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.
Perreault
Leigh
L
Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045, USA. leigh.perreault@uchsc.edu
Bergman
Bryan C
BC
Playdon
Mary C
MC
Dalla Man
Chiara
C
Cobelli
Claudio
C
Eckel
Robert H
RH
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin