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

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

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

A new type of extreme insulin resistance—type C insulin resistance syndrome and its clinical characteristics / 中华内分泌代谢杂志

We report on two cases of type C insulin resistance syndrome(TCIRS) admitted to the Department of Endocrinology, Peking Union Medical College Hospital from January 2000 to December 2020. Both patients presented with persistent hyperglycemia, low immunoreactive insulin, extreme insulin resistance, high insulin autoantibodies, high total insulin, and large insulin antibody pool. TCIRS is marked by extreme insulin resistance with ketoacidosis and respond to medium to high doses glucocorticoids rather than plasmapheresis.

Marcadores inmunológicos de diabetes tipo 1: análisis de 4.164 perfiles en un centro de salud de Chile / Analysis of 4, 164 type 1 diabetes antibody profiles in a Chilean health centre

Background: Previous studies have assessed the role of Type 1 diabetes (DM1) antibodies as predictors of the natural history of disease. Aim: To determine the frequency and combinations of positivity for DM1 antibodies in patients with DM1 and the relationship between antibody positivity and the age of the patient. To explore the relationship between history of insulin therapy or diabetic ketoacidosis (DKA) at the onset of the disease with antibody positivity in a subsample. Material and Methods: Data was gathered from every sample processed for DM1 antibodies in our laboratory between January 2015 and September 2019. Medical records from 84 patients who tested positive for at least one antibody were revised to study the relationship between insulin therapy or DKA at the onset of the disease with antibody positivity. Results: Forty percent of DM1 antibody tests were positive. Among positive tests, 1, 2, 3 or 4 DM1 antibodies were detected in 48%, 33%, 17% and 3% of cases, respectively. The likelihood of testing positive was inversely related with age for ICA, GAD, IA-2, ZnT8 and directlyproportionalforIAA (p= −0,012; −0,013; −0,014; −0,009; 0,005 respectively). An association between DKA at the onset of the disease and IA-2 positivity was observed (Odds ratio (OR) 5.38 95% confidence intervals (CI) 1.79 − 16.16, P < 0.01). No association was found between IAA positivity and history of insulin therapy (OR 2.25 95%CI 0.63 − 7.90, P = 0.2403). The results obtained from this study represent a novel local profile of DM1 antibody data, highlighting a relationship between antibody positivity and age.

Risk factors for postpartum glycometabolism in patients with gestational diabetes mellitus: a prospective study / 中国基层医药

Objective:To investigate the risk factors for postpartum glycometabolism in patients with gestational diabetes mellitus (GDM), providing a new idea for clinical prevention of type 2 diabetes mellitus.Methods:Pregnant women who underwent regular prenatal examination in Cixi People's Hospital, China between February 2019 and January 2020 were included in this prospective cohort study. The clinical data before and during pregnancy were collected. These pregnant women were followed up for 6 weeks and 6 months postpartum. Oral glucose tolerance test (OGTT) with 75 g of glucose was performed. The clinical end point was abnormal glucose metabolism. Kaplan-Meier (KM) univariate analysis and multivariate Cox regression analyses were used to analyze the risk factors for abnormal glucose metabolism postpartum in patients with GDM.Results:A total of 252 eligible patients were included in this study. Among them, 212 patients finished 6-week follow-up, and 149 patients finished 6-month follow-up. Among the 212 patients who finished 6-week follow-up postpartum, 87 (41.04%) patients had abnormal glucose metabolism, 3 (1.42%) patients had impaired fasting glucose, 66 (31.13%) had impaired glucose tolerance, and 18 (8.49%) patients had type 2 diabetes mellitus. Among the 149 patients who finished 6-month follow-up postpartum, there were 2 new patients with impaired fasting glucose, 11 new patients with impaired glucose tolerance, and 3 new patients with type 2 diabetes mellitus. Overweight before pregnancy [body mass index (BMI) ≥ 24 kg/m 2] and1-hour OGTT (≥ 10.1 mmol/L) were the independent risk factors for abnormal glucose metabolism postpartum in pregnant patients with GDM ( OR = 2.273, 2.462; P = 0.039, 0.023; 95% CI = 1.495-3.051, 1.684-3.240). The Matsuda indexes and 60-minute insulinogenic index in the normal glucose metabolism group were significantly higher than in the abnormal glucose metabolism group ( t = 7.184 and 2.011, both P < 0.05). Conclusion:The incidence of abnormal glucose metabolism in patients with GDM at 6 months postpartum remains high. Overweight before pregnancy [body mass index ≥ 24 kg/m 2] and 1-hour OGTT (≥ 10.1 mmol/L) are the independent risk factors for abnormal glucose metabolism postpartum in pregnant patients with GDM.

