Lowering cardiovascular disease risk in type 2 diabetes: novel studies of postprandial lipoprotein metabolism

[Truncated abstract] Patients with type 2 diabetes often have hypertriglyceridaemia, low high-density lipoprotein (HDL) cholesterol and a preponderance of small, dense low density lipoprotein (LDL) particles that result from dysregulated lipoprotein metabolism. Contributing to this, postprandial lipaemia is prolonged and has been identified as an independent risk factor that contributes to cardiovascular disease (CVD). Nicotinic acid (Niacin) effectively reduces postprandial chylomicron (CM) concentrations and raises HDL. Its use has been limited by flushing, but extended release formulations have improved tolerability. The mechanism of action of niacin on CM and HDL metabolism has not been studied in type 2 diabetic patients. Few studies have examined the effect of niacin on lipoprotein kinetics; these have been inconclusive and have been undertaken in very small groups of subjects with mixed hyperlipidaemia. Hence, the present work examines and discusses the effect of niacin on the metabolism of CM and HDL. This thesis tests the general hypothesis that apolipoprotein kinetics are adversely altered in well-controlled type 2 diabetic patients receiving optimal statin therapy, and that niacin can ameliorate these kinetic abnormalities. The aims were first, to describe and compare the clinical, metabolic and kinetic differences between statin-treated type 2 diabetic patients and normolipidaemic lean subjects; second, to determine the effects of the addition of niacin on apolipoprotein kinetics. Four specific hypotheses were developed from the general hypothesis and are examined in the studies described in this thesis. Study 1 (Chapter 4) comprised a case-control study of twelve statin-treated men with type 2 diabetes and fourteen lean normolipidaemic men.