Glucose-lowering effect and glycaemic variability of insulin glargine, insulin detemir and insulin lispro protamine in people with type 1 diabetes.

AIM: To compare, using a continuous glucose monitoring (CGM) system, the effect on glycaemic variability of insulin glargine, detemir and lispro protamine. METHODS: A total of 49 white people with type 1 diabetes, not well controlled by three times daily insulin lispro, taken for at least 2 months before study and on a stable dose, were enrolled. The study participants were randomized to add insulin glargine, detemir or lispro protamine, once daily, in the evening. We used a CGM system, the iPro Digital Recorder (Medtronic MiniMed, Northridge, CA, USA) for 1 week. Glycaemic control was assessed according to mean blood glucose values, the area under the glucose curve above 3.9 mmol/l (AUC(>3.9)) or above 10.0 mmol/l (AUC(>10.0)), and the percentage of time spent with glucose values >3.9 or >10.0 mmol/l. Intraday glycaemic variability was assessed using standard deviation (s.d.) values, the mean amplitude of glycaemic excursions and continuous overlapping of net glycaemic action. Day-to-day glycaemic variability was assessed using the mean of daily differences. RESULTS: The s.d. was found to be significantly lower with insulin lispro protamine and glargine compared with insulin detemir. AUC(>3.9) was higher and AUC(>10.0) was lower with insulin lispro protamine and glargine compared with detemir. The mean amplitude of glycaemic excursions and continuous overlapping net glycaemic action values were lower with insulin lispro protamine and glargine compared with detemir. In addition, the mean of daily differences was significantly lower with insulin lispro protamine and glargine compared with detemir. Fewer hypoglycaemic events were recorded during the night-time with insulin lispro protamine compared with glargine and detemir. CONCLUSIONS: The results suggest that insulin lispro protamine and glargine are more effective than detemir in reducing glycaemic variability and improving glycaemic control in people with type 1 diabetes. Insulin lispro protamine seems to lead to fewer hypoglycaemic events than other insulin regimens.

A randomized, placebo-controlled study on the effects of a nutraceutical combination of red yeast rice, silybum marianum and octasonol on lipid profile, endothelial and inflammatory parameters.

The aim of this study was to evaluate the effects of a combination of red yeast rice, Silybum marianum and octasonol compared to placebo on lipid profile, endothelial, and inflammatory parameters in low risk dislipidemic patients. One hundred and thirty-four dislipidemic patients were randomised to take placebo or a patented nutraceutical association in tablet form (Zeta ColestRT), 1 tablet /day (immediately after the dinner), for three months in a double-blind, placebo-controlled trial. At baseline and after 3 months the following were evaluated: body weight, body mass index (BMI), fasting plasma glucose (FPG), lipid profile, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), metalloprotineases-2 and -9 (MMP-2 and MMP-9), high sensitivity C-reactive protein (Hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). The nutraceutical combination decreased total cholesterol and low density lipoprotein cholesterol compared to baseline (p = 0.042, and p = 0.041, respectively) and to placebo (p = 0.039, and p = 0.037, respectively). Triglycerides were reduced by the active treatment (p = 0.039), but not by placebo, even if, in group to group comparison, no differences were recorded (p = 0.061). All adipocytokines were reduced by the nutraceutical combination, in particular p = 0.044 for sICAM-1, p = 0.045 for sVCAM-1, p = 0.040 for sE-selectin, p = 0.035 for MMP-2, p = 0.039 for MMP-9, p = 0.038 for Hs-CRP, p = 0.036 for TNF-α, and p = 0.036 for IL-6 compared to baseline, and p = 0.042 for sICAM-1, p = 0.043 for sVCAM-1, p = 0.042 for sE-selectin, p = 0.031 for MMP-2, p = 0.038 for MMP-9, p =0.038 for Hs-CRP, and p = 0.043 for TNF-alpha, espectively, compared to placebo. We can conclude that a combination of red yeast rice, Silybum marianum and octasonol was effective in improving lipid profile, endothelial, and inflammatory parameters in low risk dislipidemic patients.

Comparison of vildagliptin and glimepiride: effects on glycaemic control, fat tolerance and inflammatory markers in people with type 2 diabetes.

