Recurrent hypoglycemic coma and diabetic ketoacidosis caused by insulin antibody. A rare case of type 1 diabetes mellitus.

Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: < 5%), and the concentrations of insulin and C-peptide were > 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.

The evaluation of pancreas ß-cell autoantibodies in non-diabetic COVID-19 patients.

Objective: This study aims to evaluate potential pancreas endocrine damage due to SARS-CoV-2 by measuring ß-cell autoantibodies in COVID-19 patients. Subjects and methods: Between June and July 2020, 95 inpatients with a positive COVID-19 test result after polymerase-chain-reaction (PCR) and who met the inclusion criteria were enrolled in our study. Laboratory parameters that belong to glucose metabolism and ß-cell autoantibodies, including anti-islet, anti-glutamic acid decarboxylase, and anti-insulin autoantibodies, were measured. ß-cell autoantibodies levels of the patients were measured during COVID-19 diagnosis. Positive results were reevaluated in the 3rd month of control. Results: In the initial evaluation, 4 (4.2%) patients were positive for anti-islet autoantibody. Only one (1.1%) patient was positive for anti-glutamic acid decarboxylase autoantibody. No patient had positive results for anti-insulin autoantibody. FPG, HbA1c, and C-peptide levels were similar in patients who were split into groups regarding the initial positive or negative status of anti-islet and anti-GAD autoantibodies (p>0.05). In the 3rd month after the initial measurements, anti-islet autoantibody positivity of 2 (50%) of 4 patients and anti-glutamic acid decarboxylase positivity of 1 (100%) patient were persistent. Finally, 3 (3.1%) patients in the whole group were positive for anti-islet autoantibody in the 3rd month of control. No difference was determined between the initial and the 3rd month of parameters of glucose metabolism. Conclusion: Following an ongoing autoantibody positivity in the present study brings the mind that SARS-CoV-2 may be responsible for the diabetogenic effect. Clinicians should be aware of autoantibody-positive DM as a potential autoimmune complication in patients with SARS-CoV-2.

Autoanticuerpos anti-insulina en la diabetes tipo 1 / Anti-insulin autoantibodies in type 1 diabetes

Introducción: Los autoanticuerpos anti-insulina (AAI) representan un marcador serológico de la diabetes tipo 1 (DT1). El significado clínico de los AAI aún no ha sido determinado en la población cubana. Objetivo: Determinar el valor clínico de AAI en pacientes con DT1. Métodos: Se determinaron los niveles séricos de AAI por el ensayo inmuno-adsorbente ligado a enzima (ELISA) en 33 pacientes adultos con DT1, 78 pacientes con otras condiciones endocrinas (CEE) como diabetes tipo 2, tiroiditis de Hashimoto e hiperinsulinemia, y 49 controles normales (CN). El valor de corte se determinó con el análisis de las curvas características operativas del receptor (COR) (ROC por sus siglas en inglés). Se utilizaron pruebas no paramétricas para comparar los niveles de AAI de pacientes con DT1, CEE y CN, y determinar la correlación entre AAI y la edad. Resultados: El valor de corte óptimo de AAI para DT1 fue el índice de 1,05, con sensibilidad de 45,5 por ciento, especificidad de 81,6 por ciento, razón de verosimilitud positiva de 2,47, y razón de verosimilitud negativa de 0,67. Los niveles de AAI en DT1 (índice de 0,97) fueron significativo, más altos que los de CN (índice de 0,70; p=0,020) y los de CEE (índice de 0,63; p= 0,009). Los niveles de AAI resultaron inversamente proporcionales a la edad en pacientes diabéticos ( =-0,252; p=0,030). Conclusiones: Los pacientes con DT1 se distinguieron por niveles más altos de AAI, aunque la presencia de estos anticuerpos no fue exclusiva de DT1. Los niveles de AAI dependieron de la edad en los pacientes diabéticos(AU)

