c-peptide and Autoimmune-Diseases

To evaluate the safety and efficacy of fecal microbiota transplantation for autoimmune diseases and autoinflammatory diseases.. Relevant literature was retrieved from the PubMed database, Embase database, Cochrane Library database, etc. The search period is from the establishment of the database to January 2022. The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events. Literature screening and data extraction were independently carried out by two researchers according to the inclusion and exclusion criteria, and RevMan 5.3 software was used for statistics and analysis.. Overall, a total of 14 randomized controlled trials (RCTs) involving six types of autoimmune diseases were included. The results showed the following. 1) Type 1 diabetes mellitus (T1DM): compared with the autologous fecal microbiota transplantation (FMT) group (control group), the fasting plasma C peptide in the allogenic FMT group at 12 months was lower. 2) Systemic sclerosis: at week 4, compared with one of two placebo controls, three patients in the experimental group reported a major improvement in fecal incontinence. 3) Ulcerative colitis, pediatric ulcerative colitis, and Crohn's disease: FMT may increase clinical remission, clinical response, and endoscopic remission for patients with ulcerative colitis and increase clinical remission for patients with Crohn's disease. 4) Psoriatic arthritis: there was no difference in the ratio of ACR20 between the two groups.. Based on current evidence, the application of FMT in the treatment of autoimmune diseases is effective and relatively safe, and it is expected to be used as a method to induce remission of active autoimmune diseases.. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235055, identifier CRD42021235055.

Topics: Autoimmune Diseases; C-Peptide; Child; Colitis, Ulcerative; Crohn Disease; Fecal Microbiota Transplantation; Hereditary Autoinflammatory Diseases; Humans

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Autoimmune Diseases; C-Peptide; Dexamethasone; Diazoxide; Diet, Diabetic; Female; Glucose; Glucose Intolerance; Humans; Hyperinsulinism; Hypoglycemia; Immunosuppressive Agents; Insulin; Liver Neoplasms; Polyethylene Glycols; Proinsulin; Sigmoid Neoplasms

Latent autoimmune diabetes in Adults (LADA) is a slowly developing type 1 diabetes which presents as non-insulin dependent diabetes and progresses to insulin dependence. However, the best treatment strategy for LADA is unclear.. To compare interventions used for LADA.. Studies were obtained from searches of electronic databases (including MEDLINE, EMBASE), supplemented by hand searches, conference proceedings and consultation with experts.. Selection was in duplicate by two independent reviewers. RCT and controlled clinical trials evaluating interventions for LADA or type 2 diabetes with antibodies were included.. Two reviewers independently extracted data and assessed study quality. Studies were summarised in a descriptive manner.. Searches identified 8067 citations. Eight publications (seven studies) were included, involving 735 participants. All studies had high risk of bias. There were no data on use of metformin or glitazones alone. Rosiglitazone or sulphonylurea (SU) with insulin did not improve metabolic control significantly more than insulin alone. SU alone gave either poorer (one study, mean difference in HbA1c 2.8% (95% confidence interval (CI) 0.9 to 4.7) or equivalent metabolic control compared to insulin alone (two studies). There was evidence that SU caused earlier insulin dependence (insulin treated at two years: 60% (SU) and 5% (conventional care) (P < 0.001); classified insulin dependent: 64% (SU) and 12.5% (insulin group) (P = 0.007)). No interventions influenced fasting C-peptide, but insulin maintained stimulated C-peptide better than SU (one study, mean difference 7.7 ng/ml (95% CI 2.9 to 12.5) and insulin with rosiglitazone was superior to insulin alone (one study) at maintaining stimulated C-peptide. A pilot study showed better metabolic control at six months with subcutaneously administered glutamic acid decarboxylase (GAD) GAD65, a major autoantigen in autoimmune diabetes, compared to placebo. There was no information regarding quality of life, mortality, complications or costs in any of the publications. Time from diagnosis varied between recruitment at diagnosis to recruitment at nine years of disease duration and there was a great deal of variation in the selection criteria for LADA patients, making it difficult to generalise findings from these studies.. There are few studies on this topic and existing studies have a high risk of bias. However, there does seem to be an indication that SU should not be a first line treatment for antibody positive type 2 diabetes. There is no significant evidence for or against other lines of treatment of LADA.

Topics: Adult; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Randomized Controlled Trials as Topic; Rosiglitazone; Sulfonylurea Compounds; Thiazolidinediones

Topics: Autoimmune Diseases; C-Peptide; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Humans; Immunosuppression Therapy; Immunotherapy; Insulin; Insulin Secretion

Diabetes mellitus is a heterogeneous disorder. About 80% of the patients with this disease are categorized as having non-insulin-dependent diabetes mellitus, a disorder resulting from varied degrees of insulin resistance and impaired insulin secretion; the causes for these abnormalities are unknown. The remaining 15 to 20% of patients have insulin-dependent diabetes mellitus, a disorder caused by the destruction of insulin-producing endocrine cells within the pancreas and currently considered to be the result of an autoimmune process. During the course of both types of diabetes mellitus, the so-called long-term complications of diabetes invariably occur to some extent in all patients. These complications include retinopathy, nephropathy, neuropathy, and premature atherosclerosis. The molecular basis for these complications is not completely understood, but recent evidence obtained from both experiments in animals and prospective clinical studies indicates that metabolic derangements associated with poor glycemic control are a major determinant of the frequency and severity of these complications. Such evidence is the rationale for current attempts to maintain near-normal glycemia in patients with diabetes mellitus.

Topics: Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Diagnosis, Differential; Glucagon; Humans; Insulin; Insulin Resistance

The study of endogenous insulin secretion may provide relevant insight into the comparison of the natural history of adult onset latent autoimmune diabetes (LADA) with types 1 and 2 diabetes mellitus. The aim of this study was to compare the results of the C-peptide response to mixed-meal stimulation in LADA patients with different disease durations and subjects with type 2 and adult-onset type 1 diabetes.. Stimulated C-peptide secretion was assessed using the mixed-meal tolerance test in patients with LADA (n = 32), type 1 diabetes mellitus (n = 33) and type 2 diabetes mellitus (n = 30). All patients were 30 to 70 years old at disease onset. The duration of diabetes in all groups ranged from 6 months to 10 years. The recruitment strategy was predefined to include at least 10 subjects in the following 3 disease onset categories for each group: 6 to 18 months, 19 months to 5 years and 5 to 10 years.. At all time-points of the mixed-meal tolerance test, patients with LADA had a lower stimulated C-peptide response than the type 2 diabetes group and a higher response than the type 1 diabetes group. The same results were found when the peak or area under the C-peptide curve was measured. When the results were stratified by time since disease onset, a similar pattern of residual insulin secretory capacity was observed.. The present study shows that the magnitude of stimulated insulin secretion in LADA is intermediate between that of type 1 and type 2 diabetes mellitus.

Topics: Adult; Aged; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Female; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Male; Meals; Middle Aged; Postprandial Period; Time Factors

Previous in vitro and in vivo studies have demonstrated that vitamin D could prevent pancreatic beta-cell destruction and reduce the incidence of autoimmune diabetes. In children with type 1 diabetes, vitamin D treatment produces moderate protective effects on residual beta-cell function and has proven to be safe. Therefore, we hypothesized that vitamin D might have protective effects on beta-cell function in patients with latent autoimmune diabetes in adults (LADA), a form of slowly progressive autoimmune type 1 diabetes.. Thirty-five patients with LADA were randomly assigned to receive subcutaneous insulin alone (n = 18) or insulin plus 1-alpha-hydroxyvitamin D3 (1-alpha(OH)D3; 0.5 microg per day) (n = 17) for 1 year. Plasma C-peptide levels in fasting state (FCP) and 2 h after 75-g glucose load (PCP) were measured every 6 months with radioimmunoassay.. Both FCP and PCP levels stayed steady in the insulin plus 1-alpha(OH)D3 group, while FCP decreased in insulin-alone group (P = 0.006) during the 12-month intervention. Seventy percent of patients treated with 1-alpha(OH)D3 maintained or increased their FCP concentrations after 1 year of treatment, while only 22% of patients treated with insulin alone maintained stable FCP levels (P < 0.01). Further analysis on LADA subgroups with different durations of diabetes demonstrated that islet beta-cell function was better preserved (as reflected by significantly higher FCP and PCP levels) in the 1-alpha(OH)D3 plus insulin group only in patients with diabetes duration no longer than 1 year. No severe side effects were observed in any group.. Our data suggest that 1-alpha(OH)D3 plus insulin therapy can preserve pancreatic beta-cell function in patients with LADA.

Topics: Adult; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Drug Combinations; Female; Humans; Hydroxycholecalciferols; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Treatment Outcome

To study the effect of integrative Chinese and Western medicine (ICWM) on improvement of the islet beta cell function in treating patients with latent autoimmune diabetes mellitus in adults (LADA).. Eighty-four patients of LADA were randomly divided into 3 groups (20 in A, 33 in B and 31 in C), they were treated respectively with sulfonylurea, insulin and combination of insulin and Chinese medicine. The changes before and after treatment in blood glucose, glycohemoglobin and islet beta cell function were observed.. After treatment, the damaged islet beta cell function in Group A was not improved, the secrete peak value of C-peptide was still low and delayed in Group A, but in Group B and C, it shifted earlier, suggesting that a certain degree of improvement and recovery of islet beta cell function. The improving effect in Group C was better.. Chinese herbal medicine had effect in lowering blood glucose and improving islet beta cell function in patients with diabetes mellitus, and showed a synergistic and enhancing action when combined use with insulin. Early treatment of insulin or combination of insulin and Chinese medicine should be applied to patients with LADA.

