LDL from obese patients with the metabolic syndrome show increased lipid peroxidation and activate platelets.

AIMS/HYPOTHESIS: This study assessed oxidative stress in LDL from obese patients with the metabolic syndrome and compared it with that in LDL from type 2 diabetic patients or control volunteers. It also determined the effect on platelets of LDL from the three groups. METHODS: The profiles of lipids, fatty acids and fatty acid oxidation products were determined in LDL isolated from plasma of patients with the metabolic syndrome, patients with type 2 diabetes and volunteers (n = 10 per group). The effects of LDL from the participant groups on the platelet arachidonic acid signalling cascade and aggregation were investigated. RESULTS: Compared with LDL from control volunteers, LDL from obese metabolic syndrome and type 2 diabetic patients had lower cholesteryl ester, higher triacylglycerol and lower ethanolamine plasmalogen levels. Proportions of linoleic acid were decreased in phosphatidylcholine and cholesteryl esters in LDL from both patient groups. Among the markers of lipid peroxidation, oxidation products of linoleic acid (hydroxy-octadecadienoic acids) and malondialdehyde were increased by 59% and twofold, respectively in LDL from metabolic syndrome and type 2 diabetic patients. LDL from metabolic syndrome and type 2 diabetic patients were equally potent in activating the platelet arachidonic acid signalling cascade through increased phosphorylation of p38 mitogen-activated protein kinase and cytosolic phospholipase A(2), and through increased thromboxane B(2) formation. LDL from patients with the metabolic syndrome and type 2 diabetes potentiated platelet aggregation by threefold and 3.5-fold respectively, whereas control LDL had no activating effects on platelets. CONCLUSIONS/INTERPRETATION: The metabolic syndrome in obese patients, without or with diabetes, is associated with increased oxidative stress in LDL, which triggers platelet activation.

Glycaemic control and cardiovascular morbi-mortality: the contribution of the 2008 studies.

The year 2008 was rich in teachings and suspense in diabetology. Past studies, i.e. United Kingdom Prospective Diabetes Study (UKPDS) in type 2 diabetic patients and Diabetes Control and Complications Trial (DCCT) in type 1 diabetic patients, have shown that in the short term, intensive treatment reduces the incidence of microvascular complications linked to diabetes and in the long term that of both microvascular and macrovascular ones. The in-the-raw conclusions of the recent Action to Control Cardiovascular risk in Diabetes (ACCORD) study note an increase in mortality in type 2 diabetic patients treated intensively, while the Action in Diabetes and Vascular disease, Perindopril and Indapamide Controlled Evaluation (ADVANCE) study evidences a reduction in microvascular complications and the Veterans Affairs Diabetes Trial (VADT) study shows that intensive treatment has no significant effect. A well thought-out analysis of the studies published in 2008 (ACCORD, STENO 2 post-trial, ADVANCE, VADT, UKPDS post-trial, Epidemiology of Diabetes Interventions and Complications [EDIC]) is particularly instructive and highlights the existence of glycaemic memory, the non-existence of blood pressure memory, the need to control all cardiovascular risk factors and to treat diabetes early while avoiding hypoglycaemic incidents. The glycaemic target based on HbA1c must take into account the patient's age and the duration of his diabetes, as well as his cardiovascular risk factors and previous glycaemic control. All in all, the intensive treatment of type 2 diabetes must begin early; it must not be too rapid and must avoid hypoglycaemic incidents and be combined with a strict control of other cardiovascular risk factors.