AIMS: To compare the effects of vildagliptin with those of glimepiride on glycaemic control, fat tolerance and inflammatory markers in people with Type 2 diabetes mellitus receiving metformin treatment. METHODS: A total of 167 participants were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day, for 6 months. We evaluated the following variables: BMI; glycaemic control; fasting plasma insulin; homeostatic model assessment of insulin resistance index; fasting plasma proinsulin; glucagon; lipid profile; adiponectin; high-sensitivity C-reactive protein; interleukin-6; and tumour necrosis factor-α. A euglycaemic-hyperinsulinaemic clamp procedure and an oral fat load test were also performed. RESULTS: Despite a similar decrease in HbA1c levels (P = 0.009, and P = 0.008, respectively), body weight increased with glimepiride (P = 0.048 vs baseline) and decreased with vildagliptin (P = 0.041 vs baseline and vs glimepiride). Fasting plasma insulin and homeostatic model assessment of insulin resistance index were significantly lower with vildagliptin compared with glimepiride (P = 0.035 and 0.047). M value, an index of insulin sensitivity, increased with vildagliptin, both compared with baseline and with glimepiride (P = 0.028 and 0.039, respectively). Vildagliptin improved all post-oral fat load peaks of lipid profile compared with glimepiride. Adiponectin levels were higher (P = 0.035) and high-sensitivity C-reactive protein levels were lower (P = 0.038) with vildagliptin vs glimepiride. During the oral fat load test, interleukin-6, high-sensitivity C-reactive protein and tumour necrosis factor-α peaks were lower and adiponectin peak was higher in the vildagliptin group than in the glimepiride group. There was a higher dropout rate as a result of hypoglycaemia in the glimepiride group than in the vildagliptin group. CONCLUSIONS: Vildagliptin was more effective than glimepiride in reducing post-oral fat load peaks of lipid-trafficking adipocytokines and inflammatory markers.

Long-term predictors of impaired fasting glucose and type 2 diabetes in subjects with family history of type 2 diabetes: a 12-years follow-up of the Brisighella Heart Study historical cohort.

AIM: To identify and quantify the role of different risk factors in the long-term development of IFG and T2DM in a rural Italian population sample with family history of T2DM. METHODS: We selected a sample of 1271 adult subjects from among those 1851 consecutively visited during four consecutive Brisighella Heart Study surveys (1996-2008), then selecting those ones with a family history of T2DM. Thus, we obtained a final sample including 545 subjects and for which a full clinical and ematochemistry data set was available. RESULTS: The Cox-regression model better predicting the incident IFG and T2DM included age, gender, FPG, TG and SUA. The model best predicting the incident IFG status alone (without T2DM) is very similar to that predicting both IFG and T2DM, including the same predictors. Finally, the model best predicting T2DM (excluding IFG) simply includes FPG, BMI and ALT/AST ratio. Repeating the Cox-regression analysis using BMI as a covariate, TG appears to be also a significant predictor of T2DM (HR 1.018 95% CI 1.009-1.041, p=0.013). CONCLUSION: In a sample of subjects with a family history of diabetes the best long-term predictors of IFG are age, gender, FPG, TG and SUA, while those of T2DM are FPG and BMI.

Effects of enalapril/lercanidipine combination on some emerging biomarkers in cardiovascular risk stratification in hypertensive patients.

WHAT IS KNOWN AND OBJECTIVE: There is considerable interest in pharmacogenetic and molecular biomarkers. Our aim was to evaluate the effects of enalapril/lercanidipine combination on some emerging biomarkers for cardiovascular risk stratification of hypertensive patients, such as lipoprotein(a) [Lp(a)], soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L) and serum myeloperoxidase (MPO). RESEARCH DESIGN AND METHODS: Three hundred and forty-five patients were enrolled in this randomized, double-blind, clinical trial: 120 hypertensive patients were randomized to enalapril 20 mg, 110 to lercanidipine 10 mg and 115 to enalapril/lercanidipine 20/10 mg fixed combination. We measures the following markers at baseline and after 6, 12, 18 and 24 months: blood pressure, fasting plasma glucose (FPG), lipid profile, Lp(a), sRAGE, sCD40L and MPO. RESULTS: There was a decrease in blood pressure in all groups compared with baseline, even if, as expected, enalapril/lercanidipine combination was more effective in reducing blood pressure compared with the monotherapies. No variations in lipid profile or FPG were recorded in any of the groups. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline. The combination enalapril/lercanidipine improved it more than the single therapies. All treatments increased sRAGE levels, and decreased sCD40L and MPO, with a better effect seen with the enalapril/lercanidipine combination compared with single monotherapies. WHAT IS NEW AND CONCLUSION: The combination enalapril/lercanidipine seems to be better than the single monotherapies in reducing not only blood pressure, but also the levels of some emerging biomarkers, potentially useful for cardiovascular risk stratification of hypertensive patients.

