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

K. Færch, A. Vaag, J. J. Holst, C. Glümer, O. Pedersen, K. Borch-Johnsen

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    Abstrakt

    Aims/hypothesis: 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≥0.179). Individuals with i-IGT had peripheral insulin resistance (p=0.003 vs NGT), and consequently the disposition index (DI; insulin secretion×insulin sensitivity) during IVGTT (DIIVGTT)) was reduced in both i-IFG and i-IGT (p<0.005 vs NGT). In contrast, the DI during OGTT (DIOGTT) 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≤0.001 vs NGT). Conclusions/interpretation: We propose that differentiated preventive initiatives in prediabetic individuals should be tested, targeting the specific underlying metabolic defects.

    OriginalsprogEngelsk
    Sider (fra-til)853-861
    Antal sider9
    TidsskriftDiabetologia
    Vol/bind51
    Udgave nummer5
    DOI
    StatusUdgivet - 1 maj 2008

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