Eating Vegetables First Regardless of Eating Speed Has a Significant Reducing Effect on Postprandial Blood Glucose and Insulin in Young Healthy Women: Randomized Controlled Cross-Over Study.

People with fast eating habits have been reported to have an increased risk of diabetes and obesity. To explore whether the speed of eating a test meal (tomato, broccoli, fried fish, and boiled white rice) influences postprandial blood glucose, insulin, triglyceride, and free fatty acid levels, 18 young, healthy women consumed a 671 kcal breakfast at fast speed (10 min) and slow speed (20 min) with vegetables first and slow speed (20 min) with carbohydrate first on three separate days. This study was conducted using a within-participants cross-over design in which all participants consumed identical meals of three different eating speeds and food orders. Significant ameliorations of both fast and slow eating with vegetables first regimen on postprandial blood glucose and insulin levels at 30 and 60 min were observed compared with those of slow eating with carbohydrates first. In addition, the standard deviation, large amplitude of excursion, and incremental area under the curve for blood glucose and insulin in both fast and slow eating with vegetables first were all significantly lower than those of slow eating with carbohydrate first. Interestingly, there was no significant difference between fast and slow eating on postprandial blood glucose and insulin levels as long as vegetables were consumed first, although postprandial blood glucose at 30 min was significantly lower in slow eating with vegetables first than that of fast eating with the same food order. These results suggest that food order with vegetables first and carbohydrate last ameliorates postprandial blood glucose and insulin concentrations even if the meal was consumed at fast speed.

Association of dipeptidyl peptidase-4 inhibitor use and risk of pancreatic cancer in individuals with diabetes in Japan.

AIMS/INTRODUCTION: This study was designed and carried out to investigate the association of dipeptidyl peptidase-4 inhibitor (DPP-4i) use with pancreatic cancer (PC) in individuals with diabetes in Japan. MATERIALS AND METHODS: The JMDC Claims Database, which contains the medical and prescription information of Japanese employment-based health insurance programs, was used. The primary outcome was duration to the first occurrence of PC (International Classification of Diseases 10th Revision code C25), both all and hospitalized, from prescription of DPP-4is or other oral glucose-lowering agents (GLAs). RESULTS: Individuals with diabetes who received DPP-4is (n = 61,430) or other oral GLAs (n = 83,304) were analyzed. Follow-up periods (median [interquartile range]) were 17 months (8-33) for DPP-4is and 14 months (7-28) for other oral GLAs. Kaplan-Meier curve analysis to determine the duration of first use of DPP4i or other oral GLA to diagnosis of PC disclosed no differences between the two groups in duration to all or hospitalized PC (log-rank test: all, P = 0.7140; hospitalized, P = 0.3446). Cox proportional hazards models showed that use of DPP-4is did not affect the PC risk adjusted for medications, age, sex and risk comorbidities (all, hazard ratio 1.1, 95% confidence interval 0.8-1.3, P = 0.6518; hospitalized, hazard ratio 1.1, 95% confidence interval 0.8-1.4, P = 0.6662). Similar results were obtained when individuals with ≥2 years oral GLA treatment and those with medical checkup data (e.g., smoking or drinking habit) available were analyzed. CONCLUSION: This database study shows that there is not a significant PC risk due to DPP-4i treatment in individuals with diabetes in Japan, but larger studies with longer follow up are required to confirm these findings.

Impact of Dietitian-Led Nutrition Therapy of Food Order on 5-Year Glycemic Control in Outpatients with Type 2 Diabetes at Primary Care Clinic: Retrospective Cohort Study.

