Hypoglycemic disorders are rare in persons without diabetes, and clinical evaluation to identify its etiology can be challenging. We present a case of insulin autoimmune syndrome induced by carbimazole in a middle-aged Chinese man with underlying Graves’ disease, which was managed conservatively with a combination of dietary modification and alpha-glucosidase inhibitor.
Hypoglycemia ; Hyperinsulinism ; Insulin Antibodies

PURPOSE: Type 1 diabetes mellitus (DM) is associated with autoimmune diseases such as thyroiditis. Therefore, we aimed to investigate the prevalence of autoimmune thyroiditis in patients with type 1 DM. METHODS: A total of 102 patients who were diagnosed and followed up (mean age, 8.1±4.0 years) in Ajou University Hospital were enrolled in this study. All the patients were evaluated for beta cell autoimmunity, including insulin autoantibody, glutamic acid decarboxylase antibodies (GADA), and islet cell antibody. Moreover, autoantibodies to thyroid peroxidase and thyroglobulin were assessed at initial diagnosis and annually thereafter. RESULTS: The mean patient age (49 men and 53 women) was 19.2±4.8 years. The prevalence of at least one thyroid antibody was 30.4%. Patients with thyroid anti­bodies had a significantly higher frequency of GADA at the time of the diagnosis. Autoimmune thyroiditis was more prevalent in the older age group. GADA was a significant risk factor for development of thyroid autoantibodies after diagnosis of type 1 DM (odds ratio, 4.45; 95% confidence interval, 1.399–14.153). CONCLUSIONS: In patients with type 1 DM, the prevalence of autoimmune thyroiditis was higher than in the general population. Moreover, GADA positivity at diagnosis was associated with thyroid autoimmunity.
Antibodies ; Autoantibodies ; Autoimmune Diseases ; Autoimmunity ; Diabetes Mellitus, Type 1 ; Diagnosis ; Follow-Up Studies* ; Glutamate Decarboxylase ; Humans ; Insulin ; Iodide Peroxidase ; Islets of Langerhans ; Male ; Prevalence* ; Risk Factors ; Thyroglobulin ; Thyroid Gland ; Thyroiditis ; Thyroiditis, Autoimmune*

PURPOSE: Type 1 diabetes mellitus (T1DM) is a chronic and immune-mediated disease, which is characterized by the progressive destruction of pancreatic beta cells. T1DM precipitates in genetically susceptible individuals through environmental factors. In this study, we aimed to evaluate the impact of autoimmunity and intestinal colonization of Candida albicans on the development of T1DM. METHODS: Forty-two patients newly diagnosed with T1DM and 42 healthy subjects were included in this monocentric study. The basic and clinical characteristics of the patients were recorded. T1DM-, thyroid-, and celiac-associated antibodies were evaluated. Stool cultures for C. albicans were performed to assess whether or not gut integrity was impaired in patients with T1DM. RESULTS: The evaluation of T1DM- and thyroid-associated antibodies showed that the prevalences of islet cell antibodies and antithyroperoxidase positivity were higher in the study patients than in the patients in the control group. Furthermore, the direct examination and culture of fresh stool samples revealed that 50% of the patients with T1DM and 23.8% of the control subjects had fungi (C. albicans). CONCLUSION: Through this study, we suggest that the presence of intestinal C. albicans colonization at the time of the diagnosis of T1DM may indicate impairment of normal intestinal microbiota. We also suggest that there may be a tendency of T1DM in patients with a high prevalence of intestinal C. albicans.
Antibodies ; Autoimmunity* ; Candida albicans* ; Candida* ; Colon* ; Diabetes Mellitus, Type 1 ; Diagnosis* ; Fungi ; Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Insulin-Secreting Cells ; Islets of Langerhans ; Prevalence

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia, extremely high serum insulin levels, and high titers of autoantibodies against endogenous insulin, in the absence of exogenous insulin injection. IAS often occurs following exposure to sulfhydryl-containing drugs, including alpha-lipoic acid (ALA). A 30-year-old woman without diabetes visited our outpatient clinic with recurrent hypoglycemia. She had been taken ALA for weight reduction since 3 weeks ago. Further hypoglycemia work up revealed very high insulin levels, C-Peptide levels and positive insulin antibodies. And conventional imaging examinations were negative for insulinoma or other pancreatic tumors. Finally, the diagnosis of Insulin autoimmune syndrome (IAS) was made. Following the cessation of ALA, hypoglycemia improved, with no medication, and the patient experienced no further hypoglycemic attacks over the next month. The use of ALA as a nutritional supplement is increasing. We report a case of IAS associated with ALA in a non-diabetic patient.
Adult ; Ambulatory Care Facilities ; Autoantibodies ; C-Peptide ; Diagnosis ; Female ; Humans ; Hypoglycemia ; Insulin Antibodies ; Insulin* ; Insulinoma ; Thioctic Acid* ; Weight Loss

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia, extremely high serum insulin levels, and high titers of autoantibodies against endogenous insulin, in the absence of exogenous insulin injection. IAS often occurs following exposure to sulfhydryl-containing drugs, including alpha-lipoic acid (ALA). A 30-year-old woman without diabetes visited our outpatient clinic with recurrent hypoglycemia. She had been taken ALA for weight reduction since 3 weeks ago. Further hypoglycemia work up revealed very high insulin levels, C-Peptide levels and positive insulin antibodies. And conventional imaging examinations were negative for insulinoma or other pancreatic tumors. Finally, the diagnosis of Insulin autoimmune syndrome (IAS) was made. Following the cessation of ALA, hypoglycemia improved, with no medication, and the patient experienced no further hypoglycemic attacks over the next month. The use of ALA as a nutritional supplement is increasing. We report a case of IAS associated with ALA in a non-diabetic patient.
Adult ; Ambulatory Care Facilities ; Autoantibodies ; C-Peptide ; Diagnosis ; Female ; Humans ; Hypoglycemia ; Insulin Antibodies ; Insulin ; Insulinoma ; Thioctic Acid ; Weight Loss

PURPOSE: We investigated whether serum levels of insulin growth factor-1 (IGF-1) and insulin growth factor binding protein-3 (IGFBP-3) are valuable in predicting clinical outcomes or are correlated with other laboratory findings in children with Henoch-Schönlein purpura (HSP). METHODS: We examined 27 children who were consecutively admitted to our hospital with HSP between January 2011 and February 2012. Blood tests (C-reactive protein, white blood cell count, platelet count, erythrocyte sedimentation rate, albumin, immunoglobulin A, complement C3, antineutrophil cytoplasmic antibody, IGF-1, IGFBP-3) and urine tests were performed upon admission. IGF-1 and IGFBP-3 were resampled in the recovery phase. Controls included 473 children whose IGF-1 and IGFBP-3 were sampled for evaluating their growth, at the outpatient department of pediatric endocrinology in our hospital. IGF-1 and IGFBP-3 were compared between the HSP children and controls, and between the acute and recovery phases in HSP children. The ability of these values to predict clinical outcomes including renal involvement was analyzed using bivariate logistic regression analysis (BLRA). RESULTS: IGF-1 and IGFBP-3 were not different between the HSP children and controls (148.7±117.6 vs. 69.2±96.9, P=0.290: 3465.9±1290.9 vs. 3597.2±1,127.6, P=0.560, respectively). There was no significant difference in IGF-1 or IGFBP-3 between acute and recovery phases. Based on the BLRA, no variable, including IGF-1 and IGFBP-3, could predict clinical outcomes including the presence of nephritis. CONCLUSION: We concluded that IGF-1 and IGFBP-3 do not predict clinical outcomes of HSP, including renal involvement, in this study.
Antibodies, Antineutrophil Cytoplasmic ; Blood Sedimentation ; Child* ; Complement C3 ; Endocrinology ; Hematologic Tests ; Humans ; Immunoglobulin A ; Insulin* ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Leukocyte Count ; Logistic Models ; Nephritis ; Outpatients ; Platelet Count ; Purpura*

The incidence of type 1 diabetes is increasing worldwide, and the greatest increase has been observed in very young children under 4 years of age. A case of infantile diabetic ketoacidosis in a 10-month-old male infant was encountered by these authors. The infant's fasting glucose level was 490 mg/dL, his PH was 7.13, his pCO₂ was 15 mmHg, and his bicarbonate level was 5.0 mmol/L. The glycosylated hemoglobin level had increased to 9.4%. Ketonuria and glucosuria were detected in the urinalysis. The fasting C-peptide and insulin levels had decreased. The infant was positive for anti-insulin and antiglutamic acid decarboxylase antibodies. Immediately after the infant's admission, fluid therapy and intravenous insulin infusion therapy were started. On the second day of the infant's hospitalization and after fluid therapy, he recovered from his lethargic condition, and his general condition improved. Feeding was started on the third day, and he was fed a formula 5 to 7 times a day and ate rice, vegetables, and lean meat. Due to the frequent feeding, the frequency of rapid-acting insulin injection was increased from 3 times before feeding to 5 times, adjusted according to the feeding frequency. The total dose of insulin that was injected was 0.8-1.1 IU/kg/day, and the infant was discharged on the 12th day of his hospitalization. The case is presented herein with a brief review of the relevant literature.
Antibodies ; C-Peptide ; Child ; Diabetes Mellitus, Type 1* ; Diabetic Ketoacidosis* ; Fasting ; Fluid Therapy ; Glucose ; Hemoglobin A, Glycosylated ; Hospitalization ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Infant* ; Insulin* ; Insulin, Short-Acting ; Ketosis ; Male ; Meat ; Urinalysis ; Vegetables

