The Combination of Natural Molecules Naringenin, Hesperetin, Curcumin, Polydatin and Quercetin Synergistically Decreases SEMA3E Expression Levels and DPPIV Activity in In Vitro Models of Insulin Resistance.

Type 2 diabetes mellitus (T2DM) is a disease characterized by a prolonged hyperglycemic condition caused by insulin resistance mechanisms in muscle and liver, reduced insulin production by pancreatic ß cells, and a chronic inflammatory state with increased levels of the pro-inflammatory marker semaphorin 3E. Phytochemicals present in several foods have been used to complement oral hypoglycemic drugs for the management of T2DM. Notably, dipeptidyl peptidase IV (DPPIV) inhibitors have demonstrated efficacy in the treatment of T2DM. Our study aimed to investigate, in in vitro models of insulin resistance, the ability of the flavanones naringenin and hesperetin, used alone and in combination with the anti-inflammatory natural molecules curcumin, polydatin, and quercetin, to counteract the insulin resistance and pro-inflammatory molecular mechanisms that are involved in T2DM development. Our results show for the first time that the combination of naringenin, hesperetin, curcumin, polydatin, and quercetin (that mirror the nutraceutical formulation GliceFen®, Mivell, Italy) synergistically decreases expression levels of the pro-inflammatory gene SEMA3E in insulin-resistant HepG2 cells and synergistically decreases DPPIV activity in insulin-resistant Hep3B cells, indicating that the combination of these five phytochemicals is able to inhibit pro-inflammatory and insulin resistance molecular mechanisms and could represent an effective innovative complementary approach to T2DM pharmacological treatment.

Prediction of complications of type 2 Diabetes: A Machine learning approach.

AIM: To construct predictive models of diabetes complications (DCs) by big data machine learning, based on electronic medical records. METHODS: Six groups of DCs were considered: eye complications, cardiovascular, cerebrovascular, and peripheral vascular disease, nephropathy, diabetic neuropathy. A supervised, tree-based learning approach (XGBoost) was used to predict the onset of each complication within 5 years (task 1). Furthermore, a separate prediction for early (within 2 years) and late (3-5 years) onset of complication (task 2) was performed. A dataset of 147.664 patients seen during 15 years by 23 centers was used. External validation was performed in five additional centers. Models were evaluated by considering accuracy, sensitivity, specificity, and area under the ROC curve (AUC). RESULTS: For all DCs considered, the predictive models in task 1 showed an accuracy > 70 %, and AUC largely exceeded 0.80, reaching 0.97 for nephropathy. For task 2, all predictive models showed an accuracy > 70 % and an AUC > 0.85. Sensitivity in predicting the early occurrence of the complication ranged between 83.2 % (peripheral vascular disease) and 88.5 % (nephropathy). CONCLUSIONS: Machine learning approach offers the opportunity to identify patients at greater risk of complications. This can help overcoming clinical inertia and improving the quality of diabetes care.

Effectiveness of Ascophyllum nodosum and Fucus vesiculosus on Metabolic Syndrome Components: A Real-World, Observational Study.

INTRODUCTION: Gdue is a nutraceutical obtained from the association of two marine algae, Ascophyllum nodosum and Fucus vesiculosus, in addition to chromium picolinate, which could be useful for the treatment of dysglycemia, overweight, and the other components of the metabolic syndrome. The aim of the study was to assess the real-world effectiveness and safety of Gdue when administered to subjects with one or more components of the metabolic syndrome. METHODS: A longitudinal, retrospective, observational study, conducted among primary care physicians, nutritionists, and specialists from various disciplines. The impact of 180 days of administration of Gdue was assessed on body weight, waist circumference, fasting blood glucose, HbA1c, lipid profile, and blood pressure levels. The likelihood of experiencing a first major cardiovascular event over ten years was estimated using Italian risk charts. General linear models for repeated measures were applied to assess changes in the parameters of interest during the follow-up. Results are expressed as estimated marginal means with their 95% confidence interval. RESULTS: Overall, 505 patients were enrolled by 282 physicians. After 6 months of treatment with Gdue, body weight was reduced on average by 7.3 kg (-8.0; -6.6), waist circumference by 7.5 cm (-8.2; -6.8), fasting blood glucose by 16.3 mg/dL (-17.8; -14.7), HbA1c by 0.55% (-0.62; -0.49), systolic and diastolic blood pressure by 7.1 mmHg (-8.3; -6.0) and 4.2 mmHg (-5.0; -3.5), respectively, LDL cholesterol by 18.2 mg/dL (-21.2; -15.3), and triglycerides by 39 mg/dL (-45; -32). HDL cholesterol was significantly increased by 2.9 mg/dL (0.7; 5.0). The 10-year risk of cardiovascular events significantly decreased by 1.8%, corresponding to a relative risk reduction of 27.7%. CONCLUSION: Our real-world study shows that 6 months of treatment with Gdue have an impact on all the components of the metabolic syndrome, thus offering the potential for decreasing the cardiovascular risk associated with metabolic syndrome.

Rest energy expenditure in Parkinson's disease: role of disease progression and dopaminergic therapy.

