Exploring a Suitable Marker of Glycemic Response to Dulaglutide in Patients with Type 2 Diabetes: A Retrospective Study.

INTRODUCTION: Previous studies suggested that ß-cell function markers such as fasting and postprandial serum C-peptide and C-peptide increment (FCPR, PCPR, and ΔCPR, respectively) may be useful in estimating glycemic response to glucagon-like peptide-1 receptor agonists. However, it remains elusive whether baseline glycemic control confounds these markers. Here we aimed to identify the least confounded ß-cell function markers and investigate whether these markers could predict glycemic response to dulaglutide. METHODS: We evaluated FCPR, PCPR, and ΔCPR levels in patients with type 2 diabetes who initiated dulaglutide treatment after a standardized meal tolerance test (MTT). We first investigated the confounding effects of baseline HbA1c on ß-cell function markers using Pearson's correlation test. Then, we evaluated the association between each ß-cell function marker and glycemic response (HbA1c change 0-6 months) to dulaglutide using generalized linear model and logistic regression analysis with adjustment for baseline HbA1c. RESULTS: In 141 patients, baseline HbA1c was significantly inversely correlated with PCPR and ΔCPR (P < 0.01 for both) but not with FCPR (r = 0.02; P = 0.853), suggesting that FCPR was the marker least confounded by baseline glycemic control. Of all patients, 59 continued dulaglutide for at least 6 months without initiating any additional glucose-lowering medications. Mean ± SE HbA1c change 0-6 months was - 1.16 ± 0.17% (P < 0.001 vs. baseline). The ß-cell function markers were significantly associated with HbA1c change 0-6 months in the generalized linear model. FCPR was also a significant predictor for achieving a reduction in HbA1c of at least 1% (P = 0.044) with an area under the receiver operating characteristic curve of 0.83 (sensitivity = 0.81 and specificity = 0.79). CONCLUSION: Fasting and meal-induced C-peptide levels are associated with glycemic response to dulaglutide, among which FCPR is least confounded by baseline glycemic control, suggesting its utility as a marker for glycemic response to dulaglutide.

A propensity score-matching analysis of transthoracic echocardiography and abdominal ultrasonography for the detection of abdominal aortic aneurysms.

INTRODUCTION: We previously reported that the prevalence of abdominal aortic aneurysms (AAAs) was higher in patients undergoing scheduled transthoracic echocardiography (TTE) than in patients undergoing abdominal ultrasonography (AUS); however, intergroup patient backgrounds differed significantly in that report. PURPOSE: We tested the hypothesis that TTE could detect AAA as effectively as AUS. DESIGN: A propensity score-matching analysis of a cross-sectional study was adopted as the design for this study. METHODS: We enrolled 7,619 and 15,433 patients scheduled to undergo TTE with additional evaluation of abdominal aorta at the end of the routine study and AUS, respectively, from 2009 to 2010 in our hospital, as reported. A propensity score for profiles of patients who underwent TTE or AUS was developed to adjust for potential confounding bias. Consequently, 4,388 patients in each group were matched for analyses. RESULTS: In propensity-matched patients, AAA was detected in 59 patients of the TTE group and in 48 patients of the AUS group; the prevalence of AAA detection did not differ significantly between TTE and AUS groups (P = 0.331). Positive associations were observed between AAA detection and male sex (adjusted odds ratio [OR]: 3.25; 95% confidence interval [CI], 2.05-5.15; P < 0.001), older age (adjusted OR: 1.029; 95% CI: 1.01-1.04; P < 0.001), and the presence of ischemic heart disease (adjusted OR: 1.78; 95% CI: 1.04-3.03; P = 0.033) and hypertension (adjusted OR: 2.16; 95% CI: 1.38-3.37; P = 001). CONCLUSION: TTE detected AAA with comparable efficacy as AUS in propensity-matched groups who underwent scheduled TTE and AUS.

Ratio of peripheral blood absolute lymphocyte count to absolute monocyte count at diagnosis is associated with progression-free survival in follicular lymphoma.

