Impaired awareness of hypoglycemia (IAH) is common in diabetes. Administration of N-acetyl cysteine (NAC) during episodes of hypoglycemia (HG) prevents the development of IAH in rodents (Fioramonti 2013). Here we tested the hypothesis that NAC will be effective in preventing IAH in healthy humans using a double blind cross over study design where subjects received either NAC or saline (S) in random order on day 1 of a 2 day protocol that involved 3 HG clamps. On day 1, 350 mg NAC or S was given IV over 5 hours starting 30 min before start of IV insulin (2 mg/kg/min). Blood glucose (BG) was targeted at 50 mg/dl for 2 hours, then at 95 mg/dl for 2 hours, then 50 mg/dl for 2 hours. After BG recovery subjects were sent home to return on day 2 for a final 2-hour HG clamp. During the 1st and 3rd HG periods, serum epinephrine (EPI) and hypoglycemic symptoms (HSx) were collected. Subjects received 25 mg diphenhydramine IV at 0 and 4 hours due to a high occurrence of drug reactions. Additional doses or odansetron were given as needed.

EPI during clamp 1 was higher during NAC compared to S but the HSx were the same. No difference was seen between subjects who did or did not have a reaction to NAC. EPI and HSx on day 2 following NAC were lower than on day 1 but no different from response measured following S on day 1. NAC elicited many adverse events, enhanced EPI during HG, and did not alter EPI or HSx during HG on day 2 compared to S. Further development of IV NAC as a therapy for IAH is unwarranted.


A. Moheet: None. A. Kumar: None. L. Coles: None. N. Rubin: None. L.E. Eberly: None. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company, Zucara Therapeutics Inc. Consultant; Self; 360 Consulting, MannKind Corporation. Research Support; Self; Eli Lilly and Company, JDRF, National Institutes of Health. Other Relationship; Self; American Diabetes Association, Sanofi, WebMD.



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