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Peripheral insulin resistance (IR) is a well-documented, independent risk factor for the development of type 2 diabetes, cardiovascular disease, cancer and cellular senescence. Recently, the brain has also been identified as an insulin-responsive region, where insulin acts as regulator of the brain metabolism. Despite the clear link between IR and the brain, the exact mechanisms underlying this relationship remain unclear. Therapeutic intervention in patients showing symptoms of neurodegenerative diseases has produced little or no results. It has been demonstrated that insulin resistance plays a significant role in the pathogenesis of neurodegenerative diseases, particularly cognitive decline. Peripheral and brain IR may represent a modifiable state that could be used to prevent major brain disorders. In this review, we will analyse the scientific literature supporting IR as a risk factor for Alzheimer's disease and suggest some therapeutic strategies to provide a new proposal for the prevention of brain IR and its consequences.

Family members of older incompetent patients are increasingly playing an essential role in the decision-making process relating to medical treatment. Furthermore, rights of patients and carers and the extent of their legal involvement vary widely across the European Union. Starting with an illustrative case within the Italian legal framework, this review focuses on statutory laws in the European Union to analyse the role and the rights of surrogates on behalf of older incompetent patients. The authors have identified two main essential areas of surrogate's law in Europe, in the absence of the advance directives: the role of family members automatically accepted as surrogates by law and a legal representative appointed by a court., (© 2018. European Geriatric Medicine Society.)

Background: Homozygous mutations in acid-labile subunit (IGFALS) gene result in short stature, very low circulating levels of acid-labile subunit (ALS), insulin growth factor 1 (IGF1) and insulin growth factor binding protein 3 (IGFBP3) and a poor response to growth hormone (GH). The impact of IGFALS mutations heterozygosity on growth is unknown., Patient and Methods: We describe a 10-year-old girl with severe short stature (height -3.2 SDS), heterozygous for a new IGFALS mutation., Results: The girl showed low circulating IGF1, IGFBP3 and ALS levels and normal GH secretion. We found a novel heterozygous frameshift IGFALS mutation (c.1283delA, p.Gln428Argfs*14). Size-exclusion chromatography showed a reduction of the IGF1, IGFBP3 and ALS 150-kDa ternary complex (by about 55%) compared to a control. An IGF-1 generation test, with two different GH dosages, showed a good response in term of increase in IGF1 and in formation of the ternary complex at size-exclusion chromatography. Clinical response after 6 months of therapy with GH was satisfactory (height velocity increased from 3 to 8 cm/year)., Conclusion: We suggest that (1) heterozygous IGFALS mutations can be responsible for a subset of patients with severe short stature (below -2.5 SDS), low IGF1 (below -2 SDS) and normal GH secretion, and (2) the identification by IGFALS molecular screening of this subset of patients could help in the administration of the appropriate therapy.

Aim: To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome (MetS)., Methods: Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination (AP) consisting of berberine, policosanol and red yeast rice, in a prospective, double-blind, placebo-controlled study. Evaluations were performed at baseline and after 18 wk of treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) index was the primary outcome measure. Secondary endpoints included lipid panel, blood glucose and insulin fasting, after a standard mixed meal and after an oral glucose tolerance test (OGTT), flow-mediated dilation (FMD), and waist circumference., Results: Fifty nine patients completed the study, 2 withdrew because of adverse effects. After 18 wk there was a significant reduction in the HOMA-IR index in the AP group compared with placebo (ΔHOMA respectively -0.6 ± 1.2 vs 0.4 ± 1.9; P < 0.05). Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo (Δlow density lipoprotein cholesterol -0.82 ± 0.68 vs -0.13 ± 0.55 mmol/L; P < 0.001), while triglycerides, high density lipoprotein cholesterol, and the OGTT were not affected. In addition, there were significant reductions in blood glucose and insulin after the standard mixed meal, as well as an increase in FMD (ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %; P < 0.05) and a significant reduction in arterial systolic blood pressure in the AP arm., Conclusion: This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS.

Background: Recent application of brain natriuretic peptide and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in cardiac valvular disease is very promising., Aims: To test the usefulness of NT-proBNP in the assessment of patients with aortic or mitral regurgitation., Patients and Methods: Sixty-seven patients - 23 with aortic and 12 with mitral regurgitation vs. 32 controls - were examined by color Doppler echocardiography, cardiopulmonary exercise testing, Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and plasma NT-proBNP assay at rest (T0) and after maximal physical exercise (T1)., Results: NT-proBNP was significantly higher in patients than in controls, both at T0 (298 +/- 85 vs. 46 +/- 11 pg/ml; P < 0.01) and at T1 (366 +/- 106 vs. 50 +/- 12 pg/ml; P < 0.01). MLWHFQ score was significantly higher in patients (19 +/- 3 vs. 1 +/- 0.6; P < 0.001) with a significant inverse correlation with VO2max (r = -0.538, P < 0.001) and a direct correlation with NT-proBNP (T0: r = 0.415, P < 0.01; T1: r = 0.458, P < 0.01). NT-proBNP was inversely correlated with VO2max (T0: r = -0.444, P < 0.001; T1:r = -0.428, P < 0.001) and directly correlated with left atrial diameter (T0: r = 0.370, P < 0.01; T1: r = 0.409, P = 0.001), and left ventricular mass index (r = 0.279, P < 0.01, and r = 0.272, P < 0.01). No correlations were found between echocardiographic parameters of valvular disease severity and VO2max, NT-proBNP and MLWHFQ., Conclusions: NT-proBNP is useful in the assessment of the cardiac functional damage secondary to mitral and aortic regurgitation.