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 |
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Authors: | K Færch A Vaag J J Holst C Glümer O Pedersen K Borch-Johnsen |
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Institution: | (1) Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark;(2) Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark;(3) Research Centre for Prevention and Health, Glostrup, Capital Region of Denmark, Denmark;(4) University of Aarhus, Aarhus, Denmark |
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Abstract: | 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. |
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Keywords: | Disposition index Glucagon Impaired fasting glycaemia Impaired glucose tolerance Incretin hormones Insulin secretion Insulin sensitivity Pathophysiology Prediabetes |
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