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Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin

Andreas Festa1, Anthony J G Hanley, Russell P Tracy

  • 1Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Tex 78229-3900, USA.

Circulation
|October 1, 2003
PubMed
Summary
This summary is machine-generated.

Prediabetic individuals with insulin resistance show higher inflammatory protein levels, indicating increased cardiovascular disease risk. Those with primary beta-cell defects do not exhibit this heightened proinflammatory state.

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Area of Science:

  • Endocrinology
  • Cardiovascular Medicine
  • Metabolic Syndrome

Background:

  • Elevated proinflammatory proteins predict cardiovascular disease and type 2 diabetes.
  • Atherogenic changes in prediabetes were previously linked more to insulin resistance than impaired insulin secretion.

Purpose of the Study:

  • To investigate the relationship between inflammatory markers and defects in insulin sensitivity and secretion in prediabetic individuals.
  • To determine if insulin resistance or impaired insulin secretion in prediabetes is associated with a proinflammatory state.

Main Methods:

  • Analysis of C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-1, and fibrinogen levels in prediabetic individuals from the Insulin Resistance Atherosclerosis Study (IRAS).
  • Assessment of insulin sensitivity (SI) and first-phase insulin secretion using a frequently sampled intravenous glucose tolerance test.
  • Comparison of inflammatory markers between insulin-resistant and insulin-sensitive prediabetic individuals, and those who did or did not develop diabetes.

Main Results:

  • Prediabetic individuals with insulin resistance had significantly higher levels of PAI-1 and CRP compared to insulin-sensitive individuals.
  • Prediabetic subjects with predominant insulin resistance exhibited higher inflammatory protein levels than those with decreased insulin secretion or non-converters.
  • No significant difference in inflammatory protein levels was observed between prediabetic subjects with primary defects in insulin secretion and non-converters.

Conclusions:

  • An increased proinflammatory state is evident in prediabetic individuals with predominant insulin resistance, but not in those with primary beta-cell dysfunction.
  • These findings suggest that prediabetic subjects with high insulin resistance are at increased risk for heart disease.
  • The study highlights the distinct pathophysiological pathways contributing to cardiovascular risk in prediabetes.