Naltrexone for treatment of impaired awareness of hypoglycemia in type 1 diabetes: A randomized clinical trial.
OBJECTIVE
Impaired awareness of hypoglycemia (IAH) is a limiting factor in the treatment of type 1 diabetes (T1D) and is a challenging condition to reverse. The objective of this study was to test the hypothesis that naltrexone therapy in subjects with T1D and IAH will improve counterregulatory hormone response and recognition of hypoglycemia symptoms during hypoglycemia.


METHODS
We performed a pilot randomized double blind trial of 4weeks of naltrexone therapy (n=10) or placebo (n=12) given orally in subjects with T1D and IAH. Outcome measures included hypoglycemia symptom scores, counterregulatory hormone levels and thalamic activation as measured by cerebral blood flow using MRI during experimental hypoglycemia in all subjects before and after 4weeks of intervention.


RESULTS
After 4weeks of therapy with naltrexone or placebo, no significant differences in response to hypoglycemia were seen in any outcomes of interest within each group.


CONCLUSIONS
In this small study, short-term treatment with naltrexone did not improve recognition of hypoglycemia symptoms or counterregulatory hormone response during experimental hypoglycemia in subjects with T1D and IAH. Whether this lack of effect is related to the small sample size or due to the dose, the advanced stage of study population or the drug itself should be the subject of future investigation.
Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, United States. Electronic address: mohee002@umn.edu.
Amir
A
Moheet
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN, United States.
Silvia
S
Mangia
Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
Anjali
A
Kumar
Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
Nolawit
N
Tesfaye
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States.
Lynn E
LE
Eberly
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States.
Yun
Y
Bai
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States.
Kristine
K
Kubisiak
Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN, United States.
Elizabeth R
ER
Seaquist
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002533:Cerebral Angiography / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D059026:Diagnostic Self Evaluation; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000175:diagnosis* / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D018670:Monitoring, Ambulatory; D009271:Naltrexone / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D013788:Thalamus / Q000098:blood supply / Q000187:drug effects
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D009271:Naltrexone; D009292:Narcotic Antagonists; C517652:hemoglobin A1c protein, human
HAAF; Hypoglycemia; Impaired awareness of hypoglycemia; Naltrexone; Opioid antagonists; Type 1 diabetes