Lipoprotein metabolism and macrovascular disease in non-insulin dependent diabetes mellitus.

A case control study comparing fasting lipid and apolipoprotein concentrations in NIDDM patients and normal control subjects matched for age, sex and body mass, reveals abnormalities of high density lipoproteins and apolipoprotein B containing lipoproteins despite hypoglycaemic therapy. HDL cholesterol concentration is reduced in these NIDDM patients, whilst apolipoprotein concentrations are similar to the controls. Therefore HDL particles may be cholesterol poor, possibly reflecting reduced reverse cholesterol transport. LDL cholesterol concentration may also be reduced in these patients whilst apolipoprotein B concentrations are similar to controls. Therefore cholesterol content of apo B containing lipoproteins may also be reduced in these patients, helped by their low fat high fibre diets and relatively good glycaemic control. The ratio of HDL cholesterol to non HDL cholesterol is reduced in the NIDDM patients suggesting continued atherosclerotic risk, but the apo AI:apo B ratio is normal. The relationship between these two risk ratios is altered in the NIDDM patients and they therefore require reassessment as risk indices in such patients. Simple assay systems reveal lipoprotein compositional abnormalities and may be useful in the management of NIDDM patients. Fasting lipoprotein abnormalities are also shown to be associated with macrovascular disease in treated NIDDM patients. An association is seen between the presence of macrovascular disease and increased serum triglyceride concentrations and a low apoB:non HDL cholesterol ratio suggesting relative cholesterol enrichment of apo B containing lipoproteins. Associations with macrovascular disease are also seen with a higher body mass, increased systolic blood pressure and smoking. In male NIDDM patients studied the presence of macrovascular disease is associated with a high HbA1 in addition to the above factors but not with BMI. In multivariate analysis in addition to the above factors a high non HDL cholesterol is associated with macrovascular disease in all patients or male patients alone, as is a low HDL cholesterol and high apo AI:HDL cholesterol ratio suggesting cholesterol poor HDL particles in male patients. Smoking habit and a high cholesterol content of apo B containing lipoproteins are independently associated with macrovascular disease in the whole group or in male patients alone. The precise lipoprotein subfraction abnormality underlying this abnormal ratio is unclear. Smoking combines with lipoprotein abnormalities to increase the risk of macrovascular disease in these patients. No other potential risk factors are associated with macrovascular disease in the patients studied. Lipoprotein concentration and composition changes postprandially. Following a normal mixed meal there is a similar rise in triglyceride rich lipoproteins and fall in LDL and HDL cholesterol content in treated NIDDM patients and normal subjects of similar age and body mass. The postprandial increase in HDL triglyceride seen in normal subjects is less apparent in NIDDM patients but their LDL and HDL are already slightly triglyceride rich in the fasted state. Thus the reductions in cholesterol in LDL and HDL in these patients enhances the triglyceride richness of their core, and thus may exacerbate the atherogenic nature of these particles. The rise in TRL is related to glycaemia. NIDDM patients with coronary artery disease have abnormal fasting lipoprotein concentration and composition but these abnormalities are accentuated in the postprandial state, when compared to similarly treated NIDDM patients with no detectable macrovascular disease. They have a greater postprandial increase in triglyceride rich lipoprotein triglyceride, and a greater reduction in HDL cholesterol despite similar fasting HDL cholesterol levels. HDL triglyceride is increased in the fasting and postprandial state in patients with coronary artery disease compared to those with no macrovascular disease. Despite differences in fasting LDL concentrations between these two groups postprandially changes in LDL are similar. Patients with coronary artery disease also have worse glycaemic control and higher insulinaemia. An association is therefore described between macrovascular disease and potentially atherogenic lipoprotein abnormalities both in the fasting state and postprandially in NIDDM patients treated with diet alone or diet and sulphonylureas. (Abstract shortened by UMI.).