Glycated albumin (GA) and the GA/HbA1c ratio are higher in diabetic patients positive for insulin antibodies with high binding capacity and low affinity.

Patients with diabetes mellitus having insulin antibodies (InsAb) with properties of high binding capacity and low affinity, which are observed in insulin autoimmune syndrome (IAS), are known to have greater plasma glucose fluctuations. Glycated albumin (GA) and the GA/HbA1c ratio have been demonstrated to reflect plasma glucose fluctuations. Hence, we hypothesized that GA or the GA/HbA1c ratio in diabetic patients having InsAb with properties of high binding capacity and low affinity may be higher than those in InsAb-negative diabetic patients, and we verified this hypothesis. Subjects were 12 diabetic patients who had InsAb noted while being treated with insulin and were subjected to Scatchard analysis and whose InsAb had properties similar to those of patients with IAS (affinity constant K1 < 0.24 × 1/10-8 M, number of binding sites R1 ≥ 11.5 × 10-8 M) [four cases of type 1 diabetes (T1D) and eight cases of type 2 diabetes (T2D)]. The control group consisted of T1D and T2D cases matched to the T1D and T2D cases, respectively, according to sex, age, BMI, and HbA1c. GA and the GA/HbA1c ratio were compared between both groups. GA and the GA/HbA1c ratio in InsAb-positive patients was significantly higher than that in the control group for both T1D and T2D patients. Diabetic patients having InsAb with properties of high binding capacity and low affinity had higher GA and the GA/HbA1c ratio than those of InsAb-negative patients. Greater plasma glucose fluctuations were suggested in InsAb-positive diabetic patients.

Accuracy of a Professional Continuous Glucose Monitoring Device in Individuals with Type 2 Diabetes Mellitus.

Among continuous glucose monitoring (CGM) devices, which continuously measure glucose concentration in subcutaneous interstitial fluid for comprehensive monitoring of blood glucose profile, only FreeStyle Libre Pro® (Abbott Diabetes Care) is currently available in Japan as a professional system. FreeStyle Libre Pro® is easy to use because it does not require calibration by self-monitoring of blood glucose (SMBG), but information on its accuracy has been insufficient. To evaluate the measurement accuracy of FreeStyle Libre Pro®, we have now compared blood glucose levels determined by this device with those measured by SMBG in 40 individuals with type 2 diabetes mellitus. The mean absolute relative difference (MARD) for FreeStyle Libre Pro® measurements compared with SMBG measurements was calculated as an index of CGM accuracy. Overall blood glucose values measured by SMBG were 167.0 ± 60.1 mg/dL, and those determined by FreeStyle Libre Pro® were 155.0 ± 60.7 mg/dL, with this difference being statistically significant. The MARD for FreeStyle Libre Pro® relative to SMBG was 12.7 ± 9.3%. It was substantially higher in 2 of the 40 patients, at 49.2% and 47.5%, than in the other 38 individuals. MARD values did not differ significantly between before and 2 h after meals. However, the MARD was significantly higher for SMBG values of <100 mg/dL than for those of ≥250 mg/dL. Our results thus indicate that the measurement accuracy of FreeStyle Libre Pro® is relatively good, but that some cases in which values determined by the device deviate from SMBG values require caution in interpretation.

Elder abuse risk factors: Perceptions among older Chinese, Korean, Punjabi, and Tamil immigrants in Toronto.

