Saeko Imai

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance.

Oxidative stress is recognized widely as being associated with various disorders including diabetes, hypertension, and atherosclerosis. It is well established that hydrogen has a reducing action. We therefore investigated the effects of hydrogen-rich water intake on lipid and glucose metabolism in patients with either type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). We performed a randomized, double-blind, placebo-controlled, crossover study in 30 patients with T2DM controlled by diet and exercise therapy and 6 patients with IGT. The patients consumed either 900 mL/d of hydrogen-rich pure water or 900 mL of placebo pure water for 8 weeks, with a 12-week washout period. Several biomarkers of oxidative stress, insulin resistance, and glucose metabolism, assessed by an oral glucose tolerance test, were evaluated at baseline and at 8 weeks. Intake of hydrogen-rich water was associated with significant decreases in the levels of modified low-density lipoprotein (LDL) cholesterol (ie, modifications that increase the net negative charge of LDL), small dense LDL, and urinary 8-isoprostanes by 15.5% (P < .01), 5.7% (P < .05), and 6.6% (P < .05), respectively. Hydrogen-rich water intake was also associated with a trend of decreased serum concentrations of oxidized LDL and free fatty acids, and increased plasma levels of adiponectin and extracellular-superoxide dismutase. In 4 of 6 patients with IGT, intake of hydrogen-rich water normalized the oral glucose tolerance test. In conclusion, these results suggest that supplementation with hydrogen-rich water may have a beneficial role in prevention of T2DM and insulin resistance.

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

OBJECTIVES The aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance. DESIGN AND METHODS We studied 112 patients with T2DM and 80 age- and gender-matched control subjects. RESULTS Serum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5+/-5.2 ng/mL vs. 20.0+/-7.3 ng/mL, P<0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P<0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (rho=0.458, P<0.05) and HOMA-R (rho=0.444, P<0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F=5.294, P<0.05) in female patients with diabetes. CONCLUSIONS These findings suggest that BDNF may contribute to glucose metabolism.