The incidence of type 1 diabetes is increasing worldwide, and the greatest increase has been observed in very young children under 4 years of age. A case of infantile diabetic ketoacidosis in a 10-month-old male infant was encountered by these authors. The infant's fasting glucose level was 490 mg/dL, his PH was 7.13, his pCO₂ was 15 mmHg, and his bicarbonate level was 5.0 mmol/L. The glycosylated hemoglobin level had increased to 9.4%. Ketonuria and glucosuria were detected in the urinalysis. The fasting C-peptide and insulin levels had decreased. The infant was positive for anti-insulin and antiglutamic acid decarboxylase antibodies. Immediately after the infant's admission, fluid therapy and intravenous insulin infusion therapy were started. On the second day of the infant's hospitalization and after fluid therapy, he recovered from his lethargic condition, and his general condition improved. Feeding was started on the third day, and he was fed a formula 5 to 7 times a day and ate rice, vegetables, and lean meat. Due to the frequent feeding, the frequency of rapid-acting insulin injection was increased from 3 times before feeding to 5 times, adjusted according to the feeding frequency. The total dose of insulin that was injected was 0.8-1.1 IU/kg/day, and the infant was discharged on the 12th day of his hospitalization. The case is presented herein with a brief review of the relevant literature.
Antibodies ; C-Peptide ; Child ; Diabetes Mellitus, Type 1* ; Diabetic Ketoacidosis* ; Fasting ; Fluid Therapy ; Glucose ; Hemoglobin A, Glycosylated ; Hospitalization ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Infant* ; Insulin* ; Insulin, Short-Acting ; Ketosis ; Male ; Meat ; Urinalysis ; Vegetables

OBJECTIVETo investigate the inhibitory effect of high concentration insulin on K562 cell proliferation and its underlying mechanism.

METHODSK562 cells were treated by different concentration of insulin and/or anti-IGF-1R antibody (IGF-1R-Ab), MTT assay and flow cytometry were used to detect the K562 cells proliferation and apoptosis, respectivety; Western blot was used to measure the expression and phosphorylation level of IGE-IR, Akt, Erk1/2 in K562 cells under the different concentration of insulin.

RESULTSMTT assay showed that less than 40 mU/ml insulin could promote K562 cell proliferation, while high concentration (> 40 mU/ml) insulin has been shown to inhibit K562 cell proliferation; Flow cytometry showed that 40 mU/ml insulin suppressed K562 cell apoptosis (P < 0.05), while 200 mU/ml insulin could significantly induce K562 cell apoptosis (P < 0.01); 0.01 to 1.0 µg/ml IGF-1R-Ab has significantly enhanced the inhibitory and inducing effects of high concentration (> 40 mU/ml) of insulin on K562 cell proliferation and apoptosis respectively (r = 0.962, P < 0.001); Western blot showed that after K562 cells were treated with different concentrations of insulin ERK, and the p-ERK expression did not change significantly, after K562 cells were treated with 200 mU/ml insulin, the expression of IGF-1R and AKT also not were changed obviously, while the phosphorylation level of IGF-1R and AKT increased.

CONCLUSIONHigh concentration (>40 mU/ml) of insulin inhibits K562 cell proliferation and induces its apoptosis, and its mechanism may be related with the binding IGF-1R by insulin, competitively inhibiting the binding of IGF-1 and IGF-1R, the blocking the transduction of PI3K/AKT signal pathway.

Antibodies ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Culture Media ; chemistry ; Humans ; Insulin ; pharmacology ; Insulin-Like Growth Factor I ; metabolism ; K562 Cells ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Receptors, Somatomedin ; immunology ; Signal Transduction ; drug effects

The aim of this study was to better understand the frequency of autoimmune thyroid and diabetes antibodies in patients with type 1 diabetes mellitus (T1DM) compared with their siblings. Glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), insulin autoantibodies (IAA), and thyroid autoantibodies were studied in all subjects. The rates of positive GADA and IAA were significantly higher in probands compared to in siblings (p<0.001) or controls (p<0.001). All pancreatic autoantibodies were not significantly different between the siblings and the healthy controls. Thyroid antiperoxidase antibody (TPOAb) and antithyroglobulin antibody (TGAb) were significantly different between the probands and the control subjects (p=0.002 and p=0.018, respectively). The rates of TPOAb and TGAb positivity in siblings were higher than in those of the controls, but there was no significant difference between the two groups. However, thyroid autoimmunity (TA) was significantly different among the groups (p=0.004). Siblings of the TA-positive probands were shown to have a greater prevalence of thyroid antibodies than did the controls (p=0.022), but siblings of the TA-negative probands did not have such a prevalence compared with the control subjects. The prevalence of pancreatic and thyroid antibodies positivity in probands was statistically significant compared with the siblings and the controls. Siblings of TA-positive probands revealed a greater prevalence of thyroid antibodies than did the controls. Therefore, the screening for TA in siblings, particularly siblings of TA-positive probands, is as important as it is in probands.
Antibodies ; Autoantibodies ; Autoimmunity ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Glutamate Decarboxylase ; Humans ; Insulin ; Islets of Langerhans ; Mass Screening ; Prevalence ; Siblings ; Thyroid Gland ; Thyroiditis