From an understanding of etiopathogenesis to novel therapies-what is new in the treatment of celiac disease?

Celiac disease, a chronic autoimmune disorder caused by genetic factors and exposure to gluten, is increasingly being recognized and diagnosed in both children and adults. Scientists have been searching for a cure for this disease for many years, but despite the impressive development of knowledge in this field, a gluten-free diet remains the only recommended therapy for all patients. At the same time, the increasing diagnosis of celiac disease in adults, which was considered a childhood disease in the 20th century, has opened a discussion on the etiopathology of the disease, which is proven to be very complex and involves genetic, immunological, nutritional, environmental and gut microbiota-related factors. In this review, we extensively discuss these factors and summarize the knowledge of the proposed state-of-the-art treatments for celiac disease to address the question of whether a better understanding of the etiopathogenesis of celiac disease has opened new directions for therapy.

The role of genetic risk factors, diet, and gut microbiota in type 1 diabetes mellitus, pancreas and pancreatic islet transplantation.

Despite advances in insulin delivery and glucose monitoring technology, prevention of the progression of secondary complications in patients with type 1 diabetes (T1DM) remains a challenge. Beta cell replacement therapy in the form of islet or pancreas transplantation can restore long-term normoglycaemia with sustained periods of insulin independence among T1DM patients. However, the same genetic, behavioural, or gut microbiota-related factors that promoted autoimmunity and primary islet destruction may also affect the function of transplanted islets and the ultimate results of transplant procedures. In such cases, identifying genetic risk factors and modifying behavioural factors and those related to gut microbiota may be beneficial for the outcomes of transplant procedures. Herein, we review related literature to the identified current gap in knowledge to be addressed in future clinical trials.

A high consumption of ultra-processed foods is associated with higher total mortality in an adult Mediterranean population.

BACKGROUND & AIMS: The consumption of ultra-processed foods (UPF) has been associated with higher all-cause and cardiovascular disease (CVD) mortality, although this association has not been sufficiently investigated in Mediterranean populations. We aimed to evaluate the association between UPF consumption and all-cause, CVD and cancer mortality in an adult population in Spain. METHODS: We analysed data from 1,538 participants aged 20 years and above in the Valencia Nutrition Survey in 1995. Diet was assessed at baseline using a validated food frequency questionnaire and the consumption of UPF was calculated using the NOVA system. Information on socio-demographic characteristics, lifestyles, and presence of diseases was also collected at baseline. Cause of death was ascertained during an 18-year follow-up period. We used Cox regression and competing risk models as proposed by Fine and Gray's to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (95 %CI). RESULTS: After 18 years of follow-up, we documented 312 deaths (36.5 % of CVD and 25.6 % of cancer). Compared with participants in the lowest tertile of UPF consumption, those in the highest tertile showed 40 % higher risk of all-cause mortality, HR 1.40 (95 %CI: 1.04-1.90), and evidence of a higher CVD mortality, HR 1.39 (95 %CI: 0.80-2.41) and of cancer mortality, HR 1.53 (95 %CI: 0.83-2.82). CONCLUSIONS: This study suggests that a high UPF consumption is associated with a higher all-cause mortality in a Mediterranean population after a long follow-up period. Considering the increase in UPF consumption and their detrimental health effects on mortality, these results should be confirmed by other studies in other populations.

Genetic, Immunological, Dietary, Gut Microbiota, and Environmental Determinants of Osteoporosis in the Course of Celiac Disease: Which Factor Plays the First Violin in This Orchestra?

Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The worldwide prevalence of CD is estimated to be 0.7-1.4% of the general population. Etiopathology of this disease is multifactorial, with genetic determinants being a major contributing player to CD susceptibility. Its manifestation embraces different organs, including the musculoskeletal apparat. Patients with CD have increased risk of bone disorders. According to data, bone disorders - osteopenia and osteoporosis - can affect up to 70% of patients with CD at diagnosis, and it decreases after the initiation of a gluten-free diet. Gluten consumption in patients with CD triggers an inflammatory reaction followed by tissue damage, and both; local and systemic inflammation can increase the risk of bone mass deterioration. Other theory assumes shortages of vitamin D and an impaired calcium absorption mechanism leading to secondary hyperparathyroidism. Taking into account the increasing prevalence of CD and osteoporosis, we broadly discuss genetic, immunological, dietary, gut microbiota, and environmental factors that could increase the risk of osteoporosis in CD. Furthermore, we discuss lifestyle and pharmacological preventing and treatment measures.

