Salinity Tolerance and Osmoadaptation Strategies in Four Genera of Anammox Bacteria: Brocadia, Jettenia, Kuenenia, and Scalindua.

The salinity tolerance and osmoadaptation strategies in four phylogenetically distant anammox species, Brocadia, Jettenia, Kuenenia, and Scalindua, were investigated by using highly enriched cell cultures. The first-emerged "Ca. Scalindua sp." showed optimum growth at 1.5-3% salinity and was tolerant to ∼10% salinity (a slight halophile). The second-emerged "Ca. Kuenenia stuttgartiensis" was tolerant to ∼6% salinity with optimum growth at 0.25-1.5% (a halotolerant). These early-emerged "Ca. Scalindua sp." and ″Ca. K. stuttgartiensis" rapidly accumulated K+ ions and simultaneously synthesized glutamate as a counterion. Subsequently, part of the glutamate was replaced by trehalose. In contrast, the late-emerged "Ca. B. sinica" and "Ca. J. caeni" were unable to accumulate sufficient amounts of K+─glutamate and trehalose, resulting in a significant decrease in activity even at 1-2% salinity (nonhalophiles). In addition, the external addition of glutamate may increase anammox activity at high salinity. The species-dependent salinity tolerance and osmoadaptation strategies were consistent with the genetic potential required for the biosynthesis and transport of these osmolytes and the evolutionary history of anammox bacteria: Scalindua first emerged in marine environments and then Kuenenia and other two species gradually expanded their habitat to estuaries, freshwater, and terrestrial environments, while Brocadia and Jettenia likely lost their ability to accumulate K+─glutamate.

Collaborative metabolisms of urea and cyanate degradation in marine anammox bacterial culture.

Anammox process greatly contributes to nitrogen loss occurring in oceanic oxygen minimum zones (OMZs), where the availability of NH4+ is scarce as compared with NO2-. Remineralization of organic nitrogen compounds including urea and cyanate (OCN-) into NH4+ has been believed as an NH4+ source of the anammox process in oxygen minimum zones. However, urea- or OCN-- dependent anammox has not been well examined due to the lack of marine anammox bacterial culture. In the present study, urea and OCN- degradation in a marine anammox bacterial consortium were investigated based on 15N-tracer experiments and metagenomic analysis. Although a marine anammox bacterium, Candidatus Scalindua sp., itself was incapable of urea and OCN- degradation, urea was anoxically decomposed to NH4+ by the coexisting ureolytic bacteria (Rhizobiaceae, Nitrosomonadaceae, and/or Thalassopiraceae bacteria), whereas OCN- was abiotically degraded to NH4+. The produced NH4+ was subsequently utilized in the anammox process. The activity of the urea degradation increased under microaerobic condition (ca. 32-42 µM dissolved O2, DO), and the contribution of the anammox process to the total nitrogen loss also increased up to 33.3% at 32 µM DO. Urea-dependent anammox activities were further examined in a fluid thioglycolate media with a vertical gradient of O2 concentration, and the active collaborative metabolism of the urea degradation and anammox was detected at the lower oxycline (21 µM DO).

Comparison of Schlemm's Canal Morphology Parameters Between Propensity Score-Matched Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Purpose: This study aimed to histologically compare the status of Schlemm's canal (SC) and Schlemm's canal endothelial (SCE) cells between trabeculectomy specimens from patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). Methods: A total of 182 eyes from 152 patients with POAG and 138 eyes from 116 patients with EXG underwent immunohistochemical staining for thrombomodulin. Equal numbers of cases were selected from both groups using propensity score matching. The following parameters were evaluated: total SC length, staining positive and negative SC length (PSC and NSC, respectively), opened and closed SC length, staining positive and opened SC length, staining positive and closed SC length, staining negative and opened SC length (NOSC), and staining negative and closed SC length. Results: After matching for age and gender, 87 cases were selected in each group. The EXG group had significantly higher preoperative IOP and medication scores. PSC was significantly longer in the POAG group, while NSC and NOSC were longer in the EXG group. Multiple regression analysis of these 174 cases revealed that PSC was significantly shorter in the EXG group. After matching for age, gender, preoperative IOP, and medication score, 64 cases were selected in each group, and NOSC was significantly longer in the EXG group. Conclusions: These findings suggest that in EXG, SCE loss occurs independently of background factors such as aging and medication use. The loss of SCE may have a more critical impact on IOP elevation in EXG compared to POAG.