Topics: Adult; Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus; Drugs, Chinese Herbal; Female; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Phytotherapy

Oral administration of autoantigens can slow the progression of beta-cell destruction in non-obese diabetic mice. We investigated whether oral administration of recombinant human insulin could protect residual beta-cell function in recent-onset type 1 diabetes.. We enrolled 131 autoantibody-positive diabetic patients aged 7-40 years within 2 weeks of diagnosis (no ketoacidosis at diagnosis, weight loss <10%, polyuria for <6 weeks). They were randomly assigned 2.5 mg or 7.5 mg oral insulin daily or placebo for 1 year, in addition to subcutaneous insulin therapy. Serum C-peptide concentrations were measured in the fasting state and after stimulation, to assess beta-cell function. Autoantibodies to beta-cell antigens were assayed. Analyses were by intention to treat.. Baseline C-peptide and haemoglobin A1c concentrations were similar in the three groups. During follow-up, there were no differences between the groups assigned 2.5 mg or 7.5 mg oral insulin or placebo in subcutaneous insulin requirements, haemoglobin A1c concentrations, or measurements of fasting (mean at 12 months 0.18 [SD 0.17], 0.17 [0.17], and 0.17 [0.12] nmol/L) or stimulated C-peptide concentrations (glucagon-stimulated 0.39 [0.38], 0.37 [0.39], and 0.33 [0.24] nmol/L; meal-stimulated 0.72 [0.60], 0.49 [0.49], and 0.57 [0.51 nmol/L]. Neither age nor C-peptide concentration at entry influenced treatment effects. No differences were seen in the time-course or titres of antibodies to insulin, glutamic acid decarboxylase, or islet antigen 2.. At the doses used in this trial, oral administration of insulin initiated at clinical onset of type 1 diabetes did not prevent the deterioration of beta-cell function.

Topics: Administration, Oral; Adolescent; Adult; Autoantibodies; Autoimmune Diseases; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Insulin; Insulin Antibodies; Islets of Langerhans; Male; Recombinant Proteins

In autoimmune disease the functional deficiency of T suppressor cells, also described in Type I diabetes, may be restored through immunoglobulin (Ig) infusion, which increases antigen phagocytosis, NK activity, cell clones and antibody anti-idiotype responses. Sixteen Type I diabetic patients were studied: eight were treated soon after the initial correction of disease-onset glycemic deterioration with intensive intravenous (i.v.) 7S Ig treatment (0.4 g/kg/BW) for 1 week and once per week for 6 months, whilst the remaining patients constituted the control group. All patients were evaluated during the study for metabolic and immunological parameters. A reduction in insulin requirement compared to conventionally treated patients was observed at the third (0.17 +/- 0.06 vs 0.44 +/- 0.08 IU/kg/BW; P less than 0.02) and at the sixth month of therapy (0.19 +/- 0.07 vs 0.54 +/- 0.07 IU/kg/BW; P less than 0.005). Two patients ceased to require insulin therapy within the BW; P less than 0.005). Two patients ceased to require insulin therapy within the first month, showing a prolonged restoration of B-cell function. Serum C-peptide values were also significantly higher in the Ig-treated group compared to the control group after 3 and 6 months. As regards immunological parameters, patients showed a decrease in insulin antibody levels and a reduction in TAC+ cells. Intravenous Ig therapy seems able to affect positively the first phases of metabolic and immunological deterioration of Type I diabetes.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Humans; Immunization, Passive; Insulin; Male; Random Allocation; Receptors, Interleukin-2

Topics: Autoimmune Diseases; Azathioprine; C-Peptide; Clinical Trials as Topic; Cyclosporins; Diabetes Mellitus, Type 1; Double-Blind Method; Drug Therapy, Combination; Humans; Insulin; Prednisone; Recurrence

We compared the glycemic efficacy of treatment intensification between quadruple oral antidiabetic drug therapy and once-weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus refractory to triple oral therapy. For 24 weeks, changes in glycosylated hemoglobin (HbA1c) from baseline were compared between the two treatment groups. Of all 96 patients, 50 patients were treated with quadruple therapy, and 46 were treated with GLP-1RA therapy. Reductions in HbA1c for 24 weeks were comparable (in both, 1.1% reduction from baseline; P=0.59). Meanwhile, lower C-peptide level was associated with a lower glucose-lowering response of GLP-1RA therapy (R=0.3, P=0.04) but not with quadruple therapy (R=-0.13, P=0.40). HbA1c reduction by GLP-1RA therapy was inferior to that by quadruple therapy in the low C-peptide subgroup (mean, -0.1% vs. -1.3%; P=0.04). Treatment intensification by switching to quadruple oral therapy showed similar glucose-lowering efficacy to weekly GLP-1RA-based triple therapy. Meanwhile, the therapeutic response was affected by C-peptide levels in the GLP-1RA therapy group but not in the quadruple therapy group.

Topics: Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin

Exogenous insulin antibody syndrome (EIAS) can lead to unexpected and potentially life-threatening recurrent hypoglycemia.. We aimed to better define autoimmune hypoglycemia caused by EIAS in patients with diabetes and shed light on the improvements in the identification and intervention for this rare but possibly life-threatening condition.. We summarized the clinical characteristics of autoimmune hypoglycemia caused by EIAS in 23 patients with diabetes. Furthermore, we performed human leukocyte antigen (HLA) genotyping of 10 patients.. We identified a high frequency of autoimmune comorbidities (21.7%), food or drug allergy (48%), insulin allergy (30%), lipodystrophy at the insulin injection sites (22%), and antinuclear antibodies (25%) in the patients. Alternation between hyperglycemia and hypoglycemia was observed in more than 90% of the patients. Most patients showed a high insulin autoantibody titer (>90%) and inappropriately increased insulin concentration (insulin/C-peptide molar ratio >7, >85%). We detected similar frequencies of DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 compared with previously reported frequencies in type 1 diabetes, and a lower frequency of DRB1*0406 compared with insulin autoimmune syndrome. The spontaneous remission rate exceeded 70%.. Predisposing factors for autoimmune hypoglycemia caused by EIAS include a strong autoimmune background. Susceptible HLA genotypes for type 1 diabetes or insulin autoimmune syndrome might not explain susceptibility to this condition. Additionally, insulin autoantibodies and the insulin/C-peptide molar ratio are reliable screening options. The prognosis for this condition is favorable. Monitoring of insulin and insulin autoantibodies may contribute to treatment effectiveness.

Topics: Autoantibodies; Autoimmune Diseases; C-Peptide; China; Diabetes Mellitus, Type 1; HLA-DRB1 Chains; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Syndrome

The destruction of pancreatic β cells causes type 1 diabetes mellitus (T1D), an autoimmune disease. Studies have demonstrated that there is heterogeneity in residual β-cell function in Caucasians; therefore, we aimed to evaluate β-cell function in Chinese autoimmune T1D patients.. β-cell function was determined using oral glucose tolerance testing or standardized steamed bread meal tolerance test in 446 participants with autoantibody-positive T1D. Clinical factors, such as age onset, sex, duration, body mass index, autoantibodies, other autoimmune diseases, diabetic ketoacidosis, hypoglycemia events, glycosylated hemoglobin, and insulin dose, were retrieved. We also analyzed single nucleotide polymorphism (SNP) data for C-peptides from 144 participants enrolled in the Chinese-T1D genome-wide association study.. Of 446 T1D patients, 98.5%, 97.4%, 86.9%, and 42.6% of individuals had detectable C-peptide values (≥ 0.003 nmol/L) at durations of < 1 year, 1 to 2 years, 3 to 6 years, and ≥ 7 years, respectively. A total of 60.7% of patients diagnosed at ≥ 18 years old and 15.8% of those diagnosed at < 18 years had detectable C-peptide after ≥ 7 years from the diagnosis. Furthermore, the patients diagnosed at ≥ 18 years old had higher absolute values of stimulated C-peptide (≥ 0.2 nmol/L). Diabetic ketoacidosis, hypoglycemia events, and insulin doses were shown to be associated with β-cell function. SNPs rs1770 and rs55904 were associated with C-peptide levels.. Our results have indicated that there are high residuals of β-cell mass in Chinese patients with autoimmune T1D. These findings may aid in the consideration of therapeutic strategies seeking prevention and reversal of β-cell function among Chinese T1D patients.

Topics: Adolescent; Autoantibodies; Autoimmune Diseases; C-Peptide; China; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Genome-Wide Association Study; Humans; Hypoglycemia; Insulin

The aim was to evaluate the impact of familial autoimmunity on the age and severity of type 1 diabetes (T1D) presentation and on the coexistence of other autoimmune diseases.. We retrospectively evaluated the medical records of 121 children/adolescents (male: 63) followed in our Diabetic Clinic from 2002 to 2016.. Seventy-six patients (62.8%) had at least one relative with an autoimmune disease, Hashimoto's thyroiditis (49.5%) and T1D (22.3%) being the commonest. Children with familial autoimmunity were younger at T1D diagnosis (mean age ± SD) (6.766 ± 3.75). Median fasting c-peptide levels at presentation were not related to familial autoimmunity. Patients with familial autoimmunity more often exhibited GADA autoantibody positivity at diagnosis. The larger the number of the patient's relatives diagnosed with an autoimmune disease, the higher were the patient's GADA levels (Spearman's rho test = 0.19, p = 0.049). Children with a first-degree relative with autoimmunity had a coexisting autoimmune disorder at a significantly higher percentage (p = 0.016). Family history of autoimmunity was negatively associated with the presence of diabetic ketoacidosis (DKA) (p = 0.024). Patients with a relative with T1D less frequently exhibited DKA at diagnosis (12.8 vs. 87.2%, p = 0.003). The presence of DKA was associated with younger age (p = 0.05) and lower c-peptide levels (p = 0.033).. Familial autoimmunity was present in 62.8% of children with T1D, autoimmune thyroiditis and T1D being the two most frequent familial autoimmune diseases. Familial autoimmunity reduced the risk of DKA at diagnosis, but these patients were younger and had higher levels of pancreatic autoantibodies and a greater risk of developing additional autoimmune diseases.

Topics: Autoantibodies; Autoimmune Diseases; Autoimmunity; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Hashimoto Disease; Humans; Male; Retrospective Studies

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.

