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Background/Objectives Plasma lipoprotein composition, especially in the postprandial state, could be relevant for cardiovascular risk and could be influenced by eating habits. This study evaluated the effects of a polyphenol-rich diet on postprandial lipoprotein composition in individuals at high cardiometabolic risk. Subjects/Methods Seventy-eight individuals with high waist circumference and at least another component of the metabolic syndrome were randomized to either a high-polyphenol (HighP) or low-polyphenol (LowP) diet. Before and after the 8-week intervention, chylomicrons, VLDL1, VLDL2, IDL, LDL, HDL particles, and their lipid concentrations were determined over a 6-h high-fat test meal with high or low-polyphenol content, according to the diet assigned. Results VLDL1 postprandial areas under the curve (AUCs) were lower for cholesterol (Chol) (1.48 [plus or minus] 0.98 vs. 1.91 [plus or minus] 1.13 mmol/L × 6 h, M [plus or minus] SD, p = 0.014) and triglycerides (Tg) (4.70 [plus or minus] 2.70 vs. 6.02 [plus or minus] 3.07 mmol/L × 6 h, p = 0.005) after the HighP than after the LowP diet, with no changes in Chol/Tg ratio. IDL Chol AUCs were higher after the HighP than after the LowP diet (1.29 [plus or minus] 0.77 vs. 1.01 [plus or minus] 0.51 mmol/L × 6 h, p = 0.037). LDL Tg AUCs were higher after the HighP than after the LowP diet (1.15 [plus or minus] 0.33 vs. 1.02 [plus or minus] 0.35 mmol/L × 6 h, p < 0.001), with a lower Chol/Tg ratio (14.6 [plus or minus] 4.0 vs. 16.0 [plus or minus] 3.8, p = 0.007). HDL Tg AUCs were lower after the HighP than after the LowP diet (1.20 [plus or minus] 0.41 vs. 1.34 [plus or minus] 0.37 mmol/L × 6 h, p = 0.013). Conclusions A high-polyphenol diet reduces the postprandial lipid content of large VLDL and increases IDL cholesterol; it modifies the composition of LDL particles--which become richer in triglycerides, and of HDL--which become instead triglyceride poor. The overall changes in atherogenicity by these effects warrant further investigation on clinical cardiovascular outcomes., Author(s): Giuseppe Della Pepa [sup.1], Claudia Vetrani [sup.1], Marilena Vitale [sup.1], Lutgarda Bozzetto [sup.1], Giuseppina Costabile [sup.1], Paola Cipriano [sup.1], Anna Mangione [sup.1], Lidia Patti [sup.1], Gabriele Riccardi [sup.1], Angela [...]

Aims: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO‐IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). Materials and Methods: Hierarchical clustering based on WC and ADIPO‐IR (calculated as fasting plasma non‐esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC‐MS and LC‐MSQTOF). Indexes of fatty acid desaturation (stearoyl‐coA desaturase‐1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA‐IR) were also calculated. Results: Three clusters were identified: CL1 (ADIPO‐IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO‐IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO‐IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO‐IR, and HOMA‐IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46–50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). Conclusions: High ADIPO‐IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. Registration Number Trial: ID NCT00700856 https://clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background. High blood concentrations of triglycerides (TG) in the postprandial period have been shown to be more closely associated with the risk of cardiovascular disease (CVD) than fasting values in individuals with type 2 diabetes (T2D). Dietary changes are the primary determinants of postprandial lipid responses. Methods. We investigated the effects of an isocaloric multifactorial diet, rich in n-3 PUFA, MUFA, fiber, polyphenols, and vitamins, compared to an isocaloric diet, containing the same amount of MUFA, on the postprandial lipid response in T2D individuals. Following a randomized, controlled, parallel group design, 43 (25 male/18 female) T2D individuals were assigned to an isocaloric multifactorial (n = 21) or a MUFA-rich diet (n = 22). At the beginning and after the 8 weeks of dietary intervention, the concentrations of plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol were detected at fasting and over a 4-h test meal with the same composition as the prescribed diet. Results. The concentrations of fasting plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol did not change after both diets. Compared with the MUFA diet, the 8-week multifactorial diet significantly lowered the postprandial response, which was evaluated as the incremental area under the curve (iAUC), of triglycerides by 33% (64 ± 68 vs. 96 ± 50 mmol/L·240 min, mean ± SD, respectively, p = 0.018), total cholesterol by 105% (−51 ± 33 vs. −25 ± 29, p = 0.013), and non-HDL cholesterol by 206% (−39 ± 33 vs. −13 ± 23, p = 0.013). Conclusions. In T2D individuals, a multifactorial diet, characterized by several beneficial components, improved the postprandial lipid response compared to a MUFA diet, generally considered a healthy diet being reduced in saturated fat, and probably contributed to the reduction of cardiovascular risk. [ABSTRACT FROM AUTHOR]