Effects of Berberis aristata/Silybum marianum association on metabolic parameters and adipocytokines in overweight dyslipidemic patients.

Nutraceuticals and functional foods have attracted considerable interest as potential alternative therapies for treatment of different cardiovascular disorders and insulin resistance. We evaluated the efficacy of a combination of Berberis Aristata/Silybum Marianum extract (Berberol®) in a sample of overweight, dyslipidemic patients at low cardiovascular risk. We enrolled 105 Caucasian, euglycemic, overweight, dyslipidemic patients, of either sex. At baseline all patients underwent a 6 months run-in period during which they followed an adequate diet and practiced physical activity. At the end of the run-in period, patients were randomised to take placebo or a combination of Berberis aristata/Silybum marianum, 1 tablet during the lunch and 1 tablet during the dinner, for three months, in a double-blind, placebo-controlled design. Berberis aristata/Silybum marianum and placebo were then interrupted for 2 months (wash-out period), and all patients continued with only diet and physical activity. At the end of the wash-out period, patients re-started Berberis aristata/Silybum marianum or placebo twice a day for further 3 months. We evaluated during the run-in period, at randomisation, before and after the wash-out period these parameters: body weight and BMI, fasting plasma glucose, lipid profile, insulin resistance, retinol binding protein-4 (RBP-4), adiponectin (ADN), resistin. Total cholesterol, LDL-C, and Tg decreased, and HDL-C increase after 3 months of Berberis aristata/Silybum marianum, both compared to baseline and placebo. Berberis aristata/Silybum marianum decreased fasting plasma insulin, and HOMA-IR, both compared to baseline and to placebo. Moreover, there was a decrease of RBP-4, and resistin, and an increase of ADN after 3 months of Berberis aristata/Silybum marianum. All these positive effects disappeared after the wash-out period, and re-appeared after the re-introduction of the drug. We observed a significant correlation between HOMA-index decrease and resistin, and RBP-4 decrease, and between HOMA-index decrease and ADN increase in Berberis aristata/Silybum marianum group, but not in placebo group. Berberis aristata/Silybum marianum fixed combination seems to be safe and effective in improving lipid profile, but also in improving insulin resistance and adipocytokines levels.

Utility of AAOS OITE scores in predicting ABOS Part I outcomes: AAOS exhibit selection.

BACKGROUND: Residency programs commonly use performance on the Orthopaedic In-Training Examination (OITE) developed by the American Academy of Orthopaedic Surgeons (AAOS) to identify residents who are lagging behind their peers and at risk for failing Part I of the American Board of Orthopaedic Surgery (ABOS) Certifying Examination. This study was designed to investigate the utility of the OITE score as a predictor of ABOS Part I performance. METHOD: Results for 3132 examinees who took Part I of the ABOS examination for the first time from 2002 to 2006 were matched with records from the 1997 to 2006 OITE tests; at least one OITE score was located for 2852 (91%) of the ABOS Part I examinees. After OITE performance was rescaled to place scores from different test years on comparable scales, descriptive statistics and correlations between ABOS and OITE scores were computed, and regression analyses were conducted to predict ABOS results from OITE performance. RESULTS: Substantial increases in the mean OITE score were observed as residents progressed through training. Stronger correlations were observed between OITE and ABOS performance during later years in training, reaching a maximum of 0.53 in years 3 and 4. Logistic regression results indicated that residents with an OITE score below the 10th percentile were much more likely to fail Part I compared with those with an OITE score above the 50th percentile. CONCLUSIONS: OITE performance was a good predictor of the ABOS score and pass-fail outcome; the OITE can be used effectively for early identification of residents at risk for failing the ABOS Part I examination.

A comparison between sitagliptin or glibenclamide in addition to metformin + pioglitazone on glycaemic control and ß-cell function: the triple oral therapy.

