Association of biomarkers and Barthel Index with occurrence of age-related adverse health outcomes in individuals with diabetes.

AIMS/INTRODUCTION: The clinical significance of age-related biomarkers in patients with diabetes has not been fully elucidated. In this study, we aimed to establish models to predict the progression of aging in patients with diabetes using biomarkers. MATERIALS AND METHODS: This single-center, retrospective cohort study included 115 Japanese patients with diabetes aged ≥60 years. Age-related adverse health outcomes were defined as emergency hospitalization, any increase in the level of nursing care certification, admission to a nursing home or death. The associations of age-related biomarker levels (adiponectin, growth differentiation factor 15 [GDF15], C-X-C motif chemokine ligand 9 and apelin) and clinical indicators with age-related adverse health outcomes were evaluated. Factors that predominantly influenced the occurrence of age-related adverse health outcomes were explored using the Cox proportional hazards model. RESULTS: The mean age of the 115 participants was 73 years, 50.6% were men, the mean body mass index and hemoglobin A1c level were 25.3 kg/m2 and 9.79%, respectively. There were 26 age-related adverse health outcomes during the study period (median 1.93, range 0-4.65 years). In a model combining clinical indicators and biomarkers, including the Barthel Index, GDF15 and adiponectin, the occurrence of age-related adverse health outcomes was found to be significantly associated with GDF15 and Barthel Index. The group with both GDF15 and adiponectin levels higher than the median proved to be significantly higher than the group with both lower. CONCLUSIONS: The measurement of GDF15 and adiponectin levels and the Barthel Index might be useful for predicting age-related adverse health outcomes in patients with diabetes.

A sensor-augmented pump with a predictive low-glucose suspend system could lead to an optimal time in target range during pregnancy in Japanese women with type 1 diabetes.

Introduction: It is challenging for pregnant women with type 1 diabetes to maintain optimum glucose level to attain good neonatal outcomes. This study evaluated the efficacy of sensor-augmented insulin pump (SAP) with a predictive low-glucose suspend (PLGS) system in pregnant Japanese women with type 1 diabetes. Materials and methods: SAP with PLGS was used in 11 of the 22 women with type 1 diabetes who delivered between 2011 and 2021 at the two medical institutions in Japan. Glucose management, insulin delivery suspension time (IST) and neonatal outcomes were retrospectively studied. Results: In SAP with PLGS cases (n = 11), average glycated hemoglobin levels were < 6.5% throughout the pregnancy, and the time in range (TIR, 63-140 mg/dl) was > 70% in the second and third trimesters. PLGS was safely used without inducing ketoacidosis. Positive correlation was observed between IST and TIR (r = 0.62, p < 0.01). Negative correlation was observed between IST and time below range (TBR) (r = - 0.40, p = 0.02), and IST and time above range (TAR) (r = - 0.45, p = 0.01). Total daily insulin dose was adequately increased without increasing hypoglycemia. There was only one heavy-for-date HFD) infant among the 11 newborns in SAP with PLGS cases. In cases without SAP (n = 11), target glycemic levels were difficult to achieve and there were 5 HFD infants among the 11 newborns. Conclusion: SAP with PLGS was safely and effectively used in pregnant women with type 1 diabetes to achieve target glucose levels without increasing the risk of hypoglycemia, which may have led to good neonatal outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00716-7.

Correction: New diagnostic criteria (2023) for slowly progressive type 1 diabetes (SPIDDM): Report from Committee on Type 1 Diabetes in Japan Diabetes Society (English version).

[This corrects the article DOI: 10.1007/s13340-023-00679-1.].

A single-center retrospective study on the clinical features of thyrotoxic periodic paralysis.

PURPOSE: Thyrotoxic periodic paralysis (TPP) is characterized by muscle paralysis and significant intracellular potassium movement resulting in hypokalemia. Since TPP is a rare condition, only a few studies have explicated the clinical characteristics of patients with this disease. This study aimed to elucidate the clinical characteristics of patients with TPP by comparing them with those with thyrotoxicosis without paralysis (non-TPP) and sporadic periodic paralysis (SPP). METHODS: This was a single-center retrospective cohort study. Clinical data of patients with hyperthyroidism (n = 62) or periodic paralysis (n = 92) who were emergently admitted to our hospital was extracted from the electronic medical records and analyzed. RESULTS: All patients in the TPP group (15 males and 2 females) had Graves' disease, with 14 being newly diagnosed. The average serum potassium level on admission was 2.3±0.75 mEq/L. No significant correlation was observed among serum potassium level, amount of potassium required for normalization, and thyroid hormone levels. The TPP group showed significantly younger age, higher male ratio and body mass index (BMI), and lower serum potassium and phosphorus levels than the non-TPP group, which comprised 36 patients with Graves' disease. No significant differences were observed between the TPP and SPP (n = 11) groups in terms of age, sex, BMI, serum electrolyte levels, potassium requirement for normalization, and recovery time. MAIN CONCLUSIONS: Considering that most patients with TPP have undiagnosed Graves' disease, distinguishing TPP from SPP based on clinical information and course alone is difficult in emergency settings. Therefore, for early detection and launch of specific treatment of Graves' disease, screening for thyroid hormone and anti-thyroid stimulating hormone receptor antibody levels is necessary when treating patients with periodic paralysis.

