title: Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor.
abstract: OBJECTIVE
  Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor.
  
  
  METHODS
  Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (n = 25), during the first 18 h (mean +/- S.D. 11.1 +/- 4.3 h, n = 16) and 92 h (47.5 +/- 22.5 h; n = 14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays.
  
  
  RESULTS
  The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P < 0.05). In contrast, leptin levels were significantly lower (P < 0.05) before insulin therapy. The correlation between sOB-R and blood glucose (r = 0.49; P < 0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (r = -0.72), base excess (r = -0.70), and bicarbonate (r = -0.69) (P < 0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P < 0.001), age 16.4% (P < 0.05), and height SDS 13.9% (P < 0.01) of the sOB-R variance.
  
  
  CONCLUSIONS
  Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.
authors.affiliation: Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Germany. kraj@medizin.uni-leipzig.de
authors.forename: J
authors.initials: J
authors.lastname: Kratzsch
authors.forename: I
authors.initials: I
authors.lastname: Knerr
authors.forename: A
authors.initials: A
authors.lastname: Galler
authors.forename: T
authors.initials: T
authors.lastname: Kapellen
authors.forename: K
authors.initials: K
authors.lastname: Raile
authors.forename: A
authors.initials: A
authors.lastname: Körner
authors.forename: J
authors.initials: J
authors.lastname: Thiery
authors.forename: J
authors.initials: J
authors.lastname: Dötsch
authors.forename: W
authors.initials: W
authors.lastname: Kiess
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications* / Q000378:metabolism*; D016883:Diabetic Ketoacidosis / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007223:Infant; D020738:Leptin / Q000097:blood / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood*; D054411:Receptors, Leptin
chemical_list: D005230:Fatty Acids, Nonesterified; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin