title: Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action.
abstract: OBJECTIVE
  The impact of strategies for prevention of type 2 diabetes in isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose tolerance (i-IGT) may differ depending on the underlying pathophysiology. We examined insulin secretion during OGTTs and IVGTTs, hepatic and peripheral insulin action, and glucagon and incretin hormone secretion in individuals with i-IFG (n = 18), i-IGT (n = 28) and normal glucose tolerance (NGT, n = 20).
  
  
  METHODS
  Glucose tolerance status was confirmed by a repeated OGTT, during which circulating insulin, glucagon, glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels were measured. A euglycaemic-hyperinsulinaemic clamp with [3-3H]glucose preceded by an IVGTT was performed.
  
  
  RESULTS
  Absolute first-phase insulin secretion during IVGTT was decreased in i-IFG (p = 0.026), but not in i-IGT (p = 0.892) compared with NGT. Hepatic insulin sensitivity was normal in i-IFG and i-IGT individuals (p > or = 0.179). Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and consequently the disposition index (DI; insulin secretion x insulin sensitivity) during IVGTT (DI(IVGTT))) was reduced in both i-IFG and i-IGT (p < 0.005 vs NGT). In contrast, the DI during OGTT (DI(OGTT)) was decreased only in i-IGT (p < 0.001), but not in i-IFG (p = 0.143) compared with NGT. Decreased levels of GIP in i-IGT (p = 0.045 vs NGT) vs increased levels of GLP-1 in i-IFG (p = 0.013 vs NGT) during the OGTT may partially explain these discrepancies. Basal and post-load glucagon levels were significantly increased in both i-IFG and i-IGT individuals (p < or = 0.001 vs NGT).
  
  
  CONCLUSIONS
  We propose that differentiated preventive initiatives in prediabetic individuals should be tested, targeting the specific underlying metabolic defects.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 2, DK-2820, Gentofte, Denmark. krif@steno.dk.
authors.forename: K
authors.initials: K
authors.lastname: Faerch
authors.forename: A
authors.initials: A
authors.lastname: Vaag
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: C
authors.initials: C
authors.lastname: Glümer
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: K
authors.initials: K
authors.lastname: Borch-Johnsen
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D005215:Fasting; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D050416:Glucagon-Secreting Cells / Q000502:physiology*; D018149:Glucose Intolerance / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000502:physiology*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D017202:Myocardial Ischemia / Q000517:prevention & control; D011236:Prediabetic State / Q000097:blood / Q000503:physiopathology / Q000628:therapy
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D054795:Incretins; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide