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.
Autoantibodies ; Autoimmune Diseases ; Blood Glucose ; Diagnosis ; Humans ; Hyperinsulinism ; Hypoglycemia* ; Insulin ; Insulin Antibodies ; Insulinoma ; Korea ; Nesidioblastosis ; Pancreatectomy ; Plasma ; Prevalence ; Retrospective Studies

INTRODUCTIONInsulin resistance in latent autoimmune diabetes in adults (LADA) patients is controversial. The aim of this study was to evaluate insulin resistance and its related factors (metabolic syndrome parameters) among subjects with LADA and glutamic acid decarboxylase antibodies (GADA) negative diabetes, as well as the impact of these factors on insulin resistance.

MATERIALS AND METHODSGADA levels were investigated in 1140 diabetic patients aged between 30 and 70 years. Insulin resistance and metabolic syndrome parameters were assessed in LADA and GAD-negative diabetic patients by general linear model. In addition, the impact of metabolic syndrome factors on insulin resistance was assessed in LADA and glutamic acid decarboxylase (GAD)-negative diabetic patients.

RESULTSLADA was diagnosed in 33 subjects from 1140 Malaysian diabetic patients (prevalence = 2.9%). The results showed that LADA patients had higher insulin resistance and high density lipoprotein cholesterol (HDLc) (P = 0.003 and 0.00017 respectively) and lower body mass index (BMI) (P = 0.007) compared to GAD-negative diabetic patients. The HDLc was associated with decreased insulin resistance in LADA patients (P = 0.041), whereas HbA1c, triacylglycerides (TG) and waist were associated with increased insulin resistance in GAD-negative diabetic patients (P = 3.6×10⁻¹², 1.01×10⁻⁵ and 0.004 respectively). HbA1c was highly associated with decreasing β-cell function in both LADA (P = 0.009) and GAD-negative diabetic subjects (P = 2.2×10⁻²⁸).

CONCLUSIONInsulin resistance is significantly higher in LADA than GAD-negative diabetic Malaysian subjects.

Adult ; Antibodies ; blood ; Diabetes Mellitus, Type 1 ; blood ; metabolism ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Insulin Resistance ; Male ; Middle Aged

OBJECTIVETo observe effects of acupuncture and diet on insulin resistance (IR) and to probe the mechanism.

METHODSForty SID rats were equally divided into 5 groups: blank group (group I), model group I (group II), model group II (group III), acupuncture group I (group IV) and acupuncture group II (group V). The groups II, III, N and V were fed with high-fat-sugar-salt forage to made IR model, then the groups I, III and V were fed with normal forage, and the groups II and IV with the high-fat-sugar-salt forage, and the acupuncture groups IV and V received acupuncture treatment. Two weeks later, the fasting blood glucose (FBG), plasma insulin (INS), insulin sensitivity index (ISI), INS antibody and tumor necrosis factor alpha (TNF-alpha) were detected.

RESULTSAs compared with group I, FBG and INS increased, ISI decreased in the group II (all P < 0.01); as compared with the group II , FBG and INS decreased (all P < 0.01) and ISI increased (P < 0.05, P < 0.01) in the group [II, IV, V; no case with INS antibody (+) in all groups; TNF-alpha in the group II increased compared with that of the group I (P < 0.01), and TNF-alpha in the group III, IV, V decreased compared with that of group II (P < 0.01).

CONCLUSIONAcupuncture exerts a reversal effect on insulin resistance, and diet can promotes this effect. The mechanism is carried out possibly through decreasing the secretion of TNF-alpha.