Oxygen tolerance and detoxification mechanisms of highly enriched planktonic anaerobic ammonium-oxidizing (anammox) bacteria.

Oxygen is a key regulatory factor of anaerobic ammonium oxidation (anammox). Although the inhibitory effect of oxygen is evident, a wide range of oxygen sensitivities of anammox bacteria have been reported so far, which makes it difficult to model the marine nitrogen loss and design anammox-based technologies. Here, oxygen tolerance and detoxification mechanisms of four genera of anammox bacteria; one marine species ("Ca. Scalindua sp.") and four freshwater anammox species ("Ca. Brocadia sinica", "Ca. Brocadia sapporoensis", "Ca. Jettenia caeni", and "Ca. Kuenenia stuttgartiensis") were determined and then related to the activities of anti-oxidative enzymes. Highly enriched planktonic anammox cells were exposed to various levels of oxygen, and oxygen inhibition kinetics (50% inhibitory concentration (IC50) and upper O2 limits (DOmax) of anammox activity) were quantitatively determined. A marine anammox species, "Ca. Scalindua sp.", exhibited much higher oxygen tolerance capability (IC50 = 18.0 µM and DOmax = 51.6 µM) than freshwater species (IC50 = 2.7-4.2 µM and DOmax = 10.9-26.6 µM). The upper DO limit of "Ca. Scalindua sp." was much higher than the values reported so far (~20 µM). Furthermore, the oxygen inhibition was reversible even after exposed to ambient air for 12-24 h. The comparative genome analysis confirmed that all anammox species commonly possess the genes considered to function for reduction of O2, superoxide anion (O2•-), and H2O2. However, the superoxide reductase (Sor)-peroxidase dependent detoxification system alone may not be sufficient for cell survival under microaerobic conditions. Despite the fact that anaerobes normally possess no or little superoxide dismutase (Sod) or catalase (Cat), only Scalindua exhibited high Sod activity of 22.6 ± 1.9 U/mg-protein with moderate Cat activity of 1.6 ± 0.7 U/mg-protein, which was consistent with the genome sequence analysis. This Sod-Cat dependent detoxification system could be responsible for the higher O2 tolerance of Scalindua than other freshwater anammox species lacking the Sod activity.

Assessing the Risk of Decrease in Kidney Function in Patients Prescribed Direct-Acting Antivirals for Hepatitis C Utilizing the MID-NET® Medical Information Database Network in Japan.

An association between kidney disease and direct-acting antivirals against hepatitis C (DAAs) has been suggested, however the warning on the package insert (PI) of the drug varies among DAAs. In this study, the risk of decreased kidney function associated with DAAs marketed in Japan was investigated to determine whether the risk of kidney disease is a common adverse event and class effect of DAAs. Data for patients who were new users of DAAs marketed in Japan, with eGFR ≥ 45 mL/min/1.73 m2 and without specific risk factors, were extracted from the MID-NET® medical information database network in Japan. Changes from the baseline on estimated glomerular filtration rate (eGFR) categories (eGFR ≥ 90, 90 > eGFR ≥ 60, 60 > eGFR ≥ 45, 45 > eGFR ≥ 30, 30 > eGFR ≥ 15, 15 > eGFR; unit: mL/min/1.73 m2) were used for evaluating the risk of decreased kidney function. Exposure groups for DAAs and relevant concomitant drugs were categorized into 10 patterns based on the PI. Among the 10 patterns, a significant increase in the incidence rate ratio (P < 0.01) was observed in the prescription patterns of concomitant use of telaprevir with peginterferon alpha and ribavirin, concomitant use of daclatasvir hydrochloride with asunaprevir, and ombitasvir hydrate combined with paritaprevir hydrate and ritonavir, which were concomitantly used with ribavirin; such an increase was not observed in the other prescription patterns. The effects of DAAs on kidney function may differ among drugs, suggesting the possibility that the risk of kidney disease is not a class effect of DAAs and should be evaluated individually for each DAA.

