As observational studies showed connections between vitaminD and the prevalence of T1DM, researchers worldwide endeavored to explore its possible mechanism. Wu et al.  discovered that VDR deletion affected IκBα through mRNA transcription, protein translation, protein-protein interaction, posttranslational modiication, and protein degradation. Such deletion subsequently led to a decreasing level of IκBα protein, which in turn led to the activation of NF-κB and put the VDR-/- cell in a proinlammation state. Du et al. [43,44] found that vitamin D3 could restore the activated innate immunity destruction to a certain extent. They showed that 1,25-(OH)2D3 could inhibit the expression of CD14, Toll-like receptor (TLR4), IL-1, and TNF-α, as well as reducing the NF-kB-p65 phosphorylation levels of the monocytes in the patients with LADA and/or T1DM . This result positively corresponded to Khoo’s research . These results proved that 1,25-(OH)2D3 had the ability to regulate the innate immune system associated with over-expression of TLRs and TLR signaling. Research has conirmed that 1,25-(OH)2D3 could suppress the production of pro-inlammatory cytokines such as IFN-γ, IL-17 and IL-2 [45,46], and up-regulate CTLA- 4 and FoxP3 of T cells. Both might be important factors that suppress inlammatory outcomes of autoimmune diseases .
creatic ß-cells. Autoimmune destruction of ß-cells is due to multiple genetic predisposi- tions and is also related to environmental factors that are still poorly defined (1). When clinical symptoms are observed the autoim- mune process is markedly advanced (60- 80% of the ß-cell mass have been destroyed at the time of diagnosis (2)). The rate of ß- cell destruction is variable, being rapid in children and slow in adults (3) (Figure 1). In the later stage of disease there is little or no insulin secretion, as indicated by low or undetectable plasma levels of C-peptide. C- peptide is consecrated with insulin by the ß- cells as a by-product of the enzymatic cleav- age of proinsulin to insulin. Measurement of C-peptide provides a fully validated means of quantifying endogenous insulin secretion, being closely related to the amount of ß-cell mass (4). Patients with type1diabetes de- pend on exogenous insulin administration for survival. The best classical treatment is based on 3-4 subcutaneous injections ofin- sulin per day, i.e., intensive insulin therapy (5). This treatment is responsible for a 35- 90% reduction of the risk of retinopathy, nephropathy and neuropathy compared with conventional therapy with 1-2 injections per day (6).
This was an observational retrospective study of a pop- ulation of T1D patients followed in a tertiary eye care center (Centro Hospitalar Universitário de S. João - CHUSJ, Porto, Portugal). All procedures were performed in accordance with the ethical standards of the Ethics Committee of Centro Hospitalar de São João/Faculty of Medicine of Porto Uni- versity and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards, having the present study been approved by this institution without the need of written informed consent given the nature of the study.
Diabetesmellitus (DM) integrates a heterogeneous group of metabolic disorders characterized by the body's inability to maintain glucose homeostasis. In 2019, this public health problem affected 463 million adults, and this will rise to 700 million in 2045 (International Diabetes Federation, 2020). Furthermore, 30% to 80% of cases remain undiagnosed, this being a major challenge in public health (World Health Organization [WHO], 2011). Type 2 DM (T2DM) is the most common, being responsible for 95% or more of the total cases. It is closely associated with lifestyle factors (e.g., diet and physical activity levels). T2DM is has a higher prevalence among middle-aged and older individuals, although it is increasingly appearing in overweight children, adolescents, and young adults (WHO, 2016). T1DM is less prevalent (3-5% of all cases of DM) and affects children and young adults, particularly. T1DM is characterized by the pancreatic beta-cell mass destruction, being these cells responsible for producing insulin. Although not fully understood, the origin of T1DM seems to be related to an overaggressive autoimmune response, which leads to the failure of pancreatic endocrine function (Kahanovitz et al., 2017).
Fasting plasma glucose levels of poorly controlled and well-controlled diabetic subjects were 209 (89- 422) mg/dl and 126 (78-294) mg/dl, respectively. The difference was statistically significant, as expected (p<0.001). Similarly, HbA1c of poorly controlled di- abetics (9.7 [8-16.6] %) was significantly higher than that of the relatively well-controlled diabetic subjects (6.9 [5.4-7.7] %), again expectedly (p<0.001). General characteristics and laboratory data of study popula- tion were expressed in table 1.
There was a low incidence of asthma in immigrant children from South Asia, but higher rates in adult immigrants, and the children of South Asian immigrants. The higher risk of asth- ma in adults may be secondary to environmental or occupational exposures in South Asia, not a contributing factor in children who arrive to Canada. We have demonstrated that the inci- dence of asthma in the children of South Asian mothers, and those of other immigrant moth- ers, was significantly higher that the incidence in children of non-immigrant mothers. Early life or in utero exposures to environmental factors specific to the Canadian context may be im- plicated. For example, Cesarean section rates, antibiotic usage, low maternal vitaminD levels, and a hygienic environment have all been suggested to be involved . All of these are more prevalent in Canada compared to South Asian and other developing nations.