Introduction: Anti-insulin autoantibodies (AAI) represent a serological marker of type 1 diabetes (T1D). The clinical significance of AAIs has not yet been determined in the Cuban population. Objective: To determine the clinical value of AAI in patients with T1D. Methods: AAI serum levels were determined by enzyme-linked immunosorbent assay (ELISA) in 33 adult patients with T1D, 78 patients with other endocrine conditions (CEE) such as type 2 diabetes, Hashimoto's thyroiditis, and hyperinsulinemia, and 49 normal controls (CN). The cut-off value was determined by receiver operating characteristic (ROC) curve analysis. Nonparametric tests were used to compare the AAI levels of patients with T1D, CEE, and CN, and to determine the correlation between AAI and age. Results: AAI optimal cut-off value for T1D was the index of 1.05, with 45.5 percent of sensitivity, 81.6 percent specificity, 2.47 positive likelihood ratio, and 0.67 negative likelihood ratio. AAI levels in DT1 (index of 0.97) were significant, higher than those of CN (index of 0.70; p= 0.020) and CEE levels (index of 0.63; p= 0.009). AAI levels were inversely proportional to age in diabetic patients (ρ = -0.252; p=0.030). Conclusions: Patients with T1D were distinguished by AAI higher levels, although the presence of these antibodies was not exclusive to T1D. AAI levels depended on age in diabetic patients(AU)

Recurrent hypoglycemic coma and diabetic ketoacidosis caused by insulin antibody: a rare case of type 1 diabetes mellitus / Hipoglicemia hiperinsulinémica causada por anticuerpos antiinsulina: informe de un caso

ABSTRACT Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.

Los anticuerpos contra la insulina (AI) inducidos por la insulina exógena raramente causan hipoglucemia. No obstante, los autoanticuerpos contra la insulina (AIA) en el síndrome autoinmune de insulina (SAI) pueden causar hipoglucemia. Las manifestaciones típicas del SAI son la hipoglucemia en ayunas o posprandial, niveles elevados de insulina, la disminución del nivel de péptido C y AIA positivos. Presentamos un paciente hombre de 45 años con diabetes mellitus de tipo 1 (DMT1) tratado con análogos de insulina, que sufría comas hipoglucémicos recurrentes y cetoacidosis diabética (CAD). Sus síntomas fueron causados por la insulina exógena y fueron similares al SAI. La posible razón fue que la insulina exógena indujo AI. El título de AI era del 61,95% (Normal: 300 mU/L y < 0,02 nmol/L cuando se producía la hipoglucemia. Basados en sus síntomas clínicos y otros exámenes, se le diagnosticó hipoglucemia hiperinsulinémica causada por la AI. Sus síntomas mejoraron después de cambiar el régimen de insulina de lispro más insulina detemir a insulina humana recombinante (Gensulin R) y de empezar a tomar prednisona.

Síndrome de Hirata, causa poco frecuente de hipoglucemia / Hirata syndrome, a rare cause of hypoglycemia

Mujer de 32 años, asmática en tratamiento irregular con prednisona (ultima dosis hace 1 mes), Enfermedad de Graves Basedow desde hace 3 años, reiniciótratamiento hace 3 meses (metimazol 40 mg/día), antecedente de aborto dos semanas previas al ingreso. Acude por pérdida del conocimiento, constatándose hipoglucemia. Al persistir el cuadro de hipoglucemia a pesar del tratamiento instaurado y descartadas otras causas etiológicas, la evaluación endocrinológica confirma hipoglucemia autoinmune, niveles de autoanticuerpos contra la insulina e insulina extremadamente elevados.

A 32-year-old woman, asthmatic on irregular treatment with prednisone (last dose 1 month ago), Graves Basedow's disease for 3 years, restartedtreatment 3 months before(methimazole 40 mg / day).History of abortion two weeks prior to admission. She came for loss of consciousness, finding hypoglycemia. As hypoglycemia persists despite the treatment instituted and other etiological causes ruled out, the endocrinological evaluation confirms autoimmune hypoglycemia,autoantibody levelsagainst insulinandextremely high insulin.

Pitfalls in the diagnosis of insulin autoimmune syndrome (Hirata's disease) in a hypoglycemic child: a case report and review of the literature.

