Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients.

The aim of the study was to compare the effects of vildagliptin added to pioglitazone or glimepiride on metabolic and insulin resistance related-indices in poorly controlled type 2 diabetic patients (T2DM). 168 patients with T2DM were randomized to take either pioglitazone 30 mg once a day plus vildagliptin 50 mg twice a day or glimepiride 2 mg 3 times a day plus vildagliptin 50 mg twice a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index (HOMA-beta), fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), adiponectin (ADN), resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein (Hs-CRP) at their baseline values, and after 3, 6, 9, and 12 months of treatment. We observed a similar improvement of HbA1c, FPG, PPG, and Hs-CRP compared to baseline in the 2 groups. Fasting plasma insulin, FPPr, Pr/FPI ratio, R, and TNF-alpha were significantly decreased and ADN was significantly increased with pioglitazone plus vildagliptin, but not with glimepiride plus vildagliptin. HOMA-IR, and HOMA-beta values obtained with pioglitazone plus vildagliptin were significantly better than the values obtained with glimepiride plus vildagliptin. Pioglitazone plus vildagliptin were found to be more effective in preserving beta-cell function, and in reducing insulin resistance, and inflammatory state parameters.

Exenatide versus glibenclamide in patients with diabetes.

BACKGROUND: Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes. METHODS: One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months. RESULTS: Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide. CONCLUSIONS: Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and beta-cell function, giving also a decrease of body weight and of inflammatory state.

Oral glucose tolerance test effects on endothelial inflammation markers in healthy subjects and diabetic patients.

The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

Effects of long chain omega-3 fatty acids on metalloproteinases and their inhibitors in combined dyslipidemia patients.

We evaluate the effect of a standardized dietary supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) on the level of some markers of vascular remodeling in patients with combined dyslipidemia. Three hundred and thirty-three patients received placebo or n-3 PUFAs for 6 months. We evaluated body mass index, glycemic profile, blood pressure, lipid profile, lipoprotein(a), plasminogen activator inhibitor-1, homocysteine, fibrinogen, high-sensitivity C reactive protein, ADP, MMP-2 and MMP-9, and tissue inhibitors of metalloproteinase-1 and -2. A significant increase of high-density lipoprotein-cholesterol, and a significant decrease of triglycerides were present after 3 and 6 months with n-3 PUFAs intake. A significant plasminogen activator inhibitor-1, fibrinogen and high-sensitivity C reactive protein decrease was obtained after 3 and 6 months and a significant ADP increase was observed after 3 and 6 months of n-3 PUFAs. A significant MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 decrease was obtained after 6 months compared to the baseline value with n-3 PUFAs intake. n-3 PUFAs give a better lipid profile and a better improvement of coagulation, fibrinolytic and inflammatory parameters than placebo. Furthermore, lowers levels of MMP-2, MMP-9 and their tissue inhibitors are obtained with n-3 PUFAs compared to placebo.

Matrix metalloproteinase-2 and -9 levels in obese patients.

The data reported in literature revealed a novel function for matrix metalloproteinases (MMPs) as modulators of adipogenesis. However, their expression profile and role in the cellular microenvironment during obesity-mediated adipose tissue development remain poorly defined. The authors hypothesized that MMP-2 and MMP-9 levels might be abnormal in obesity, reflecting alterations in extracellular matrix (ECM) turnover. One hundred and sixty three obese patients and 165 controls were enrolled. The following were measured: body mass index (BMI), waist circumference (WC), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) (Lp(a)), and plasma levels of MMP-2 and MMP-9. A significant increase of BMI and WC (p< .0001) was observed in obese patients. No FPG change was present in obese group, whereas FPI and HOMA index increases (p< .0001) were obtained in obese patients compared to control subjects. No SBP and DBP variations were observed in obese group. Significant TC and LDL-C increases (p< .0001) were present in obese patients, whereas no HDL-C, Tg, and Lp(a) changes were obtained in both groups. MMP-2 and MMP-9 levels were significantly higher in obese group (p< .0001). Plasma levels of MMP-2 and MMP-9 are increased in obese patients which may reflect abnormal ECM metabolism.

Metabolic effects of telmisartan and irbesartan in type 2 diabetic patients with metabolic syndrome treated with rosiglitazone.

