title: Studying progression from glucose intolerance to type 2 diabetes in obese children.
abstract: OBJECTIVE
  Identification of metabolic and genetic factors capable to mediate progression from normal glucose tolerance (NGT) through impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in childhood obesity.
  
  
  METHODS
  Three groups of obese children with NGT (n=54), IGT (n=35), and T2D (n=62) were evaluated. A control group of non-obese normal children (n=210) was also studied. In obese patients, an oral glucose tolerance test (OGTT) was performed. Insulin resistance (IR) was assessed using HOMA-IR index. Insulin sensitivity (IS) was assessed according to the Matsuda formula. Genomic DNA from obese and control children was genotyped for genetic variants of PPARG, ADIPOQ, ADIPOR1, FTO, TCF7L2, and KCNJ11 using a real-time PCR strategy. The unpaired Student's t-test and Kruskal-Wallis one-way test were used to compare quantitative data in two and more groups. To assess the extent to which the various genetic variants were associated with pathology, ORs (odds ratios) and 95% CI (confidence interval) were estimated.
  
  
  RESULTS
  In T2D children, HOMA-IR value (7.5±3.1) was significantly (P<0.001) higher than that in IGT (4.21±2.25) and NGT (4.1±2.4) subjects. The Matsuda IS index was significantly increased in normoglycemic patients compared to IGT individuals (2.8±1.75 vs. 2.33±1.2, P<0.05). The Pro12Ala polymorphism of PPARG was significantly associated with obesity (OR=1.74, 95% CI=1.19-2.55, P=0.004) and T2D in obesity (OR=2.01, 95% CI=1.24-3.26, P=0.004).
  
  
  CONCLUSIONS
  IR is a major risk factor that mediates progression from NGT to clinical T2D in Russian obese children. This progression may be genetically influenced by the Pro12Ala variant of PPARG.
authors.affiliation: Department of Pediatrics, Endocrinology Research Center, Moscow, Russia.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Dubinina
authors.affiliation: Department of Medical Bionanotechnology, Pirogov Russian State Medical University, Moscow, Russia. Electronic address: dimitry.chistiakov@lycos.com.
authors.forename: Dimitry A
authors.initials: DA
authors.lastname: Chistiakov
authors.affiliation: Department of Pediatrics, Endocrinology Research Center, Moscow, Russia.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Eremina
authors.affiliation: Federal Research Clinical Center of Federal Medical and Biological Agency of Russia, Moscow, Russia.
authors.forename: Alexei N
authors.initials: AN
authors.lastname: Brovkin
authors.affiliation: Department of Pediatrics, Endocrinology Research Center, Moscow, Russia.
authors.forename: Lyubov I
authors.initials: LI
authors.lastname: Zilberman
authors.affiliation: Federal Research Clinical Center of Federal Medical and Biological Agency of Russia, Moscow, Russia.
authors.forename: Alexei G
authors.initials: AG
authors.lastname: Nikitin
authors.affiliation: Department of Pediatrics, Endocrinology Research Center, Moscow, Russia.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Kuraeva
authors.affiliation: Federal Research Clinical Center of Federal Medical and Biological Agency of Russia, Moscow, Russia.
authors.forename: Valery V
authors.initials: VV
authors.lastname: Nosikov
authors.affiliation: Department of Pediatrics, Endocrinology Research Center, Moscow, Russia.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Peterkova
authors.affiliation: Department of Pediatrics, Endocrinology Research Center, Moscow, Russia.
authors.forename: Ivan I
authors.initials: II
authors.lastname: Dedov
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002648:Child; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D047495:PPAR gamma / Q000378:metabolism*; D063766:Pediatric Obesity / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012426:Russia / Q000453:epidemiology
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D047495:PPAR gamma; C517652:hemoglobin A1c protein, human
keywords: Glucose tolerance; Insulin resistance; Insulin sensitivity; Obesity; PPARG