Acupuncture Therapy ; Animals ; Insulin Antibodies ; blood ; Insulin Resistance ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

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.
Diabetic Ketoacidosis/*complications/*immunology/pathology ; Human ; Hypoglycemia/*complications/*immunology/pathology ; Insulin Antibodies/*blood ; Magnetic Resonance Imaging ; Male ; Middle Aged

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.
Adult ; Aged ; Aged, 80 and over ; Cross Reactions ; Diabetes Mellitus, Type 2/blood/immunology ; Female ; Humans ; Infusions, Subcutaneous ; Insulin/analogs & derivatives/*blood/chemistry/immunology ; Insulin Antibodies/*blood ; Male ; Middle Aged ; Polyethylene Glycols/chemistry ; Radioimmunoassay/instrumentation/*methods ; Recombinant Proteins/analysis/immunology/metabolism

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

BACKGROUND/AIMS: We conducted this study to identify the risk factors for finding gallbladder polyps (GBP) in Korean subjects during health screening, and to determine the nature of the association between the presence of metabolic syndrome (MS) and the development of GBP. METHODS: A total of 1,523 subjects were enrolled, comprising 264 with GBP (81 women and 183 men) and 1,259 controls (696 women and 563 men with normal GB). Body mass index (BMI), waist circumference (WC), blood pressure (BP), insulin, fasting blood sugar (FBS), lipids, liver enzymes, hepatitis B antigens (HBs Ag), and hepatitis C antibodies (HCV Ab) were measured. MS was considered to be present when three or more of the NCEP-ATPIII (National Cholesterol Education Program-Adult Treatment Panel III) criteria were satisfied. Insulin resistance was calculated by homeostasis model assessment of insulin resistance (HOMA-IR). Independent risk factors were analyzed by logistic regression analysis. RESULTS: Univariate analysis revealed that the risk factors for GBP were age, sex, WC, smoking history, BP, BMI, FBS, serum lipids, HOMA-IR score, and MS. Multivariate logistic regression analysis revealed that the risk factors for GBP were presence of MS (Odds Ratio (OR)=2.35, 95%Confidence Interval (CI)=1.53-3.60), being male (OR=2.34, 95%CI=1.72-3.18), HOMA-IR score>2.5 (OR=1.64, 95%CI=1.19-2.26), and higher WC (OR=1.4, 95%CI=1.05-1.88). MS was present in 20.8% and 5.9% of GBP patients and controls, respectively, and was the highest risk factor for GBP. CONCLUSIONS: MS, male, insulin resistance, and abdominal obesity are probably risk factors for GBP, with MS appearing to be strongly associated with GBP in Koreans.
Blood Glucose ; Blood Pressure ; Body Mass Index ; Cholesterol ; Education ; Fasting ; Female ; Gallbladder* ; Hepatitis B Antigens ; Hepatitis C Antibodies ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Liver ; Logistic Models ; Male ; Mass Screening* ; Obesity, Abdominal ; Polyps* ; Risk Factors* ; Smoke ; Smoking ; Ultrasonography* ; Waist Circumference

A novel subtype of type 1B diabetes with rapid onset and no evidence of autoimmunity has been recently proposed as fulminant type 1 diabetes. The pathogenesis of fulminant type 1 diabetes has not been fully understood. We report a case of fulminant type 1 diabetes with diabetic ketoacidosis. A 31-year-old male was referred to our hospital because of high plasma glucose level and acidosis. Laboratory findings were rendering a diagnostic picture of diabetic ketoacidosis with acute renal insufficiency. While there was high plasma glucose, normal HbA1c and other laboratory findings suggested a very recent onset of diabetes mellitus. A test to detect antibodies to islet cell antigen IA-2 was negative, but those of glutamic acid decarboxylase (GAD) was weakly positive. The patient successfully recovered without any serious complication after fluid and insulin based management.
Acidosis ; Acute Kidney Injury ; Adult ; Antibodies ; Autoimmunity ; Blood Glucose ; Diabetes Mellitus ; Diabetes Mellitus, Type 1* ; Diabetic Ketoacidosis ; Glutamate Decarboxylase ; Humans ; Insulin ; Islets of Langerhans ; Male

