Davide Romano

Effects of a combination of sitagliptin plus metformin vs metformin monotherapy on glycemic control, β-cell function and insulin resistance in type 2 diabetic patients

AIMS To evaluate the impact on glycemic control, insulin resistance, and insulin secretion of sitagliptin+metformin compared to metformin in type 2 diabetic patients. METHODS Patients were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to sitaglipin 100 mg or placebo for 12 months. We evaluated at 3, 6, 9, and 12 months: body mass index (BMI), glycemic control, fasting plasma insulin (FPI), HOMA-IR, HOMA-β, fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, adiponectin (ADN), and high sensitivity-C reactive protein (Hs-CRP). Before, and after 12 months since the addition of sitagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation. RESULTS Both treatments similarly decreased body weight, and BMI; on the other hand, they both improved glycemic control, glucagon and HOMA-IR, but sitagliptin+metformin were more effective in reducing these parameters. Sitagliptin+metformin, but not placebo+metformin, decreased FPPr, FPPR/FPI ratio, and increased C-peptide values, even if no differences between the groups were recorded. Sitaglitin+metformin gave also a greater increase of HOMA-β, M value, C-peptide response to arginine and disposition index compared to placebo+metformin group. CONCLUSIONS Other than improving glycemic control, sitagliptin+metformin also improved β-cell function better than metformin alone.

Adipocytokine Levels in Obese and Non-obese Subjects: an Observational Study

We evaluated the levels of some inflammatory adipocytokines in 363 obese and 365 non-obese subjects. We measured: body mass index (BMI), waist circumference (WC), fasting plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, blood pressure, lipid profile, retinol binding protein-4 (RBP-4), vaspin, omentin-1, leptin, interleukin-6 (IL-6), visfatin, resistin, adiponectin (ADN), adipsin, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (Hs-CRP). We observed higher BMI, WC, FPI, HOMA index, TC, LDL-C, RBP-4, leptin, IL-6, adipsin, Hs-CRP, vaspin, resistin and TNF-α levels, and lower visfatin, and ADN levels in obese compared to non-obese subjects. Higher WC correlated with lower ADN and visfatin levels, and higher vaspin levels. Higher HOMA index correlated with higher resistin, adipsin, RBP-4, and leptin concentrations, while higher leptin levels correlated with higher TNF-α, Hs-CRP, and IL-6 concentration, and lower ADN values. We confirmed obese subjects’ predisposition to develop dysmetabolic disease and hormonal dysfunctions.

Vildagliptin added to metformin on β-cell function after a euglycemic hyperinsulinemic and hyperglycemic clamp in type 2 diabetes patients.

BACKGROUND This study evaluated the effect of vildagliptin + metformin on glycemic control and β-cell function in type 2 diabetes patients. SUBJECTS AND METHODS One hundred seventy-one type 2 diabetes patients, naive to antidiabetes therapy and with poor glycemic control, were instructed to take metformin for 8±2 months up to a mean dosage of 2,500±500 mg/day; then they were randomly assigned to add vildaglipin 50 mg twice a day or placebo for 12 months. We evaluated at 3, 6, 9, and 12 months: body mass index, glycemic control, fasting plasma insulin, homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment β-cell function index (HOMA-β), fasting plasma proinsulin, proinsulin/fasting plasma insulin ratio, C-peptide, glucagon, adiponectin, and high-sensitivity C-reactive protein. Before and at 12 months after the addition of vildagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation, to assess insulin sensitivity and insulin secretion. RESULTS After 12 months of treatment, vildagliptin + metformin gave a better decrease of body weight, glycemic control, HOMA-IR, and glucagon and a better increase of HOMA-β compared with placebo + metformin. Regarding the measures of β-cell function, treatment-induced changes in M-value, first- and second-phase C-peptide response to glucose, and C-peptide response to arginine were significantly higher in the vildagliptin + metformin group compared with the placebo + metformin group. CONCLUSION The addition of vildagliptin to metformin gave a better improvement of glycemic control, insulin resistance, and β-cell function compared with metformin alone.