Aseptic Cavernosal Abscess: An Unrecognized Feature of Neutrophilic Dermatosis.

A 50-year-old man developed a sterile cavernosal abscess followed by prominent features of necrotizing neutrophilic dermatosis. We conducted a literature review, which revealed that aseptic abscesses in the corpus cavernosum occur in association with neutrophilic dermatosis. Patients with this condition frequently receive unnecessary antibiotic treatment and surgical interventions. Although this condition responds to systemic corticosteroids, the functional prognosis of the penis is poor. Abscess formation may be the initial presentation of neutrophilic dermatoses, and underlying conditions may even be absent. Clinicians need to be aware of this condition to distinguish it from bacterial infection and initiate early disease-specific treatments.

Maintenance power requirements of anammox bacteria "Candidatus Brocadia sinica" and "Candidatus Scalindua sp."

Little is known about the cell physiology of anammox bacteria growing at extremely low growth rates. Here, "Candidatus Brocadia sinica" and "Candidatus Scalindua sp." were grown in continuous anaerobic membrane bioreactors (MBRs) with complete biomass retention to determine maintenance energy (i.e., power) requirements at near-zero growth rates. After prolonged retentostat cultivations, the specific growth rates (µ) of "Ca. B. sinica" and "Ca. Scalindua sp." decreased to 0.000023 h-1 (doubling time of 1255 days) and 0.000157 h-1 (184 days), respectively. Under these near-zero growth conditions, substrate was continuously utilized to meet maintenance energy demands (me) of 6.7 ± 0.7 and 4.3 ± 0.7 kJ mole of biomass-C-1 h-1 for "Ca. B. sinica" and "Ca. Scalindua sp.", which accorded with the theoretically predicted values of all anaerobic microorganisms (9.7 and 4.4 kJ mole of biomass-C-1 h-1at 37 °C and 28 °C, respectively). These me values correspond to 13.4 × 10-15 and 8.6 × 10-15 watts cell-1 for "Ca. B. sinica" and "Ca. Scalindua sp.", which were five orders of magnitude higher than the basal power limit for natural settings (1.9 × 10-19 watts cells-1). Furthermore, the minimum substrate concentrations required for growth (Smin) were calculated to be 3.69 ± 0.21 and 0.09 ± 0.05 µM NO2- for "Ca. B. sinica" and "Ca. Scalindua sp.", respectively. These results match the evidence that "Ca. Scalindua sp." with lower maintenance power requirement and Smin are better adapted to energy-limited natural environments than "Ca. B. sinica", suggesting the importance of these parameters on ecological niche differentiation in natural environments.

Evaluation of the outcome of long-tube shunt implant surgery in uveitic glaucoma patients by analyzing the background of uveitis.

PURPOSE: To evaluate the efficacy of long-tube shunt surgery (LTSS) without valve in uveitic glaucoma (UG) eyes. METHODS: We retrospectively analyzed the data of 45 UG eyes that underwent only LTSS or LTSS combined with trabeculectomy (TLE) (LTSS/TLE). The UG eyes were analyzed by categorizing them into granulomatous/non-granulomatous, steroid responder/non-responder, and primary open-angle glaucoma (POAG) (POAG background)/non-POAG (non-POAG background). All granulomatous UG eyes received a continuous 3-times-daily administration of topical betamethasone post-LTSS. RESULTS: The eyes consisted of granulomatous (37 eyes, 82%)/non-granulomatous (5 eyes, 11%), steroid responder (19 eyes, 42%)/non-steroid responder (13 eyes, 29%), and 20 eyes with POAG or POAG background (p = 0.0022, 83%) among 24 cases of unilateral UG. The 5-year survival rates of only LTSS and LTSS/TLE were 66% and 100%, respectively. Kaplan-Meier survival-curve estimates in the non-granulomatous group were 100% for 6-year postoperative period, while the granulomatous group showed a gradual decrease along the 6-year (81%) postoperative period. The 5-year survival rates in the steroid responder group and the non-steroid responder group eyes were 74% and 78%, respectively. No intraocular pressure (IOP) elevation was observed in the positive steroid responder eyes post-LTSS. CONCLUSIONS: LTSS and LTSS/TLE were both effective in UG. Positive steroid response may be masked by LTSS in the positive responder eyes. Continuous administration of topical betamethasone post-LTSS may be important for preventing an IOP spike by suppressing inflammation in the anterior chamber. LTSS combined with TLE may be recommended in eyes with granulomatous UG, and the coexistence of a POAG/POAG background.

