Blood pressure control in type 2 diabetes mellitus with arterial hypertension. The important ancillary role of SGLT2-inhibitors and GLP1-receptor agonists.

Type 2 diabetes mellitus and arterial hypertension are major cardiovascular risks factors which shares metabolic and haemodynamic abnormalities as well as pathophysiological mechanisms. The simultaneous presence of diabetes and arterial hypertension increases the risk of left ventricular hypertrophy, congestive heart failure, and stroke, as compared to either condition alone. A number of guidelines recommend lifestyle measures such as salt restriction, weight reduction and ideal body weight mainteinance, regular physical activity and smoking cessation, together with moderation of alcohol consumption and high intake of vegetables and fruits, as the basis for reduction of blood pressure and prevention of CV diseases. Despite the availability of multiple drugs effective for hypertension, BP targets are reached in only 50 % of patients, with even fewer individuals with T2DM-achieving goals. It is established that new emerging classes of type 2 diabetes mellitus treatment, SGLT2 inhibitors and GLP1-receptor agonists, are efficacious on glucose control, and safe in reducing HbA1c significantly, without increasing hypoglycemic episodes. Furthermore, in recent years, many CVOT trials have demonstrated, using GLP1-RA or SGLT2-inihibitors compared to placebo (in combination with the usual diabetes medications) important benefits on reducing MACE (cardio-cerebral vascular events) in the diabetic population. In this hypothesis-driven review, we have examined the anti-hypertensive effects of these novel molecules of the two different classes, in the diabetic population, and suggest that they could have an interesting ancillary role in controlling blood pressure in type 2 diabetic patients.

NAFLD/NASH in patients with type 2 diabetes and related treatment options.

Type 2 diabetes may reduce life expectancy and patients' quality of life due to its micro- and macro-vascular complications and to the higher risk of several types of cancer. An emerging important factor is represented by the hepatic involvement; it is recognized that excessive hepatic fat accumulation represents a typical feature of diabetic patients and that it also plays an important pathogenic role. It is now evident that non-alcoholic fatty liver disease (NAFLD), generally perceived as a benign condition, may have on the contrary an important deleterious impact for diabetic patients increasing the risk to develop cardiovascular complications but also serious hepatic diseases, in particular non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Lifestyle intervention, bariatric surgery and several drug therapies have now accumulated evidence of efficacy in treating NASH. On the other hand, their durability and safety in the long-term is yet to be proven and their use may be sometimes associated with side effects or higher risk of adverse events limiting the regular administration or contraindicating it. Professional health care providers, building awareness about the importance of these hepatic complications, should put more efforts in primary prevention using a behavioral therapy needing a multidisciplinary approach, in secondary prevention applying on a regular basis in the clinical setting available predictive algorithms to identify the patients at higher cardiovascular and hepatologic risk, and in tertiary prevention treating, when not contraindicated, the diabetic patients preferentially with drugs with proven benefit on NAFLD/NASH.

Increased intestinal permeability precedes clinical onset of type 1 diabetes.

AIMS/HYPOTHESIS: Recent observations have shown subclinical intestinal abnormalities in human type 1 diabetes. Whether these are related to the pathogenetic process or secondary to the diabetes remains to be clarified. The aim of this study was to investigate this issue by examining intestinal permeability to sugars in subjects at different stages of type 1 diabetes: preclinical, new-onset and long-term established disease. METHODS: Eighty-one subjects with islet autoimmunity (18 preclinical, 28 new-onset and 35 long-term type 1 diabetes) and 40 healthy control subjects were investigated by a lactulose-mannitol test, consisting of oral administration of the two sugars and measurement of their urinary excretion. RESULTS: All groups of subjects with islet autoimmunity showed an increase in intestinal permeability (p < or = 0.009 vs controls) to the disaccharide lactulose, indicative of a damaged barrier, but a similar permeability to the monosaccharide mannitol (NS vs controls), indicative of an integral surface mucosa; consequently there was an increase in the lactulose:mannitol excretion ratio (p < or = 0.025 vs controls). CONCLUSIONS/INTERPRETATION: These findings indicate the presence of a subclinical enteropathy associated with type 1 diabetes that is already detectable before clinical onset of the disease, and suggest that the small intestine is an organ participating in the pathogenetic process of type 1 diabetes.