Studies in rodents have demonstrated that
insulin in the central nervous system induces satiety. In humans, these effects are less well established.
Insulin detemir is a basal
insulin analog that causes less
weight gain than other basal
insulin formulations, including the current standard intermediate-long acting Neutral
Protamine Hagedorn (
NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that
insulin detemir enters the brain more readily than other
insulins. The aim of this study was to investigate whether
insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to
NPH insulin. In addition, cerebral spinal fluid (CSF)
insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with
insulin detemir and
NPH insulin, respectively, both combined with prandial
insulin aspart. CSF
insulin levels were determined in a subgroup.
Insulin detemir decreased
body weight by 0.8 kg and
NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar
glycemic control.
After treatment with
insulin detemir, as compared to
NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF
insulin levels were higher compared to those with
NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of
insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00626080.