Immunohistochemical Profiling of SSTR2 and HIF-2α with the Tumor Microenvironment in Pheochromocytoma and Paraganglioma.

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, p = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, p = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.

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.

New diagnostic criteria (2023) for slowly progressive type 1 diabetes (SPIDDM): Report from Committee on Type 1 Diabetes of the Japan Diabetes Society (English version).

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for 'a definitive diagnosis of SPIDDM': (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement for insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and the presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity <0.6 ng/mL) at the last observed point in time. When a patient fulfills only (1) and (2), but not (3), he/she is diagnosed with 'SPIDDM (probable)' because the diabetes is non-insulin-dependent type.

New diagnostic criteria (2023) for slowly progressive type 1 diabetes (SPIDDM): Report from Committee on Type 1 Diabetes in Japan Diabetes Society (English version).

The diagnostic criteria for slowly progressive type 1 diabetes (slowly progressive insulin-dependent diabetes mellitus; SPIDDM) have been revised by the Committee on Type 1 Diabetes of the Japan Diabetes Society. All of the following three criteria must be met for "a definitive diagnosis of SPIDDM": (1) presence of anti-islet autoantibodies at some point in time during the disease course; (2) absence of ketosis or ketoacidosis at the diagnosis of diabetes with no requirement of insulin treatment to correct hyperglycemia immediately after diagnosis in principle; and (3) gradual decrease of insulin secretion over time, with insulin treatment required at more than 3 months after diagnosis, and presence of severe endogenous insulin deficiency (fasting serum C-peptide immunoreactivity < 0.6 ng/mL) at the last observed point in time. When a patient fulfills the only (1) and (2), but not (3), he/she is diagnosed with "SPIDDM (probable)" because the diabetes is non-insulin-dependent state.

A case of type 2 diabetes mellitus with weight gain and worsening of glycemic management after tezepelumab administration for severe bronchial asthma.

Some cases of bronchial asthma are refractory to conventional therapies. As the pathogenesis of bronchial asthma has been clarified, new treatments, such as bronchial thermoplasty and biological drugs, have been developed. Tezepelumab, an anti-thymic stromal lymphopoietin antibody, has been reported to inhibit the exacerbation of severe asthma; however, its adverse effects on glucose metabolism have not yet been reported. We encountered a case of weight gain and worsening glycemic management in a patient with type 2 diabetes and refractory bronchial asthma after the initiation of tezepelumab treatment. It has been reported that the overexpression of thymic stromal lymphopoietin in mice resulted in an enhanced release of free fatty acids from adipose tissues and the liver; thus, the administration of anti-thymic stromal lymphopoietin antibodies in the present case might have caused obesity, fatty liver and lower glucose tolerance.

Continuous low serum levels of advanced glycation end products and low risk of cardiovascular disease in patients with poorly controlled type 2 diabetes.

BACKGROUND: Type 2 diabetes is associated with an increased risk of developing cardiovascular events. Previous studies have reported that advanced glycation end products (AGEs) were related to cardiovascular events in type 2 diabetes. However, data on associations between long-term AGEs and cardiovascular events in type 2 diabetes are lacking. This study aimed to determine whether a long-time shift in the levels of serum AGEs is associated with cardiovascular events in patients with poorly controlled type 2 diabetes. METHODS: Two-time serum methyl-glyoxal-hydroimidazoline (MG-H1) levels were measured in 138 patients with type 2 diabetes whose mean glycated hemoglobin level was 10.1%. We categorized patients whose serum MG-H1 levels were < 2.8 µg/mL at both times as the continuous low MG-H1 group. The primary endpoints of this study were combined cardiovascular events, which were defined as heart disease, peripheral arterial disease, stroke, and all-cause death. Hazard ratios (HRs) for combined cardiovascular events with 95% confidence intervals (CIs) were calculated using the Cox proportional hazard models to compare the outcomes between the continuous low MG-H1 group and others. RESULTS: The continuous low MG-H1 group was associated with a significantly lower risk than others in combined cardiovascular events after adjusting for possible confounders (HR: 0.50; 95% CI, 0.28-0.87; P = 0.02). Furthermore, the same relationship was observed in patients without a history of cardiovascular events. CONCLUSIONS: Continuous low serum MG-H1 levels are associated with a low frequency of diabetes-related complications in patients with poorly controlled type 2 diabetes.