OBJECTIVES: Elder abuse is a significant concern worldwide. Several factors are reported to increase the risk for elder abuse, but little is known about which factors are most relevant to immigrant communities. This study explored perceptions of risk factors for elder abuse among older immigrants, which is the first step toward designing effective interventions. METHODS: This cross-sectional quantitative study was conducted between 2017 and 2019 in the Greater Toronto Area, Ontario, Canada and involved a convenience sample (N = 173) of older women and men from Chinese, Korean, Punjabi, and Tamil immigrant communities. Participants completed a questionnaire about the frequency and importance of risk factors of elder abuse in their respective community. Descriptive statistics were used to analyze the data within each immigrant community and analysis of variance to compare the factor ratings across communities. RESULTS: The immigrant communities differed (p < .05) in their perception of the risk factors. Factors rated as frequent and important (x̅ > 2.0 - midpoint of the rating scale) were social isolation, financial dependence, and lack of knowledge of English for Korean; financial dependence, physical dependence, and emotional dependence for Chinese; lack of knowledge of English, emotional dependence, and physical dependence for Tamil; and social isolation for Punjabi. CONCLUSION: The findings highlight the need for collaboration among public health and social services to work with immigrant communities in co-designing interventions to address these key risk factors and thereby reduce the risk of elder abuse.

Accurate prediction of HbA1c by continuous glucose monitoring using a kinetic model with patient-specific parameters for red blood cell lifespan and glucose uptake.

BACKGROUND: A recent kinetic model proposed a new individualized glycaemic marker, calculated HbA1c (cHbA1c), based on kinetic parameters and glucose levels that are specific to each person. The aims of the current work were to validate the accuracy of this glucose metric for clinical use and evaluate data requirements for the estimation of personal kinetic factors. METHODS: We retrieved HbA1c and glucose data from a group of 51 Japanese T1D patients under sensor-augmented pump (SAP) therapy. Two patient-specific kinetic parameters were identified by data sections, defined as continuous glucose data between two laboratory HbA1c measurements. The cHbA1c was prospectively validated employing subsequent HbA1c data that were not originally used to determine personal kinetic parameters. RESULTS: Compared to estimated HbA1c (eHbA1c) and glucose management indicator (GMI), cHbA1c showed clinically relevant accuracy improvement, with 20% or more within ±0.5% (±5.5 mmol/mol) of laboratory HbA1c. The mean absolute deviation of the cHbA1c calculation was 0.11% (1.2 mmol/mol), substantially less than for eHbA1c and GMI at 0.54% (5.9 mmol/mol) and 0.47% (5.1 mmol/mol), respectively. CONCLUSION: Our study shows superior performance of cHbA1c compared with eHbA1c and GMI at reflecting laboratory HbA1c, making it a credible glucose metric for routine clinical use.

Usefulness of the index calculated as the product of levels of fasting plasma glucose and hemoglobin A1c for insulinoma screening.

Hypoglycemia is the major symptom of insulinoma. Chronic and recurrent hypoglycemia leads to the disappearance of autonomic symptoms and persistence of non-specific symptoms alone, possibly contributing to the delayed diagnosis of insulinoma and accounting for several undiagnosed cases. We previously reported the usefulness of hemoglobin A1c (HbA1c) and glycated albumin as markers for early insulinoma screening; however, their diagnostic prediction performance and diagnostic performance were not satisfactory. We hypothesized that the product of fasting plasma glucose (FPG) and HbA1c levels (FPG × HbA1c index) is low in insulinoma, and this index may be a useful marker for screening. This cross-sectional multicenter study compared 82 insulinoma patients with 100 age-, sex-, and body mass index-matched controls with normal glucose tolerance based on 75-g oral glucose tolerance test. The FPG × HbA1c index was significantly lower in the insulinoma group than in the control group. Receiver operating curve analysis showed that the optimal cutoff point of the FPG × HbA1c index to diagnose insulinoma was 447.1, and the area under the curves (AUCs) of the FPG × HbA1c index and HbA1c were 0.998 and 0.966, respectively. The AUC of the index was significantly higher than that of HbA1c (p = 0.010). Conversely, no significant difference existed between the AUC of the FPG × HbA1c index and that of the FPG/fasting immunoreactive insulin index. Thus, in apparently healthy population, the product of FPG and HbA1c yields a useful index for insulinoma screening in terms of accuracy and versatility.

Relationship between glycated hemoglobin level and duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas: A multicenter cross-sectional study.

AIMS/INTRODUCTION: Sulfonylurea-related hypoglycemia increases the risk of cardiovascular sequela, such as cardiac arrhythmia. This study aimed to clarify the relationship between the level of glycated hemoglobin (HbA1c ) and the duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas. MATERIALS AND METHODS: Glucose levels in the enrolled patients (n = 300) were investigated with a professional continuous glucose monitoring device in the outpatient setting at six diabetes centers in Japan. RESULTS: A total of 269 participants completed the study. The duration of hypoglycemia with glucose values of <54 mg/dL was significantly longer in patients with an HbA1c level of ≤6.4% than in those with an HbA1c level of ≥8.0%, and that of hypoglycemia with glucose values of <70 mg/dL was significantly longer in patients with an HbA1c level of ≤6.4%, 6.5-6.9% or 7.0-7.4% than in those with an HbA1c level of ≥8.0%. Patients with an HbA1c level of ≤6.4% were exposed to glucose values of <70 mg/dL for >10% of the time in daily life (6.8 ± 5.6 min/h). The duration of hypoglycemia with glucose values of <70 mg/dL was longer at night than during the daytime, and the nadir of glucose values occurred between 03.00 and 05.00 hours irrespective of HbA1c level. The duration of hypoglycemia was associated with the duration of diabetes and sulfonylurea dose. CONCLUSIONS: The duration of hypoglycemia was inversely correlated with HbA1c level and was longer during the night-time than daytime in type 2 diabetes patients treated with sulfonylureas.

Usefulness of hemoglobin A1c and glycated albumin measurements for insulinoma screening: an observational case-control study.

BACKGROUND: Insulinoma represents hypoglycemia as a predominant symptom; the autonomic symptoms may be resolved by chronically recurrent hypoglycemia resulting in the persistence of non-specific symptoms alone. Therefore, it has been estimated that there are many patients in whom the disease takes longer to diagnose and has remained undiagnosed. Although some parameters exist for the definitive diagnosis of the disease, there are currently no indices for early screening. Indices of glycemic control, hemoglobin A1c (HbA1c), and glycated albumin (GA) may be useful for the screening of patients with insulinoma having chronic hypoglycemia because the values become low in such a condition. Because there are no articles that have reported the point, we examine the effective cutoff values of HbA1c and GA for the diagnosis of insulinoma in the present study. METHODS: In a multicenter cross-sectional study, 31 patients with insulinoma were included for comparison with 120 control subjects with normal glucose tolerance based on 75 g oral glucose tolerance tests whose characteristics were matched to the patients. The primary outcomes were optimal cutoff values of HbA1c and GA for the screening of insulinoma. RESULTS: HbA1c was significantly lower in the insulinoma group at 4.7 ± 0.4% compared to the healthy control group at 5.7 ± 0.3% (p < 0.001), and GA was significantly lower in the insulinoma group at 11.6 ± 1.8% compared to the healthy control group at 14.5 ± 1.0% (p < 0.001). According to a receiver operating characteristic (ROC) analysis, optimal cutoff values of HbA1c and GA for the diagnosis of insulinoma were 5.0 and 12.4%, respectively. Area under the curve values of HbA1c and GA were 0.970 and 0.929, respectively, showing no significant difference (p = 0.399). CONCLUSIONS: In the present study, HbA1c and GA values in patients with insulinoma were significantly lower compared to the healthy controls, and effective cutoff values for screening were shown in the diagnosis of insulinoma for the first time. HbA1c and GA can be useful indices for insulinoma screening. Because malignant insulinoma have a similar diagnostic process to that of benign insulinoma, these could be useful for malignant insulinoma.

Developing a comprehensive understanding of elder abuse prevention in immigrant communities: a comparative mixed methods study protocol.

