Destruction Of Pancreatic Beta Cells Research Articles

Levels of 25(OH)D3, IL-2, and C-peptide in Children with Type 1 Diabetes Mellitus (T1DM) Receiving Vitamin D3 Supplementation

Type 1 Diabetes Mellitus (T1DM) has become a health problem in many countries. T1DM is the consequence of autoimmune destruction process of β cells. There was relationship between vitamin D deficiency with T1DM. The destruction process was caused by an imbalance of pro-inflammatory and anti-inflammatory cytokines. One of the pro-inflammatory cytokines is IL-2. C-peptide examination to see the function of beta cells due to destruction of pancreatic beta cell. Administration of vitamin D 3 supplementation still cause controversy and give varying results. This randomized clinical trial was conducted to determine the levels of 25(OH)D 3 , IL-2, and C-peptide in people with T1DM who received vitamin D 3 supplementation. The subjects were 26 children with T1DM, divided into K1 group (received vitamin D 3 supplementation) and K2 group (received placebo). The results showed higher levels of 25(OH)D 3 in the K1 group and statistically found a significant difference (p = 0.00). Higher levels of IL-2 and lower C-peptide were obtained in the K1 group and no statistically significant differences were found (p = 0.76 and p= 0.26). The insignificant relationship and the negative correlation were found between 25(OH)D 3 and IL-2 (p = 0.71; r = - 0.12), 25(OH)D 3 and C-peptide (p = 0.59; r = -0.16), also levels of IL-2 and C-peptide (p = 0.13; r = -0.44) in children with type 1 diabetes who received vitamin D3 supplementation. From this study can be concluded that administration vitamin D 3 supplementation in patients with T1DM can increase levels 25(OH)D 3 significantly. This increase has not significantly lowered levels of IL-2 and increased levels of C-peptide. However, there was an absolute decrease in the rate of slower C-peptide in the supplemented group than in the placebo group.

Type 1 Diabetes Mellitus: Cellular and Molecular Pathophysiology at A Glance.

Type 1 diabetes mellitus (T1DM) is a disease where destruction of the insulin producing pancreatic beta-cells leads to increased blood sugar levels. Both genetic and environmental factors play a part in the development of T1DM. Currently, numerous loci are specified to be the responsible genetic factors for T1DM; however, the mechanisms of only a few of these genes are known. Although several environmental factors are presumed responsible for progression of T1DM, to date, most of their mechanisms remain undiscovered. After several years of hyperglycemia, late onsets of macrovascular (e.g., cardiovascular) and microvascular (e.g., neurological, ophthalmological, and renal) complications may occur. This review and accompanying figures provides an overview of the etiological factors for T1DM, its pathogenesis at the cellular level, and attributed complications.

T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes.

Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications. Ideally a successful approach would target only the destructive immune cells and leave the remaining immune system intact to fight foreign pathogens. This review discusses the autoimmune diabetes disease process, diabetic complications that warrant a transplant, and alloimmunity. First, we describe the current understanding of autoimmune destruction of beta cells including the roles of CD4 and CD8 T cells and several possibilities for antigen-specific tolerance induction. Second, we outline diabetic complications necessitating beta cell replacement. Third, we discuss transplant recognition, potential sources for beta cell replacement, and tolerance-promoting therapies under development. We hypothesize that a better understanding of autoreactive T cell targets during disease pathogenesis and alloimmunity following transplant destruction could enhance attempts to re-establish tolerance to beta cells.

Oral histone deacetylase inhibitor synergises with T cell targeted immunotherapy to preserve beta cell metabolic function and induce stable remission of new-onset autoimmune diabetes in NOD mice.