AIMS: To evaluate which triple oral therapy between metformin + pioglitazone + sitagliptin and metformin + pioglitazone + glibenclamide can be more useful in improving glycaemic control and should be preferred in clinical practice. METHODS: During the 2-year run-in period, patients were instructed to take metformin monotherapy for the first year, then a combination of metformin and pioglitazone for the second year, then patients were randomized to add glibenclamide or sitagliptin to the dual combination of metformin and pioglitazone for another year. RESULTS: Body weight reached with sitagliptin at 36 months was lower than that reached with glibenclamide. Fasting plasma insulin and homeostasis model assessment of insulin resistance were significantly increased by triple therapy with glibenclamide and decreased by that with sitagliptin. While sitagliptin did not change homeostasis model assessment of ß-cell function, this value was significantly increased by glibenclamide. Fasting plasma proinsulin was not influenced by triple oral therapy including glibenclamide, while it was decreased by the therapy including sitagliptin compared to glibenclamide. Triple oral therapy with sitagliptin better improved ß-cell function measures compared with the glibenclamide therapy. CONCLUSIONS: Sitagliptin should be preferred to glibenclamide as an addition to the metformin + pioglitazone combination for its better protection of ß-cell secretion and its neutral effect on body weight.

Effects of an olmesartan/amlodipine fixed dose on blood pressure control, some adipocytokines and interleukins levels compared with olmesartan or amlodipine monotherapies.

WHAT IS KNOWN AND OBJECTIVE: To evaluate the effects of an olmesartan/amlodipine single pill combination compared with olmesartan or amlodipine monotherapies on blood pressure control, lipid profile, insulin sensitivity and some adipocytokines levels. METHODS: Two hundred and seventy-six patients were enroled in the study and were randomly assigned to take olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20 mg/5 mg for 12 months. We evaluated at the baseline, and after 6 and 12 months: body weight, body mass index, systolic and diastolic blood pressure (SBP and DBP), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, adiponectin (ADN), resistin (r), interleukin-1ß (IL-1ß) and interleukin-5 (IL-5). At the baseline, and after 6 and 12 months, patients underwent an euglycemic, hyperinsulinemic clamp to assess insulin sensitivity (M value). RESULTS AND DISCUSSION: There was a similar decrease in SBP and DBP after 6 and 12 months in all groups, even if olmesartan/amlodipine combination gave a major decrease in SBP and DPB compared with amlodipine and olmesartan monotherapies. Olmesartan/amlodipine combination decreased FPG after 12 months compared with amlodipine monotherapy. Olmesartan/amlodipine combination decreased FPI and HOMA index and increased M value both compared with baseline and compared with olmesartan and amlodipine monotherapies. Both olmesartan and olmesartan/amlodipine increased ADN and reduced r, without significant differences between the two groups. Regarding interleukins, no differences emerged in group to group comparison. WHAT IS NEW AND CONCLUSION: Olmesartan/amlodipine combination resulted more effective than olmesartan and amlodipine monotherapies in reducing blood pressure, and in increasing insulin sensitivity parameters, but not resulted more effective in improving adipocytokines and interleukins levels analysed, compared with amlodipine or olmesartan monotherapy in hypertensive patients in this double-blind, randomized clinical trial.

Evaluation of emerging biomarkers in cardiovascular risk stratification of hypertensive patients: a 2-year study.

