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BACKGROUND AND AIM: To evaluate the combined contribution of UCP3-55CT and PPAR?2 Pro12Ala polymorphisms as correlates of BMI, energy expenditure (REE) and substrate oxidation in people with type 2 diabetes. METHODS AND RESULTS: Two independent population with type 2 diabetes were studied: population A, n = 272; population B, n = 269. Based on both UCP3 and PPAR?2 genotypes three groups were created. Carriers of the PPAR?2 Pro12Ala in combination with the CC genotype of UCP3 (ProAla/CC, group 1); carriers of only one of these genotypes (either CC/ProPro or CT-TT/ProAla, group 2); people with neither variants (CT-TT/ProPro, group 3). In both populations BMI (kg/m(2)) was highest in group 1, intermediate in group 2 and lowest in group 3, independent of energy intake (i.e 35.3 ± 6.7 vs 33.4 ± 5.4 vs 31.8 ± 3, p < 0.02, population A; 32.4 ± 4.2 vs 31.7 ± 3.8 vs 30.1 ± 2.7; p < 0.03, population B). People with the ProAla/CC genotype (group 1) showed similar REE, but lower lipid oxidation (10.9 vs 13.9 g/kg fat free mass/day; p = 0.04) and higher carbohydrate oxidation (23.6 vs 15.6 g/kg fat free mass/day; p = 0.02) than carriers of other genotypes. CONCLUSIONS: The combination of UCP3-55 CC and PPAR?2 Pro12Ala genotypes is associated with significantly higher BMI than other PPAR?2-UCP3 genotype combinations, partly due to a reduced ability in lipids oxidation. The relative importance of these mechanism(s) may be different in non diabetic people. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

The aim of this study was to determine the diagnostic performance of ultrasound (US) in the quantitative assessment of steatosis by comparison with proton magnetic resonance spectroscopy ((1)H-MRS) as a reference standard. Three liver echo-intensity indices were derived: US hepatic mean gray level, hepatic-renal echo-intensity ratio (H/R), and hepatic-portal blood echo-intensity ratio. The (1)H-MRS degree of steatosis was determined as percentage fat by wet weight. Regression equations were used to estimate quantitatively hepatic fat content. The hepatic fat content by (1)H-MRS analysis ranged from 0.10% to 28.9% (median value, 4.8%). Ultrasound H/R was correlated with the degree of steatosis on (1)H-MRS (R(2)= 0.92; P < .0001), whereas no correlation with (1)H-MRS was found for hepatic mean gray level and hepatic-portal blood echo-intensity ratio. A receiver operating characteristic curve identified the H/R of 2.2 as the best cutoff point for the prediction of (1)H-MRS of at least 5%, yielding measures of sensitivity and specificity of 100% and 95%, respectively. In this pilot study, US H/R exhibits high sensitivity and specificity for detecting liver fatty changes. Our results indicate that quantitative evaluation of hepatic fat content can be performed using US H/R and could therefore be a valuable analytic tool in clinical investigation.

Postprandial metabolic abnormalities are considered important and independent risk factors for cardiovascular diseases. However, the effects of the Mediterranean diet on postprandial metabolism and the mechanism underpinning the effects on clinical variables have not been exhaustively explored. Therefore, the aims of the present study were to evaluate the acute and medium-term effects (8 weeks) on postprandial glucose and lipid metabolism of a diet resembling a typical Mediterranean diet (Med-D) compared to a western-type diet (Control-D), and the mechanisms underlying those effects.Twenty-nine overweight/obese individuals of both genders, aged 20-60 years, were enrolled and randomly assigned to two isoenergetic dietary interventions: 1) a Med-D (n = 16), and 2) a Control-D (n = 13). Adherence to the dietary interventions was assessed by a 7-day food record. A meal test resembling the assigned diet was performed at baseline and after 8 weeks of intervention. Blood samples at fasting and over 4-h after the meal were collected to assess metabolic parameters and short chain fatty acid (SCFA) levels. Fecal samples were also collected to evaluate the microbiota composition.Glucose and insulin responses were significantly reduced at baseline after the Med test meal compared to the Control meal (p 0.05) and this effect was strengthened after 8 weeks of intervention with the Mediterranean diet (p 0.05); together with an improvement in OGIS. At the end of the intervention, postprandial plasma butyric acid incremental area under the curve (IAUC) was significantly increased in the Med-D group (p = 0.019) and correlated inversely with plasma insulin IAUC and directly with oral glucose insulin sensitivity (OGIS) (r: -0.411, p = 0.046 and r: 0.397, p = 0.050 respectively). These metabolic changes were accompanied by significant changes in gut microbiota, such as an increase in the relative abundance of Intestinimonas butyriciproducens and Akkermansia muciniphila (p 0.05) in the Med-D compared to Control-D group.Our study provides strong evidence that a diet resembling the traditional Med-D improves postprandial glucose metabolism and insulin sensitivity. Furthermore, the study highlights a possible involvement of gut microbiota metabolites - such as butyric acid, and of dietary fiber as a precursor - in improving glucose metabolism and insulin sensitivity.

Dixon-based methods for the detection of fatty liver have the advantage of being non-invasive, easy to perform and analyze, and to provide a whole-liver coverage during the acquisition. The aim of the study was to assess the feasibility of a whole-liver Dixon-based approach for liver fat quantification in type 2 diabetes (T2D) patients who underwent two different isocaloric dietary treatments: a diet rich in monosaturated fatty acids (MUFA) and a multifactorial diet. Thirty-nine T2D patients were randomly assigned to MUFA diet (n = 21) and multifactorial diet (n = 18). The mean values of the proton density fat fraction (PDFF) over the whole liver and over the ROI corresponding to that chosen for MRS were compared to MRS-PDFF using Spearman’s correlation (ρ). Before–after changes in percentage of liver volume corresponding to MRI-PDFF above thresholds associated with hepatic steatosis (LV%TH, with TH = 5.56%, 7.97% and 8.8%) were considered to assess the proposed approach and compared between diets using Wilcoxon rank-sum test. Statistical significance set at p < 0.05. A strong linear relationship was found between MRS-PDFF and MRI-PDFFs (ρ = 0.85, p < 0.0001). Changes in LV%TH% were significantly higher (p < 0.05) in the multifactorial diet than in MUFA diet (25% vs. 9%, 35% vs. 12%, and 38% vs. 13% decrease, respectively, for TH = 5.56%, 7.97%, and 8.8%) and this was reproducible compared to results obtained using the standard liver fat analysis. A volumetric approach based on Dixon method could be an effective, non-invasive technique that could be used for the quantitative analysis of hepatic steatosis in T2D patients.

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.

Achieving optimal postprandial glucose control remains a major issue in people with type 1 diabetes (T1D), including those using innovative technologies (1,2). Eating pizza is challenging for patients with T1D (3) because of its high and extremely variable glycemic index (4) and prolonged postprandial hyperglycemia. Bread leavened by sourdough instead of brewer’s yeast may reduce postprandial glucose response (PGR), and duration of sourdough leavening could play a beneficial role (5). Whether this holds true for pizza and in patients with T1D is unknown. We compared PGR for pizzas differing in type and duration of dough leavening in 16 T1D patients (9 men, 7 women) on an insulin pump. The study was approved by the institutional ethics committee (reg. no. NCT03619031, ClinicalTrials.gov). According to a randomized crossover design, participants consumed—at home, on three nonconsecutive evenings over 3 weeks—a pizza prepared with 1 ) brewer’s yeast and wheat flour, 5-h leavening (usual leavening time) (Brew5); 2 ) sourdough and flour mix, 5-h leavening (Sour5); or 3 ) sourdough and flour mix, 60-h leavening (Sour60). Premeal insulin doses, calculated by the individual insulin–to–glycemic load ratio (2) (the same for each participant on the three occasions, range 6–14 IU) were given as an 80/20% dual-wave bolus extended for 4 h. PGR was evaluated by the real-time continuous glucose monitoring system (Dexcom, Guardian, or Freestyle) used by …

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.

Cardiovascular diseases (CVDs) are the main causes of mortality and disability worldwide. Although the initial therapeutic approach to improve the main cardiovascular (CV) risk factors is based on nonpharmacological measures, mainly lifestyle modifications, compliance to recommendations is often poor and inadequate. Therefore, in recent years the use of several nutraceuticals, i.e., nutrients and/or bioactive compounds of plant or microbial origin with potentially healthful effects, has become widespread. However, to date, the scientific data on the possible benefits of the use of nutraceuticals are still inconclusive, due to the absence of adequately controlled intervention studies at least for some of them. Against this background, the scientific evidence derived from controlled intervention studies in relation to the effects of some nutraceuticals (i.e. fiber, phytosterols, soy products, red yeast rice, polyphenols and berberine) on the main CV risk factors (body weight, blood pressure, blood glucose levels and plasma lipids) in humans will be reviewed.

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.

37 Objective: Short chain fatty acids (SCFAs) derived from dietary fibre fermentation by gut 38 microbiota have been identified as one of the mechanisms behind the association between habitual 39 whole-grain intake and a lower risk of cardiometabolic diseases. The aims of the present work are: 40 (1) to evaluate whether a whole-grain wheat-based diet may increase SCFAs concentration; (2) to 41 identify possible associations between SCFAs and metabolic changes observed after the nutritional 42 intervention. 43 Research Methods & Procedures: Fifty-four subjects participated in the trial. They underwent a 44 12-week dietary intervention based on whole-grain or refined cereal products. At baseline and after 45 the intervention, glucose, insulin, triglyceride, inflammatory markers (hs-CRP, IL-1ra, IL-6 and 46 TNF-?) and SCFAs plasma concentrations were evaluated. 47 Results: After the intervention, in the whole-grain group fasting plasma propionate concentrations 48 were higher than at baseline, whereas a reduction was detected in the control group. Thence, the 49 absolute changes (end of trial minus baseline) in fasting plasma propionate concentrations were 50 significantly different between the two groups (p=0.048). The absolute changes of fasting 51 propionate correlated with cereal fibre intake (r= 0.358, p= 0.023) but no significant correlations 52 with clinical outcomes were found. However, postprandial insulin was significantly decreased in the 53 group having the absolute changes of fasting propionate concentration above the median value 54 (p=0.022 vs subjects with fasting propionate changes below the median value). 55 Conclusions: A 12 week whole-grain wheat-based diet increases fasting plasma propionate. This 56 increase correlates with the cereal fibre intake and is associated with lower postprandial insulin 57 concentrations.

IntroductionTreatment options for non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) are still a matter of debate. We compared the effects of a diet including different components versus a proven beneficial diet rich in monounsaturated fatty acids (MUFAs) on liver fat in T2D.Research design and methodsAccording to a parallel design, 49 individuals with T2D, overweight/obese, with high waist circumference, 35–75 years-old, in satisfactory blood glucose control with diet or drugs not affecting liver fat content, were randomly assigned to an 8-week isocaloric intervention with a MUFA diet (n=26) or a multifactorial diet rich in fiber, MUFA, n-6 and n-3 polyunsaturated fatty acids, polyphenols, and vitamins D, E, and C (n=23). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS complete data were available for n=21 (MUFA diet) and n=18 (multifactorial diet) participants.ResultsAdherence to dietary interventions was optimal. No significant differences between groups in body weight reduction, plasma glycated hemoglobin, insulin, glucose, lipids and liver enzymes were observed. Liver fat significantly decreased after both the multifactorial diet (9.18%±7.78% vs 5.22%±4.80%, p=0.003) and the MUFA diet (9.47%±8.89% vs 8.07%±8.52%, p=0.027) with a statistically significant difference between changes either in absolute terms (−4.0%±4.5% vs −1.4%±2.7%, p=0.035) or percent (−40%±33% vs −19%±25%, p=0.030).ConclusionsAn isocaloric multifactorial diet including several beneficial dietary components induced a clinically relevant reduction of liver fat in patients with T2D, more pronounced than that induced by simply replacing saturated fat with MUFA. This suggests that the ‘optimal diet’ for NAFLD treatment in T2D should be based on synergic actions of different dietary components on multiple pathophysiological pathways.Trial registration numberNCT03380416.

Summary Objective To explore the possible mechanisms behind the lower glycemic response observed when extra-virgin olive oil (EVOO) is added to a high-glycemic index meal in patients with type 1 diabetes (T1D). Research design and methods According to a randomized cross-over design, eleven T1D patients (6 women, 5 men) on insulin pump consumed in the metabolic ward, one week apart, three high-glycemic index meals differing only for amount and quality of fat: high-monounsaturated fat (EVOO), high-saturated fat (Butter), and low-fat (LF). Before and after the meals, blood glucose (continuous glucose monitoring), gastric emptying rate (ultrasound technique), and plasma concentrations of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide GIP (ELISA), glucagon (RIA), and lipids (colorimetric assays) were evaluated. Results Blood glucose iAUC (mmol/lx360 min) was lower after the EVOO (690 ± 431) than after the Butter (1320 ± 600) and LF meals (1007 ± 990) (M ± SD, p = 0.041 by repeated measures ANOVA). Gastric antrum volume was significantly larger in the early (60–90 min) postprandial phase (106 ± 21 vs. 90 ± 16 ml, p = 0.048) and significantly smaller in the late phase (330–360 min) (46 ± 10 vs. 57 ± 22 ml, p = 0.045) after the EVOO than after Butter meal. EVOO significantly increased postprandial GLP-1 iAUC (261 ± 311) compared to Butter (189 ± 349) (pmol/Lx180 min, p = 0.009). Postprandial GIP and glucagon responses were not significantly different between EVOO and Butter. Postprandial triglyceride iAUC was significantly higher after EVOO (100 ± 53) than after Butter (65 ± 60) (mmol/l × 360 min, p = 0.048). Conclusions Changes in gastric emptying and GLP-1 secretion and reduced glucose absorption through glucose-lipid competition may contribute to lower glycemia after a high-glycemic index meal with EVOO in T1D patients. Clinical trials number NCT02330939.

Purpose: The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet—within the ranges recommended by different guidelines—with metabolic risk factors. Methods: We studied 1785 people with type 2 diabetes, aged 50–75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured. Results: Increasing fat intake from

Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3) are associated with lower cardiovascular risk. This may relate to their influence on glucose metabolism and diabetes risk. We evaluated the effects of diets naturally rich in polyphenols and/or LCn3 of marine origin on glucose metabolism in people at high cardiometabolic risk. According to a 2 × 2 factorial design, individuals with high waist circumference and at least one more component of the metabolic syndrome were recruited at the obesity outpatient clinic. Eighty-six participants were randomly assigned by MINIM software to an isoenergetic diet: (1) control, low in LCn3 and polyphenol (analysed n = 20); (2) rich in LCn3 (n = 19); (3) rich in polyphenols (n = 19); or (4) rich in LCn3 and polyphenols (n = 19). The assigned diets were known for the participants and blinded for people doing measurements. Before and after the 8 week intervention, participants underwent a 3 h OGTT and a test meal with a similar composition as the assigned diet for the evaluation of plasma glucose, insulin and glucagon-like peptide 1 (GLP-1) concentrations, and indices of insulin sensitivity and beta cell function. During OGTT, polyphenols significantly reduced plasma glucose total AUC (p = 0.038) and increased early insulin secretion (p = 0.048), while LCn3 significantly reduced beta cell function (p = 0.031) (two-factor ANOVA). Moreover, polyphenols improved post-challenge oral glucose insulin sensitivity (OGIS; p = 0.05 vs control diet by post hoc ANOVA). At test meal, LCn3 significantly reduced GLP-1 total postprandial AUC (p

To evaluate feasibility and effectiveness on short-term blood glucose control of using glycaemic load counting (GLC) versus carbohydrate counting (CC) for prandial insulin dosing in patients with type 1 diabetes (T1D).Nine T1D patients on insulin pump, aged 26-58 years, HbA1c 7.7 ± 0.8 % (61 ± 8.7 mmol/mol), participated in this real-life setting study. By a crossover design, patients were randomised to calculate their pre-meal insulin dose based on the insulin/glycaemic load ratio (GLC period) or the insulin/carbohydrate ratio (CC period) for 1 week, shifting to the alternate method for the next week, when participants duplicated their first week food plan. Over either week, a blind subcutaneous continuous glucose monitoring was performed, and a 7-day food record was filled in.Total daily insulin doses (45 ± 10 vs. 44 ± 9 I.U.; M ± SD, p = 0.386) and basal infusion (26 ± 7 vs. 26 ± 8 I.U., p = 0.516) were not different during GLC and CC periods, respectively. However, the range of insulin doses (difference between highest and lowest insulin dose) was wider during GLC, with statistical significance at dinner (8.4 ± 6.2 vs. 6.0 ± 3.9 I.U., p = 0.041). Blood glucose iAUC after lunch was lower, albeit not significantly, during GLC than CC period (0.6 ± 8.6 vs. 3.4 ± 8.2 mmol/l∙3 h, p = 0.059). Postprandial glucose variability, evaluated as the maximal amplitude after meal (highest minus lowest glucose value), was significantly lower during GLC than CC period at lunch (4.22 ± 0.28 vs. 5.47 ± 0.39 mmol/l, p = 0.002) and dinner (3.89 ± 0.33 vs. 4.89 ± 0.33, p = 0.026).Calculating prandial insulin bolus based on glycaemic load counting is feasible in a real-life setting and may improve postprandial glucose control in people with T1D.

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.

Postprandial lipid abnormalities are considered an independent cardiovascular risk factor. Hence, it is important to find nutritional strategies that are able to positively influence these abnormalities. Since the effect of n-3 polyunsaturated fatty acids (PUFA) and polyphenols on postprandial lipids in humans is still under debate, we evaluated the acute response of triglyceride-rich lipoproteins to test meals that are naturally rich in polyphenols and/or marine long-chain (LC) n-3 PUFAs. We hypothesized that LC n-3 PUFA would have a different effect on chylomicron and very low density lipoproteins when compared with polyphenols or their combination. We randomly assigned 78 individuals who were at high cardiometabolic risk to 4 isoenergetic diets. These diets only differed in amount of LC n-3 PUFA and/or polyphenols. Prior to starting the intervention, each subject underwent a test meal similar to the type of diet assigned: low in LC n-3 PUFA and polyphenols (control), rich in LC n-3 PUFA and low in polyphenols, rich in polyphenols and low in LC n-3 PUFA, or rich in both. Blood samples were taken before and up to 6 hours after the test meal in order to evaluate cholesterol and triglycerides (plasma and triglyceride-rich lipoprotein), apolipoprotein B-48 (large very low density lipoprotein), glucagon-like peptide-1, and free fatty acid plasma levels. The levels of chylomicron cholesterol and triglyceride in response to the test meal rich in LC n-3 PUFA were significantly higher than after the control meal (P = .037 and P = .018); there was no difference in the other variables. In conclusion, this study indicates that acute administration of marine LC n-3 PUFA increases postprandial chylomicron response in contrast with their lowering chronic effects. These differences underline the importance of understanding the acute and chronic effects of nutritional, as well as of other types of, interventions.

The Look AHEAD trial, evaluating the effects of weight loss on cardiovascular (CV) morbidity and mortality in overweight/obese people with type 2 diabetes (T2D), was interrupted after a median 9.5-year follow-up because the incidence of CV events was not different between the Intensive Lifestyle Intervention (ILI) and the control groups, and unlikely to statistically change thereafter. This made health providers and patients wondering about clinical value of diet and physical exercise in diabetic patients. Many factors may have made difficult to ascertain benefits of lifestyle intervention, besides the lower than predicted CV event rates. Among others, LDL-cholesterol was lowered more, with a higher use of statins, in the control group. Anyhow, ILI significantly improved numerous health conditions, including quality of life, CV risk factors and blood glucose control, with more diabetes remissions and less use of insulin. The intervention aimed at weight loss by reducing fat calories, and using meal replacements and, eventually, orlistat, likely underemphasizing dietary composition. There is suggestive evidence, in fact, that qualitative changes in dietary composition aiming at higher consumption of foods rich in fiber and with a high vegetable/animal fat ratio favorably influence CV risk in T2D patients. In conclusion, the Look AHEAD showed substantial health benefits of lifestyle modifications. Prevention of CV events may need higher attention to dietary composition, contributing to stricter control of CV risk factors. As a better health-related quality of life in people with diabetes is an important driver of our clinical decisions, efforts on early implementation of behavioral changes through a multifactorial approach are strongly justified.

The study explores the degree of control of hyperglycaemia and cardiovascular (CV) disease risk factors in men and women with type 2 diabetes and the impact thereon of obesity, central adiposity, age and use of medications.A cross-sectional survey was conducted at 10 hospital-based outpatients diabetes clinics. 1297 men and 1168 women with no previous CV events were studied. Women were slightly (only one year) older and more obese than men: average BMI was respectively 30.7 ± 5.7 vs 28.6 ± 4.1 kg/m(2) (p0.001), and prevalence of abdominal obesity was 86% vs 44% (p0.001). Women smoked less, but had higher HbA1c, LDL cholesterol, non-HDL cholesterol, systolic blood pressure and serum fibrinogen than men. Accordingly optimal targets for HbA1c (7%), LDL cholesterol (100 mg/dL), HDL cholesterol (40 for men,50 for women, mg/dL), and systolic blood pressure (130 mmHg) were less frequently achieved by women than men (respectively 33.8% vs 40.2%; 14.6% vs 19.2%; 34.1% vs 44.5%; 68.8% vs 72%; p0.05 for all). Findings were confirmed after stratification for waist circumference (or ≥ 88 cm for women;or ≥ 102 cm for men), BMI (or ≥ 25 kg/m(2)) or age (or ≥ 65 years). As for treatment, women were more likely than men to take insulin, alone or in combination with oral hypoglycaemic drugs, to be under anti-hypertensive treatment, whereas the use of lipid lowering drugs was similar in men and women.Control of hyperglycaemia and major CVD risk factors is less satisfactory in women than men. The gender disparities are not fully explained by the higher prevalence of total and central obesity in women; or by a less intensive medical management in women.