The prognosis of follicular lymphoma (FL) is significantly associated with host immunity and tumor microenvironment. Lymphopenia has been identified as a negative prognostic factor for FL. The association between monocytosis and progression-free survival (PFS) in FL remains controversial. It is unknown whether the ratio of peripheral blood absolute lymphocyte count to absolute monocyte count (ALC/AMC) at diagnosis is associated with FL prognosis. We studied 99 consecutive patients with FL who were treated with rituximab-containing chemotherapy at Kitano Hospital or Kyoto University Hospital between 2000 and 2012. We analyzed individual variables associated with the ALC/AMC ratio before treatment, as well as known prognostic factors of FL, and found that an ALC/AMC ratio of 4.7 was the best cut-off value for PFS. Kaplan-Meier analysis showed that a decreased ALC/AMC ratio was associated with inferior PFS (P = 0.022). Multivariate analysis showed that a decreased ALC/AMC ratio was a significant poor prognostic factor independent of other variables (hazard ratio, 2.714; 95 % confidence interval, 1.060-6.948; P = 0.037). The ALC/AMC ratio before treatment may be a significant prognostic factor predicting PFS of FL.

The Eradication of Helicobacter pylori does not Affect Glycemic Control in Japanese Subjects with Type 2 Diabetes.

Since infection with Helicobacter pylori has been suggested to play a pathogenic role in diabetes mellitus, we investigated whether eradication therapy for H. pylori might affect glycemic control in Japanese subjects with type 2 diabetes. A total of 72 subjects (55 males, 17 females; aged 63.7 years) with type 2 diabetes who received eradication therapy for H. pylori were included. The change of their blood glycosylated hemoglobin (A1C) levels 3 months before (-3 m) the H. pylori eradication, as well as 3 months (3 m) and 6 months (6 m) after were evaluated. Their A1C levels did not show any significant change after therapy {6.9 [0.1]% (-3 m) to 7.0 [0.1]% (3 m); P = 0.3, 7.0 [0.1] (6 m); P = 0.3}. Our findings suggest that the eradication therapy for H. pylori does not, at least profoundly, affect glycemic control in Japanese subjects with type 2 diabetes.

Safety, humoral and cell-mediated immune responses to herpes zoster vaccine in subjects with diabetes mellitus.

OBJECTIVE: To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. METHODS: A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. RESULTS: The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. CONCLUSION: The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus.

Possible link of pioglitazone with bladder cancer in Japanese patients with type 2 diabetes.

We retrospectively examined the frequency of bladder cancer in Japanese patients with type 2 diabetes in relation to use of pioglitazone. Among a total of 663 patients identified to be taking pioglitazone, 9 had bladder cancer (1.36%). Overall the hazard ratio of 1.75 [95% CI: 0.89-3.45] for pioglitazone for bladder cancer was not significant. However the prevalence of bladder cancer was 2.10% in patients taking pioglitazone for less than 24 months which was significant increased (HR 2.73 [95% CI: 1.11-6.72]).

Clinical heterogeneity of adult Japanese diabetes depending on titers of glutamic acid decarboxylase autoantibodies.

UNLABELLED: Aims/Introduction: We examined whether levels of glutamic acid decarboxylase autoantibodies (GADAb) might show the clinical heterogeneity of adult Japanese diabetes. MATERIALS AND METHODS: In this cross-sectional study, the serum levels of GADAb were measured in a total of 1857 consecutive adult diabetic patients aged 20 years or older. The patients with positive GADAb, arbitrarily defined as ≥1.5 U/mL, were divided into quartiles according to the number of patients. The age- and sex-matched diabetic patients without GADAb were selected as a control group. RESULTS: A total of 103 (5.5%) of the diabetic patients had GADAb, and showed higher HbA1c and serum high-density lipoprotein (HDL) cholesterol levels, lower body mass index (BMI), urinary C-peptide immunoreactivity (CPR), serum triglycerides (TG) and uric acid (UA) levels, and lower prevalence of metabolic syndrome than the control group (P < 0.05). Quartiles 3 and 4 (i.e. GADAb ≥4.6 U/mL) showed a higher HbA1c level, lower BMI, urinary CPR, serum TG and UA levels, quartile 2 (2.5 ≤ GADAb < 4.6 U/mL) showed a lower BMI level than the control group (P < 0.05). Among the clinical parameters, we observed significant upward trends for both HbA1c and serum HDL cholesterol levels, and significant downward trends for BMI, serum TG and UA, urinary CPR levels, and prevalence of metabolic syndrome across GADAb quartiles (P < 0.05 for trend). CONCLUSIONS: These results show that the clinical phenotype of adult Japanese diabetes correlates with GADAb levels, and that patients with GADAb (≥2.5 U/mL) show different characteristics from those without GADAb, although further longitudinal studies are required. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00190.x, 2011).

