Examination of the fasting and 2-h plasma glucose in the light of impairment in beta-cell function: what does the epidemiological data tell us?

We re-assess the fasting plasma glucose (FPG) and 2-h post-load glucose (2HPG) in the diagnosis of both prediabetes and type 2 diabetes mellitus by developing a gold standard based on beta-cell function. The gold standard was developed in a cohort of 2,152 adult subjects without severe renal or liver dysfunction that also had a 2-h oral glucose tolerance test (OGTT) during the Third National Health and Nutrition Examination Survey. Beta-cell function was computed based on a composite of insulin secretion (determined based on the insulin and glucose responses to the OGTT) and the homeostasis model insulin resistance index. The X-tile program was used to generate the most appropriate categories of minor, moderate and severe impairment of beta-cell function based on the best discrimination of ln(insulin secretion). Subjects with a moderate or severe impairment in beta-cell function were used to define prediabetes and diabetes, respectively, and was the standard against which the FPG and 2HPG were evaluated. It is shown that the current definitions of diabetes by the FPG and 2HPG mirror those derived using impairment of beta-cell function as the gold standard. It is also shown that lowering the cutoff for the FPG does little to improve its use in the screening for prediabetes. A major finding is that the current 2HPG cutoff is inadequate and thus in need of revision to >6.7 mmol/L (>120 mg/dL) from 7.8 mmol/L (140 mg/dL) for the lower cutoff. The use of a model of beta-cell function and impairment of insulin secretion has thus put the utility of the FPG and 2HPG into perspective: We recommend that performing an OGTT be considered pivotal for accurate identification of subjects with impaired beta-cell function (and thus prediabetes) and a revision of the OGTT lower cutoff be considered based on the results of this study.