title: Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?
abstract: Prior to the development of type 2 diabetes, glucose levels increase into the prediabetic states of isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding of the aetiology and pathophysiology of the prediabetic states might give a basis for the development of individualised prevention and treatment strategies for type 2 diabetes. Several studies have examined mechanisms and potential aetiological factors leading to the development of the different prediabetic states. The pathophysiology of i-IFG seems to include the following key defects: reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion and inappropriately elevated glucagon secretion. Conversely, the prediabetic state i-IGT is characterised by reduced peripheral insulin sensitivity, near-normal hepatic insulin sensitivity, progressive loss of beta cell function, reduced secretion of glucose-dependent insulinotropic polypeptide and inappropriately elevated glucagon secretion. Individuals developing combined IFG/IGT exhibit severe defects in both peripheral and hepatic insulin sensitivity as well as a progressive loss of beta cell function. The aetiologies of i-IFG and i-IGT also seem to differ, with i-IFG being predominantly related to genetic factors, smoking and male sex, while i-IGT is predominantly related to physical inactivity, unhealthy diet and short stature. Since the transition from the prediabetic states to overt type 2 diabetes is characterised by a non-reversible vicious cycle that includes severe deleterious effects on glucose metabolism, there are good reasons to use the well-established aetiological and pathophysiological differences in i-IFG, i-IGT and IFG/IGT to design individualised preventive strategies.
authors: Steno Diabetes Center, Niels Steensens Vej 2, 2820, Gentofte, Denmark. krif@steno.dk
authors: K
authors: K
authors: Faerch
authors: K
authors: K
authors: Borch-Johnsen
authors: J J
authors: JJ
authors: Holst
authors: A
authors: A
authors: Vaag
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control* / Q000628:therapy*; D015444:Exercise / Q000502:physiology*; D005215:Fasting; D005260:Female; D018149:Glucose Intolerance / Q000517:prevention & control*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007590:Jogging / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D050177:Overweight / Q000503:physiopathology* / Q000534:rehabilitation*; D011236:Prediabetic State / Q000097:blood / Q000503:physiopathology; D012865:Skiing; D016138:Walking / Q000502:physiology
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin