Cellular cholesterol synthesis--the relationship to post-prandial glucose and insulin following weight loss

Hyperinsulinaemia is a risk factor for atherosclerosis. We have previously demonstrated a relationship between hyperinsulinaemia and cellular cholesterol synthesis. In this paper we examine the separate relationship of glucose and insulin to cholesterol synthesis in three groups of obese patients. The first group was a group of non-insulin-dependent diabetic patients with a low post-prandial insulin response (n=8). The second group had non-insulin-dependent diabetes and a high insulin response (n=9). The third group were non-diabetic patients with a high post-prandial insulin (n=12). Six diabetic and seven non-diabetic patients who were hyperinsulinaemic on initial analysis, were re-examined following an 8% body weight reduction. Insulin resistance was defined as the ratio of area under curve for insulin/area under curve for glucose. Cellular cholesterol synthesis was measured in freshly isolated mononuclear leucocytes. Fasting cholesterol synthesis was similar in the three groups. In both diabetic and non-diabetic high insulin subjects cholesterol synthesis rose significantly after the meal (p < 0.05). Both hyperinsulinaemic groups showed a significantly greater change from baseline than did the non-hyperinsulinaemic group. There was a positive correlation between post-prandial cellular cholesterol synthesis and insulin resistance (p < 0.05). Following weight reduction patients were divided into two groups, those who did reduce insulin resistance (group 1) and those who did not reduce insulin resistance (group 2). The significant post-prandial increase in cholesterol synthesis was no longer seen in group 1 after weight loss whereas in group 2 after a similar weight loss the post-prandial cholesterol synthesis remained elevated. These results demonstrate that post-prandial hyperinsulinaemia is associated with increased cellular cholesterol synthesis. This increase in cholesterol synthesis is no longer seen in those patients in whom insulin resistance improved with weight reduction. This study suggests a mechanism for the association between insulin resistance and atherosclerosis.