ALTERED REGULATION OF CHOLESTEROL-METABOLISM IN TYPE-I DIABETIC WOMENDURING THE MENSTRUAL-CYCLE

This study examines the relationship of cellular cholesterol metabolis m to oestrogen and progesterone during the menstrual cycle in diabetic and non-diabetic subjects. Nine premenopausal diabetic women were com pared to nine non-diabetic women of the same age. Oestrogen, progester one, lipoproteins, including lipoprotein (a) (Lp(a)) and cholesteryl e ster transfer protein (CETP) were determined in serum. Cellular choles terol content and cellular cholesterol synthesis were measured in mono nuclear leucocytes. There was no significant change in serum lipoprote ins including Lp(a) during the cycle in either group. CETP activity wa s significantly higher over the 4 weeks in the diabetic patients compa red with non-diabetic subjects (mean 463 +/- 30 mumol l-1 h-1 vs 405 /- 28 mumol l-1 h-1, p < 0.01). Serum high density lipoprotein (HDL) c holesterol was significantly lower during the 4 weeks in the diabetic patients (1.7 +/- 0.1 mmol l-1 vs 1.8 +/- 0.1 mmol-1, p < 0.05). Cellu lar cholesterol synthesis decreased steadily up to the third week in c ells from the control subjects whereas there was no significant change in cells from diabetic patients whose cellular cholesterol synthesis was higher at week 3 compared with non-diabetic subjects (663 +/- 54 n mol mg-1 cell protein vs 432 +/- 43 nmol mg-1 cell protein, two-way in teraction p < 0.05). There was a significant negative correlation betw een cellular cholesterol synthesis and serum oestrogen in the non-diab etic subjects (p < 0.05) but not in the diabetic patients. These resul ts show that cellular cholesterol synthesis is not down-regulated duri ng the menstrual cycle in diabetic patients, a finding which may help to explain the increased incidence of atherosclerosis in the diabetic, pre-menopausal woman.