Background Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycemia (HH) not addressed as a potential differential diagnosis in current pediatric guidelines. We present a case of IAS in a child with no previous history of autoimmune disease, no previous intake of triggering medications and absence of genetic predisposition. Case presentation A 6-year-old boy presented with recurrent HH (blood glucose of 26 mg/dL [1.4 mmol/L] and insulin of 686 µU/mL). Abdominal imaging was normal. After multiple therapeutic failures, we hypothesized misuse of exogenous insulin and factitious hypoglycemia. Council of Guardianship had the child separated from his mother, but insulin levels remained high. A chromatography test was then performed which showed high titers of endogenous insulin autoantibody (IAA) with early dissociation from the insulin molecule. The human leukocyte antigen (HLA) test showed a DRB1 *13:01/*08:02 genotype. The patient was advised to control food intake and physical activity routines. During a 5-year follow-up, hypoglycemic episodes were sparse, despite high insulin levels. Conclusions Misdiagnosis of IAS with factitious hypoglycemia may happen if IAS is not considered as a differential diagnosis, leading to potential traumatic consequences. Further efforts should be made to increase awareness of IAS as a differential diagnosis of hypoglycemia and to include it in pediatric guidelines.

Insulin autoimmune syndrome in an occidental woman: a case report and literature review.

Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.

Insulin autoimmune syndrome in an occidental woman: a case report and literature review

SUMMARY Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.

Acantosis nigricans y su asociación con insulinorresistencia en población infantil menor a 15 años con sobrepeso u obesidad / Acanthosis nigricans and its association with insulin resistance in children under 15 years of age with overweight or obesity

Contexto: la acantosis nigricans en sujetos adultos con obesidad es un marcador cutáneo de insulinorresistencia.Objetivo: determinar la asociación entre acantosis nigricans e insulinorresistencia en pacientes pediátricos. Sujetos y métodos: estudio de caso-control que evaluó a niños y adolescentes entre 6 a 15 años de edad que asistieron a consulta externa de Dermatología del Hospital Pediátrico Baca Ortiz de Quito, en el período julio a septiembre de 2015. Los pacientes se reclutaron por muestreo no probabilístico, conformándose dos grupos: casos y controles, con 25 sujetos cada uno. Resultados: se determinó en 15 pacientes (60%) con acantosis nigricans presentaron insulinorresistencia; de éstos, se calificó como acantosis nigricans moderada a 6 pacientes (24%) y severa 19 pacientes (76%) siendo más predictivas de insulinorresistencia en sujetos con obesidad (p=0,001). Los pacientes con obesidad y acantosis nigricans severa presentaron un OR de 54 (2,85-99,32) mientras que los pacientes diagnosticados de obesidad y acantosis nigricans moderada presentaron un OR de 12 (1,29-86,20). Conclusión: se encontró que la acantosis nigricans moderada y severa en niños y adolescentes con obesidad constituyo un signo cutáneo de insulinorresistencia. (AU)

Context: acanthosis nigricans in adult subjects with obesity is a cutaneous marker of insulin resistance. Objective: to determine the association between acanthosis nigricans and insulin resistance in pediatric patients. Subjects and methods: a case control study that evaluated children and adolescents between 6 and 15 years of age who attended the outpatient clinic of Dermatology of the Baca Ortiz Pediatric Hospital of Quito, from July to September 2015, were studied. Patients were recruited by non-probabilistic sampling, conforming two groups: cases and controls, with 25 subjects each. Results: it was determined in 15 patients (60%) with acanthosis nigricans presented insulin resistance; Of these, 6 patients (24%) and 19 patients (76%) were classified as moderate acanthosis nigricans, being more predictive of insulin resistance in subjects with obesity (p = 0.001). Patients with severe obesity and acanthosis nigricans had an OR of 54 (2.85-99.32) while patients diagnosed with obesity and moderate acanthosis nigricans had an OR of 12 (1.29-86.20). Conclusion: moderate and severe acanthosis nigricans in children and adolescents with obesity constitutes a cutaneous sign of insulin resistance. (AU)

Histochemistry and immunolocalisation of glucokinin in antidiabetic plants used in traditional Mexican medicine.

