Impaired fasting glucose with or without impaired glucose tolerance: progressive or parallel states of prediabetes?

Our objective was to determine whether defects underlying impaired fasting glucose (IFG) are maintained and additive when combined with impaired glucose tolerance (IGT) (representing a progressive form of prediabetes) or are distinct in IFG/IGT (reflecting a parallel form of prediabetes). Volunteers with IFG (n = 10), IFG/IGT (n = 14), or normal glucose tolerance (NGT; n = 15) were matched for demographics and anthropometry. Insulin secretion was assessed using the glucose step-up protocol and insulin action through the use of a two-stage hyperinsulinemic euglycemic clamp with infusion of [6,6-(2)H(2)]glucose. Modeling of insulin secretory parameters revealed similar basal (Phi(b)) but diminished dynamic (Phi(d)) components in both IFG and IFG/IGT (P = 0.05 vs. NGT for both). Basal glucose rate of appearance (R(a)) was higher in IFG compared with NGT (P < 0.01) and also, surprisingly, with IFG/IGT (P < 0.04). Moreover, glucose R(a) suppressed more during the low-dose insulin clamp in IFG (P < 0.01 vs. NGT, P = 0.08 vs. IFG/IGT). Insulin-stimulated glucose uptake [glucose rate of disappearance (R(d))] was similar in IFG, IFG/IGT, and NGT throughout the clamp. We conclude that nuances of beta-cell dysfunction observed in IFG were also noted in IFG/IGT. A trend for additional insulin secretory defects was observed in IFG/IGT, possibly suggesting progression in beta-cell failure in this group. In contrast, basal glucose R(a) and its suppressability with insulin were higher in IFG, but not IFG/IGT, compared with NGT. Together, these data indicate that IFG/IGT may be a distinct prediabetic syndrome rather than progression from IFG.

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