Are variants of the RBP4 gene associated with serum retinol-binding protein 4 concentrations and carotid intima-media thickness values in women with obesity?

INTRODUCTION: Several studies showed the correlation of retinol-binding protein 4 (RBP4) with increased cardiovascular risk - including higher values of carotid intima-media thickness (cIMT) - particularly in individuals with obesity. OBJECTIVES: Our study aimed to investigate the impact of rs10882273; rs3758538; rs3758539, and rs7094671 RBP4 gene variants on RBP4 serum concentrations as well as cIMT values (a marker of subclinical atherosclerosis) among female patients with obesity. PATIENTS AND METHODS: We recruited 74 women with obesity and 24 women without obesity as a study and control group, respectively. The genotypic and allelic frequencies of RBP4 gene variants were evaluated for associations with serum RBP4 and cIMT. RESULTS: The median serum RBP4 concentrations were 20.30 µg/mL and 19.80 µg/mL in the patients and control group, respectively (p = 0.740). No significant differences were seen in cIMT values between the two studied groups (0.60 [0.50-1.00] vs. 0.60 ± 0.10 in the patient and control group, respectively); however, the results were close to reaching significance (p = 0.071), similar as in observed association of the minor haplotype AA for rs7084671 and rs375839 with female obesity (p = 0.0559). The correlation analysis showed no significant differences between RBP4 gene variants with serum RBP4 and cIMT. CONCLUSIONS: According to our knowledge, this is the first study investigating the association between RBP4 gene variants and serum RBP4 and cIMT among Polish female patients with obesity. However, our results show that genetic variants rs10882273, rs3758538, rs3758539, and rs7094671 of the RBP4 gene are not associated with RBP4 serum concentrations or cIMT values among women with obesity.

Physical activity, quality of diet and bone mineral density in patients with inflammatory bowel disease.

BACKGROUND: The aim of this study was to find an association between moderate, vigorous and total physical activity (PA); diet quality; and bone mineral density (BMD) among patients suffering from inflammatory bowel disease (IBD). METHODS: We enrolled 54 IBD patients, including those with Crohn's disease (CD) and ulcerative colitis (UC), and 24 healthy adults. All subjects completed the Questionnaire of Eating Behaviour based on which prohealthy and nonhealthy diet indexes were calculated, and the questionnaire included questions from the International Physical Activity Questionnaire. Prohealthy and nonhealthy diet indexes were divided into low-, medium- and high scores. BMD and T- and Z-scores of the lumbar spine (L1-L4) and femoral neck (FN) were assessed using dual-energy X-ray absorptiometry method. RESULTS: BMD, T- and Z-scores of the FN and the Z-score of L1-L4 were significantly lower among patients with CD and UC than healthy controls. We did not find any differences in the time of PA among CD, UC and control groups (CG). The prohealthy diet index was higher among healthy subjects than the CD and UC groups. The nonhealthy diet index was lower among UC patients compared with the CG or CD patients. Prohealthy diet index positively correlated with BMD and T- and Z-scores of L1-L4 and FN in IBD. The prohealthy diet index correlated negatively with C-reactive protein and positively with body mass index. The prohealthy diet index correlated only with total PA in the CD group. CONCLUSION: A well-balanced diet and proper PA may decrease the risk of osteoporosis in IBD, so education of patients referring to nutrition and PA is needed.

Why Does Obesity as an Inflammatory Condition Predispose to Colorectal Cancer?

