Pancreatic Autoimmunity Research Articles

Time of introducing solid food into infant’s diet and risk of Type I Diabetes: a systematic review

Abstract Background Type I Diabetes mellitus (DT1) is a multifactorial disease with various genetic and environmental factors involved in its pathophysiology. Several nutritional factors such as the timing of exposure to solid foods may increase the risk of DT1. The aim of this systematic review was to investigate the association between the time of introducing solid food into infant's nutrition during the first year of life and the risk of developing DT1. Methods PubMed and Science Direct were searched from inception to October 2019 for observational studies that investigated the above association. No restrictions on language or publication date were applied. Specific inclusion and exclusion criteria were set for the selection of articles. Title and abstract screening were performed by two independent researchers and data were extracted from shortlisted articles. Results In total, 76 studies were screened, and 7 articles met the inclusion criteria. The analysis shows that early exposure (before or during 3 or 4 months) and subsequent exposure (during or after 6 or 7 months) was associated with an increased risk of developing DT1 and/or pancreatic islet autoimmunity, compared to an intermediate exposure period (4-6 months, 4-5 months or 3-6 months). Conclusions The evidence suggests that an interim exposure period of genetically predisposed infants to DT1 from 4 to 5 months of age may reduce the risk of developing DT1 in later life as compared to early or later exposure. However, due to the limitations of the studies, further investigation is required to inform DT1 prevention practices. Key messages There is some evidence indicating that early exposure and later exposure to solid food may increase the risk of developing DT1 in children with a genetic predisposition. Due to the methodological heterogeneity across the studies included, more reliable data from large prospective studies and randomized clinical trials are needed.

Effects of Early MSC Intervention on Preventing the Streptozotocin-Induced T1DM Progression in Mice

Type 1 diabetes mellitus is characterized by progressive pancreatic β-cells failure and progressive autoimmunity. It is difficult to diagnose T1DM and to prevent the pancreatic β-cells destruction because of the undetectable pancreatic β-cell necrosis and abnormal autoimmunity. Here, we built streptozotocin-induced T1DM mouse model and performed MSC injection at the early stage of T1DM. We found that MSC infusion displayed enhanced effects on reducing the pathological damage and improving the survival quality. Moreover, the delivery of MSCs inhibited Th1 cell polarization and downregulated the Th1 subset ratio. The immunomodulatory mechanism of MSC was further investigated. Real-time PCR and ELISA assays demonstrated that IFN-γ expression at both mRNA and protein level in MSC infusion T1DM mice was downregulated, partially regulated by MSC-exosome-derived miR-148a-3p. Taken together, this early therapeutic strategy may improve the clinical efficacy of MSC-based therapy in T1DM.

Gluten-free diet impact on dynamics of pancreatic islet-specific autoimmunity detected at celiac disease diagnosis.

Almost 6% of celiac disease (CD) patients at diagnosis are positive for at least one of the main pancreatic islet autoantibodies that characterize type 1 diabetes (T1D). Few information, dated back to almost two decades ago, exist as to whether a gluten-free diet (GFD) could reduce the islet-specific autoimmunity detected in patients at CD diagnosis. Aim of the study was to evaluate the impact of GFD on 31 patients who presented islet-specific autoimmunity at CD diagnosis. CD patient sera collected at diagnosis and throughout the GFD were analyzed for the main humoral autoantibodies so far identified in T1D, directed against one or more among insulin, glutamic-acid decarboxylase, tyrosine-phosphatase 2, and zinc cation-efflux transporter autoantigens. GFD (median duration 39 months) was associated to a decrease or disappearance of the islet-specific autoantibodies in 71% of CD patients. Almost 80% of the patients who became autoantibody-negative during the GFD were positive for only one of the islet-specific autoimmune markers at CD diagnosis, with none of them developing diabetes. Conversely, 80% of the CD patients positive at diagnosis for ≥2 islet-specific autoantibodies were still positive after more than two years of GFD, with 25% of them developing T1D. Various factors appear to influence, individually or in combination, the effects of the GFD on pancreatic islet-specific autoimmune response detected at CD diagnosis. These factors include the number of diabetes autoantibodies found at CD diagnosis, the adherence to the GFD, its duration and an asymptomatic clinical presentation of CD.

SUN-687 MODY-14: A Rare Cause of Inherited Diabetes

Case: A 29-year-old physically active, lean man presented with a three-year history of poorly controlled diabetes diagnosed during a flu-like illness and no history diabetic ketoacidosis. Despite treatment with various oral hypoglycemic medications his glycated hemoglobin was consistently above target (never falling below 9.3%) and correlated with home blood glucose readings. His mother had gestational diabetes with all three of her pregnancies. His maternal grandmother was also known to have diabetes. Pancreatic islet antibodies were negative. C-peptide levels were low. Monogenic diabetes (MODY) was suspected. Discussion: Genetic testing revealed a mutation in the Adaptor Protein, Phosphotyrosine Interaction, PH domain, and leucine zipper containing 1 (APPL1) gene. APPL1 is involved in insulin secretion and insulin signaling via the Akt pathway [1,2,3]. Other mutations of APPL1 causing MODY-14 have been previously described [4]. In our case, the substitution of glutamate for aspartate at the 265 position occurs within the unique fourth alpha helix of the BAR domain of APPL1 [5]. Generally, BAR domains contribute to APPL1 dimerization and plasma membrane association [5]. Substitution of glutamate could disrupt protein folding, impairing dimerization and phosphorylation of Akt, thereby decreased insulin secretion as seen in other mutations of the BAR domain of APPL1 [4]. Although this remains a hypothesis, loss-of-function of APPL1 would explain the lack of insulin secretion without evidence of pancreatic autoimmunity. If the hypothesis is correct, it would be a novel mutation attributable to this MODY subtype. 1. Cheng KKY, Lam KSL, Wu D, et al. APPL1 potentiates insulin secretion in pancreatic β cells by enhancing protein kinase Akt-dependent expression of SNARE proteins in mice. Proc Natl Acad Sci U S A. 2012;109(23):8919–8924. doi:10.1073/pnas.1202435109 2. Ryu J, Galan AK, Xin X, et al. APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor. Cell Rep. 2014;7(4):1227–1238. doi:10.1016/j.celrep.2014.04.006 3. Saito T, Jones CC, Huang S, Czech MP, Pilch PF. The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation. J Biol Chem. 2007;282(44):32280–32287. doi:10.1074/jbc.M704150200 4. Prudente S, Jungtrakoon P, Marucci A, et al. Loss-of-Function Mutations in APPL1 in Familial Diabetes Mellitus. Am J Hum Genet. 2015;97(1):177–185. doi:10.1016/j.ajhg.2015.05.011 5. Li J, Mao X, Dong LQ, Liu F, Tong L. Crystal Structures of the BAR-PH and PTB Domains of Human APPL1. Structure. 2007;15(5):525–533. doi:10.1016/j.str.2007.03.011

Çocuklarda Pankreatit: Tek Merkez Deneyimi

Objective: The aim of this study was to evaluate the clinical, laboratory and etiological differences between children having acute pancreatitis, acute recurrent pancreatitis and chronic pancreatitis. Method: Medical records of children who were diagnosed with pancreatitis between January 2014 and December 2017 were evaluated retrospectively. The study was approved by the Ethics Committee of Afyonkarahisar University of Health Sciences. Our cases were classified as acute pancreatitis, acute recurrent pancreatitis and chronic pancretitis according to INSPPIRE group definitions. Results: Etiology, demographic characteristics, laboratory and radiological findings were compared between acute pancreatitis (group 1) and acute recurrent and chronic pancreatitis (group 2) groups. 43 patients (78.2%) were enrolled in acute pancreatitis group (group 1). In group 2; 8 cases had acute recurrent pancreatitis and 4 cases had chronic pancreatitis [a total of 12 cases (21.8%)]. the etiologies of our cases were examined; Group 1 had idiopathic (88.5%), stone (2.3%), trauma (2.3%), infections (4.6%) and choledochal cyst (2.3%), respectively. In group 2, they were found to be idiopathic (50%), congenital anomalies of the pancreatic duct (8.3%), allergy (8.3%), autoimmunity (8.3%) and genetic causes (25%). There was no statistical difference between the groups in terms of laboratory values. In our study, the cause of pancreatitis could not be generally identified in all groups. Conclusions: In cases having acute pancreatitis, infections were the second most common etiology; and common causes of acute recurrent and chronic pancreatitis have been found as genetic causes.

