A case of IgG4-related hypophysitis maintained remission of diabetes insipidus for over 3 months after completion of steroid treatment.

Summary: IgG4-related disease is a multiorgan disorder in which nodules and hypertrophic lesions are observed simultaneously, or separately, in areas including the pancreas, liver, lungs, salivary glands, thyroid glands, and pituitary glands. IgG4-related hypophysis is one of several IgG4-related diseases and is characterized by pituitary gland and pituitary stalk thickening, various degrees of hypopituitarism, and increased serum IgG4 levels. Steroid therapy is effective for patients with IgG4-related hypophysis, but the reported effectiveness of steroid therapy for restoring pituitary function differs between studies. Following an episode of autoimmune pancreatitis 10 years prior, enlargement of the pituitary gland and stalk along with panhypopituitarism and polyuria developed in a 73-year-old male. A high serum IgG4 level and biopsy of the submandibular gland showing infiltration of IgG4-positive plasma cells led to a clinical diagnosis of IgG4-related hypophysitis. Prednisolone treatment reduced the swelling of the pituitary gland and stalk and improved anterior pituitary function. Although arginine vasopressin secretion remained insufficient, polyuria was relieved and kept in remission even after prednisolone treatment was completed. This is the first reported case in which prednisolone was able to maintain both normal anterior pituitary function and remission of polyuria caused by IgG4-related hypophysitis. IgG4-related hypophysitis has previously been associated with a relapse of symptoms during treatment. However, the patient reported in this case study remained in remission for over 3 months after completion of steroid treatment and should be monitored closely for changes in pituitary function. Learning points: Steroid therapy is the first-line therapy for pituitary dysfunction and pituitary stalk swelling in IgG4-related hypophysitis. In this case, although posterior pituitary function remained insufficient, polyuria was relieved and kept in remission for over 3 months even after prednisolone treatment was completed. IgG4-related hypophysitis has been associated with the relapse of symptoms during steroid tapering, and changes in pituitary function and symptoms should be monitored closely. When we encounter cases of adrenal insufficiency and polyuria during observation of autoimmune pancreatitis or other IgG4-related disease, we should consider the possibility of IgG4-related hypophysitis in mind.

Glucose control in the early phase of hospitalization is associated with severe prognosis in coronavirus disease 2019 (COVID-19) patients with diabetes in Japan.

We investigated the association of glycemic control in the early phase of hospitalization with the prognosis of COVID-19 in patients with diabetes. We analyzed the relationship between various clinical indices, including preprandial blood glucose levels measured by self-monitoring devices in the early phase after admission, and severe prognosis in 189 patients with complicated diabetes who were admitted to our hospital between February 22, 2020 and June 20, 2021. Enrolled patients had a median age of 72 years, median body mass index of 24.7, median HbA1c of 7.1%, and median mean preprandial capillary glucose (PPCG) of 179.1 mg/dL. Sixty-six patients progressed to severe disease, and the mean PPCG in severe cases was significantly higher than that in non-severe cases, 195.2 vs 167.8 mg/dL (p = 0.005). Analysis of the receiver operating characteristic curve showed that 179 mg/dL was the cut-off value, and the risk of severity was significantly higher in patients with a mean PPCG of 180 mg/dL or higher (odds ratio (OR) 3.210, p = 0.017) in multiple regression analysis. In this study, we found that the risk of severe COVID-19 increased in patients with a high mean PPCG in the early phase of hospitalization, suggesting that good glucose control in the early phase of COVID-19 with diabetes may be effective in preventing disease severity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00656-8.

Acid-Sensing Histidine Kinase With a Redox Switch.

The EvgS/EvgA two-component signal transduction system in Escherichia coli is activated under mildly acidic pH conditions. Upon activation, this system induces the expression of a number of genes that confer acid resistance. The EvgS histidine kinase sensor has a large periplasmic domain that is required for perceiving acidic signals. In addition, we have previously proposed that the cytoplasmic linker region of EvgS is also involved in the activation of this sensor. The cytoplasmic linker region resembles a Per-ARNT-Sim (PAS) domain, which is known to act as a molecular sensor that is responsive to chemical and physical stimuli and regulates the activity of diverse effector domains. Our EvgS/EvgA reporter assays revealed that under EvgS-activating mildly acidic pH conditions, EvgS was activated only during aerobic growth conditions, and not during anaerobic growth. Studies using EvgS mutants revealed that C671A and C683A mutations in the cytoplasmic PAS domain activated EvgS even under anaerobic conditions. Furthermore, among the electron carriers of the electron transport chain, ubiquinone was required for EvgS activation. The present study proposes a model of EvgS activation by oxidation and suggests that the cytoplasmic PAS domain serves as an intermediate redox switch for this sensor.