INTRODUCTION: Older adults are the fastest growing age group in Canada. Elder abuse has significant individual and societal implications, so it is critical to address. While interest in this topic is increasing, little is known about the risk factors for elder abuse in immigrant communities in Canada, or about culturally relevant strategies to address these risk factors. METHODS AND ANALYSIS: This mixed-methods study is guided by the intersectionality and ecological frameworks. We will include two long-term (ie, established) and two recent immigrant communities from East Asian and South Asian communities in the Greater Toronto Area: Chinese, Korean, Punjabi and Tamil. Through structured group interviews, we will first identify factors that contribute to elder abuse within and across each of the immigrant communities and then explore culturally relevant strategies to address those risk factors. Group interviews will be conducted separately with five stakeholder groups in each of the four languages: older women, older men, family members, community leaders and service providers. Quantitative and qualitative data will be analysed at the level of the particular interview groups, subgroups and communities, and will be integrated across communities to identify common and unique risk factors and strategies to address elder abuse. ETHICS AND DISSEMINATION: The study protocol has received ethics approval from the two universities associated with the research team. Given the comprehensive approach to incorporate local knowledge and expert contributions from multi-level stakeholders, the empirical and theoretical findings will facilitate practice change and improve the well-being of older men and women in immigrant communities.

The prescription rates of glucagon for hypoglycemia by pediatricians and physicians are low in Japan.

PURPOSE: Hypoglycemia is a common and life-threatening complication in type 1 diabetes mellitus (T1DM) patients. Current guidelines recommend glucagon for treating hypoglycemia in out-of-hospital settings; however, glucagon is reportedly underused in such patients. We conducted a doctor-oriented, questionnaire-based survey of pediatricians and physicians to determine the glucagon prescription rate and identify the reason(s) for its underuse in T1DM patients. METHODS: A questionnaire was mailed to 415 pediatricians and 200 physicians employed at 66 facilities with >100 general wards throughout Hyogo, Japan. The following variables were surveyed: doctor's specialty, glucagon prescription rate, familiarity with glucagon use guidelines, barriers to prescribing glucagon, and attitude changes after education. RESULTS: After 16 doctors were found to have retired, 599 doctors were enrolled; 305 (187 pediatricians and 118 physicians) returned a completed questionnaire. In all, 45 pediatricians and 104 physicians were treating T1DM patients, of whom 24% and 28% reported prescribing glucagon, respectively. The guideline familiarity rate among pediatricians was lower than that among physicians. The major barrier to prescribing glucagon was the complex preparation procedure required by patients/caregivers. More than half of the doctors who did not prescribe glucagon began doing so after being educated about the guidelines. CONCLUSION: The glucagon prescription rate was low among both pediatricians and physicians in Japan.

Treatment of a case of severe insulin resistance as a result of a PIK3R1 mutation with a sodium-glucose cotransporter 2 inhibitor.

A Japanese woman aged in her late 30s with severe insulin resistance and bodily features including a triangular face, prominent forehead, small chin, large and low-set ears, and ocular depression was investigated. A similar phenotype was not observed in other family members with the exception of her son, suggesting that the condition was caused by a de novo mutation that was transmitted from mother to son. Exome analysis showed the presence in the proband and her son of a c.1945C>T mutation in PIK3R1, a common mutation associated with SHORT (short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay) syndrome. Administration of a sodium-glucose cotransporter 2 inhibitor lowered the proband's hemoglobin A1c level and allowed a reduction in her insulin dose without treatment-related adverse events including ketoacidosis, exaggerated loss of body mass or hypoglycemia. Sodium-glucose cotransporter 2 inhibitors might thus offer an additional option for the treatment of genetic syndromes of severe insulin resistance.

Effect of switching from conventional continuous subcutaneous insulin infusion to sensor augmented pump therapy on glycemic profile in Japanese patients with type 1 diabetes.

