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

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

Analysis of clinical characteristics of insulin autoimmune syndrome and related literature review / 中国综合临床

Objective:A retrospective study was conducted to analysis the clinical characteristics of 7insulin autoimmune syndrome (IAS) patients.Methods:Clinical data were collected by searching the computerized database.Results:The male-female ratio of these seven patients was 4:3; age of the four patients was between 60-70 years old;two patients with the history of Hashimoto's disease. Of the seven cases, six wereexogenous IAS. The level of insulin was excessively high, the level of C-peptide was not low, and insulin auto-antibodies (IAA) were positive of all the seven patients. The lowest blood glucose of one patient was 4.2 mmol/L. The insulin to C-peptide molar ratios were >1 in five patients. Symptoms were relieved after discontinuing use of the suspicious drugs, small frequent meals, taking acarbose and metformin.Conclusions:IAS should not be easily excluded in patients without hypoglycemia record. For diabetes patients receiving insulin therapy, exogenous IAS might be mistaken as hypoglycemia induced by insulin overdose. The identification of the genotype might be meaningful in the diagnosing and prevention of IAS.

A case of insulin autoimmune syndrome which might be induced by Chinese herbal extracts / 中华内分泌代谢杂志

Insulin autoimmune syndrome ( IAS) is a rare type of hypoglycemia. Chinese herbal extract may induce IAS, which seems to be associated with some Chinese herb medicine ingredients of paste which contains sulfhydryl group. In order to attract the attention of the clinicians, we should raise awareness of the disease, and avoid unnecessary operation or serious adverse consequences. This paper reviewed domestic reports in lately 30 years of diagnosis and treatment of IAS, evaluated traditional Chinese medicine and traditional Chinese medicine compound preparations which contain sulfhydlyl group.

Clinical Pharmacists'Participation in Drug Treatment Analysis on 1 Case of Insulin Aspart-induced Autoimmune Hypoglycemia / 中国药师

Objective:To provide reference for clinical pharmacists' participation in treatment of drug-induced autoimmune hypo-glycemia. Methods:Clinical pharmacists participated in drug treatment of a case of insulin aspart-induced autoimmune hypoglycemia, analyzed treatment and provided suggestion and pharmaceutical care. Results:Clinical pharmacists' suggestion was accepted and the patient was cured and discharged from the hospital. Conclusion: Clinical pharmacists' participation could help doctors to make safe and effective medication, provide good pharmaceutical care and medication education for patients.

Comparison of the prevalence of islet autoantibodies according to age and disease duration in patients with type 1 diabetes mellitus

PURPOSE: This study investigated the prevalence of islet autoantibodies in children and adults with T1DM according to their age and the duration of disease. METHODS: We measured the levels of islet autoantibodies, including antiglutamic acid decarboxylase antibody (anti-GAD Ab), and combined these with anthropometric measurements and laboratory tests of 137 patients newly diagnosed with T1DM during the last 20 years. The subjects were subdivided into four groups according to their age at the onset of the disease. We then compared the prevalence of islet autoantibodies in the different age groups with the duration of disease. RESULTS: Among the 137 patients, 68.9% tested positive for islet autoantibodies (71.4% within 1 year; 67.7% after 1 year of the disease onset). Within 1 year of the onset of the disease, 66.3% of the patients were positive for the anti-GAD Ab, and 35.6% were positive for IAAs. The prevalence of islet autoantibodies was significantly higher in the prepubertal groups than in the postpubertal groups (80.0% vs. 58.3%). The rate of positive islet autoantibodies changed with the duration of disease, and it differed according to the type of autoantibody and the age of the patient. CONCLUSION: The rates of positive islet autoantibodies were significantly higher in younger than in older patients at the time of the diagnosis of the disease. The positive rates were significantly changed 1 year after the onset of the disease in the preschool and the children groups. So these findings suggest that we need to diagnose type 1B diabetes distinguished T2DM in aldolescent group, carefully.

Comparison of the prevalence of islet autoantibodies according to age and disease duration in patients with type 1 diabetes mellitus

PURPOSE: This study investigated the prevalence of islet autoantibodies in children and adults with T1DM according to their age and the duration of disease. METHODS: We measured the levels of islet autoantibodies, including antiglutamic acid decarboxylase antibody (anti-GAD Ab), and combined these with anthropometric measurements and laboratory tests of 137 patients newly diagnosed with T1DM during the last 20 years. The subjects were subdivided into four groups according to their age at the onset of the disease. We then compared the prevalence of islet autoantibodies in the different age groups with the duration of disease. RESULTS: Among the 137 patients, 68.9% tested positive for islet autoantibodies (71.4% within 1 year; 67.7% after 1 year of the disease onset). Within 1 year of the onset of the disease, 66.3% of the patients were positive for the anti-GAD Ab, and 35.6% were positive for IAAs. The prevalence of islet autoantibodies was significantly higher in the prepubertal groups than in the postpubertal groups (80.0% vs. 58.3%). The rate of positive islet autoantibodies changed with the duration of disease, and it differed according to the type of autoantibody and the age of the patient. CONCLUSION: The rates of positive islet autoantibodies were significantly higher in younger than in older patients at the time of the diagnosis of the disease. The positive rates were significantly changed 1 year after the onset of the disease in the preschool and the children groups. So these findings suggest that we need to diagnose type 1B diabetes distinguished T2DM in aldolescent group, carefully.