Topics: Autoimmune Diseases; C-Peptide; Coma; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Male; Middle Aged

The number of case reports of insulin autoimmune syndrome (IAS) induced by methimazole (MMI) is increasing. The purpose of this study is to explore the clinical characteristics and provide a scientific reference for clinical diagnosis, treatment and prevention.. The literature on IAS cases and case series induced by MMI in Chinese and English was collected for retrospective analysis.. A total of 106 patients (males 33, females 73) were described in the Chinese and English literature. The median age of patients with IAS induced by MMI was 37 years (range 15-76) occurring during both regular and irregular MMI therapy or after resumption of medication. The onset of symptoms occurred at night or early morning, within days in some and up to 6 months in others; the symptoms were neuropathic in 65.31% and related to the autonomic nervous system in 33.67%. Blood glucose concentration in samples presumably taken during the hypoglycaemic phase was 1.7 mmol/L (median; range 0.03-4.7); insulin concentrations were elevated ≥100 mU/L (ref range) and associated with low C-peptide levels (<10 μg/L; ref range). Tests for IgG insulin autoantibodies (IAA) were positive in 104 patients (98.02%) and negative in two patients (1.98%). The 75-g oral glucose tolerance test (OGTT) showed impaired glucose tolerance and diabetic curves. Pancreatic imaging was unremarkable on computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Withdrawal of MMI alone or with corticosteroid treatment reduced hypoglycaemic episodes within days to 3 months. IAA decreased and became negative in 3 months (median; range 1-12). Follow-up showed no recurrent hypoglycaemic episodes at 5 months (median; range 1-60).. Methimazole-induced IAS is a clinically rare autoimmune disease with hypoglycaemia that occurs during medication treatment that should be treated promptly.

Topics: Adolescent; Adult; Aged; Antithyroid Agents; Autoimmune Diseases; Blood Glucose; C-Peptide; Female; Humans; Immunoglobulin G; Insulin; Male; Methimazole; Middle Aged; Syndrome; Young Adult

Alpha-lipoic acid (ALA) is widely used as a dietary supplement and antiageing agent. Insulin autoimmune syndrome (IAS) is the most serious adverse reaction reported with the use of ALA. The purpose of this study was to explore the clinical characteristics of ALA-induced IAS and provide a scientific reference for clinical diagnosis, treatment and prevention.. We collected literature on IAS cases induced by ALA for retrospective analysis in Chinese and English.. The median age of 37 patients (28 females and 9 males) was 61 years (range 32-82). The symptoms occurred at night and in the early morning (60.7%), in the late postprandial period (50.0%) or after fasting (35.7%), within hours in some patients and up to 2 months in others after stopping ALA or during medication treatment. Autonomic nervous system symptoms (81.1%) and neurological hypoglycaemia (64.9%) are the main clinical manifestations of hypoglycaemia. The blood glucose concentration at the onset of hypoglycaemia was 2.19 mmol/L (median, range 1.09-3.52), the insulin concentration was ≥100 μIU/ml (94.6%), and the C-peptide concentration was ≤20 ng/ml (83.3%). Testing for IgG insulin autoantibodies (IAAs) was positive in 37 patients. Pancreatic imaging was unremarkable on computed tomography (CT), magnetic resonance imaging (MRI) and abdominal sonography. Hypoglycaemia disappeared within 5 days to 8 months after withdrawing ALA alone or using corticosteroid treatment. IAA turned negative in 7 months (median; range 2-36). Follow-up showed no recurrent hypoglycaemic episodes at 7.25 months (median; range 1-36).. ALA-induced IAS is a clinically rare autoimmune disease with hypoglycaemia that occurs during medication treatment or after drug withdrawal that should be treated promptly.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Blood Glucose; C-Peptide; Female; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Retrospective Studies; Thioctic Acid

Determination of C-peptide is important in the investigation of unexplained hyperinsulinemic hypoglycemia because a high C-peptide concentration usually indicates endogenous insulin hypersecretion. Insulin autoimmune syndrome (IAS) denotes hyperinsulinemic hypoglycemia due to insulin-binding antibodies that prolong insulin half-life. C-peptide clearance is considered to be unaffected, and although a marked C-peptide immunoreactivity in hypoglycemic samples has been reported, it has been suspected to be artifactual. High-resolution mass spectrometry enables examination of the basis of C-peptide-immunoreactivity in IAS.. Precipitation of plasma with polyethylene glycol was followed by C-peptide immunoassay. Plasma peptides extracted by solvent precipitation were characterized by nano-LC-MS/MS and analyzed using an untargeted data-dependent method. Peptides related to proinsulin, in amino acid sequence, were identified using proprietary bioinformatics software and confirmed by repeat LC-MS/MS analysis. Gel filtration chromatography coupled to LC-MS/MS was used to identify proinsulin-related peptides present in IAS immunocomplexes. Results were compared with those from C-peptide immunoassay.. Polyethylene glycol precipitation of IAS plasma, but not control plasma, depleted C-peptide immunoreactivity consistent with immunoglobulin-bound C-peptide immunoreactivity. LC-MS/MS detected proinsulin and des 31,32 proinsulin at higher abundance in IAS plasma compared with control plasma. Analysis by gel filtration chromatography coupled to LC-MS/MS demonstrated proinsulin and des 31,32 proinsulin, but no C-peptide, in plasma immunocomplexes.. Antibody binding can enrich proinsulin and des 31,32 proinsulin in IAS immunocomplexes. Proinsulin cross-reactivity in some C-peptide immunoassays can lead to artifactually increased C-peptide results.

Topics: Autoimmune Diseases; C-Peptide; Chromatography, Liquid; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Antibodies; Molecular Weight; Peptides; Polyethylene Glycols; Proinsulin; Tandem Mass Spectrometry

The relationship of chromogranin A (CgA) levels above the normal range with various outcomes, such as glycated hemoglobin levels, enterochromaffin-like cell hyperplasia and autoimmune gastritis, was investigated in type 1 diabetes patients with special regard to the progression of comorbidities.. A cohort study on 153 type 1 diabetes patients was carried out with a prospective branch on clinical and laboratory data, and a retrospective branch on histological data obtained by gastroscopy.. Patients with CgA levels above the upper limit of the normal range (n = 28) had significantly higher glycated hemoglobin levels (P = 0.0160) than those with CgA in the normal range (n = 125). The correlation between CgA and glycated hemoglobin was significant (P < 0.0001), but weak (R = +0.32). A slight, but steady elevation (P = 0.0410) in CgA level was observed to co-vary with the duration of type 1 diabetes. Enterochromaffin-like cell hyperplasia and autoimmune gastritis was significantly more frequent (P = 0.0087 for both) in the high CgA group. Detailed analyses on gastric tissue samples confirmed a progression of enterochromaffin-like cell hyperplasia (P = 0.0192) accompanied by CgA elevation (P = 0.0316).. The early detection and follow up of the later progression of enterochromaffin-like cell hyperplasia and autoimmune gastritis into gastric neuroendocrine tumors, which have ~100-fold greater incidence in type 1 diabetes patients, can be achieved by assessment of CgA levels. Therefore, the use of CgA could be considered as a novel auxiliary biomarker in the care of these type 1 diabetes complications.

Topics: Adult; Autoantibodies; Autoimmune Diseases; C-Peptide; Chromogranin A; Diabetes Mellitus, Type 1; Disease Progression; Enterochromaffin-like Cells; Female; Gastritis; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hungary; Hyperplasia; Islets of Langerhans; Male; Prospective Studies

Insulin autoimmune syndrome (IAS) is a relatively rare cause of hypoglycemia characterized by endogenous hyperinsulinism and autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. We present a series of IAS cases and describe the clinical characteristics of these cases.. The medical records of inpatients with the final diagnosis of IAS were collected from August 2007 to August 2017 in Peking Union Medical College Hospital. Clinical characteristics and laboratory test results were summarized. The results of serum glucose, insulin, true insulin, and C-peptide testing during 5-h oral glucose tolerance tests were also summarized. Circulating immune complexes were assessed qualitatively by precipitation with polyethylene glycol (PEG) in some patients.. Sixteen patients were included in this study. Insulin autoimmune antibody test results were found positive in 12 patients and weakly positive in 1 patient. Nine patients had an insulin to C-peptide molar ratio >1, whereas 6 patients had an insulin to C-peptide molar ratio <1. Circulating immune complexes were verified in all 4 patients who had been assessed with PEG. During 5-h oral glucose tolerance tests, the C-peptide level responded earlier to the glucose tolerance and had a shorter peak value period compared with insulin, although C-peptide's fluctuation still lagged behind the glucose fluctuation. Three patients presented with self-limited disease courses or limited disease course after discontinuing use of the sulfhydryl group drugs. Some patients' symptoms were relieved after small frequent meals, and some were relieved after taking acarbose. Only 3 patients took glucocorticoids as the anti-immune therapy.. The insulin to C-peptide molar ratios were not consistently >1 in patients with confirmed diagnoses of IAS in our study, which suggested the low sensitivity of insulin to C-peptide molar ratio to detect IAS. The therapy in our study also revealed the self-limited disease course of IAS, and despite the effectiveness of anti-immunity therapy, convenient therapy, such as frequent small meals and adding acarbose, performed well in many patients.

