Prostaglandin E2-Transporting Pathway and Its Roles via EP2/EP4 in Cultured Human Dental Pulp.

INTRODUCTION: Prostaglandin E2 (PGE2) exerts biological actions through its transport pathway involving intracellular synthesis, extracellular transport, and receptor binding. This study aimed to determine the localization of the components of the PGE2-transporting pathway in human dental pulp and explore the relevance of PGE2 receptors (EP2/EP4) to angiogenesis and dentinogenesis. METHODS: Protein localization of microsomal PGE2 (mPGES)synthase, PGE2 transporters (multidrug resistance-associated protein-4 [MRP4] and prostaglandin transporter [PGT]), and EP2/EP4 was analyzed using double immunofluorescence staining. Tooth slices from human third molars were cultured with or without butaprost (EP2 agonist) or rivenprost (EP4 agonist) for 1 week. Morphometric analysis of endothelial cell filopodia was performed to evaluate angiogenesis, and real-time polymerase chain reaction was performed to evaluate angiogenesis and odontoblast differentiation markers. RESULTS: MRP4 and PGT were colocalized with mPGES and EP2/EP4 in odontoblasts and endothelial cells. Furthermore, MRP4 was colocalized with mPGES and EP4 in human leukocyte antigen-DR-expressing dendritic cells. In the tooth slice culture, EP2/EP4 agonists induced significant increases in the number and length of filopodia and mRNA expression of angiogenesis markers (vascular endothelial growth factor and fibroblast growth factor-2) and odontoblast differentiation markers (dentin sialophosphoprotein and collagen type 1). CONCLUSIONS: PGE2-producing enzyme (mPGES), transporters (MRP4 and PGT), and PGE2-specific receptors (EP2/EP4) were immunolocalized in various cellular components of the human dental pulp. EP2/EP4 agonists promoted endothelial cell filopodia generation and upregulated angiogenesis- and odontoblast differentiation-related genes, suggesting that PGE2 binding to EP2/EP4 is associated with angiogenic and dentinogenic responses.

Melanotic neuroectodermal tumor of infancy in the mandible: A case report.

RATIONALE: Melanocytic neuroectodermal tumor of infancy (MNTI) is a rare benign pigmented neoplasm that arises from the neural crest and has an aggressive growth pattern. It is predominantly seen in infants under 1 year of age, and the most common site of involvement is the maxilla. The currently accepted treatment is removal by surgical resection. Herein, we report a case of MNTI that involved the anterior alveolar ridge of the mandible in a 6-month-old infant. PATIENT CONCERNS: A case of a 6-month-old male child with a huge mass in the anterior alveolar ridge of the mandible. DIAGNOSIS: The tumor was diagnosed using histopathological and immunohistochemical techniques on the biopsy specimen obtained following incisional biopsy. Based on the findings, a final diagnosis of MNTI was established. INTERVENTIONS: Radical resection of the tumor was performed, after determining the extent of resection by referring to the mandibular 3D model created using the pre-operative CT data. OUTCOMES: The postoperative course was uneventful, and no recurrence has been observed to date for more than 4 years after surgery. LESSONS: This case emphasizes that early diagnosis and radical surgery are critical to the effective treatment, as MNTI exhibits rapid and destructive growth. It also requires careful and close follow-up because of high recurrence rates.

Relationship between nonalcoholic fatty liver disease and muscle quality as well as quantity evaluated by computed tomography.

BACKGROUND & AIMS: Sarcopenia is reported to be associated with nonalcoholic fatty liver disease (NAFLD). Evaluation of skeletal muscle attenuation and area by computed tomography (CT) may represent a promising approach for evaluation of the risk of NAFLD. We examined the association between skeletal muscle characteristics and NAFLD and investigated the combined effect of these parameters on the prevalence of NAFLD. METHODS: In this cross-sectional study, we analysed data from 632 middle-aged Japanese subjects without daily alcohol intake (353 men and 279 women) from a cohort of employees undergoing annual health examinations. The cross-sectional skeletal muscle area was evaluated on the basis of CT data at the level of the third lumbar vertebrae, and the skeletal muscle index (SMI) and density (SMD) were calculated. The subjects were divided into four study groups according to their SMI and SMD relative to median values. RESULTS: One hundred forty men and forty-three women had NAFLD. Total SMI (odds ratio [OR] per 1.0 cm2 /kg/m2 increase 0.43, 95% confidence interval [CI] 0.29-0.64 in men and OR 0.21, 95% CI 0.10-0.42 in women) and total SMD (OR, per 1.0 Hounsfield Unit increase 0.88, 95% CI 0.83-0.93 in men and 0.88, 0.82-0.95 in women) were significantly associated with the prevalence of NAFLD after adjusting for covariates. The subgroup with simultaneous presence of low SMI and low SMD was associated with a significantly higher prevalence of NAFLD compared with other groups. CONCLUSIONS: Both SMI and SMD are independently associated with the prevalence of NAFLD.

Relationship between metabolic syndrome and trunk muscle quality as well as quantity evaluated by computed tomography.

BACKGROUND & AIMS: Metabolic syndrome is a cluster of metabolic abnormalities. Skeletal muscle attenuation and area evaluated by computer tomography (CT) may provide valuable information about patients with metabolic disorder. Therefore, we examined the association between skeletal muscle characteristics and metabolic syndrome, and investigated the combined effect of quantitative and qualitative muscle parameters. METHODS: In this cross-sectional study, we analyzed 808 middle-aged Japanese subjects. The cross-sectional area of skeletal muscle was evaluated based on CT at the third lumbar vertebrae. The subjects were divided into four groups according to the median levels of skeletal muscle index (SMI) and density (SMD). RESULTS: Eighty-five men and twenty-two women had metabolic syndrome. In the adjusted model, SMI and SMD had an interaction effect on the number of metabolic syndrome components (p = 0.0398 in men and p = 0.0306 in women). When SMI and SMD were considered as independent variables for multiple regression analysis, SMI (ß = -0.155, p = 0.0019 in men and ß = -0.295, p < 0.0001 in women) and SMD (ß = -0.355, p < 0.0001 in men and ß = -0.324, p < 0.0001 in women) were both independently associated with the number of metabolic syndrome components. The subgroup with presence of low SMI and low SMD levels had a significantly higher prevalence of metabolic syndrome than that observed in other groups. CONCLUSIONS: Therefore, we suggest that not only muscle quantity but also quality is independently associated with metabolic syndrome.

Gut microbiota differences in elderly subjects between rural city Kyotango and urban city Kyoto: an age-gender-matched study.

Several outcomes have been reported on the role of gut microbiota in health promotion and disease prevention. Kyotango, one of the longevity areas with various centenarians, is a provincial city located in the northern part of Kyoto Prefecture in Japan. To understand the relationship between gut microbiota and urbanization, we compared the diversity, abundance, and function of gut microbiota in older healthy subjects between Kyotango and Kyoto cities; Kyoto is an urban city located in the southern part of Kyoto Prefecture. In total, 51 subjects at Kyotango and 51 subjects at Kyoto matched by age and gender were recruited, and their fecal samples were obtained to analyze the gut microbiota using 16S rRNA gene sequencing. Principal coordinate analysis for ß-diversity revealed significant differences in the gut microbiota between two cities. In contrast, the analysis of α-diversity revealed no significant differences between the groups. On comparison at the phylum levels, the abundance of Firmicutes was decreased with the urbanization, whereas that of Proteobacteria and Bacteroidetes increased. On comparison at the genus levels, with urbanization, a significant decrease was observed in Lachnospiraceae families including genus Roseburia and Coprococcus, and significant increases was observed in Bacteroides, Oscillospira, Parabacteroides, and Ruminococcus. The most markedly increased functional pathway with urbanization was lipopolysaccharide biosynthesis proteins and lipopolysaccharide biosynthesis, and decreased pathway was transporters and ABC transporters. In conclusion, the present findings indicate significant differences in the gut microbiota between the provincial city and urban cities at Kyoto Prefecture. These alterations in the microbiota may provide new insights to consider the relationship between longevity and gut microbiota.

Potential impact of the joint association of total bilirubin and gamma-glutamyltransferase with metabolic syndrome.

