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

An increased cholesterogenesis has been described in obese dyslipidemic typ e 2 diabetic patients and in a small number of patients with poor glucose c ontrol. So far, it is not clear if increased cholesterogenesis in type 2 di abetes is related to the degree of glycemic control or depends on the commo nly associated dyslipidemia or both. Therefore, the aim of the present stud y was to investigate the relationships among cholesterogenesis and degree o f 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, respecti vely, 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 de termination of 24-h urinary mevalonate excretion (MVA). In the diabetic gro up the mean glycated hemoglobin was 8.47 +/- 2.2% (range 4.6-14.6%), the me an total cholesterol, triglycerides, HDL and LDL cholesterol were, respecti vely, 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 mu mol/24 h in contr ol subjects and 1.66 +/- 0.7 mu mol/24 h in diabetics (P = 0.05). In diabet ics, urinary mevalonate excretion was significantly correlated with glycate d 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 dem onstrate that lower the degree of blood glucose control, higher is the whol e body cholesterol production even in the absence of overt dyslipidemia. In conclusion, the relationship between mevalonate excretion rate and glycate d hemoglobin gives further weight to the importance of intensive blood-gluc ose control in diabetic disease and adds a new element to the list of poten tially atherogenic factors strictly related to hyperglycemia in type 2 diab etic patients. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.