Topics: Acarbose; Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; C-Peptide; Child; Female; Glucocorticoids; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Male; Middle Aged; Syndrome; Young Adult

Objectives We aimed to evaluate children with type 1 diabetes (T1D) with early age at onset (EAO) for clinical, immune and metabolic features in order to identify age-related disease phenotypes. Methods Comparative study of two groups of T1D children: EAO (≤5 years) and later age at onset (LAO; >5 years), regarding the presence of other autoimmune (AI) diseases, diabetes ketoacidosis and immunologic profile at onset and metabolic data 1 year after diagnosis. Statistical analysis was performed with significance set for p < 0.05. Results The study included 137 children (EAO = 52, mean age 3.6 ± 1.5 [mean ± standard deviation (SD)] and LAO = 85, mean age 10.4 ± 2.9). EAO was more associated with concomitant AI diseases (p = 0.032). Despite no differences in disease onset, EAO presented with lower C-peptide levels (p = 0.01) and higher absolute lymphocyte number (p < 0.0001), with an inverse correlation between these two variables (p = 0.028). Additionally, the EAO group had a higher frequency of serum detection of three antibodies (Abs) (p = 0.0008), specifically insulin Abs (p = 0.0001). One year after diagnosis, EAO had higher total daily insulin (TDI) dose (p = 0.008), despite similar hemoglobin A1c (HbA1c). Conclusions Our data show an association of EAO T1D with more AI diseases, higher number of Abs, lower initial insulin reservoir and higher insulin requirements 1 year after diagnosis. In this group, immune imbalance seems more evident and disease progression faster, probably reflecting distinct "immune environment" with different ages at disease onset. Further studies in the field of immunogenetics and immune tolerance are required, to improve patient stratification and find novel targets for therapeutic intervention.

Topics: Adolescent; Age of Onset; Autoantibodies; Autoimmune Diseases; Biomarkers; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin; Male; Phenotype; Prognosis; Retrospective Studies

We recently established that hybrid insulin peptides (HIPs), formed in islet β-cells by fusion of insulin C-peptide fragments to peptides of chromogranin A or islet amyloid polypeptide, are ligands for diabetogenic CD4 T-cell clones. The goal of this study was to investigate whether HIP-reactive T cells were indicative of ongoing autoimmunity. MHC class II tetramers were used to investigate the presence, phenotype, and function of HIP-reactive and insulin-reactive T cells in NOD mice. Insulin-reactive T cells encounter their antigen early in disease, but they express FoxP3 and therefore may contribute to immune regulation. In contrast, HIP-reactive T cells are proinflammatory and highly diabetogenic in an adoptive transfer model. Because the frequency of antigen-experienced HIP-reactive T cells increases over progression of disease, they may serve as biomarkers of autoimmune diabetes.

Topics: Animals; Autoantigens; Autoimmune Diseases; Autoimmunity; Biomarkers; C-Peptide; CD4-Positive T-Lymphocytes; Cells, Cultured; Chromogranin A; Clone Cells; Crosses, Genetic; Diabetes Mellitus, Type 1; Disease Progression; Female; Islet Amyloid Polypeptide; Lymphocyte Activation; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Peptide Fragments; Recombination, Genetic; Specific Pathogen-Free Organisms

Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia, including surreptitious insulin administration. No standardized treatment regimen exists.. To evaluate an analytic approach to IAS and responses to different treatments.. Observational study in the UK Severe Insulin Resistance Service.. Six patients with hyperinsulinemic hypoglycemia and detectable circulating anti-insulin antibody (IA).. Glycemia, plasma insulin, and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using ELISA and RIA, and IA were further characterized using radioligand binding studies.. All patients were diagnosed with IAS (five IgG, one IgA) based on a high insulin/C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. One patient was managed conservatively, four were treated with diazoxide without sustained benefit, and four were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis.. IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin/C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response.

Topics: Adult; Aged; Autoimmune Diseases; Biomarkers; Blood Glucose; C-Peptide; Chromatography, Gel; Congenital Hyperinsulinism; Diazoxide; Female; Humans; Immunosuppressive Agents; Insulin; Insulin Antibodies; Insulin Resistance; Male; Middle Aged; Syndrome

Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction.. Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R.. The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 μg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 μU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP.. Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

Topics: Autoimmune Diseases; C-Peptide; Calcinosis; Humans; Pancreas; Pancreatitis; Pancreatitis, Chronic

This study investigated the relationship between GAD autoantibody (GADA) titers and changing of β-cell function in patients with latent autoimmune diabetes in adults (LADA).. This 3-year prospective study enrolled 95 subjects from 15 Chinese cities including 25 high-titer (GADA ≥180 units/mL) LADA patients, 42 low-titer (GADA <180 units/mL) LADA patients, and 28 type 2 diabetic patients, the latter two groups as controls of similar age, sex, and BMI. Clinical characteristics were determined annually, including glycosylated hemoglobin (HbA1c), fasting C-peptide (FCP), and 2-h postprandial C-peptide (PCP).. Despite similar initial FCP and PCP, FCP and PCP both decreased more in subjects with high GADA titer (FCP from mean 0.49 nmol/L at entry to 0.13 nmol/L at the third year; P < 0.05) than with low GADA titer (FCP from mean 0.48 to 0.38 nmol/L) and type 2 diabetes (FCP from mean 0.47 to 0.36 nmol/L); the latter two groups being similar. After 3 years, residual β-cell function (FCP >0.2 nmol/L) was detected in only 42% with an initial high GADA titer compared with 90% with a low GADA titer and 97% with type 2 diabetes (P < 0.01 for both). GADA positivity at the third year persisted more in subjects with initially high GADA (92%) than with low GADA (26%) titers (P < 0.01).. In selected LADA patients, initial GADA titers identified subjects with different degrees of persistent autoimmunity and disease progression. LADA patients with a low GADA titer had metabolic phenotypes and loss of β-cell function similar to type 2 diabetic patients.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Autoimmunity; C-Peptide; China; Diabetes Mellitus, Type 2; Disease Progression; Fasting; Female; Follow-Up Studies; Glucose Intolerance; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Insulin-Secreting Cells; Male; Middle Aged; Prospective Studies

Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin.. A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated.. In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out.

Topics: Adolescent; Autoantibodies; Autoimmune Diseases; Blood Glucose; C-Peptide; Diet, Carbohydrate-Restricted; Diet, Diabetic; Female; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Syndrome

Insulin autoimmune syndrome (IAS) is an extremely rare cause of hypoglycemia, particularly in non-Asian populations.. In this report, we describe a white male patient with elevated total insulin (>100.0 μIU/mL), C-peptide, and proinsulin levels who was diagnosed with IAS due to anti-insulin antibodies. He also had a small IgG κ M-protein.. We show that anti-insulin antibodies and/or the monoclonal protein can significantly interfere with insulin and C-peptide immunoassays and propose polyethylene glycol precipitation to quantitate free C-peptide levels as a useful assay in differentiating IAS due to anti-insulin antibodies from insulinoma.. In patients presenting with hypoglycemia with excessively high insulin levels, consideration needs to be given to autoimmune hypoglycemia due to anti-insulin antibodies as a cause. Additionally, if total C-peptide levels are increased, free C-peptide needs to be quantitated following polyethylene glycol precipitation.

Topics: Autoantibodies; Autoimmune Diseases; C-Peptide; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Male; Middle Aged

Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (< 69 mmol/mol, 8.5%), (3) rapid progression to diabetic ketoacidosis, (4) very low C-peptide level, and (5) often associated with elevated serum pancreatic enzymes, and absence of diabetes-related autoantibodies. We encountered a case of fulminant Type 1 diabetes that developed with an initial manifestation of the insulin autoimmune syndrome and rapidly progressed to diabetic ketoacidosis during pregnancy. A 31-year-old Korean woman presented with recurrent sudden onset of sweating and change of consciousness during sleep at 19 weeks gestation. During a 72-h fasting test, hypoglycaemia (1.72 mmol/l) occurred at 4 h after the start of the test. At that time, there was a high insulin level (370.2 μU/ml), a paradoxically low C-peptide level (0.01 nmol/l) and a positive insulin autoantibody test. An oral glucose tolerance test revealed postprandial hyperglycaemia. She was initially diagnosed as the insulin autoimmune syndrome. On the day 5 of admission, she developed diabetic ketoacidosis. Her HbA(1c) was 62 mmol/mol (7.8%). The rapid progression of diabetic ketoacidosis altered the diagnosis to fulminant Type 1 diabetes. This case differed from typical fulminant Type 1 diabetes because it presented with hypoglycaemia, and positive insulin and anti-phospholipid antibody tests. Her HLA typing was HLA-DQA1*0302, 0501, HLA-DRB1*0301 (DR3), 0901(DR9). Her glucose level was subsequently very well controlled with multiple insulin injections and she successfully delivered a healthy baby.

Topics: Adult; Antibodies, Antiphospholipid; Autoantibodies; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Female; Glucose Tolerance Test; Glycated Hemoglobin; HLA-DQ alpha-Chains; HLA-DRB1 Chains; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Syndrome

Topics: Aged; Autoantibodies; Autoimmune Diseases; Autoimmunity; C-Peptide; China; Diagnosis, Differential; Humans; Hypoglycemia; Immune System; Immunoglobulins; Insulin; Insulin Antibodies; Male; Syndrome

The aim of this study was to evaluate if GADA+ and detectable CP had any influence in other autoimmune diseases, glycemic control, and risks of retinopathy in diabetes mellitus type 1 (T1DM) lasting longer than 3 years of duration.. Fifty T1DM subjects were interviewed, performed fundoscopic examination, and measured CP before and after glucagon, HbA1C, and GADA.. GADA+ (n = 17) had a higher frequency of other autoimmune diseases when compared to GADA (p = 0.02). Detectable CP was also associated with a higher prevalence of these diseases (p = 0.03), although, retinopathy was not influenced by either one. Detectable CP had no influence in the glycemic control (mean HbA1C) (p = 0.28). However, insulin daily doses were lower in this group (0.62 vs. 0.91 U/kg/day; p = 0.004).. Although not recommend as a marker of other autoimmune diseases, GADA+ seems to be not only a pancreatic autoimmunity signal. Detectable CP may also have some promising influence in detecting these diseases. Neither influenced the presence of retinopathy, but insulin daily requirements were smaller when CP was present.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Biomarkers; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Glucagon; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male

Topics: Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Factitious Disorders; Humans; Hypoglycemia; Insulin Antibodies; Insulin Resistance; Insulin-Secreting Cells

Topics: Adult; Autoantibodies; Autoimmune Diseases; Biomarkers; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Humans; Immunologic Factors

To determine the clinical and laboratory parameters and the progression to insulin requirement in two groups of LADA patients separated according to GADA titers, and to evaluate the benefit of early insulinization in patients at high risk of premature beta-cell failure (high GADA titers).. Among the diabetic adults seen at our service and screened for GADA at diagnosis, 54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2 U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes (GADA-) were selected for comparison. In addition, 24 patients who had GADA titers > 20 U/ml and who were not initially insulinized were compared to 16 patients who were insulinized at diagnosis.. Insulin resistance was higher in the GADA- group, followed by patients with low GADA titers. BMI and the frequency of arterial hypertension, elevated triglycerides and reduced HDL cholesterol were lower in the high GADA+ group, with no difference between the GADA- or low GADA+ groups. The high GADA+ group showed a greater reduction and lower levels of C-peptide and required insulin earlier during follow-up. Patients with GADA titers > 20 U/ml and insulinized early presented no significant variation in C-peptide levels, had better glycemic control and required a lower insulin dose than patients who were insulinized later.. We agree that patients with LADA should be differentiated on the basis of GADA titers and that patients with GADA titers > 20 U/ml benefit from early insulinization.