Usefulness of Plasma Glucose Adjusted #C (labile HbA1c fraction) Levels for the Screening of Variant Hemoglobin with Diabetes Mellitus.

Labile HbA1c migrates in the #C fraction with modified hemoglobin (Hb) (such as carbamylated Hb, acetaldehyde Hb, and acetylated Hb) when HbA1c is measured by Arkray's high-performance liquid chromatography (HPLC). We previously reported the usefulness of #C levels for the screening of variant Hb without diabetes mellitus. Because the #C levels are affected by plasma glucose levels, we investigated the usefulness of plasma glucose adjusted #C (PGa#C) for the screening of variant Hb complicated with diabetes mellitus. In this study, nine types of variant Hb in nine diabetic patients were included. HbA1c and the #C fraction were measured by Arkray's HPLC. Furthermore, we established a calculation formula for PGa#C by using the regression equation of #C and plasma glucose of 2,299 diabetic patients without variant Hb. If the cutoff value of PGa#C for the screening of variant Hb with diabetes mellitus was set at 1.3% or lower and 2.3% or higher, sensitivity and specificity were 89% and 99.8%, respectively. The PGa#C levels in all four slow moving variant Hb with diabetes were less than 1.3%, while the PGa#C levels of fast moving variant Hb with diabetes were abnormal values in four out of five patients [high #C level in one and low #C levels in three patients]. The screening of variant Hb with diabetes with high sensitivity and high specificity was possible by using the same cutoff values for the reference range of PGa#C as the #C values reported in non-diabetic subjects.

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.

HbA1c levels measured by enzymatic assay during off-site health checkups are lower than those measured by on-site HPLC assay.

HbA1c is widely used as a therapeutic target marker and as a diagnostic marker for diabetes mellitus. This has led to an increasing frequency of HbA1c measurements in current health checkups throughout Japan. In the present study, we compared the HbA1c levels measured by an enzymatic assay (EA-HbA1c) off-site during health checkups with the HbA1c levels measured by on-site ion-exchange high-performance liquid chromatography (HPLC; HPLC-HbA1c) in a hospital. A total of 96 individuals (53 males and 43 females; age, 68.9 ± 8.4 years old; 70 diabetic and 26 non-diabetic individuals) whose HbA1c levels were measured by both the methods listed above were included in the study. Since no HPLC-HbA1c levels were measured on the day of the health checkup, HPLC-HbA1c levels were estimated using HPLC-HbA1c levels measured before and after the health checkup. A significant correlation of HbA1c levels was observed between the two groups (R = 0.973; p < 0.001). However, EA-HbA1c levels measured off-site during health checkups are lower than estimated HPLC-HbA1c levels measured on-site (6.37 ± 0.75% vs. 6.69 ± 0.75%; p < 0.001). Since lower EA-HbA1c levels measured during health checkups, which diverged from on-site measurements, may lead to underestimating diabetes mellitus, accurate measurement of HbA1c is required irrespective of the measuring method. Further investigation of the cause of falsely low EA-HbA1c levels and the strategy for reconciling HbA1c to reflect plasma glucose accurately are warranted.

IFCC-HbA1c May Be More Useful than NGSP-HbA1c in the Comparison between HbA1c Values in Variant Hemoglobin with a Mutation on α Chain and ß Chain.

