Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state. MATERIALS AND METHODS: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques. RESULTS: Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively. CONCLUSIONS: Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.

External Beam Radiotherapy in Advanced Pheochromocytoma and Paraganglioma: An Observation of a Rare Abscopal Effect.

Metastatic pheochromocytoma and paraganglioma are incurable, and effective treatment of systemic symptoms resulting from catecholamine excess and local symptoms from tumor growth are crucial to prolong survival and improve quality of life. We report the first case of metastatic pheochromocytoma wherein external beam radiotherapy (EBRT) demonstrated efficacy in both target and nontarget lesions, demonstrating the "abscopal effect." EBRT reduced tumor volume and catecholamine secretion and improved catecholamine excess-related complications, including glycemic control. EBRT is an effective treatment option for metastatic pheochromocytoma and paraganglioma because of its minimal invasiveness, safety, and potential for the rare abscopal effect.

Graft failure after allogeneic islet transplantation in a patient with type 1 diabetes and a high anti-glutamic acid decarboxylase antibody titer.

Pancreatic islet transplantation is a ß-cell replacement therapy for people with insulin-deficient diabetes who have difficulty in glycemic control and suffer from frequent severe hypoglycemia. However, the number of islet transplantations carried out is still limited in Asia. We report a case of allogeneic islet transplantation in a 45-year-old Japanese man with type 1 diabetes. Although the islet transplantation was successfully carried out, graft loss was observed on the 18th day. Immunosuppressants were used in accordance with the protocol, and donor-specific anti-human leukocyte antigen antibodies were not detected. Autoimmunity relapse was also not observed. However, the patient had a high titer of anti-glutamic acid decarboxylase antibody from before the islet transplantation, and autoimmunity might thus have affected the ß-cells in the transplanted islet. The evidence is still scarce to reach conclusions, and further data accumulation is required to enable proper patient selection before islet transplantation.

Living and working environments are important determinants of glycemic control in patients with diabetes during the COVID-19 pandemic: A retrospective observational study.

AIM: To investigate (1) the association of lifestyle changes and living and working conditions with glycemic control and (2) whether treatment was intensified appropriately in patients with diabetes under the first COVID-19 state of emergency in Japan. MATERIALS AND METHODS: A total of 321 participants were included. Participants completed a questionnaire regarding lifestyle changes, including diet, physical activity, and living and working conditions during the COVID-19 pandemic. The change in hemoglobin A1c (HbA1c) levels was estimated before (June 1, 2019 to August 31, 2019) and during (June 1, 2020 to August 31, 2020) the pandemic. Factors associated with changes in HbA1c levels were examined by multiple linear regression analysis. The proportion of patients who received treatment intensification for diabetes was compared between before and during the pandemic. RESULTS: There was no significant change in HbA1c levels before the pandemic and during the pandemic (7.13 ± 0.98% vs 7.18 ± 1.01%, P = 0.186). Teleworking (estimate 0.206, P = 0.004) and living with a dog (estimate -0.149, P = 0.038) were significantly associated with changes in HbA1c levels after adjusting for covariates. There was no significant difference in the proportion of patients who received treatment intensification for diabetes during the pandemic and before the pandemic in either the elderly or non-elderly patients. CONCLUSIONS: Overall glycemic control did not worsen during the pandemic. Nonetheless, environmental factors, including telework, were found to influence glycemic control in patients with diabetes. Further studies are needed to clarify whether the COVID-19 pandemic could affect treatment intensification for diabetes.

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist: A case report.

RATIONALE: Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA. PATIENT CONCERNS: A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day. DIAGNOSIS: She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5. INTERVENTIONS: The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated. OUTCOMES: Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy. LESSONS: GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.