Topics: Adult; Analysis of Variance; Autoantibodies; Autoimmune Diseases; Biomarkers; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Follow-Up Studies; Glutamate Decarboxylase; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Statistics, Nonparametric

To investigate the characteristics of the progression of islet beta cell function in Chinese latent autoimmune diabetes in adult (LADA) patients with glutamic acid decarboxylase antibody (GAD-Ab) positivity, and to explore the prognostic factors for beta cell function.. Forty-five LADA patients with GAD-Ab positivity screened from phenotypic type 2 diabetic (T2DM) patients and 45 T2DM patients without GAD-Ab matched as controls were followed-up every 6 mo. Sixteen patients in LADA1 and T2DM1 groups respectively have been followed-up for 6 years, while 29 patients in LADA2 and T2DM2 groups respectively for only 1.5 years. GAD-Ab was determined by radioligand assay, and C-peptides (CP) by radioimmune assay.. The percentage of patients whose fasting CP (FCP) decreased more than 50% compared with the baseline reached to 25.0% at 1.5(th) year in LADA1 group, and FCP level decreased (395.8+/-71.5 vs 572.8+/-72.3 pmol/L, P<0.05) at 2.5(th) year and continuously went down to the end of follow-up. No significant changes of the above parameters were found in T2DM1 group. The average decreased percentages of FCP per year in LADA and T2DM patients were 15.8% (4.0-91.0%) and 5.2% (-3.5 to 35.5%, P=0.000) respectively. The index of GAD-Ab was negatively correlated with the FCP in LADA patients (r(s)=-0.483, P=0.000). The decreased percentage of FCP per year in LADA patients were correlated with GAD-Ab index, body mass index (BMI) and age at onset (r(s)=0.408, -0.301 and -0.523 respectively, P<0.05). Moreover, GAD-Ab was the only risk factor for predicting beta cell failure in LADA patients (B=1.455, EXP (B)=4.283, P=0.023).. The decreasing rate of islet beta cell function in LADA, being highly heterogeneous, is three times that of T2DM patients. The titer of GAD-Ab is an important predictor for the progression of islet beta cell function, and age at onset and BMI could also act as the predictors.

Topics: Adult; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 2; Disease Progression; Female; Follow-Up Studies; Humans; Islets of Langerhans; Male; Middle Aged; Prognosis; Risk Factors

A 53-year-old Caucasian woman presented with repeated episodes of hypoglycemia. Self-monitored blood glucose levels during the attacks were between 40 and 60 mg/dl (2.2-3.3 mmol/l).. An oral glucose tolerance test performed over 210 minutes showed normal baseline glucose levels, markedly elevated levels of serum insulin and slightly elevated C-peptide concentrations. During the test, a marked increase of insulin and a normal increment of C-peptide were observed. The tentative diagnosis of an insulinoma was raised and a 72 h fasting test performed, throughout which the insulin-glucose-ratio was pathologically elevated, whereas C-peptide levels were only slightly elevated.. Strongly positive levels of insulin antibodies led to the diagnosis of an insulin autoimmune syndrome.. This syndrome is caused by IgG-insulin-complexes with prolonged plasma half-life in the presence of reduced insulin action. The therapy consisted of fractionated meals to avoid hyperinsulinism and following hypoglycemic episodes. After four months a spontaneous clinical remission was observed.. The autoimmune insulin syndrome is a rare cause of recurrent, spontaneous hypoglycemia in Europe in non diabetic patients. Its prognosis is good as there is a high rate of spontaneous clinical remission in up to 80 % of patients.

Topics: Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Immunoglobulin G; Insulin; Insulin Antibodies; Middle Aged; Prognosis; Remission, Spontaneous; Syndrome

Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of hypoglycemia in Western countries. It is characterized by hypoglycemic episodes, elevated insulin levels, and positive insulin antibodies. Our objective is to report a case of IAS identified in South America.. A 56-year-old Caucasian male patient started presenting neuroglycopenic symptoms during hospitalization due to severe trauma. Biochemical evaluation confirmed hypoglycemia and abnormally high levels of insulin. Conventional imaging examinations were negative for pancreatic tumor. Insulin antibodies were above the normal range. Clinical remission of the episodes was not achieved with verapamil and steroids. Thus, a subtotal pancreatectomy was performed due to the lack of response to conservative treatment and because immunosuppressants were contraindicated due to bacteremia. Histopathological examination revealed diffuse hypertrophy of beta cells. The patient continues to have high insulin levels but is almost free of hypoglycemic episodes.

Topics: Autoimmune Diseases; C-Peptide; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Antibodies; Male; Middle Aged; Syndrome

The simultaneous occurrence of juvenile dermatomyositis (DMS) and diabetes mellitus is described in 2 pediatric patients. Both these patients presented with significant weight loss, polyuria, and polydypsia within a short time of being diagnosed with JDMS, while these patients were taking oral prednisone (40-60 mg/day in divided doses). Laboratory evaluation detected ketonuria, significant hyperglycemia (696 and 913 mg/dL) and low serum levels of insulin and C-peptide. Both these patients were treated with high doses of insulin. Islet cell and GAD65 antibodies were found to be positive in 1 of the patients, pointing toward a diagnosis of insulin-dependent diabetes mellitus. The other patient tested negative for these antibodies and required insulin therapy for approximately 6 months. Steroid-induced diabetes mellitus seemed highly likely in this case. We hypothesize that a common environmental trigger possibly a viral infection might have been responsible in causing 2 different autoimmune pathologies in these genetically predisposed individuals.

Topics: Adolescent; Adrenal Cortex Hormones; Autoimmune Diseases; C-Peptide; Dermatomyositis; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Risk Assessment; Treatment Outcome

We report the case of a 69-year-old woman with insulin autoimmune syndrome first misdiagnosed as insulinoma. The case demonstrates the difficulties to correctly diagnose this rare disorder as both insulin and proinsulin levels were increased by crossreactive autoantibodies. No known triggering agent could be identified. We suggest that this diagnosis should be considered more often also in caucasian patients to avoid useless operations for such patients.

Topics: Aged; Antibody Specificity; Autoantibodies; Autoimmune Diseases; C-Peptide; Diagnosis, Differential; Female; Humans; Hypoglycemia; Insulin; Insulinoma; Pancreatic Neoplasms; Proinsulin

ABSTRACT AIMS/HYPOTHESIS: This study aimed to define the immunological parameters which could be used to identify patients with the distinct metabolic features of adult latent autoimmune diabetes.. Sera of 312 patients with short-term diabetes (duration < 5 years) over 35 years of age at diagnosis were screened for ICA, GAD- and IA2-Ab by antibody assays validated in workshops. The antibody status was correlated with age, BMI, residual beta-cell function, measured by fasting C-peptide, onset of diabetes-related complications and markers of the metabolic syndrome (hypertension and hyperlipidaemia).. A total of 51 antibody positive patients were identified. These patients had lower fasting C-peptide and less neuropathy and hypertension compared with matched antibody-negative patients. However, only patients with two or more antibodies had reduced residual beta-cell function compared with antibody-negative or single antibody-positive (ICA or GAD-Ab only) patients. Patients with two or more antibodies were also leaner and had diabetes-related complications or hypertension less frequently than single antibody-positive or antibody negative-patients. IA2 antibody status did not substantially contribute to the diagnosis or differentiation of LADA patients.. We concluded that the combination of ICA and GAD antibodies and high titre of GAD antibodies are characteristic of patients with insulin deficiency with the clinical features of Type I (insulin-dependent) diabetes mellitus (LADA-type 1). Single antibody positivity and low titre antibodies are markers for LADA-type 2 associated with the clinical and metabolic phenotype of Type II (non-insulin-dependent) diabetes patients.

Topics: Adult; Autoantibodies; Autoimmune Diseases; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Fasting; Glutamate Decarboxylase; Humans; Islets of Langerhans; Middle Aged

To assess the prevalence of markers of autoimmune insulitis (AII) in patients classified originally as having Type-2 diabetes mellitus (Type-2 DM). 386 patients subdivided according to the BMI, C-peptide and type of treatment.. Age, BMI, C-peptide, Glutamic acid decarboxylase autoantibodies (GADA), HLA-DR/,-DQ alleles. Prevalence of GADA varied from < 5% in obese patients with normal/increased C-peptide to > 30% in non-obese patients with low C-peptide. In majority of GADA positive patients, the Type-1 DM high-risk HLA-DRB1*, HLA-DQB1* alleles have been found. Among them HLA-DRB1*0302 and HLA-DRB1*0201 were more frequent than HLA-DRB1*040x and HL:A-DQB1*0302.. Significant fraction of patients classified initially as Type-2 DM may have in fact Type-1 DM. Such patients can be recognized on the basis of assessment of serological (GADA) and immuno-genetical (HLA-DR/,-DQ alleles) markers. In some patients clinical, metabolic, immune, and immunogenetic markers may disagree. This divergence stresses multifactorial genesis of diabetes. Moreover, it can also suggest that both autoimmune insulitis and insulin resistance may coexist in parallel.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Biomarkers; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glutamate Decarboxylase; HLA-DQ Antigens; HLA-DR Antigens; Humans; Male; Middle Aged

To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis.. Patients (n = 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohistological analysis. These patients were divided into two groups based on the presence or absence of islet immunological abnormalities (insulitis or hyperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A1c and daily insulin doses were recorded. The clinical course of patients with islet immunological abnormalities was compared with that of patients without those abnormalities.. Patients with and without islet immunological abnormalities did not differ with regard to HLA type or islet cell antibodies. Antibodies to glutamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A1c values (p < 0.05) and a trend towards greater insulin requirements. Further, patients with the islet abnormalities had higher fasting plasma glucose concentrations 2 years after the biopsy than at the time of the biopsy (p < 0.05).. The heterogeneous clinical course observed following diagnosis in patients with Type I diabetes correlates with islet immunological abnormalities. Insulitis and hyperexpression of MHC class I correlate with deteriorating glycaemic control.

