Aldosterone-to-Renin Ratio Is Associated with Diabetic Nephropathy in Type 2 Diabetic Patients: A Single-Center Retrospective Study.

BACKGROUND It is well established that primary aldosteronism (PA) and aldosterone-to-renin ratio (ARR) are associated with kidney disease. The aim of this study was to retrospectively investigate the relationship between ARR, urinary albumin excretion (UAE), and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes from a single center. MATERIAL AND METHODS We included 70 patients with type 2 diabetes, UAE ≤100 mg/day, not taking renin-aldosterone system inhibitors, did not meet the diagnostic criteria for PA, and had an ARR <20. The patients were divided into 3 groups: the normal low (NL) group (33 patients) with a UAE <10 mg/day, the normal (N) group (22 patients) with a UAE of 10-29 mg/day, and the microalbuminuria (M) group (15 patients) with a UAE of 30-100 mg/day. The ARR, plasma renin activity (PRA), and plasma aldosterone (PAC) were compared among groups. RESULTS The ARR was highest in group M (10.1±4.6), 6.5±0.3 in group NL, and 7.0±2.7 in group N. The PRA and PAC were significantly lower in group M (P<0.001). The ARR showed a significant positive correlation with log UAE (r=0.37, P<0.001) and a significant negative correlation with eGFR (r=-0.33, P<0.01). CONCLUSIONS High levels of aldosterone relative to renin, which did not fulfill confirmatory criteria for PA, may be one of the risk factors for the development of diabetic nephropathy in patients with diabetes. The present results are supported by previous research showing that an increased ARR without PA was a risk factor for kidney disease.

Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR).

BACKGROUND: Few prospective studies have compared the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. We aimed to clarify the efficacy of dapagliflozin versus sitagliptin for modulating cardiometabolic risk factors including high glycated hemoglobin (HbA1c) levels, hypoglycemia, and body weight. METHODS: This prospective, randomized, open-label, blinded-endpoint, parallel-group trial enrolled 340 Japanese patients with early-stage type 2 diabetes receiving metformin alone or no glucose-lowering agents, who were randomized to receive dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was the proportion of patients who achieved the composite endpoint of HbA1c level maintenance < 7.0% (53 mmol/mol), avoidance of hypoglycemia (maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL), and ≥ 3.0% body weight loss from baseline. Secondary endpoints included components of the primary endpoint, other metabolic indices, and glucose variability indices measured using flash glucose monitoring. RESULTS: Clinical characteristics of patients were age, 58.1 ± 12.2 years; known duration of diabetes, 5.8 ± 6.1 years; body weight, 74.7 ± 14.2 kg; body mass index, 27.9 ± 4.1 kg/m2; and HbA1c level, 7.8 ± 0.8% at baseline. The achievement ratio of primary endpoint was significantly higher in the dapagliflozin group than in the sitagliptin group (24.4% vs. 13.8%, P < 0.05). While the rates of HbA1c level maintenance < 7.0% (53 mmol/mol) and avoidance of hypoglycemia were comparable between the groups (49.4 vs. 50.0% and 88.7 vs. 92.3% for dapagliflozin vs. sitagliptin, respectively), body weight loss of ≥ 3.0% was significantly achieved in the dapagliflozin group (54.4 vs. 19.6%, P < 0.001). Moreover, dapagliflozin was superior to sitagliptin regarding several secondary endpoints that modulate cardiometabolic risk, namely reducing fasting plasma glucose, insulin, uric acid, increasing high-density lipoprotein cholesterol, and suppressing the increase in serum creatinine and the decrease in estimated glomerular filtration rate. On the other hand, sitagliptin was superior to dapagliflozin in suppressing glucose variability. CONCLUSIONS: Compared to sitagliptin, dapagliflozin was significantly more effective at improving cardiometabolic risk factors, suggesting that SGLT2 inhibitors might be more suitable than DPP-4 inhibitors for preventing cardiovascular events in patients with early-stage but inadequately controlled type 2 diabetes. Trial registration Trial number, UMIN000028014; registered on June 30, 2017.

Tescalcin is a potential target of class I histone deacetylase inhibitors in neurons.

Class I histone deacetylase (HDAC) inhibitors are believed to have positive effects on neurite outgrowth, synaptic plasticity, and neurogenesis in adult brain. However, the downstream molecular targets of class I HDAC inhibitors in neurons are not clear. Although class I HDAC inhibitors are thought to broadly promote transcription of many neuronal genes through enhancement of histone acetylation, the affected gene set may include unidentified genes that are essential for neuronal survival and function. To identify novel genes that are targets of class I HDAC inhibitors, we used a microarray to screen transcripts from neuronal cultures and evaluated changes in protein and mRNA expression following treatment with four HDAC inhibitors. We identified tescalcin (Tesc) as the most strongly up-regulated gene following treatment with class I HDAC inhibitors in neurons. Moreover, hippocampal neurons overexpressing TESC showed a greater than 5-fold increase in the total length of neurites and number of branch points compared with controls. These findings highlight a potentially important role for TESC in mediating the neuroprotective effect of class I HDAC inhibitors. TESC may also be involved in the development of brain and neurodegenerative diseases through epigenetic mechanisms.

Efficacy and Safety of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin on Atherosclerosis, ß-Cell Function, and Glycemic Control in Japanese Patients with Type 2 Diabetes Mellitus Who are Treatment Naïve or Poorly Responsive to Antidiabetes Agents: A Multicenter, Prospective Observational, Uncontrolled Study.

BACKGROUND: Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is widely used in patients with type 2 diabetes. However, the pleiotropic effects of sitagliptin is not well understood. OBJECTIVE: To assess the clinical efficacy and safety of sitagliptin on atherosclerosis, ß-cell function, and glycemic control in Japanese patients with type 2 diabetes. METHODS: A prospective observational study of 270 patients with type 2 diabetes mellitus was carried out. Patients (aged 64.3 [12.4] years, body mas index 25.2 [4.3]) with glycated hemoglobin >6.9% (52 mmol/mol) or fasting plasma glucose >130 mg/dL were treated with sitagliptin for 12 months. The primary end point was glycated hemoglobin level changes from baseline to 3 months. The secondary end points included changes in several biomarkers related to inflammation and ß-cell function from baseline to 3 months, as well as changes in glycated hemoglobin level from baseline to 12 months. RESULTS: Glycated hemoglobin levels were significantly lower in patients treated with sitagliptin for 3 months than at baseline (8.1% [1.4%]-7.3% [1.2%]) (65 [16.9]-56 [13.1] mmol/mol]) (P < 0.0001), which continued after 12 months (7.4% [1.3%]) (56 [15.2] mmol/mol) (P < 0.0001). In addition, a marker of vascular-specific inflammation, pentraxin-3, and a marker of ß-cell function (proinsulin/insulin ratio), respectively, were lower after treatment with sitagliptin for 3 months than at baseline (1.88 [0.78]-1.65 [0.63] ng/mL [P = 0.0038] and 0.20 [0.14]-0.17 [0.11] [P = 0.01], respectively). On the other hand, a biomarker reflecting whole body inflammation; that is, high-sensitivity C-reactive protein level, was unchanged. Adverse events occurred in 14 patients (5.18%). CONCLUSIONS: Sitagliptin may have beneficial effects on vascular inflammation and ß-cell function in Japanese patients with type 2 diabetes. Pentraxin-3 may be an early predictive marker for detecting the antiatherosclerotic effects of dipeptidyl peptidase-4.

