Therapeutic association of atorvastatin and insulin in cardiac ischemia: study in a model of type 2 diabetes with hyperlipidemia.
Combination therapy recently emerged as a potential therapeutic option in order to improve cardiovascular risk in diabetics, since therapies commonly used in monotherapy failed in significantly optimizing this risk.


METHODS
A type 2 diabetes animal model was used to test the effects of a high-fat diet, atorvastatin and insulin (isolated or in association), in glycemic, lipid and inflammatory profiles, oxidative stress markers and cardiac mitochondrial function in ischemia-reperfusion conditions.


RESULTS
High-fat diets significantly worsened fasting glycemia and lipid profile; it also increased C-reactive protein (CRP) and oxidative stress and compromised mitochondrial response to ischemia. Insulin decreased fasting glucose and free fatty acid levels and insulin resistance, while increasing HDL-cholesterol, but had no effect in inflammatory markers. Atorvastatin decreased circulating adiponectin levels and did not improve inflammatory markers, although it improved fasting glycemia, glucose tolerance, free fatty acids and HDL-cholesterol. The combined use of atorvastatin and insulin improved several parameters, as did each of the treatments separately. However, treatment association went beyond these results, by decreasing atherogenicity index and circulating CRP levels. Insulin and its association with atorvastatin significantly prevented mitochondrial dysfunction observed in the high-fat diet group, while atorvastatin showed some beneficial effects but in much less extent.


CONCLUSIONS
Altogether, these results show that administration of an high-fat diet in a model of type 2 diabetes increases cardiovascular risk and combined use of atorvastatin and insulin provides a superior control of cardiovascular risk markers in diabetic and hyperlipidemic subjects.
Matafome
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Institute of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. paulomatafome@gmail.com
Monteiro
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Nunes
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Gonçalves
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D052242:Adiponectin / Q000097:blood; D000818:Animals; D000069059:Atorvastatin; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004041:Dietary Fats / Q000494:pharmacology; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D066298:In Vitro Techniques; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010477:Perfusion; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D004041:Dietary Fats; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin