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Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents

Antonino Di Pino1, Ralph A DeFronzo1

  • 1Diabetes Division, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, Texas.

Endocrine Reviews
|May 4, 2019
PubMed

Insights

Patients with type 2 diabetes mellitus face high cardiovascular risk. Insulin resistance and the insulin resistance syndrome contribute to this risk, but insulin-sensitizing drugs like pioglitazone may reduce cardiovascular events.

Area of Science:

  • Endocrinology
  • Cardiology
  • Metabolic Syndrome

Background:

  • Type 2 diabetes mellitus (T2DM) patients have a high risk of macrovascular complications, a leading cause of mortality.
  • Despite managing traditional cardiovascular (CV) risk factors, a significant unexplained CV risk persists in T2DM.
  • Insulin resistance and the associated insulin resistance syndrome (IRS) are linked to this residual CV risk.

Purpose of the Study:

  • To review the contribution of insulin resistance and IRS to atherosclerotic cardiovascular disease in T2DM.
  • To discuss the impact of insulin-sensitizing agents, specifically pioglitazone, on CV outcomes.
  • To examine the effects of other antihyperglycemic medications on CV outcomes in T2DM.

Main Methods:

  • Review of existing scientific literature and clinical trial data.
  • Analysis of evidence linking insulin resistance and IRS to cardiovascular events.
  • Evaluation of cardiovascular outcome trials for pioglitazone and other antidiabetic medications.

Main Results:

  • Insulin resistance and IRS are implicated as contributors to unexplained CV risk in T2DM.
  • Pioglitazone, an insulin-sensitizing thiazolidinedione, has demonstrated a reduction in CV events in high-risk T2DM patients.
  • The review discusses the CV effects of various antihyperglycemic agents.

Conclusions:

  • Insulin resistance and IRS play a significant role in the development of cardiovascular disease in T2DM.
  • Insulin-sensitizing agents show promise in mitigating CV risk in T2DM patients.
  • Further research into the CV effects of different antihyperglycemic medications is warranted.

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