BACKGROUND: Weight loss affects more than 50% of subjects suffering from Parkinson's Disease (PD) and is associated with reduced life expectancy. The pathogenesis is multifactorial and the mechanism of PD metabolism control is unresolved. This cross-sectional study aimed to ascertain the relationship between rest energy expenditure (REE), PD duration, Hoehn & Yahr (H&Y) stage, drug therapy and body mass index (BMI), in order to determine possible predictors of weight loss. METHODS: We studied fifty-eight PD subjects, after excluding conditions with a known influence on metabolism and weight (severe tremor, dyskinesias, dementia, fever, on-going infections, thyroid disease, and dysphagia). Subjects underwent REE measurement, through indirect calorimetry, in both the OFF state (12 h fasting and off medications) and in the ON state (60 min after taking dopaminergic drugs). RESULTS: OFF state. In the majority of PD patients REE values did not differ from those expected (based upon age, gender and BMI), being significantly higher in subjects in H&Y stage IV than H&Y stage II (t = 3.5; p = 0.001). Disease duration and rigidity were significantly associated with increased REE (r(2) = 0.31, F = 3.6; p = 0.0045). ON state. REE decreased by approximately 8% in all subjects, irrespective of disease duration or H&Y stage. BMI was inversely related to disease duration and UPDRS motor score in the OFF state and directly related to UPDRS motor score in the ON state (r(2) = 0.333, F = 3.5; p = 0.003). CONCLUSIONS: In PD REE increases as a function of disease duration; its adverse role in the decrease in BMI seems to be compensated for by dopaminergic medication.

Expression of renal 11beta-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function.

OBJECTIVE: Renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) enables selective access of aldosterone to the mineralocorticoid receptor (MR). Impaired 11beta-HSD2 activity has been suggested in patients with hypertension as well as in patients with renal disease, where it may contribute to sodium retention, oedema and hypertension. To date, these studies have relied upon urinary cortisol (F) metabolite levels as surrogate markers of renal 11beta-HSD2 activity. METHODS: We have directly analysed renal 11beta-HSD2 mRNA expression in 95 patients undergoing kidney biopsy using TaqMan real-time PCR. Serum and 24-h urine samples were used to document underlying renal function and endocrine parameters. Urinary F and cortisone (E) metabolites were analysed using gas chromatography/mass spectrometry. RESULTS: Expression of 11beta-HSD2 did not correlate with blood pressure or urinary Na/K ratio, but a significant positive correlation with creatinine clearance was observed (r = 0.284; P < 0.01). Immunofluorescence and confocal laser microscopy confirmed decreased 11beta-HSD2 expression in patients with impaired renal function. For the first time, we showed that 11beta-HSD2 mRNA expression correlated negatively with the urinary free (UF) F/E (UFF/UFE) ratio (r = 0.276; P < 0.05) as well as with the urinary tetrahydrocortisol + 5alpha-tetrahydrocortisol/tetrahydrocortisone ((THF + alphaTHF)/THE) ratio (r = 0.256; P < 0.05). No difference in 11beta-HSD2 mRNA expression or in the UFF/UFE ratio was found between groups with no proteinuria, microalbuminuria, moderate or severe proteinuria. In contrast, the urinary (THF + alphaTHF)/THE ratio increased significantly (P < 0.05) in patients with severe albuminuria, suggesting increased hepatic 11beta-HSD1 in those patients. CONCLUSIONS: These data suggest that renal 11beta-HSD2 expression may be represented only marginally better, if at all, by the UFF/UFE than by the (THF + alphaTHF)/THE ratio. Reduced renal 11beta-HSD2 expression may lead to occupancy of the MR by glucocorticoids such as cortisol and may contribute to the increased sodium retention seen in patients with impaired renal function.

[Efficacy and limits of the bariatric surgery]. / Efficacia e limiti della chirurgia bariatrica.

Morbid obesity is associated with and increased risk of serious comorbidities, including type 2 diabetes, sleep apnoea, cardiovascular diseases, and orthopedic disabilities. Not operative treatments for superobese patients have not been shown to produce reliable long-term benefits, therefore surgical therapy has became the treatment of choice. The number of surgical procedures increased in the last year confirm these data. However, before recommended a specific surgical procedures to a superobese patients it is necessary to consider some variables, such as: patient, health structure, and multidisciplinary equipe. Since there are not recommended or condemned surgical procedures, in this paper the Authors tried to evaluate the effectiveness and limits of the most performed surgical procedures for the treatment of pathologic obesity: gastric by-pass, biliopancreatic diversion (duodenal switch), vertical gastroplasty, banding gastric. The Authors used some pointer of outcome to measure effectiveness and limits: five year post-operative percentage excess weight loss >/< 50, peri-operative >/< 1%, early and late complications >/< 15%, reoperation >/< 3%, improvement of quality of life. Thanks to new surgical technique, restrictive options are losing ground, while malabsorbitive bariatric procedures are collecting successful.

Laparoscopic adjustable gastric banding: essential role of psychological support.

BACKGROUND: A follow-up study of laparoscopic adjustable gastric banding (LAGB) in morbidly obese patients was conducted, with special emphasis on psychological aspects. MATERIALS AND METHODS: 128 patients (98/30 females/males) underwent LAGB between October 1995 and March 2001. Age was 38 +/- 9 years, body mass index (BMI) 42.72 +/- 4.25 kg/m2 and body weight 124 +/- 25 kg (mean +/- SD). Weight loss, early and late complications, band calibrations and difference between patients with and without psychotherapy were analysed. Psychological status was investigated before and during LAGB treatment using MMPI. Quality of life was investigated using MOS SF36. RESULTS: Median BMI decreased from 42.7 preoperatively to 31.0 kg/m2 after 12 months. Reduction of BMI was already significant (P < 0.01) after 3 months. In the following 12 months, median BMI wavered between 31.0 and 29.5 kg/m2. Best results were achieved in patients who followed psychotherapy. CONCLUSION: LAGB gave therapeutic success (progressive and significant weight loss). Psychotherapy was not only a simple support to diet but also an important part of the multidiscipline treatment. For best results, the team must care for patients individually and not just follow the same fixed protocol.