Effect of Berberine on endoplasmic reticulum stress and insulin resistance in skeletal muscle of metabolic syndrome rats and its mechanism / 中华老年医学杂志

Objective To investigate the effect of Berberine on insulin resistance and its mechanism in Otsuka Long-Evans Tokushima Fatty(OLETF) rats with metabolic syndrome(MS).Methods LETO(Long-evans Tokushima Otsuka)rats(the control group receiving standard normal diet,n=10)and diabetic OLETF rats(the MS group receiving high-fat diet for 24 weeks,n=30).Rats in the MS group were randomly divided into 3 subgroups(n=10,each subgroup).Each subgroup was gavaged with normal saline,high-dose Berberine(100 mg · kg-1 · d-1)and low-dose Berberine (50 mg · kg-1 · d-1) respectively,and the high-fat diet remained unchanged.After 6 weeks of berberine treatment,body weight,blood glucose and lipid metabolism parameters were determined.The oral glucose tolerance test(OGTT) and insulin tolerance test(ITT) were used to detect insulin resistance.Expression levels of the protein and mRNA of 78 kDa glucose-regulated protein (GRP7 8),Caspase-12 and CCAAT/enhancer-binding protein(C/EBP) homologous protein(CHOP) in skeletal muscles were detected by Western blot and RT-PCR.Results After Berberine treatment,the body weight,fasting plasma glucose,fasting insulin[(28.9 ± 2.0) mU/L,(31.5± 2.4) mU/L vs.(36.9 ± 4.7) mU/L],total cholesterol,triglycerides,and low-density lipoprotein cholesterol were decreased,while the high-density lipoprotein cholesterol(HDL-C) levels were increased in MS rats with high-dose berberine and low-dose berberine as compared with the control group (P ＜ 0.05) respectively.Berberine treatment could reduce the protein and mRNA expression levels of GRP78,Capase-12 and CHOP in the skeletal muscle of MS rats(P＜0.05).Conclusions Berberine may alleviate insulin resistance in rats with metabolic syndrome by reducing endoplasmic reticulum stress in skeletal muscle.

Effect of low-frequency electroacupuncture on pancreatic endocrine system in patients with simple obesity / 针灸推拿医学（英文版）

Objective:To observe different efficacies of low-frequency electroacupuncture (EA) on pancreatic endocrine system in male and female patients with simple obesity due to spleen deficiency-related dampness.Methods:A total of 80 simple obesity patients were assigned to a male group (n=37) and a female group (n=43). Both groups received a 30-minute low-frequency EA at Yinlingquan (SP 9), Sanyinjiao (SP 6), Zusanli (ST 36), Fenglong (ST 40), Quchi (LI 11), Tianshu (ST 25), Zhongwan (CV 12), Shuifen (CV 9), Qihai (CV 6) and Guanyuan (CV 4). The treatment was done once a day, and 10 times made up a course of treatment. Patients in both groups were treated for 2 courses. Then the changes in body mass index (BMI), serum insulin, insulin antibodies and leptin level in the two groups were observed and analyzed.Results:After treatment, the BMI, serum insulin, insulin antibodies and leptin levels were significantly reduced in both groups (P<0.01 orP<0.05); the BMI and serum insulin concentration were more significantly reduced in the male group than those in the female group (bothP<0.01); and the leptin level was more significantly reduced in the female group than that in the male group (P<0.01).Conclusion: EA can significantly regulate BMI and pancreatic endocrine system in both men and women with simple obesity; however, there is a gender difference: better effect for men in reducing BMI and serum insulin and better effect for women in reducing serum leptin level.