The aim of this retrospective cohort study was to evaluate the effect of 5-year follow-up of dietitian-led medical nutrition therapy (eating vegetables before carbohydrates) on glycemic control in outpatients with type 2 diabetes (T2DM) at a primary care clinic. A total of 138 patients with dietitian-led medical nutrition therapy (intervention group) and 104 patients without dietitian-led nutrition therapy (control group) were compared for glycemic control, serum lipid, blood pressure, and diabetic complications for 5 years. Each patient in the intervention group received dietary education focused on food order (eating vegetables before carbohydrates) by dietitians. A significant improvement in HbA1c after 5 years in the intervention group [8.5 ± 1.7% (69 mmol/mol) to 7.6 ± 1.1% (59 mmol/mol), p < 0.001] was observed, whereas no change was observed in the control group [7.9 ± 1.2% (62 mmol/mol) to 8.0 ± 1.2% (63 mmol/mol)]. Dietary intake of protein, fat, carbohydrates, cholesterol, and salt in the intervention group demonstrated significant reduction, while the intake of dietary fiber significantly increased after the dietary education. Simple dietary education of 'eating vegetables before carbohydrates' presented by dietitians achieved good glycemic control after a 5-year period in outpatients with T2DM at primary care clinic.

Adverse effect of switching only once low-carbohydrate diet to high-carbohydrate diet on postprandial glucose concentration in healthy women.

BACKGROUND AND OBJECTIVES: Our aim was to evaluate the acute effect of switching low-carbohydrate diet (LCD) to high-carbohydrate diet (HCD) on glycemic parameters in healthy women. METHODS AND STUDY DESIGN: Twen-ty-two women (age 21.7±4.0 years; HbA1c 5.3±0.3 %, mean±SD) wore flash glucose monitoring system and consumed test meals for 3 days from Day 4 to 6. Participants consumed identical HCD meals except LCD dinner on Day 5. The energy ratio of carbohydrate, fat, and protein were 64%, 21%, and 15% for HCD and 47%, 35%, and 18% for Day 5 with LCD dinner (19%, 59%, and 22%). RESULTS: The incremental glucose peak (IGP, both p<0.001) and incremental area under the curve for glucose (IAUC, both p<0.001) 3h of LCD dinner were all sig-nificantly lower than those of HCD dinner on Day 4 and 6. However, after consuming LCD dinner on Day 5, IGP breakfast (2.33±0.15 vs 1.71±0.15 mmo/L, p<0.01), IGP lunch (3.31±0.25 vs 2.54±0.18 mol/L, p<0.01), IAUC 3h of breakfast (210±18 vs 136±14 mmol/L×min, p<0.001), mean blood glucose (5.72±0.11 vs 5.40±0.11 mmol/L, p<0.01), and standard deviation (1.11±0.06 vs 0.88±0.04 mmol/L, p<0.01) on Day 6 were all signifi-cantly higher than those of corresponding meals before LCD dinner on Day 4, in spite of consuming all identical HCD meals. The glycemic parameters returned to the levels before consuming LCD on Day 7. CONCLUSIONS: Consuming LCD only once is enough to cause 24-h higher postprandial blood glucose concentration in subse-quent consumption of HCD in healthy women.

Eating Fast Has a Significant Impact on Glycemic Excursion in Healthy Women: Randomized Controlled Cross-Over Trial.

Epidemiological studies have shown that self-reported fast eating increases the risk of diabetes and obesity. Our aim was to evaluate the acute effect of fast eating on glycemic parameters through conducting a randomized controlled cross-over study with young healthy women. Nineteen healthy women wore a flash glucose monitoring system for 6 days. Each participant consumed identical test meals with a different eating speed of fast eating (10 min) or slow eating (20 min) on the 4th or the 5th day. The daily glycemic parameters were compared between the 2 days. The mean amplitude of glycemic excursion (MAGE; fast eating 3.67 ± 0.31 vs. slow eating 2.67 ± 0.20 mmol/L, p < 0.01), incremental glucose peak (IGP; breakfast 2.30 ± 0.19 vs. 1.71 ± 0.12 mmol/L, p < 0.01, lunch 4.06 ± 0.33 vs. 3.13 ± 0.28 mmol/L, p < 0.01, dinner 3.87 ± 0.38 vs. 2.27 ± 0.27 mmol/L, p < 0.001), and incremental area under the curve for glucose of dinner 2 h (IAUC; 256 ± 30 vs. 128 ± 18 mmol/L × min, p < 0.001) for fast eating were all significantly higher than those for slow eating. The results suggest that fast eating is associated with higher glycemic excursion in healthy women.

Tomato juice preload has a significant impact on postprandial glucose concentration in healthy women: A randomized cross-over trial.

BACKGROUND AND OBJECTIVES: Our aim was to evaluate the effect of consuming tomato juice before carbohydrate on postprandial glucose concentrations in healthy women. METHODS AND STUDY DESIGN: In this randomized controlled cross-over study, 25 healthy women (age 21.6±3.8 years, HbA1c 5.3±0.2 %, mean±SD) consumed either 200 g of tomato juice, tomato, or water (control) at 30 min before consuming 200 g of boiled white rice at 9:00 and consumed identical lunch at 13:00 for 3 days. The blood glucose concentrations were measured by selfmonitoring blood glucose at 0, 30, 45, 60, 90, 150, and 210 min pre- and post-breakfast, and at 0, 30, 60, 120, 150, and 180 min pre- and post-lunch. The concentration of postprandial glucose, incremental glucose peak (IGP), and incremental area under the curve for glucose after the test meals were compared among 3 days. RESULTS: Incremental blood glucose concentrations at 60 min (2.32±0.16 vs 2.97±0.19 mmol/L, p<0.05, mean±SEM), 90 min (2.36±0.23 vs 3.23±0.24 mmol/L, p<0.01), and IGP (2.77±0.19 vs 3.68±0.22 mmol/L, p<0.001) in consuming tomato juice 30 min before carbohydrate were all significantly lower than those of water, while IGP of consuming tomato was tended to be lower than that of water (2.82±0.19 mmolL, p=0.023). No significant difference was observed in glycaemic parameters after consuming lunch among 3 days. CONCLUSIONS: Consuming tomato juice half hour before carbohydrate ameliorates the postprandial blood glucose concentrations, although total amounts of energy and carbohydrate of tomato juice are higher than those of water.

Late-night-dinner deteriorates postprandial glucose and insulin whereas consuming dinner dividedly ameliorates them in patients with type 2 diabetes: A randomized crossover clinical trial.

BACKGROUND AND OBJECTIVES: The aims of this study is to explore the acute effect of consuming dinner at different timing on postprandial glucose and hormone in patients with type 2 diabetes. METHODS AND STUDY DESIGN: Eight patients (age 70.8±1.9 years, HbA1c 7.6±0.6 %, BMI 23.3±3.2, mean±SD) were randomly assigned in this crossover study. Patients consumed the test meals of dinner at 18:00 on the first day, and dinner at 21:00 or divided dinner (vegetable and rice at 18:00 and vegetable and the main dish at 21:00) on the second or third day. Postprandial glucose, insulin, glucagon, free fatty acid (FFA), active glucagon-like peptide-1 (GLP-1), and active glucose- dependent insulinotropic polypeptide (GIP) concentration after dinner were evaluated. RESULTS: Both incremental area under the curve (IAUC) 2h for glucose and insulin were higher in dinner at 21:00 than those in dinner at 18:00 (IAUC glucose: 449±83 vs 216±43 mmol/L×min, p<0.01, IAUC insulin:772±104 vs 527±107 µU/mL×min, p<0.01, mean±SEM). However, in divided dinner both IAUC 4h for glucose and insulin tended to be lower than those of dinner at 21:00 (IAUC glucose: 269±76 mmol/L×min, p=0.070, IAUC insulin: 552±114 µU/mL×min, p=0.070). IAUC of active GLP-1 and active GIP demonstrated no difference among different dinner regimen. CONCLUSIONS: Consuming late-night-dinner (21:00) deteriorates postprandial glucose and insulin compared with those of early-evening-dinner (18:00) whereas consuming dinner dividedly ameliorates them.

Resolution of dopamine agonist-resistant hyperprolactinemia by hysterectomy: a case report.

Prolactin-producing uterine leiomyomas are very rare. Although hyperprolactinemia rapidly improves after removal of such leiomyomas, no preoperative diagnostic test has been established for prolactin-producing uterine leiomyomas. A 45-year-old Japanese woman, gravida 3 para 3, was referred to our hospital for further examination of hyperprolactinemia resistant to a dopamine agonist. A pituitary prolactinoma was undetectable by brain magnetic resonance imaging. A bromocriptine loading test revealed an increased serum prolactin concentration after loading. Examination for the detection of an ectopic prolactinoma revealed a 9.0 cm diameter uterine leiomyoma that had measured 6.6 cm in diameter about six months before the first visit to our hospital. The hyperprolactinemia rapidly improved after hysterectomy. A prolactin-producing uterine leiomyoma should be considered as a possible cause of hyperprolactinemia resistant to dopamine agonists. Responsiveness to dopamine agonists; deterioration of hyperprolactinemia may be diagnostic for prolactin-producing uterine leiomyomas, although further research is required.