Objective: The risk of developing micro- andmacrovascular complications is higher for individuals with type 1 diabetes (T1D). Numerous studies have indicated variations in gutmicrobial composition between healthy individuals and those with T1D. These changes in the gut ecosystem may lead to inflammation, modifications in intestinal permeability, and alterations in metabolites. Such effects can collectively impact the metabolic regulation system, thereby influencing blood glucose control. This review aims to explore the relationship between the gut microbiome, inflammation, and blood glucose parameters in patients with T1D. Methods: Google Scholar, PubMed, and Web of Science were systematically searched from 2003 to 2023 using the following keywords: “gut microbiota,” “gut microbiome,” “bacteria,” “T1D,” “type 1 diabetes,” “autoimmune diabetes,” “glycemic control,” “glucose control,” “HbA1c,” “inflammation,” “inflammatory,” and “cytokine.” The examination has shown 18,680 articles with relevant keywords. After the exclusion of irrelevant articles, seven observational papers showed a distinct gut microbial signature in T1D patients. Results: This review shows that, in T1D patients, HbA1c level was negatively correlated with abundance of Prevotella, Faecalibacterium, and Ruminococcaceae and positively correlated with abundance of Dorea formicigenerans, Bacteroidetes, Lactobacillales, and Bacteriodes. Instead, Bifidobacteria was negatively correlated with fasting blood glucose. In addition, there was a positive correlation between Clostridiaceae and time in range. Furthermore, a positive correlation between inflammatory parameters and gut dysbiosis was revealed in T1D patients. Conclusion: We draw the conclusion that the gut microbiome profiles of T1D patients and healthy controls differ. Patients with T1D may experience leaky gut, bacterial translocation, inflammation, and poor glucose management due to microbiome dysbiosis. Direct manipulation of the gut microbiome in humans and its effects on gut permeability and glycemic control, however, have not been thoroughly investigated. Future research should therefore thoroughly examine other potential pathophysiological mechanisms in larger studies. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the validity of a web-based 7-day food-record using METADIETA-web link (Meteda s.r.l.) – a professional software used in nutritional practice and research – compared with the traditional paper format. Twenty-six healthy adults of both sexes were recruited in this cross-over study based on the number coming from the sample size calculation, and randomly assigned to start with METADIETA-web or traditional 7-Day Food-Diary. All the 7-day food-diaries were recorded in the Metadieta-software. The System Usability Scale (SUS) questionnaire was administered to evaluate the participants' preferences in terms of usability, acceptability, and feasibility. Differences in energy intake, nutrient composition, and SUS between the digital and traditional modalities were evaluated. Energy and nutrients were not significantly different between the two methods with a variation <15%, with alcohol intake showing the strongest relation (0.1% variation). The Interclass Correlation Coefficient showed a grade of consistency between the two methods excellent for alcohol, good for proteins, carbohydrates, and fibre, moderate for energy and saturated fat, and poor for total fat and cholesterol. SUS suggested that the web-based platform was in general well accepted, but highlighted some inconsistencies and complexity compared to the written food diary. The web-based 7-day food-record may allow an accurate and quicker analysis of food timing than conventional approaches, seeming reliable for energy and macronutrient composition, making it a potentially attractive tool for nutritional research. However, the reported inconsistencies and complexity must be considered and addressed. [ABSTRACT FROM AUTHOR]

