title: Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.
abstract: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00626080.
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Larissa W
authors.initials: LW
authors.lastname: van Golen
authors.affiliation: Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ĳzerman
authors.affiliation: Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands.
authors.forename: Jan Berend
authors.initials: JB
authors.lastname: Deijen
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Heijboer
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands; Department of Internal Medicine/Endocrine Section, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Madeleine L
authors.initials: ML
authors.lastname: Drent
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D001069:Appetite Regulation / Q000187:drug effects; D001812:Blood-Brain Barrier; D001835:Body Weight / Q000187:drug effects; D001931:Brain Mapping; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000134:cerebrospinal fluid; D000069057:Insulin Detemir; D007336:Insulin, Isophane / Q000009:adverse effects / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D010775:Photic Stimulation
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane
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