title: Beta-cell dysfunction in subjects with impaired glucose tolerance and early type 2 diabetes: comparison of surrogate markers with first-phase insulin secretion from an intravenous glucose tolerance test.
abstract: OBJECTIVE
  Methods to assess beta-cell function in clinical studies are limited. The aim of the current study was to compare a direct measure of insulin secretion with fasting surrogate markers in relation to glucose tolerance status.
  
  
  METHODS
  In 1,380 individuals from the Insulin Resistance Atherosclerosis Study, beta-cell function was assessed using a frequently sampled intravenous glucose tolerance test (first-phase insulin secretion; acute insulin response [AIR]), homeostasis model assessment of beta-cell function (HOMA-B), proinsulin levels, and the proinsulin-to-insulin ratio. Beta-cell function was cross-sectionally analyzed by glucose tolerance categories (normal glucose tolerance [NGT], n = 712; impaired glucose tolerance [IGT], n = 353; newly diagnosed diabetes by 2-h glucose from an oral glucose tolerance test [OGTT] [DM2h], n = 80; newly diagnosed diabetes by fasting glucose [DMf], n = 135; or newly diagnosed diabetes by fasting and 2-h glucose and established diabetes on diet/exercise only [DM], n = 100).
  
  
  RESULTS
  In Spearman correlation analyses, proinsulin and the proinsulin-to-insulin ratio were only modestly inversely related to AIR (r values from -0.02 to -0.27), and AIR was strongly related to HOMA-B (r values 0.56 and 0.58). HOMA-B markedly underestimated the magnitude of the beta-cell defect across declining glucose tolerance, especially for IGT and new DM by OGTT compared with AIR. Analyses adjusting for insulin sensitivity showed that beta-cell function was compromised in IGT, DM2h, DMf, and DM, relative to NGT, by 13, 12, 59, and 62% (HOMA-B) and by as much as 40, 60, 80, and 75%, using AIR.
  
  
  CONCLUSIONS
  Subjects with IGT and early-stage, asymptomatic type 2 diabetic patients have more pronounced beta-cell defects than previously estimated from epidemiological studies using homeostasis model assessment.
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Festa
authors.forename: Ken
authors.initials: K
authors.lastname: Williams
authors.forename: Anthony J G
authors.initials: AJ
authors.lastname: Hanley
authors.forename: Steven M
authors.initials: SM
authors.lastname: Haffner
mesh_terms: D000368:Aged; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000378:metabolism; D012016:Reference Values; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin; D005947:Glucose