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- Title
Β-Cell Dysfunction in Subjects With Impaired Glucose Tolerance and Early Type 2 Diabetes.
- Authors
Festa, Andreas; Williams, Ken; Hanley, Anthony J. G.; Haffner, Steven M.
- Abstract
OBJECTIVE--Methods to assess β-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. RESEARCH DESIGN AND METHODS--In 1,380 individuals from the Insulin Resistance Atherosclerosis Study, β-cell function was assessed using a frequently sampled intravenous glucose tolerance test (first-phase insulin secretion; acute insulin response [AIR]), homeostasis model assessment of β-cell function (HOMA-B), proinsulin levels, and the proinsulin-to-insulin ratio. β-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 β-cell defect across declining glucose tolerance, especially for IGT and new DM by OGTT compared with AIR. Analyses adjusting for insulin sensitivity showed that β-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 β-cell defects than previously estimated from epidemiological studies using homeostasis model assessment. Diabetes 57:1638-1644, 2008
- Subjects
CELL physiology; PANCREATIC beta cells; BLOOD sugar; TYPE 2 diabetes; INSULIN; GLUCOSE tolerance tests
- Publication
Diabetes, 2008, Vol 57, Issue 6, p1638
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db07-0954