BACKGROUND: Metabolic syndrome is characterized by the clustering of different metabolic abnormalities. Total bilirubin and gamma-glutamyltransferase (GGT) levels have been reported to be associated with this condition. However, the extent to which the interaction between these parameters affects metabolic syndrome is unknown. Therefore, we examined the association of total bilirubin and GGT levels with metabolic syndrome, and investigated the combined effect of the two parameters. METHODS: In this retrospective cohort study, we analyzed 8992 middle-aged Japanese subjects (4586 men, 4406 women; mean age, 44.8 ± 9.3 years) without metabolic syndrome from a cohort of employees undergoing annual health examinations. They were divided into four groups according to median total bilirubin and GGT levels: both-low, GGT-high, total bilirubin-high, and both-high. The incident of metabolic syndrome was evaluated during a follow-up of 2.8 ± 1.2 years. RESULTS: The incident rate of metabolic syndrome during the follow-up was 4.6% in the both-low group, 12.1% in the GGT-high group, 2.7% in the total bilirubin-high group, and 10.6% in the both-high group. Total bilirubin and GGT have an interaction effect on the risk of incident metabolic syndrome (p = 0.0222). The both-low [hazard ratio (HR), 1.37; 95% confidence interval (CI) 1.002-1.89], GGT-high (HR, 1.88; 95% CI 1.42-2.52), and both-high (HR, 2.07; 95% CI 1.56-2.80) groups showed an increased adjusted HR for incident metabolic syndrome after adjusting for covariates compared with the total bilirubin-high group. CONCLUSIONS: The simultaneous presence of high total bilirubin and low GGT levels may be associated with a lower incidence of metabolic syndrome.

Understanding of antidiabetic medication is associated with blood glucose in patients with type 2 diabetes: At baseline date of the KAMOGAWA-DM cohort study.

AIMS/INTRODUCTION: Medication adherence, which is decreased by a poor understanding of medications, has a close association with blood glucose level in patients with type 2 diabetes. However, a relationship between the understanding of antidiabetic medication and blood glucose level in patients with type 2 diabetes is unclear. Here, we aimed to investigate the relationship between the understanding of antidiabetic medication and blood glucose level in patients with type 2 diabetes. MATERIALS AND METHODS: Lifestyle factors were evaluated by a questionnaire method, in the present cross-sectional study. Poor understanding of antidiabetic medication (PUAD) was defined as a discrepancy between the answer and the actual use of oral antidiabetic medication on the questionnaire. Poor blood glucose level was defined as hemoglobin A1c ≥8%. To investigate the impact of PUAD on poor blood glucose level, propensity-score matching analysis was used to remove the bias of confounding variables, including sex, age, log (duration of diabetes +1), body mass index, number of oral antidiabetic medications, smoking status, alcohol drinking, exercise, nephropathy, neuropathy, oral antidiabetic medications and insulin. RESULTS: Among 479 patients, 40 patients (8.4%) were categorized into the PUAD group. The hemoglobin A1c of patients with PUAD was higher than that of patients without (7.5 [1.3] vs 7.2 [0.9]%, P = 0.041). In the propensity-matched 74 patients, PUAD was associated with poor blood glucose level (odds ratio 5.45, 95% confidence interval 1.54-25.8, P = 0.007) by logistic regression analysis. CONCLUSION: A poor understanding of antidiabetic medication is associated with poor blood glucose level in patients with type 2 diabetes.

Successful Endovascular Treatment for Aortic Thrombosis Due to Primary Antiphospholipid Syndrome: A Case Report and Literature Review.

A 60-year-old man with a history of Raynaud's phenomenon presented with bilateral intermittent claudication and an ulcer on his right toe. The ankle-brachial index of the right and left legs was 0.77 and 0.75, respectively. Laboratory data showed prolongation of the activated partial thromboplastin time and a positive result on the lupus anticoagulant test. Computed tomography angiography revealed isolated infrarenal aortic stenosis with irregular surface and noncalcified plaques. Intravascular ultrasonography examination demonstrated a noncalcified, irregular, and mobile plaque, suggestive of abdominal aortic thrombosis. In addition to anticoagulant and dual antiplatelet therapy, endovascular treatment was performed. A total of three 40-mm-long balloon-expandable stents were successfully implanted on a 15-mm balloon. The final angiography showed good results except for minimal plaque shifting in the terminal aorta. Three months later, the ulcer resolved and a final diagnosis of primary antiphospholipid syndrome (APS) was made. Clinicians should recognize that APS can affect the abdominal aorta, leading to aortic thrombosis. Endovascular treatment may be the one good treatment option for this rare condition.

Fatal heart failure caused by severe pulmonary regurgitation, tricuspid regurgitation and late-onset mitral stenosis in an adult patient with Noonan syndrome: a case report.

