Effects of the Selective Serotonin Reuptake Inhibitor, Fluoxetine, on Counterregulatory Responses to Hypoglycemia in Individuals with T1DM

Abstract

Objective: Previous work has demonstrated that chronic administration of the serotonin reuptake inhibitor (SSRI), fluoxetine, augments counterregulatory responses to hypoglycemia in healthy man. However, virtually no information exists regarding the effects of fluoxetine on integrated physiologic counterregulatory responses during hypoglycemia in type 1 diabetes mellitus (T1DM). Therefore, the specific aim of this study was to test the hypothesis that 6 weeks use of the SSRI, fluoxetine, would amplify autonomic nervous system (ANS) counterregulatory responses to hypoglycemia in individuals with T1DM.

Research Design and Methods: Eighteen T1DM (14M/4F) (age 19yrs - 48yrs, BMI 25±3 kg/m², and HbA1c 7.0±0.4%) participated in randomized, double-blind 2 h hyperinsulinemic (9pmol/kg/min) hypoglycemic clamp studies before and after either 6 weeks of fluoxetine (n=8) or identical placebo (n=10). Glucose kinetics were determined by 3-tritiated glucose. Muscle sympathetic nerve activity (MSNA) was determined by microneurography.

Results: Hypoglycemia (2.8±0.1 mmol/L) and insulinemia (646±52 pmol/L) were similar during all clamp studies. Autonomic nervous system, neuroendocrine and metabolic counterregulatory responses remained unchanged in the placebo group. However, fluoxetine administration significantly (p<0.05) increased key ANS (epinephrine, norepinephrine, MSNA), metabolic (Endogenous glucose production (EGP), lipolysis) and cardiovascular (systolic blood pressure) counterregulatory responses during hypoglycemia.

Conclusion: This study has demonstrated that 6 weeks administration of the SSRI, fluoxetine, can amplify ANS and metabolic counterregulatory mechanisms during moderate hypoglycemia in patients with type 1 diabetes. These data also suggest that the use of fluoxetine may be useful in increasing epinephrine responses during hypoglycemia in clinical practice.