Metabolic alterations in immune cells associate with progression to type 1 diabetes

Aims/hypothesisPrevious metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes.MethodsIn a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D, n = 34), (2) seroconverted to ≥1 islet autoantibody without progressing to type 1 diabetes (P1Ab, n = 27) or (3) remained autoantibody negative during follow-up (CTRL, n = 10).ResultsDuring the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression.Conclusions/interpretationOur data suggest that systemic dysregulation of lipid metabolism, as observed in plasma, may impact the metabolism and function of immune cells during progression to overt type 1 diabetes.Data availabilityThe GEMs for PBMCs have been submitted to BioModels (www.ebi.ac.uk/biomodels/), under accession number MODEL1905270001. The metabolomics datasets and the clinical metadata generated in this study were submitted to MetaboLights (https://www.ebi.ac.uk/metabolights/), under accession number MTBLS1015.

Plasma Fucosylated Glycans and C-Reactive Protein as Biomarkers of HNF1A-MODY in Young Adult-Onset Nonautoimmune Diabetes.

Maturity-onset diabetes of the young (MODY) due to variants in HNF1A is the most common type of monogenic diabetes. Frequent misdiagnosis results in missed opportunity to use sulfonylureas as first-line treatment. A nongenetic biomarker could improve selection of subjects for genetic testing and increase diagnosis rates. We previously reported that plasma levels of antennary fucosylated N-glycans and high-sensitivity C-reactive protein (hs-CRP) are reduced in individuals with HNF1A-MODY. In this study, we examined the potential use of N-glycans and hs-CRP in discriminating individuals with damaging HNF1A alleles from those without HNF1A variants in an unselected population of young adults with nonautoimmune diabetes. We analyzed the plasma N-glycan profile, measured hs-CRP, and sequenced HNF1A in 989 individuals with diabetes diagnosed when younger than age 45, persistent endogenous insulin production, and absence of pancreatic autoimmunity. Systematic assessment of rare HNF1A variants was performed. We identified 29 individuals harboring 25 rare HNF1A alleles, of which 3 were novel, and 12 (in 16 probands) were considered pathogenic. Antennary fucosylated N-glycans and hs-CRP were able to differentiate subjects with damaging HNF1A alleles from those without rare HNF1A alleles. Glycan GP30 had a receiver operating characteristic curve area under the curve (AUC) of 0.90 (88% sensitivity, 80% specificity, cutoff 0.70%), whereas hs-CRP had an AUC of 0.83 (88% sensitivity, 69% specificity, cutoff 0.81 mg/L). Half of rare HNF1A sequence variants do not cause MODY. N-glycan profile and hs-CRP could both be used as tools, alone or as adjuncts to existing pathways, for identifying individuals at high risk of carrying a damaging HNF1A allele.

Pancreatic autoimmunity: An unknown etiology on patients with assisted reproductive techniques (ART)-recurrent reproductive failure.

Pancreatic Autoimmunity is defined as the presence of autoantibodies and more frequent need for insulin treatment. Affected women presenting recurrent implantation failure (RIF) or recurrent miscarriage (RM) are often misdiagnosed. The objective of thestudy was to describe clinical and metabolic profiles suggestive of Pancreatic Autoimmunity and therapeutic strategy in patients with RIF/RM. We analyzed retrospectively 735 patients, and have identified a subset (N = 20) with similar metabolic characteristics. At the same time, we included a control group (n = 39), with similar demographic characteristics and negative for pancreatic, thyroid or celiac disease autoimmunity. The patients identified with autoimmune metabolic problem (N = 20) had relatives with diabetes mellitus. At 120 minutes after Oral Glucose Tolerance Test (OGTT) low level of insulin secretion (<2 IU/ml) was found in 70% of patients. Glutamic acid decarboxylase 65 (GAD 65) antibodies, with or without other autoantibodies, were positive in80% of patients and anti-IA2 alone were positive I the rest. Since pregestational period, insulin administration was recommended for 10 patients, metformin for 4 patients and exclusively diet control in 5 of them. Significantly increased live bith rates (LBR) per cycle were observed after metabolic control (52%) compared with live birth rate (LBR) after cycles without control (7.5%) (p<0.0001). We noticed 2 cases of pre-eclampsia and 6 low-birth weights. Insulin administration was needed during the pregnancy in 68% of patients and after childbirth in 31.57% of them. In our control group, all of patients (n = 39) underwent ART (53.8% SET and 46.1% DET) with a 50% (SET) and 61.9% (DET) live birth rate (LBR) per cycle. Patients with RIF/RM, normal BMI, low insulin levels after OGTT could benefit from additional metabolic immune testing. A correct diagnosis and treatment could have a positive impact on their reproductive results and live birth rate.