Mexico is a megadiverse country that has 3,600 to 4,000 species of medicinal plants, of which approximately 800 are used to treat conditions related to diabetes mellitus (DM). DM is a chronic degenerative disease of energy metabolism that exists as two types: type 1 (DM1) and type 2 (DM2). DM is considered a public health problem that affects 7% of the Mexican population older than 20 years. DM is clinically controlled with hypoglycaemic drugs, alpha-glucosidase inhibitors, insulin secretion stimulants or the direct application of insulin. The hypoglycaemic effectiveness of specific molecules has been determined only for some medicinal plants in Mexico used to treat DM2. The presence of molecules called glucokinins, wich are similar to animal insulin molecules, has been reported in some plant species; glucokinins act as both growth factors and regulators of glucose metabolism in plants. Therefore, we hypothesized that the hypoglycaemic effectiveness of some of the popularly used species for the control of DM could be due to the presence of glucokinin, as reported for Bauhinia variegata. The goal of this work was to use histochemistry to detect, the accumulation of protein that is immunocytochemically compatible with glucokinin in slide sections of hypoglycaemic species used as remedies for DM2. The top fourteen most used medicinal plants in Mexico were selected for study via microscopic sections. Proteins were histochemically detected using naphthol blue black and Johansen's quadruple stain, and the immunocytochemical correspondence of the proteins with glucokinin was investigated using an insulin antibody. All species studied reacted positively to proteins and glucokinin in the same structures. The presence of glucokinin in these structures and the corresponding hypoglycaemic effects are discussed in the contex of the actions of other compounds.

Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

OBJECTIVE: To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. RESEARCH DESIGN AND METHODS: TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,287 subjects developed diabetes. RESULTS: Univariate analyses showed that autoantibodies by radioimmunoassays (RIAs), ECL-IAA, ECL-GADA, age, sex, number of positive autoantibodies, presence of HLA DR3/4-DQ8 genotype, HbA1c, and oral glucose tolerance test (OGTT) measurements were all significantly associated with progression to diabetes. Subjects who were ECL positive had a risk of progression to diabetes within 6 years of 58% compared with 5% for the ECL-negative subjects (P < 0.0001). Multivariate Cox proportional hazards models were compared, with the base model including age, sex, OGTT measurements, and number of positive autoantibodies by RIAs. The model with positivity for ECL-GADA and/or ECL-IAA was the best, and factors that remained significantly associated with time to diabetes were area under the curve (AUC) C-peptide, fasting C-peptide, AUC glucose, number of positive autoantibodies by RIAs, and ECL positivity. Adding ECL to the Diabetes Prevention Trial risk score (DPTRS) improved the receiver operating characteristic curves with AUC of 0.83 (P < 0.0001). CONCLUSIONS: ECL assays improved the ability to predict time to diabetes in these autoantibody-positive relatives at risk for developing diabetes. These findings might be helpful in the design and eligibility criteria for prevention trials in the future.

[Insulin autoimmune syndrome: Report of two cases]. / Síndrome de hipoglicemia autoinmune: Primeros casos en Chile.

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia with extremely high insulin levels and the presence of circulating autoantibodies against insulin, in patients who have never been exposed to exogenous insulin. We report two patients with the syndrome. A 36 years old male presenting with hypoglycemia in the emergency room had an oral glucose tolerance test showed basal and 120 min glucose levels of 88 and 185 mg/dl. The basal and 120 min insulin levels were 2,759 and 5,942 µUI/ml. The presence of an insulin secreting tumor was discarded. Anti-insulin antibodies were positive. He was successfully treated with a diet restricted in carbohydrates and frequent meals in small quantities. A 65 years old female presenting with hypoglycemia in the emergency room had the fasting insulin levels of 1,910 µUI/ml. No insulin secreting tumor was detected by images and anti-insulin antibodies were positive. The polyethylene glycol precipitation test showed a basal and after exposition insulin level 1,483 and 114 µUI/ml, respectively. She responded partially to diet and acarbose and required the use of prednisone with a good clinical response.

Síndrome de hipoglicemia autoinmune: Primeros casos en Chile / Insulin autoimmune syndrome: Report of two cases

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia with extremely high insulin levels and the presence of circulating autoantibodies against insulin, in patients who have never been exposed to exogenous insulin. We report two patients with the syndrome. A 36 years old male presenting with hypoglycemia in the emergency room had an oral glucose tolerance test showed basal and 120 min glucose levels of 88 and 185 mg/dl. The basal and 120 min insulin levels were 2,759 and 5,942 μUI/ml. The presence of an insulin secreting tumor was discarded. Anti-insulin antibodies were positive. He was successfully treated with a diet restricted in carbohydrates and frequent meals in small quantities. A 65 years old female presenting with hypoglycemia in the emergency room had the fasting insulin levels of 1,910 µUI/ml. No insulin secreting tumor was detected by images and anti-insulin antibodies were positive. The polyethylene glycol precipitation test showed a basal and after exposition insulin level 1,483 and 114 µUI/ml, respectively. She responded partially to diet and acarbose and required the use of prednisone with a good clinical response.

Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY).

OBJECTIVE: While it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined. RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months. RESULTS: Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes. CONCLUSIONS: In the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.

Early immunotherapy using autologous adult stem cells reversed the effect of anti-pancreatic islets in recently diagnosed type 1 diabetes mellitus: preliminary results.

BACKGROUND: Bone marrow stem cell treatment has been proven a promising therapeutic strategy and showed significant results given the strong immune modulating properties. We have investigated the safety and efficacy of autologous bone marrow stem cell transplantation through liver puncture in two patients with recently diagnosed type 1 diabetes mellitus. MATERIAL AND METHODS: The procedure was approved by the Institutional Ethics Committee. In 2011, in three young patients, type 1 diabetes mellitus diagnosis was confirmed, with the presence of positive antibodies and ketoacidosis. Two patients was treated with autologous bone marrow stem cell stimulated with filgrastim and transplantation, through liver puncture, as immune modulators. One patients was treated with conventional treatment and participate in this experiment as a control group. The families of the patients signed the informed consent. No specific statistical analysis was performed. The patients had less than 8 years old, diagnosis of type 1 diabetes for less than 60 days, body mass index less than 22 kg/m2, normal complete blood count, coagulation and renal function, no lesions in target organs, glycosylated hemoglobin (HbA1c) level less than 13.70%, c-peptide level less than 0.67 ng/ml, positive results of Islets Cells Antibody (ICA), Glutamic Acid Decarboxylase (GAD) and insulin antibody. RESULTS: In two patients treated, the follow up at 12 months showed negative value in ICA, GAD and anti insulin antibody levels, with an increased levels of c peptide and decreased levels of blood glucose and HbA1c. CONCLUSIONS: Treatment with autologous bone marrow stem cells is easy and effective as it reversed the production and effect of anti pancreatic islet antibody and significantly resulted in an increased c-peptide concentration.

Characterization of insulin antibodies by Surface Plasmon Resonance in two clinical cases: brittle diabetes and insulin autoimmune syndrome.

In this study, the characterization of insulin (auto)antibodies has been described, mainly in terms of concentration (q), affinity (Ka) and Ig (sub)isotypes by Surface Plasmon Resonance (SPR) in two particular clinical cases of individuals with severe episodes of impaired glycemia. Subject 1 suffers from brittle diabetes associated with circulating insulin antibodies (IA) due to insulin treatment. Subject 2 has insulin autoantibodies (IAA) associated with hypoglycemia in spite of not being diabetic and not having ever received exogenous insulin therapy. After conventional screening for IA/IAA by radioligand binding assay (RBA), we further characterized IA/IAA in sera of both patients in terms of concentration (q), affinity (Ka) and Ig (sub)isotypes by means of SPR technology. In both cases, q values were higher and Ka values were lower than those obtained in type 1 diabetic patients, suggesting that IA/IAA:insulin immunocomplexes could be responsible for the uncontrolled glycemia. Moreover, subject 1 had a predominat IgG1 response and subject 2 had an IgG3 response. In conclusion, SPR technology is useful for the complete characterization of IA/IAA which can be used in special cases where the simple positive/negative determination is not enough to achieve a detailed description of the disease fisiopathology.

[Obesity and risk factors for metabolic syndrome in young people with type 1 diabetes]. / Obesidad y factores de riesgo del síndrome metabólico en jóvenes con diabetes tipo 1.

