Hyperinsulinaemia and hypertriglyceridaemia.

Hyperinsulinaemia and hypertriglyceridaemia are frequently associated. This may be as a part of the syndrome of insulin resistance or in diabetes, particularly non-insulin-dependent diabetes (NIDDM). The importance of this association lies in the facts that atherosclerosis is the most frequent complication of diabetes, that hypertriglyceridaemia is a risk factor for coronary artery disease in diabetic populations and that hyperinsulinaemia also appears to be a risk factor for atherosclerosis. Hypertriglyceridaemia, even without obesity, is associated with resistance to insulin. This can result in compensatory hyperinsulinaemia. Chronic hyperinsulinaemia has been shown to increase the production of triglyceride (TG)-rich lipoproteins. The vast majority of particles in the TG-rich lipoprotein spectrum are in the intermediate-density-lipoprotein (IDL) range. Furthermore, increased levels of TG result primarily from increased numbers of these particles, rather than from increased particle size. This is important because, at least in nondiabetic individuals, increased levels of IDL are associated with increased atherosclerosis. Thus, there may be a vicious cycle of insulin resistance, hyperinsulinaemia, hypertriglyceridaemia and atherosclerosis. We have found that by reducing plasma TG levels alone, one can increase sensitivity to insulin and break this cycle.