Pathogenesis of pre-diabetes: mechanisms of fasting and postprandial hyperglycemia in people with impaired fasting glucose and/or impaired glucose tolerance.
Thirty-two subjects with impaired fasting glucose (IFG) and 28 subjects with normal fasting glucose (NFG) ingested a labeled meal and 75 g glucose (oral glucose tolerance test) on separate occasions. Fasting glucose, insulin, and C-peptide were higher (P < 0.05) in subjects with IFG than in those with NFG, whereas endogenous glucose production (EGP) did not differ, indicating hepatic insulin resistance. EGP was promptly suppressed, and meal glucose appearance comparably increased following meal ingestion in both groups. In contrast, glucose disappearance (R(d)) immediately after meal ingestion was lower (P < 0.001) in subjects with IFG/impaired glucose tolerance (IGT) and IFG/diabetes but did not differ in subjects with IFG/normal glucose tolerance (NGT) or NFG/NGT. Net insulin action (S(i)) and insulin-stimulated glucose disposal (S(i)*) were reduced (P < 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT or IFG/NGT. Defective insulin secretion also contributed to lower postprandial R(d) since disposition indexes were lower (P < 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT and IFG/NGT. We conclude that postprandial hyperglycemia in individuals with early diabetes is due to lower rates of glucose disappearance rather than increased meal appearance or impaired suppression of EGP, regardless of their fasting glucose. In contrast, insulin secretion, action, and the pattern of postprandial turnover are essentially normal in individuals with isolated IFG.
Bock
Gerlies
G
Mayo Clinic, 200 1st St. SW, Rm 5-194 Joseph, Rochester, MN 55905, USA.
Dalla Man
Chiara
C
Campioni
Marco
M
Chittilapilly
Elizabeth
E
Basu
Rita
R
Toffolo
Gianna
G
Cobelli
Claudio
C
Rizza
Robert
R
D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000097:blood; D018149:Glucose Intolerance / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011236:Prediabetic State / Q000503:physiopathology*; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon