Comprehensive Approach to Medical Nutrition Therapy in Patients with Type 2 Diabetes Mellitus: From Diet to Bioactive Compounds.

In the pathogenesis of type 2 diabetes mellitus (T2DM), diet plays a key role. Individualized medical nutritional therapy, as part of lifestyle optimization, is one of the cornerstones for the management of T2DM and has been shown to improve metabolic outcomes. This paper discusses major aspects of the nutritional intervention (including macro- and micronutrients, nutraceuticals, and supplements), with key practical advice. Various eating patterns, such as the Mediterranean-style, low-carbohydrate, vegetarian or plant-based diets, as well as healthy eating plans with caloric deficits have been proven to have beneficial effects for patients with T2DM. So far, the evidence does not support a specific macronutrient distribution and meal plans should be individualized. Reducing the overall carbohydrate intake and replacing high glycemic index (GI) foods with low GI foods have been shown as valid options for patients with T2DM to improve glycemic control. Additionally, evidence supports the current recommendation to reduce the intake of free sugars to less than 10% of total energy intake, since their excessive intake promotes weight gain. The quality of fats seems to be rather important and the substitution of saturated and trans fatty acids with foods rich in monounsaturated and polyunsaturated fats lowers cardiovascular risk and improves glucose metabolism. There is no benefit of supplementation with antioxidants, such as carotene, vitamins E and C, or other micronutrients, due to the lack of consistent evidence showing efficacy and long-term safety. Some studies suggest possible beneficial metabolic effects of nutraceuticals in patients with T2DM, but more evidence about their efficacy and safety is still needed.

Probiotics and Prebiotics: Any Role in Menopause-Related Diseases?

PURPOSE OF REVIEW: The aim of this review is to provide an overview of the menopause-related changes in microbiota and their role in the pathogenesis of menopause-related diseases. In addition, evidence on probiotic supplementation as a therapeutic strategy is discussed. RECENT FINDINGS: The human microbiota is a complex community that lives in a mutualism relationship with the host. Menopause is associated with dysbiosis, and these changes in the composition of microbiota in different sites (gut, vaginal, and oral microbiota) might play a role in the pathogenesis of menopause-related diseases (i.e., osteoporosis, breast cancer, endometrial hyperplasia, periodontitis, and cardiometabolic diseases). The present review highlights the pivotal role of microbiota in postmenopausal women health, in particular it (a) may increase intestinal calcium absorption thus preventing osteoporosis, (b) is associated with reduced risk of breast cancer and type 1 endometrial hyperplasia, (c) reduces gingival inflammation and menopausal periodontitis, and (d) beneficially affects multiple cardiometabolic risk factors (i.e., obesity, inflammation, and blood glucose and lipid metabolism). However, whether oral probiotic supplementation might be used for the treatment of menopause-related dysbiosis requires further clarification.

Supplementation with medium-chain fatty acids increases body weight loss during very low-calorie ketogenic diet: a retrospective analysis in a real-life setting.

BACKGROUND: Very low-calorie ketogenic diet (VLCKD) has shown to significantly reduce body weight and fat mass, as well as inflammation. These effects are supported by nutritional ketosis, which triggers the utilization of the ketone body as an energy source. Medium-chain fatty acids (MCTs) might serve as potential enhancers of ketone bodies production with a greater effect on weight loss. Nevertheless, no clinical studies have evaluated the effect of MCTs supplementation in addition to VLCKD. Therefore, the present study aimed to evaluate whether the supplementation with MCTs can induce a greater weight reduction during the ketogenic phase of VLCKD. METHODS: In this retrospective study, 263 women with overweight/obesity (body mass index, BMI: 35.7 ± 5.3 kg/m2) aged 37.5 ± 14.2 years followed one of these dietary protocols for 45 days: (a) Control group, 83 participants (31.6%) (VLCKD without MCTs), (b) VLCKD + MCTs group, 86 participants (32.7%) (MCTs supplementation - 20 g/day- during VLCKD starting from the first day of the active phase), (c) VLCKD + earlyMCTs, 94 participants (35.7%) (MCTs supplementation - 20 g/day-starting from 5 days before the beginning of the VLCKD active phase. Anthropometric measures, body composition, and c-reactive protein (CRP) concentrations were collected at the beginning and at the end (45 days) of the VLCKD intervention. RESULTS: MCTs supplementation significantly decreased body weight, BMI, and waist circumference as compared to the control group, with a greater effect in the VLCKD + earlyMCTs group. A two-fold decrease in fat mass and an increase in muscle mass were observed in the VLCKD + earlyMCTs group as compared to the control group. As for inflammation, hs-CRP concentrations (assessed as absolute percent change) were significantly lower in the VLCKD + MCTs group (p = 0.009) and the VLCKD + earlyMCTs group (p = 0.011) than in the control group. A logistic regression model showed that VLCKD + earlyMCTs increase the likelihood of improvement of BMI classes (OR: 1.85, 95% CI 1.02-3.36) also after adjusting for the potential confounding factors. CONCLUSION: MCTs supplementation (20 g/day) may be a useful tool to enhance the beneficial effect of VLCKD on the reduction of body weight and fat mass. In particular, MCTs supplementation before the beginning of the VLCKD active phase might facilitate ketosis thus contributing to the effectiveness of the nutritional intervention.

Nutritional management of type 2 diabetes in subjects with obesity: an international guideline for clinical practice.

Type 2 diabetes mellitus (T2DM) and obesity represent a global public health problem. Current nutritional recommendations focused on weight loss and overall dietary quality. However, there is no consensus on the optimal macronutrient composition of the diet, particularly for the long-term management of T2DM in subjects with obesity. An international panel of experts reviewed and critically appraised the updated literature published on the topic. This review primarily examines the evidence for areas of consensus and uncertainty about nutritional therapy in patients with T2DM and obesity. The aim of this article is to provide nutritional advice to manage these patients in clinical practice.

Prader-Willi Syndrome in Adults: An Update On Nutritional Treatment and Pharmacological Approach.

PURPOSE OF REVIEW: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder with multiple effects on the metabolic, endocrine, and neurological systems, as well as behavioral and intellectual difficulties. Despite advances in understanding the genetic basis of obesity in PWS, there are conflicting data on its management. Therefore, the present manuscript aims to provide an update on the nutritional treatment and pharmacological approach in adult patients with PWS. RECENT FINDINGS: The management of obesity in patients with PWS is challenging and requires the cooperation of an experienced multidisciplinary team, including the nutritionist. An adequate clinical evaluation including nutritional and biochemical parameters should be performed to tailor the best therapeutic strategy. Both lifestyle and pharmacological interventions may represent useful strategies to prevent the high rate of morbidity and mortality related to PWS. The use of bariatric surgery is still controversial. Although it is imperative to adopt an obesity prevention strategy in childhood, there is promising evidence for the treatment of obesity in adulthood with current obesity medications in conjunction with lifestyle interventions.

Vitamin D: A Role Also in Long COVID-19?

Coronavirus disease 2019 (COVID-19) has quickly become a global pandemic. Reports from different parts of the world indicate that a significant proportion of people who have recovered from COVID-19 are suffering from various health problems collectively referred to as "long COVID-19". Common symptoms include fatigue, shortness of breath, cough, joint pain, chest pain, muscle aches, headaches, and so on. Vitamin D is an immunomodulatory hormone with proven efficacy against various upper respiratory tract infections. Vitamin D can inhibit hyperinflammatory reactions and accelerate the healing process in the affected areas, especially in lung tissue. Moreover, vitamin D deficiency has been associated with the severity and mortality of COVID-19 cases, with a high prevalence of hypovitaminosis D found in patients with COVID-19 and acute respiratory failure. Thus, there are promising reasons to promote research into the effects of vitamin D supplementation in COVID-19 patients. However, no studies to date have found that vitamin D affects post-COVID-19 symptoms or biomarkers. Based on this scenario, this review aims to provide an up-to-date overview of the potential role of vitamin D in long COVID-19 and of the current literature on this topic.

Dietary Recommendations for Post-COVID-19 Syndrome.

At the beginning of the coronavirus disease (COVID-19) pandemic, global efforts focused on containing the spread of the virus and avoiding contagion. Currently, it is evident that health professionals should deal with the overall health status of COVID-19 survivors. Indeed, novel findings have identified post-COVID-19 syndrome, which is characterized by malnutrition, loss of fat-free mass, and low-grade inflammation. In addition, the recovery might be complicated by persistent functional impairment (i.e., fatigue and muscle weakness, dysphagia, appetite loss, and taste/smell alterations) as well as psychological distress. Therefore, the appropriate evaluation of nutritional status (assessment of dietary intake, anthropometrics, and body composition) is one of the pillars in the management of these patients. On the other hand, personalized dietary recommendations represent the best strategy to ensure recovery. Therefore, this review aimed to collect available evidence on the role of nutrients and their supplementation in post-COVID-19 syndrome to provide a practical guideline to nutritionists to tailor dietary interventions for patients recovering from COVID-19 infections.

An Oily Fish Diet Improves Subclinical Inflammation in People at High Cardiovascular Risk: A Randomized Controlled Study.

Interest has arisen on the anti-inflammatory action of dietary components, including long-chain n-3 fatty acids (LCn3) and polyphenols (PP). The aim of this study was to evaluate the effects of diets rich in PP and oily fish (high-LCn3 diets) on markers of subclinical inflammation and growth factors in people at high cardiometabolic risk. Individuals with high waist circumference and one more component of metabolic syndrome were randomized to one of the following isoenergetic diets: low LCn3&PP, high LCn3, high PP, high LCn3&PP. Before and after 8 weeks, fasting and postprandial plasma concentrations of hs-CRP and fasting serum concentrations of IL-1, IL-4, IL-6, IL-10, IL-17, INF-, TNF-, FGF, VEGF, PDGF-, G-CSF, and GM-CSF were determined. An oily fish diet reduced fasting plasma hs-CRP (1.28 ± 12.0, -12.5 ± 6.9, 22.5 ± 33.6, -12.2 ± 11.9; 8-week percent change, Mean ± SEM; low LCn3&PP, high LCn3, high PP, high LCn3&PP group, respectively), postprandial 6h-AUC hs-CRP (4.6 ± 16.3, -18.2 ± 7.2, 26.9 ± 35.1, -11.5 ± 11.8, 8-week percent change) and fasting IL-6 (20.8 ± 18.7, -2.44 ± 12.4, 28.1 ± 17.4, -9.6 ± 10.2), IL-17 (2.40 ± 4.9, -13.3 ± 4.9, 3.8 ± 4.43, -11.5 ± 4.7), and VEGF (-5.7 ± 5.8, -5.6 ± 7.5, 3.5 ± 5.8, -11.1 ± 5.5) (8-week percent change; p < 0.05 for LCn3 effect for all; no significant effect for PP; 2-factor ANOVA). An oily fish diet improved subclinical inflammation, while no significant effect was observed for dietary polyphenols.

Diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic-risk individuals.