Independent risk factors of rapid glomerular filtration rate decline in patients with type 2 diabetes with preserved kidney function and normoalbuminuria: A multicenter cohort study.

AIMS/INTRODUCTION: Research on the incidence and underlying mechanisms of rapid renal function decline in patients with type 2 diabetes mellitus with preserved renal function and normoalbuminuria is limited. This study aimed to investigate the involvement of hemoglobin level as a risk factor for rapid decliners among patients with type 2 diabetes with preserved renal function and normoalbuminuria. MATERIALS AND METHODS: This was a retrospective observational study of 242 patients with type 2 diabetes with a baseline estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 and normoalbuminuria (<30 mg/gCr), followed up for >1 year. The annual rate of estimated glomerular filtration rate decline during the follow-up period was calculated using least square regression analysis; rapid decliners defined at ≥3.3%/year. Risk factors associated with rapid decliners were identified using a logistic regression analysis of variables previously identified as risk factors of rapid decliners. RESULTS: The median follow-up period was 6.7 years, and 34 patients showed rapid decliners. On multivariate analysis, lower baseline hemoglobin level was a risk factor of rapid decliners (odds ratio 0.69, 95% confidence interval 0.47-0.99; P = 0.045). Furthermore, the baseline hemoglobin levels were correlated positively with iron and ferritin levels, implying that an impaired iron metabolism might cause lower hemoglobin levels in rapid decliners. CONCLUSIONS: In patients with type 2 diabetes with preserved renal function and normoalbuminuria, lower hemoglobin levels were a risk factor for rapid decliners, where disturbed iron metabolism might precede the development of diabetic kidney disease.

Quality of life after total pancreatectomy with islet autotransplantation for chronic pancreatitis in Japan.

BACKGROUND: Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations. METHODS: We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28). RESULTS: Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical (p = 0.03125), general health perception (p = 0.03125) and vitality (p = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly. CONCLUSION: The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.

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.

False-positive 123I-metaiodobenzylguanidine scintigraphy in a patient with a gastrointestinal stromal tumor presenting as a left adrenal incidentaloma.

Summary: A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. On computed tomography scan, the mass appeared to localize within the tip of the lateral limb of the left adrenal gland, and between the left adrenal gland and the posterior wall of the stomach. The plasma corticotropin and cortisol concentrations and the 24-h urine fractionated metanephrine levels were normal. 123I-metaiodobenzylguanidine scintigraphy showed tumor avidity consistent with a hormonally inactive pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal computed tomography postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a gastrointestinal stromal tumor. Clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathological analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies. Learning points: Anatomic structures and tumors that develop in neighboring tissues to the adrenal glands may be confused with primary adrenal tumors. 123I- metaiodobenzylguanidine (MIBG) scintigraphy is specific for diagnosing pheochromocytomas and paragangliomas; however, it has been reported that 123I-MIBG may accumulate in neuroendocrine tumors as well as other tumors. Clinicians should recognize the limitations of imaging studies and the uncertainty of an imaging-based preoperative diagnosis.

New-onset type 1 diabetes and Graves' disease after antiretroviral therapy in a patient with human immunodeficiency virus infection.

Patients with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy can develop autoimmune diseases, referred to as immune-inflammatory reconstitution syndrome. Nevertheless, only a few reports on the onset of type 1 diabetes as immune-inflammatory reconstitution syndrome are available. A 40-year-old Japanese man with HIV infection was initiated with antiretroviral therapy at the age of 29 years. He developed Graves' disease at 35 years and diabetes, with a hemoglobin A1c of 6.5%, and maintained insulin secretion at 38 years. His antiglutamic acid decarboxylase antibody level was >2,000 U/mL, and he was diagnosed with slowly progressive type 1 diabetes. At the age of 40 years, he was admitted to our hospital with diabetic ketosis. We retrospectively assayed his stored plasma samples for thyroid-stimulating hormone receptor antibody and antiglutamic acid decarboxylase antibody, which showed positive conversion after initiating antiretroviral therapy, suggesting that Graves' disease and type 1 diabetes developed as a probable result of immune-inflammatory reconstitution syndrome.

Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes.

AIM/INTRODUCTION: To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA-GADA) and ELISA (ELISA-GADA) in patients with type 1 diabetes. METHODS: A total of 415 patients with type 1 diabetes were enrolled, including 199 acute-onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C-peptide (F-CPR) were examined. RESULTS: While the ELISA-GADA displayed a higher sensitivity than the RIA method in diagnosing type 1 diabetes in acute-onset patients, about 40% of SPIDDM patients with low-titer RIA-GADA were determined as negative by the ELISA method. Patients with type 1 diabetes with RIA-GADA alone had an older age of onset, less diabetic ketoacidosis, a higher BMI, and a higher F-CPR compared with patients positive for both RIA-GADA and ELISA-GADA. Additionally, 36% of RIA-GADA-positive patients had low-affinity GADA (<1010 L/mol), which was significantly higher than in the ELISA-GADA-positive patients (4%, P < 0.0001). Furthermore, over a 3 year monitoring period, F-CPR levels decreased in ELISA-GADA-positive SPIDDM, whereas it was maintained in patients with RIA-GADA alone, regardless of GADA affinity. CONCLUSIONS: These results suggest that bivalent ELISA for GADA is superior to the RIA method in diagnosing type 1 diabetes. Moreover, the diagnostic superiority of the ELISA-GADA made possible the concurrent identification of SPIDDM patients at high-risk of early progression, and allowed for more accurate clinical diagnosis and management.

Association of acute-to-chronic glycemic ratio and outcomes in patients with COVID-19 and undiagnosed diabetes mellitus: A retrospective nationwide cohort study.

AIMS/INTRODUCTION: To assess the association of undiagnosed diabetes mellitus and its acute-to-chronic glycemic ratio with clinical outcome in patients hospitalized with coronavirus disease 2019 (COVID-19) using a large-scale nationwide registry in Japan. MATERIALS AND METHODS: Overall, 4,747 patients were included between July 2021 and January 2022. We evaluated blood glucose and glycated hemoglobin levels at admission, and calculated the acute-to-chronic glycemic ratio for each non-diabetes mellitus, undiagnosed diabetes mellitus and pre-existing diabetes mellitus group. The primary composite outcome comprised in-hospital mortality, invasive mechanical ventilation, extracorporeal membrane oxygenation support, intensive care unit admission and transfer to a more advanced medical facility. RESULTS: Compared with the non-diabetes mellitus group, the undiagnosed diabetes mellitus group was significantly associated with a worse COVID-19 outcome (odds ratio 2.18, 95% confidence interval 1.50-3.18). In patients with undiagnosed diabetes mellitus, the 3rd tertile of the acute-to-chronic glycemic ratio was linked with a worse COVID-19 outcome compared with the 1st tertile (odds ratio 3.33, 95% confidence interval 1.43-7.77), whereas glycated hemoglobin levels were not; among patients with pre-existing diabetes mellitus, glycated hemoglobin levels were linked with a worse outcome. CONCLUSIONS: Among patients with undiagnosed diabetes mellitus with COVID-19, the magnitude of elevation of blood glucose from chronic to acute levels is associated with worse outcomes.

Clinical significance of tumor markers in patients with type 2 diabetes: a retrospective observational study.

Aim: To cross-sectionally and longitudinally investigate the association between tumor markers (Cancer embryonic antigen (CEA) Carbohydrate antigen 19-9 (CA19-9)) and malignancies in type 2 diabetes patients without evidence of malignancy. Materials and Methods: The study included 707 patients admitted for the treatment of diabetes from 1 August 2010 to 1 September 2018. Serum CEA and CA19-9 levels were measured for screening of malignancies at admission. Abdominal ultrasonography, computed tomography, and endoscopy were performed for close examination. The percentage of patients diagnosed with malignancy was calculated, and among those without malignancy, the incidence of malignancies was examined after discharge. Results: A total of 26 patients (3.7%) were newly diagnosed with malignancy during hospitalization. The optimal cut-off value of CEA and CA19-9 by receiver operating characteristic analysis was 5.0 ng/mL and 75 U/mL, and their positive predictive values (PPV) were 8.7% and 22.5%, respectively. The addition of CA19-9 to age, smoking status, body mass index, and glycated hemoglobin significantly improved classification performance for malignancy using net reclassification improvement (0.682, 95% CI 0.256-1.107) and integrated discrimination improvement (0.150, 95% CI 0.007-0.294). Among 681 patients without malignancies during hospitalization, 30 patients (4.4%) developed malignancies during an average follow-up of 3.9 years. CA19-9 (hazard ratio: 1.005, 95% CI: 1.003-1.008) was associated with the development of malignancies. Conclusions: PPV of serum CEA and CA19-9 for detecting malignancy was high in type 2 diabetes patients with poor glycemic control. Measuring CA19-9 was found to be valuable to cross-sectionally and longitudinally detect malignancies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00594-x.

