The effect of antidiabetic drugs on genes regulating lipid metabolism.
OBJECTIVE
Hyperglycaemia and dyslipidaemia are closely linked, yet, there has been difficulty in demonstrating that lowering blood sugar reduces cardiovascular events. The pathways linking abnormalities in fatty acid metabolism, insulin resistance and diabetes with abnormalities in cholesterol metabolism are being rapidly unravelled with new understandings of the effect of antidiabetic drugs on lipoprotein metabolism. The purpose of this review is to explore the recent literature.


RESULTS
Postprandial lipoproteins are now firmly established as a postprandial risk factor. Both insulin resistance and diabetes are associated with abnormalities in chylomicron production, and clearance and regulatory genes have been identified. Metformin, the most commonly used drug in type 2 diabetes, has multiple actions affecting numerous genes. The peroxisome proliferator-activated receptor-gamma regulation of insulin sensitivity and the important effects on lipoproteins are described. The entero-insulin axis and glucagon-like peptide-1 agonists, together with inhibitors of dipeptidyl peptidase 4 may have lipoprotein implications, but the evidence at present is sparse even though glucagon-like peptide-1 is found in high concentrations in the lymph.


CONCLUSIONS
Although antidiabetic drugs affect lipid metabolism, there is little evidence to suggest that these drugs can prevent atherosclerosis in diabetes and some may promote atherosclerosis through their adverse effect on lipoproteins.
Tomkin
Gerald H
GH
Diabetes Institute of Ireland, Beacon Hospital, Dublin, Ireland. gerald.tomkin@tcd.ie
D000818:Animals; D004150:Dipeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics*
D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1; D004150:Dipeptidases