Incretin-based therapies for treatment of postprandial dyslipidemia in insulin-resistant states.

Abstract

PURPOSE OF REVIEW:

In prediabetes and diabetes, hyperglycemia is often accompanied by fasting and postprandial hyperlipidemia. Incretin-based therapies are in increasing clinical use for treating hyperglycemia, but recent evidence emphasizes their ability to improve lipoprotein abnormalities. This is significant as heightened postprandial chylomicron levels during insulin resistance contribute to atherogenic diabetic dyslipidemia. This review summarises the evidence supporting a beneficial effect of incretin-based therapies on diabetic dyslipidemia through modulation of intestinal lipoprotein metabolism.

RECENT FINDINGS:

Preclinical and clinical trials have involved administering dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists to healthy and insulin-resistant individuals. Results indicate that enhancing GLP-1R signalling decreases postprandial apoB48-containing triglyceride-rich lipoproteins. These effects may be direct or may be secondary to reduced gastric emptying, increased insulin secretion, or enhanced chylomicron clearance.

SUMMARY:

Enhancing GLP-1R activity improves intestinal lipoprotein metabolism. GLP-1-mediated control of postprandial chylomicron production may be lost in type 2 diabetes in which the incretin response is impaired and in which associated dyslipidemia involves an excess of atherogenic chylomicron remnants. Further human studies are needed to better establish the impact of incretin-based therapies on dyslipidemia, as this offers a major new therapeutic approach to reduce cardiovascular risk in type 2 diabetic patients.

• Authors: Sarah Farr, Khosrow Adeli
• Journal: Current opinion in lipidology (Curr Opin Lipidol) Vol. 23 Issue 1 Pg. 56-61 (Feb 2012) ISSN: 1473-6535 [Electronic] England
• PMID: 22123671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Chylomicrons
• Incretins
• Glucagon-Like Peptide 1

Topics

• Animals
• Chylomicrons (metabolism)
• Dyslipidemias (drug therapy)
• Glucagon-Like Peptide 1 (pharmacology, therapeutic use)
• Humans
• Hyperglycemia (drug therapy)
• Incretins (pharmacology, therapeutic use)
• Insulin Resistance
• Intestinal Absorption (drug effects)
• Lipid Metabolism (drug effects)
• Postprandial Period