Zinc transporter 8 (ZnT8) is an important candidate antigen for type Ⅰ diabetes. The autoantibody detection kit based on ZnT8 can be used to help diagnose type Ⅰ diabetes, and the related products have been launched in Europe and the United States. Since the recombinant production system of active ZnT8 has not been established in China, this key raw material is heavily dependent on imports. We used Saccharomyces cerevisiae to carry out the recombinant expression of ZnT8. First, multiple antigenic forms of ZnT8 were designed as C-terminal haploid (C), C-terminal diploid (C-C), and N-terminal and C-terminal concatemers (N-C). The proteins were expressed, purified and tested for antigenicity by bridging-type ELISA. The serum of 13 patients with type Ⅰ diabetes and the serum of 16 healthy volunteers were detected. C, N-C, and C-C proteins had similar detection rates, which were 53.8% (7/13), 61.5% (8/13) and 53.8% (7/13). The specificity of the three groups was 100% (16/16). The detection value on positive samples P3, P4, and P8 increased by more than 90%, indicating better serum antibody recognition ability. Finally, N-C protein was selected for further serum sample testing, and the test results were characterized by receiver operating characteristic (ROC) curve for sensitivity and specificity. Compared with imported gold standard antigen, the sensitivity was 76.9% (10/13) and the specificity was 87.5% (14/16). There was no significant difference in the sensitivity of the method, but the specificity needed to be improved. In conclusion, the ZnT8 N-terminal and C-terminal concatemer protein developed based on S. cerevisiae expression system is expected to be a key alternative raw material in the development of in vitro diagnostic reagents for type Ⅰ diabetes.
Antigens ; Autoantibodies ; Diabetes Mellitus, Type 1/diagnosis* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Saccharomyces cerevisiae/genetics* ; Zinc Transporter 8/genetics*

Adult ; Diabetes Mellitus, Type 1/therapy* ; Diabetes Mellitus, Type 2/diagnosis* ; Genetic Predisposition to Disease ; Glucose Intolerance ; Humans ; Islets of Langerhans ; Latent Autoimmune Diabetes in Adults/therapy*

Asian Continental Ancestry Group ; Child ; Consensus ; Diabetes Mellitus, Type 1 ; diagnosis ; therapy ; Humans ; Medicine, Chinese Traditional ; Practice Guidelines as Topic

In recent years, reports of diabetes mellitus (DM) cases that do not fit the traditional classification system have increased in prevalence. While insulin deficiency appears as type 1 DM (T1DM), the new type also has the clinical features of type 2 DM (T2DM); as such, this new type of DM is called ketosis-prone diabetes (KPD) and is correlated with findings of severe hyperglycemia and ketoacidosis. To provide a clear, clinical classification of DM, new classification systems are being studied. Among these, the Aβ system demonstrates the highest sensitivity and specificity in predicting clinical features and prognosis. We report 2 cases of KPD in Korean pediatric patients. The first patient was referred while in a state of diabetic ketoacidosis (DKA) and was considered to have T1DM. However, their blood glucose was well-controlled even with small doses of insulin, and the treatment was able to be changed to metformin therapy. The second patient seemed to be a typical case of T2DM because of his obesity and strong family history. However, blood glucose was not well-controlled with a regular diet, and ketosis occurred. After performing a glucagon stimulation test, both patients showed different clinical features that were finally diagnosed as type A-β+ KPD. The rapid and accurate diagnosis of KPD can reduce the duration of inappropriate insulin use and improve patients' quality of life. Further, the treatment of KPD children should be individualized according to each patient's lifestyle to preventing recurrent DKA.
Adolescent ; Blood Glucose ; Child ; Classification ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetic Ketoacidosis ; Diagnosis ; Diet ; Glucagon ; Humans ; Hyperglycemia ; Insulin ; Ketosis ; Life Style ; Metformin ; Obesity ; Prevalence ; Prognosis ; Quality of Life ; Sensitivity and Specificity

Treatment-induced neuropathy (TIN) in diabetes is an acute and painful yet completely reversible small fiber neuropathy precipitated by a rapid improvement in glycemic control. TIN is rare in children. A 16-year-old girl developed symmetrical painful neuropathy of the foot, autonomic neuropathy, and retinopathy 5 weeks after the diagnosis of type 1 diabetes. All causative workups were negative except for a drop-in hemoglobin A(1c) (HbA(1c)) from 17.4% to 7%, which fit with a diagnosis of TIN. Following symptomatic management, her neuropathy and retinopathy completely resolved in 2 months. Currently, she is 18 years old and doing well (HbA(1c), 7.4%) without any recurrence of TIN. TIN should be suspected in any child presenting with recent-onset type 1 diabetes and acute onset neuropathy. Our case represents an unreported scenario of the rapid progression in TIN. Awareness among clinicians about this rare but completely reversible condition is necessary to ensure proper management and adherence to glycemic control.
Adolescent ; Child ; Diabetes Mellitus, Type 1 ; Diagnosis ; Erythromelalgia ; Female ; Foot ; Humans ; Recurrence ; Tin