[Development of a Web-based laboratory data browser integrated with heterogeneous clinical information].

OBJECTIVE: To demonstrate the feasibility of a Web-based laboratory data browser integrated with heterogeneous clinical information in a hospital setting. METHODS: A Java-based web application was developed in-house, using free open-source software. The server side manages queries to heterogeneous hospital databases containing patient data. Order entry information including laboratory test results, drug prescriptions, injection orders, physiological test orders and, imaging test orders, was retrieved from a replication database, and integrated with nursing data from a nursing system database. The result was visualized in a time-series table format, and accessed by web browsers on computers connected to the hospital intranet. RESULTS: The laboratory data browser system achieved practical response times over huge databases (> 90 million records). The medical personnel accepted the system well, and applied the system to various clinical situations. CONCLUSION: Integrating heterogeneous data from hospital databases in a Web-based laboratory data browser is a practical approach. Presenting relevant medical information simultaneously added value to the laboratory data, and may promote better medical management.

Usefulness of serum cystatin C in Japanese patients with type 2 diabetes mellitus and nephropathy.

We examined usefulness of serum cystatin C to detect chronic kidney disease (CKD) stage >or=3, which was defined by Modification of Diet in Renal Disease formula. Serum cystatin C could detect CKD stage >or=3 with high efficacy in 289 Japanese patients with type 2 diabetes and nephropathy.

[Combining the use of dipstick protein and specific gravity accurately predicts pathological proteinuria in Japan].

UNLABELLED: Dipstick urine analysis is the most common and convenient examination in routine health care. The criteria for abnormal proteinuria is a level of more than (+). However, the interference of urine concentration should be considered in the judgement. OBJECTIVE: The purpose is to demonstrate the effect of the combined use of specific gravity (SG) in the dipstick judgement to evaluate pathological proteinuria in Japanese people. METHODS: The hospital laboratory database of Kitano hospital was searched for urine samples, for patients consulted at our nephrology department from Oct. 2004 to Sep. 2005 (n=1767), and simultaneously assayed for dipstick proteinuria(DSP), SG, urinary protein, urine creatinine (UC) and urinary protein-creatinine ratio (UPC ratio). To generate a model table, samples were stratified according to DSP and SG values. A DSP versus SG matrix (5 x 6)was created, and then all 30 cells were color-coded by the pathological proteinuria proportion (white: < 5%, gray: 5-95%, black: <95%). RESULTS: SG was positively associated with UC. In the patients, SG < or = 1.005 and DSP(-), 12/70 (17.1%) was > or =300 mg/gCr. Moreover in the patients, both 1.005 < SG < or = 1.010 and DSP(+/-), 21/32 (65.6%) had pathological proteinuria. We confirmed the consistency for this combination table in the urine samples of another 1111 out-patients. Moreover, the area under the curve in DSP(+/-) suggests that the patients whose SG was < or = 1.011 might have pathological proteinuria (sensitivity; 82.1%, specificity; 89.3%). CONCLUSION: We recognized that the combination of DSP and SG enhances a more accurate proteinuria judgement. DSP(- approximately +/-) in diluted urine (SG < or = 1.1011) has the potential for pathological proteinuria. Therefore, diluted urine samples should be re-examined.