TY - JOUR

T1 - Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?

AU - Faerch, K

AU - Borch-Johnsen, K

AU - Holst, Jens Juul

AU - Vaag, A

N1 - Keywords: Blood Glucose; Diabetes Mellitus, Type 2; Exercise; Fasting; Female; Glucose Intolerance; Heart Rate; Hemoglobin A, Glycosylated; Humans; Insulin; Jogging; Male; Middle Aged; Obesity; Overweight; Prediabetic State; Skiing; Walking

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1007/s00125-009-1443-3

DO - 10.1007/s00125-009-1443-3

M3 - Journal article

C2 - 19590846

VL - 52

SP - 1714

EP - 1723

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 9

ER -