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.
Blood Pressure ; Diabetes Mellitus, Type 2 ; Diagnosis ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Korea ; Obesity ; Overweight

PURPOSE: To investigate the risk factors of diabetic nephropathy in patients with diabetic retinopathy requiring panretinal photocoagulation (PRP) and the visual prognosis. METHODS: A retrospective review of electronic medical records was conducted at Seoul St. Mary's Hospital, comprising 103 patients with type 2 diabetes mellitus and diabetic retinopathy who underwent PRP from 1996 to 2005. Patients with type 1 diabetes mellitus, non-diabetic renal disease, non-diabetic retinal disease, visually significant ocular disease, high-risk proliferative diabetic retinopathy, and advanced diabetic retinopathy were excluded. The patients were divided into three groups: no nephropathy (group 1, n = 45), microalbuminuria (group 2, n = 16), and advanced nephropathy (group 3, n = 42). Duration of diagnosis of retinopathy and nephropathy, glycosylated hemoglobin, visual acuity, complications, and treatment history were investigated. RESULTS: The mean glycosylated hemoglobin of group 3 (8.4 ± 1.2) was higher than that of group 1 (7.7 ± 1.0) or group 2 (7.7 ± 1.0) (p = 0.04). Mean interval from PRP to diagnosis of nephropathy was 8.8 ± 6.0 years in group 2 and 8.7 ± 4.9 years in group 3. The significant decrease in visual acuity in group 3 (28 eyes, 35.9%) was significantly higher than that in group 1 (15 eyes, 18.1%, p = 0.01) or group 2 (6 eyes, 20.7%, p = 0.03). Only vitreous hemorrhage showed a significantly higher incidence in groups 2 and 3 than in group 1 (p = 0.02). Multivariate regression analysis revealed that female sex and lower glycosylated hemoglobin were significantly associated with a protective effect on development of nephropathy. CONCLUSIONS: In the clinical setting, many patients with PRP-requiring diabetic retinopathy develop nephropathy an average of 8 to 9 years after PRP. Male sex and higher glycosylated hemoglobin could be risk factors of nephropathy.
Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Diabetic Retinopathy ; Diagnosis ; Electronic Health Records ; Female ; Hemoglobin A, Glycosylated ; Humans ; Incidence ; Light Coagulation ; Male ; Prognosis ; Retinal Diseases ; Retrospective Studies ; Risk Factors ; Seoul ; Visual Acuity ; Vitreous Hemorrhage

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

PURPOSE: Low vitamin D level is common in adults with diabetes mellitus (DM). We assessed vitamin D level and its associated factors in Korean youth with type 1 DM. METHODS: Type 1 DM cases (n=85) and healthy controls (n=518) aged < 20 years were included and grouped into 3 categories according to vitamin D level: deficiency ( < 20 ng/mL), insufficiency (20–30 ng/mL), or sufficiency (≥30 ng/mL). RESULTS: The mean serum vitamin D level was significantly lower (21.6±8.5 ng/mL vs. 28.0±12.0 ng/mL, P < 0.001) and vitamin D deficiency prevalence was significantly higher (48% vs. 26%, P < 0.001) in type 1 DM cases than in healthy controls. Logistic regression analysis revealed that type 1 DM cases were more likely to have vitamin D deficiency (P=0.004), independent of sex, age, and body mass index. Type 1 DM cases with vitamin D deficiency/insufficiency were mainly diagnosed in winter (November to April) (P=0.005), and the duration of diabetes was longer than in those with vitamin D sufficiency (P=0.046). However, season of diagnosis, duration of diabetes, prescribed daily insulin dose, and glycosylated hemoglobin and C-peptide levels were not associated with 25-hydroxyvitamin D (25(OH)D) level in type 1 DM cases after adjustment for other factors. CONCLUSIONS: We recommend assessment of serum 25(OH)D level in type 1 DM cases and to treatment if findings indicate insufficiency. Further studies investigating the mechanisms underlying vitamin D deficiency in youth with type 1 DM are needed.
Adolescent* ; Adult ; Body Mass Index ; C-Peptide ; Case-Control Studies ; Child* ; Diabetes Mellitus ; Diabetes Mellitus, Type 1* ; Diagnosis ; Hemoglobin A, Glycosylated ; Humans ; Insulin ; Logistic Models ; Prevalence ; Seasons ; Vitamin D ; Vitamin D Deficiency

Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.
Adult* ; Autoantibodies ; C-Peptide ; Diabetes Complications ; Diabetes Mellitus, Type 1* ; Diabetes Mellitus, Type 2 ; Diagnosis ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptide 1 ; Humans ; Hypoglycemic Agents ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Phenotype ; Population Characteristics