title: Proinsulin and the proinsulin/insulin ratio in overweight and obese children and adolescents: relation to clinical parameters, insulin resistance, and impaired glucose regulation.
abstract: BACKGROUND
  In adults with impaired glucose regulation (IGR) or type 2 diabetes mellitus (T2DM), proinsulin (PI) and its ratio to insulin (ins; PI/I ratio) are frequently elevated.
  
  
  OBJECTIVE
  Here we assessed the relationship among fasting PI, clinical parameters, and carbohydrate metabolism, a potential difference of the PI/I ratio between overweight and obese youth with or without IGR in an oral glucose tolerance test (OGTT) and the predictive power of PI levels for IGR.
  
  
  METHODS
  In a cross-sectional study, data of n = 259 children and adolescents attending our obesity clinic were studied.
  
  
  METHODS
  Fasting PI levels were determined in all patients and matched to the standard assessment of obesity. In n = 154 subjects at risk for T2DM, an OGTT was performed sampling for glucose, ins, and PI.
  
  
  METHODS
  ins, glucose, PI, PI/I ratio, insulin resistance [homeostasis model assessment of insulin resistance index (HOMA-IR)].
  
  
  RESULTS
  Puberty (by Tanner) and relative body weight [body mass index (BMI)-standard deviation of BMI (SDS)] showed a linear relationship to fasting PI levels (p < 0.001 for Tanner I vs. II-V; p = 0.04 and p = 0.026 for BMI-SDS < 2 vs. 2-2.5 and 2-2.5 vs. > 2.5, respectively). Subjects with ins resistance (HOMA-IR > 95th percentile, n = 140) had higher fasting PI levels than those without (p < 0.001), with no significant difference in fasting PI/I ratio (p > 0.05). As compared to subjects with normal glucose regulation, subjects with IGR (n = 35) had higher fasting PI (p = 0.001) and an increased PI/I ratio, both during fasting and at 30 min during OGTT (p = 0.049 and p = 0.014, respectively).
  
  
  CONCLUSIONS
  Children and adolescents with IGR have disproportionately elevated PI levels, both during fasting and after acute glucose stimulation indicating β-cell dysfunction.
authors.affiliation: Department of Pediatric Endocrinology and Diabetology, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Carlotta
authors.initials: C
authors.lastname: von Berghes
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant
authors.forename: Heike
authors.initials: H
authors.lastname: Biebermann
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
authors.forename: Susanna
authors.initials: S
authors.lastname: Wiegand
mesh_terms: D000293:Adolescent; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006801:Humans; D007223:Infant; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000208:ethnology; D011384:Proinsulin / Q000097:blood*; D011627:Puberty; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D011384:Proinsulin