Rapid identification and subtyping of Helicobacter cinaedi strains by intact-cell mass spectrometry profiling with the use of matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Helicobacter cinaedi infection is recognized as an increasingly important emerging disease in humans. Although H. cinaedi-like strains have been isolated from a variety of animals, it is difficult to identify particular isolates due to their unusual phenotypic profiles and the limited number of biochemical tests for detecting helicobacters. Moreover, analyses of the 16S rRNA gene sequences are also limited due to the high levels of similarity among closely related helicobacters. This study was conducted to evaluate intact-cell mass spectrometry (ICMS) profiling using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) as a tool for the identification of H. cinaedi. A total of 68 strains of H. cinaedi isolated from humans, dogs, a cat, and hamsters were examined in addition to other Helicobacter species. The major ICMS profiles of H. cinaedi were identical and differed from those of Helicobacter bilis, which show >98% sequence similarity at the 16S rRNA sequence level. A phyloproteomic analysis of the H. cinaedi strains examined in this work revealed that human isolates formed a single cluster that was distinct from that of the animal isolates, with the exception of two strains from dogs. These phyloproteomic results agreed with those of the phylogenetic analysis based on the nucleotide sequences of the hsp60 gene. Because they formed a distinct cluster in both analyses, our data suggest that animal strains may not be a major source of infection in humans. In conclusion, the ICMS profiles obtained using a MALDI-TOF MS approach may be useful for the identification and subtyping of H. cinaedi.

A Case of Acute-Onset Type 1 Diabetes Mellitus with Diabetic Ketoacidosis Triggered by COVID-19.

BACKGROUND It is well known that diabetes mellitus contributes to COVID-19 severity. Recently, there have been reports of an increase in the number of children with type 1 diabetes after the COVID-19 pandemic. CASE REPORT A 52-year-old woman presented to the Emergency Department with disturbance of consciousness, accompanied by a 1-day history of thirst, a fever of 38°C, and breathlessness. She had a positive coronavirus antigen test. Her initial vital signs assessment showed a heart rate of 120 beats per minute, blood pressure 90/50 mmHg, temperature 37.3°C, and respiratory rate 30 breaths/minute with an oxygen saturation of 100% with 10 L oxygen inhalation. Her initial laboratory test results showed a blood glucose level of 1507 mg/dl, HbA1c of 10.1%, ketone 2+, and blood gas pH 7.113. The patient was diagnosed with diabetic ketoacidosis (DKA). There were mild inflammatory findings with blood CRP 0.14 mg/dl and a white cell count of 12 400/µL, but no pneumonia on a chest CT scan. Therefore, the patient was diagnosed with COVID-19 and DKA. The patient was positive for anti-glutamic acid decarboxylase (anti-GAD antibody) and had markedly low levels 24-h urine C-peptide (CPR). She was diagnosed with acute-onset type 1 diabetes mellitus, as her blood examination showed a postprandial blood glucose level of 100 mg/dl and HbA1c of 5.7% 2 months before admission. After admission, fluid replacement and continuous intravenous insulin infusion therapy were started, and blood glucose and blood gas pH improved over 10 h. CONCLUSIONS There have been reports of cases of type 1 diabetes consequences of COVID-19, but the mechanism has not been elucidated.

New microbial mannan catabolic pathway that involves a novel mannosylglucose phosphorylase.

The consecutive genes BF0771-BF0774 in the genome of Bacteroides fragilis NCTC 9343 were found to constitute an operon. The functional analysis of BF0772 showed that the gene encoded a novel enzyme, mannosylglucose phosphorylase that catalyzes the reaction, 4-O-ß-d-mannopyranosyl-d-glucose+Pi→mannose-1-phosphate+glucose. Here we propose a new mannan catabolic pathway in the anaerobe, which involves 1,4-ß-mannanase (BF0771), a mannobiose and/or sugar transporter (BF0773), mannobiose 2-epimerase (BF0774), and mannosylglucose phosphorylase (BF0772), finally progressing to glycolysis. This pathway is distributed in microbes such as Bacteroides, Parabacteroides, Flavobacterium, and Cellvibrio.

A comparison of meal tolerance test and oral glucose tolerance test for predicting insulin therapy in patients with gestational diabetes.

