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

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.

Carotid intima-media thickness in patients with Type 2 diabetes and hypercholesterolemia.

Both patients with Type 2 diabetes mellitus (T2DM) and with hypercholesterolemia have a more extensive and accelerated atherosclerosis with higher common carotid artery intima-media thickness (CIMT) values than the general population. The aim of this study was to compare the CIMT in polygenic hypercholesterolemia (HP; n=41: 30 females and 11 males, aged 52+/-15 yr) and in T2DM (n=43: 22 females and 21 males, aged 59+/-11 yr), with a duration of disease less than 5 yr and no evidence of coronary heart disease. A control group (C) of 40 sex- and age-matched healthy subjects was studied. We evaluated the CIMT on the far wall of the distal segment of the common carotid arteries on sites free of plaque. The mean of the CIMT measurements (Tmean; 9 on each side) and the maximal CIMT measured (Tmax) were used as the representative values for each subject. Tmax values were 0.96+/-0.2 mm and 0.82+/-0.2 mm in T2DM and HP, respectively, which were significantly higher than C (0.74+/-0.1 mm). Corresponding values of Tmean were 0.8+/-0.1 mm and 0.71+/-0.2 mm, both significantly higher than C (0.68+/-0.1 mm). In HP, both Tmax and Tmean values were positively correlated to age (p=0.0001 and p=0.0001, respectively), body mass index (BMI; p=0.05 and p=0.05, respectively), presence of hypertension (p=0.003 and p=0.0008, respectively) and fibrinogen (p=0.0009 and p=0.001, respectively); Tmean was also correlated to apolipoprotein B (ApoB; p=0.03). The multiple "stepwise" regression analysis revealed fibrinogen and age as the only significant determinants of Tmax and Tmean. In T2DM Tmax and Tmean were positively correlated to age only (p=0.04 and p=0.01, respectively). In conclusion, T2DM patients have a more accelerated atherosclerosis than subjects with HP. This is evident after a short duration of disease, probably for a longer latency period of disease and the presence of multiple risk factors.