Divided consumption of late-night-dinner improves glucose excursions in young healthy women: A randomized cross-over clinical trial.

AIMS: Our aim was to explore the acute effect of the late-night-dinner and the divided-dinner on postprandial glucose levels in young healthy women. METHODS: Fourteen women (22.6 ±â€¯2.6 years, BMI 20.2 ±â€¯1.5 kg/m2: mean ±â€¯SD) were randomly assigned to this crossover study. Each participant wore a continuous glucose monitor for 5 days and consumed identical test meals from the second to the fourth day at home. Each participant consumed the test meals of breakfast at 0800 h, lunch at 1300 h, and the half of the participants consumed dinner at 2100 h (D21) on the second day, 1800 h (D18) on the third day, and divided dinner (DD: vegetable and rice at 1800 h, and vegetable and the main dish at 2100 h) on the fourth day. The rest of the participants consumed DD on the second day, and D21 on the fourth day. RESULTS: D21 demonstrated higher incremental glucose peak (IGP 2.74 ±â€¯0.38 vs. 1.57 ±â€¯0.23 mmol/L, p < .05, mean ±â€¯SEM) and incremental area under the curve for glucose (IAUC) 2300-0800 h (271 ±â€¯63 vs. 111 ±â€¯37 mmol/L × min, p < .05) than D18. On the other hand, DD ameliorated IGP (1.96 ±â€¯0.29 mmol/L, p < .05), IAUC 2300-0800 h (80 ±â€¯29 mmol/L × min, p < .001), and the mean amplitude of glycemic excursion (DD 2.34 ±â€¯0.25 vs. D21 2.91 ±â€¯0.28 mmol/L, p < .05) than D21. CONCLUSIONS: Consuming late-night-dinner increased postprandial glucose levels, compared to DD, suggesting DD could be a practical strategy for reduction of postprandial glucose levels in young healthy women.

Divided consumption of late-night-dinner improves glycemic excursions in patients with type 2 diabetes: A randomized cross-over clinical trial.

AIMS: To explore the acute effect of late-night-dinner and divided dinner on postprandial glucose levels in patients with type 2 diabetes. METHODS: Sixteen patients were randomly assigned to this cross-over study. Each patient wore a continuous glucose monitor for 5days and consumed identical test meals for 3days. Patients consumed the test meals of dinner at 2100h (D21) or divided dinner (vegetable and rice at 1800h and the vegetable and the main dish at 2100h) on the second or fourth day, and dinner at 1800h (D18) on the third day. The daily glucose parameters were compared within-patient for 3days. RESULTS: D21 demonstrated significantly higher values of incremental area under the curve (IAUC) for glucose 2300 to 0800h (644±156vs. 147±63mmol/L×min, p<0.01, mean±standard error of the mean) and incremental glucose peak (IGP) after dinner (6.78±0.79 vs. 3.09±0.62mmol/L, p<0.01) compared to those of D18. Moreover, the mean amplitude of glycemic excursion (MAGE) of D21 tended to be higher than that of D18 (6.99±0.60 vs. 5.35±0.51mmol/L, p=0.077). However, the divided dinner significantly reduced IAUC 2300 to 0800h (142±60mmol/L×min, p<0.01), IGP after dinner (3.75±0.58mmol/L, p<0.01), and MAGE (5.33±0.41mmol/L, p<0.01) compared to those of D21. CONCLUSION: Our findings demonstrated that consuming late-night-dinner led to postprandial hyperglycemia, and this postprandial hyperglycemia can be ameliorated by consuming a divided dinner.

Steroid Pulse Therapy for De Novo Minimal Change Disease During Pregnancy.