Overweight Individuals with Type 1 Diabetes Are Less Likely to Present with Diabetic Ketoacidosis—Data from the After Diabetes Diagnosis Research Support System (ADDRESS-2) Cohort

Introduction: Insulin resistance has been proposed to accelerate progression to type 1 diabetes (T1D) in antibody positive relatives of affected individuals. We hypothesised that overweight individuals with confirmed T1D would be less likely to present with diabetic ketoacidosis (DKA), signifying an earlier onset of T1D, due to concomitant insulin resistance. Methods: The ADDRESS-2 study recruits incident clinician-assigned T1D cases within 6-months of diagnosis and systematically assesses pancreatic autoimmunity by GAD-65, IA-2 and ZnT8 antibodies. People with at least two positive antibodies were selected to confirm diagnosis of T1D and categorised for adiposity according to BMI (adults) or Z-scores (children). Odds ratios (OR) for presentation with DKA were compared, adjusted for potential confounders and sub-analysed by whether adult or child at recruitment. Results: 31% (969/ 3132) were positive for two or more pancreatic antibodies. Of these 44% (424/969) presented with DKA. The proportions with DKA varied significantly by adiposity: 59% underweight (16/27), 47% normal (280/601), 39% overweight (103/263), 30% obese (19/63) and 40% severely obese (6/15) (p=0.02). When adjusted for age, being overweight or obese was associated with lower risk of DKA in adults (OR 0.58, p=0.006; 0.44, p=0.03, respectively) not children (OR 0.9, p=0.81; 0.51, p=0.12, respectively). Higher adiposity category was associated with higher daily insulin-requirements independent of age, with obesity associated with a 4 unit/day increase (p=0.03) and severe obesity, 11 units/day increase (p=0.008). Conclusion: Adults with T1D are less likely to present with DKA if overweight or obese. Despite smaller proportions of DKA, insulin requirements are higher. These data suggest that, in adults, T1D presentation is unmasked by the insulin resistance of obesity prior to absolute insulin deficiency and ketoacidosis. Disclosure S. Misra: None. A. Kaur: None. I.F. Godsland: None. H.C. Walkey: None. D.G. Johnston: None. N. Oliver: Advisory Panel; Self; Dexcom, Inc., Roche Diabetes Care Health and Digital Solutions, Medtronic. Research Support; Self; Dexcom, Inc., Roche Diabetes Care Health and Digital Solutions. Other Relationship; Self; Novo Nordisk A/S, Takeda Development Centre Europe Ltd..

Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet.

To evaluate glycemic control among children and adults with type 1 diabetes mellitus (T1DM) who consume a very low-carbohydrate diet (VLCD). We conducted an online survey of an international social media group for people with T1DM who follow a VLCD. Respondents included adults and parents of children with T1DM. We assessed current hemoglobin A1c (HbA1c) (primary measure), change in HbA1c after the self-reported beginning of the VLCD, total daily insulin dose, and adverse events. We obtained confirmatory data from diabetes care providers and medical records. Of 316 respondents, 131 (42%) were parents of children with T1DM, and 57% were of female sex. Suggestive evidence of T1DM (based on a 3-tier scoring system in which researchers took into consideration age and weight at diagnosis, pancreatic autoimmunity, insulin requirement, and clinical presentation) was obtained for 273 (86%) respondents. The mean age at diagnosis was 16 ± 14 years, the duration of diabetes was 11 ± 13 years, and the time following a VLCD was 2.2 ± 3.9 years. Participants had a mean daily carbohydrate intake of 36 ± 15 g. Reported mean HbA1c was 5.67% ± 0.66%. Only 7 (2%) respondents reported diabetes-related hospitalizations in the past year, including 4 (1%) for ketoacidosis and 2 (1%) for hypoglycemia. Exceptional glycemic control of T1DM with low rates of adverse events was reported by a community of children and adults who consume a VLCD. The generalizability of these findings requires further studies, including high-quality randomized controlled trials.

NOD mice, susceptible to pancreatic autoimmunity, demonstrate delayed growth of pancreatic cancer.

