Abstract

Objective: The acylated long-acting insulin analog detemir is more lipophilic than human insulin (HI) and likely crosses the blood-to-brain barrier more easily than does HI. Aim of these studies was to assess the brain/hypothalamus responses to euglycemia and hypoglycemia in humans during i.v. infusion of equipotent doses of detemir and HI.

Research Design And Methods: Ten normal, non-diabetic subjects (6 males, age 36±7 years, BMI 22.9±2.6 kg/m2) were studied on 4 occasions at random, during i.v. infusion of either detemir or HI in euglycemia (plasma glucose, PG, 90 mg/dl) or during stepped hypoglycemia (PG 90, 78, 66, 54, and 42 mg/dl steps).

Results: Plasma counterregulatory hormone response to hypoglycemia did not differ between detemir and HI. The glycemic thresholds for adrenergic symptoms were higher with detemir (51±7.7) vs HI (56±7.8) (mg/dl, p=0.029). However, maximal responses were greater with detemir vs HI for adrenergic (3±2.5 vs 2.4±1.8) and neuroglycopenic (4±3.9 vs 2.7±2.5) symptoms (score, p<0.05). Glycemic thresholds for onset of cognitive dysfunction were lower with detemir vs HI (51±8.1 vs 47±3.6 mg/dl, p=0.031) and cognitive function was more deteriorated with detemir vs HI (p<0.05).

Conclusions: As compared to HI, responses to hypoglycemia with detemir resulted in higher glycemic thresholds for adrenergic symptoms, greater maximal responses for adrenergic and neuroglycopenic symptoms, with an earlier and greater impairment of cognitive function. Additional studies are needed to establish the effects of detemir on responses to hypoglycemia in subjects with diabetes mellitus.