BACKGROUND: In patients with Noonan syndrome (NS), cardiac disorders such as pulmonary valve stenosis (PS) or hypertrophic cardiomyopathy (HCM) are common. While some patients can develop heart failure associated with HCM, the long-term outcome of adult patients with NS is reported to be good. Fatal outcomes of heart failure in patients with NS but without HCM are rare. CASE PRESENTATION: We report a 25-year-old Japanese woman diagnosed with NS in adulthood. She exhibited short stature and minor facial dysmorphism and was diagnosed with PS at 1 year of age. After surgical valvuloplasty for PS at 6 years of age, her general condition became stable without specific medical treatment. She discontinued regular medical follow-up for PS. At 21 years of age, she developed acute decompensated heart failure, which was mainly right-sided heart failure due to severe pulmonary regurgitation (PR) and tricuspid regurgitation (TR). There was no evidence of HCM or PS recurrence. On the basis of the history of PS and characteristic physical features including short stature, webbed neck, and hypertelorism, she was clinically diagnosed with NS. At 25 years of age, she developed heart failure of both sides due to PR, TR and late-onset severe mitral stenosis (MS). The etiology of MS was uncertain. Owing to the patient's condition, surgical options were considered to be extremely high risk. She was treated with optimal medical treatment as well as the occasional abdominal cavity drainage for recurrent ascites; however, she died of decompensated heart failure at 27 years of age. CONCLUSIONS: We describe an adult patient with NS without HCM who died of heart failure caused by severe PR, TR and MS. Clinicians should recognize that ongoing or late-onset cardiac disorders can develop in patients with NS, and lead to fatal heart failure. Optimal medical follow-up to monitor cardiac function and early identification of heart failure are important.

The Association Between Taste Impairment and Serum Zinc Concentration in Adult Patients With Type 2 Diabetes.

OBJECTIVES: In this study, we aimed to elucidate the association between taste acuity and serum zinc concentration in patients with type 2 diabetes. METHODS: We enrolled 29 patients who were hospitalized and asked them to attend a 2-week diabetes education program. Fasting blood samples were obtained on the morning of the first day and 2 weeks after hospitalization. The acuity of sweet, salty, sour or bitter taste was evaluated by a filter-paper disc method. Correlations among taste acuity, glycemic control and serum zinc concentration were analyzed using the Spearman rank correlation coefficient. RESULTS: The following parameters (mean ± standard deviation) were improved after 2 weeks' hospitalization: taste acuity (sweet: 3.5±1.0 to 2.9±1.1; salty: 3.3±1.1 to 2.6±1.0; sour: 3.6±1.2 to 2.7±0.8; and bitter: 3.3±1.3 to 2.7±1.1; all p<0.001); glycemic control (fasting plasma glucose, 9.4±3.0 to 7.1±1.8 mmol/L, and glycoalbumin, 26.3±7.7 to 22.7±5.9 %; both p<0.001); and serum zinc concentration (1.2±0.2 to 1.3±0.2 mmol/L; p<0.001). Sour and bitter taste acuity were significantly associated with serum zinc concentration (sour, r=-0.50, p=0.005; bitter, r=-0.40, p=0.033). CONCLUSIONS: Glycemic control, serum zinc concentration and taste acuity were improved after the short-duration education program. Sour and bitter taste acuity were significantly associated with serum zinc concentrations.

Impact of masked hypertension on diabetic nephropathy in patients with type II diabetes: a KAMOGAWA-HBP study.

The prognostic significance of masked hypertension (MH) on the progression of diabetic nephropathy among patients with type II diabetes is not well documented. We examined the relationship between clinic systolic blood pressure (SBP) and morning home SBP measurements and progression to macroalbuminuria in patients with type II diabetes. We analyzed prospective cohort study data from 712 patients with type II diabetes. We classified the patients into the following four groups according to their clinic (130 mm Hg) and home (125 mm Hg) SBP measurements: controlled blood pressure group, white-coat hypertension group, MH group, and sustained hypertension (SH) group. The patients were instructed to perform triplicate morning and evening blood pressure measurements for 14 consecutive days. During the 2-year follow-up period, 23 patients progressed to macroalbuminuria. The unadjusted odds ratio (95% confidence interval) for progression to macroalbuminuria among the patients with MH was significantly higher than that among the patients with controlled blood pressure (8.89 [1.06-74.88]). No significant relationship was observed between white-coat hypertension or SH and progression to macroalbuminuria. In analyses adjusted for various potential confounders, the adjusted odds ratio for progression to macroalbuminuria in the MH group was more than 8-fold higher than that in the controlled blood pressure group. MH might be a predictor of progression to macroalbuminuria among patients with type II diabetes. This rate of progression is comparable with or greater than the results reported for patients with SH.

