Hyperinsulinemia due to impaired insulin clearance associated with fasting hypoglycemia and postprandial hyperglycemia: An analysis of a patient with antiinsulin receptor antibodies

Hiroaki Kiyokawa*, Norio Kono, Tomoya Hamaguchi, Masanori Kawachi, Koji Tajima, Ikuo Mineo, Yuya Yamada, Takao Shimizu, Masamichi Kuwajima, Seiichiro Tarui

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Antiinsulin receptor antibodies were detected in the serum of a patient with insulin-resistant diabetes. Fasting hypoglycemia and postprandial hyperglycemia recurred every day. The plasma insulin level was 553±359 pmol/L [77±50 μ/mL (mean±SD)] in the fasting state and rose above 7500 pmol/L postprandially. The glycemic clamp at 2.8 mmol/L (50mg/dL) without insulin infusion revealed that the half-life of plasma endogenous insulin was 173 min, indicating severely impaired plasma insulin clearance. During the clamp the glucose infusion rate was almost constant (0.9–1.2 mg;/kg·min) despite an exponential decline in the plasma insulin level from 460 pmol/L (65 μU/mL) to 129 pmol/L (18 μU/mL). Intravenous insulin administration did not appreciably accelerate the basal constant decrease in the plasma glucose level during the postabsorptive period. These results indicate the coexistence of marked insulin resistance and constant ability to decrease plasma glucose level. In in vitro experiments, antireceptor immunoglobulin G from this patient increased the fructose 2, 6-bisphosphate concentration in the presence of glucagon (<0.1 nmol/L) in primary cultured rat hepatocytes. The antireceptor immunoglobulin G stimulated autophosphorylation of rat liver insulin receptor. We conclude that antiinsulin receptor antibodies could impair plasma insulin clearance, resulting in persistent hyperinsulinemia, and that continuous receptor stimulation by the antibodies was responsible for the development of hypoglycemia.

Original languageEnglish (US)
Pages (from-to)616-621
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume69
Issue number3
DOIs
StatePublished - Sep 1989

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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