OBJECTIVE: To evaluate if there is a correlation between some new emerging biomarkers, such as lipoprotein(a) (Lp[a]), apo(a) isoform phenotyping, soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L), serum myeloperoxidase (MPO), and cardiovascular risk stratification. RESEARCH DESIGN AND METHODS: Three hundred patients were enrolled in this open-label, case-control design trial: 156 hypertensive patients and 144 healthy subjects as control group. Hypertensive patients were treated according to the latest ESH/ESC guidelines, until the desirable goal of systolic blood pressure (SBP)<140 mmHg, and diastolic blood pressure (DBP)<90 mmHg was reached. We evaluated at baseline and after 6, 12, 18, and 24 months: SBP, DBP, lipid profile, Lp(a), apo(a) isoform phenotyping, sRAGE, sCD40L, and MPO. RESULTS: Hypertensive patients presented higher levels of blood pressure, Lp(a), sCD40L, and MPO and lower levels of sRAGE compared with controls. We observed a decrease of blood pressure, Lp(a), sCD40L, and MPO and an increase of sRAGE after anti-hypertensive treatment. Moreover we observed moderate, but statistically significant, correlations between blood pressure decrease and Lp(a), MPO, and sCD40L decrease and between blood pressure decrease and sRAGE increase. There was also a modest, positive correlation between low molecular weight apo(a) isoforms and hypertension. A limitation of this study is that we cannot exclude a role for lifestyle measures. Furthermore the studied markers seem to improve with blood pressure lowering treatment, but we do not have enough statistical power to definitely state which drug used has a specific action on the various variables measured. CONCLUSION: Lp(a), sRAGE, MPO, sCD40L, and low molecular weight apo(a) isoforms are associated with hypertension and may represent an increased cardiovascular risk. Longer studies are needed to see if these parameters can be also used to predict specific complications linked to hypertension.

Exenatide plus metformin compared with metformin alone on ß-cell function in patients with Type 2 diabetes.

AIM: To quantify how much exenatide added to metformin improves ß-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone. METHODS: A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 µg twice a day for the first 4 weeks and forced titration to 10 µg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and ß-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation. RESULTS: Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment ß-cell function index (HOMA-ß) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin. CONCLUSION: Exenatide is effective not only on glycaemic control, but also in protecting ß-cells and in reducing inflammation.

Losartan and amlodipine on myocardial structure and function: a prospective, randomized, clinical trial.

AIMS: To compare the effects of losartan and amlodipine on myocardial structure and function in hypertensive patients with Type 2 diabetes and left ventricular hypertrophy. METHODS: After a 4-week placebo period, patients were randomized to losartan 50 mg (n = 90) or amlodipine 5 mg (n = 91) for 12 months, with a doubling of the dose in patients who did not respond after 4 weeks. Blood pressure was measured in the clinic every month, while conventional echocardiography and acoustic densitometry (integrated backscatter analysis) were performed at the end of the placebo period and after 12 months of treatment. RESULTS: Both drugs reduced systolic/diastolic blood pressure to a comparable extent. Losartan significantly reduced left ventricular mass index (-19%, P < 0.001), interventricular septal thickness (-16.6%, P < 0.01) and left ventricular posterior wall thickness in diastole (-13.7%, P < 0.01). Amlodipine also decreased such measurements (-10%, P < 0.01 for left ventricular mass index, -9.3%, P < 0.05 for interventricular septal thickness in diastole and -10.1%, P < 0.05 for posterior wall thickness in diastole), but to a lesser extent than losartan. Both drugs significantly increased the ratio of peak filling velocity at early diastole to that at atrial contraction (E/A ratio) and decreased isovolumetric relaxation time: +13.7% and -8.5% with losartan,(both P < 0.01), and +7.9% and -4.9%, with amlopidine (both P < 0.05). Losartan, but not amlodipine, significantly reduced the relative integrated backscatter compared to baseline of the intraventricular septum (-10%, P < 0.01), and of the left ventricular posterior wall (-12%, P < 0.01), while increasing the cyclic variation of integrated backscatter of both the intraventricular septum (+35%, P < 0.001) and the left ventricular posterior wall (+32%, P < 0.001). CONCLUSIONS: Losartan provided a greater attenuation of left ventricular hypertrophy than amlodipine, seemingly as a result of a greater reduction of myocardial fibrosis.

Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes.

WHAT IS KNOWN AND OBJECTIVE: The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes. METHODS: Two hundred and fifty-four obese, diabetic patients were enrolled in this study and randomized to take orlistat 360mg or placebo for 1year. We evaluated at baseline and after 3, 6, 9 and 12months body weight, waist circumference (WC), body mass index (BMI), glycated haemoglobin (HbA(1c) ), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), lipid profile, retinol-binding protein-4 (RBP-4), resistin, visfatin and high-sensitivity C-reactive protein (Hs-CRP). RESULTS AND DISCUSSION: We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP-4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA(1c) , PPG, FPI, HOMA-IR, resistin and Hs-CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA-IR) were RBP-4 and resistin concentration in the orlistat group (r=-0·53, P<0·05, and r=-0·59, P<0·01, respectively). WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP-4 and visfatin, effects not observed with placebo.