Insulin Autoimmune Syndrome with Diabetic Ketoacidosis / 임상당뇨병

Insulin autoimmune syndrome is characterized by spontaneous hypoglycemia, elevated insulin level and a high level of insulin autoantibodies without previous insulin exposure. Among the clinical manifestations of insulin autoimmune syndrome, diabetic ketoacidosis is extremely rare. A 72-year-old diabetic woman was hospitalized with diabetic ketoacidosis. She suffered repeated fasting hypoglycemia after treatment of the diabetic ketoacidosis. Here we describe this case of insulin autoimmune syndrome manifested as diabetic ketoacidosis followed by recurrent hypoglycemia with a review of the relevant literature.

A case of insulin autoimmune syndrome / 대한내과학회지

Insulin autoimmune syndrome is an uncommon cause of hypoglycemia. According to the type of antibody, it can be classified as caused by insulin or insulin receptor autoantibodies. Generally, insulin autoimmune syndrome develops following exposure to exogenous insulin or sulfhydryl medications, although insulin or insulin receptor antibody may also occur spontaneously. We treated a 54-year-old woman who developed spontaneous hypoglycemia. The patient had repeated hypoglycemia despite the infusion of dextrose solution. Her serum insulin, c-peptide, and insulin autoantibody were elevated, even during the hypoglycemic periods. Insulin receptor autoantibody and HLA-cw4/B62/DR4 were positive. After steroid and diazoxide treatment, the hypoglycemic symptoms improved gradually. No further hypoglycemic episodes occurred after tapering the medication over 1 year. We present a case of insulin autoimmune syndrome with positive insulin and insulin receptor autoantibodies.

A case of autoimmune hypoglycemia during treatment with anti-tuberculosis drugs / 대한내과학회지

Autoimmune hypoglycemia is characterized by insulin autoantibody, hyperinsulinemia and fasting hypoglycemia without previous insulin immunization. Negative results on the anatomic studies of the pancreas and an inability to reproduce hypoglycemia during a prolonged fast may be helpful in excluding insulinoma. Autoimmune hypoglycemia is self-limited disorder. We recently experienced a case of autoimmune hypoglycemia in a patient with insulin antibody, and the patient was without previous insulin injection therapy or any evidence of insulinoma, during treatment with anti-tuberculosis drugs. We present this case along with a review of the literature.

A Case of Autoimmune Hypoglycemia Complicated with Diabetic Ketoacidosis

Autoimmune hypoglycemia is characterized by hyperinsulinemia, fasting hypoglycemia, and the presence of insulin auto- antibodies without previous exposure to exogenous insulin. We experienced a case of autoimmune hypoglycemia without diabetes mellitus or any evidence of insulinoma. The insulin auto-antibody and insulin receptor auto-antibody were present. We diagnosed the patient as having autoimmune hypoglycemia and treated with glucocorticoid. After treatment, the hypoglycemic symptoms were resolved. However, four months later, the patient was readmitted with transient diabetic ketoacidosis. After recovery, he showed no signs of diabetes mellitus. We believe that insulin auto-antibodies may play a role in autoimmune hypoglycemia and diabetic ketoacidosis, but its role and mechanism are not precisely known. Further studies are needed to define the action mechanisms and the functions of insulin auto-antibodies: here we present case with a relevant literature.

Two Cases of Autoimmune Insulin Syndrome with Hypoglycemia / 대한내분비학회지

Autoimmune insulin syndrome is characterized by insulin autoantibody, hyperinsulinemia, and fasting hypoglycemia without previous insulin immunization. This syndrome shows discordant levels between immunoreactive insulin and C-peptide. Negative results of an anatomic study of the pancreas and an inability to reproduce hypoglycemia during a prolonged fast may be helpful in excluding insulinoma. Symptomatic hypoglycemia usually develops during an oral glucose tolerance test. This syndrome is a self-limited disorder. Recently, we experienced one case that developed symptomatic hypoglycemia during both the fasting & oral glucose tolerance test, and another that developed symptomatic hypoglycemia during the oral glucose tolerance test but not the fasting test. Hereby, we present these cases with a review of the literature.

