Metabolic and Vascular Effects of Silybin in Hypertensive Patients With High One-hour Post-load Plasma Glucose: a Single Arm Pilot Study

Insulin resistance (IR) represents a common pathophysiological mechanism of type 2 diabetes and arterial hypertension, both associated with the appearance and progression of cardiovascular disease (CVD).

Recently, it has been reported that a value of one-hour (1-h) post-load plasma glucose ≥155 mg/dL (1-h high), during an oral glucose tolerance test (OGTT), is able to identify subjects with normal glucose tolerance (NGT) but at high risk of incident type 2 diabetes; according with this, 1-h high NGT hypertensive patients show an unfavorable metabolic profile characterized by higher IR, subclinical inflammation and multiple target organ damage, similar to that observed in individuals with impaired glucose tolerance (IGT).

Experimental and clinical studies have demonstrated that silybin, the main active component extracted from the milk thistle, presents important anti-inflammatory, antifibrotic and metabolic effects, particularly, in the liver. In patients with non-alcoholic fatty liver disease (NAFLD), the complex silybin-vitamin E-phospholipids may improve all metabolic syndrome parameters, reducing IR and ameliorating glucose metabolism and liver histology. Given the common pathophysiological pathways shared by both cardiovascular and metabolic diseases, it's plausible that silybin may be protective also for tissues other than the liver, and in different clinical settings. According with this, silybin showed to markedly improve IR and endothelial dysfunction in an animal model of diabetes and obesity. On the basis of these considerations, the aim of this study was to evaluate the effects of the complex silybin-vitamin E and phospholipids (®Realsil) on inflammatory, metabolic and vascular parameters in a group of never treated 1-h high NGT hypertensive patients.

This is a pilot, single arm, interventional, longitudinal study for which the investigators have planned to enroll 50 Caucasian never-treated hypertensive outpatients, who resulted NGT with 1-h post load plasma glucose >155 mg/dl, during OGTT. All patients will undergo physical examination and review of their medical history. Causes of secondary hypertension will be excluded by appropriate clinical and biochemical tests. Other exclusion criteria are: history or clinical evidence of ischemic or valvular heart disease, congestive heart failure, peripheral vascular and chronic gastrointestinal diseases associated with malabsorption, chronic pancreatitis, history of any malignant or autoimmune disease, alcohol or drug abuse, liver or kidney failure, treatments able to modify glucose metabolism and smoking.

All subjects will undergo anthropometrical evaluation by measuring weight, height, body mass index (BMI) and waist. After 12-h fasting, a 75 g OGTT will be performed with 0, 30-, 60-, 90- and 120-min sampling for plasma glucose and insulin. Glucose tolerance status will be defined on the basis of OGTT using the World Health Organization (WHO) criteria.