Hyperinsulinaemia is associated with stimulation of cholesterol synthesis in both type 1 and type 2 diabetes.
The effect of hyperinsulinaemia and hyperglycaemia on cholesterol synthesis was examined in lymphocytes from diabetic subjects. The first part of the study involved the provocation of hyperinsulinaemia by consumption of a carbohydrate-rich meal, in obese patients with Type 2 diabetes mellitus. Cholesterol synthesis was measured before and 4 h after completing the meal. Results were compared to groups of obese non-diabetic patients and to control subjects. Analysis of the three groups demonstrated that the percentage change in cholesterol synthesis was directly proportional to the percentage rise in serum insulin (r = 0.49, p < 0.05). This physiological study demonstrated that postprandial hyperinsulinaemia promoted cholesterol synthesis; however, we could not estimate the effect of the meal on cholesterologenesis. To study hyperinsulinaemia in isolation, we examined the effects of varying insulin infusion rates for 4 h at either low or high levels of serum glucose using the glucose clamp technique in young Type 1 diabetic patients. Cholesterol synthesis in lymphocytes was again measured before and after the study period. Hyperinsulinaemia stimulated cholesterol synthesis (+28.6%, p < 0.05) but hyperglycaemia alone did not exhibit this effect (-1.7% NS). The combination of hyperinsulinaemia and hyperglycaemia produced the greatest increase in cholesterol synthesis (+51.4%, p < 0.05) but this increase was not significantly different from hyperinsulinaemia alone. The percentage increase in serum insulin levels was again proportional to the percentage change in cholesterol synthesis (r = 0.46, p < 0.05).
Stinson
J C
JC
Department of Diabetes and Endocrinology, Adelaide Hospital, Dublin, Ireland.
Owens
D
D
Collins
P
P
Johnson
A
A
Tomkin
G H
GH
D000085:Acetates / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis*; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D004040:Dietary Carbohydrates; D004435:Eating; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009765:Obesity; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D000085:Acetates; D001786:Blood Glucose; D002784:Cholesterol; D004040:Dietary Carbohydrates; D006442:Glycated Hemoglobin; D006903:Hydroxymethylglutaryl CoA Reductases; D007328:Insulin; D002785:Sterol O-Acyltransferase