A clinical analysis of insulin antibody in type 2 diabetic patients / 中华内科杂志

This study was conducted to evaluate the relationship between serum insulin levels and the production of insulin antibody (IA) in type 2 diabetes (T2DM).A total of 647 T2DM were included.Among them,20.9％ patients were IA positive,who were elder and had a longer duration,lower BMI,a higher positive rate of glutamic acid decarboxylase antibody(GADAb) and higher serum insulin levels during an insulin secretion test.More patients were treated with insulin in IA positive group than in IA negative group (65.9％ vs 41.0％,P =0.000).Fasting serum insulin level was associated with occurrence of IA in all patients (OR =1.02,P =0.001) and insulin treated patients (OR =1.033,P =0.002).The cut-off point of fasting serum insulin level for predicting IA positive was 17.87 mIU/L (sensitivity 55.1％,specificity 89.0％).Exogenous insulin use is associated with the presence of IA.Fasting serum insulin level can be used as a predictor for the production of IA in insulin-treated patients.

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

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

Allergic reaction to recombinant human insulin

Insulin-induced allergy is a rare adverse drug reaction since the introduction of recombinant human insulin. However, recombinant insulin-induced allergy is still being reported in 0.1% to 2% of all patients treated with insulin. This allergic reaction varies from mild localized skin reactions to life-threatening anaphylaxis. It has been shown that one-third of insulin allergy cases is related to insulin itself and the remaining occur due to preservatives contained in the insulin preparations, such as protamine, zinc, or metacresol. This case report describes a 75-year-old woman with poorly controlled diabetes who experienced insulin allergy. She complained of urticaria with itching after the injection of insulin. Allergic skin tests showed positive responses to all available human insulin preparations, and specific IgE to human insulin was also detected, which suggested that her urticaria was developed by insulin itself. This is the first case of insulin allergy that was sensitive to all available human insulin preparations and confirmed by the presence of specific IgE to human insulin. It is important to remember that allergic reactions to insulin may be directly associated with adherence and can be the reason of poor glucose control.

Clinical Features and Causes of Endogenous Hyperinsulinemic Hypoglycemia in Korea

BACKGROUND: Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare. METHODS: To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital. RESULTS: Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 microIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis. CONCLUSION: The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Correlation between expression of resistin in adipose tissues and glycometabolism in rats with traumatic brain injury / 中华创伤杂志

Objective To investigate the expression pattern of resistin in subcutaneous adipose tissue and its effect on glycometabolism in rats with traumatic brain injury (TBI).Methods Fifty-six SD rats were randomly divided into TBI group (n =48) and control group (n =8) according to the random number table.mRNA and protein expressions of resistin in subcutaneous adipose tissue were detected with real-time PCR and Western-blot.Concentrations of serum insulin and serum fasting blood glucose were evaluated using the ELISA method and quantitative estimation of insulin sensitivity was performed.Indices measured and their correlations were statistically analyzed.Results Levels of the resistin,serum insulin and FBG were significantly higher in TBI group than in control group (P ＜ 0.05).Quantitative estimation of insulin sensitivity lowered in TBI group compared to control group (P ＜ 0.05).Single factor linear correlation analysis showed negative correlation between resistin expression and quantitative insulin sensitivity check index in TBI group (P ＜ 0.05).Conclusions Resistin is shown to have significant expression in subcutaneous adipose tissue and involve in glycometabolism.Obviously,resistin may play a significant role in insulin resistance after TBI in rats.

