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

Diabetologia. 2009 Sep;52(9):1714-23. doi: 10.1007/s00125-009-1443-3. Epub 2009 Jul 10.

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.

MeSH terms

  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Diabetes Mellitus, Type 2 / therapy*
  • Exercise / physiology*
  • Fasting
  • Female
  • Glucose Intolerance / prevention & control*
  • Glycated Hemoglobin / metabolism
  • Heart Rate / physiology
  • Humans
  • Insulin / physiology
  • Jogging / physiology
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / physiopathology
  • Overweight / physiopathology*
  • Overweight / rehabilitation*
  • Prediabetic State / blood
  • Prediabetic State / physiopathology
  • Skiing
  • Walking / physiology

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin