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.

Fulminant type 1 diabetes patients display high frequencies of IGRP-specific type 1 CD8+ T cells.

The role of cellular autoimmunity in the pathogenesis of fulminant type 1 diabetes (FT1D) remains largely unknown. In this study, we performed an integrated assay using peripheral blood mononuclear cells to determine the islet antigen-specific CD8+ T cell responses in FT1D and compare the responses among acute-onset T1D (AT1D) and slowly progressive T1D (SP1D). IGRP- and ZnT8-specific IL-6, G-CSF, and TNF-α responses were significantly upregulated in patients with FT1D, while IGRP- and ZnT8-specific IP-10 responses were significantly upregulated in patients with AT1D than in non-diabetics (ND). Furthermore, the frequencies of IGRP-specific type 1 CD8+ cytotoxic T (Tc1) cells were significantly higher in the FT1D group than in the ND, SP1D, and AT1D groups. Additionally, IGRP-specific Tc1 cells were more abundant in the FT1D with HLA-A2 group than in the FT1D without A2 group. In conclusion, our study suggests that IGRP-specific CD8+ T cells significantly contribute to the pathogenesis of FT1D.

No beneficial effects of aspirin on secondary cardiovascular prevention in patients with type 2 diabetes using non-steroidal anti-inflammatory drugs.

There is little evidence on whether non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin interact in secondary cardiovascular prevention in type 2 diabetic patients. This is an observational study using data from the Action to Control Cardiovascular Risk in Diabetes and Follow-on studies. Hazard ratios (HRs) for mortality with 95% confidence intervals (95% CIs) were calculated using Cox proportional hazard models to compare time to death in patients using and not using aspirin who were simultaneously using or not using NSAIDs. A total of 3600 type 2 diabetic patients with cardiovascular disease were included. During a mean follow-up period of 8.8 years, 948 patients died. After adjustments, the risk of all-cause mortality in patients not using NSAIDs was significantly lower in those using aspirin than in those not using aspirin (HR, 0.81; 95% CI, 0.70-0.93; P = 0.004). The risk in patients using NSAIDs did not differ significantly between the two groups. There was a significant interaction between aspirin use and NSAIDs use. In type 2 diabetic patients with cardiovascular disease, aspirin use was not beneficial for those using NSAIDs.

Prevalence and associated factors of overweight and obesity among schoolchildren in Hanoi, Vietnam.

BACKGROUND: The prevalence of overweight and obesity (OW/OB) has increased rapidly in Vietnam. This study aimed to elucidate the factors influencing OW/OB among secondary schoolchildren. METHOD: A survey was conducted in January 2014 in four randomly selected state schools in two Hanoi urban districts, and 821 students in grade six (11-12 years old) participated. Definitions of OW/OB followed the World Health Organization standard cut-offs. RESULTS: Overall, 4.1% of children were underweight, 59.7% were normal weight, 17.1% were overweight, and 19.1% were obese. The odds of OW/OB were lowest among children whose parents had college/university degrees [father (aOR =0.65, 95% CI: 0.42-1.00); mother (aOR =0.63, 95% CI: 0.41-0.97)] compared with those whose parents had only a primary education. Children with an OW/OB family history had an increased risk of OW/OB. Other associated factors include parental OW/OB and birth weight (BW). The odds of OW/OB were highest among children with parents with OW/OB [father (aOR =2.022, 95% CI: 1.34-3.04); mother (aOR =2.83, 95% CI: 1.51-5.30)] compared with those with normal-weight parents. Children with both parents having OW/OB [both parents (aOR =6.59, 95% CI: 1.28-33.87) had the highest risk, followed by one parent (aOR =2.22, 95% CI: 1.50-3.27)] and then neither parent having OW/OB. Moreover, high-birth-weight children [BW ≥ 3500 g (aOR =1.52, 95% CI: 1.07-2.15)] had greater odds than did normal-birth-weight children. Children who slept 11 h per day [8-11 h (aOR =0.57, 95% CI: 0.40-0.81) or more (aOR =0.44, 95% CI: 0.22-0.87)] had lower OW/OB odds than those who slept 8 h or less. Children with specific positive lifestyle behaviours had lower risk of OW/OB than those who did not engage in positive lifestyle behaviours. The odds were lower among children who exercised for weight reduction (OR = 0.16, 95% CI: 0.11-0.23), lowered food intake (aOR = 0.12, 95% CI: 0.09-0.17), and added vegetables to their diet (aOR = 0.26, 95% CI: 0.19-0.35). CONCLUSION: The results suggest that parents and children with OW/OB parents or a high BW should be educated to prevent OW/OB at an early stage. Positive lifestyle behaviours should be adopted by the students.

Favourable changes in mortality in people with diabetes: US NHANES 1999-2010.

AIMS: Diabetes-related complications have declined during the past two decades. We aimed to examine whether mortality in people with diabetes improved over time in the 1999 to 2010 National Health and Nutrition Examination Survey (NHANES). METHODS: We conducted a prospective cohort study using 1999 to 2004 and 2005 to 2010 data from the NHANES. For primary analyses, we compared the unadjusted, age-adjusted and multivariable-adjusted hazard ratios (HR) for mortality outcomes (total, cardiovascular, cardiac and cancer deaths) of the participants with diabetes with those without diabetes using Cox proportional hazard models. RESULTS: For each mortality outcome, HR (95% confidence interval) in diabetic participants during the period 2005 to 2010 was lower than that during the period 1999 to 2004 (all-cause death, 2.76 [1.87-4.08] vs 4.23 [2.57-6.98]; cardiovascular death, 2.70 [1.20-6.04] vs 8.82 [3.28-23.70]; cardiac death, 2.45 [0.98-6.09] vs 15.55 [7.01-34.50]; cancer death, 2.33 [0.87-6.23] vs 3.03 [1.20-7.65]). Compared with mortality outcome during the period 1999 to 2004, greater declines in mortality during the period 2005 to 2010 were observed for cardiovascular (-54.0%) and cardiac deaths (-64.8%). In age-adjusted and multivariable-adjusted models, the cumulative event rates for total, cardiovascular and cardiac deaths were not significantly different between participants with and without diabetes during the period 2005-2010; this was not the case during the period 1999-2004. The leading cause of death was malignant neoplasm during the period 2005-2010. CONCLUSION: Considerably improved outcomes for total, cardiovascular and cardiac deaths were observed in people with diabetes during the 2005 to 2010 NHANES compared to the 1999 to 2004 NHANES.

Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population-based observational study.

Obesity, metabolic syndrome and type 2 diabetes are associated with cancer-related mortality. We assessed whether hyperinsulinemia is a risk factor for cancer death in nonobese people without diabetes. We conducted a prospective cohort study using data from the National Health and Nutrition Examination Survey 1999-2010 and followed up the participants until December 31, 2011. For the primary analysis of cancer mortality, we used Cox proportional hazard models to estimate hazard ratios (HRs) in the participants with hyperinsulinemia and those without. Hyperinsulinemia was defined as a fasting insulin level of ≥10 µU/mL. To identify causes of deaths, the International Classification of Diseases, Tenth Revision codes were used. This study included 9,778 participants aged 20 years or older without diabetes or a history of cancer: 6,718 nonobese participants (2,057 with hyperinsulinemia [30.6%]) and 3,060 obese participants (2,303 with hyperinsulinemia [75.3%]). A total of 99.9% completed follow-up. Among all study participants, cancer mortality was significantly higher in those with hyperinsulinemia than in those without hyperinsulinemia (adjusted HR 2.04, 95% CI 1.24-3.34, p = 0.005). Similarly, among nonobese participants, multivariable analysis showed that cancer mortality was significantly higher in those with hyperinsulinemia than in those without (adjusted HR 1.89, 95% CI 1.07-3.35, p = 0.02). Considering that nonobese people with hyperinsulinemia were at higher risk of cancer mortality than those without hyperinsulinemia, improvement of hyperinsulinemia may be an important approach for preventing cancer regardless of the presence or absence of obesity.

Effects of ß-blockers on all-cause mortality in patients with type 2 diabetes and coronary heart disease.

AIMS: To assess whether the use of beta-blockers influences mortality and the incidence of major cardiovascular events in patients with diabetes and coronary heart disease (CHD). MATERIALS AND METHODS: Using data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, we performed Cox proportional hazards analysis to assess the effects of ß-blockers on all-cause mortality in 2244 patients with type 2 diabetes who had stable CHD with and without a history of myocardial infarction (MI)/heart failure with reduced left ventricular ejection fraction (HFrEF). RESULTS: All-cause mortality in patients with MI/HFrEF was significantly lower in those receiving ß-blockers than in those not receiving ß-blockers (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.37-0.98; P = .04), whereas that in patients without MI/HFrEF did not significantly differ (adjusted HR 0.91, 95% CI 0.76-1.32; P = .64). Among patients with MI/HFrEF, all-cause mortality in those who received intensive medical therapy alone for CHD was significantly lower in those on ß-blockers than in those not on ß-blockers (adjusted HR 0.45, 95% CI 0.23-0.88; P = .02); however, mortality in patients who received early revascularization for CHD was not significantly lower in those on ß-blockers (adjusted HR 0.81, 95% CI 0.40-1.65; P = .57). The risk of major cardiovascular events in patients without MI/HFrEF was not significantly different between those on and those not on ß-blocker treatment. CONCLUSIONS: In patients with diabetes and CHD, the use of ß-blockers was effective in reducing all-cause mortality in those with MI/HFrEF but not in those without MI/HFrEF.

A positive family history of hypertension might be associated with an accelerated onset of type 2 diabetes: Results from the National Center Diabetes Database (NCDD-02).

Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.

Prevalence, perception and factors associated with diabetes mellitus among the adult population in central Vietnam: a population-based, cross-sectional seroepidemiological survey.

BACKGROUND: Diabetes Mellitus (DM) has rapidly become a major public health concern in Vietnam. Although the prevalence of DM has been studied in northern and southern Vietnam, little data are available for the central region. Therefore, the aims of this survey were to estimate the prevalence of DM and to identify the perception of and factors associated with DM among the adult population in central Vietnam. METHODS: We conducted a cross-sectional, population-based survey in Khánh Hòa Province, Vietnam in December 2014 using three-stage cluster sampling and probability proportional to size sampling in line with the World Health Organization STEPwise approach. Four hundred and eighty residents aged 20-70 years were selected from 30 villages in 10 wards/communes. After obtaining informed consent, all residents participated in interviews regarding lifestyle, medical history, and perception of DM and underwent physical measurements and blood examination for fasting blood glucose and glycated hemoglobin. Factors associated with DM were analyzed using a logistic regression model. RESULTS: A total of 376 residents were enrolled (response rate: 78.3%; females: 59%; rural residents: 61%). Among the participants, 14.3% and 18.9% of males and females, respectively, were classified as overweight/obese according to body mass index (BMI), 37.7% and 22.1%, respectively, had hypertension, and 36.4% and 11.7% had metabolic syndrome. The prevalence of DM in the entire population was 7.2% (27/376; 95% confidence interval [CI]: 4.6-9.8). Participants aged 60-70 years were more likely to have DM than those aged 30-39 years (adjusted odds ratio [aOR]: 8.7; 95%CI: 1.4-56.0), and participants classified as obese were more likely to have DM than those with normal or low BMI (aOR: 10.2; 95%CI: 2.2-50.2). Furthermore, more than two-thirds (254/376, 67.6%) of the participants either did not understand or had never heard of DM, and less than half of the DM cases (12/27, 44%) were aware of their history of DM. CONCLUSIONS: The results of this study suggested that the prevalence of DM among the adult population in central Vietnam was slightly higher than that in other areas. Additional research is needed to further explore perceptions of and practices regarding DM.

Postprandial Glucose Surges after Extremely Low Carbohydrate Diet in Healthy Adults.

Carbohydrate-restricted diets are prevalent not only in obese people but also in the general population to maintain appropriate body weight. Here, we report that extreme carbohydrate restriction for one day affects the subsequent blood glucose levels in healthy adults. Ten subjects (median age 30.5 years, BMI 21.1 kg/m2, and HbA1c 5.5%), wearing with a continuous glucose monitoring device, were given isoenergetic test meals for 4 consecutive days. On day 1, day 2 (D2), and day 4 (D4), they consumed normal-carbohydrate (63-66% carbohydrate) diet, while on day 3, they took low-carbohydrate/high-fat (5% carbohydrate) diet. The daily energy intake was 2,200 kcal for males and 1,700 kcal for females. On D2 and D4, we calculated the mean 24-hr blood glucose level (MEAN/24h) and its standard deviation (SD/24h), the area under the curve (AUC) for glucose over 140 mg/dL within 4 hours after each meal (AUC/4h/140), the mean amplitude of the glycemic excursions (MAGE), the incremental AUC of 24-hr blood glucose level above the mean plus one standard deviation (iAUC/MEAN+SD). Indexes for glucose fluctuation on D4 were significantly greater than those on D2 (SD/24h; p = 0.009, MAGE; p = 0.013, AUC/4h/140 after breakfast and dinner; p = 0.006 and 0.005, and iAUC/MEAN+SD; p = 0.007). The value of MEAN/24h and AUC/4h/140 after lunch on D4 were greater than those on D2, but those differences were not statistically significant. In conclusion, consumption of low-carbohydrate/high-fat diet appears to cause higher postprandial blood glucose on subsequent normal-carbohydrate diet particularly after breakfast and dinner in healthy adults.

