Non-Alcoholic Fatty Liver Disease Is not Related to the Prevalence of Diabetic Polyneuropathy in Diabetes

Aim: Nonalcoholic fatty liver disease (NAFLD) has been suggested as independent predictor for kidney disease and proliferative retinopathy in patients with type 2 diabetes (T2D), while the association with diabetic polyneuropathy (DPN) is debated. The aim of this study is to evaluate the association between DPN and predictive tools and ultrasonography diagnosis of NAFLD. Methods: Forty-two diabetic patients (mean age 57.83 ± 11.47 years, duration 9.44 ± 8.92 years, HbA1c 59.19 ± 13.85 mmol/mol, 27 males, 93% T2DM), underwent clinical evaluation of DPN by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS) and Diabetic Neuropathy Index (DNI). NAFLD was evaluated by predictive tools Fatty Liver Index (FLI) and Hepatic Steatosis Index (HIS), and confirmed by liver ultrasonography. Results: DPN was present in 22 (52.4%) participants. DPN patients were older (p=0.04) and characterized by higher prevalence of impaired urinary albumin excretion (p=0.035), hypertension (p=0.011) and dyslipidemia (p=0.041). High risk FLI and HIS scores were detected in 81% and 64.3% of subjects, while ultrasonography NAFLD was present in 31 out of 36 (85.7%%) patients (20 with mild and 11 with moderate-severe grade), resulting more frequent in females than males (93.3% versus 63.0%, p=0.032). 87 No significant difference was found in DPN prevalence in patients with NAFLD than those without (54.8 versus 45.2 %, p=0.338), also considering only high grade steatosis. No association was identified between DPN and non-invasive predictive tools of NAFLD. Conclusion: Although in a small sample of diabetic subjects, liver steatosis is not independently associated with clinical diagnosis of DPN

Cardioprotective effects of sodium glucose cotransporter 2 inhibition in angiotensin II-dependent hypertension are mediated by the local reduction of sympathetic activity and inflammation

The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks. Blood pressure was measured by plethysmographic method. Myocardial hypertrophy and fibrosis were analysed by histomorphometry, and inflammatory cell infiltration and tyrosine hydroxylase expression, implemented as a marker of sympathetic activity, were evaluated by immunohistochemistry. Ang II increased blood pressure, myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase expression, as compared to the control group. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase overexpression in Ang II-treated rats, without affecting blood glucose and the Ang II-dependent increase in blood pressure. These data demonstrate that the cardioprotective effects of SGLT2 inhibition in Ang II-dependent hypertension may result from the myocardial reduction of sympathetic activity and inflammation and are independent of the modulation of blood pressure and blood glucose levels

Renal Anti-Fibrotic Effect of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension.

Background: Clinical trials have shown that empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, promotes nephroprotective effects in diabetic patients. The mechanisms underlying nephroprotection are not com- pletely known and it is not known whether the renal benefi- cial action is present even in non-diabetic kidney disease. The aim of this study was to evaluate the effect of Empa ad- ministration on the development of renal fibrosis in an ex- perimental model of angiotensin II (Ang II)-dependent hy- pertension. Methods: Sprague Dawley rats (n = 31) were di- vided into 4 experimental groups. Ang II (200 ng/kg/min, osmotic minipumps, s.c., n = 9) or Ang II + Empa (10 mg/kg/ day, per os, n = 10) were administered for 2 weeks. Control rats were treated with placebo (physiological saline, n = 6), and another group was treated with placebo plus Empa (n = 6) for the same period. Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental protocol. After 2 weeks, the rats were eu- thanized and the kidneys were excised for histomorphomet- ric evaluation of glomerular and tubulo-interstitial fibrosis and for the immunohistochemical evaluation of inflamma- tory infiltrates (monocytes/macrophages) and types I and IV collagen expression. Results: The administration of Ang II re- sulted in an increase in blood pressure (p < 0.01), glomerular (p < 0.05) and tubulo-interstitial (p < 0.01) fibrosis, renal in- flammatory infiltrates (p < 0.01) and type I (p < 0.01) and type IV collagen expression (p < 0.05) compared to the control group. Treatment with Empa did not significantly modify the increase in blood pressure due to Ang II, but prevented the development of renal glomerular and tubulo-interstitial fi- brosis, and the increase in inflammatory infiltrates and types I and IV collagen expression in Ang II-treated rats (p < 0.01). Conclusions: These data demonstrate that the treatment with Empa prevents the development of renal fibrosis in AngII-dependent hypertension. In Ang II-dependent hyperten- sion, the anti-fibrotic effect due to SGLT2 inhibition is caused by the reduction of inflammatory infiltrates and it is inde- pendent on the modulation of blood pressure increase