Association of major dietary patterns with advanced glycation end products and high-sensitivity C-reactive protein in people with type 1 diabetes mellitus.

BACKGROUND: The associations of diet with serum levels of advanced glycation end products (AGEs) and high-sensitivity C-reactive protein (hs-CRP) have been examined in patients with type 2 diabetes mellitus (T2DM). However, data on patients with type 1 diabetes mellitus (T1DM) are limited. Therefore, this study was conducted to investigate the associations of major dietary patterns with serum levels of AGEs and hs-CRP among patients with T1DM. METHODS: A total of 229 patients with T1DM participated in this current cross-sectional study. We collected dietary data using a validated food frequency questionnaire (FFQ). The factor analysis approach was used to determine major dietary patterns. A fasting blood sample was collected from each participant to assess serum levels of AGEs and hs-CRP. The associations of dietary patterns with elevated levels of AGEs and hs-CRP were assessed using binary logistic regression. RESULTS: Patients with T1DM in the highest tertile of a Western dietary pattern had 4.32 times higher odds of having elevated AGEs than those in the lowest tertile (OR: 4.32, 95% CI: 1.86-10.05). Additionally, adherence to the Western diet was associated with 2.97 times greater odds of having elevated hs-CRP (> 3 mg/L) (OR: 2.97, 95% CI: 1.22-7.24) in these patients. Such positive associations were not observed for unhealthy and traditional dietary patterns. Moreover, higher adherence to a semi-healthy diet (characterized by high consumption of white meat, whole grains, processed meat, and a low salt intake) was associated with 87% lower odds of having elevated hs-CRP (OR: 0.13, 95% CI: 0.05-0.35). However, we found no significant association between the semi-healthy diet and AGEs levels. CONCLUSION: We found that adherence to a Western dietary pattern was associated with elevated levels of AGEs/hs-CRP in patients with T1DM. Also, we discovered a significant inverse association between adherence to a semi-healthy diet and hs-CRP levels.

Vitamin D Regulates MerTK-Dependent Phagocytosis in Human Myeloid Cells.

Vitamin D deficiency is a major environmental risk factor for the development of multiple sclerosis. The major circulating metabolite of vitamin D (25-hydroxyvitamin D) is converted to the active form (calcitriol) by the hydroxylase enzyme CYP27B1 In multiple sclerosis lesions, the tyrosine kinase MerTK expressed by myeloid cells regulates phagocytosis of myelin debris and apoptotic cells that can accumulate and inhibit tissue repair and remyelination. In this study, we explored the effect of calcitriol on homeostatic (M-CSF, TGF-ß-treated) and proinflammatory (GM-CSF-treated) human monocyte-derived macrophages and microglia using RNA sequencing. Transcriptomic analysis revealed significant calcitriol-mediated effects on both Ag presentation and phagocytosis pathways. Calcitriol downregulated MerTK mRNA and protein expression in both myeloid populations, resulting in reduced capacity of these cells to phagocytose myelin and apoptotic T cells. Proinflammatory myeloid cells expressed high levels of CYP27B1 compared with homeostatic myeloid cells. Only proinflammatory cells in the presence of TNF-α generated calcitriol from 25-hydroxyvitamin D, resulting in repression of MerTK expression and function. This selective production of calcitriol in proinflammatory myeloid cells has the potential to reduce the risk for autoantigen presentation while retaining the phagocytic ability of homeostatic myeloid cells.

GABRIC Diabetes School: an innovative education centre for people with diabetes.

Diabetes prevalence and deaths attributable to diabetes continue to rise across globally. Diabetes Self-Management Education and Support (DSME/S) is a critical resource designed to help people with diabetes (PWD) successfully selfmanage their disease; however, its utilization is too low. In the Islamic Republic of Iran, there are currently limited structured educational programmes and no national standards for DSME/S protocol. In response to this, the GABRIC Diabetes Education Association (GDEA) has been developed as a school for diabetics, which has a comprehensive DSME/S programme for PWD with 18 distinct courses on 5 levels for 8 target groups. In addition, GABRIC has developed a database registry with more than 100 000 members throughout the country, of whom 95% are diabetic with a proportion of 82% Type 2 diabetes and 13% Type 1 diabetes. The success of the GABRIC school model results is yet to be investigated through study trials, and offers a fruitful line of research.

A Review of the Evidence for Tryptophan and the Kynurenine Pathway as a Regulator of Stem Cell Niches in Health and Disease.