Obesity is a complex and multifactorial problem of global importance. Additionally, obesity causes chronic inflammation, upregulates cell growth, disturbs the immune system, and causes genomic instability, increasing the risk of carcinogenesis. Colorectal cancer is one of the most common cancers, and it has become a global problem. In 2018, there were around 1.8 million new cases and around 881,000 deaths worldwide. Another risk factor of colorectal cancer associated with obesity is poor diet. A Western diet, including a high intake of red and processed meat and a low consumption of whole grains, fruits, vegetables, and fiber, may increase the risk of both colorectal cancer and obesity. Moreover, the Western diet is associated with a proinflammatory profile diet, which may also affect chronic low-grade inflammation. In fact, people with obesity often present gut dysbiosis, increased inflammation, and risk of colorectal cancer. In this article, the association between obesity and colorectal cancer is discussed, including the most important mechanisms, such as low-grade chronic inflammation, gut dysbiosis, and poor diet.

Personality traits favourable for non-adherence to treatment in patients with chronic myeloid leukaemia: role of type A and D personality.

BACKGROUND: The introduction of BCR-ABL tyrosine kinase inhibitors (TKIs) to chronic myeloid leukemia (CML) therapy has revolutionized the treatment of this disease. Although regular TKI intake is a prerequisite for successful therapy, it has been shown that a significant proportion of patients are non-compliant. Recently there is growing evidence that personality traits may influenced the tendency for non-adherence to treatment in patients with chronic diseases. As far as we know, such a relationship in patients with CML has not been examined, yet. The aim of our study was to determine if personality traits favor non-adherence to treatment recommendations. We investigated the relationship between five-factor model personality factors (conscientiousness, neuroticism, agreeableness, extraversion, and openness) and medication non-adherence. We also checked if the patients with type A and type D personality, were at higher risk of poor medication adherence. METHODS: The following tools were used: self-constructed survey, the NEO-Five Factor Inventory, the Framingham Type A Scale, the D-Scale 14. The study included 140 CML patients treated with imatinib, dasatinib, or nilotinib. RESULTS: 39% of patients reported skipping at least one dose of medication in the month prior to follow-up visit. 51% admitted to skipping such doses from the start of their treatment to the time at which our assessment was performed. We did not find any relationship between the mean values of the analyzed factors of the Big Five (neuroticism, extraversion, openness, agreeableness, conscientiousness) and adherence. However, our analysis revealed that CML patients who admitted to missing doses of drugs during the entire course of treatment demonstrated greater intensity of type A personality traits (p = 0.020). Regarding both factors of type D personality, it was revealed that higher level of negative affectivity significantly decreased the adherence (p = 0.020). CONCLUSION: The results of our study indicate that screening for type D and A personalities may help to identify patients who are at higher risk of poor medication adherence.

Impact of Folate Intake on Bone Mineral Density in Patients with Inflammatory Bowel Disease.

BACKGROUND: Decreased bone mineral density (BMD) is a common problem among patients with inflammatory bowel disease (IBD). We hypothesised that an insufficient intake of folate might affect BMD. METHODS: The study subjects included 26 with Crohn's disease-CD, 30 with ulcerative colitis-UC, and 31 healthy adults (control group-CG) aged 18-50 years. Participants were asked to follow their usual diet, and dietary intake was assessed by a 4-day, 24 h dietary recall. All the participants filled in a questionnaire referring to folic acid supplementation. The BMD, T-score, and Z-score of the lumbar spine (L1-L4) and femoral neck (FN) were assessed. RESULTS: We found significant differences in the body mass, BMI (body mass index), CRP (C-reactive protein), BMD, Z-score, and T-score of the L1-L4 and FN between groups. There were no differences in energy and folate intake or the percentage coverage of recommended dietary allowances (RDA) of folate in all groups. Moreover, 70% of patients with UC, 92% of patients with CD, and 77% of CG patients showed insufficient folate intake. Folic acid was supplemented with a similar frequency in patients covering and not covering the RDA of folate. The intake of folate per 1000 kcal correlated positively with the CD group's BMD and T-score of L1-L4. CONCLUSIONS: Insufficient folate intake is common in patients with IBD and healthy individuals. The impact of folate on BMD in IBD is not clear. We need more studies on the association between folate intake, folic acid concentration, and BMD in IBD.

Pleiotropic Effects of Vitamin D in Patients with Inflammatory Bowel Diseases.

The multifaceted activity of vitamin D in patients with inflammatory bowel disease (IBD) presents a challenge for further research in this area. Vitamin D is involved in the regulation of bone mineral metabolism, it participates in the regulation of the immune system, and it is an underlying factor in the pathogenesis of IBD. Additionally, vitamin D affects Th1 and Th2 lymphocytes, influencing the release of cytokines and inhibiting tumor necrosis factor (TNF) expression and the wnt/ß-catenin pathway. As far as IBDs are concerned, they are associated with microbiota dysbiosis, abnormal inflammatory response, and micronutrient deficiency, including vitamin D hypovitaminosis. In turn, the biological activity of active vitamin D is regulated by the vitamin D receptor (VDR) which is associated with several processes related to IBD. Therefore, in terms of research on vitamin D supplementation in IBD patients, it is essential to understand the metabolic pathways and genetic determinants of vitamin D, as well as to identify the environmental factors they are subject to, not only in view of osteoporosis prevention and therapy, but primarily concerning modulating the course and supplementation of IBD pharmacotherapy.

Accumulation of Advanced Glycation End-Products in the Body and Dietary Habits.

The formation of advanced glycation end-products (AGE) in tissues is a physiological process; however, excessive production and storage are pathological and lead to inflammation. A sedentary lifestyle, hypercaloric and high-fructose diet and increased intake of processed food elements contribute to excessive production of compounds, which are created in the non-enzymatic multi-stage glycation process. The AGE's sources can be endogenous and exogenous, mainly due to processing food at high temperatures and low moisture, including grilling, roasting, and frying. Accumulation of AGE increases oxidative stress and initiates various disorders, leading to the progression of atherosclerosis, cardiovascular disease, diabetes and their complications. Inborn defensive mechanisms, recovery systems, and exogenous antioxidants (including polyphenols) protect from excessive AGE accumulation. Additionally, numerous products have anti-glycation properties, occurring mainly in fruits, vegetables, herbs, and spices. It confirms the role of diet in the prevention of civilization diseases.

Treatment of Diabetes and Osteoporosis-A Reciprocal Risk?

Diabetes mellitus is a metabolic and systematic disorder that requires individualized therapy. The disease leads to various consequences, resulting in the destruction of tissues and organs. The aforementioned outcomes also include bone mineral disorders, caused by medications as well as diet therapy and physical activity. Some drugs may have a beneficial effect on both bone mineral density and the risk of fractures. Nevertheless, the impact of other medications remains unknown. Focusing on pharmacotherapy in diabetes may prevent bone mineral disorders and influence both the treatment and quality of life in patients suffering from diabetes mellitus. On the other hand, anti-osteoporosis drugs, such as antiresorptive or anabolic drugs, as well as drugs with a mixed mechanism of action, may affect carbohydrate metabolism, particularly in patients with diabetes. Therefore, the treatment of diabetes as well as osteoporosis prevention are vital for this group of patients.

Associations between vitamin D, bone mineral density, and the course of inflammatory bowel disease in Polish patients.

INTRODUCTION: There are various factors contributing to the pathogenesis of osteoporosis in inflammatory bowel disease (IBD), including steroid therapy, malnutrition, and vitamin D deficiency. OBJECTIVES: The study aimed to assess the vitamin D level among IBD patients and to investigate the relationship between vitamin D concentration and bone mineral density (BMD). PATIENTS AND METHODS: The study participants included 239 adult patients with IBD and a control group of 45 healthy adults. Densitometric measurements of the lumbar spine (L1-L4) and femoral neck (FN) were conducted using dual­energy X­ray absorptiometry. All patients completed a questionnaire referring to vitamin D supplementation. RESULTS: Significant differences were observed with regard to the body mass, body mass index, BMD, the Z­score, and the T­score of the FN and L1-L4. Only approximately 25% of all participants presented optimal or high concentrations of vitamin D. The research revealed no differences in vitamin D levels with regard to the disease extent and severity among the patients with ulcerative colitis. No differences were observed in terms of the disease localization, behavior, and the patient age at the time of diagnosis in the patients with Crohn disease. Furthermore, no differences were found in BMD, T­score, and Z­score of the FN and L1-L4 between the group of patients who supplemented and did not supplement vitamin D. CONCLUSIONS: Vitamin D may not be the only factor affecting BMD. Patients with IBD should supplement a higher dose of vitamin D than healthy adults.