Pancreatic cancer is a high mortality form of cancer, with a median survival only six months. There are multiple associated risk factors associated, most importantly type 2 diabetes, obesity, pancreatitis and smoking. The relative rarity of the disease, however, has made it difficult to dissect causative risk factors, especially with related risk factors. A major unanswered question with important therapeutic implications is the effect of immunological responses on pancreatic cancer formation, with data from other cancers suggesting the potential for local immunological responses to either increase cancer development or increase cancer elimination. Due to the rarity and late diagnosis of pancreatic cancer direct epidemiological evidence is lacking, thus necessitating a reliance on animal models. Here we investigated the relationship between pancreatic autoimmunity and cancer by backcrossing the well characterised Ela1-Tag transgenic model of pancreatic cancer onto the pancreatic autoimmune susceptible NOD mouse strain. Through longitudinal magnetic resonance imaging we found that the NOD genetic background delayed the onset of pancreatic tumours and substantially slowed the growth rate of tumours after development. These results suggest that elevated autoimmune surveillance of the pancreas limits tumour formation and growth, identifying pancreatic cancer as a promising target for immune checkpoint blockade therapies that unleash latent autoimmunity.

Long-lasting response to oral therapy in a young male with monogenic diabetes as part of HNF1B-related disease.

Mutations in hepatocyte nuclear factor 1β gene (HNF1B) are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5) and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations.Learning points:HNF1B mutations are a rare cause of monogenic diabetes, often being a part of a multisystemic syndrome.The combination of young-onset diabetes and genitourinary anomalies with slowly progressive nephropathy of non-diabetic origin in non-obese subjects should rise the suspicion of such occurrence. A family history may not be present.Once diagnosis is made, treatment of diabetes with oral agents is worth trying, since the response can be sustained for a longer period than the one usually described. Oral treatment can help postpone insulinization and, once this is necessary, can help reduce the required doses.

The Influence of the Microbiome on Type 1 Diabetes.

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β cells. The rapid rise in T1D incidence during the past 50 y suggests environmental factors contribute to the disease. The trillion symbiotic microorganisms inhabiting the mammalian gastrointestinal tract (i.e., the microbiota) influence numerous aspects of host physiology. In this study we review the evidence linking perturbations of the gut microbiome to pancreatic autoimmunity. We discuss data from rodent models demonstrating the essential role of the gut microbiota on the development and function of the host's mucosal and systemic immune systems. Furthermore, we review findings from human longitudinal cohort studies examining the influence of environmental and lifestyle factors on microbiota composition and pancreatic autoimmunity. Taken together, these data underscore the requirement for mechanistic studies to identify bacterial components and metabolites interacting with the innate and adaptive immune system, which would set the basis for preventative or therapeutic strategies in T1D.

Islet Autoantibodies.

Islet autoantibodies are the main markers of pancreatic autoimmunity in type 1 diabetes (T1D). Islet autoantibodies recognize insulin (IAA), glutamic acid decarboxylase (GADA), protein phosphatase-like IA-2 (IA-2A), and ZnT8 (ZnT8A), all antigens that are found on secretory granules within pancreatic beta cells. Islet antibodies, measured by sensitive and specific liquid phase assays, are the key parameters of the autoimmune response monitored for diagnostics or prognostics in patients with T1D or for disease prediction in at-risk individuals before T1D onset. Islet autoantibodies have been the main tool used to explore the natural history of T1D; this review summarizes the current knowledge about the autoantigens and the phenotype of islets autoantibodies acquired in large prospective studies from birth in children at risk of developing T1D.

Anti-Thyroid Peroxidase Antibodies and Male Gender Are Associated with Diabetes Occurrence in Patients with Beta-Thalassemia Major.

Background. Intensive transfusion schedule and iron-chelating therapy prolonged and improved quality of life in patients with β-thalassemia (β-T) major. However, this led to an increased risk of developing impaired glucose tolerance or diabetes. In this study we analyzed variables associated with the occurrence of impaired glucose tolerance or diabetes in patients with β-T major. Methods. 388 Sardinian patients were included. Age, gender, duration of chelation therapy, body mass index, and markers of pancreatic and extrapancreatic autoimmunity were analyzed. Results. Multiple logistic regression analysis showed that anti-thyroid peroxidase (TPO) antibodies (Ab) (OR = 3.36; p = 0.008) and male gender (OR = 1.98; p = 0.025) were significantly associated with glucose impairment, while the other variables were not. Ferritin levels were significantly higher in TPOAb positive compared to TPOAb negative patients (4870 ± 1665 μg/L versus 2922 ± 2773 μg/L; p < 0.0001). Conclusions. In patients with β-T major a progressive damage of insulin-producing cells due to secondary hemosiderosis appears to be the most reasonable mechanism associated with glucose metabolism disorders. The findings need to be confirmed with additional well designed studies to address the question of whether TPOAb may have a role in the management of these patients.