Two-Wire Technique With a Gooseneck Snare to Bail Out the Tip Separation of a Crosser Catheter.

Tip separation of a Crosser catheter is a serious complication; however, there is limited information on bailout methods. Here, we describe a case of successful retrieval of the separated tip of a Crosser catheter using a 2-wire technique with a gooseneck snare. A 76-year-old woman with a history of hemodialysis and diabetes mellitus who developed ulcers on her right toes was diagnosed as having critical limb ischemia and underwent transfemoral antegrade endovascular treatment of the anterior tibial artery (ATA). A 0.014-inch guidewire was passed through the ATA chronic total occlusion, and then a Crosser catheter was advanced along the wire. During catheter withdrawal, the tip completely detached from the shaft and remained in the ATA. We passed another 0.014-inch guidewire into the distal ATA through the small space beside the tip. A gooseneck snare catheter was advanced to the distal side of the tip along the new wire, and subsequently the 2 wires were entrapped by the snare. The detached tip was finally retrieved with the entire system as a unit and successfully withdrawn into the guiding sheath with no complications. Interventionists should be familiar with the bailout method of this unfavorable complication. Our technique may be widely adapted for various situations involving this complication.

Late-night-dinner is associated with poor glycemic control in people with type 2 diabetes: The KAMOGAWA-DM cohort study.

Skipping breakfast or irregular breakfast is associated with poor glycemic control. However, a relationship between the timing of dinner and glycemic control in people with type 2 diabetes remains indefinite. Therefore, we investigated the relationship between late-night-dinner and glycemic control in people with type 2 diabetes. We performed questionnaire survey for lifestyle factors in this cross-sectional study. We defined having dinner later than eight pm as late-night-dinner. We examined the differences in clinical and metabolic parameters between those who have late-night-dinner and those who do not have. We also examined the relationship between late-night-dinner and HbA1c, using multiple regression analysis. Ninety-five people (23.2%) had a late-night-dinner, among 409 people with type 2 diabetes. Metabolic parameters (mean (SD) or median (interquartile range)) of people with late-night-dinner were worse than those of without, including body mass index (BMI) (24.4 (4.0) vs. 23.2 (3.4) kg/m2, p = 0.006), triglycerides (1.5 (1.1-2.1) vs. 1.2 (0.8-1.7) mmol/L, p < 0.001), HDL-cholesterol (1.4 (0.4) vs. 1.6 (0.4) mmol/L, p = 0.004) and hemoglobin A1c (58.1 (13.3) vs. 55.2 (10.2) mmol/mol, (7.5 (1.2) vs. 7.2 (0.9) %), p = 0.023)). Late-night-dinner (standardized regression coefficient = 0.13, p = 0.028) was associated with hemoglobin A1c after adjusting for age, BMI, sex, duration of diabetes, smoking, exercise, alcohol, snacking after dinner, nighttime sleep duration, time from dinner to bedtime, skipping breakfast, and medication for diabetes. Late-night-dinner is independently associated with poor glycemic control in people with type 2 diabetes.

Prognostic significance of day-by-day variability of home blood pressure on progression to macroalbuminuria in patients with diabetes.

OBJECTIVES: Previously, we have shown in cross-sectional analysis of patients with type 2 diabetes mellitus that the presence of diabetic nephropathy is associated with increased home blood pressure (HBP) variability. We now examine the prognostic significance of HBP variability in substantially the same cohort. METHODS: We performed a prospective cohort study of type 2 diabetes patients. We analyzed 714 patients. Major exclusion criteria are missing data of urinary albumin excretion and newly prescribed or stopped renin-angiotensin system inhibitors during 2-year follow-up. Patients were instructed to perform triplicate morning and evening HBP measurements for 14 consecutive days. We computed day-by-day HBP variability as within-patient standard deviation (SD) and coefficient of variation (CV) of measurements. RESULTS: During the follow-up period of 2 years, 23 patients progressed to macroalbuminuria. The changing risk of progression to macroalbuminuria with increasing day-by-day variability of morning SBP was better depicted using smoothing spline analyses. Patients with greater SD of morning SBP tended to significantly progress to macroalbuminuria [odds ratio: 5.24 (95% confidence interval: 2.10-13.03; P > 0.001)]. Patients with greater CV of morning SBP also tended to significantly progress to macroalbuminuria [odds ratio: 3.36 (95% confidence interval: 1.39-8.12; P = 0.007)]. CONCLUSION: Day-by-day variability of morning SBP was proven as an independent predictor for progression to macroalbuminuria in patients with type 2 diabetes.

