title: Independent relationships of obesity and insulin resistance with serum proinsulin level in prepubertal children with normal glucose tolerance.
abstract: OBJECTIVE
  We compared the fasting serum proinsulin levels in lean, overweight, and obese prepubertal children with normal glucose tolerance (NGT). We also evaluated the relationship between fasting proinsulin level and indices of insulin resistance (IR).
  
  
  METHODS
  One hundred nine prepubertal children (mean age, 8.6 yr) with NGT were included. The indices of IR included the homeostasis model assessment of IR (HOMA-IR) and adiponectin level. We recorded the presence of one or more of the following metabolic derangements: triglycerides ≥ 150 mg/dL, HDL-cholesterol < 35 mg/dL, and hypertension.
  
  
  RESULTS
  Fasting proinsulin levels significantly increased with body mass index (BMI) category from lean (n = 52, 7.22 ± 3.01 pmol/L) to overweight (n = 14, 12.31 ± 2.91 pmol/L) to obese (n = 43, 16.51 ± 7.27 pmol/L) (p < 0.001), after controlling for HOMA-IR. The ratio of the fasting levels of proinsulin to insulin did not differ significantly between the three groups. Both BMI z-score and HOMA-IR were significant independent factors related to the fasting proinsulin level (p < 0.001 for each). A significant inverse association was found between fasting proinsulin level and adiponectin level (r = -0.464, p < 0.001). Children with NGT who had at least one metabolic derangement had higher proinsulin levels than those without metabolic derangement.
  
  
  CONCLUSIONS
  Obesity itself or obesity-related IR may independently impose β-cell overload on prepubertal children with NGT, leading to hyperproinsulinemia without causing failure to convert proinsulin to insulin when some degree of IR and metabolic derangement appears.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Pediatrics, Seoul National University College of Medicine, Seoul 110-769, Republic of Korea.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Yoo
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Han Hyuk
authors.initials: HH
authors.lastname: Lim
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Kang
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Chung
authors.forename: Seong Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Choong Ho
authors.initials: CH
authors.lastname: Shin
authors.forename: Sei Won
authors.initials: SW
authors.lastname: Yang
mesh_terms: D052242:Adiponectin / Q000097:blood; D002648:Child; D005260:Female; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood*; D011384:Proinsulin / Q000097:blood*
chemical_list: D052242:Adiponectin; D011384:Proinsulin