AIMS: Evidence suggests that sensor augmented pump (SAP) therapy is superior to conventional continuous subcutaneous insulin infusion (CSII) for achieving glycemic control in patients with type 1 diabetes. However, the clinical benefit of SAP therapy in East Asians has not yet been demonstrated. METHODS: The effect of switching from conventional CSII to SAP therapy on glycemic profile was examined in 18 Japanese patients with type 1 diabetes. The glycemic profile of the patients was determined by retrospective continuous glucose monitoring (CGM) within 1 month before the treatment switch, whereas that at 6 and 12 months after the switch was evaluated with the CGM function of the SAP device. Hemoglobin A1c levels were also measured before and after the switch to SAP therapy. RESULTS: The duration of hypoglycemia was significantly decreased at both 6 and 12 months after the change in treatment (6.6 ± 4.5, 3.2 ± 4.1, and 3.0 ± 2.8 min/h for before and 6 and 12 months, respectively), as was the HbA1c level at 12 months (7.8 ± 1.0 and 7.4 ± 0.9%, respectively). The duration of hyperglycemia did not differ between before and after the treatment switch. The decline in HbA1c level at 12 months after the switch to SAP was negatively correlated with age. CONCLUSION: Switching from conventional CSII to SAP therapy was associated with a decrease in both the duration of hypoglycemia and the level of HbA1c in Japanese patients with type 1 diabetes.

[Polyploidy induction by spherical size standard polystyrene particles in a Chinese hamster cell line CHL].

To investigate relationships between particle (as a model of aggregates) size in a nanomaterial test suspension and its cytotoxicity, a series of eleven sizes of polystyrene (PS) particles were tested in the cytotoxicity test and the chromosome aberration test by using a Chinese hamster cell line CHL. The PS particles were spheres with defined diameters ranging from 0.1 to 9.2 µm. A series of eight sizes of particles with diameters ranging from 0.92 to 4.45 µm showed stronger cytotoxicity than the others. There was a marked difference in cytotoxicity between the 4.45- and 5.26-µm particles. The 0.92- to 4.45-µm particles did not induce structural chromosome aberrations but induced a high frequency of polyploidy in the chromosome aberration test. The 5.26-µm particles showed very weak induction of polyploidy. The incorporation of the 4.45-µm particles into CHL cells was observed by scanning electron microscopy (SEM). Some cells incorporated more than 10 particles. The semi-quantitative measurement of incorporation of particles into cells was performed by flow cytometry with a parameter of side scattered light (SSC) intensity. It showed that CHL cells preferably incorporated the 4.45-µm particles to the 5.26-µm particles. These findings suggest that CHL cells may have a kind of size-recognition ability and incorporate a particular size of particles. The particles may prevent a normal cytokinesis resulting in polyploidy induction. Nanomaterials also may show size-dependent toxicity. Data on particle (or aggregate) size distribution in the test suspension should be provided to evaluate properly the results of toxicity tests of nanomaterials.

Development and performance evaluation of a positive reference material for hemolysis testing.

This study deals with the development and performance evaluation of a positive reference material for hemolysis testing, which is used for evaluating the biological safety of medical devices. Genapol X-080, a nonionic detergent, was selected as a candidate hemolytic substance in a survey of 23 chemical compounds; it showed significant hemolytic activity against rabbit defibrinated blood at concentrations more than 20 µg/mL. A polyvinyl chloride (PVC) sheet spiked with 0.6% (w/w) of the compound exhibited weak hemolytic activity in direct contact and/or extract-based assays after 4 h incubation at 37°C. A PVC sheet containing 5.8% (w/w) Genapol X-080 induced complete hemolysis in both assays. The amount of Genapol X-080 eluted from each PVC sheet during hemolysis testing using the direct contact method increased time-dependently and reached 25.6 (former sheet) or 1154 (later sheet) µg/mL after 4 h incubation, which was similar to or much higher than the critical micelle concentration, respectively. Similar elution behavior was observed using the extract-based method, and the Genapol X-080 content in test solutions prepared by autoclave extraction of both sheets was 22.5 and 358 µg/mL, respectively, indicating a clear relationship between the degree of hemolytic activity and the eluted amount of Genapol X-080. Thus, a PVC sheet spiked with a compound exhibiting different hemolytic activity depending on its concentration may be useful as a positive reference material to validate the hemolysis tests.