Combination therapy targeting the major actors involved in the immune-mediated destruction of pancreatic beta cells appears to be an indispensable approach to treat type 1 diabetes effectively. We hypothesised that the combination of an orally active pan-histone deacetylase inhibitor (HDACi: givinostat) with subtherapeutic doses of CD3 antibodies may provide ideal synergy to treat ongoing autoimmunity. NOD mice transgenic for the human CD3ε (also known as CD3E) chain (NOD-huCD3ε) were treated for recent-onset diabetes with oral givinostat, subtherapeutic doses of humanised CD3 antibodies (otelixizumab, 50μg/day, 5days, i.v.) or a combination of both drugs. Disease remission, metabolic profiles and autoreactive T cell responses were analysed in treated mice. We demonstrated that givinostat synergised with otelixizumab to induce durable remission of diabetes in 80% of recently diabetic NOD-huCD3ε mice. Remission was obtained in only 47% of mice treated with otelixizumab alone. Oral givinostat monotherapy did not reverse established diabetes but reduced the in situ production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Importantly, the otelixizumab + givinostat combination strongly improved the metabolic status of NOD-huCD3ε mice; the mice recovered the capacity to appropriately produce insulin, control hyperglycaemia and sustain glucose tolerance. Finally, diabetes remission induced by the combination therapy was associated with a significant reduction of insulitis and autoantigen-specific CD8+ T cell responses. HDACi and low-dose CD3 antibodies synergised to abrogate in situ inflammation and thereby improved pancreatic beta cell survival and metabolic function leading to long-lasting diabetes remission. These results support the therapeutic potential of protocols combining these two drugs, both in clinical development, to restore self-tolerance and insulin independence in type 1 diabetes.

Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

Blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n=11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n=10). To our knowledge, the current study represents the largest (>2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA. Biological significanceThe temporal changes of >2000 plasma proteins (at least quantified in two subjects), spanning the entire period of T1D natural progression were provided to the research community. Oxidative stress related proteins have consistently different dysregulated patterns in T1D group than in age-sex matched healthy controls, even prior to appearance of islet autoantibodies – the earliest sign of islet autoimmunity and pancreatic beta cell stress.

The Role of Protein Tyrosine Phosphatase Nonreceptor Type 22 Gene polymorphism in Patients With Type 1 Diabetes Mellitus.

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune multifactorial disease characterized by progressive destruction of pancreatic beta cells by genetic and environmental factors which leads to an absolute dependence of insulin for survival and maintenance of health. Materials and methods: One polymorphic sites of PTPN22 gene was genotyped in 64 patients with T1DM, and 25 healthy controls. Genotypes were determined by the polymerase chain restriction fragment length polymorphism (PCR-RFLP) method. Results: The single nucleotide polymorphisms T/T, of the PTPN22 gene may be participate in the susceptibility of T1DM in the Iraqi population. Conclusion: Although PTPN22-T/T polymorphism not associated with T1DM in many population, our study confirmed significant correlation between PTPN22 and T1DM.

Coxsackievirus-Induced Proteomic Alterations in Primary Human Islets Provide Insights for the Etiology of Diabetes.

Enteroviral infections have been associated with the development of type 1 diabetes (T1D), a chronic inflammatory disease characterized by autoimmune destruction of insulin-producing pancreatic beta cells. Cultured human islets, including the insulin-producing beta cells, can be infected with coxsackievirus B4 (CVB4) and thus are useful for understanding cellular responses to infection. We performed quantitative mass spectrometry analysis on cultured primary human islets infected with CVB4 to identify molecules and pathways altered upon infection. Corresponding uninfected controls were included in the study for comparative protein expression analyses. Proteins were significantly and differentially regulated in human islets challenged with virus compared with their uninfected counterparts. Complementary analyses of gene transcripts in CVB4-infected primary islets over a time course validated the induction of RNA transcripts for many of the proteins that were increased in the proteomics studies. Notably, infection with CVB4 results in a considerable decrease in insulin. Genes/proteins modulated during CVB4 infection also include those involved in activation of immune responses, including type I interferon pathways linked to T1D pathogenesis and with antiviral, cell repair, and inflammatory properties. Our study applies proteomics analyses to cultured human islets challenged with virus and identifies target proteins that could be useful in T1D interventions.

Comparative quantitative proteomic analysis of disease stratified laser captured microdissected human islets identifies proteins and pathways potentially related to type 1 diabetes.

Type 1 diabetes (T1D) is a chronic inflammatory disease that is characterized by autoimmune destruction of insulin-producing pancreatic beta cells. The goal of this study was to identify novel protein signatures that distinguish Islets from patients with T1D, patients who are autoantibody positive without symptoms of diabetes, and from individuals with no evidence of disease. High resolution high mass accuracy label free quantitative mass spectrometry analysis was applied to islets isolated by laser capture microdissection from disease stratified human pancreata from the Network for Pancreatic Organ Donors with Diabetes (nPOD), these included donors without diabetes, donors with T1D-associated autoantibodies in the absence of diabetes, and donors with T1D. Thirty-nine proteins were found to be differentially regulated in autoantibody positive cases compared to the no-disease group, with 25 upregulated and 14 downregulated proteins. For the T1D cases, 63 proteins were differentially expressed, with 24 upregulated and 39 downregulated, compared to the no disease controls. We have identified functional annotated enriched gene families and multiple protein-protein interaction clusters of proteins are involved in biological and molecular processes that may have a role in T1D. The proteins that are upregulated in T1D cases include S100A9, S100A8, REG1B, REG3A and C9 amongst others. These proteins have important biological functions, such as inflammation, metabolic regulation, and autoimmunity, all of which are pathways linked to the pathogenesis of T1D. The identified proteins may be involved in T1D development and pathogenesis. Our findings of novel proteins uniquely upregulated in T1D pancreas provides impetus for further investigations focusing on their expression profiles in beta cells/ islets to evaluate their role in the disease pathogenesis. Some of these molecules may be novel therapeutic targets T1D.

Targeting innate immunity to downmodulate adaptive immunity and reverse type 1 diabetes.

Type 1 diabetes (T1D) is characterized by specific destruction of pancreatic insulin-producing beta cells accompanied by evidence of beta-cell-directed autoimmunity such as autoreactive T cells and islet autoantibodies (IAAs). Currently, T1D cannot be prevented or reversed in humans. T1D is easy to prevent in the nonobese diabetic (NOD) spontaneous mouse model but reversing new-onset T1D in mice is more difficult. Since the discovery of the T-cell receptor in the 1980s and the subsequent identification of autoreactive T cells directed toward beta-cell antigens (eg, insulin, glutamic acid decarboxylase), the dream of antigen-specific immunotherapy has dominated the field with its promise of specificity and limited side effects. While such approaches have worked in the NOD mouse, however, dozens of human trials have failed. Broader immunosuppressive approaches (originally cyclosporine, subsequently anti-CD3 antibody) have shown partial successes (e.g., prolonged C peptide preservation) but no major therapeutic efficacy or disease reversal. Human prevention trials have failed, despite the ease of such approaches in the NOD mouse. In the past 50 years, the incidence of T1D has increased dramatically, and one explanation is the “hygiene hypothesis”, which suggests that decreased exposure of the innate immune system to environmental immune stimulants (e.g., bacterial products such as Toll-like receptor (TLR) 4-stimulating lipopolysaccharide [LPS]) dramatically affects the adaptive immune system and increases subsequent autoimmunity. We have tested the role of innate immunity in autoimmune T1D by treating acute-onset T1D in NOD mice with anti-TLR4/MD-2 agonistic antibodies and have shown a high rate of disease reversal. The TLR4 antibodies do not directly stimulate T cells but induce tolerogenic antigen-presenting cells (APCs) that mediate decreased adaptive T-cell responses. Here, we review our current knowledge and suggest future prospects for targeting innate immunity in T1D immunotherapy.

Distribution of Thyroid Autoantibodies in Saudi Children with Type 1 DM and their Effect on Glycemic Control

Introduction Type1 diabetes mellitus (T1DM) is a chronic autoimmune disease result in destruction of pancreatic beta cells lead to the clinical form of the disease (1). Unfortunately a recent study reported increasing in the incidence of the disease by 2-5% globally (2). However the prevalen

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes

Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and, eventually, destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this study was to explore the effectiveness of a novel, non-pharmacological approach that uses the application of ultrasound energy to augment insulin release from rat INS 832/13 beta cells. The cells were exposed to unfocused ultrasound for 5 min at a peak intensity of 1 W/cm2 and frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz. Insulin release was measured with enzyme-linked immunosorbent assay and cell viability was assessed via the trypan blue dye exclusion test. A marked release (approximately 150 ng/106 cells, p < 0.05) of insulin was observed when beta cells were exposed to ultrasound at 400 and 600 kHz as compared with their initial control values; however, this release was accompanied by a substantial loss in cell viability. Ultrasound application at frequencies of 800 kHz resulted in 24 ng/106 cells released insulin (p < 0.05) as compared with its unstimulated base level, while retaining cell viability. Insulin release from beta cells caused by application of 800-kHz ultrasound was comparable to that reported by the secretagogue glucose, thus operating within physiological secretory capacity of these cells. Ultrasound has potential as a novel and alternative method to current approaches aimed at correcting secretory deficiencies in patients with type 2 diabetes.

Polymorphisms in genes encoding miR-155 and miR-146a are associated with protection to type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation. Abnormal miRNA expressions have been described in autoimmune diseases and T1DM. Polymorphisms in genes codifying miRNAs may alter the expression of the corresponding miRNA and, thus, confer susceptibility for a given disease. Therefore, the aim of this study was to investigate whether polymorphisms in genes encoding miR-155, miR-146a, and miR-375 are associated with T1DM. Frequencies of the miRNA-146a rs2910164, miRNA-155 rs767649 and miRNA-375 rs6715345 polymorphisms were analyzed in 490 T1DM patients and in 469 nondiabetic subjects. The miR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM, and the strongest association was observed for the dominant model [odds ratio (OR)=0.557 95% CI 0.355-0.874 and OR=0.508, 95% CI 0.265-0.973, respectively, after adjustment for age, ethnicity, and risk HLA loci]. However, miR-375 rs6715345 frequencies did not differ between cases and controls. MiR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM.

C-Peptide as a Marker for Diabetic Nephropathy

Diabetes mellitus is a metabolic disorder of multiple aetiology. Destruction of pancreatic beta cells, hyperglycaemia, and insulin deficiency cause type 1 diabetes mellitus. Diabetic nephropathy is the damage to kidneys because of diabetes. It is predominantly seen in patients with type 1 diabetes (insulin-dependent type) and type 2 diabetes (non-insulin-dependent type). An active peptide hormone, C-peptide has the likelihood of causing major physiological effects. C-peptide is the best indication of endogenous insulin secretion occurring in patients with diabetes. In this regard, the current study undertakes a comprehensive study of C-peptide and kidney (renal) failure in patients with diabetes mellitus in order to assess their association. A prospective cross sectional study is conducted at King Abdul Aziz University Hospital. The subjects for this study were patients with type 2 DM. Laboratory tests such as HbA1c, serum creatinine, urine albumin and creatinine, fasting serum C-peptide, and blood urea nitrogen are conducted. Data was analysed using analysis of variance (ANOVA) test to compare the values between different category patients. The study also found that there exists a significant mean difference between Cystacin C and C-peptide levels. However, the study has certain limitations. Firstly, the number of patients with elevated levels of serum C-peptide was very small, and hence, valid conclusions with respect to the association of serum C-peptide with renal parameters could not be discerned. Therefore, there is a need for further studies with more number of patients.

Oral health and characteristics of saliva in diabetic and healthy children

Diabetes is the most common metabolic disorder. Idiopathic destruction of pancreatic beta cells will result in progressive loss of insulin, increase in ketone bodies, PH reduction and changes in bicarbonate neutralizing system in all body fluids including saliva and the oral cavity. The aim of this study was to compare the quality and quantity of saliva and oral health in children and adolescents with diabetes compared to healthy children. In this study, 27 diabetic patients (9 males, 18 females, age range 10 ± 5 years) were studied. A control group (27 persons) was selected from health persons with the same condition of gender and age. The amount of saliva was evaluated in 5 minutes, by non-stimulant collecting, in plastic vials. The PH and Total Antioxidant Capacity (TAC) were measured using paper strip and TAC kit. Oral and dental health was measured using DMFT (Decayed, missed, filled teeth) and MGI (Modified Gingival Index) indexes. Saliva in patients had less secretion (1.09 ± 0.13, 5.28 ± 0.23, P < 0.01), PH (5.28 ± 0.09, 7.11 ± 0.10, P < 0.001), and total antioxidant capacity (0.36 ± 0.04, 0.5 ± 0.04, P < 0.001) in compare with controls group. DMF and MGI indicators were more in patients than in control group (P < 0.001). Patients with type 1 diabetes had less secretion, PH and antioxidant defense and as a result had more dental and oral problems in compare with healthy children that with higher DMFT and MGI these patients require further training in this field and regularly examinations.

Assessment of preservation of beta-cell function in children with long-standing type 1 diabetes with „ultrasensitive c-peptide” method