Effects of berberine on lipid profile in subjects with low cardiovascular risk

Objective: To evaluate the efficacy as antihypercholesterolemic agent of berberine in patients with low cardiovascular risk. Research design and methods: 144 Caucasian subjects were enrolled. After a 6-month run-in period following diet and practicing physical activity, patients were randomized to take placebo or berberine 500 mg twice a day, for 3 months, in a double-blind, placebo-controlled design. Berberine and placebo were then interrupted for 2 months (washout period), and all patients continued with only diet and physical activity. At the end of the washout period, patients restarted berberine or placebo twice a day for further 3 months. Anthropometric and metabolic parameters were assessed during the run-in period, at randomization, before and after the washout period. Results: A decrease of body weight and BMI was observed after the run-in period. Berberine reduced total cholesterol, triglycerides and LDL cholesterol and increased HDL cholesterol after 3 months from randomization and compared with placebo. After the washout period, lipid profile worsened; afterward, when berberine was reintroduced, lipid profile improved again both compared with the washout period, and with placebo. Conclusions: Berberine is effective and safe to mildly improve lipid profile in subjects with low risk for cardiovascular disease.

Vildagliptin compared to glimepiride on post-prandial lipemia and on insulin resistance in type 2 diabetic patients

OBJECTIVES To evaluate the effects of vildagliptin compared to glimepiride on glycemic control, insulin resistance and post-prandial lipemia. MATERIAL AND METHODS 167 type 2 diabetic patients, not adequately controlled by metformin, were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day for 6 months, in a double blind, randomized clinical trial. We evaluated: body mass index (BMI), glycemic control, fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), fasting plasma proinsulin (FPPr), glucagon, lipid profile, resistin, retinol binding protein-4 (RBP-4), visfatin and vaspin. Furthermore, at the randomization and at the end of the study all patients underwent an euglycemic hyperinsulinemic clamp to evaluate M value and an oral fat load. RESULTS Despite a similar decrease of glycated hemoglobin, there were an increase of body weight with glimepiride + metformin and a decrease with vildagliptin + metformin. Fasting plasma insulin increased with glimepiride + metformin, while it did not change with vildagliptin + metformin. Vildagliptin + metformin improved lipid profile. Regarding insulin sensitivity, vildagliptin + metformin increased M value. Resistin, RBP-4, vaspin and visfatin were decreased by vildagliptin + metformin, but in group to group comparison, only vaspin reduction resulted statistically significant. Vildagliptin + metformin reduced post-prandial lipemia and insulinemia compared to glimepiride + metformin. CONCLUSION Vildagliptin, in addition to metformin, was more effective than glimepiride + metformin in reducing insulin resistance and post-prandial lipemia.

Berberis aristata/Silybum marianum fixed combination on lipid profile and insulin secretion in dyslipidemic patients.

Background: Relatively large number of dietary supplements and nutraceuticals have been studied for their supposed or demonstrated ability to reduce cholesterolemia in humans. Objectives: The aim of this study was to evaluate the efficacy as antihypercholesterolemic and insulin-sensitizing agent of a combination of Berberis aristata/Silybum marianum extract (Berberol®) in a sample of dyslipidemic patients. A total of 102 dyslipidemic subjects were enrolled. After a 6 months run-in period of diet and physical activity, the patients were randomized to placebo or Berberis aristata/Silybum marianum extract 588 mg/105 mg, twice a day for 3 months. Berberis aristata/Silybum marianum and placebo were then interrupted for 2 months (washout period), and then restarted for further 3 months. Anthropometric and metabolic parameters were assessed; moreover, all patients underwent a glucagon stimulation test. Results: Berberis aristata/Silybum marianum reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol after 3 months from randomization and compared to placebo group. When Berberis aristata/Silybum marianum was interrupted, lipid profile worsened, and it improved again when nutraceutical combination was reintroduced. During the glucagon stimulation test, a higher increase of C-peptide levels and a lower increase in glycemia after the test with Berberis aristata/Silybum marianum compared to placebo, to baseline and to randomization were recorded. No patients had serious adverse events in both groups. Conclusion: Berberis aristata/Silybum marianum is effective and safe in improving lipid profile and insulin secretion in euglycemic dyslipidemic patients.

Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year study evaluation

The aim of this study was to evaluate whether the positive effects of sitagliptin on glycemic control and insulin resistance were maintained also after 2 years of therapy and whether sitagliptin could be effective also in improving lipid profile. In this randomized, double‐blind, placebo‐controlled trial, 205 patients with type 2 diabetes in therapy with different antidiabetic drugs were randomized to add sitagliptin 100 mg once a day or placebo to their current therapy. We evaluated at the baseline and after 6, 12, 18, and 24 months the following parameters: body mass index, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA‐IR), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (Tg). Sitagliptin, added to previously taken antidiabetic agents, proved to be effective in improving glycemic profile, reducing HbA1c by −17.5%, FPG by −12.7%, PPG by −20.5%. Regarding insulin resistance, sitagliptin decreased FPI by −8.3% and HOMA‐IR by −20.0%, confirming that what have been already reported in short‐term studies can be applied also after 2 years of treatment. Sitagliptin also reduced body weight by −4.3%. Our study also showed the positive effect of sitagliptin on lipid profile; in particular, sitagliptin decreased TC by −13.3%, LDL‐C by −20.4%, and Tg by −32.3%, and also increased HDL‐C by + 13.6%. Sitagliptin proved to be effective on glycemic profile and insulin resistance even after 2 years of therapy and to be effective in improving body weight and lipid profile.

Prevalence and associations of erectile dysfunction in a sample of Italian males with type 2 diabetes

AIM The aim of this study was to evaluate the prevalence of erectile dysfunction (ED) in a sample of type 2 diabetic patients. As secondary endpoint, we evaluated the levels of some adipocytokines in patients with and without ED. MATERIAL AND METHODS We enrolled 220 males affected by type 2 diabetes mellitus. We administered the IIEF (International Index of Erectile Function), SAS (self-rating anxiety scale) and SDS (self-rating depression scale) questionnaires. We evaluated body mass index, glycemic control, fasting plasma insulin (FPI), homeostasis model assessment of insulin resistance index (HOMA-IR), lipid profile, sexual hormones, adiponectin (ADN), resistin, retinol binding protein-4 (RBP-4), visfatin, vaspin. RESULTS 52.9% of patients were affected by ED. Patients with a HbA1c <7% (53 mmol/mol) in all measurements in the two previous years had a lower incidence of ED, while the prevalence of ED increased with the increasing of times HbA1c was >7% (53 mmol/mol). Patients with ED had higher levels of triglycerides, and higher levels of FPI, 9.9 μU/ml vs 8.2 μU/ml (p<0.05). Resistin levels were higher in patients with ED compared to those without ED (p<0.05) and free testosterone was lower in patients affected by ED. CONCLUSIONS Almost half of type 2 diabetic patients attending our clinic were affected by ED and glycemic control seems to play a role in ED pathogenesis.

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

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.

Effects of canrenone in patients with metabolic syndrome

Background: Metabolic syndrome is becoming a common disease due to a rise in obesity rates among adults. Objectives: The aim was to evaluate the effects of canrenone compared to placebo on metabolic and inflammatory parameters in patients affected by metabolic syndrome. A total of 145 patients were treated with placebo or canrenone, 50 mg/day, for 3 months and then 50 mg b.i.d. till the end of the study. Blood pressure, body weight, body mass index, fasting plasma glucose (FPG), fasting plasma insulin, HOMA-IR, lipid profile, plasma aldosterone, brain natriuretic peptide, high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor-α (TNF-α) and M value were evaluated. Results: A decrease of blood pressure was observed in canrenone group compared to baseline; moreover, systolic blood pressure value recorded after 6 months of canrenone therapy was lower than the one recorded with placebo. Canrenone gave a significant decrease of FPI and HOMA index, and an increase of M value both compared to baseline and to placebo. Canrenone also decreased triglycerides and FPG was not observed with placebo. Canrenone also decreased plasma aldosterone, Hs-CRP and TNF-α compared to baseline and to placebo. Conclusion: Canrenone seems to be effective in reducing some factors involved in metabolic syndrome and in improving insulin-resistance and the inflammatory state observed in these patients.