Topics: Adolescent; Adult; Autoantibodies; Autoimmune Diseases; Biopsy; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Histocompatibility Testing; Humans; Inflammation; Islets of Langerhans; Male; Middle Aged

In order to study the clinical characteristics, time course of beta cell function and glutamic acid decarboxylase antibodies (GAD65Ab) in Thai patients with adult-onset Type 1 diabetes and to examine the distinctive features between patients with rapid-and slow-onset, 61 Thai patients with Type 1 diabetes who had age of disease onset at or after 20 years were studied. All patients were treated with insulin at the time of study and had fasting C-peptide levels +/-0.33 nmol/l. Twenty-six (42.6%) were in rapid-onset and 35 (57.4%) were in slow-onset groups. Fourty-four of 61 (70.5%) were male. About three-fourths had body mass index (BMI) < 19 kg/m2 at the time of insulin therapy. Only 7 of 61 (11.5%) patients had ketoacidosis at first presentation. Five patients had associated autoimmune thyroid disease and 10 (16.7%) patients had family history of diabetes in first-degree relatives. GAD65Ab was positive in 31 patients (50.8%); 10 (38.5%) were in rapid-onset and 21 (60.0%) were in slow-onset groups. GAD65Ab particularly of high levels were persistently elevated during 3-4 years follow-up period. The persistence of GAD65Ab were not associated with changes in fasting C-peptide levels. At the time of insulin dependency, there were no distinctive clinical features between rapid- and slow-onset patients except higher fasting C-peptide (0.08+/-0.08 vs. 0.14+/-0.10 nmol/l; p = 0.023) and GAD65Ab levels (19.6+/-17.4 vs. 46.1+/-49.7 U/ml; p = 0.036) in slow-onset patients. Fasting C-peptide levels of patients in the latter group were also demonstrated to be higher after 3-4 years of follow-up. In conclusion, most Thai patients with adult-onset Type 1 diabetes in this study were male and had significant degree of weight loss and lean BMI prior to insulin therapy. The presence of GAD65Ab did not predict clinical features or rate of beta cell loss. Patients in rapid-onset group had lower fasting C-peptide and GAD65Ab levels than those of slow-onset group which confirms the slower process of beta cell failure in the latter.

Topics: Adult; Aged; Autoantibodies; Autoimmune Diseases; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Fasting; Female; Glutamate Decarboxylase; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Thailand; Thyroid Diseases; Time Factors

We report the case of a Caucasian patient with insulin autoimmune syndrome (IAS), defined as the association of hypoglycaemic attacks with insulin autoantibodies in individuals not previously treated with exogenous insulin. This rare syndrome (more than 200 published cases) has been reported mainly in Japan. Most affected patients present with other autoimmune disorders, most often Graves' disease. In most cases, insulin autoantibodies appear a few weeks after the beginning of treatment with a drug containing a sulphyldryl group. A significant increase in insulin and C-peptide plasma concentrations and the presence of other antiorgan antibodies are observed. The susceptibility haplotype is present in the Japanese population, which may account for the high frequency of IAS. Spontaneous remission is observed in 80% of cases, with cessation of hypoglycaemic attacks and disappearance of insulin autoantibodies some months after withdrawal of the drug. This rare cause of hypoglycaemia in Caucasian subjects should be considered in aetiologic investigation of spontaneous hypoglycaemia.

Topics: Antithyroid Agents; Autoantibodies; Autoimmune Diseases; C-Peptide; Carbimazole; Humans; Hyperthyroidism; Hypoglycemia; Insulin; Japan; Male; Middle Aged; Morocco; Paris; Propylthiouracil; Syndrome; White People

The autoimmune insulin syndrome (AIS) is a rare, benign syndrome characterized by hyperinsulinaemia and hypoglycaemia associated with the presence of autoantibodies to insulin in patients who have not been treated with insulin. We report here the case of a 52-year-old patient with recurrent attacks of severe postprandial hypoglycaemia and we also present the effect of anti-insulin antibodies on insulin immunoassays. The patient was submitted to the following diagnostic tests: 5-h oral glucose tolerance test (OGTT), a prolonged 72-h fast and an insulin tolerance test (ITT). Serum glucose, total and free insulin, C-peptide, proinsulin, insulin antibodies and other autoantibodies were measured. Insulin concentrations were measured by two methods: a double antibody radioimmunoassay (RIA) and an immunoradiometric assay (IRMA). Insulin concentration measured by RIA was extremely high in the OGTT and 72-h fast. In contrast, insulin concentrations measured by IRMA were between 120 and 888 pmol/L in the OGTT and between 37 and 133 pmol/L during the 72-h fast. Fasting free-insulin concentrations measured by RIA were between 2224 and 2669 pmol/L, whereas free-insulin concentrations measured by IRMA ranged between 93 and 237 pmol/L. Total insulin concentrations measured by RIA and IRMA were 57,615 and 94,021 pmol/L, respectively. The C-peptide concentrations were moderately high in the three tests. Serum insulin antibody concentrations were extremely high (62-71%), compared with less than 3% in normal serum samples. In conclusion, the high insulin concentrations measured by RIA were caused by insulin autoantibodies. However, insulin concentrations measured by IRMA were not influenced by them. We conclude that IRMA is the more accurate method for measuring insulin concentrations in such cases.

Topics: Autoantibodies; Autoimmune Diseases; C-Peptide; Chromatography, Gel; Glucose Tolerance Test; Humans; Immunoradiometric Assay; Insulin; Insulin Antibodies; Male; Middle Aged; Radioimmunoassay

To understand latent autoimmune diabetes mellitus in adults (LADA), we compared the clinical characteristics, fasting plasma glucose and C-peptide level, genetic frequency of HLA-DQA1, -DQB1 chain in 25 patients with LADA, 57 patients with insulin-dependent diabetes mellitus (IDDM, 21 patients with children-onset IDDM, 36 patients with adult-onset IDDM with ketosis), 38 patients with NIDDM (mild and moderate 30 patients and severe 8) and 42 normal persons. The onset of age was 20-48 years old associated with obvious polyphagia, and weight loss. Body mass index (BMI) was < or = 25 and fasting plasma glucose was > or = 16.5 mmol/L (297 mg/dl). Fasting and 1, 2 hour post prandial C-peptide level showed low and flatter curve (0.4, 0.8 and 0.8 nmol/L respectively). Glutamate decarboxylase (GAD) antibody was positive. HLA-DQ beta chain substitution of aspartate molecule was at position 57 (susceptic gene). LADA could be diagnosed if a patient has the first point and any point of the second to the fourth point. Patients with LADA should take diet, exercises, especially insulin as early as possible in order to control fasting and post prandial plasma glucose, and prevent from further destroy of residue islet B cells and reduce diabetic complications of eye, kidney and nerve.

Topics: Adult; Antibodies; Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Gene Frequency; Glutamate Decarboxylase; HLA-DQ alpha-Chains; HLA-DQ Antigens; Humans; Ketosis; Male

The initiation of the immunological processes leading to type I diabetes is still not understood. The potential of endogenous peptides to induce autoimmune reactions was investigated. Peptides generated in the beta-cell by proteolysis could bypass antigen processing by binding to MHC molecules. Selfreactive T and B lymphocytes could be activated by these MHC peptide complexes. The antibody production of peptide-induced B lymphocytes was investigated in mice. Insulin A chain, B chain, C-peptide or amylin were tested for potential induction of antibodies to antigens other than the immunizing peptide. Lymph node B lymphocytes were characterized with an avidin at solid phase ELISA-spot assay. In BALB/c mice insulin A chain induced more spots to B29biotin- and to B1biotinDOP insulin than to A chain itself (P < 0.01, each). Spots to insulin were not inhibited by insulin A chain. Spots to B1DOP insulin were not inhibited by A chain or insulin, excluding crossreaction. Inbred strains of mice with H-2d but not with H-2k or H-2b showed the effect. Application of A chain without adjuvant produced the effect. The antigens recognized by A chain-induced B lymphocytes had to be included in the natural IgM antibody repertoire of the spleen. The study supports the hypothesis that endogenous breakdown peptides can bypass antigen processing resulting in an autoreactive T-B cell interaction. A potential to induce type I diabetes could exist.