Type 1 diabetes mellitus is a disease caused by the autoimmune destruction of pancreatic beta-cells. It was previously believed that the loss of the endocrine function of the pancreas is total and inevitable. With the rise of new knowledge and new methods allowing to reliably measure c-peptide in the low plasma concentration range, we have learned otherwise. Some residual function of the beta-cells can be present even after decades of the course of the disease. The aim of the study was to evaluate the c-peptide level with routine laboratory and ultrasensitive methods in children with long-standing type 1 diabetes in relation to clinical characteristics. We recruited 178 consecutive children with type 1 diabetes mellitus lasting at least 1 year, mean diabetes duration was 5.6 years. Basic anthropometric measurements were performed and blood samples were drawn. From patients history records we gathered data regarding the course of the disease and laboratory results previously acquired. Laboratory tests performed on the blood samples included HbA1c levels and c-peptide level measurement using classic (n=178) and ultrasensitive (n=160) method (Mercodia). Clinically relevant c-peptide level was set at 0.23 ng/ml according to the DCCT recommendations. Clinically relevant c-peptide was found in 54 of 160 (33.75%) patients. Patients with preserved c-peptide were older at the time of diagnosis, had longer clinical remission, and required lower total and basal doses of insulin. Significantly lower mean HbA1c from the last year, but higher HbA1c at the time of the diabetes diagnosis were found in the group with higher c-peptide levels. The comparison of the classic and ultrasensitive c-peptide tests revealed that both yield similar results. Our observation shows that 34% of young patients with long-standing type 1 diabetes have prolonged c-peptide secretion. We confirm the long-standing assumption that residual beta-cell function is beneficial for metabolic control of the patients. Classic method of the c-peptide measurement can be just as useful in clinical practice as the ultrasensitive one.

Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3.

SummaryType 1 diabetes mellitus (T1DM) is a chronic disease characterized by autoimmune destruction of pancreatic beta cells and inadequate insulin production. Remission criteria in T1DM take into account serum levels of C-peptide and glycosylated hemoglobin, as well as the dose of insulin administered to the patient. However, remission of T1DM lasting longer than 1 year is rare. We describe here the cases of two young women who presented with positive glutamic acid decarboxylase (GAD) antibody and classic clinical manifestations of T1DM. Both patients had a prior history of Hashimoto’s thyroiditis. They were initially treated with a basal-bolus regimen of insulin (glargine and lispro/glulisine). Once their blood glucose levels were controlled, they were started on oral sitagliptin 100 mg and vitamin D3 5000 IU daily. After this therapy, both patients achieved clinical diabetes remission for 4 years, along with a decrease in anti-GAD antibody levels. These benefits were probably associated with immunological effects of these medications. Inhibition of dipeptidyl peptidase 4 (DPP-4) in animal models deregulates Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells and prevents IL-17 production. Vitamin D3 also activates CD4+CD25+FoxP3+ regulatory T-cells, and these medications combined can improve the immune response in patients with new-onset T1DM and probably promote sustained clinical remission.Learning points:The use of sitagliptin and vitamin D3 in patients with new-onset type 1 diabetes mellitus (T1DM) may help decrease the daily insulin requirement by delaying beta cell loss and improving endogenous insulin production.The use of sitagliptin and vitamin D3 in new-onset T1DM could help regulate the imbalance between Th17 and Treg cells.Age 14 years or above, absence of ketoacidosis and positive C-peptide levels in patients with T1DM are good criteria to predict prolonged T1DM remission.The determination of anti-GAD antibodies and C-peptide levels could be helpful in the follow-up of patients in use of sitagliptin and vitamin D3, which could be associated with prolonged T1DM clinical remission.

Impact of T-cell-specific Smad4 deficiency on the development of autoimmune diabetes in NOD mice.

Type 1 diabetes results from autoimmune-mediated pancreatic beta-cell destruction and transforming growth factor-beta (TGF-β) is known to play a preventive role in type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we investigated the role of Smad4, a key molecule for Smad-dependent TGF-β signaling, in T cells of NOD mice in the pathogenesis of autoimmune diabetes. We generated T-cell-specific Smad4 knockout (Smad4 tKO) NOD mice and assessed the pathological and immunological changes. Smad4 tKO showed earlier onset and increased incidence of diabetes than wild type (WT) NOD mice. Pathological features such as insulitis, anti-glutamic acid decarboxylase auto-antibody levels and serum IFN-γ levels were significantly increased in Smad4 tKO compared with WT NOD mice. Proportion and number of activated/memory CD4+ T cell were significantly increased in pancreatic lymph nodes of Smad4 tKO compared with WT NOD mice. However, the proportion and function of regulatory T cells was not different. Effector CD4+ T cells from Smad4 tKO were more resistant to suppression by regulatory T cells than effector cells from WT NOD mice. The proliferative potential of effector T cells from Smad4 tKO was significantly elevated compared with WT NOD mice, and activation of sterol regulatory element binding protein-1c (SREBP-1c) in T cells of Smad4 tKO NOD mice was correlated with this proliferative activity. We conclude that Smad4 deletion in T cells of NOD mice accelerated the development of autoimmune diabetes and increased the incidence of the disease by dysregulation of T cell activation at least in part via SREBP-1c activation.