AIMS: To identify factors predicting a need for insulin therapy in gestational diabetes mellitus (GDM) by comparing plasma glucose (PG) levels in a 75-g oral glucose tolerance test (75-g OGTT) with those in a 500-kcal meal tolerance test (MTT) containing 75 g of carbohydrate. SUBJECTS AND METHODS: The MTT was performed in 61 patients who diagnosed with GDM by a 75-g OGTT (age, 33.2 ± 4.5 years; prepregnancy body mass index, 22.6 ± 4.7 kg/m2; number of gestational weeks, 25.1 ± 6.4 weeks). PG and serum insulin levels were measured before the meal and up to 180 min after the meal. The insulin secretion capacity and resistance index were calculated. RESULTS: PG levels increased from 86.8 ± 8.8 mg/dL at fasting to 132.7 ± 20.1 mg/dL at 30 min, and 137.8 ± 27.7 mg/dL at 60 min after MTT in the 35 patients with needed insulin therapy; these levels were significantly higher than those in the 26 patients, who only needed diet therapy. The patients with needed insulin therapy had significantly higher fasting PG levels in the 75-g OGTT, PG levels at fasting and 30 min after the MTT, and homeostasis model assessment of insulin resistance (HOMA-IR), and a significantly lower disposition index (DI) and insulin index than patients treated by diet alone. Receiver operating characteristic curve analysis was performed for factors involved in insulin therapy, with the following cutoff values: fasting PG in the 75-g OGTT, 92 mg/dL; PG 30 min after MTT, 129 mg/dL; HOMA-IR, 1.51; DI, 3.9; HbA1c, 5.4%. Multivariate analysis revealed that the 30-min PG level after MTT and HOMA-IR predicted insulin therapy. CONCLUSION: PG levels at 30 min after MTT may be useful for identifying patients with GDM, who need insulin therapy.

Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy.

Osimertinib has demonstrated efficacy against stable or asymptomatic central nervous system (CNS) metastases of epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) in phase 2 and 3 clinical trials that allowed prior CNS radiotherapy. However, the efficacy of osimertinib only or the optimal treatment combination or sequence of radiotherapy has not been investigated. A 74-year-old woman diagnosed with T4N1M1c Stage IVB lung adenocarcinoma with EGFR mutation presented with a left upper lobe mass and multiple bilateral lung metastases. A total of more than 20 asymptomatic multiple brain metastases with a maximum diameter of 12 mm were diagnosed simultaneously. Osimertinib was administered as first-line treatment. Whole brain radiotherapy was deferred because she had no neurological symptoms. After 5 weeks, the multiple brain metastases disappeared completely, together with the response in the lung lesions. This case demonstrated that first-line treatment with osimertinib could even achieve complete remission of multiple brain metastases comprising as many as twenty lesions of EGFR-mutated NSCLC without radiation therapy. Radiation therapy for brain metastases can be deferred or even withheld. A new treatment strategy for EGFR mutated NSCLC with CNS metastases should be investigated using osimertinib, especially regarding optimal combination or sequence of radiotherapy.

Stanford type IV venous collateral blood flow following complete chronic occlusion of the superior vena cava in a patient with lung cancer.

In superior vena cava occlusion, multiple collateral pathways develop to maintain venous drainage. Major patterns and pathways of venous collateral blood flow are well described, but rarely in complete chronic superior vena cava occlusion secondary to malignancy. A 59-year-old man with facial and upper extremity edema had a severely compressed superior vena cava at the initial diagnosis of stage IV mediastinal lung adenocarcinoma. The occlusion of superior vena cava progressed. After 10 months of treatment, the complete occlusion led to mild symptoms of hoarseness, muscle weakness, cough, and slight upper extremity edema. Venography clearly illustrated well-developed venous collateral blood flow through lateral thoracic, azygos-hemiazygos, and vertebral collateral venous pathways classified as Stanford type IV. The patient survived for a total of 20 months. He maintained Eastern Cooperative Oncology Group performance status of 1-2 until 2 months before death without severe symptoms of superior vena cava occlusion. This case described a rarely occurring venographic demonstration of well-developed Stanford type IV collateral pathway. Moreover, even with complete superior vena cava occlusion, well-developed Stanford type IV lateral thoracic collateral pathway can compensate for the venous flow without deterioration of performance status for a long period in certain cases.

Effect of High ß-glucan Barley on Postprandial Blood Glucose and Insulin Levels in Type 2 Diabetic Patients.

The aim of our study was to investigate whether high ß-glucan-containing barley (7.2 g per 100 g) improves postprandial plasma glucose levels and suppresses postprandial insulin levels during a meal tolerance test in type 2 diabetic patients. A meal tolerance test (500 kcal) was conducted using two types of test meals: a test meal with white rice (WR) alone (WR diet) and a test meal with WR mixed with 50% barley (BR diet) as staple food. The side dish was the same in the both meals. The changes in plasma glucose and serum C-peptide immunoreactivity (CPR) levels for 180 minutes after ingestion of the test meals were compared. Ten patients with type 2 diabetes (age 52.5 ± 15.1 years, and 7 males and 3 females) were included in this study. The mean HbA1c level and body mass index were 8.8 ± 1.4%, and 29.7 ± 4.5 kg/m2, respectively. Plasma glucose levels after ingestion of the WR diet or BR diet peaked at 60 minutes, which showed no significant differences between the two types of test meals. However, the incremental area under the curve (IAUC) of plasma glucose levels after ingestion of BR diet was significantly lower than that of WR diet. The serum CPR levels at 180 min and their IAUC over 180 minutes after ingestion of BR diet were significantly lower than those of WR diet. Conclusion: Increase in postprandial plasma glucose and insulin levels was suppressed by mixing high-ß-glucan barley with WR in type 2 diabetic patients.

Effect of High ß-glucan Barley on Postprandial Blood Glucose Levels in Subjects with Normal Glucose Tolerance: Assessment by Meal Tolerance Test and Continuous Glucose Monitoring System.

The effect of white rice (WR) mixed with high ß-glucan-containing barley at 50% on improvement of postprandial blood glucose levels was assessed by meal tolerance test and continuous glucose monitoring (CGM) in 15 healthy subjects with normal glucose tolerance (age 31.6 ± 12.9 years old, 4 males and 11 females). A meal tolerance test (500 kcal) was conducted using 2 types of test meals: a test meal only with WR and a test meal WR mixed 50% barley, and the side dish was the same in both meals. Blood glucose levels of the subjects 180 minutes after ingestion of the test meals were compared. In addition, a CGM device was attached to the subjects for 2 days when the WR or barley as a staple food was provided 3 times a day for consecutive days, and the daily variation of glucose was investigated. The glucose levels 30 minutes after dietary loads and the area under the blood concentration-time curve over 180 minutes were significantly decreased in the barley consumption group. In CGM, 24-hour mean blood glucose and 24-hour standard deviation of blood glucose were also significantly decreased after ingestion of the barley. Postprandial glucose level elevation was suppressed by mixing high-ß-glucan barley with WR in subjects with normal glucose tolerance.

Characteristics of fulminant type 1 diabetes mellitus.

BACKGROUND: Fulminant type 1 diabetes is characterized by acute onset and rapid development of ketoacidosis. CASE REPORT: We present three cases of fulminant type 1 diabetes we experienced at our hospital. All three patients showed extremely high levels of plasma glucose, low HbA1c levels, positivity for urinary ketone bodies, ketoacidosis, and low C-peptide excretion. Flu-like symptoms were noted a few days before hospitalization, and increases in the WBC and CRP levels were observed. Interestingly, case 1 was negative for anti-GAD antibody at the time of hospitalization but became positive 22 days later. Moreover, this patient reverted to being negative for anti-GAD antibody 93 days later. Cases 1 and 3 were positive for HLA-DR4 and HLA-DR9, and Case 2 was positive for HLA-DR4. All three individuals had flu-like symptoms and showed inflammatory markers in the blood. CONCLUSIONS: Although autoimmune abnormalities are not usually linked with fulminant type 1 diabetes, the conclusion drawn from the present study is that patients with this disease should be monitored on several different occasions for autoimmune antibodies.