BACKGROUND Nephrotic syndrome occurs very rarely, in only about 0.01%-0.02% of all pregnancies, and de novo minimal change disease during pregnancy is especially rare. Nephrotic syndrome and, especially, minimal change disease are highly responsive to steroids, and preterm labor may be avoidable if the maternal condition is improved with steroid therapy. Therefore, prompt diagnosis and proper management are critical to maternal and fetal outcome when severe proteinuria occurs during pregnancy. CASE REPORT A 30-year-old pregnant Japanese woman presented with systemic edema, oliguria, and severe proteinuria and hypoalbuminemia at 25 weeks of gestation, although she was normotensive. The patient had high urinary protein selectivity. Her illness was diagnosed as de novo nephrotic syndrome with high steroid responsiveness rather than pre-eclampsia. She began steroid pulse therapy the day after admission. Complete remission was confirmed after 3 weeks. The patient did not relapse during pregnancy and delivered a healthy male baby at 37 weeks of gestation. A renal biopsy at a relapse after delivery confirmed minimal change disease. CONCLUSIONS In pregnant women with de novo minimal change disease, serious maternal and/or fetal complications may occur if severe proteinuria and hypoalbuminemia are unabated for an extended time. Evaluation of urinary protein selectivity is noninvasive and useful for prediction of steroid responsiveness. Results of urinary protein selectivity can be obtained earlier than results of renal biopsy. Renal biopsy during pregnancy is not always necessary for initiation of steroid therapy. Rapid initiation of steroid pulse therapy may enable quicker achievement of remission and prevent serious perinatal complications.

Combination of Aprepitant, Azasetron, and Dexamethasone as Antiemetic Prophylaxis in Women with Gynecologic Cancers Receiving Paclitaxel/Carboplatin Therapy.

BACKGROUND The aim of this study was to evaluate the antiemetic effect of aprepitant and to determine how to provide triple combination therapy (aprepitant/azasetron/dexamethasone) to women receiving paclitaxel/carboplatin moderately emetogenic chemotherapy (MEC). MATERIAL AND METHODS The current study was a prospective study of 163 women with gynecologic cancers. We compared the digestive symptoms scores (nausea, vomiting, appetite loss, and dietary intake) of 37 women with ovarian cancers before and after aprepitant administration. We also compared these symptoms in women who underwent 193 cycles of triple combination therapy with symptoms of women who underwent 226 cycles of double combination therapy. For triple combination therapy, azasetron, dexamethasone (reduced dose: 40% of 20 mg), and aprepitant (125 mg) were administered on Day 1, followed by only aprepitant (80 mg) administration on Days 2 and Day 3. RESULTS In 37 women with ovarian cancer, three symptoms, nausea, appetite loss, and dietary intake, were significantly improved by primarily adding aprepitant to double combination therapy in the delayed phase of MEC. Upon comparing their digestive symptoms in all cycles, however, these three symptoms were not significantly different in the delayed phase. Furthermore, all four symptoms in all cycles were worse following triple combination therapy than following double combination therapy in the acute phase (p<0.02). The control of digestive symptoms was generally insufficient without the administration of dexamethasone. CONCLUSIONS Primary aprepitant as an addition to MEC demonstrated efficacy in improving digestive symptoms in the delayed phase. However, its effect may decrease with repeated use. To improve the antiemetic effect, the dose reduction of dexamethasone should be restricted on Day 1 and dexamethasone should be used throughout the delayed phase as well.

Effect of eating vegetables before carbohydrates on glucose excursions in patients with type 2 diabetes.

The aim of this review was to evaluate whether eating vegetables before carbohydrates could reduce the postprandial glucose, insulin, and improve long-term glycemic control in Japanese patients with type 2 diabetes. We studied the effect of eating vegetables before carbohydrates on postprandial plasma glucose, insulin, and glycemic control for 2.5 y in patients with type 2 diabetes. The postprandial glucose and insulin levels decreased significantly when the patients ate vegetables before carbohydrates compared to the reverse regimen, and the improvement of glycemic control was observed for 2.5 y. We also compared the postprandial glucose and glucose fluctuations assessed by continuous glucose monitoring system for 72-h in patients with type 2 diabetes and subjects with normal glucose tolerance when subjects ate vegetables before carbohydrates and carbohydrates before vegetables in a randomized crossover design. The glycemic excursions and incremental glucose peak were significantly lower when the subjects ate vegetables before carbohydrates compared to the reverse regimen. This evidence supports the effectiveness of eating vegetables before carbohydrates on glucose excursions in the short-term and glycemic control in the long-term in patients with type 2 diabetes.