HbA1c values in variant hemoglobin with a mutation on α chain and ß chain are assumed to be different because the α chain and ß chain of the globin gene have two and one gene(s), respectively. We examined whether the differentiation between HbA1c values in variant hemoglobin with a mutation on α chain (C1α) and ß chain (C1ß) is possible. Three patients with C1α and 9 patients with C1ß were included. HbA1c was measured by standard mode high-performance liquid chromatography (HPLC) (HPLC-HbA1c) and immunoassay (IA: IA-HbA1c). Glycated albumin (GA) was determined, and each ratio was compared. HbA1c is expressed in National Glycohemoglobin Standardization Program (NGSP) units (A1C) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (iA1c). Both the HPLC-A1C/IA-A1C ratio and the HPLC-iA1c/IA-iA1c ratio in C1α were significantly lower than those in C1ß. Although there were no significant differences between the GA/HPLC-A1C ratios in both groups, the GA/HPLC-iA1c ratio in C1α was significantly higher than those in C1ß. If the cutoff values for the HPLC/IA-iA1c ratio and GA/HPLC-iA1c ratio were set at 65% and 5.3, respectively, both sensitivity and specificity were 100%. Differentiation between C1α and C1ß might be possible by using the HPLC-iA1c/IA-iA1c ratio or GA/HPLC-iA1c ratio.

HbA1c adjusted by erythrocyte creatine is a useful glycemic control indicator in patients with hemolysis.

OBJECTIVES: HbA1c shows low in patients with hemolysis, whereas glycated albumin (GA) is not affected by hemolysis. Therefore, the GA/HbA1c ratio reflects hemolysis in diabetic patients with hemolysis. Erythrocyte creatine (EC) is an indicator of hemolysis that reflects the mean erythrocyte age. The aim of this study was to examine whether HbA1c adjusted by EC accurately reflected glycemic control in patients with hemolysis. MATERIALS AND METHODS: A total of 238 individuals, consisting of 131 diabetic patients and 107 non-diabetic subjects, and consisting of 42 patients with hemolysis, and 196 subjects without hemolysis were selected for the study. HbA1c expressed in the IFCC units (iA1c) as well as in the NGSP units (A1C) were used. From the fact that EC and the GA/iA1c ratio showed a significant positive correlation, a formula for iA1c adjusted by EC (ECadj-iA1c) was created from a regression equation between EC and the GA/iA1c ratio. RESULTS: Significant correlations were observed between the GA/iA1c ratio and various hemolytic indicators but not between the GA/ECadj-iA1c ratio and those hemolytic indicators. The GA/iA1c ratio in individuals with hemolysis was significantly higher than in individuals without hemolysis, while no significant differences were observed in the GA/ECadj-iA1c ratio between the groups. Further, iA1c concentrations in non-diabetic patients with hemolysis were significantly lower than in the non-diabetic subjects without hemolysis, whereas ECadj-iA1c and GA concentrations showed no significant difference between the two groups. CONCLUSIONS: These results suggested that ECadj-iA1c accurately reflected glycemic control in patients with hemolysis.

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.

Shortened mean erythrocyte age in female patients with type 2 diabetes mellitus.

BACKGROUND: The hyperglycemic state is known to shorten the erythrocyte life span. Erythrocyte creatine (EC) reflects the mean erythrocyte age and is useful as an indicator of hemolysis. Here, we studied the relationship between EC and glycemic control indicators [HbA1c or glycated albumin (GA)] in non-diabetic subjects and diabetic patients. METHODS: This study included 119 patients with type 2 diabetes mellitus (T2DM) and 76 non-diabetic subjects matched by sex and age. We studied the relationships between EC and HbA1c or GA in patients with T2DM and non-diabetic subjects. RESULTS: Erythrocyte creatine in T2DM patients was significantly higher than that in non-diabetic subjects, and the ratio of high EC levels (>1.8 µmol/g Hb) in T2DM patients was significantly higher as well. Furthermore, female EC was significantly higher than male EC, and the ratio of high EC levels in females was significantly higher than in the males as well. While male EC had no significant correlation with HbA1c or GA, female EC had significant positive correlations with both. Male EC had no significant difference between T2DM patients and non-diabetic subjects, while the EC in female patients with T2DM was significantly higher than in female non-diabetic subjects. CONCLUSIONS: The significant positive correlations of EC with HbA1c and GA in female patients with T2DM suggested that the mean erythrocyte age decreased in female diabetic patients with poor glycemic control.

HbA1c and Glycated Albumin Levels Are High in Gastrectomized Subjects with Iron-Deficiency Anemia.