[Clinical epidemiology of fungal infection in diabetes].

It is well-known that diabetes is a risk for infection. According to our analysis of the cause of death in 221 diabetic patients over 10 years, infection and pneumonia accounted for 22% of all deaths. Diabetes may increase the risk of mycotic infections; however, few data are available on the prevalence of fungal infections in diabetic patients. The purpose of this paper was to analyze the clinical epidemiology of fungal infections in diabetic patients. Onychomycosis, oral candidiasis and vulvovaginal candidiasis are observed frequently in diabetic patients. Urinary tract candidiasis in diabetic patients frequently develops into systemic candidiasis and fungus ball formation in the kidney. An estimated 50-75% of cases of rhinocerebral mucomycosis occur in diabetic patients, and ketoacidosis is thought to be the most likely predisposing factor. Invasive otitis externa is almost exclusively found in diabetic patients, and generally caused by Pseudomonas. This has been described secondary to Aspergillus in diabetic patients. Regarding cryptococcosis in non-AIDS patients, approximately 10 to 20% of these patients have diabetes. Clinicians must be aware of mycotic infection in diabetic patients with infectious disease.

Rivaroxaban Treatment for Warfarin-Refractory Thrombosis in a Patient with Hereditary Protein S Deficiency.

Protein S (PS) deficiency, an autosomal dominant hereditary thrombophilia, is more prevalent in East Asian populations than in Caucasians. PS-deficient patients have historically been administered a heparin product followed by warfarin for the treatment and secondary prevention of venous thromboembolism (VTE). However, warfarin can be ineffective or causes detrimental effects in rare cases. While direct oral anticoagulants (DOACs) are being increasingly used for the treatment and prevention of VTE, their efficacy in PS-deficient patients has not been established. We describe a 91-year-old woman who presented with chronic bilateral lower leg swelling with VTE that was refractory to warfarin anticoagulation therapy for over 1 year. Her recurrent VTE was diagnosed as quantitative hereditary PS deficiency. Rivaroxaban was administered as maintenance therapy instead of warfarin; after 8 weeks, the severities of the patient's leg swelling and venous ulcerations were significantly reduced with rivaroxaban compared to warfarin, thus demonstrating the efficacy of rivaroxaban for warfarin-refractory chronic VTE associated with hereditary PS deficiency. This case illustrates that rivaroxaban can potentially serve as therapeutic agents to treat warfarin-refractory VTE in PS-deficient patients. Further investigations are required to confirm the efficacy of rivaroxaban on the long term in this regard.

Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm.

INTRODUCTION: It is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be injected without dose adjustment, unlike basal insulin. Our objective was to examine the efficacy of changing patients inadequately controlled with oral DPP-4i-based OAD therapy to injectable GLP-1RA and discontinuing the DPP4i versus adding basal insulin glargine (IGlar) with the continuation of the oral DPP4i. METHODS: Sixty patients with type 2 diabetes (T2DM) and glycated hemoglobin (HbA1c) between 7.0% and 10.0% on DPP-4i-based OAD therapy were randomized to either adding IGlar and remaining on the DPP-4i or liraglutide and discontinuing the DPP-4i for 24 weeks. Patients in the IGlar group started with 0.1 unit/kg and were titrated according to the algorithm. In the liraglutide group, the DPP-4i was replaced with liraglutide 0.9 mg/day, the maximum dose in Japan. We evaluated HbA1c, glycated albumin (GA), and anthropometrics. RESULTS: HbA1c was significantly lower at week 24 (- 1.0 ± 0.9% in the IGlar group and - 0.6 ± 0.8% in the liraglutide group), but the difference between groups was not significant. Changes in GA were similar (- 2.9 ± 3.2% vs. - 2.6 ± 3.2%) in both groups. Body weight (BW) was significantly lower only in the liraglutide group (+ 0.5 ± 2.6 kg vs. - 2.2 ± 2.0 kg). The rate of minor hypoglycemic episodes was similar for both groups. CONCLUSION: For poorly controlled T2DM on DPP-4i-based OAD therapy, switching to single-dose liraglutide to enhance incretin signaling is as effective as dose-titrated basal IGlar, but significant BW reduction was only seen in the liraglutide group. These results suggest that enhancing incretin signaling with a single-dose injectable GLP-1 RA might be an alternative to dose-titrated basal insulin therapy in patients with T2DM poorly controlled with DPP-4i-based OAD therapy. These findings should be confirmed in a longer and larger trial. TRIAL REGISTRATION: Trial Registry (UMIN-CTR) as UMIN000012224.