Changes in the clinical presentation of diabetes mellitus in childhood and adolescence associated with obesity have resulted in an overlap of the two most common types of diabetes with a greater clinical heterogeneity. In order to characterize the type of diabetes at onset and assess the effect of obesity, 50 children with diabetes were studied. The patients were divided into two groups according to their nutritional status at diagnosis (over-weight/obese vs. normal weight). Insulin reserve was evaluated by measuring basal C-peptide and stimulated C-peptide in response to a mixed meal (MMTT) as well as HLA-DQB1 genotype, antibodies, and family history of risk factors for metabolic disease. Of all 50 patients, 38% was overweight/obese, 84% had a positive family history of metabolic syndrome, 82% had positive antibodies, and 100% were positive for the high-risk HLA-DQB1 genotype. No significant differences were found in fasting C-peptide or glycemic index/C-peptide levels between the two groups. In the overweight/obese group C-peptide response to MMTT showed higher levels at 60 and 120 minutes (p = 0.02 and 0.03) and the area under the curve for C-peptide was also higher (1.77 ng / ml vs. 5.5 ng/ ml, p = 0.0007) than in the normal-weight group. In conclusion, overweight/obese patients with type 1A diabetes had a greater pancreatic reserve, suggesting that nutritional status may accelerate disease onset.

Pancreatic autoantibodies, HLA DR and PTPN22 polymorphisms in first degree relatives of patients with type 1 diabetes and multiethnic background.

AIM: To evaluate the prevalence of pancreatic auto-antibodies (PAb) as well as its relationship with HLA DR B1 and PTPN22 polymorphisms in first degree relatives (FDR) of Brazilian patients with Type 1 diabetes (T1D) and multiethnic background. METHODS: FDR of patients with T1D were interviewed and blood was sampled for PAb measurement, HLA DRB1 and PTPN22 genotyping. Genotyping was also performed in index cases. RESULTS: In FDR (n=78), 16.7% presented at least one PAb. These individuals had a higher prevalence of HLA DRB1* 03 than others (p=0.03), without differences in PTPN22 genotyping. While the genetic profile was similar in FDR with PAb and their index cases, those without PAb had a lower frequency of HLA DR B1 * 03 than their correspondent patients (p=0.009). CONCLUSION: In this multiethnic population, a significant proportion of FDR of T1D patients had PAb, which was associated with HLA DR B1 * 03 but not with the PTPN22 polymorphism.

Efficacy and safety of AIR inhaled insulin compared to insulin lispro in patients with type 1 diabetes mellitus in a 6-month, randomized, noninferiority trial.

BACKGROUND: Patients with type 1 diabetes may prefer features of AIR inhaled insulin (developed by Alkermes, Inc. [Cambridge, MA] and Eli Lilly and Company [Indianapolis, IN]; AIR is a registered trademark of Alkermes, Inc.) over insulin injection, but the two methods need to be compared for efficacy and safety. METHODS: This multicenter, 6-month, parallel-group, noninferiority trial had 500 patients with type 1 diabetes randomized to morning doses of basal insulin glargine plus either preprandial injectable insulin lispro or preprandial AIR insulin. We hypothesized that AIR insulin is noninferior (upper bound of the 95% confidence interval < or = 0.4%) to insulin lispro for change-from-baseline hemoglobin A1C (A1C). RESULTS: Baseline A1C was 7.95 +/- 0.08% for both groups. At end point, A1C was lower with insulin lispro than with AIR insulin by 0.27% (95% confidence interval 0.11, 0.43; P< 0.001). Noninferiority of AIR insulin to insulin lispro was not demonstrated, but similar percentages of patients in each group achieved A1C <7.0% (P = 0.448). Overall daily blood glucose was similar between groups at baseline (P = 0.879) and end point (P = 0.161). Two-hour postprandial blood glucose change from baseline was significantly (P < 0.001) higher with AIR insulin (20.77 +/- 4.33 mg/dL at 3 months and 15.85 +/- 3.08 mg/dL at end point) than with insulin lispro (3.29 +/- 4.14 mg/dL at 3 months and 1.67 +/- 2.91 mg/dL at end point). Overall hypoglycemia was similar between treatment groups (P = 0.355). The AIR insulin group had greater decrease in diffusing capacity of the lung for carbon monoxide at end point (P = 0.020) and greater incidence of cough (P = 0.024) and dyspnea (P = 0.030). Body weight decreased in the AIR insulin group and increased in the insulin lispro group. CONCLUSIONS: Insulin lispro provided lower A1C than AIR insulin, but the difference may not be clinically relevant.