Possible discrepancy of HbA1c values and its assessment among patients with chronic renal failure, hemodialysis and other diseases.

BACKGROUND: Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. However, these markers are influenced by alterations in hemoglobin and albumin metabolism. Thus, conditions such as anemia, chronic renal failure, hypersplenism, chronic liver diseases, hyperthyroidism, hypoalbuminemia, and pregnancy need to be considered when interpreting HbA1c or GA values. Using data from patients with normal albumin and hemoglobin metabolism, we previously established a linear regression equation describing the GA value versus the HbA1c value to calculate an extrapolated HbA1c (eHbA1c) value for the accurate evaluation of glycemic control. In this study, we investigated the difference between the measured HbA1c and the eHbA1c values for patients with various conditions. METHODS: Data sets for a total of 2461 occasions were obtained from 731 patients whose HbA1c and GA values were simultaneously measured. We excluded patients with missing data or changeable HbA1c levels, and patients who had received transfusions or steroids within the previous 3 months. Finally, we included 44 patients with chronic renal failure (CRF), 10 patients who were undergoing hemodialysis (HD), 7 patients with hematological malignancies and a hemoglobin level of less than 10 g/dL (HM), and 12 patients with chronic liver diseases (CLD). RESULTS: In all the groups, the eHbA1c values were significantly higher than the measured HbA1c values. The median difference was 0.75 % (95 % CI 0.40-1.10 %, P for the difference is <0.001) in the CRF group, 0.80 % (95 % CI 0.30-1.65 %, P for the difference is 0.041) in the HD group, 0.90 % (95 % CI 0.90-1.30 %, P for the difference is 0.028) in the HM group, and 0.85 % (95 % CI 0.40-1.50 %, P for the difference is 0.009) in the CLD group. CONCLUSIONS: We found that the measured HbA1c values were lower than the eHbA1c values in each of the groups.

A newer conversion equation for the correlation between HbA1c and glycated albumin.

Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. These markers are influenced by either altered hemoglobin metabolism or albumin metabolism. We investigated the correlation between HbA1c and GA by collecting only data that had not been affected by the turnover of either HbA1c or GA and proposed a novel equation for accurately estimating the extrapolated HbA1c (eHbA1c) value based on the GA value. Data sets for a total of 2461 occasions were obtained from 731 patients (including non-diabetes patients) whose HbA1c and GA values were simultaneously measured. Data sets obtained from patients undergoing hemodialysis, patients with hematological malignancies, pregnancy, chronic liver diseases, hyperthyroidism, steroid treatment or a blood transfusion during the past 3 months, or patients without albumin, hemoglobin, eGFR, or urinary protein measurements and data sets with an eGFR of less than 30 mL/min/1.73 m(2), a hemoglobin level of less than 10 mg/dL, an albumin level of below 3.0 g/mL, or a urinary protein level of 3+ were excluded. Finally, we selected 284 data sets. We then analyzed these data sets, performed a scatter plot to examine the correlation between HbA1c and GA, and established an equation describing the resulting correlation. Based on all the data points, the resulting equation was HbA1c = 0.216 × GA + 2.978 [R(2) = 0.5882, P < 0.001].

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.

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.

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.

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.

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.

A case of malignant insulinoma: successful control of glycemic fluctuation by replacing octreotide injections with octreotide LAR injections.

A 73-year-old woman with malignant insulinoma was treated with 100 µg/day octreotide for unresected insulinoma and liver metastases. The daily administration of the drug induced hyperglycemia after dinner in addition to existing fasting hypoglycemia possibly because this drug suppressed both insulin and glucagon secretion and its blood concentration was unstable. After replacing a daily injection of octreotide with a monthly injection of octreotide long-acting repeatable (LAR), blood glucose levels stabilized within the normal range. The findings of the present study showed that octreotide LAR could be useful for the long-term treatment of unresectable insulinomas.

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.

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.