Longitudinal Progression of Beta Cell Dysfunction: Comparison of a Direct Method vs. a Fasting Surrogate Measure. The Insulin Resistance Atherosclerosis Study (IRAS)
Abstract Number: 1005-P
Authors: STEVEN M. HAFFNER, ANDREAS FESTA, LYNNE E. WAGENKNECHT, ANTHONY J. HANLEY
Institutions: San Antonio, TX, Winston-Salem, NC, Toronto, Canada
Results: Pancreatic beta cell dysfunction is a core disorder in the pathogenesis of type 2 diabetes mellitus (T2DM). In addition to being a significant predictor of T2DM, beta cell function (BCF) is known to decline over the course of the disease, with UKPDS data suggesting a 50% loss of BCF at the time of T2DM diagnosis. However, only limited longitudinal data are available regarding changes in BCF across glucose tolerance status (GTS) categories, and few studies have compared direct vs. surrogate measures. Our objective, therefore, was to compare longitudinal changes in BCF using a direct method vs. a fasting surrogate measure. We used data on 1304 subjects from the baseline and 5-year follow up exams of IRAS. Subjects were categorized according to baseline GTS: NGT (n=547), IFG/IGT (n=341), T2DM (n=416). BCF was assessed using the acute insulin response (AIR) from a frequently sampled intravenous glucose tolerance test as well as the homeostasis model assessment of BCF (HOMA B), with changes over time calculated as follow-up minus baseline and transformations used to normalize distributions as appropriate. Change in HOMA B was modestly correlated with change in AIR (r=0.15 p<0.001). In crude analysis, NGT and IFG/IGT subjects increased their BCF over 5 years (161 to 185 and 168 to 185, respectively, for HOMA B, and 73 to 98 and 56 to 63 µU/ml, respectively, for AIR), while those with T2DM experienced little change (HOMA B: 100.1 to 97.8; AIR: 27.5 to 28.7 µU/ml). After adjustment for age, insulin sensitivity (Si) declined over time in all groups. We therefore further adjusted for sex, ethnicity and change in fasting insulin or Si, and found that change in HOMA B underestimated the magnitude of changes in BCF as assessed by change in AIR. Relative to NGT, change in BCF in IFG/IGT and T2DM was 33 and 30% lower (by HOMA B) and 54 and 82% lower (by AIR), respectively. In conclusion, surrogate BCF measures may underestimate BCF changes in both subjects with IFG/IGT and T2DM.