Oral Health and Characteristics of Saliva in Diabetic and Healthy Children

&lt;p&gt;Diabetes is the most common metabolic disorder. Idiopathic destruction of pancreatic beta cells will result in progressive loss of insulin, increase in ketone bodies, PH reduction and changes in bicarbonate neutralizing system in all body fluids including saliva and the oral cavity. The aim of this study was to compare the quality and quantity of saliva and oral health in children and adolescents with diabetes compared to healthy children. In this study, 27 diabetic patients (9 males, 18 females, age range 10 ± 5 years) were studied. A control group (27 persons) was selected from health persons with the same condition of gender and age. The amount of saliva was evaluated in 5 minutes, by non-stimulant collecting, in plastic vials. The PH and Total Antioxidant Capacity (TAC) were measured using paper strip and TAC kit. Oral and dental health was measured using DMFT (Decayed, missed, filled teeth) and MGI (Modified Gingival Index) indexes. Saliva in patients had less secretion (1.09 ± 0.13, 5.28 ± 0.23, P &amp;lt; 0.01), PH (5.28 ± 0.09, 7.11 ± 0.10, P &amp;lt; 0.001), and total antioxidant capacity (0.36 ± 0.04, 0.5 ± 0.04, P &amp;lt; 0.001) in compare with controls group. DMF and MGI indicators were more in patients than in control group (P &amp;lt; 0.001). Patients with type 1 diabetes had less secretion, PH and antioxidant defense and as a result had more dental and oral problems in compare with healthy children that with higher DMFT and MGI these patients require further training in this field and regularly examinations.&lt;/p&gt;

Ameliorative Effects of &lt;i&gt;Cussonia arborea&lt;/i&gt; Methanol Root Bark Extract on Histomorphology of Pancreas of Alloxan-Induced Diabetic Rats

Diabetes mellitus is an endocrine and a metabolic disease resulting from the destruction of pancreatic beta cells; thus assessment of the pancreas in diabetic rats is important in monitoring therapy. The hereby study assessed pancreatic status of diabetic rats treated with methanol root bark extract of Cussonia arborea. A total of seventy two (72) male albino wistar rats weighting between 100-105 g were assigned into six (6) groups of twelve (12) rats per group. Groups 1-5 were diabetic infected by single intraperitoneal injection with alloxan monohydrate, at the dose of 160 mg/kg and treated with 62.5, 125, 250 mg/kg bw of the extract, 2 mg/kg bw glibenclamide and 10 ml/kg distilled water (DW) respectively, while the non diabetic rats, represented by Group 6, received 10 ml/kg DW and served as normal control rats. The treatment was applied daily through the oral route for 84 days. At the end of the experiment, the pancreas organs were acquired under light ether anaesthesia for histomorphometric assessment. The results indicated that the cells of the islet of langerhans of the diabetic untreated rats (Group 5) were severely depleted when compared to that of the normal rats (Group 6). The islet cells of the diabetic rats treated with 125 mg/kg Cussonia arborea extract (Group 2) was comparable to that of the diabetic rats treated with glibenclamide (Group 4) and the normal control rats. It was concluded that the methanol extract of C. arborea, especially at the dose of 125 mg/kg, ameliorated pancreatic lesions induced by diabetes occasioned by alloxan.

Diabetes mellitus in childhood: an emerging condition in the 21st century.

The International Diabetes Federation (IDF-2015) estimates the existence of 30,900 children under 15 years old with type 1 diabetes mellitus (DM1) in Brazil, and an increase of 3.0% per year is expected. This review focused on meta-analysis and pediatric diabetes update articles in order to draw attention to the need of planning coping strategies to support this serious public health problem in coming years. DM1 is considered an immuno-mediated disease with a complex transmission influenced by genetic and environmental factors responsible for a gradual destruction of the insulin producing pancreatic beta cells. Seroconversion to DM1-associated autoantibodies and abnormalities in metabolic tests that assess insulin secretion and glucose tolerance can be used as predictive criteria of beta cells functional reserve and the onset of the clinical disease. Symptomatic DM1 treatment is complex and the maintenance of good metabolic control is still the only effective strategy for preserving beta cell function. Disease duration and hyperglycemia are both risk factors for the onset of chronic vascular complications that negatively affect the quality of life and survival of these patients. In this regard, health teams must be trained to provide the best possible information on pediatric diabetes, through continuing education programs focused on enabling these young people and their families to diabetes self-management.