP patients often complain of faintness before or after meals, suggesting that symptoms might result from hypoglycemia. Histochemical analysis reveals that amyloid deposition occurs in pancreatic stroma and visceral nerves although Langerhans islets remain intact. Thus, pancreatic regulation of insulin or glucagon secretion might be affected in FAP patients through a mechanism of denervation hypersensitivity. To investigate the possibility of perturbed glucose metabolism in the pathogenesis of faintness in FAP patients, changes in plasma levels of glucose and related hormones were examined in 12 fasted FAP patients without obesity (35-56 Kg body weight, 23-73 years old) by administering 75 gm oral glucose (OG'IT) to them after they received their usual diet for at least three days prior to study. N o subject had a family history of diabetes. Fasting plasma levels of glucose and insulin were within normal range. However, following OGTT plasma levels of glucose, insulin and glucagon changed abnormally in all 12 FAP patients. Although plasma insulin levels of control individuals during OGTT were 12 to 5 5 U/ml, 4 FAP patients showed marked hyperinsulinemia (>110 U/ml) followed by hypoglycemia (