Observation on pioglitazone combined with repaglinide for treatment of external insulin antibody positive patients with type 2 diabetic nephropathy / 中国基层医药

Objective To observe the efficacy of pioglitazone combined with repaglinide in the treatment of external insulin antibody (IAb)-positive patients with type 2 diabetic nephropathy.Methods 44 cases with IAb positive diabetes nephropathy were divided into the treatment group (22 cases) and control group (22 cases).The treatment group moved gradually insulin to pioglitazone 15 mg once daily add repaglinide 1 mg three times daily oral and gradually adjustment dose.The control group continued to use insulin treatment,a total of 12 weeks.Before and after treatment,blood sugar,blood fat,glycosylated hemoglobin,etc were detected.Results Mter treatment,the blood glucose,glycosylated hemoglobin,urine albumin and urine creatinine ratio of the treatment group were significantly decreased (all P ＜ 0.01),the above indicators had statistically significant differences compared with the control group at the same period (P ＜ 0.05).Conclusion Pioglitazone combined with repaglinide is an effective method for treatment of IAb positive type 2 diabetic nephropathy.

Recurrent Insulin Autoimmune Syndrome Caused by alpha-Lipoic Acid in Type 2 Diabetes

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia caused by insulin autoantibodies in the absence of exogenous insulin administration. Some drugs containing sulfhydryl compounds are known to initiate the onset of IAS. A 67-year-old female who had diabetes for 5 years visited the outpatient clinic at our institution due to diabetic peripheral polyneuropathy. She was prescribed alpha-lipoic acid (ALA), which contains two sulfur atoms. Two weeks later, she complained of recurrent hypoglycemic symptoms. We detected a high level of insulin and high titers of insulin autoantibodies. Her human leukocyte antigen (HLA) genotype included the DRB1*0406 allele, which indicates a high level of susceptibility to IAS. She was treated with prednisolone. After this episode, she experienced two more hypoglycemic events after taking ALA for diabetic neuropathy in other hospitals. As ALA can be used to treat diabetic peripheral polyneuropathy, physician discretion is advised based on the possibility of IAS due to ALA in diabetic patients.

Recurrent Insulin Autoimmune Syndrome Caused by alpha-Lipoic Acid in Type 2 Diabetes

Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia caused by insulin autoantibodies in the absence of exogenous insulin administration. Some drugs containing sulfhydryl compounds are known to initiate the onset of IAS. A 67-year-old female who had diabetes for 5 years visited the outpatient clinic at our institution due to diabetic peripheral polyneuropathy. She was prescribed alpha-lipoic acid (ALA), which contains two sulfur atoms. Two weeks later, she complained of recurrent hypoglycemic symptoms. We detected a high level of insulin and high titers of insulin autoantibodies. Her human leukocyte antigen (HLA) genotype included the DRB1*0406 allele, which indicates a high level of susceptibility to IAS. She was treated with prednisolone. After this episode, she experienced two more hypoglycemic events after taking ALA for diabetic neuropathy in other hospitals. As ALA can be used to treat diabetic peripheral polyneuropathy, physician discretion is advised based on the possibility of IAS due to ALA in diabetic patients.

Unusually Elevated Serum Insulin Level in a Diabetic Patient during Recombinant Insulin Therapy

Herein, we report a case of unusually elevated serum insulin level as a result of increased anti-insulin antibody (IA)-bound insulin after continuous subcutaneous insulin infusion therapy. Detecting free insulin (unbound IAs) levels after polyethylene glycol pre-treatment could be useful to assess functional insulin levels in diabetic patients receiving insulin therapy. The E170 insulin assay can estimate total insulin (bound IAs and free insulin) levels, but it does not measure the levels of exogenous insulin analogues.

The Effects of Anti-insulin Antibodies and Cross-reactivity with Human Recombinant Insulin Analogues in the E170 Insulin Immunometric Assay / 대한진단검사의학회지

BACKGROUND: Insulin assays are affected by varying degrees of interference from anti-insulin antibodies (IAs) and by cross-reactivity with recombinant insulin analogues. We evaluated the usefulness of the E170 insulin assay by assessing IA effects and cross-reactivity with 2 analogues. METHODS: Sera were obtained from 59 type 2 diabetes patients receiving continuous subcutaneous insulin infusion and 18 healthy controls. Insulin levels were determined using an E170 analyzer. To investigate the effects of IAs, we performed IA radioimmunoassays, and analyzed the differences between directly measured insulin (direct insulin) and polyethylene glycol (PEG)-treated insulins (free, IA-unbound; total, IA-bound and unbound insulin). We performed in-vitro cross-reactivity tests with insulin aspart and insulin glulisine. RESULTS: In IA-positive patients, E170 free insulin levels measured using the E170 analyzer were significantly lower than the direct insulin levels. The mean value of the direct/free insulin ratio and IA-bound insulin, which were calculated as the difference between total and free insulin, increased significantly as endogenous IA levels increased. The E170 insulin assay showed low cross-reactivities with both analogues (< 0.7%). CONCLUSIONS: IAs interfered with E170 insulin assay, and the extent of interference correlated with the IA levels, which may be attributable to the increase in IA-bound insulin, and not to an error in the assay. The E170 insulin assay may measure only endogenous insulin since cross-reactivity is low. Our results suggest that the measurement of free insulin after PEG pre-treatment could be useful for beta cell function assessment in diabetic patients undergoing insulin therapy.

Relationship between benign prostatic hyperplasia and insulin resistance in elderly men / 中华老年医学杂志

Objective To explore the relationship between insulin resistance (IR) and benign prostatic hyperplasia (BPH) in elderly men. Methods All BPH outpatients in Geriatric department of the second Xiang Ya Hospital in Feb 2008 were recruited in this study. Bioche assays including insulin (FINS), prostate specific antigen (PSA), HbAlc, fasting plasma glucose, 2 hours postprandial blood glucose were performed and HOMA-IR were calculated. The blood pressure, body weight, height and waist circumference were measured, and the body mass index (BMI) was calculated. Prostate volume (PV) was measured by abdominal ultrasound, lower urinary tract symptoms (LUTS) was evaluated by International Prostate Symptom Score (IPSS) and inquired about the history of LUTS in detail. Results (1) HOMA-IR＞ 2.8 was diagnosed as insulin resistance (IR). The patients were divided into two groups: insulin sensitivity (IS) group (n=48) and IR group (n=20). The PV level was higher in IR group than in IS group [(61.1-32. 9) ml vs. (40.4±16.5)ml, P＜0. 05], there were no statistical differences in PSA [(3.3±2.3) μg/L vs. (2.91±1.3) μg/L, P＞0.05], the history of LUTS [(13.4±6.6)years vs. (8.7±6.0)years, P＞0.05], IPSS [(16.42±6.67)scores vs. (13. 29±7.09)scores, P＞0. 05] between the two groups. (2)According to BPH progressivity evaluation provided by MTOPS study (age≥62 years, PSA≥1. 6 μg/L, PV≥31 ml), the patients were divided into two groups: low progressive risk group (n= 30) and high progressive risk group (n= 38). The FINS and HOMA-IR levels were significantly higher in highprogressive risk group than in low progressive risk group (all P＜0. 01). (3)The PV was positively correlated with HOMA-IR level and FINS level (r= 0. 431, 0. 492, P＜0. 01). Conclusions IR exists in majority of elderly BPH patients, the degree of IR and relative high level of FINS are related to the enlargement of PV and the development of BPH.

