Comparison of the effects of pioglitazone and voglibose on circulating total and high-molecular-weight adiponectin, and on two fibrinolysis inhibitors, in patients with Type 2 diabetes.

BACKGROUND: To investigate short-term effects of pioglitazone and voglibose on serum concentrations of both total and high-molecular-weight (HMW) adiponectin measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) ,and on plasma fibrinolysis indicators, in Type 2 diabetic patients with inadequate glycaemic control on sulphonylureas. METHODS: Thirty-four diabetic patients were randomized to receive pioglitazone or voglibose treatment for 12 weeks, after which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor (PAI) 1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors. RESULTS: At baseline, serum HMW adiponectin correlated negatively with plasma TAFI in all patients with Type 2 diabetes (r = -0.367, P = 0.0423). Both groups showed similar improvements in glycaemic control. Serum total and HMW adiponectin increased in patients treated with pioglitazone, but did not change in patients treated with voglibose. The HMW : total adiponectin ratio increased significantly after treatment with pioglitazone (P = 0.0004). The change in HbA(1c) correlated negatively with changes in serum HMW adiponectin in patients treated with pioglitazone (r = -0.694, P = 0.0034). Plasma PAI-1 and TAFI did not change with pioglitazone treatment. CONCLUSION: Increased serum HMW adiponectin may contribute to the improvement in glycaemic control after pioglitazone treatment. Plasma PAI-1 and TAFI were unchanged by either drug.

Small low-density lipoprotein and small low-density lipoprotein/total low-density lipoprotein are closely associated with intima-media thickness of the carotid artery in Type 2 diabetic patients.

BACKGROUND: The intima-media thickness (IMT) of the carotid artery, as determined by ultrasonography, is useful for reflecting the extent of subclinical atherosclerosis. We investigated the relationship between IMT and the serum concentrations of small low-density lipoprotein (LDL) in diabetic patients. METHODS: The study was conducted with 27 Type 2 diabetic patients (14 males and 13 females; mean age=62.6+/-8.3 years) and 12 age-matched healthy controls. The LDL subfraction was measured using a polyacrylamide gel electrophoresis method. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) concentrations were measured by an enzyme immunoassay. The IMT was expressed as the maximum IMT (Max-IMT) and average IMT (Ave-IMT) of the carotid artery, measured by ultrasonography. RESULTS: Both the IMT and the small LDL concentrations were significantly increased in the diabetic patients compared with the healthy participants. The IMTs were significantly correlated with small LDL concentration and small LDL/total LDL more than LDL concentrations by multivariate analysis. The IMTs were not significantly correlated with the serum VEGF or PDGF concentrations. The patients with a larger IMT had a significantly higher prevalence of hypertension or ischemic heart disease than did the patients with a normal IMT. CONCLUSIONS: The increased small LDL concentrations and small LDL/total LDL, in addition to total LDL concentrations, in Type 2 diabetic patients are closely associated with increased IMT of the carotid artery.

Assessment of peripheral neuropathy using measurement of the current perception threshold with the neurometer in patients with type 2 diabetes mellitus.

Measurement of current perception threshold (CPT) using the Neurometer at 2000, 250 and 5 Hz assesses function in three different nerve fibre types. This method was used to investigate peripheral neuropathy in 116 patients with type 2 diabetes mellitus and 38 healthy controls. The CPT at 2000 Hz was significantly higher in diabetic patients than in controls, and showed a significant negative correlation with motor and sensory nerve conduction velocities. At 250 Hz, CPT showed a significant positive correlation with the vibration perception threshold. At 5 Hz, the change in systolic blood pressure in the Schellong test in patients with hypoaesthesia tended to be less than in those with normal sensation or hyperaesthesia. Significantly higher CPT values were obtained in patients with proliferative diabetic retinopathy and macroalbuminuria. These data suggest that CPT is useful in detecting abnormalities of myelinated as opposed to unmyelinated nerve fibres in patients with type 2 diabetes.

Clinical usefulness of doxazosin in patients with type 2 diabetes complicated by hypertension: effects on glucose and lipid metabolism.

This uncontrolled study investigated the effects of using the alpha 1-blocker doxazosin (2 mg or 4 mg daily for 3 months) to treat 21 hypertensive patients with type 2 diabetes, including eight obese individuals (body mass index [BMI] > or = 25.0 kg/m2). A significant reduction in systolic and diastolic blood pressure, beginning after 1 month of treatment, was seen. There was no significant change in BMI. Although there was no obvious improvement in glucose metabolism, doxazosin treatment noticeably reduced insulin resistance and significantly lowered triglyceride and free fatty acid levels. No significant changes were found in total cholesterol, high- or low-density lipoprotein-cholesterol, atherosclerotic index, or small or large subfractions of low-density lipoprotein-cholesterol. None of the patients showed any adverse effects. The beneficial effects of doxazosin on blood pressure and lipid and glucose metabolism shown in this study suggest that this drug is clinically useful as an anti-hypertensive agent for patients with diabetes.

Relation between the serum level of C-peptide and risk factors for coronary heart disease and diabetic microangiopathy in patients with type-2 diabetes mellitus.

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.