No significant differences were found in the percentage increase in the arterial FMD (%) between the control group (11.45 ± 2.86%) and subgroup T1DM < 5 (10.21 ± 2.70%, p = 0.078), but a significant difference was observed when the control group was compared with the subgroup T1DM ≥ 5 (7.04 ± 1.38%, p = 0.0001). The timing of the maximal dilation after stimulation did not change with the division into subgroups. There was no significant difference in the percentage of increase in FMD between genders (data not shown), both in the control group and diabetics subgroups in the four repeated measurements performed after post-occlusive reactive hyperemia. Similarly, no significant differences between groups were observed in the analysis of parameters related to the brachial artery, including systolic peak (SP), pulsatility index (PI), resistivity index (RI), maximum acceleration time (AT max), end diastolic speed (ED), and the ratio peak systolic velocity/peak diastolic velocity (S/D). The results from the measurements of the carotid arteries obtained with the IMT technique are shown in Table 4.
There are several treatment options including a multidisciplinary clinical approach designed to promote weight loss, pharmacological therapies, and bariatric and metabolic surgical techniques [8, 9]. The ileal transposition involves the segment removal of the distal ileum and its insertion into the proximal small intestine, a procedure that promoting early satiety and exerting benefits on glucose metabolism and weight loss. These effects probably can be attributed to incretins stimulation such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), increasing insulin sensitivity in the short-and medium-term, allowing clinical type 2 DM patient control without the need for insulin or oral hypoglycemic agents [10 - 13].
Development: VitaminD is obtained either endogenously through sun exposure, or exogenously from dietary sources (<10%). The functions in calcium and phosphate homeostasis are well known. The existence of the vitaminD receptor in various tissues, as well as its role on the immune system have been discovered recently and allowed to relate it to other physiological processes and disorders, including various autoimmune diseases (in which is included diabetesmellitustype1), cardiovascular diseases, metabolic diseases, amongst others. Diabetesmellitustype1 is a chronic autoimmune disease characterized by selective and progressive destruction of β cells in the pancreas that produce insulin. Multiple genetic and environmental factors contribute to its etiology. Several studies suggest an association between vitaminD deficiency and this disease, which may be justified by the modulating effect of this vitamin and several polymorphisms existing on their receptor, in enzymes involved in their metabolism and their carrier proteins.
In addition to its role in calcium homeostasis, it is believed that the active form ofvitaminD has immunomodulatory effects on cells of the immune system, particularly T lymphocytes, as well as on the production and action of several cytokines. The interaction ofvitaminD with the immune system has been the target of a growing number of publications in recent years. Current studies have linked the deiciency ofvitaminD with different autoimmune diseases, including insulin-dependent diabetesmellitus (IDDM), multiple sclerosis (MS), inlammatory bowel disease (IBD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). This article reviews the physiology and immunomodulatory role ofvitaminD, emphasizing its involvement in rheumatic diseases such as SLE and RA.
W e are thankful to Kurt, O. for his keen interest in the study “High prevalence ofvitaminD deiciency among newly diagnosed youth-onset diabetesmellitusin north India” published recently in Arquivos Brasileiros de Endocrinologia & Metabolo- gia (1). It is also appreciated that the researcher has gone into the details of the study. The authors have rightly pointed out that vitaminD deiciency was more common in youth-onset diabetes (age less than 25 years) when compared with age, body mass index (BMI) and gender-matched healthy control population.
Methodology/Principal Findings: We measured the left ventricular ejection fraction (EF), ratio of early to late left ventricular filling velocity (E/A) and ratio of early diastolic mitral inflow to annular velocity (E/Ea) by ultrasonography in 110 patients with type 2 diabetesmellitus for more than 5 years. Anthropometric and fasting blood values were obtained from medical records. The plasma Ang-(1-7) level in patients with a poor EF (,50%) was significantly lower than that in patients with EF $50%; the level in patients with E/A ,1 was significantly lower than that in patients with E/A $1; and the level in patients with E/Ea .15 was significantly lower than that in patients with E/Ea #15. Ang-(1–7) level was negatively correlated with E/ Ea and Log-N-terminal pro-B-type natriuretic peptide and positively with EF and E/A. Stepwise multiple regression analysis revealed that Ang-(1–7), hemoglobin A1c and Ang-II levels as well as duration ofdiabetes predicted EF; Ang-(1–7) level, fasting blood glucose, low-density lipoprotein cholesterol level and duration ofdiabetes predicted E/A; and Ang-(1–7) and hemoglobin A1c levels predicted E/Ea.
About 2/3 of patients with AD have a Th2 (T- he|per2) immune reactivity pattern  . AD is a common disease. The consequence of the rising prevalence of AD is a heavy burden on medical Services and budgets  The prevalence of AD in Iran is about 2%  .