We report that glycated albumin (GA) is higher relative to HbA1c in non-diabetic, gastrectomized subjects without anemia, and thus is a sign of oxyhyperglycemia. It is known that gastrectomized subjects are prone to iron-deficiency anemia (IDA), and that the HbA1c levels of subjects with IDA are falsely high. In the present study, the HbA1c and GA levels of gastrectomized subjects with IDA were compared with gastrectomized subjects without anemia. Seven non-diabetic gastrectomized subjects with IDA were enrolled in the present study. Twenty-eight non-diabetic gastrectomized subjects without anemia matched with the subjects with IDA in terms of age, gender, and body mass index were used as the controls. Although there were no significant differences in fasting plasma glucose and OGTT 2-hour plasma glucose (2-h PG) between the two groups, the HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than the controls. For all of the gastrectomized subjects (n=35), ferritin exhibited a significant negative correlation with HbA1c and GA, and a significant positive correlation with 2-h PG. In addition, the HbA1c and GA levels exhibited a significant negative correlation with the mean corpuscular hemoglobin and hemoglobin. The HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than those in controls. The high GA levels are attributed to a tendency in which patients with total gastrectomy, who are prone to IDA, are susceptible to postprandial hyperglycemia and reactive hypoglycemia, which in turn leads to large fluctuations in plasma glucose.

The Glycated Albumin (GA) to HbA1c Ratio Reflects Shorter-Term Glycemic Control than GA: Analysis of Patients with Fulminant Type 1 Diabetes.

BACKGROUND: Glycated albumin (GA) reflects shorter-term glycemic control than HbA1c. We have reported that HbA1c is paradoxically increased in diabetic patients whose glycemic control deteriorated before ameliorating. In this study, we analyzed paradoxical increases of glycemic control indicators after treatment in patients with fulminant type 1 diabetes (FT1D). We also investigated whether the GA/HbA1c ratio may reflect shorter-term glycemic control than GA. METHODS: Five FT1D patients whose post-treatment HbA1c and GA levels were measured were enrolled. We also used a formula to estimate HbA1c and GA from the fictitious models of changes in plasma glucose in FT1D patients. In this model, the periods during which HbA1c, GA, and the GA/HbA1c ratio were higher than at the first visit were compared. In addition, the half-life for the GA/HbA1c ratio was calculated in accordance with the half-lives for HbA1c and GA (36 and 14 days, respectively). RESULTS: In all FT1D patients, HbA1c levels 2-4 weeks after treatment were increased, with three patients (60%) experiencing an increase of GA levels. In contrast, an increase of the GA/HbA1c ratio was observed in only one patient. In all of the different models of changes in plasma glucose in FT1D patients, the length of time during which the values were higher than at the first visit was in the order of HbA1c > GA > GA/HbA1c ratio. The half-life for the GA/HbA1c ratio was 9 days, shorter than GA. CONCLUSIONS: These findings suggest that the GA/HbA1c ratio reflects shorter-term glycemic control than GA.

Usefulness of glycated albumin in decisions regarding the discontinuation of a diabetes drug and factors associated with poor glycemic control following discontinuation in patients with type 2 diabetes mellitus.

We studied the usefulness of glycated albumin (GA) for decisions regarding the discontinuation of a diabetes drug in type 2 diabetic patients with good glycemic control, and the factors associated with increases in GA following discontinuation of a diabetes drug in patients with type 2 diabetes mellitus. Sixteen patients (12 males and 4 females) were enrolled in the present study and discontinued one diabetes drug. When the change in GA was less than 1 % at 4 weeks after the discontinuation of the diabetes drug (ΔGA4w), discontinuation was continued (the continuous group, n = 10), but when the change in GA was more than a 1 %, the discontinued diabetes drug was resumed (the resume group, n = 6). In the continuous group, HbA1c at 12 weeks after discontinuation (6.2 ± 0.6 %) remained unchanged from its value at discontinuation (6.2 ± 0.7 %) , but it was significantly elevated at 12 weeks after discontinuation in the resume group (changing from 6.3 ± 0.1 to 7.0 ± 0.6 %). Age, duration of diabetes, and GA were significantly lower while body mass index (BMI) was significantly higher in the continuous group than in the resume group, but no significant difference in HbA1c was observed between the groups. The discontinuation of a diabetes drug in patients with low insulin secretion must be performed carefully because factors such as duration of diabetes, BMI, and GA showed significant differences between the continuous group and resume group in our study, and these indicators are known to be linked with insulin secretion.