Effects of aliskiren on QT duration and dispersion in hypertensive patients with type 2 diabetes mellitus.

AIM: To evaluate the effect of aliskiren compared to amlodipine on QT duration and dispersion in hypertensive patients with type 2 diabetes. METHODS: A total of 170 outpatients aged 50-75 years with mild to moderate hypertension (SBP >130 and <180 mmHg and DBP >80 and <100 mmHg) and type 2 diabetes were randomly treated with aliskiren 300 mg or amlodipine 10 mg, both given once daily for 24 weeks, according to a prospective, open label, blinded-end point, parallel group design. At the end of the placebo run-in, and after 12, and 24 weeks of treatment blood pressure (BP) measurements (by mercury sphygmomanometer, Korotkoff I and V), plasma biochemistry and a standard 12-lead surface ECG were evaluated. RESULTS: Both aliskiren and amlodipine significantly reduced systolic blood pressure (SBP)/diastolic blood pressure (DBP) values (-27.2/-14.3 mmHg, p < 0.001 vs. placebo and -27.8/-14.2 mmHg, p < 0.001 vs. placebo, respectively), with no statistical difference between the two drugs. Aliskiren, but not amlodipine, significantly reduced maximum QT interval (QTmax) (-14 ms at 12 weeks and -17 ms at 24 weeks, both p < 0.05 vs. placebo) and corrected QT max (QTc max) (-26 ms and -31 ms, p < 0.01) as well as the dispersion of both QT (-11 ms and -13 ms, p < 0.01) and QTc (-18 ms and -19 ms, p < 0.01). CONCLUSIONS: Despite similar BP lowering effect, aliskiren, but not amlodipine, reduced QT duration and dispersion, which might be related to the ability of aliskiren to interfere with mechanisms underlying myocardial electrical instability in the heart of diabetic hypertensive patients.

Pioglitazone compared to glibenclamide on lipid profile and inflammation markers in type 2 diabetic patients during an oral fat load.

The aim of the study was to evaluate the effect of pioglitazone and glibenclamide on lipid profile and inflammatory parameters during an oral fat load (OFL). A total of 201 type 2 diabetic patients on treatment with metformin were enrolled in the study; pioglitazone was titrated till 45 mg/day and glibenclamide till 15 mg/day, in association with metformin, respectively. The patients underwent an OFL at baseline and after 12 months. The OFL was given between 08.00 and 09.00 h after a 12-h fast. Blood samples were drawn before and 3, 6, 9, and 12 h after the OFL. We evaluated glycemic-metabolic parameters [glycated hemoglobin (HbA (1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (Homa) index], total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tgs), interleukin-6 (IL-6), high sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α), and adiponectin (ADN). Pioglitazone was better than glibenclamide in decreasing HbA (1c), FPG, FPI, lipid profile, and in improving inflammatory parameters such as Hs-CRP, and ADN. Comparing the OFL performed at baseline, and the OFL performed at the end of the study, pioglitazone, but not glibenclamide, improved all post-OFL peaks for all parameters. Comparing the 12 months OFL in the group treated with pioglitazone and in the group treated with glibenclamide, the values recorded with pioglitazone were significantly better than the ones obtained with glibenclamide. We can conclude that pioglitazone was better than glibenclamide in mitigating the variations of lipid components and inflammation parameters in type 2 diabetic patients.

Thiazolidinediones plus metformin association on body weight in patients with type 2 diabetes.

There are different studies about the efficacy and safety and tolerability of thiazolidinediones added to metformin. The reported improved glycemic control with thiazolidinediones use seems to be associated with an increase in weight with an estimated 2-3 kg weight gain suggesting that maybe thiazolidinediones are not safe for the clinical use. Other authors reported that thiazolidinediones give an improvement in the glycemic without giving weight gain. With our review, we want to evaluate the effects of thiazolidinediones plus metformin combination in diabetic patients on the body weight. From the data emerged from our review we can conclude that even if a small increase in mean body weight was observed in patients treated with thiazolidinediones plus metformin therapy, the weight gain was less than previously reported and it was also considerably less than what might have been expected given the large improvements in glycemic control. For these reasons we can safely say that thiazolidinediones in combination with metformin are effective and well tolerated in patients with type 2 diabetes.