Background: The use of dressings is an essential component of the standard of care for diabetic foot ulcers (DFUs); however, despite the wide variety of dressings available, there is a lack of evidence from head-to-head randomized controlled trials. We evaluated the efficacy and safety of Triticum vulgare extract and polyhexanide (Fitostimoline® hydrogel/Fitostimoline® Plus gauze) versus saline gauze dressings in patients with DFUs. Methods: This study involved a monocentric, two-arm, open-label, controlled trial in patients with DFUs (Grades I or II, Stage A or C, based on the Texas classification) randomized to 12 weeks of dressing with Fitostimoline® hydrogel/Fitostimoline® Plus gauze or saline gauze. The number of patients with complete healing, the reduction in DFU size, and the presence of local signs and symptoms of the wound and perilesional skin were evaluated every two weeks and at the end of treatment. Results: A total of 40 adult patients were recruited (20 patients in each treatment group). The proportion of patients with complete healing was similar between the two groups (61% vs. 74%, p = 0.495, Fitostimoline® hydrogel/Fitostimoline® Plus gauze vs. saline gauze, respectively), without significant differences, as well as the reduction in DFU size. A significant improvement in local signs and symptoms of the wound and signs of perilesional skin in the Fitostimoline® hydrogel/Fitostimoline® Plus gauze compared with the saline gauze group was observed. Conclusions: In a clinical setting, the use of Fitostimoline® hydrogel/Fitostimoline® Plus gauze dressing in patients with DFUs significantly improves signs and symptoms of the wound and signs of perilesional skin compared with saline gauze dressing with a similar efficacy in terms of wound healing. [ABSTRACT FROM AUTHOR]

Background: There are still open questions with respect to the optimal dietary treatment in patients with type 2 diabetes (T2D) and coexisting non-alcoholic steatohepatitis (NASH). The aim of this study is to investigate, in patients with T2D, the association between NASH, dietary component intake, food groups and adherence to the Mediterranean diet. Methods: Cross-sectional analysis of 2026 people with T2D (1136 men and 890 women). The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. NASH was identified by the Index Of NASH (ION). Based on the cluster analysis two dietary patterns were identified: the NASH and the NO-NASH pattern. Results: The macronutrient composition of the diet was similar in the two patterns. However, the NASH pattern compared with the NO-NASH pattern was characterized by a significantly lower content of fibre (p < 0.001), β-carotene (p < 0.001), vitamin C (p < 0.001), vitamin E (p < 0.001), polyphenols (p = 0.026) and antioxidant capacity (p < 0.001). With regard to food consumption, the NASH pattern compared with NO-NASH pattern was characterized by higher intake of rice (p = 0.021), potatoes (p = 0.013), red (p = 0.004) and processed meat (p = 0.003), and a lower intake of wholegrain bread (p = 0.019), legumes and nuts (p = 0.049), vegetables (p = 0.047), fruits (p = 0.002), white meat (p = 0.001), fatty fish (p = 0.005), milk and yogurt (p < 0.001). Conclusions: NO-NASH dietary pattern was characterized by a food consumption close to the Mediterranean dietary model, resulting in a higher content of polyphenols, vitamins, and fibre. These finding highlight the potential for dietary components in the prevention/treatment of NASH in people with T2D. [ABSTRACT FROM AUTHOR]

Aim: aim of the study was to evaluate serum short chain fatty acids (SCFA) concentrations in patients with Type 2 diabetes (T2D) and overweight/obese individuals. Methods: In forty-three patients with T2D and twenty-eight overweight/obese patients SCFA were determined by Gas-Chromatography/Flame Ionization Detector (GC/FID). Results: Acetic acid, propionic acid, butyric acid, and total SCFA were significantly reduced in T2D patients compared to overweight/obese in the unadjusted model. Adjusting for all variables only propionic acid remained significantly lower in T2D. Conclusion: Only reduction of propionic acid was closely related to diabetes itself, regardless of all other factors. [ABSTRACT FROM AUTHOR]

Objective: To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D).Research Design and Methods: According to a randomized controlled parallel-group design, 39 individuals with T2D, 35-75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet.Results: After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0-120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = -0.383; P = 0.023).Conclusions: In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and/or β-oxidation. Methods: According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma β-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively. Results: Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs. 1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma β-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). Conclusions: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416. [ABSTRACT FROM AUTHOR]