Serum allograft inflammatory factor-1 is a novel marker for diabetic nephropathy.

AIMS: Recent studies have identified macrophage-mediated injury as an important component in the development of diabetic nephropathy. The aim of this study was to investigate the correlations between serum allograft inflammatory factor-1 (AIF-1) concentration, which is a marker of activated macrophages, and diabetic nephropathy. METHODS: Serum AIF-1 concentrations were measured in 284 patients with type 2 diabetes. We evaluated relationships of serum AIF-1 concentrations to degree of urinary albumin excretion (UAE) or estimated glomerular filtration rate (eGFR) in univariate and multivariate linear regression analyses. RESULTS: Serum AIF-1 concentrations positively correlated with logarithm of UAE (r=0.260, P<0.0001), whereas serum AIF-1 concentrations inversely correlated with eGFR (r=-0.312, P<0.0001). Mean serum AIF-1 concentration was higher in patients with macroalbuminuria than that in patients with normoalbuminuria (P=0.0001) or that in patients with microalbuminuria (P=0.0093). In multivariate linear regression analyses, serum AIF-1 concentrations were independently correlated with logarithm of UAE (ß=0.213, P=0.0120) and with eGFR (ß=-0.286, P=0.0011). CONCLUSIONS: Serum AIF-1 concentration correlated with albuminuria and eGFR in patients with type 2 diabetes and it could be a marker of diabetic nephropathy as well as activated macrophages.

Toe-brachial index is associated more strongly with albuminuria or glomerular filtration rate than ankle-brachial index in patients with type 2 diabetes.

The aim of this study was to investigate whether toe-brachial index (TBI) is more strongly associated with albuminuria or estimated glomerular filtration rate (eGFR) than ankle-brachial index (ABI), and thus is a more suitable tool for evaluating the association between peripheral artery disease (PAD) and diabetic nephropathy than ABI in patients with type 2 diabetes. We evaluated the relationships between ABI or TBI and the degree of urinary albumin excretion or eGFR, as well as the major cardiovascular risk factors, in 390 patients with type 2 diabetes. Furthermore, we compared the area under the receiver-operator characteristic curve (AUC) of TBI or ABI for albuminuria or chronic kidney disease (CKD). Low-density lipoprotein cholesterol was negatively associated with ABI. Age and duration of diabetes were negatively associated with TBI, and diastolic blood pressure and high-density lipoprotein cholesterol were positively associated with TBI. Log (urinary albumin excretion) was associated more strongly with TBI (r=-0.265, P<0.0001) than with ABI (r=-0.132, P=0.0111), and eGFR was positively associated with TBI (r=0.195, P=0.0002) but not with ABI (r=0.023, P=0.6571). The AUCs of TBI for albuminuria (P=0.0002) and CKD (P=0.0322) were significantly greater than those of ABI. In conclusion, TBI is associated more strongly with albuminuria and eGFR than ABI in patients with type 2 diabetes. Our study suggests that TBI may be a more suitable tool for evaluating the association between PAD and diabetic nephropathy than ABI in patients with type 2 diabetes.

The serum concentration of allograft inflammatory factor-1 is correlated with metabolic parameters in healthy subjects.