Another piece of evidence of the complex role of 25(OH)D is the extensive genetic analyses linking the polymorphic variation in the genes for several components of the 25(OH)D metabolic and signaling system to T1D. Some speciic VDR gene haplotypes appear to protect against diabetes, while polymorphisms in the CYP27B1 gene have been shown to affect diabetes susceptibility (56,57). Given the evidence that variation in the CYP27B1 etiologically contributes to T1D risk, other genes that control vitaminD metabolism are also biologically plausible candidates, and should be studied. In a clinical setting, two recent trials found no signiicant effect of 1,25(OH) 2 D on the preservation of β-cell function after type1diabetes onset (58,59). Nevertheless, the dose and mechanistic action ofvitaminD are still under discussion. On the other hand, in a randomized, double-blind, placebo-controlled trial in new-onset T1D, we studied the effect of 2000 IU of 25(OH)D on peripheral cytokine levels, Treg cells and the decline of residual β-cell function. We found that the cumulative incidence of progression to undetectable (≤ 0.1 ng/ml) fasting serum C-peptide during the 18 months of follow-up reached 18.7% in the 25 (OH)D group, and 62.5% in the placebo group (P = .012) while stimulated C-Peptide reached this level in 6.2% of the 25(OH)D and 37.5% of placebo group (P = .047). We also found a tendency to increase IL-10 and Treg cells (CD4 + CD25 + Foxp 3 ), which might
Considering the above mentioned, we may infer that the T1DM prevention is difficult. It is supposed that, in the autoimmune process evolution, individuals produce dif- ferent proteins, antigens with the expression of different epitopes which were not detected initially, contributing to the process perpetuation. According to the suggestion of a recent article in the beginning of the autoimmune process against pancreatic beta cells, we may have three or more antigens, but at the end, there are endless antigens which are activating the process, i.e., the greater the beta cell lesion, the more antigens are expressed, which will reactivate the process. This proposal covers a new concept for the natural history of T1ADM which, in its preclinical stage, would be characterized by a succession of relapses and remissions with interrelation between regulatory T cells (T-regs) and effectors cells, and regeneration of beta cells up to the moment when the percentage of beta cell destruction would no longer allow a proper insulin secre- tion, resulting in the expression of hyperglycemia. Within this context, it becomes important to mention the low capacity of regeneration/neogenesis of beta cells mainly when they are exposed to hyperglycemia, which is a stim- ulus metabolic factor to the insulin secretion, but it is also glycotoxic. When proper glycemic control is instituted at the beginning of the disease, these cells have acquiescence and may to keep the levels of C-peptide secretion for a additional period of time.
The relationship between increased UAE levels with a higher risk of cardiovascular disease in DM1 patients has been demonstrated by several authors (21,32,33). After the onset of proteinuria, median survival is only about seven years, and this increased mortality is mainly due to cardiovascular death rather than renal failure (34). High levels of serum creatinine and reduced eGFR have also been demonstrated to be indicative of progressive cardiovascular disease among diabetic patients (35,36), and increased levels of cystatin C have been associated with the development of cardiovascular events (37-40). Some authors have even shown that cystatin C is a stronger predictor of cardiovascular outcomes in patients with diabetes and elderly adults than creatinine and eGFR (39,40).
Insulin is the most efective anti-hyperglycemic agent with a glucose-lowering efect of HbA1c reduction by 1.5% to 3.5%. Due to the progressive decline of β-cell function with increas- ing age, insulin replacement therapy is frequently required in older adults with type 2 diabetes with long duration of disease. However, there are many barriers to appropriate insulin use in elderly with diabetes. he most common obstacles are concern about hypoglycemia and complex nature of insulin adminis- tration. Multiple comorbid conditions in older adults with dia- betes, e.g., impaired vision, poor physical function, and/or cog- nitive impairment, make it diicult to perform self-injection of insulin and also self-monitoring of glucose. In these situations, external resources, including family support and care givers, should be evaluated and insulin regimens need to be simpli- ied and modiied according to patient resources.
c) A efectividade da implementação da presente Norma nos cuidados de saúde primários e a emissão de directivas e instruções para o seu cumprimento é da responsabilidade dos conselhos clínicos dos agrupamentos de centros de saúde. d) A Direcção-Geral da Saúde, através do Departamento da Qualidade na Saúde e do
The readability index estimated in this study received a classification of easy reading. As limitation to this study, it is recognized that, for the age of the public in question, the ideal would be the classification of the content as very easy, however, the specificity of the topic of the booklet motivated the writing of some polysyllable words and technical terms. These terms were repeated several times, which may raise the quantitative evaluation of the index. However, it is believed that it did not increase the level of difficulty of reading, since these words are part of the everyday life of children with DM1 and knowing them is a sine qua non strategy for the promo- tion of self-care. Among these words, the following stand out: insulin, diabetes, treatment, blood glucose, monitoring, and feeding.
A. Em Portugal, de acordo com os últimos dados do Observatório Nacional da Diabetes (adaptados a partir do estudo PREVADIAB), a prevalência da diabetes registada entre os 20-79 anos é de 12,7%, ajustada à população de 2011. Esta prevalência refere-se à diabetes na globalidade, mas tendo em conta o grupo etário estudado e a baixa incidência de DM1 em Portugal, pode-se estimar que cerca de 90% destes casos correspondem a DM2. 21,22