Euglycemic infusion of insulin detemir compared with human insulin appears to increase direct current brain potential response and reduces food intake while inducing similar systemic effects.
OBJECTIVE
In the treatment of diabetic patients, the long-acting insulin analog insulin detemir is less prone to induce weight gain than other insulin formulations. Assuming that because of its pharmacologic properties, detemir displays stronger central nervous anorexigenic efficacy than human insulin, we compared acute effects of human insulin and detemir on electroencephalography (EEG) measures and food intake.


METHODS
Frontocortical EEG direct current (DC) potentials were recorded in 15 healthy men during two hyperinsulinemic-euglycemic clamps that included an insulin bolus injection (human insulin, 17.75 mU/kg body wt; detemir, 90 mU/kg body wt) followed by a steady 90-min infusion (1.0 vs. 2.0 mU x kg(-1) x min(-1)). A higher dosage was chosen for detemir to compensate for its delay in impact relative to human insulin and to elicit similar systemic effects. At 20 min after infusion, subjects were allowed to eat ad libitum from a test buffet.


RESULTS
Mean glucose infusions to maintain euglycemia (P > 0.93) and blood glucose concentrations (P > 0.34) did not differ between conditions. Detemir infusion induced a negative DC-potential shift, averaging -372.2 microV from 21 to 90 min that was not observed during human insulin infusion (146.5 microV, P = 0.02). Detemir, in comparison with human insulin, reduced subsequent food intake by 303 kcal (1,257 vs. 1,560, P < 0.04).


CONCLUSIONS
While inducing comparable peripheral effects, detemir exerts stronger acute effects on brain functions than human insulin and triggers a relative decrease in food consumption, suggesting an enhanced anorexigenic impact of detemir compared with human insulin on central nervous networks that control nutrient uptake.
Hallschmid
Manfred
M
Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany. hallschmid@kfg.uni-luebeck.de
Jauch-Chara
Kamila
K
Korn
Oliver
O
Mölle
Matthias
M
Rasch
Björn
B
Born
Jan
J
Schultes
Bernd
B
Kern
Werner
W
D000328:Adult; D000339:Affect / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D004585:Electrooculography; D002149:Energy Intake; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; D008297:Male
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D005947:Glucose