BACKGROUND: Intraperitoneal (IP) insulin administration in peritoneal dialysis (PD) patients has several advantages, including the prevention of major fluctuations of blood glucose and hyperinsulinemia and the formation of insulin antibodies. However, the effects of IP insulin on dialysis efficacy, ultrafiltration and the ultimate peritoneal function have not been investigated. Ultrafiltration failure is the most important functional abnormality during PD, which is now known to be associated with increased peritoneal vascular remodeling and vascular endothelial growth factor (VEGF) synthesis. There are also some evidences of insulin-induced vascular remodeling in other organs. Therefore, we investigated whether insulin regulates VEGF synthesis in human peritoneal mesothelial cells (HPMC), and also compared its signaling pathway to the glucose-induced signaling for VEGF synthesis. METHODS: The expression of VEGF mRNA and protein was evaluated in HPMC stimulated with insulin (0.1-100 mM) and high glucose (30 mM); the evaluation was done by RT-PCR and ELISA with an examination of related signal transduction system, including p38, p42/44 MAPkinase, protein kinase C (PKC) and PI3 kinase (PI3K). RESULTS: Insulin (10 nM) increased VEGF mRNA and protein synthesis of the HPMCs from 3 and 24 hours, respectively. Pretreatment with inhibitors of p38 MAPK (SB203580, 10 micrometer), p42/p44 MAPK (PD98059, 50 micrometer) or PI3K (wortmannin, 50 nM) suppressed the insulin-induced VEGF synthesis, whereas there was no effect with PKC inhibition. High glucose (D-glucose, 30 mM)-induced increase in VEGF synthesis was inhibited by pretreatment with inhibitors of p38, p42/p44 MAPK or PKC. CONCLUSIONS: Insulin per se can induce VEGF synthesis from HPMC via differential mechanisms and signaling pathways from high glucose, which may be related to the later development of peritoneal angiogenesis and ultrafiltration failure. The long-term effects of IP insulin on peritoneal function need to be evaluated in relevant animal models and human subjects.
Blood Glucose ; Dialysis ; Enzyme-Linked Immunosorbent Assay ; Glucose ; Humans ; Hyperinsulinism ; Insulin Antibodies ; Insulin* ; Models, Animal ; p38 Mitogen-Activated Protein Kinases ; Peritoneal Dialysis ; Phosphotransferases ; Protein Kinase C ; RNA, Messenger ; Signal Transduction ; Ultrafiltration ; Vascular Endothelial Growth Factor A*

BACKGROUND: Remnant lipoproteins are the lipolytic degradation product of the triglyceride-rich lipoproteins produced by the liver (very-low-density lipoprotein cholesterol) and intestine (chylomicrons). Recent studies have demonstrated a correlation between remnant lipoproteins and cardiovascular risk. Our study assessed the relationship between obesity and remnant lipoproteins and evaluated the factors related to remnant lipoprotein in children and adolescents. METHODS: Body mass index (BMI), waist circumference, systolic and diastolic blood pressures, body fat mass, total abdominal fat, visceral and subcutaneous fat areas, total cholesterol, triglyceride (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C) and remnant lipoprotein cholesterol (RLP-C) were measured in 135 children and adolescents (67 boys and 68 girls). Plasma RLP fractions were isolated using an immunoaffinity gel containing specific anti-apoB-100 and anti-apoA-I antibodies. The subjects were divided into three groups: the low (< 50 percentile), mid (50~84 percentile), and high (> or = 85 percentile) BMI groups. RESULTS: RLP-C was significantly correlated with age, sex, BMI, waist circumference, systolic and diastolic blood pressures, visceral and subcutaneous fat areas, visceral fat area to subcutaneous fat area ratio (VSR), total cholesterol, TG, HDL-C, apoB, and HOMA-IR. From a multivariate regression analysis, TG (beta = 0.928, P < 0.001) was found to be independently correlated with RLP-C. After excluding TG as an independent variable, a multivariate regression analysis revealed that the HOMA-IR (beta=0.231, P=0.007) and systolic blood pressure (beta=0.169, P=0.046) were independently associated with RLP-C. CONCLUSION: RLP-C was significantly higher in obese children and adolescents. TG, systolic blood pressure, and insulin resistance were related to remnant lipoproteins.
Abdominal Fat ; Adipose Tissue ; Adolescent* ; Antibodies ; Apolipoproteins B ; Blood Pressure ; Body Mass Index ; Child ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Dyslipidemias ; Humans ; Insulin Resistance ; Intestines ; Intra-Abdominal Fat ; Lipoproteins* ; Liver ; Obesity ; Pediatric Obesity* ; Plasma ; Subcutaneous Fat ; Triglycerides ; Waist Circumference