Obesity is associated with low-grade chronic inflammation characterized by inflamed adipose tissue with increased infiltration of macrophages. The aim of this study was to investigate the correlations between the serum concentration of allograft inflammatory factor-1 (AIF-1), which is a marker of activated macrophages, and metabolic parameters. The serum AIF-1 concentrations were measured in 303 healthy subjects (163 men and 140 women). We then evaluated the relationships between the serum AIF-1 concentrations and metabolic parameters, including fasting plasma glucose levels, serum lipid concentration, uric acid concentration, and waist circumference. The serum AIF-1 concentrations positively correlated with levels of fasting plasma glucose (r = 0.159, P =.0056), hemoglobin A(1c) (r = 0.169, P = .0032), triglycerides (r = 0.137, P = .0172), and uric acid (r = 0.146, P = .0108) and with waist circumference (r = 0.221, P = .0001) and body mass index (r = 0.185, P = .0012), whereas the serum AIF-1 concentrations inversely correlated with high-density lipoprotein cholesterol level (r = -0.178, P = .0019). Stepwise multiple regression analysis demonstrated that hemoglobin A(1c) level (ß = .133, F = 5.490, P < .05) and waist circumference (ß = .197, F = 11.954, P < .05) were independent predictors of the serum AIF-1 concentrations. The serum AIF-1 concentrations correlated with clinical and biochemical metabolic parameters. Allograft inflammatory factor-1 may be a significant predictor of activated macrophages as well as cardiovascular disease in humans.

Low urine pH Is a predictor of chronic kidney disease.

BACKGROUND/AIMS: A variety of risk factors for chronic kidney disease (CKD), including the metabolic syndrome, were recently reported. It has been suggested that a low urine pH is another characteristic of the metabolic syndrome. However, the relationship between urine pH and CKD remains to be elucidated. METHODS: A cohort study was performed on 1,811 subjects who underwent a health check-up, and we examined whether low urine pH could be a predictor of CKD. The following risk factors for CKD were evaluated: age, gender, history of alcohol intake and smoking, BMI, systolic blood pressure, fasting plasma glucose, total cholesterol, uric acid, total leukocyte count, CKD stage, fasting urine pH, and protein at baseline. RESULTS: We followed 1,811 subjects for a median period of 7.7 years. Three hundred and thirty-nine subjects developed stage 3 CKD defined as progression to estimated glomerular filtration rate < 60 ml/min/1.73 m(2). Multiple Cox regression analysis revealed that the adjusted HR (95% CI) for stage 3 CKD was 1.32 (1.06-1.65; p = 0.0129) in subjects with fasting urine pH 5.0-5.5 compared to subjects with pH 6.5-7.0. CONCLUSION: Our study suggests that low urine pH is an independent predictor of stage 3 CKD.

High plasma 5-hydroxyindole-3-acetic acid concentrations in subjects with metabolic syndrome.

OBJECTIVE: Serotonin mediates vasoconstriction and induces the activation of platelets, which may promote atherosclerosis. The aim of this study was to investigate whether plasma 5-hydroxyindole-3-acetic acid (5-HIAA; a derivative end product of serotonin) concentrations are high in subjects with metabolic syndrome (MetS) and to investigate the relationship between plasma 5-HIAA concentrations and clinical and biochemical metabolic parameters. RESEARCH DESIGN AND METHODS: Plasma 5-HIAA concentrations were measured in 311 subjects (152 men and 159 women) recruited from the Oike Clinic, which provides regular health check-ups for employees. We evaluated the relationship between plasma 5-HIAA concentrations and clinical and biochemical metabolic parameters, including waist circumference, serum lipid concentrations, fasting plasma glucose, or blood pressure. RESULTS: Plasma 5-HIAA concentrations were higher in subjects with MetS than in those without, in both men (6.5 ± 4.4 vs. 4.9 ± 1.3 ng/mL, P < 0.005) and women (7.9 ± 6.5 vs. 5.2 ± 1.6 ng/mL, P < 0.005). In men, fasting plasma glucose (r = 0.197, P = 0.0146) was positively correlated, whereas HDL cholesterol (r = -0.217, P = 0.0071) was negatively correlated, with logarithmic (log) (plasma 5-HIAA concentrations). In women, triglycerides (r = 0.252, P = 0.0013) and fasting plasma glucose (r = 0.344, P < 0.0001) were positively correlated, whereas HDL cholesterol (r = -0.328, P < 0.0001) was negatively correlated, with log (5-HIAA concentrations). Furthermore, log (plasma 5-HIAA concentrations) were higher in subjects with more components of MetS. CONCLUSIONS: Plasma 5-HIAA concentrations are high in subjects with MetS, suggesting the potential importance of serotonin in the development of cardiovascular disease in MetS.