Effect of insulin on airway responsiveness in patients with type 2 diabetes mellitus: a cohort study.

BACKGROUND: The correlation between low insulin levels and a decreased sensitivity of the muscarinic receptor has been shown on induced-diabetes animal models. We designed a cohort study with the aim of evaluating the effects of insulin therapy on airway responsiveness (AR) in human patients with type 2 diabetes mellitus. METHODS: We enrolled 92 patients with type 2 diabetes who had switched from oral anti-diabetic therapy to treatment by insulin subcutaneous injection. Patients were administered the methacholine challenge test (MCT) at time 0 (pre-insulin therapy) and at intervals of 15, 30, 90, 180, and 360 days after insulin treatment. The decline of forced expiratory volume in 1 second (FEV(1))% from baseline (Delta FEV(1)) in response to inhaled methacholine (MCH) was determined to assess airway hyper-responsiveness (AHR). RESULTS: A total of 81 patients (18 women and 63 men) completed the study. Their mean age was 58 +/- 7 years and the mean duration of disease was 13.5 +/- 7.7 years. The mean decrease of FEV(1) at pre-insulin assessment was 2.96 +/- 2.6%. Compared with the pre-insulin value, a significant increase of Delta FEV(1) was observed at 15, 30, and 90 days after treatment (6.25%, CI 95% 5.4 to 7.2, p = 0.0005; 7.64%, CI 95% 6.6 to 8.1, p < 0.001; 6.45%, CI 95% 5.5 to 7.3, p = 0.0004, respectively), while after 180 and 360 days AR was similar to pre-insulin values (Delta FEV(1), 3.62%, CI 95% 2.7 to 3.5 and 3.11%, CI 95% 7.9 to 9.3, respectively). CONCLUSIONS: The finding of an increased AR in patients with type 2 diabetes during the first 3 months of insulin therapy may underline the importance of monitoring pulmonary function and respiratory symptoms in patients switching from oral anti-diabetic drugs to insulin therapy, especially in the subset of individuals with respiratory disorders.

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy.

AIM: To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema (DME) resistant to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Thirty-two DME patients were enrolled. A 700 microgram slow release Intravitreal Dexamethasone Implant (Ozurdex®) was placed in the vitreous cavity. All patients were followed for 18mo. Best-corrected visual acuity (BCVA) measured with Early Treatment Diabetic Retinopathy Study (ETDRS) and central macular thickness (CMT) exams were carried out at baseline (T0) and after 1 (T1), 3 (T3), 4 (T4), 6 (T6), 9 (T9), 12 (T12), 15 (T15), and 18mo (T18) post injection. RESULTS: Repeated measures ANOVA showed an effect of treatment on ETDRS (P<0.0001). Post hoc analyses revealed that ETDRS values were significantly increased at T1, T3, T4, T9, and T15 (P<0.001) as compared to baseline value (T0). At T6, T12, and T18, ETDRS values were still statistically higher than baseline (P<0.001 vs T0). However, at these time points, we observed a trend to return to baseline conditions. ANOVA also showed an effect of treatment (P<0.0001). CMT decreased significantly at T1, T3, T4, T9, and T15 (P<0.001). At T6 (P<0.01), T12 and T18 (P<0.001) CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed. CONCLUSION: Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improve BCVA and CMT in DME patients resistant to anti-VEGF therapy. Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes.

INTRODUCTION: Dapagliflozin (DAPA) (Farxiga or Forxiga) is a sodium glucose cotransporter 2 (SGLT2) inhibitor approved for type 2 diabetes mellitus(T2DM) treatment. AREAS COVERED: The review focuses on the pharmacokinetics (PK), pharmacodynamics(PD) and clinical studies published on DAPA. The authors searched PubMed database for English language studies describing DAPA characteristics and use in T2DM subjects published through June 2014. EXPERT OPINION: DAPA exhibits favorable PK and PD properties and is effective in reducing glycemic levels. In addition, DAPA shows beneficial/neutral effects on other risk factors contributing to T2DM metabolic control. Increased risk of genital and urinary infections and episodes of volume depletion represent the major concerns for its use. FDA requires additional data to assess imbalances in bladder cancer and drug cardiovascular safety. The mechanism of action and the very low risk of drug-drug interaction make it an ideal drug for rapidly reducing glucotoxicity and restoring clinical response to other antidiabetic drugs.

Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and TNFalpha levels in type 2 diabetes.

AIM: Type 2 diabetes increases the risk for cardiovascular disease, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce cardiovascular events in these patients. The benefits of statin therapy cannot be explained only by the lipid-lowering effect. The aim of this study was to test the effect of atorvastatin therapy on CD36 scavenger receptor expression, nuclear factor-kappaB (NFkappaB) levels and markers of inflammation (C-reactive protein, CRP, Tumor Necrosis Factor-alpha, TNF-alpha) in circulating monocytes from diabetic patients. METHODS: Twenty-two type 2 diabetic patients were treated for 8 weeks with atorvastatin (20 mg/day). At baseline and after treatment a blood sample was collected for measurement of glucose, lipid profile (total cholesterol, HDL, LDL cholesterol, triglycerides), glycated hemoglobin (HbA1c), CRP and for isolation of monocytes. RESULTS: Atorvastatin decreased total (p<0.0001) and LDL (p<0.01), and incresased HDL choles-terol (p<0.02). CD36 surface protein expression (anti-CD36 fluorescein isothiocyanate-FITC) was reduced in circulating monocytes after atorvastatin therapy (p<0.02) while immunoblot analysis showed reduced nuclear and increased cytoplasm NFkappaB levels (p<0.05). Finally, TNFalpha production in lipopolysaccharide-activated monocytes from patients treated with atorvastatin was reduced (p<0.05). CONCLUSION: These results suggest that atorvastatin therapy, beside lowering serum cholesterol levels, could exert anti-atherogenic and anti-inflammatory effects in type 2 diabetic patients.