BACKGROUND AND OBJECTIVE: Angiotensin II receptor blockers represent a class of effective and well-tolerated orally active antihypertensive drugs in the general hypertensive population and in diabetic patients. The aim of our study was to investigate the metabolic effects of telmisartan and irbesartan in diabetic subjects treated with rosiglitazone. METHODS: We evaluated 188 type 2 diabetic patients with metabolic syndrome. All patients took a fixed dose of 4 mg rosiglitazone/day. We administered 40 mg telmisartan/day or 150 mg irbesartan/day and evaluated their body mass index, glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment-index (Homa-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol, triglycerides, systolic blood pressure, diastolic blood pressure, adiponectin and resistin during 12 months of this treatment. RESULTS AND DISCUSSION: In addition to a comparable antihypertensive effect for telmisartan and irbesartan after 6 and 12 months, both treatments were associated with a significant reduction in TC and LDL-C plasma levels compared with baseline. After 6 months of treatment, only the telmisartan group experienced a significant improvement in (HbA(1c)), FPG, Homa-IR, adiponectin and resistin compared with the baseline values, whereas both drug regimens were associated with a significant improvement in these parameters after 12 months. However, the improvements observed in the telmisartan group were significantly larger than that noted in the irbesartan group after 12 months of treatment. FPI significantly decreased only after 12 months of treatment in both groups, but again, the reduction was significantly larger in the telmisartan-treated subjects. CONCLUSIONS: Telmisartan seemed to improve glycaemic and lipid control and metabolic parameters of the metabolic syndrome better than irbesartan. These differences could be relevant in the choice of therapy for this condition and diabetes.

Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and metabolic syndrome treated with metformin.

BACKGROUND: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin, whereas the combination of metformin with thiazolidinediones is relatively less studied. The aim of the present study was to assess the differential effect on glycaemic metabolism and lipid variables of the combination of metformin plus pioglitazone or metformin plus rosiglitazone in diabetic patients with metabolic syndrome. METHODS: All patients began metformin and were randomized to receive pioglitazone or rosiglitazone for 12 months. We assessed body mass index, glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, postprandial plasma insulin, homeostasis model assessment index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B. RESULTS: Significant decreases in glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, and postprandial plasma insulin were seen after 9 and 12 months in both groups. Homeostasis model assessment index improved at 12 months in both groups. Significant total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement was observed in pioglitazone group after 12 months, but not in the rosiglitazone group. These variations were significant between groups. CONCLUSION: The combination of metformin plus thiazolidinediones was able to improve glycaemic control compared with previous therapy. Pioglitazone was associated with a significant improvement in lipid and lipoprotein variables.

Metformin-pioglitazone and metformin-rosiglitazone effects on non-conventional cardiovascular risk factors plasma level in type 2 diabetic patients with metabolic syndrome.

BACKGROUND AND OBJECTIVE: Metformin is considered the gold standard for type 2 diabetes treatment as monotherapy and in combination with sulphonylureas and insulin. The combination of metformin with thiazolidinediones is less well studied. The aim of the present study was to assess the differential effect, and tolerability, of metformin combined with pioglitazone or rosiglitazone on glucose, coagulation and fibrinolysis parameters in patients with type 2 diabetes mellitus and metabolic syndrome. METHODS: This 12-month, multicentre, double-blind, randomized, controlled, parallel-group trial was conducted at three study sites in Italy. We assessed patients with type 2 diabetes mellitus (duration >or=6 months) and with metabolic syndrome. All patients were required to have poor glycaemic control with diet, or experienced adverse effects with diet and metformin, administered up to the maximum tolerated dose. Patients were randomized to receive either pioglitazone or rosiglitazone self-administered for 12 months. We assessed body mass index (BMI), glycaemic control [glycosylated haemoglobin (HbA(1c)), fasting and postprandial plasma glucose and insulin levels (FPG, PPG, FPI, and PPI respectively), homeostasis model assessment (HOMA) index], lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)], lipoprotein (a) [Lp(a)] and homocysteine (HCT) at baseline and at 3, 6, 9 and 12 months of treatment. RESULTS AND DISCUSSION: No BMI change was observed at 3, 6, 9 and 12 months in either group. Significant HbA(1c) decreases were observed at 9 and 12 months in both groups. After 9 and 12 months, mean FPG and PPG levels decreased in both groups. Decreases in FPI and PPI were observed at 9 and 12 months compared with the baseline in both groups. Furthermore, in both groups, the HOMA index improved but only at 12 months. Significant TC, LDL-C, HDL-C, TG improvement was present in the pioglitazone group at 12 months compared with the baseline values, and these variations were significantly different between groups. No TC, LDL-C, TG improvement was present in the rosiglitazone group after 12 months. Significant Lp(a) and HCT improvement was present in the pioglitazone group at 12 months compared with the baseline values, and Lp(a) change was significant compared with the rosiglitazone group. Significant HCT decrease was observed in the rosiglitazone group at the end of the study. In our type 2 diabetic patients, both drugs were safe and effective for glycaemic control and improving HCT plasma levels. However, long-term treatment with metformin plus pioglitazone significantly reduced Lp(a) plasma levels, whereas metformin + rosiglitazone did not. CONCLUSION: For patients with type 2 diabetes mellitus and metabolic syndrome, combined treatment with metformin and rosiglitazone or pioglitazone is safe and effective, However, the pioglitazone combination also reduced the plasma Lp(a) levels whereas the rosiglitazone combination did not.