Comparing the clinical significance and antigen specificity of insulinoma-associated antigen-2 autoantibodies between radioimmunoassay and enzyme-linked immunosorbent assay in Japanese patients with type 1 diabetes.

AIMS/INTRODUCTION: This study aimed to investigate the clinical significance and antigen specificity of autoantibodies to insulinoma-associated antigen-2 (IA-2A) by radioimmunoassay (RIA; IA-2A-RIA) and enzyme-linked immunosorbent assay (ELISA; IA-2A-ELISA) in Japanese patients with type 1 diabetes. MATERIALS AND METHODS: A total of 338 type 1 diabetic patients were enrolled, including 38 fulminant type 1 diabetes, 168 acute-onset type 1 diabetes and 137 slowly-progressive type 1 diabetes (SPIDDM). The concordance, correlation of autoantibody titer, and the relationship between IA-2A and progression to the insulin-deficient state were examined. Also, competitive assay was used to examine the antigen specificity. RESULTS: The prevalence of IA-2A-ELISA was 4-5% lower than that of IA-2A-RIA in both the acute-onset type 1 diabetes and SPIDDM, but the diagnostic sensitivities of both subtypes, when measured in combination with glutamic acid decarboxylase autoantibody, were comparable. The diagnosis of type 1 diabetes using either the RIA or ELISA methods showed substantial agreement with the exponential correlation of autoantibody titers detected by RIA and ELISA. Among the SPIDDM patients, the fasting C-peptide for IA-2A-positive cases by ELISA, but not the RIA method, was significantly lower than in the negative cases (P < 0.05). Furthermore, IA-2A-ELISA proved superior to the RIA method in predicting the progression to insulin deficiency in SPIDDM. Competitive analysis showed that even sera with discrepant results by RIA and ELISA have IA-2-specific autoantibodies. CONCLUSION: These results suggest that IA-2A-ELISA is a reliable marker not only for the diagnosis of type 1 diabetes, but also for the prediction of future insulin dependency; that is, detection of IA-2A-ELISA helps identify a subtype of SPIDDM patients who would likely progress onto insulin-deficient state.

Negative-High Titer of Helicobacter pylori Antibody and Lipid Profiles.

Background: Helicobacter pylori (HP) is a causative factor for several gastrointestinal diseases. A HP seropositive antibody titer (i.e., ≥10 U/mL), a threshold indicating an HP infection, is known to be associated with changes in lipid metabolism. There is evidence that HP infection can be found in some individuals with HP antibody titer of between 3 and 9.9 U/mL (termed as "negative-high titer"). However, it is unknown about the relationship between HP negative-high titer and lipid metabolism. The present study aimed to quantify the association between HP negative-high antibody titer and lipid profiles. Materials and Methods: We surveyed 2,478 people who underwent a Ningen Dock examination and had serological HP antibody data, from May 2016 to December 2020 at National Center for Global Health and Medicine, Tokyo, Japan. Multiple regression models were used to quantify the association between HP antibody titer and serum lipid levels. Results: The adjusted odds ratio (95% confidence interval [CI]) for dyslipidemia in HP negative-high and positive titer was 1.24 (0.96, 1.79) and 1.36 (1.10, 1.68), respectively, compared with HP negative-low titer; p trend =0.005. The adjusted mean (95% CI) of high-density lipoprotein cholesterol (HDL-C) in HP negative-low, negative-high, and positive titer was 58.78 (57.86-59.71), 55.30 (53.70-56.91), and 53.76 (52.90-54.63) mg/dL, respectively; p trend <0.001. Higher HP antibody titers were also associated with higher ratio of low-density lipoprotein cholesterol (LDL-C) to HDL-C, but not triglycerides, or total cholesterols. Conclusion: The present cross-sectional study suggests that a HP negative-high antibody titer may be associated with dyslipidemia, HDL-C, and LDL-C to HDL-C ratio among Japanese Ningen Dock's participants.