Urinary mevalonate excretion rate in type 2 diabetes: role of metabolic control

Abstract

An increased cholesterogenesis has been described in obese dyslipidemic type 2 diabetic patients and in a small number of patients with poor glucose control. So far, it is not clear if increased cholesterogenesis in type 2 diabetes is related to the degree of glycemic control or depends on the commonly associated dyslipidemia or both. Therefore, the aim of the present study was to investigate the relationships among cholesterogenesis and degree of metabolic control in a group of non-obese normolipidemic type 2 diabetic patients. Fifty four (25 men and 29 postmenopausal women) non-obese type 2 diabetic patients with cholesterol and triglyceride plasma levels, respectively, below 6.40 and 2.85 mmol/l and 20 normal subjects matched for age and sex were studied. Endogenous cholesterol synthesis was evaluated by the determination of 24-h urinary mevalonate excretion (MVA). In the diabetic group the mean glycated hemoglobin was 8.47+/-2.2% (range 4.6-14.6%), the mean total cholesterol, triglycerides, HDL and LDL cholesterol were, respectively, 4.86+/-0.7, 1.64+/-0.5, 1.19+/-0.3 and 2.87+/-0.7 mmol/l. The mean 24-h MVA urine excretion rates were 1.41+/-0.3 micromol/24 h in control subjects and 1.66+/-0.7 micromol/24 h in diabetics (P=0.05). In diabetics, urinary mevalonate excretion was significantly correlated with glycated hemoglobin concentrations (HbA(1c)) (r=0.65; P=0.0001) and body mass index (BMI) (r=0.33; P=0.009). In the multivariate analysis both HbA(1c) and BMI were independent predictors of urinary mevalonate. These data demonstrate that lower the degree of blood glucose control, higher is the whole body cholesterol production even in the absence of overt dyslipidemia. In conclusion, the relationship between mevalonate excretion rate and glycated hemoglobin gives further weight to the importance of intensive blood-glucose control in diabetic disease and adds a new element to the list of potentially atherogenic factors strictly related to hyperglycemia in type 2 diabetic patients.