BACKGROUND AND AIMS: The role of the different factors associated with fatty liver is still poorly defined. We evaluated the relationships between liver fat content (LF) and metabolic, inflammatory and nutritional factors in a homogeneous cohort of individuals at high cardio-metabolic risk. METHODS AND RESULTS: In 70 individuals with high waist circumference and at least one more criterion for metabolic syndrome enrolled in a nutritional intervention study, LF was evaluated at baseline by hepatic/renal echo intensity ratio (H/R), together with dietary habits (7-day dietary record), insulin sensitivity and β-cell function (fasting and OGTT-derived indices), fasting and postprandial plasma GLP-1 and lipoproteins, and plasma inflammatory markers. H/R correlated positively with fasting and OGTT plasma glucose and insulin concentrations, HOMA-IR and β-cell function, and IL-4, IL-17, IFN-γ, TNF-α, FGF and GCSF plasma concentrations (p < 0.05 for all), and negatively with insulin sensitivity (OGIS), dietary, polyphenols and fiber (p < 0.05 for all). By multiple stepwise regression analysis, the best predictors of H/R were OGIS (β = -0.352 p = 0.001), postprandial GLP-1 (β = -0.344; p = 0.001), HDL-cholesterol (β = -0.323; p = 0.002) and IFN-γ (β = 0.205; p = 0.036). CONCLUSION: A comprehensive evaluation of factors associated with liver fat, in a homogeneous population at high cardio-metabolic risk, indicated a pathogenic combination of the same pathways underlying the atherosclerotic process, namely whole body insulin sensitivity and inflammation. The higher predictive value of postprandial variables suggests that liver fat is essentially a postprandial phenomenon, with a relevant role possibly played by GLP-1.

The paper presents a post-hoc analysis of the intensity of dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type-2-Diabetes.ITaly (MIND.IT) study.MIND.IT is a multicentric, randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at high cardiovascular (CV) risk. The study compares the usual care (UC) of CV prevention with a multifactorial intensive care (IC) approach aiming at achieving target values for the main CV risk factors according to a step-wise treat-to-target approach.Proportion of patients on target for low-density lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased significantly more with IC than UC (43 vs. 27%; p 0.001). However, the majority (57%) of patients, in this intended intensively treated cohort, failed to achieve the proposed target. Average LDL-C decreased from 144 ± 35 to 108 ± 31 mg/dl with IC and from 142 ± 28 to 118 ± 32 with UC (p-for-interaction0.0001). IC was associated with a significantly greater increase in statin prescription and lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively; both p 0.001). However, the new treatments were characterized in both groups by the use of low starting doses (≤ 10 mg of atorvastatin, equivalent dose in more than 90% of patients) without increase in case of missed target.The application of a multifactorial treat-to-target intervention is associated with a significant improvement in LDL-C beyond usual practice. However, the change in LDL-C appears to be more related to an increased number of treated patients and a decreased treatment withdrawal than to a true treat-to-target approach.

The literature on the impact of dietary carbohydrates in the regulation of blood glucose levels and other metabolic abnormalities in diabetic patients over the last 3 years is reviewed. We try to differentiate the metabolic effects due to the amount of carbohydrates from those due to their different types. The review comprises a part dealing with the effects of diets having low or high carbohydrate content on body weight reduction, and a part in which the amount and the quality of carbohydrates are discussed in relation to isoenergetic diets. Overall, the data accumulated in the period considered seem to confirm that the decrease in energy intake is more important than the qualitative composition of the diet to reduce body weight, but that both the amount and the quality of carbohydrates are important in modulating blood glucose levels and other cardiovascular risk factors in both the fasting and the postprandial phases in diabetic individuals.

The consumption of foods containing trans fatty acids (TFA), especially those produced by food industries, induces pleiotropic negative effects on health. Therefore, it is important to assess the amount of TFA consumed, especially in age groups more exposed to the consumption of TFA-containing foods. The present pilot study evaluates TFA intake in 54 young people with and without type 1 diabetes (29 young subjects with type 1 diabetes and 25 healthy subjects) through both dietary records (7-day food record) and the measurement of TFA levels in serum phospholipids, a possibly more objective marker of TFA intake. The comparison between the two groups was made by the student t test for independent samples. The intake of synthetic TFA was low in both groups (type 1 diabetic patients: 0.25 ± 0.25 g/day; healthy subjects 0.48 ± 0.37 g/day), but significantly lower in diabetic patients vs controls (P < 0.05); TFA levels in serum phospholipids also confirmed a low intake of these fatty acids. These data indicate that the intake of trans fatty acids is relatively low in our population, i.e.