High glycated albumin (GA) levels and the GA/HbA1c ratio in patients with insulin autoimmune syndrome.

Insulin autoimmune syndrome (IAS) involves not only fasting hypoglycemia, but also postprandial hyperglycemia. In the present study, we hypothesized that glycated albumin (GA) levels and the GA/HbA1c ratio, which reflect fluctuations in plasma glucose levels, are elevated in IAS patients. Four IAS patients were enrolled in the present study. Thirty-two non-diabetic subjects matched for gender, age, and BMI were used as the control group. The fasting plasma glucose levels in the IAS patients were significantly lower than in the control group. However, the oral glucose tolerance test (OGTT) revealed impaired glucose tolerance or diabetes mellitus in all the IAS patients, and thus the OGTT 2-h plasma glucose levels were significantly higher than in the control group. The GA levels and the GA/HbA1c ratio in the IAS patients were significantly higher than in the control group, despite no significant difference in the HbA1c levels between the two groups. In one case in which IAS spontaneously went into remission, there was a significant correlation between anti-insulin antibodies and GA, but not HbA1c. Improvement in glucose fluctuations was observed by continuous glucose monitoring in another patient along with improvement in the clinical symptoms. Furthermore, anti-insulin antibodies, GA, and the GA/HbA1c ratio decreased, but HbA1c did not change significantly in three IAS patients along with the improvement in clinical symptoms. These results suggest that GA and the GA/HbA1c ratio are useful indicators for determining the level of disease activity in IAS patients.

Effects of alogliptin on the ratio of glycated albumin to HbA1c in patients with type 2 diabetes mellitus.

The ratio of glycated albumin (GA) to HbA1c (the GA/HbA1c ratio) has been used as a glycemic control indicator that reflects postprandial plasma glucose levels or glycemic variability. In this study, we investigated the effects of alogliptin, a DPP-4 inhibitor, on the GA/HbA1c ratio in patients with type 2 diabetes mellitus. Thirty-eight patients with type 2 diabetes mellitus whose glycemic control was stable were enrolled, and alogliptin (12.5 or 25 mg/day) was then administered to them for 24 weeks. HbA1c and GA levels both significantly decreased after 24 weeks (P < 0.0001), whereas the GA/HbA1c ratio did not (P = 0.129). No correlation was observed between the change in the GA/HbA1c ratio (the ΔGA/HbA1c ratio) and HbA1c or GA level before the administration of alogliptin; however, a negative correlation was found between the ΔGA/HbA1c ratio and the GA/HbA1c ratio before the administration of alogliptin (R = -0.322, P = 0.049). Although the GA/HbA1c ratio in the low-value group (<2.80) was not significantly affected by the administration of alogliptin, that in the high-value group (≥2.80) significantly decreased (P = 0.008). The administration of alogliptin significantly decreased the GA/HbA1c ratio in the high-value group after 24 weeks. Alogliptin may be more useful for patients with high postprandial plasma glucose levels than in those with low postplandial plasma glucose levels.

Alcohol consumption reduces HbA1c and glycated albumin concentrations but not 1,5-anhydroglucitol.

Background The effect of alcohol consumption on glycaemic control indicators is not well known. In this study, we studied the effect of alcohol consumption on the plasma glucose and glycaemic control indicators in non-diabetic men. Methods The study enrolled 300 non-diabetic men who received a complete medical checkup (age: 52.8 ± 6.5 years, body mass index: 24.4 ± 2.8 kg/m2). The subjects were divided into four groups by the amount of alcohol consumed, and the plasma glucose, HbA1c, glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) concentrations of the groups were compared. Results As the level of alcohol consumption increased, significantly high concentrations of fasting plasma glucose (FPG) were observed, and the oral glucose tolerance test 2-h plasma glucose concentrations tended to rise. While no significant effect of alcohol consumption on HbA1c, 1,5-AG, and the 1,5-AG/FPG ratio was observed, the HbA1c/FPG ratio, GA and the GA/FPG ratio exhibited significantly low values as the level of alcohol consumption increased. In stepwise multivariate regression analysis, alcohol consumption was a significant negative independent variable for HbA1c and GA, but not for 1,5-AG. Conclusions As the level of alcohol consumption increased, the plasma glucose concentrations rose, but the HbA1c and GA concentrations were lower compared with the plasma glucose concentrations. These findings suggest that alcohol consumption may reduce HbA1c and GA concentrations, but not 1,5-AG.