Antioxidant effects of vitamin E and risk of cardiovascular disease in women with obesity - A narrative review.

Proper dietary habits are a vital element of cardiovascular (CV) treatment, and - according to the current guidelines - a diet rich in antioxidants is generally recommended. It remains, however, inconclusive whether antioxidant nutrients should be supplemented for CV health, and if so, in which form and dosage. Currently available data suggest that vitamin E may be essential in preventing CVD, especially in coronary heart disease and atherosclerosis - nevertheless, vitamin E supplementation may be questionable and may even be associated with adverse outcomes. Further, current studies highlight a strong need for identifying sex-specific strategies, which could improve guidelines for both the prevention and management of cardiovascular disease (CVD). It should also be emphasized that understanding the role of genetic variants in genes involved in VE metabolism may also be crucial for more precise nutritional recommendations for patients suffering from CVD. Therefore, we summarize the current knowledge regarding vitamin E antioxidant properties, which could be essential from CV perspective, and aim to assess whether vitamin E supplementation can be beneficial in CV prevention, especially in the high-risk group of women with obesity.

Where Do We Stand in the Behavioral Pathogenesis of Inflammatory Bowel Disease? The Western Dietary Pattern and Microbiota-A Narrative Review.

Despite the increasing knowledge with regard to IBD (inflammatory bowel disease), including ulcerative colitis (UC) and Crohn's disease (CD), the etiology of these conditions is still not fully understood. Apart from immunological, environmental and nutritional factors, which have already been well documented, it is worthwhile to look at the possible impact of genetic factors, as well as the composition of the microbiota in patients suffering from IBD. New technologies in biochemistry allow to obtain information that can add to the current state of knowledge in IBD etiology.

Why are western diet and western lifestyle pro-inflammatory risk factors of celiac disease?

The prevalence of celiac disease increased in recent years. In addition to the genetic and immunological factors, it appears that environmental determinants are also involved in the pathophysiology of celiac disease. Gastrointestinal infections impact the development of celiac disease. Current research does not directly confirm the protective effect of natural childbirth and breastfeeding on celiac disease. However, it seems that in genetically predisposed children, the amount of gluten introduced into the diet may have an impact on celiac disease development. Also western lifestyle, including western dietary patterns high in fat, sugar, and gliadin, potentially may increase the risk of celiac disease due to changes in intestinal microbiota, intestinal permeability, or mucosal inflammation. Further research is needed to expand the knowledge of the relationship between environmental factors and the development of celiac disease to define evidence-based preventive interventions against the development of celiac disease. The manuscript summarizes current knowledge on factors predisposing to the development of celiac disease including factors associated with the western lifestyle.

Does the VDR gene polymorphism influence the efficacy of denosumab therapy in postmenopausal osteoporosis?

Introduction: One of the challenges of personalized medicine is a departure from traditional pharmacology toward individualized, genotype-based therapies. Postmenopausal osteoporosis is a prevalent condition requiring intensive treatment, whose effects are measurable only after a long time, and the goal is bone fracture prevention. This study aimed to determine the influence of VDR gene variation on anti-osteoporotic one-year treatment with denosumab in 63 Polish women with postmenopausal osteoporosis. Materials and methods: The correlation between bone mineral density (BMD) of the lumbar vertebral column (L1-L4) and femoral neck, and genotype distributions for the ApaI, BsmI, FokI, and TaqI variants of the VDR gene was analyzed. Bone fractures during denosumab therapy were also investigated. Results: In the case of the Bsml polymorphism, female patients with BB and Bb genotypes had statistically significantly higher values of BMD and T-score/Z-score indicators, which persisted after a year of denosumab treatment. Our results indicated that the Bsml polymorphism contributes to better bone status, and, consequently, to more efficient biological therapy. The study did not reveal significant differences between changes (delta) in BMD and genotypes for the analyzed VDR gene loci. In the entire study group, one bone fracture was observed in one patient throughout the yearlong period of denosumab therapy. Conclusions: BB and Bb genotypes of the Bsml polymorphism of the VDR gene determine higher DXA parameter values both before and after one-year denosumab therapy in postmenopausal women with osteoporosis.