Combined effect of body mass index and waist-height ratio on incident diabetes; a population based cohort study.

We investigated the impact of combined effect of body mass index and waist-to-height ratio on risk of diabetes. Overweight and abdominal obesity were defined as body mass index ≥23 kg/m2 and waist-to-height ratio ≥0.5, respectively. We divided participants into four groups according to presence of overweight and/or abdominal obesity. About 20% individuals with overweight did not complicated with an abdominal obesity. Among 3,737 participants, 286 participants had diabetes at baseline-examination. Adjusted odds ratios for prevalence of diabetes compared with non-overweight participants without abdominal obesity were as follow: 1.87 (95% confidence interval 1.09-3.14, p = 0.024) in non-overweight participants with abdominal obesity, 1.51 (0.87-2.55, p = 0.141) in overweight participants without abdominal obesity and 3.25 (2.37-4.52, p<0.001) in overweight participants with abdominal obesity. In the follow-up examination, 86 participants were diagnosed as diabetes among 2,263 participants. Adjusted odds ratios for incident diabetes were as follow: 2.59 (0.98-6.44, p = 0.056) in non-overweight participants with abdominal obesity, 1.65 (0.64-4.00, p = 0.288) in overweight participants without abdominal obesity and 2.77 (1.55-5.15, p<0.001) in overweight participants with abdominal obesity. Non-overweight individuals with abdominal obesity as well as overweight individuals with abdominal obesity was associated with diabetes compared with non-overweight individuals without abdominal obesity.

A simple technique for repositioning of the mandible by a surgical guide prepared using a three-dimensional model after segmental mandibulectomy.

BACKGROUND: Mandibular reconstruction is performed after segmental mandibulectomy, and precise repositioning of the condylar head in the temporomandibular fossa is essential for maintaining preoperative occlusion. METHODS: In cases without involvement of soft tissue around the mandibular bone, the autopolymer resin in a soft state is pressed against the lower border of the mandible and buccal and lingual sides of the 3D model on the excised side. After hardening, it is shaved with a carbide bar to make the proximal and distal parts parallel to the resected surface in order to determine the direction of mandibular resection. On the other hand, in cases that require resection of soft tissue around the mandible such as cases of a malignant tumor, right and left mandibular rami of the 3D model are connected with the autopolymer resin to keep the preoperative position between proximal and distal segments before surgical simulation. The device is made to fit the lower border of the anterior mandible and the posterior border of the mandibular ramus. The device has a U-shaped handle so that adaptation of the device will not interfere with the soft tissue to be removed and has holes to be fixed on the mandible with screws. RESULTS: We successfully performed the planned accurate segmental mandibulectomy and the precise repositioning of the condylar head by the device. CONCLUSIONS: The present technique and device that we developed proved to be simple and useful for restoring the preoperative condylar head positioning in the temporomandibular fossa and the precise resection of the mandible.

Sodium-chloride Difference and Metabolic Syndrome: A Population-based Large-scale Cohort Study.