AIMS: Gut microbiota significantly impacts human health and is influenced by dietary changes. We evaluated the effects of diets naturally rich in polyphenols (PP) and/or long-chain n-3 polyunsaturated fatty acids (LCn3) on microbiota composition in an ancillary analysis of a randomized controlled trial in individuals at high cardiometabolic risk. METHODS: Seventy-eight individuals with high waist circumference and at least one additional component of the metabolic syndrome were randomized to an isoenergetic 8-week diet: (a) low LCn3 and PP; (b) high LCn3; (c) high PP; or (d) high LCn3 and PP. Microbiota analysis was performed on feces collected before and after the intervention. DGGE analysis of the predominant bacteria, Eubacterium rectale and Blautia coccoides group (Lachnospiraceae, EREC), Clostridium leptum (Ruminococcaceae, CLEPT), Bacteroides spp., Bifidobacteria, and Lactobacillus group was performed. A quantitative real-time PCR was performed for the same group, additionally including Atopobium cluster (Coriobatteriaceae). Before and after the intervention, participants underwent a 75 g OGTT and a high-fat test meal to evaluate glucose and lipid response. RESULTS: Adherence to the four diets was optimal. PP significantly increased microbial diversity (p = 0.006) and CLEPT (p = 0.015), while it reduced EREC (p = 0.044). LCn3 significantly increased the numbers of Bifidobacteria (p = 0.041). Changes in CLEPT numbers correlated with changes in early insulin secretion (r = 0.263, p = 0.030). Changes in Atopobium numbers correlated with postprandial triglycerides in plasma (r = 0.266, p = 0.026) and large VLDL (r = 0.313, p = 0.009), and cholesterol in large VLDL (r = 0.319, p = 0.008). CONCLUSIONS: Diets naturally rich in PP or LCn3 influenced gut microbiota composition in individuals at high cardiometabolic risk. These modifications were associated with changes in glucose/lipid metabolism.

Fibre-enriched buckwheat pasta modifies blood glucose response compared to corn pasta in individuals with type 1 diabetes and celiac disease: Acute randomized controlled trial.

AIM: People with type 1 diabetes and celiac disease (T1D&CD) have high blood glucose variability. Processed gluten-free foods have shown to induce a worse metabolic profile whereas naturally gluten-free foods may represent healthier options. On the other hand, dietary fibre has shown to reduce postprandial glycemic excursions in individuals with diabetes. Thus, we evaluated the acute effect of fibre-enriched buckwheat (FBP) and corn pasta (CP) on postprandial blood glucose response (PP-BGR). METHODS: Ten adult patients with T1D&CD consumed two meals with the same amount of carbohydrate while differing only for pasta type (FBP or CP) preceded by the same insulin bolus. Participants utilized continuous glucose monitoring (CGM) and data over 6 h after meal were analyzed. RESULTS: PP-BGR differed between the two meals, being significantly lower in the first period (0-3 h) after the CP than the FBP meal (iAUC: -38 ±â€¯158 vs. 305 ±â€¯209 mmol/L ·â€¯180 min, p = 0.040), whereas significantly higher in the second period (3-6 h) after the CP than the FBP meal (iAUC: 432 ±â€¯153 vs. 308 ±â€¯252 mmol/L ·â€¯180 min, p = 0.030). Overall, a less variable postprandial profile was observed after FBP than CP consumption. CONCLUSIONS: In individuals with T1D&CD, the acute consumption of FBP induces significant differences in PP-BGR compared with CP that may be clinically relevant.

The Possible Role of Nutraceuticals in the Prevention of Cardiovascular Disease.

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.

Bioavailability and pharmacokinetic profile of grape pomace phenolic compounds in humans.

Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-γ-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basis.

Metabolic transformations of dietary polyphenols: comparison between in vitro colonic and hepatic models and in vivo urinary metabolites.

Studies on metabolism of polyphenols have revealed extensive transformations in the carbon backbone by colonic microbiota; however, the influence of microbial and hepatic transformations on human urinary metabolites has not been explored. Therefore, the aims of this study were (1) to compare the in vitro microbial phenolic metabolite profile of foods and beverages with that excreted in urine of subjects consuming the same foodstuff and (2) to explore the role of liver on postcolonic metabolism of polyphenols by using in vitro hepatic models. A 24-h urinary phenolic metabolite profile was evaluated in 72 subjects participating in an 8-week clinical trial during which they were randomly assigned to diets differing for polyphenol content. Polyphenol-rich foods and beverages used in the clinical trial were subjected to human fecal microbiota in the in vitro colon model. Metabolites from green tea, one of the main components of the polyphenol-rich diet, were incubated with primary hepatocytes to highlight hepatic conversion of polyphenols. The analyses were performed using targeted gas chromatography with mass spectrometer (GCxGC-TOFMS:colon model; GC-MS: urine and hepatocytes). A significant correlation was found between urinary and colonic metabolites with C1-C3 side chain (P=.040). However, considerably higher amounts of hippuric acid, 3-hydroxybenzoic acid and ferulic acid were detected in urine than in the colon model. The hepatic conversion showed additional amounts of these metabolites complementing the gap between in vitro colon model and the in vivo urinary excretion. Therefore, combining in vitro colon and hepatic models may better elucidate the metabolism of polyphenols from dietary exposure to urinary metabolites.