Graves' disease with intractable diarrhea, chylous ascites, and chylothorax: a case report.

A 50-year-old woman was admitted to our hospital because of severe diarrhea, irritableness, and severe pitting edema of the legs. The patient had been well until 5 years before admission, when a tremor and tachycardia developed and a diagnosis of Graves' disease was made. Treatment with methimazole was effective in reducing her tremor and tachycardia; however, she was often nonadherent with her antithyroid medication because of improvement of her symptoms. On admission, a thyroid swelling, exophthalmos, a pleural effusion, and ascites were observed. The results of thyroid function tests (free triiodothyronine: 21.5 pg/mL; free thyroxine: 7.17 ng/dL; thyroid-stimulating hormone (TSH): <0.01 microIU/mL; TSH receptor antibodies: 95.9%) were consistent with Graves' disease. Biochemical analysis of pleural and ascitic fluid was consistent with chylothorax and chylous ascites, respectively. Serum calcium, total protein, and albumin were very low. Her symptoms and signs except severe diarrhea, edema, pleural effusion, and ascites disappeared after receiving intravenous drip infusion of fluid replacement, and methimazole and iodine. Because of malnutrition, she was given a high-calorie intravenous infusion. Three months after admission, her pleural effusion and ascites began to improve, as did her diarrhea and hypoalbuminemia. An appropriate treatment of Graves' disease is crucial to avoid serious sequelae of longstanding, poorly controlled hyperthyroidism.

[A case of gas-forming pyogenic liver abscess].

A 62-year-old man with a 20-year history of diabetes mellitus presented with appetite loss was found and a large niveau was found in the right subphrenic space on abdominal X-ray film. Ultrasonography and computed tomography showed a large hepatic abscess with gas formation and cholecystitis with a gallstone. Klebsiella pneumoniae was isolated from the abscess, which communicated with the bile duct and was treated with antibiotics and percutaneous drainage. It should thus be noted that increased anaerobic catabolism by microbes and impaired transport of end products may cause gas-formation in patients with diabetes mellitus.

[A case of sho-seiryu-to-induced pneumonia with a marked increase in peripheral eosinophils].

A 25-year-old woman presented with a high temperature, cough and dyspnea three days after taking sho-seiryu-to, a Chinese herbal preparation, for a cough and throat pain. A chest X-ray film and computed tomography (CT) scan revealed diffuse infiltrative shadows in both the middle and lower lung fields. Arterial blood gas analysis showed hypoxemia (PaO2 43Torr under room air). The white cell count was 40,800/mm3, with eosinophilic cells accounting for 56.5% of the cells. The patient was treated with methylprednisolone under a diagnosis of drug-induced pneumonia and the administration of sho-seiryu-to was discontinued. Immediately after the prednisolone administration, her chest X-ray film findings, clinical symptoms and laboratory data markedly improved. A lymphocyte stimulation test for sho-seiryu-to using peripheral lymphocytes was positive. In 29 cases of herbal medicine-induced pneumonia reported in Japanese medical literature over a 10-year period, sho-saiko-to has been the predominant cause of drug-induced pneumonia. This is the second case of sho-seiryu-to-induced pneumonia.