Topics: Amyloid; Animals; Antibodies; Antibody Formation; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Immunity, Cellular; Insulin; Islet Amyloid Polypeptide; Male; Mice; Mice, Inbred Strains

Among autoantibodies detected in patients with insulin-dependent diabetes mellitus (IDDM), antibodies to 64,000(Mr) islet protein(64k), now recognized as glutamic acid decarboxylase(GAD), appear to be an even more predictive marker of IDDM than islet cytoplasmic antibody (ICA) or insulin autoantibody (IAA). We examined the relationships among 64k autoantibodies, pancreatic beta-cell function, HLA-DR antigens and HLA-DQ genes in patients with IDDM in Korea.. To identify the 64k autoantibody, the immunoprecipitation method was performed for 35 patients with IDDM and 10 normal controls. In patients with IDDM, serum C-peptide levels were measured and HLA-DR typings and HLA-DQA1 and DQB1 gene typings were performed.. 12 of 35 (34%) patients with IDDM were positive for 64k autoantibody in contrast to none of 10(0%) normal controls. There were no differences in residual pancreatic beta-cell function between 64k autoantibody positive and negative groups. 64k autoantibody was detected more frequently in patients with recent (duration < 6 months, 10/25[40%]) and young -aged(aged < 15 years, 7/18[39%]) onset of IDDM. All of 3(100%) patients with HLA-DR3/DR4 heterotypes were positive in 64k autoantibody, in contrast to 1 of 7(14%) patients without HLA-DR3 nor DR4. The frequencies of HLA-DQA1*0301, HLA-DQB1*0201, DQB1* 0302 and DQB1*0303 gene types were higher in patients with 64k autoantibody (12/12 [100%]) vs. without 64k autoantibody 18/22[81%], 5/11[45%] vs. without 64k autoantibody 5/22[23%], 5/11[45%] vs. without 64k autoantibody 8/22[36%] and 6/11 [55%] vs. without 64k autoantibody 9/22[41%].. There results suggest that 64k autoantibodies have some relationship with HLA-DR, DQA1 and DQB1 genes, but not with residual pancreatic beta-cell function in Korean patients with IDDM.

Topics: Adolescent; Adult; Alleles; Animals; Antibody Specificity; Asian People; Autoantibodies; Autoantigens; Autoimmune Diseases; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Susceptibility; Female; Genetic Predisposition to Disease; Glutamate Decarboxylase; HLA-DQ alpha-Chains; HLA-DQ Antigens; HLA-DQ beta-Chains; HLA-DR Antigens; Humans; Islets of Langerhans; Korea; Male; Rats; White People

Islet cell antibodies (ICA), insulin autoantibodies (IAA) and islet cell surface antibodies (ICSA) together with C-peptide were determined in 1031 healthy schoolchildren to evaluate the frequency of autoimmune reactions towards endocrine pancreas and its relation to insulin secretion in non-diabetic children. The prevalence of ICA (levels > 6 JDF units) was 1.4% (14/1012) while 44 children (4.3%) were ICSA-positive and 40 (4%) had IAA. Girls had higher titres of ICSA than boys. Young children (7-8 years) more often had IAA than 12-13-year-old children who, however, had ICA three times more often than the young children. There were no clear associations between the different antibodies. Of the children, 2.4% had very low post-prandial serum C-peptide values (< or = 0.25 nmol/l). Serum C-peptide was higher in girls than in boys (P < 0.001) and in older children than in younger (P < 0.001). Girls with low levels of ICA had high C-peptide values, while girls with high ICA titers had low C-peptide values, the latter perhaps indicating partial beta cell loss. IAA and ICSA were not related to C-peptide values but both positive ICSA and high C-peptide values were most common in the autumn (P < 0.02 and P < 0.0001, respectively). One of the ICA-positive children developed diabetes in 1991, 4 years after the blood sample was taken. Since after 5 years only one of the children has developed IDDM, it can be concluded autoimmune reactions towards endocrine pancreas and insulin may occur in many children without the development of manifest diabetes. Those with high ICA titers may have lost so many beta cells that their insulin secretion is affected, which in some cases might lead to diabetes many years later.

Topics: Adolescent; Age Factors; Autoantibodies; Autoimmune Diseases; C-Peptide; Child; Diabetes Mellitus, Type 1; Eating; Family; Female; Humans; Incidence; Insulin; Insulin Antibodies; Insulin Secretion; Islets of Langerhans; Male; Regression Analysis; Sex Characteristics; Sweden

Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3-4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden ('North') and Pittsburgh were younger (< 10 years old) at diagnosis compared with those in the other clinics in Europe (P < 0.05 versus P < 0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (< 8 days; P < 0.001) and higher blood glucose (> 20 mmol/l; P < 0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%; P < 0.01) or in France (70%; P < 0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (< 0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.

Topics: Adolescent; Adult; Age of Onset; Austria; Autoantibodies; Autoimmune Diseases; Biomarkers; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Family; Female; Finland; France; Geography; Germany; Humans; Incidence; Infant; Infant, Newborn; Islets of Langerhans; Italy; Male; Pennsylvania; Seasons; Sex Characteristics; Sweden

Type 1 diabetes mellitus in adults may present in a manner similar to that of Type 2 diabetes but with a late development of insulin dependency. We studied 65 patients who presented with 'adult-onset' diabetes after the age of 30 years. Of these patients, 19 required insulin therapy. The insulin-treated patients were significantly younger, their onset of diabetes was at an earlier age, and their postprandial serum C-peptide levels were lower than those of the non-insulin-treated group. Moreover, the insulin-treated subjects had a higher mean concentration of antibodies to glutamic acid decarboxylase (GAD) (66.8 +/- 10.2 units) than the patients who did not require insulin (9.9 +/- 1.9 units) (p < 0.001) and their frequency of anti-GAD positivity was 73.7% versus 4.3% (p < 0.001). Thus, among patients attending a diabetes clinic, the majority (73.7%) of subjects who presented with diabetes after 30 years of age and who subsequently required therapy with insulin, actually have the islet cell lesion of Type 1 diabetes which progresses at a slower tempo than in children. We conclude that testing for anti-GAD in adult-onset non-obese diabetic patients should be a routine procedure in order to detect latent insulin-dependency at the earliest possible stage, since this assay can assist in the correct classification of diabetes, and more appropriate therapy.

Topics: Adult; Age of Onset; Aged; Autoantibodies; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet, Diabetic; Female; Glutamate Decarboxylase; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Predictive Value of Tests

Patients with autoimmune insulin antibody are characterized by hypoglycemic attacks and antibodies to insulin in serum without prior insulin administration. In the present report, a patient with hypoglycemia due to autoimmune insulin antibody associated with primary empty sella syndrome and polymyositis appeared to have high urinary immunoreactive insulin (IRI) in the face of normal urinary C peptide. Consequently, the urinary IRI/C peptide ratio was apparently high. The amelioration of hypoglycemic attacks and polymyositis by prednisolone treatment was accompanied by the disappearance of the antibodies and complete normalization of the urinary IRI and IRI/C peptide ratio. No comparable rise in the urinary IRI and IRI/C peptide ratio was observed in the patients with other disorders studied. Glucose clamp and glucose tolerance study showed decreased sensitivity to exogenous or newly secreted insulin, prolonged half disappearance time of serum insulin, and normal disappearance of blood glucose. These results were consistent with the idea that autoantibodies buffered the effect of exogenous or newly secreted insulin and maintained a relatively constant level of serum free insulin which was not high enough when a large amount of glucose was loaded, but was too high after prolonged fasting, which eventually caused hypoglycemic attacks.

Topics: Autoantibodies; Autoimmune Diseases; Blood Glucose; C-Peptide; Child; Empty Sella Syndrome; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Middle Aged; Muscles; Myositis; Prednisolone; Time Factors

It is still a matter of debate whether patients who develop islet-cell antibody positive autoimmune diabetes during adulthood represent slowly evolving Type 1 (insulin-dependent) diabetes mellitus or a separate subgroup of Type 2 (non-insulin-dependent) diabetes. To address this question, we measured C-peptide response to a test meal, and energy metabolism in the basal state and during a euglycaemic, hyperinsulinaemic clamp in (1) 29 patients with Type 2 diabetes; (2) 10 patients with autoimmune diabetes developing after the age of 40 years; (3) 11 patients with Type 1 diabetes and (4) 15 non-diabetic control subjects. While C-peptide response to a test meal was lacking in Type 1 diabetes and nearly normal in Type 2 diabetes, the C-peptide response in autoimmune diabetes was markedly reduced. Patients with Type 2 diabetes, autoimmune diabetes and Type 1 diabetes showed a 47%, 45% and 42%, respectively, reduction in the rate of non-oxidative glucose metabolism compared with control subjects (p less than 0.05-0.01). Similarly, patients with Type 2 diabetes (+52%), autoimmune diabetes (+27%) and Type 1 diabetes (+33%) presented with an enhanced basal rate of hepatic glucose production, which was less suppressed by insulin compared with healthy control subjects (p less than 0.01). However, patients with autoimmune diabetes derived more energy from oxidation of glucose and proteins and less energy from oxidation of lipids than patients with either Type 1 or Type 2 diabetes (p less than 0.05-0.01). In conclusion, patients who develop autoimmune diabetes during adulthood share the defects in hepatic glucose production and in non-oxidative glucose metabolism with both Type 1 and Type 2 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autoantibodies; Autoimmune Diseases; Blood Glucose; C-Peptide; Cholesterol; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Eating; Female; Glycated Hemoglobin; Humans; Islets of Langerhans; Male; Middle Aged; Thyroid Gland; Thyroxine; Triglycerides

Topics: Autoimmune Diseases; C-Peptide; Diabetes Mellitus; Diagnosis, Differential; Glucagon; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Islets of Langerhans; Radioimmunoassay; Specimen Handling

Insulin autoimmune syndrome is a syndrome consisting of fasting hypoglycemia, hyperinsulinemia and detectable insulin-binding antibodies in patients who have never been exposed to exogenous insulin. Four cases who developed symptoms of hypoglycemic attack with self-limited duration and spontaneous remission were collected in our hospital from 1984 to 1988. The elevated serum total and free insulin and C-peptide levels, as well as the titer of insulin autoantibodies, decreased gradually; but insulin autoantibodies were still present in the serum for more than six months after the initial episodes of hypoglycemia. Three of four patients had Graves' disease and developed the syndrome after methimazole treatment. The fourth one had a history of hemorrhagic cystitis and denied history of specific drug exposure. The cause or stimulus for insulin autoantibody formation is still unknown, but drugs containing a sulfhydryl group like methimazole may play a role in the development of the syndrome. Extremely high insulin antibodies in patients with fasting hypoglycemia along with elevated serum levels of insulin and C-peptide suggest a diagnosis of insulin autoimmune syndrome and usually exclude the possibility of insulinoma or factitious hypoglycemia.