Glycogen metabolism of the anammox bacterium "Candidatus Brocadia sinica".

Presence of glycogen granules in anaerobic ammonium-oxidizing (anammox) bacteria has been reported so far. However, very little is known about their glycogen metabolism and the exact roles. Here, we studied the glycogen metabolism in "Ca. Brocadia sinica" growing in continuous retentostat cultures with bicarbonate as a carbon source. The effect of the culture growth phase was investigated. During the growing phase, intracellular glycogen content increased up to 32.6 mg-glucose (g-biomass dry wt)-1 while the specific growth rate and ATP/ADP ratio decreased. The accumulated glycogen begun to decrease at the onset of entering the near-zero growth phase and was consumed rapidly when substrates were depleted. This clearly indicates that glycogen was synthesized and utilized as an energy storage. The proteomic analysis revealed that "Ca. B. sinica" synthesized glycogen via three known glycogen biosynthesis pathways and simultaneously degraded during the progress of active anammox, implying that glycogen is being continuously recycled. When cells were starved, a part of stored glycogen was converted to trehalose, a potential stress protectant. This suggests that glycogen serves at least as a primary carbon source of trehalose synthesis for survival. This study provides the first physiological evidence of glycogen metabolism in anammox bacteria and its significance in survival under natural substrate-limited habitat.

Influence of δ18 O of water on measurements of δ18 O of nitrite and nitrate.

RATIONALE: Oxygen isotope ratio measurements of NO2 - and NO3 - by the azide method and denitrifier method are sensitive to the δ18 O value of the sample water. However, the influence of δ18 OH2O on those measurements has not been quantitatively evaluated and documented so far. Therefore, we investigated the influence of δ18 OH2O of a sample on the δ18 O analysis of NO2 - and NO3 - . METHODS: We prepared NO2 - and NO3 - standards (with known δ18 ONO2- and δ18 ONO3- values) dissolved in waters having different δ18 OH2O values (δ18 OH2O = -12.6, 25.9, 56.7, and 110.1‰). Nitrite and nitrate were converted into N2 O using the azide method and the denitrifier method, respectively. The isotope ratios of the generated N2 O were measured with a Sercon purge-and-trap gas chromatography/isotope ratio mass spectrometry (PT-GC/IRMS) system. The measured δ18 O values of the produced N2 O were plotted against known δ18 ONO2- and δ18 ONO3- values to evaluate the influence of exchange of an oxygen atom with H2 O during the conversion of NO2 - into N2 O and NO3 - into N2 O, respectively. RESULTS: The degree of oxygen isotope exchange was 10.8 ± 0.3% in the azide method and 5.5 ± 1.0% in the denitrifier method, indicating that the azide method is more susceptible to artifacts arising from differences in the δ18 OH2O value of water than the denitrifier method. Thus, the intercept of the standard calibration curve must be corrected to account for differences in δ18 OH2O . Abiotic NO2 -H2 O equilibrium isotope effect experiments yielded a rate constant of (1.13 ± 007) × 10-2 (h-1 ) and an equilibrium isotope effect of 11.9 ± 0.1‰ under the condition of pH = 7.5, 30°C, and 2.5% salinity. CONCLUSIONS: Oxygen isotope ratio measurements of NO2 - by the azide method are highly sensitive to δ18 OH2O as a result of significant oxygen isotope exchange between NO2 - and H2 O. Therefore, to obtain the most accurate measurements water with the same δ18 OH2O value as that of the sample must be used to make the NO2 - and NO3 - standards.

Dual nitrogen and oxygen isotope fractionation during anaerobic ammonium oxidation by anammox bacteria.