A novel microtiter plate radioimmunoassay of insulin autoantibody / 中华核医学杂志

Objective Insulin autoantibody (IAA) is known to exist in sera of type 1 diabetes mellitus (T1DM) patients and pre-T1DM individuals. The aim of this study was to establish a novel microtiter plate radioimmunoassay (RIA) for IAA and evaluate its clinical value. Methods Diluted 125Ⅰ-insulin was mixed with 5 ul serum samples in a 96-well microtiter plate and then incubated for 72 h on an orbital plate shaker (4℃). The immunocomplexes were transferred to another protein a coated Millipore plate, and then the plate was washed with Tri-Buffered Saline Tween-20 (TBT) buffer. Counts per minute (CPM) was measured with liquid scintillation and luminescence counter. The positive cut-off point of IAA index was defined as ≥0.06 based on the 99-percentile of the distribution in 317 healthy individuals. The specificity and sensitivity of the assay were calculated from the samples provided by the fourth Diabetes Autoantibodies Standardization Program (DASP 2005). The IAA levels were determined in 71 T1 DM and 551 newly diagnosed type 2 diabetes (T2DM) patients, and 317 healthy controls. The t test, non-parametric test, x2 test and linear correlation analysis were performed on the data using SPSS 11.5 software. The concordance rate was estimated with Kappa value. Results (1) The optimized testing condition was described as 2×104 CPM of 125Ⅰ-insulin, 5 ul serum sample and slowly horizontal shaking for 72 h. (2) The intra-assay CV was 4.8%-8.9% and inter-assay CV was 6.4%-10.5%. Based on DASP 2005 samples, the specificity and sensitivity of the assay were 97% (97/100) and 50% (25/50), respectively. Ninety-six serum samples with different IAA levels were selected and tested to compare between our new method and a domestic IAA RIA kit. The results showed that the IAA indices from the two methods were positively correlated (r= 0.678, P<0.001). The concordance rate was 72.9 %(Kappa value=0.402). There were 25 samples with discordant results, which were positive for IAA titer using the corresponding microtiter plate RIA but negative using the novel RIA kit. (3) In TIDM group the positive rate of IAA was 19.7% (16/71), higher than the healthy controls (0.9%, x2=54.36, P<0.001). The subgroup of T1DM children (with 0-9 years) showed the highest IAA positive rate (55.6% ,x2=4.85, P<0.05). In T2DM group the frequency of IAA was 1.5% (8/551), which had no significant difference comparing with that of healthy controls (x2= 0.95, P >0.05). Conclusions Our proposed microtiter plate RIA method for IAA is highly sensitive and specific, likely to be feasible for clinical application. The frequency of IAA is high in children with T1DM.

Serum insulin immunoassays and relevant issues / 中华内分泌代谢杂志

Serum insulin immunoassay plays an important role in the investigation of glucose metabolic disorders. Insulin assay has undergone method innovations for 50 years. Diverse insulin molecular immunogenicity and multiform biological activities, in addition to the immunoassay complexity, make serum insulin assays practically interfered by the factors such as blood sample qualities, serum anti-insulin antibodies and immunological cross-reactivity. Meanwhile, lack of standardization has imposed obstacles in the comparative studies among different reference laboratories.

A case of autoimmune insulin syndrome / 대한내과학회지

Autoimmune insulin syndrome is characterized by a combination of fasting hypoglycemia, high total serum insulin concentrations, and the presence of autoantibodies to the native human insulin in serum. A healthy 69-year-old man developed spontaneous hypoglycemia after being given some medications for the common cold. His laboratory finding shows endogenous hyperinsulinism. Therefore, an insulinoma was suspected but the imaging study shows no mass lesion in the pancreas and the anti-insulin antibody titer was high(>100U/mL). He had no specific medication history except for a treatment of a current upper respiratory infection (URI). Among the URI medication, it was found that N-acetylcysteine contains a sulfhydryl group and could induce autoimmunization. The patient was treated with corticosteroid for 3 months. His anti-insulin antibody titer had decreased to normal level and has not shown any hypoglycemic episodes for more than one and a half years. We present this case with a review of relevant literature.