Topics: Adult; Aged; Autoimmune Diseases; C-Peptide; Female; Humans; Hypoglycemia; Insulin Antibodies; Methimazole

In 19 patients with newly diagnosed Type I diabetes mellitus a single transfusion of 1.9 x 10(9) to 1.5 x 10(10) lymphocytes was performed. Fifteen Type I diabetic patients who did not receive a transfusion were used as controls. Anti-beta-cell cell-mediated cytotoxicity was measured using an insulin release assay. Stimulated C-peptide secretion (100 g glucose orally, 1 mg glucagon i.v.) was used to estimate residual beta-cell function. Both parameters were measured prior to transfusion and after 12 months. The transfusions were followed by a fall of cytotoxicity below the 95% confidence limit of the controls in 11 of the 19 patients ('responders') (15.7 +/- 1.7 ng insulin/islet/20 h vs 6.7 +/- 1.3 P less than 0.001), while the other eight transfused patients ('non-responders') (13.5 +/- 1.9 vs 17.1 +/- 2.9, ns) and the non-transfused control patients (11.6 +/- 1.1 vs 14.2 +/- 2.4, ns) displayed persistently high cytotoxicity levels. In the responder group a slight improvement in stimulated C-peptide secretion was observed (136 +/- 43 pmol/dl vs 148 +/- 38, ns) whereas in the non-responder (127 +/- 28 vs 106 +/- 25, ns) and in the control group (130 +/- 17 vs 97 +/- 19, P less than 0.05) the stimulated C-peptide responses declined during the 12-month follow-up. Thus, lymphocyte transfusion may have beneficial effects by suppressing anti-beta-cell cytotoxicity and preserving C-peptide secretion.

Topics: Adolescent; Adult; Autoimmune Diseases; Blood Transfusion; C-Peptide; Child; Cytotoxicity, Immunologic; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Histocompatibility Testing; Humans; Insulin; Islets of Langerhans; Lymphocyte Transfusion; Lymphocytes; Male

The insulin autoimmune syndrome is characterised by high titres of autoantibody to insulin, a high circulating concentration of total insulin and later, reactive hypoglycaemia. We have studied a patient with this syndrome whose insulin autoantibody bound exclusively human insulin. This permitted us to investigate the disappearance of bound (human) and unbound (porcine) insulin in the same patient, using i.v. injections of 0.075 U/g of each insulin on separate days. The peak plasma free insulin concentration following porcine insulin was four times greater than that following the same dose of human insulin. The plasma disappearance half-time of porcine insulin following injection was 11 min compared with 32 min following human insulin injection, and the area beneath the disappearance curve of free insulin during the 120 min of sampling was greater for porcine insulin by a factor of 3.15. The nadir in plasma glucose occurred at 45 min following porcine insulin and at 90 min following human insulin injection. The restoration of basal glucose concentration was correspondingly slower following human insulin, but the absolute fall in glucose achieved was no different. There was no evidence of insulin resistance. Insulin autoantibodies can seriously disturb the kinetics and effect of free insulin.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Antibodies; Kinetics; Middle Aged; Recombinant Proteins; Swine

Initially reported in Japan, autoimmune hypoglycemia is related to the presence of insulin-binding antibodies, even in patients who have never been treated with insulin. The authors report a case of spontaneous autoimmune hypoglycemia in a French woman receiving pyritinol. The difference between insulin and C peptide radioimmunoassay levels prompted a search for insulin antibodies. In vitro studies confirmed their presence and showed that they were immunoglobulins G with two binding sites without species specificity. The outcome of autoimmune hypoglycemia is usually favourable, with a rapid decrease of insulin antibodies but steroid therapy is needed when serious clinical manifestations are present. The differential diagnosis with factitious hypoglycemia may be difficult. The reasons for the appearance of the insulin antibodies and the exact mechanisms of hypoglycemia remain hypothetical. However, drugs with a sulfhydril group, such as pyritinol, could play a causative role in this syndrome.

Topics: Aged; Aged, 80 and over; Autoimmune Diseases; Blood Glucose; C-Peptide; Female; Humans; Hypoglycemia; Immunoglobulin G; Insulin; Insulin Antibodies; Pyridines; Pyrithioxin

Islet cell antibodies (ICAs), thyrogastric antibodies, and HLA-DR antigens were determined in 204 patients with type II (non-insulin-dependent) diabetes controlled with diet and/or oral hypoglycemic agents (NIR) and in 108 age-matched patients who required insulin to control their hyperglycemia (IR). beta-Cell function measured as C-peptide response to glucagon was evaluated in relation to the presence of ICAs and HLA-DR antigens. The IR patients differed from the NIR patients with respect to higher frequency of ICAs (P less than .001), thyroid antibodies (P less than .02), and the HLA antigen DR4 (P less than .02). The highest frequency of ICAs and thyroid antibodies was observed in female insulin-treated subjects (51.2 and 46.4%). Patients who were heterozygous for HLA-DR3/DR4 showed significantly higher frequency of ICAs (P less than .01) and complement-fixing ICAs (P less than .001) than patients without the heterozygous form DR3/DR4. Neither the presence of ICA alone nor DR3/DR4 alone was associated with a significant impairment of beta-cell function. However, when both ICA and DR3/DR4 were present in a diabetic individual, beta-cell function was markedly impaired (P less than .001), suggesting that both genetic and autoimmune factors are necessary to facilitate the process leading to beta-cell destruction of the patients. Our findings suggest that type II diabetes is a heterogeneous disorder including at least two major subgroups, which can be further characterized by HLA-DR antigens and organ-specific antibodies.

Topics: Autoantibodies; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Heterozygote; HLA-D Antigens; HLA-DR Antigens; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Insulin; Islets of Langerhans; Male; Parietal Cells, Gastric; Thyroid Gland

A 43-year-old woman with spontaneous episodes of neuroglycopenic hypoglycemia was found to have immune-mediated thrombocytopenic purpura and primary biliary cirrhosis. Hypoglycemia along with hyperinsulinemia suggested insulinoma. Serum c-peptide levels were disproportionately low, raising the possibility of factitious hypoglycemia. The patient's plasma contained circulating insulin receptor autoantibodies, thought to cause hypoglycemia by their insulin-like actions. With prednisone therapy, her other autoimmune features improved, and the hypoglycemia eventually resolved. Hypoglycemia mediated by insulin receptor autoantibodies should be considered in patients with fasting hypoglycemia and features suggesting an underlying autoimmune disorder before pursuing more invasive procedures. High-dose steroids may be life-saving in this disorder.

Topics: Adult; Autoantibodies; Autoimmune Diseases; C-Peptide; Diagnosis, Differential; Fasting; Female; Humans; Hypoglycemia; Insulin; Liver Cirrhosis, Biliary; Prednisone; Receptor, Insulin; Syndrome; Thrombocytopenia

Twenty five cases of insulin autoimmune syndrome including this case has been reported so far without having the pathogenesis clarified. This paper describes a case which suggests one aspect of pathogenesis. The patient, a housewife concurrently had insulinoma and severe rheumatoid arthritis, complaining of hypoglycemic syncope attacks. During the attacks her blood sugar levels ranged from 19 to 22 mg%. Her serum extractable immunoreactive insulin (IRI) and insulin binding antibody levels were 557 microunits/ml and 0.390 mU/ml, respectively. gamma-Globulin-bound insulin was also measured electrophoretically. Bio-Gel P 10 column chromatography eluted almost all IRI at the void volume at pH 7.4 and a smaller but significant IRI peak also at pH 3.0. Selective angiography revealed a tumor-like staining in the pancreas body. Pancreatectomy relieved her of hypoglycemic attacks. Histology disclosed two small insulinomas. Insulinoma, rheumatoid arthritis and insulin autoimmune syndrome coexisted in this case, suggesting some causal relationship among them.

Topics: Adenoma, Islet Cell; Arginine; Arthritis, Rheumatoid; Autoimmune Diseases; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Antibodies; Middle Aged; Pancreatectomy; Pancreatic Neoplasms

Topics: Autoimmune Diseases; C-Peptide; Diabetes Mellitus; Humans; Insulin; Insulin Antibodies; Peptides; Syndrome

A 21-year-old female patient complaining of frequent hypoglycemic attacks in the presence of a large amount of circulating insulin-binding antibodies without previous known immunization is described. In order to clarify the possible mechanism of the hypoglycemic attacks occurring in this new syndrome, changes in plasma glucose, plasma total and free immunoreactive insulin (IRI), and C peptide immunoreactivity (CPR) levels were investigated in the patient before, during, and after a three-hour glucose infusion. The character of her antibodies were also examined. An abrupt discontinuation of the glucose infusion caused a sharp decline in the plasma glucose level, reaching a nadir of 30 mg./100 nk, at 270 minutes; then she became unconscious. A huge amount of total IRI of 2,834 micron U./ml. was registered at 180 minutes, while the peak value of free IRI of 208 micronU./ml. was observed 45 minutes after the cessation of the glucose infusion. Plasma CPR was increased from high basal level, 19.6 ng./ml., to the maximum level of 29.2 ng./ml. The maximum insulin-binding capacity of IgG in the patient's serum was 6.25 mU./ml. The antibody-combining site was homogeneous, showing one high-affinity site (K: 1.1 X 10(9)M-1). Neither the prolonged fasting nor the administration of tolbutamide induced the hypoglycemic attack in the patient. The hypoglycemia may be explained by an unduly excessive amount of insulin liberated from a large pool of bound insulin irrespective of blood sugar level. The cause of the antibody production is also discussed.

Topics: Adult; Antibodies; Antigens; Autoimmune Diseases; C-Peptide; Chromatography, Gel; Female; Glucose; Humans; Hypoglycemia; Infusions, Parenteral; Insulin; Syndrome