Natural abundance of stable nitrogen (N) and oxygen (O) isotopes are invaluable biogeochemical tracers for assessing the N transformations in the environment. To fully exploit these tracers, the N and O isotope effects (15ε and 18ε) associated with the respective nitrogen transformation processes must be known. However, the N and O isotope effects of anaerobic ammonium oxidation (anammox), one of the major fixed N sinks and NO3- producers, are not well known. Here, we report the dual N and O isotope effects associated with anammox by three different anammox bacteria including "Ca. Scalindua japonica", a putative marine species, which were measured in continuous enrichment culture experiments. All three anammox species yielded similar N isotope effects of NH4+ oxidation to N2 (15εNH4→N2) ranging from 30.9‰ to 32.7‰ and inverse kinetic isotope effects of NO2- oxidation to NO3- (15εNO2→NO3 = -45.3‰ to -30.1‰). In contrast, 15εNO2→N2 (NO2- reduction to N2) were significantly different among three species, which is probably because individual anammox bacteria species might possess different types of nitrite reductase. We also report the combined O isotope effects for NO2- oxidation (18ENO2→NO3) by anammox bacteria. These obtained dual N and O isotopic effects could provide significant insights into the contribution of anammox bacteria to the fixed N loss and NO2- reoxidation (N recycling) in various natural environments.

Sulfur-based denitrification treating regeneration water from ion exchange at high performance and low cost.

Autotrophic denitrification with sulfur is an underexplored alternative to heterotrophic denitrification to remove nitrate from wastewater poor in organics. The application on ion exchange regeneration water (19.4-32.1 mS cm-1) is novel. Three fixed bed reactors were tested at 15 °C for >4 months, inoculated with activated sludge from sewage treatment. All were fast in start-up (<10 days) with high performance (94 ±â€¯2% removal efficiency). pH control with NaOH rendered higher nitrate removal rates than limestone addition to the bed (211 ±â€¯13 vs. 102 ±â€¯13 mg N L-1 d-1), related to higher pH (6.64 vs. 6.24) and sulfur surface area. Bacterial communities were strongly enriched in Sulfurimonas (63-67%) and Thiobacillus (24-26%). In an economic comparison, sulfur-based denitrification (€5.3 kg-1 N) was 15% cheaper than methanol-based denitrification (€6.22 kg-1 N) and both treatments were opex dominated (85.9 vs. 86.5%). Overall, the technological and economic feasibility should boost further implementation of sulfurotrophic denitrification.

Low serum bilirubin concentration is a novel risk factor for the development of albuminuria in patients with type 2 diabetes.

OBJECTIVE: Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes. MATERIALS AND METHODS: We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2±0.9years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria. RESULTS: During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93). CONCLUSIONS: Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.

A difference in systolic blood pressure between arms is a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes.

OBJECTIVE: Recent studies have suggested that a difference in systolic blood pressure (SBP) between arms is associated with both vascular disease and mortality. The aim of this study was to investigate the relationship between a difference in SBP between arms and change in urinary albumin excretion or development of albuminuria in patients with type 2 diabetes. METHODS: We measured SBP in 408 consecutive patients with type 2 diabetes, and calculated a difference in SBP between arms. We performed follow-up study to assess change in urinary albumin excretion or development of albuminuria, mean interval of which was 4.6 ± 1.7 years. We then evaluated the relationship of a difference in SBP between arms to diabetic nephropathy using multiple regression analysis and multiple Cox regression model. RESULTS: Multiple regression analyses demonstrated that a difference in SBP between arms was independently associated with change in urinary albumin excretion (ß = 0.1869, P = 0.0010). Adjusted Cox regression analyses demonstrated that a difference in SBP between arms was associated with an increased hazard of development of albuminuria; hazard ratio was 1.215 (95% confidence interval 1.077-1.376). Moreover, the risk of development of albuminuria was increased in patients with a difference in SBP of equal to or more than 10 mmHg between arms; hazard ratio was 4.168 (95% confidence interval 1.478-11.70). CONCLUSION: A difference in SBP between arms could be a novel predictor of the development and progression of diabetic nephropathy in patients with type 2 diabetes.

Effects of liraglutide on postprandial insulin and glucagon responses in Japanese patients with type 2 diabetes.

