title: Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study.
abstract: OBJECTIVE
  To investigate insulin sensitivity and secretion indices and determinants of glycemic control in youth with recent-onset type 2 diabetes (T2DM) at randomization in the TODAY study, the largest study of youth with T2DM to date.
  
  
  METHODS
  We examined estimates of insulin sensitivity [1/fasting insulin (1/I(F)), fasting glucose/insulin (G(F) /I(F)), 1/fasting C-peptide (1/C(F)), G(F) /C(F)], β-cell function [insulinogenic index (ΔI30/ΔG30), and ΔC30/ΔG30], and disposition index (DI) in the TODAY cohort of 704 youth (14.0 ± 2.0 yr; diabetes duration 7.8 ± 5.8 months; 64.9% female; 41.1% Hispanic, 31.5% Black, 19.6% White, 6.1% American Indian, and 1.7% Asian) according to hemoglobin A1c (HbA1c) quartiles at study randomization. The randomization visit followed a run-in period (median 71 d) during which glycemic control (HbA1c ≤ 8% for at least 2 months) was achieved with metformin alone. These measures were also examined in relation to screening HbA1c levels before run-in.
  
  
  RESULTS
  Insulin secretion indices declined with increasing HbA1c quartiles, at randomization (ΔC30/ΔG30: 0.11 ± 0.09, 0.10 ± 0.19, 0.07 ± 0.06, and 0.03 ± 0.03 ng/mL per mg/dL, p < 0.0001; DI: 0.03 ± 0.03, 0.03 ± 0.05, 0.02 ± 0.02, and 0.01 ± 0.01 mg/dL(-1) , p < 0.0001) and at screening, with no significant difference in insulin sensitivity. There were no significant differences in estimates of insulin sensitivity or secretion between genders or across the different racial groups. At randomization and screening, HbA1c correlated with DI (r = -0.3, p < 0.001), with ΔC30/ΔG30, but not with insulin sensitivity estimates.
  
  
  CONCLUSIONS
  In youth with recent-onset T2DM treated with metformin, glycemic control, as measured by HbA1c, appears to be associated with residual β-cell function and not insulin sensitivity.
authors.affiliation: Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: Fida
authors.initials: F
authors.lastname: Bacha
authors.forename: Laura
authors.initials: L
authors.lastname: Pyle
authors.forename: Kristen
authors.initials: K
authors.lastname: Nadeau
authors.forename: Leona
authors.initials: L
authors.lastname: Cuttler
authors.forename: Robin
authors.initials: R
authors.lastname: Goland
authors.forename: Morey
authors.initials: M
authors.lastname: Haymond
authors.forename: Lynne
authors.initials: L
authors.lastname: Levitsky
authors.forename: Jane
authors.initials: J
authors.lastname: Lynch
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Weinstock
authors.forename: Neil H
authors.initials: NH
authors.lastname: White
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
authors.forename: Silva
authors.initials: S
authors.lastname: Arslanian
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D011897:Random Allocation
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D008687:Metformin