Identification of the Presence of Variant Hemoglobin Using a Measurement of the Labile HbA1c (#C) Fraction.

Labile HbA1c migrates in the #C fraction together with modified hemoglobin (such as carbamylated hemoglobin, acetaldehyde hemoglobin, and acetylated hemoglobin) when HbA1c is measured by Arkray's high-performance liquid chromatography (HPLC). It is assumed that most of the labile glycation products of variant hemoglobin do not migrate in #C fraction; in addition, a part of the stable glycation products of variant hemoglobin migrates in #C fraction. We hypothesized that subjects with variant hemoglobin are likely to show abnormally low or high values of #C fraction. In this study, we investigated this hypothesis. Twenty-one non-diabetic subjects with nine types of variant hemoglobin, and 103 non-diabetic subjects without variant hemoglobin were used. HbA1c and #C fraction were measured by Arkray's HPLC (HA-8180) using standard mode. The values of #C fraction in the control group were 1.75 ± 0.15% (range: 1.5-2.1%). The variant hemoglobin group reported #C fraction values of ≤1.3% in twelve subjects, ≥2.3% in five subjects, and within the reference range (1.4-2.2%) in three subjects. When the cutoff values of #C fraction were set at ≤1.3% and ≥2.3%, sensitivity and specificity were 86% and 100%, respectively. Most non-diabetic subjects with variant hemoglobin showed abnormal values of #C fraction. Measurement of #C fraction is a useful screening test for variant hemoglobin in non-diabetic subjects.

Aldimine Formation Reaction, the First Step of the Maillard Early-phase Reaction, Might be Enhanced in Variant Hemoglobin, Hb Himeji.

Hb Himeji (ß140Ala→Asp) is known as a variant hemoglobin in which glycation is enhanced and HbA1c measured by immunoassay shows a high value. The phenomenon of enhanced glycation in Hb Himeji is based on the fact that the glycation product of variant hemoglobin (HbX1c) shows a higher value than HbA1c. In this study, we investigated whether aldimine formation reaction, the first step of the Maillard early-phase reaction, is enhanced in Hb Himeji in vitro. Three non-diabetic subjects with Hb Himeji and four non-diabetic subjects without variant hemoglobin were enrolled. In order to examine aldimine formation reaction, whole blood cells were incubated with 500 mg/dl of glucose at 37°C for 1 hour and were analyzed by high-performance liquid chromatography. Both HbA1c and HbX1c were not increased in this condition. After incubation with glucose, labile HbA1c (LA1c) fraction increased in the controls (1.1±0.3%). In subjects with Hb Himeji increases in the labile HbX1c (LX1c) fraction as well as the LA1c fraction were observed, and the degree of increase in the LX1c fraction was significantly higher than that of the LA1c fraction (1.8±0.1% vs. 0.5±0.2%, P<0.01). We have shown for the first time that aldimine (LX1c) formation reaction might be enhanced in Hb Himeji in vitro. The 140th amino acid in ß chain of hemoglobin is suggested to be involved in aldimine formation reaction.

Anaplastic large cell lymphoma mimicking fibrosing mediastinitis.

Fibrosing mediastinitis is rare. One type of this disease is idiopathic fibrosing mediastinitis. It is necessary to rule out malignancy in order to accurately diagnose fibrosing mediastinitis. We herein report a case of anaplastic large cell lymphoma diagnosed three months after a preliminary diagnosis of fibrosing mediastinitis. Glucocorticoid therapy was not successful in controlling disease progression. Immediately after initiating chemotherapy for lymphoma, the patient's symptoms improved dramatically and the mediastinal lesion decreased in size. Although few similar cases have been reported, hidden malignancy may present as fibrosing mediastinitis. Therefore, physicians should consider the probability of malignancy in patients with fibrosing mediastinitis because treatments may vary accordingly.