Liver Injury in Patients with Coronavirus Disease 2019 (COVID-19)-A Narrative Review.

While respiratory symptoms are prevalent in SARS-CoV-2 infected patients, growing evidence indicates that COVID-19 affects a wide variety of organs. Coronaviruses affect not only the respiratory system, but also the circulatory, nervous and digestive systems. The most common comorbidities in COVID-19 patients are hypertension, followed by diabetes, cardiovascular, and respiratory disease. Most conditions predisposing to SARS-CoV-2 infection are closely related to the metabolic syndrome. Obesity and chronic diseases, including liver disease, are associated with the induction of pro-inflammatory conditions and a reduction in immune response disorders, leading to the suspicion that these conditions may increase the susceptibility to SARS-CoV2 infection and the risk of complications. The definition of liver damage caused by COVID-19 has not yet been established. COVID-19 may contribute to both primary and secondary liver injury in people with pre-existing chronic disease and impaired liver reserves, leading to exacerbation of underlying disease, liver decompensation, or acute chronic liver failure. Therefore, many researchers have interpreted it as clinical or laboratory abnormalities in the course of the disease and treatment in patients with or without pre-existing liver disease. The research results available so far indicate that patients with liver disease require special attention in the event of COVID-19 infection.

Iron Deficiency Anemia in Inflammatory Bowel Diseases-A Narrative Review.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. IBD has been associated with numerous symptoms and complications, with the most common being iron deficiency anemia (IDA). Iron deficiency in IBD is caused by inadequate intake, malabsorption (including duodenal involvement and surgical removal), and chronic blood loss by mucosal ulcerations. Therefore, an appropriate diet should be enforced. Iron deficiency and iron supplementation have been associated with alterations to gut microbiota. IBD-associated anemia, in particular iron deficiency anemia, is associated with a significant decrease in quality of life and with clinical symptoms such as chronic fatigue, headaches and dizziness, reduced exercise tolerance, pale skin, nails, conjunctiva, and fainting. However, despite these numerous adverse symptoms, IDA remains undertreated. The European Crohn's and Colitis Organisation (ECCO) guidelines state that patients should be monitored for anemia. Adequate treatment, whether oral or intravenous, should be implemented while taking into consideration C-reactive protein values (CRP), hemoglobin levels, and therapeutic response. It should be stressed that every case of anemia in IBD patients should be treated. Intravenous iron formulations, which are more superior compared to the oral form, should be used. There is a need to increase awareness and implementation of international guidelines on iron supplementation in patients with IBD.

Does Folic Acid Protect Patients with Inflammatory Bowel Disease from Complications?

Folic acid, referred to as vitamin B9, is a water-soluble substance, which participates in the synthesis of nucleic acids, amino acids, and proteins. Similarly to B12 and B6, vitamin B9 is involved in the metabolism of homocysteine, which is associated with the MTHFR gene. The human body is not able to synthesize folic acid; thus, it must be supplemented with diet. The most common consequence of folic acid deficiency is anemia; however, some studies have also demonstrated the correlation between low bone mineral density, hyperhomocysteinemia, and folic acid deficiency. Patients with inflammatory bowel disease (IBD) frequently suffer from malabsorption and avoid certain products, such as fresh fruits and vegetables, which constitute the main sources of vitamin B9. Additionally, the use of sulfasalazine by patients may result in folic acid deficiency. Therefore, IBD patients present a higher risk of folic acid deficiency and require particular supervision with regard to anemia and osteoporosis prevention, which are common consequences of IBD.