Objective Metabolic syndrome (MetS) is associated with cardiovascular disease, which is the leading cause of mortality and morbidity. Hypernatremia and hypochloremia are also associated with an increased mortality. Thus, the aim of this study was to evaluate the association between the sodium-chloride difference (Na+-Cl-) and MetS. Methods In this cross-sectional and retrospective cohort study, we enrolled 3,875 subjects and evaluated the relationship between Na+-Cl- and MetS using logistic regression analyses. MetS was diagnosed according to the joint interim statement when a subject had three or more of the following criteria: hypertension; hyperglycemia; hypertriglyceridemia; low high-density lipoprotein (HDL) cholesterol; and abdominal obesity. Results There were 3,354 subjects without MetS and 521 subjects with MetS at baseline. The highest Na+-Cl- quartile (≥43 mmol/L) was associated with an increased risk of the presence of MetS compared to the lowest Na+-Cl- quartile (≤38 mmol/L) after adjusting for covariates, including age, sex, the body mass index, systolic blood pressure, fasting plasma glucose, triglycerides, HDL cholesterol, creatinine, uric acid and lifestyle factors [multivariate odds ratio (OR) 1.81, 95% confidence interval (CI) 1.17-2.84, p=0.0078]. After an 8-year follow-up, 658 out of 3,352 subjects were newly diagnosed with MetS. The highest Na+-Cl- quartile (≥43 mmol/L) was associated with an increased risk of the development of MetS compared to the lowest Na+-Cl- quartiles (≤38 mmol/L) after adjusting for covariates (multivariate OR 1.76, 95% CI 1.27-2.45, p=0.0007). Conclusion The sodium and chloride difference is associated with MetS.

Caffeine intake enhances the benefits of sodium glucose transporter 2 inhibitor.

BACKGROUND: The effect of sodium glucose transporter 2 (SGLT-2) inhibitors is dependent on the glomerular filtration rate. It has been reported that caffeine intake increases glomerular filtration rate. However, the effect of caffeine intake on urinary glucose excretion in patients who take SGLT-2 inhibitors is unclear. METHODS: Six patients with type 2 diabetes took part in a randomized, open-label, crossover pilot study. The patients took SGLT-2 inhibitors (ipragliflozin) for 9 days. On day 3, 6 and 9, the patients were assigned to one of three studies: Water 500, patients drank 500 mL of water in 3 h; Water 1500, patients drank 1500 mL of water in 3 h; and Caffeine 500, patients drank 500 mL of water with 400 mg of caffeine in 3 h. In all of the studies, the patients' urine was collected over a 6-h period. In addition, we enrolled 60 patients with type 2 diabetes who newly took SGLT-2 inhibitors in a 3-month follow-up cohort study to investigate the effect of caffeine intake on glucose control. Caffeine intake was evaluated using questionnaires. RESULTS: The 6-h median (interquartile range) urinary glucose excretion was 9.5 (8.5-9.7) g in Water 500, 12.2 (10.3-27.2) g in Water 1500 and 15.7 (11.4-21.4) g in Caffeine 500 (p = 0.005 vs Water 500). In the cohort study, multiple regression analysis demonstrated that log (caffeine intake) was associated with a change in HbA1c (ß = -0.299, p = 0.043) after adjusting for covariates. CONCLUSIONS: Caffeine intake enhanced the effect of SGLT-2 inhibitors. Copyright © 2016 John Wiley & Sons, Ltd.

Postprandial hyperglycemia was ameliorated by taking metformin 30 min before a meal than taking metformin with a meal; a randomized, open-label, crossover pilot study.

Taking metformin with a meal has been shown to decrease bioavailability of metformin. We hypothesized that taking metformin 30 min before a meal improves glucose metabolism. As an animal model, 18 Zucker-rats were divided into three groups as follows: no medication (Control), metformin (600 mg/kg) with meal (Met), and metformin 10 min before meal (pre-Met). In addition, five diabetic patients were recruited and randomized to take metformin (1000 mg) either 30 min before a meal (pre-Met protocol) or with a meal (Met protocol). In the animal model, the peak glucose level of pre-Met (7.8 ± 1.5 mmol/L) was lower than that of Control (12.6 ± 2.5 mmol/L, P = 0.010) or Met (14.1 ± 2.9 mmol/L, P = 0.020). Although there was no statistical difference among the three groups, total GLP-1 level at t = 0 min of pre-Met (7.4 ± 2.7 pmol/L) tended to be higher than that of Control (3.7 ± 2.0 pmol/L, P = 0.030) or Met (3.9 ± 1.2 pmol/L, P = 0.020). In diabetic patients, the peak glucose level of pre-Met protocol (7.0 ± 0.4 mmol/L) was lower than that of Met protocol (8.5 ± 0.9 mmol/L, P = 0.021). Total GLP-1 level at t = 30 min of pre-Met protocol (11.0 ± 6.1 pmol/L) was higher than that of Met protocol (6.7 ± 3.9 pmol/L, P = 0.033). Taking metformin 30 min before a meal ameliorated postprandial hyperglycemia. This promises to be a novel approach for postprandial hyperglycemia.