Background Plasma trimethylamine N-oxide (TMAO) has drawn much attention as a marker of several chronic diseases. Data on the relation between diet and TMAO are discordant and few human intervention studies have assessed causality for this association. Objectives We aimed to evaluate the effects on plasma TMAO of diets based on foods rich in polyphenols (PP) and/or long-chain n–3 fatty acids (LCn3) or whole-grain cereals (WGCs), in individuals at high cardiometabolic risk. Methods An ancillary study was performed within 2 randomized controlled trials, aimed at evaluating the medium-term effects on cardiometabolic risk factors of diets naturally rich in PP and/or LCn3 (Etherpaths Project) or WGCs (HealthGrain Project). Results In the Etherpaths study (n = 78), the changes in TMAO (8-wk minus baseline) were statistically significant for the diets rich in LCn3 (+1.15 ± 11.58 μmol/L) (P = 0.007), whereas they were not for the diets rich in PP (−0.14 ± 9.66 μmol/L) (P  = 0.905) or their interaction (P  = 0.655) (2-factor ANOVA). In the HealthGrain Study (n  = 48), the TMAO change (12-wk minus baseline) in the WGC group (+0.94 ± 3.58 μmol/L) was significantly different from that in the Refined Cereal group (−1.29 ± 3.09 μmol/L) (P  = 0.037). Considering the pooled baseline data of the participants in the 2 studies, TMAO concentrations directly correlated with LCn3, EPA (20:5n–3), and protein intake, but not SFAs, fiber, MUFAs, and PP intake. Among food groups, TMAO directly correlated with the intake of fish, vegetables, and whole-grain products, but not meat, processed meat, and dairy products. Conclusions Diets rich in LCn3 of marine origin or WGCs significantly increased plasma TMAO concentration. These changes mirrored the direct associations between TMAO concentrations and intakes of fish and WGCs, suggesting that TMAO reflects intakes of these healthy foods and, therefore, it is not a universally valid biomarker of cardiometabolic risk independent of the background diet. These trials were registered at clinicaltrials.gov as NCT01154478 and NCT00945854. [ABSTRACT FROM AUTHOR]

Background: Here, we evaluate the effects of a diet rich in low‐glycaemic index carbohydrates and fibre (CHO/Fibre diet) or monounsaturated fatty acids (MUFA diet), on fasting and postprandial adiponectin concentrations and their relationship with the beneficial effects of the experimental diets on postprandial glucose metabolism and liver fat in type 2 diabetes (T2D). Methods: Fasting and postprandial adiponectin plasma concentrations were measured before and after dietary interventions in the participants to a randomized controlled trial (NCT01025856), wherein 37 men and 8 women with T2D, aged 35‐70 years, followed a CHO/Fibre diet or a MUFA diet for an 8‐week period. Hepatic fat content by 1H NMR and fasting and postprandial plasma glucose and insulin measurements were also available. Results: Fasting adiponectin plasma levels did not change after both diets. Postprandial adiponectin significantly increased after the CHO/fibre diet (9.9 ± 1.6 μg/mL vs. 10.8 ± 2.3 μg/mL; P =.033) but not after the MUFA diet (10.6 ± 1.8 μg/mL vs. 10.6 ± 1.6 μg/mL; P =.935) with a significant difference between changes (P =.035). In the combined CHO/Fibre and MUFA groups, fasting and postprandial adiponectin significantly and inversely correlated with postprandial insulin iAUC at baseline and after intervention, and with liver fat content after intervention. Conclusions: A diet rich in CHO/Fibre increased postprandial plasma adiponectin significantly more than a MUFA diet in patients with T2D. Independently of diet, adiponectin levels associated with postprandial insulin concentrations. The dietary interventions modulated the relationship between adiponectin and liver fat. [ABSTRACT FROM AUTHOR]

Abstract Background The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT) of subjects with both obesity and type 2 diabetes (OBT2D), characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB). Design and Methods The levels of anandamide and 2-AG, and of the anandamide-related PPARα ligands, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW) subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p < 0.05), and 2-AG levels 2.3-fold reduced (p < .05), in OBT2D but not in OB subjects. Anandamide, OEA and PEA correlated positively (p < .05) with SAT leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all specifically altered in OBT2D subjects. Conclusions The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners) and 2-AG in obesity and type 2 diabetes.

Abnormalities in postprandial lipemia (PPL), particularly those related to triglyceride-rich lipoproteins, are considered an independent cardiovascular risk factor. As diet is known to be one of the main modulators of PPL, the aim of this review was to summarize and discuss current knowledge on the impact of diet and its components on PPL in humans; specifically, the impact of weight loss, different nutrients (quantity and quality of dietary fats, carbohydrates, and proteins), alcohol and other bioactive dietary components (i.e., polyphenols), as well as the effect of different dietary patterns. The possible mechanisms behind the metabolic effects of each dietary component were also discussed. [ABSTRACT FROM AUTHOR]