This study assessed the endocrine pancreatic responses to liraglutide (0.9 mg once a day) during normal living conditions in Japanese patients with type 2 diabetes. The study included 14 hospitalized patients with type 2 diabetes. Meal tests were performed after improvement of glycemic control achieved by two weeks of multiple insulin injection therapy and after approximately two weeks of liraglutide treatment. Continuous glucose monitoring was performed to compare daily variation in glycemic control between multiple insulin injection therapy and liraglutide treatment. Liraglutide reduced plasma glucose levels after the test meals (60-180 min; p<0.05), as a result of significant increases in insulin secretion (0-180 min; p<0.05) and decreases in the incremental ratio of plasma glucagon (15-60 min; p<0.05). Continuous glucose monitoring showed that liraglutide treatment was also associated with a decrease in glucose variability. We also demonstrated that optimal glycemic control seen as a reduction in 24-h mean glucose levels and variability was obtained only with liraglutide monotherapy. In conclusion, liraglutide treatment increases insulin secretion and suppresses glucagon secretion in Japanese patients with type 2 diabetes under normal living conditions. The main therapeutic advantages of liraglutide are its use as monotherapy and its ability to decrease glucose variability.

Suppression of camptothecin biosynthetic genes results in metabolic modification of secondary products in hairy roots of Ophiorrhiza pumila.

Camptothecin is a monoterpenoid indole alkaloid that exhibits anti-tumor activity. In Ophiorrhiza pumila, production of camptothecin and its related alkaloids was high in the hairy roots, but not in the cell suspension culture derived from hairy roots. To identify the intermediates in camptothecin biosynthesis, expression of genes encoding tryptophan decarboxylase (TDC) and secologanin synthase (SLS), the two enzymes catalyzing the early steps in camptothecin biosynthesis, were suppressed in the hairy roots of O. pumila by RNA interference (RNAi), and metabolite changes were investigated. In most TDC- and SLS-suppressed lines, accumulation of camptothecin and related alkaloids, strictosidine, strictosamide, pumiloside, and deoxypumiloside was reduced. The accumulation levels of secologanin exhibited a strong negative correlation with the expression level of TDC, and that of loganin exhibited a negative correlation with the expression level of SLS. Some hairy root-specific chromatographic peaks detected by liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) exhibited positive or negative correlation with TDC expression, suggesting their possible involvement in camptothecin biosynthesis.

Dipeptidyl-peptidase IV inhibitor is effective in patients with type 2 diabetes with high serum eicosapentaenoic acid concentrations.

UNLABELLED: Aims/Introduction: Eicosapentaenoic acid (EPA) stimulates glucagon-like peptide-1 (GLP-1) secretion in mice. We investigated the relationship between serum EPA concentrations and the efficacy of dipeptidyl-peptidase IV (DPP-4) inhibitor in patients with type 2 diabetes. MATERIALS AND METHODS: Serum EPA concentrations were measured in 62 consecutive patients with type 2 diabetes who were newly given DPP-4 inhibitor as a monotherapy or as an add-on therapy to oral hypoglycemic agents. The dosage of oral hypoglycemic agents was maintained during the observation period. After 24 weeks of treatment with DPP-4 inhibitor, we evaluated the relationships between a decrease in hemoglobin A1c from baseline and serum EPA concentrations, as well as age, sex, body mass index (BMI), hemoglobin A1c at baseline and usage of antidiabetic concomitant drugs. RESULTS: Hemoglobin A1c was significantly decreased from 8.1 ± 1.1% to 7.2 ± 1.0% by DPP-4 inhibitor. A decrease in hemoglobin A1c correlated with BMI (r = -0.396, P = 0.0013), age (r = 0.275, P = 0.0032), hemoglobin A1c at baseline (r = 0.490, P < 0.0001) and log EPA (r = 0.285, P = 0.0246). Multiple regression analysis showed that BMI (ß = -0.419, P = 0.0002), hemoglobin A1c at baseline (ß = 0.579, P < 0.0001) and log EPA (ß = 0.220, P = 0.0228) were independent determinants of decrease in hemoglobin A1c. CONCLUSIONS: DPP-4 inhibitor is effective in patients with type 2 diabetes with high serum EPA concentrations. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00220.x , 2012).