Stem cells are ubiquitously found in various tissues and organs in the body, and underpin the body's ability to repair itself following injury or disease initiation, though repair can sometimes be compromised. Understanding how stem cells are produced, and functional signaling systems between different niches is critical to understanding the potential use of stem cells in regenerative medicine. In this context, this review considers kynurenine pathway (KP) metabolism in multipotent adult progenitor cells, embryonic, haematopoietic, neural, cancer, cardiac and induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stromal cells. The KP is the major enzymatic pathway for sequentially catabolising the essential amino acid tryptophan (TRP), resulting in key metabolites including kynurenine, kynurenic acid, and quinolinic acid (QUIN). QUIN metabolism transitions into the adjoining de novo pathway for nicotinamide adenine dinucleotide (NAD) production, a critical cofactor in many fundamental cellular biochemical pathways. How stem cells uptake and utilise TRP varies between different species and stem cell types, because of their expression of transporters and responses to inflammatory cytokines. Several KP metabolites are physiologically active, with either beneficial or detrimental outcomes, and evidence of this is presented relating to several stem cell types, which is important as they may exert a significant impact on surrounding differentiated cells, particularly if they metabolise or secrete metabolites differently. Interferon-gamma (IFN-γ) in mesenchymal stromal cells, for instance, highly upregulates rate-limiting enzyme indoleamine-2,3-dioxygenase (IDO-1), initiating TRP depletion and production of metabolites including kynurenine/kynurenic acid, known agonists of the Aryl hydrocarbon receptor (AhR) transcription factor. AhR transcriptionally regulates an immunosuppressive phenotype, making them attractive for regenerative therapy. We also draw attention to important gaps in knowledge for future studies, which will underpin future application for stem cell-based cellular therapies or optimising drugs which can modulate the KP in innate stem cell populations, for disease treatment.

Association of Polycyclic Aromatic Hydrocarbons Urine Metabolites with Type 1 Diabetes.

Purpose: Polycyclic aromatic hydrocarbons (PAHs) are believed to be a possible factor in the development of cancer, ischemic heart disease, obesity, and cardiovascular disease. The objective of this study was to explore the association between certain metabolites of urinary PAH and type 1 diabetes (T1D). Methods: In Isfahan City, a case-control study was carried out involving 147 T1D patients and an equal number of healthy individuals. The study measured the levels of urinary metabolites of PAHs, specifically 1-hydroxynaphthalene, 2-hydroxynaphthalene, and 9-hydroxyphenanthrene, in both the case and control groups. The levels of these metabolites were then compared between the two groups to assess any potential association between the biomarkers and T1D. Results: The mean (SD) age of participants in the case and control groups was 8.4 (3.7) and 8.6 (3.7) years old, respectively, (P > 0.05). In terms of gender distribution, 49.7% and 46% of participants in the case and control groups were girls, respectively (P > 0.05). Geometric mean (95% CI) concentrations were: 36.3 (31.4-42) µg/g creatinine for 1-hydroxynaphthalene, 29.4 (25.6-33.8) µg/g creatinine for 2-hydroxynaphthalene, and 72.26 (63.3-82.5) µg/g creatinine for NAP metabolites. After controlling for variables such as the child's age, gender, maternal and paternal education, duration of breastfeeding, exposure to household passive smoking, formula feeding, cow's milk consumption, body mass index (BMI), and five dietary patterns, it was observed that individuals in the highest quartile of 2-hydroxynaphthalene and NAP metabolites had a significantly greater odd ratio for diabetes compared to those in the lowest quartile (P < 0.05). Conclusion: Based on the findings of this study, it is suggested that exposure to PAH might be linked to an increased risk of T1D in children and adolescents. To clarify a potential causal relationship related to these findings, further prospective studies are needed.

Use of ambulatory glucose monitoring and analysis of ambulatory glucose profile in clinical practice for diabetes management; a position statement of the Arab Society of Paediatric Endocrinology and diabetes.

BACKGROUND AND AIM: Diabetes mellitus imposes a significant burden around the world generally and in the Middle East and North Africa specifically. Glucose monitoring is a cornerstone of diabetes management. METHODS: Glycated haemoglobin has always been the main metric for assessing glycaemic control, but its use is linked with multiple pitfalls. As an alternative, continuous glucose monitoring is becoming a standard of care in many countries. Intermittent scanning glucose monitoring (isCGM) has acquired a worldwide popularity and has been proven to improve glycaemic control, hypoglycaemia detection and prevention, and quality of life. RESULTS: The most recent International Society of Paediatric and Adolescent Diabetes practice. guidelines recommended its use in young people with diabetes observing Ramadan to ensure safe fasting. At a meeting in Abu Dhabi in November 2019, the Arab Society for Paediatric. Endocrinology and Diabetes brought together a number of regional diabetes experts, patient. representatives and international expert advisors to review the evidence for isCGM and propose. guidelines for its use in the Middle East and North Africa region. CONCLUSION: In this paper, the authors strongly recommend the use of isCGM for patients in MENA and present general recommendations and compressive specific guidance for physicians and patients, which they believe will also have wider resonance.