Background and Aims: Plasma apolipoprotein C3 (ApoC3) is associated with higher plasma triglyceride and type 2 diabetes incidence. We evaluated whether body mass index (BMI) or glucose metabolism were associated with ApoC3 in healthy monozygotic (MZ) twins.Methods and Results: Forty-seven MZ twin-pairs (20 man, 27 women), aged 23-42 years, were divided in subgroups according to discordance or concordance for (a) BMI (within-pair difference (Δ) in BMI≥3.0 or<3.0 kg/m2), or (b) 2-h glucose iAUC, during oral glucose tolerance test (ΔGlucose iAUC ≥97.5 or<97.5 mmol × 120 minutes). Within these discordant or concordant subgroups, we tested (Wilcoxon signed-rank test) co-twin differences in ApoC3, adiposity measures, insulin-resistance and beta-cell function indices, and plasma and lipoprotein lipids. In BMI-Discordant (p = 0.92) or BMI-Concordant (p = 0.99) subgroups, ApoC3 did not differ between leaner and heavier co-twins. In the Glucose-Discordant subgroup, ApoC3 was significantly higher in twins with higher Glucose iAUC than in their co-twins with the lower Glucose iAUC (10.03 ± 0.78 vs. 8.48 ± 0.52 mg/dl; M ± SE; p = 0.032). Co-twins with higher Glucose iAUC also had higher waist circumference, body fat percentage, liver fat content, worse insulin-sensitivity and beta-cell function and higher cholesterol and triglyceride in plasma VLDL, IDL, and LDL. In Glucose-Concordant twin-pairs, no significant differences were observed in the explored variables. In all twin-pairs, ΔApoC3 correlated with Δ in lipids and glucose metabolism variables, the closest relationship being between ΔApoC3 and ΔVLDL triglyceride (r = 0.74, p < 0.0001).Conclusions: While ApoC3 was not related to acquired differences in BMI, it associated with early dysregulation of glucose metabolism independently of obesity and genetic background. [ABSTRACT FROM AUTHOR]

Background and Aims: Overweight/obesity is a clinical concern also in patients with Type 1 diabetes (T1DM). These patients' body weight may vary depending on whether treatment consists in continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI), as these treatments lead to different blood glucose control, insulin doses, and eating behaviors. We compared long-term body weight trajectories in persons with diabetes on CSII or MDI regimens.Methods and Results: Annual changes in body weight, HbA1c, and daily insulin doses over 6-10 years were retrospectively analyzed in T1DM adult patients on CSII (n = 90) or MDI (n = 90), strictly matched for sex, age, BMI, and diabetes duration. Mean follow-up was 9.1 ± 1.4 years. Body weight increased linearly (∼0.5 kg per year) throughout the observation period (p = 0.001, repeated measures ANOVA) with no significant difference between the CSII and MDI cohorts (p = 0.74), in either normal-weight or overweight/obese patients. HbA1c over follow-up was lower with CSII than with MDI (p = 0.037), maintaining the initial reduction after starting pump therapy. Insulin doses over follow-up were stably lower than baseline (∼20%) with CSII, while linearly increasing (∼20% from baseline to the end of observation) with MDI (p = 0.002). Mean annual weight changes correlated directly with total insulin dose changes (r = 0.191; p = 0.011) and baseline HbA1c level (r = 0.267; p = 0.001), and inversely with HbA1c changes (-0.173; p = 0.021) and baseline age (r = -0.254; p = 0.001).Conclusion: T1DM patients on CSII or MDI showed comparable body weight gain over a 10-year follow-up, despite improved glycemic control and decreased insulin doses with CSII. [ABSTRACT FROM AUTHOR]

Obesity is a pandemic carrying the heavy burden of multiple and serious co-morbidities including metabolic syndrome, type 2 diabetes and cardiovascular diseases. The pathophysiological processes leading to the accumulation of body fat slowly evolve to fat accumulation in other body compartments than subcutaneous tissue. This abnormal fat deposition determines insulin resistance which in turn causes blood glucose and lipid metabolism derangement, non-alcoholic fatty liver disease, hypertension, and metabolic syndrome. All these conditions contribute to increase the cardiovascular risk of obese people. Several randomized clinical trials demonstrated that moderate weight loss (5–10%) in obese patients improves obesity-related metabolic risk factors and coexisting disorders. Therefore, nutritional strategies able to facilitate weight management, and in the meantime positively influence obesity-associated cardiovascular risk factors, should be implemented. To this aim, a suitable option could be dietary fibres that may also act independently of weight loss. The present narrative review summarizes the current evidence about the effects of dietary fibres on weight management in obese people. Moreover, all of the different cardiovascular risk factors are individually considered and evidence on cardiovascular outcomes is summarized. We also describe the plausible mechanisms by which different dietary fibres could modulate cardio-metabolic risk factors. Overall, despite both epidemiological and intervention studies on weight loss that show statistically significant but negligible clinical effects, dietary fibres seem to have a beneficial impact on main pathophysiological pathways involved in cardiovascular risk (i.e., insulin resistance, renin-angiotensin, and sympathetic nervous systems). Although the evidence is not conclusive, this suggests that fibre would be a suitable option to counteract obesity-related cardio-metabolic diseases also independently of weight loss. However, evidence is not consistent for the different risk factors, with clear beneficial effects shown on blood glucose metabolism and Low Density Lipoprotein (LDL) cholesterol while there is fewer, and less consistent data shown on plasma triglyceride and blood pressure. Ascribing the beneficial effect of some foods (i.e., fruits and vegetables) solely to their fibre content requires more investigation on the pathophysiological role of other dietary components, such as polyphenols. [ABSTRACT FROM AUTHOR]