Clinical and Biological Characteristics of Patients Aged 65 and Older with Newly Developed Type 1 Diabetes

Objective: Diabetes of elder subjects is characterized by onset after the age of 65, absence of Ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. Methods: This is a retrospective study related to the observation of 5 patients aged over 65 years old, diagnosed with diabetes. All patients have had a dosage of pancreatic antibodies: anti glutamic acid decarboxylase antibodies (GAD antibodies) and tyrosine phosphatase antibodies IA2 (IA2 antibodies), with positivity to at least one of them. Their clinical and biological data, namely clinical aspects, family and personal history, metabolic and biological profile, autoimmune context, and degenerative complications, have been determined at the moment of the diagnosis. Results: This study was carried out on 4 female patients and one male, with an age between 65 and 71 years with a mean of 68 years. The clinical diagnosis is dominated by an insulinopenia in 3 cases with cardinal syndrome, an average blood glucose at admission=17.88 mmol/L, and an average HbA1C=13.24%. This insulinopenia has occurred in 2 cases immediately, realizing an inaugural ketosis. As far as the other 3 cases are concerned, the insulinopenia has taken place, right after a monitored oral anti-diabetic treatment for an average period of 21 months, fulfilling slow Mellitus Diabetes. An average BMI of 25.8 (Extremities 19 and 39) and a waist circumference>80 cm among all patients (range: minimum: 80, maximum 117 cm) with an average of 92.4 cm are also noted. Retinopathy has been recorded among one female patient. Pancreatic antibodies are all directed against GAD-65 antigen while IA-2 antibodies are found negative. Conclusions: These observations suggest that auto immune Diabetes is possible among the elderly subjects. The absence of any autoimmune context associated with insulin resistance stigma indicates a specific pathophysiology of pancreatic autoimmunity among the elderly subjects. It emphasizes the importance of testing for an appropriate classification of persons with Elder Diabetes. Early diagnosis of LADA would help direct appropriate therapy to optimize glycemic control.

Diabetes Risk and the Early Microbiome

The potential relationship between the intestinal microbiome and autoimmune disease is a novel area of study. As part of an ongoing birth-cohort study, researchers examined the association between probiotic supplementation in infants and childhood risk for persistent pancreatic islet autoimmunity (IA) in approximately 7500 children with genetic susceptibility to type 1 diabetes mellitus (T1DM). Children were followed for up …

Type 1 diabetes and polyglandular autoimmune syndrome: A review.

Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome.

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus.

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.

Glycemic control and insulin requirements in type 1 diabetic patients depending on the clinical characteristics at diabetes onset

Introduction: The long-term prognosis of type 1 diabetes (T1DM) was evaluated in relation to the clinical characteristics at the time of diabetes onset. Patients and methods: We examined retrospectively the clinical and laboratory characteristics present at the time of diagnosis in 301 adult patients (187 men) consecutively admitted to hospital with T1DM onset and evaluated the clinical outcome of T1DM during 6 ± 4.8 years following diagnosis. Results: Women needed a greater insulin dose per kg of body weight over the first 2 years following diagnosis. Younger patients at diagnosis had greater insulin requirements during follow-up. Patients with at least one positive pancreatic antibody needed a greater insulin dose 2 years after diagnosis and developed poorer glycemic control during follow-up than patients with no detectable pancreatic antibodies at onset. Diabetic ketoacidosis at onset was associated with greater insulin requirements over the first 2 years of follow-up and with poorer glycemic control during the course of the illness. C-peptide levels at diagnosis correlated with insulin requirements during the first 2 years of follow-up. Patients with higher HbA1c levels at diagnosis had greater insulin requirements in the first year of follow-up. A correlation was found between the HbA1c levels at the consecutive years of follow-up. Conclusions: Female sex, younger age, humoral pancreatic autoimmunity, diabetic ketoacidosis, lower pancreatic reserve and higher HbA1c levels at onset could predict a poor long-term clinical outcome of T1DM in terms of insulin requirements and glycemic control.