Polyphenol-rich diets improve glucose metabolism in people at high cardiometabolic risk: a controlled randomised intervention trial.

AIM/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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 < 0.001; two-factor ANOVA). CONCLUSION/INTERPRETATION: Diets naturally rich in polyphenols reduce blood glucose response, likely by increasing early insulin secretion and insulin sensitivity. These effects may favourably influence diabetes and cardiovascular risk. The implications of the decrease in insulin secretion and postprandial GLP-1 observed with diets rich in marine LCn3 need further clarification. TRIAL REGISTRATION: ClinicalTrials.gov NCT01154478. FUNDING: The trial was funded by European Community's Seventh Framework Programme FP7/2009-2012 under grant agreement FP7-KBBE-222639, Etherpaths Project and 'Ministero Istruzione Università e Ricerca' PRIN 2010-2011 - 2010JCWWKM.

Isoenergetic diets differing in their n-3 fatty acid and polyphenol content reflect different plasma and HDL-fraction lipidomic profiles in subjects at high cardiovascular risk.

SCOPE: Dysregulation of lipid homeostasis is related to multiple major healthcare problems. The aim of this study was to investigate the effects of n-3 fatty acid (FA) and polyphenol rich diets on plasma and HDL fraction lipidomic profiles in subjects at high cardiovascular risk. METHODS AND RESULTS: Ultra performance LC coupled to quadrupole TOF/MS mass spectrometry global lipidomic profiling was applied to plasma and HDL fraction from an 8 wk randomized intervention with four isoenergetic diets, differing in their natural n-3 FA and polyphenols content, in 78 subjects with a high BMI, abdominal obesity, and at least one other feature of the metabolic syndrome. Dependency network analysis showed a different pattern of associations between lipidomics, dietary, and clinical variables after the dietary interventions. The most remarkable associations between variables were observed after the diet high in n-3 FA and polyphenols, as the inverse association between gallic acid intake and LDL cholesterol levels, which was indirectly associated with a HDL cluster exclusively comprised lysophospholipids. CONCLUSION: This is the first human randomized controlled trial showing direct and indirect associations with lipid molecular species and clinical variables of interest in the evaluation of the metabolic syndrome after diets naturally rich in polyphenols.

Diets naturally rich in polyphenols improve fasting and postprandial dyslipidemia and reduce oxidative stress: a randomized controlled trial.

BACKGROUND: The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk. OBJECTIVE: This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress. DESIGN: According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured. RESULTS: Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane. CONCLUSIONS: Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk.

Vitamin D and cardiovascular disease: is there evidence to support the bandwagon?

In the last 3 years, more evidence accumulated that vitamin D (vitD)deficiency associates with cardiovascular disease (CVD) and risk factors. The association with higher cardiovascular (CV) mortality was stronger than with nonfatal CVD events. A higher incidence of type 2 diabetes was also shown. Many factors related to lifestyle (physical activity in particular) influence both vitD levels and CVD, and may contribute to explain these observational data. Whether the association between vitD and CVD is causal can only be established through randomized controlled trials (RCTs), and to date the results of the randomized trials, which were not designed for investigating CV outcomes, do not support the association data. Answers on the effects of vitD supplementation on primary and secondary prevention of CV may be found in the specifically designed ongoing RCTs. In the mean time, low vitamin D levels should be regarded as a marker of unhealthy lifestyle, requiring a more aggressive attempt at modifying individual lifestyle.