Background and Aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII).Methods and Results: Questionnaires investigating the organisation of diabetes care centres, individuals' clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. <58 mmol/mol for age <18 years and <53 mmol/mol for age >18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis.Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia.Clinical Trial Registration Number: NCT 02620917 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Aims: Due to their different chemical structures and metabolism, polyphenol subclasses may have specific impact on cardiometabolic risk factors. Our aim was to evaluate whether the intake of different polyphenol subclasses is associated with clinical outcomes beneficially improved by polyphenols in a nutritional trial performed by our group (postprandial lipid response, glucose homeostasis, early insulin secretion and oxidative stress).Methods: The present study is a secondary analysis of a nutritional intervention study with a diet naturally rich in polyphenols. The data are derived from 78 participants at high cardiovascular risk who completed the ETHERPATH trial. The associations between variations in polyphenol subclasses (phenolic acids, anthocyanidins, flavones, flavan-3-ols, flavonols and flavanones) and clinical outcomes beneficially influenced by polyphenols were firstly explored by Spearman’s correlation. Thereafter, adjustment for gender, age and body mass index (BMI) was run. Linear regression analysis was used to assess the class of polyphenols that best predicted the outcome. Results: Flavanone intake was inversely correlated with postprandial lipid response, whereas flavone intake was related to postchallenge glucose response. Anthocyanidins and flavan-3-ols associated positively with early insulin secretion. The decrease in urinary isoprostanes correlated with anthocyanidins, flavan-3-ols and flavonols. Correlations did not change after adjustment for gender, age, and BMI. Linear regression analysis showed an independent association between flavonols and urinary isoprostanes, whereas early insulin secretion was mainly associated with flavan-3-ols intake. Conclusions: The results of this study show that a polyphenol-rich diet may have a pleiotropic effect on cardiometabolic risk factors thanks to the specific action of different polyphenol subclasses. [ABSTRACT FROM AUTHOR]

Micronutrients are of fundamental importance in maintaining health status. However, data on their dietary intake are few particularly in persons with diabetes. The aim of this study was to evaluate in adults with type 1 diabetes (T1DM) attending a tertiary-level diabetes center in Southern Italy the intake of micronutrients (both vitamins and minerals) and the adherence to recommendations. Seven-day food records of 60 T1DM patients were analyzed. Micronutrient intake was evaluated based on the Italian food composition tables and expressed as amount per 1000 kcal of energy intake to adjust for possible underreporting. Adherence to recommendations for vitamins A, B6, B12, and C and niacin was acceptable in both sexes (ranging from 77% to 100%). Half of the patients did not adhere to folate recommendation, even less to vitamin E, and no patient reached the recommended intake for vitamin D. As for minerals, adherence was low for potassium and selenium (0–23%); intermediate for zinc, copper, and magnesium; low and intermediate for calcium in men and women, respectively; and low for iron in women. In conclusion, the diet followed by T1DM patients may not have a sufficient content of different micronutrients. Therefore, an adequate intake of low-fat dairy products, fish, legumes, and vegetables should be encouraged as components of a healthier dietary pattern. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) incorporates an extensive spectrum of histologic liver abnormalities, varying from simple triglyceride accumulation in hepatocytes non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), and it is the most frequent chronic liver disease in the industrialized world. Beyond liver related complications such as cirrhosis and hepatocellular carcinoma, NAFLD is also an emerging risk factor for type 2 diabetes and cardiovascular disease. Currently, lifestyle intervention including strategies to reduce body weight and to increase regular physical activity represents the mainstay of NAFLD management. Total caloric intake plays a very important role in both the development and the treatment of NAFLD; however, apart from the caloric restriction alone, modifying the quality of the diet and modulating either the macro- or micronutrient composition can also markedly affect the clinical evolution of NAFLD, offering a more realistic and feasible treatment alternative. The aim of the present review is to summarize currently available evidence from randomized controlled trials on the effects of different nutrients including carbohydrates, lipids, protein and other dietary components, in isocaloric conditions, on NAFLD in people at high cardiometabolic risk. We also describe the plausible mechanisms by which different dietary components could modulate liver fat content. [ABSTRACT FROM AUTHOR]