Predictive value of combined determination of ICA、64KDAb and IAA in the first-degree relatives of type Ⅰ diabetics / 中国糖尿病杂志

Objective To study the predictive value of islet cell antibody (ICA),64KD protein antibody(64KDAb) and insulin auto-antibody (IAA) in the first-degree relatives of type 1 diabetics. Methods The determination of islet autoantibody distribution in type 1 diabetes patients,first-degree relatives without diabetes and normal individuals was made. Results The results revealed that ICA and 64KDAb positive rate in type I diabetes patients and their first-degree relatives was significantly higher than normal individuals. The positive rate of 64KDAb is higher than that of ICA and IAA. Conclusion These results suggest that 64KDAb's sensitivity is higher than ICA and IAA's,so 64KDAb is more valuable as the marker of predicting type 1 diabetes. The combined determination of ICA, 64KDAb and IAA might improve the value for predicting diabetes.

Predictive value of combined determination of ICA、64KDAb and IAA in the first-degree relatives of type I diabetics / 中国糖尿病杂志

Objective　To study the predictive value of islet cell antibody (ICA),64KD protein antibody(64KDAb) and insulin auto-antibody (IAA) in the first-degree relatives of type 1 diabetics.Methods　The determination of islet autoantibody distribution in type 1 diabetes patients,first-degree relatives without diabetes and normal individuals was made.Results　The results revealed that ICA and 64KDAb positive rate in type I diabetes patients and their first-degree relatives was significantly higher than normal individuals.The positive rate of 64KDAb is higher than that of ICA and IAA. Conclusion　These results suggest that 64KDAb's sensitivity is higher than ICA and IAA's,so 64KDAb is more valuable as the marker of predicting type 1 diabetes.The combined determination of ICA,64KDAb and IAA might improve the value for predicting diabetes.

Prevalence of Autoimmune Antibodies in Type I Diabetic Children and Their Siblings / 대한소아내분비학회지

Background:Insulin dependent diabetes mellitus(IDDM) is known to be a disease characterized by a deficiency of insulin caused by destruction of the pancreatic beta-cells. It has been suggested that the clinical and immunological characteristics of IDDM in Korean are different from those of Caucasian. This study was undertaken to investigate the clinical characteristics and the prevalence of autoimmune markers in type I diabetic children and their prediabetic siblings in Korea. METHODS:Insulin autoantibody(IAA), antiglutamic acid decarboxylase(Anti-GAD) antibody, thyroid autoantibodies such as antithyroid antibody(ATA) and antimicrosomal antibody(AMA), and rheumatoid facter(RF) in 54 type I diabetic children have been measured. Diabetic autoimmune antibodies were also measured in 48 siblings. RESULTS: 1)Clinical characteristics of type I diabetic children were that age of onset was 8.6+/-4.4 years, duration of diabetes was 4.1+/-3.3 years. C-peptide at onset of diabetes was fasting 0.7+/-0.5ng/ml, and postprandial 1.2+/-0.5ng/ml, and HbA1c was 12.5+/-4.3%. 2)The positivity of IAA and anti-GAD antibody of type I diabetic children was 74% and 50% respectively. ATA and AMA positivity of type I diabetic children was 3.7% and 5.6%. however RF was not detected at all. Among the diabetic siblings, 48 persons for anti-GAD antibody, 21 for IAA, 27 for ICA were measured but 1 case was positive for IAA. 3)Clinical characteristics of type I diabetic children were not specific different between IAA and anti-GAD antibody positivity. But the mean age of onset of type I diabetic children was younger in case of both positivity of IAA and anti-GAD antibody than both negativity(7.8 vs 11.4 years old, P<0.05). 4)A case in whose brothers are diagnosed as IDDM has shown that autoantibody of elder brother was positive in both IAA and anti-GAD antibody, and younger brother was also strongly positive in IAA. Another case in whose sisters were IDDM, has shown that, while elder sister was positive in IAA, younger sister strongly positive in both IAA and anti-GAD antibody. 5)In a case of identical twin brother, the elder is type I diabetic child and the younger is normal, elder brother's onset of age was 6 years and 8 months old, and titer of anti-GAD antibody was measured as strong positive. Both ICA and anti- GAD antibody were negative in normal younger brother. First phase insulin release in IV GTT and the insulin levels in oral GTT showed reduction from the normal level in normal brother, and repeat check up showed normal ranges but on-going study is needed under observation. CONCLUSION: The prevalence of autoantibody positivity of type I diabetic children of Korea in this study were IAA 74%, and anti-GAD antibody 50%. Cases with both IAA and anti-GAD antibody positive were shown to be earlier onset. Though titers of auto-antibody in IDDM twins, brothers and sisters were strongly positive, auto-antibodies in siblings of IDDM patients were detected only one case with IAA positive(0.47%). We suggest that the pathogenesis of IDDM in Korean is different from foreign countries in terms of prevalence of autoimmune antibodies and more numbers of diabetic siblings should be tested for further study.