Introduction: Prescription of statins for low-density lipoprotein cholesterol (LDL-C) reduction is the standard of care in primary and secondary prevention of cardiovascular disease; nevertheless, a large number of patients treated with statins are unable to reach the recommended LDL-C targets. Therefore, there is need for safe and effective novel therapies for the pharmacological management of hypercholesterolaemia, in addition or as alternative to lipid-lowering therapies (LLT) currently in use. Areas covered: In 2015, the Food and Drug Administration and the European Medicines Agency approved alirocumab (Praluent®; Sanofi), a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), for the treatment of hypercholesterolaemic patients unable to meet LDL-C targets, as an adjunct to diet in addition/alternative to LLT. The authors review the pharmacological features, clinical efficacy, and safety of alirocumab in lowering LDL-C, and discuss its therapeutic perspectives based on the most recent clinical trials. Expert commentary: Alirocumab causes a marked reduction in LDL-C, presents good safety and tolerability, and represents a promising approach for LDL-C lowering, particularly in patients with intolerance to statin or elevated LDL-C despite maximal statin therapy; nevertheless, further long-term data on safety and efficacy are necessary, such as data on the improvement of cardiovascular outcomes. [ABSTRACT FROM PUBLISHER]

Aims/hypothesis: The aim of this work was to investigate hepatic lipid metabolic processes possibly involved in the reduction of liver fat content (LF) observed in patients with type 2 diabetes after an isoenergetic diet enriched in monounsaturated fatty acids (MUFAs). Methods: This is an ancillary analysis of a published study. In a parallel-group design, 30 men and eight women, aged 35-70 years, with type 2 diabetes and whose blood glucose was controlled satisfactorily (HbA < 7.5% [58 mmol/mol]) by diet or diet plus metformin, were randomised by MINIM software to follow either a high-carbohydrate/high-fibre/low-glycaemic index diet (CHO/fibre diet, n = 20) or a high-MUFA diet (MUFA diet, n = 18) for 8 weeks. The assigned diets were known for the participants and blinded for people doing measurements. Before and after intervention, LF was measured by H-MRS (primary outcome) and indirect indices of de novo lipogenesis (DNL) (serum triacylglycerol palmitic:linoleic acid ratio), stearoyl-CoA desaturase activity (SCD-1) (serum triacylglycerol palmitoleic:palmitic acid ratio) and hepatic β-oxidation of fatty acids (β-hydroxybutyrate plasma concentrations) were measured. Results: LF was reduced by 30% after the MUFA diet, as already reported. Postprandial β-hydroxybutyrate incremental AUC (iAUC) was significantly less suppressed after the MUFA diet ( n = 16) (−2504 ± 4488 μmol/l × 360 min vs baseline −9021 ± 6489 μmol/l × 360 min) while it was unchanged after the CHO/fibre diet ( n = 17) (−8168 ± 9827 μmol/l × 360 min vs baseline −7206 ± 10,005 μmol/l × 360 min, p = 0.962) (mean ± SD, p = 0.043). In the participants assigned to the MUFA diet, the change in postprandial β-hydroxybutyrate iAUC was inversely associated with the change in LF ( r = −0.642, p = 0.010). DNL and SCD-1 indirect indices did not change significantly after either of the dietary interventions. Conclusions/interpretation: Postprandial hepatic oxidation of fatty acids is a metabolic process possibly involved in the reduction of LF by a MUFA-rich diet in patients with type 2 diabetes. Trial registration : ClinicalTrials.gov NCT01025856 Funding : The study was funded by Ministero Istruzione Università e Ricerca and Italian Minister of Health. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether fat quality, in the context of meals with high- (HGI) or low-glycemic index (LGI), influences postprandial blood glucose (PPG) response in patients with type 1 diabetes.Research Design and Methods: According to a randomized crossover design, 13 patients with type 1 diabetes on insulin pump consumed two series (HGI or LGI) of meals with the same carbohydrate quantity while differing for amount and quality of fat: 1) low in fat ("low fat"), 2) high in saturated fat (butter), or 3) high in monounsaturated fat (extra-virgin olive oil) (EVOO). Premeal insulin doses were based on insulin-to-glycemic load ratios. Continuous glucose monitoring was performed and 6-h PPG evaluated.Results: PPG was significantly different between HGI and LGI meals (P = 0.005 for time × glycemic index interaction by repeated-measures analysis [RMA]), being significantly higher during the first 3 h after the HGI meals with a later tendency to an opposite pattern. In the context of HGI meals, PPG was significantly lower after EVOO than after low fat or butter (P < 0.0001 for time × meal interaction by RMA), with a marked difference in the 0- to 3-h glucose incremental area under the curve between EVOO (mean ± SD 198 ± 274 mmol/L × 180 min) and either low fat (416 ± 329) or butter (398 ± 355) (P < 0.05). No significant differences were observed in PPG between the three LGI meals.Conclusions: Carbohydrate quality of a mixed meal influences shape and extent of PPG. Besides, using EVOO in a HGI meal attenuates the early postprandial glucose response observed when this meal is consumed with either low fat or butter. Therefore, an optimal prandial insulin administration would require considering, in addition to the quantity of carbohydrates, the quality of both carbohydrate and fat. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Type 2 diabetes is associated with atherogenic abnormalities of postprandial triglyceride-rich lipoproteins. This study evaluated whether ezetimibe, by inhibiting intestinal cholesterol absorption, influences chylomicrons and VLDL particles at fasting and after a standard meal. Methods: By a double blind cross-over design 15 subjects with type 2 diabetes and hypercholesterolaemia followed in random order a 6-week treatment with ezetimibe 10mg+simvastatin 20mg (EZE+S) or placebo+simvastatin 20mg (P+S) and, after a 6-week wash-out period, crossed over to the other treatment (NCT00699023). At the end of each period lipids, apoB-48, and apoB-100 concentrations in plasma and lipoprotein fractions (separated by discontinuous density gradient ultracentrifugation) were determined before and over 6h following a high-fat test meal. Results: Compared with P+S, EZE+S induced, (a) beside a greater decrease in LDL cholesterol, (b) a significant decrease in chylomicron lipid content both at fasting and postprandially (4.4±2.7 vs. 8.3±8.7mg/dl×6h total AUC for cholesterol, p <0.05; 18±12 vs. 29±24mg/dl triglyceride concentrations at 6h, p <0.05), (c) a significant decrease in chylomicron postprandial apoB-48 (0.03±0.03 vs. 0.09±0.08mg/l at 4h, p <0.05), and (d) significant fasting and postprandial decreases in the cholesterol content of VLDL, IDL, and LDL, as shown by the significant reduction of the cholesterol/triglyceride ratio in these lipoproteins. Conclusions: A 6-week treatment with ezetimibe and simvastatin, compared to simvastatin alone, positively influences lipoprotein profile both at fasting and postprandially in type 2 diabetic patients by favouring the production of cholesterol-poor chylomicrons and VLDL particles that have less atherogenic potential. [Copyright &y& Elsevier]

Background: The endocannabinoids, anandamide and 2-AG, are produced by adipocytes, where they stimulate lipogenesis via cannabinoid CB1 receptors and are under the negative control of leptin and insulin. Endocannabinoid levels are elevated in the blood of obese individuals and nonobese type 2 diabetes patients. To date, no study has evaluated endocannabinoid levels in subcutaneous adipose tissue (SAT) of subjects with both obesity and type 2 diabetes (OBT2D), characterised by similar adiposity and whole body insulin resistance and lower plasma leptin levels as compared to non-diabetic obese subjects (OB). Design and Methods: The levels of anandamide and 2-AG, and of the anandamide-related PPARa ligands, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), in the SAT obtained by abdominal needle biopsy in 10 OBT2D, 11 OB, and 8 non-diabetic normal-weight (NW) subjects, were measured by liquid chromatography-mass spectrometry. All subjects underwent a hyperinsulinaemic euglycaemic clamp. Results: As compared to NW, anandamide, OEA and PEA levels in the SAT were 2-4.4-fold elevated (p < 0.05), and 2-AG levels 2.3-fold reduced (p < .05), in OBT2D but not in OB subjects. Anandamide, OEA and PEA correlated positively (p < .05) with SAT leptin mRNA and free fatty acid during hyperinsulinaemic clamp, and negatively with SAT LPL activity and plasma HDL-cholesterol, which were all specifically altered in OBT2D subjects. Conclusions: The observed alterations emphasize, for the first time in humans, the potential different role and regulation of adipose tissue anandamide (and its congeners) and 2-AG in obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]