Eating vegetables before carbohydrates improves postprandial glucose excursions

Large fluctuations in blood glucose are reported to promote the micro- and macrovascular complications associated with Type 2 diabetes. Postprandial plasma glucose and glycaemic spikes are more strongly associated with atherosclerosis than fasting plasma glucose or HbA1c level 1. Therefore, safe and effective interventions, including diet, are needed to reduce glycaemic variability and minimize hypoglycaemic events. The continuous glucose monitoring system is capable of detecting hypoglycaemia and hyperglycaemia that may be undetectable by self monitoring blood glucose and HbA1c 2. In particular, the mean amplitude of glycaemic excursions is a significant determinant of overall metabolic control, as well as increased risk of diabetes complications. We reported acute effects of eating vegetables before carbohydrates on postprandial glucose and insulin levels 3 and the long-term glycaemic improvements in patients with Type 2 diabetes 4. The method of the education included nutritional advice given in the form of a simple and easy meal plan of eating vegetables before carbohydrates. In order to reduce postprandial hyperglycaemia, patients were encouraged to consume every meal by eating vegetables prior to carbohydrates. In this study we evaluated whether eating vegetables before carbohydrates could reduce the daily postprandial glucose excursions assessed by continuous glucose monitoring system in Japanese patients with Type 2 diabetes and subjects with normal glucose tolerance. Consecutive patients with Type 2 diabetes were recruited among outpatients regularly attending a diabetes clinic, the Kajiyama Clinic located in Kyoto, Japan, from 2011 to 2012. Diagnosis of diabetes was made according to the World Health Organization criteria. Confirmation of normal glucose tolerance was based on fasting blood glucose < 5.6 mmol/l and 2-h glucose concentration in an oral glucose tolerance test < 7.8 mmol/l. All participants were assigned to perform the continuous glucose monitoring system (CGMS, Medtronic Minimed Gold; Medtronic Minimed, Northridge, CA, USA) for 72 h by eating test meals of vegetables before carbohydrates and carbohydrates before vegetables on the 2nd and the 3rd day in a randomized crossover design. The test meals consisted of rice/bread, meat/fish and 500 g of vegetables, and contained 21 g of dietary fibre and 125.6 kJ kg−1 per day. The energy ratio of protein, fat and carbohydrates was 17, 25 and 58%, respectively. The subjects ate the first dish of vegetables for 5 min, then the main dishes, and consumed rice or bread with a 10-min interval between vegetables and carbohydrates in each meal, and then vice versa. The glucose fluctuations were assessed by the following parameters obtained from the continuous glucose monitoring system and compared between the day of eating vegetables before carbohydrates and the day of eating the carbohydrates before the vegetables: the mean plasma glucose, standard deviation (sd), mean amplitude of glycaemic excursions and the largest amplitude of glycaemic excursions, postprandial plasma glucose, incremental area under the curve 0–3h (IAUC0–3h), and incremental glucose peak. Nineteen outpatients with Type 2 diabetes [men/women 6/13; age 65.5 ± 9.4 years, duration of diabetes 16.4 ± 10.2 years; BMI 22.5 ± 3.1 kg/m2; HbA1c 55.0 ± 10.9 mmol/mol (7.2 ± 1.0%); fasting plasma glucose 8.06 ± 2.67 mmol/l, diet/oral hypoglycaemic agents/insulin + oral hypoglycaemic agents 3/3/13; mean ± sd or n] and 21 subjects with normal glucose tolerance [men/women 2/19; age 29.8 ± 11.3 years; BMI 20.8 ± 3.0 kg/m2; HbA1c 36.0 ± 6.6 mmol/mol (5.4 ± 0.6%); fasting plasma glucose 4.89 ± 0.50 mmol/l] were enrolled in the study. The levels of standard deviation, mean amplitude of glycaemic excursions, largest amplitude of glycaemic excursions, 1-h postprandial plasma glucose of breakfast, IAUC0–3h of lunch and dinner, mean IAUC0–3h and incremental glucose peak were significantly reduced when the participants ate vegetables before carbohydrates compared with the reverse regimen in both subjects with Type 2 diabetes and those with normal glucose tolerance; however, the values of mean plasma glucose were not different in either of the subject groups (Table 1). Two-hour postprandial plasma glucose levels of lunch and dinner, and IAUC0–3h of breakfast were also significantly reduced in patients with Type 2 diabetes, while 1-h postprandial plasma glucose levels of lunch and dinner were significantly decreased in subjects with normal glucose tolerance. The reason for the reduction of postprandial plasma glucose levels by eating vegetables before carbohydrates can be explained, partly, by the dietary fibre content in the vegetables taken before the carbohydrates. Dietary carbohydrates consumed after vegetables were digested slowly and required less insulin for subsequent metabolic disposal 5. Other factors may influence the glycaemic response and digestion of carbohydrates in the small intestine, including the rate of digestion, cooking method, transit time and rate of intestinal absorption. Vegetables given before carbohydrates might stimulate incretin hormone secretion, which leads to the reduction in glycaemic excursions 6. Table 1 Characteristics of glycaemic excursion in subjects with Type 2 diabetes and normal glucose tolerance In this study, we demonstrated that eating vegetables before carbohydrates reduced the postprandial glucose excursions compared with the reverse regimen in both subjects with Type 2 diabetes and those with normal glucose tolerance using continuous glucose monitoring system for the first time. The result of this study is important because eating vegetables before carbohydrates could be a novel method to reduce the incidence of cardiovascular disease 7–10. As one of the educational points in nutrition, the advice to patients with Type 2 diabetes should be to eat vegetables before carbohydrates, and this advice could even be applicable to healthy subjects in order to prevent future cardiovascular events.

Low serum bilirubin concentration in haemodialysis patients with Type 2 diabetes

Diabet. Med. 28, 96–99 (2011)

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.

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 m2. 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.

Risk factors for development of diabetes mellitus, hypertension and dyslipidemia

We investigated the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia simultaneously in a community-based observational cohort study (n=4304). When hypertension or dyslipidemia was present at baseline, hazard ratio (95% CI) of developing diabetes mellitus at year 5 is 3.014 (2.131-4.264) or 2.112 (1.520-2.936), respectively.

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.

Intervention with Delivery of Diabetic Meals Improves Glycemic Control in Patients with Type 2 Diabetes Mellitus

The aim of this study was to investigate the effects of a diabetic meal delivery system on glycemic control over a 12 month period in patients with type 2 diabetes. A total of 77 patients with type 2 diabetes were assigned randomly into three dietary intervention groups: group M, diabetic meal delivery; group D, individual dietary counseling; and group C, conventional dietary education. In group M, HbA1c levels decreased significantly from 8.2 ± 1.2% to 7.4 ± 0.8% after 12 months (p<0.05), while in group D, HbA1c levels decreased significantly throughout the entire 12 month period, from 8.5 ± 1.7% at baseline to 7.4 ± 1.1% at the endpoint. Similarly, fasting blood glucose (FBG) levels decreased significantly between 1 and 12 months in group M (p<0.05), and decreased significantly during the entire 12 month period in group D (p<0.01). There were no significant changes in either HbA1c or FBG levels in group C. This study provides evidence that intervention with delivery of diabetic meals to patients with type 2 diabetes can be equally effective for achieving glycemic control as individual dietary counselling by a dietitian. Diabetic meal delivery can therefore be used successfully to provide diabetes education to outpatients.

The α-glucosidase inhibitor acarbose reduces the net electronegative charge of low-density lipoprotein in patients with newly diagnosed type 2 diabetes

BACKGROUND Several epidemiological studies have shown that postprandial hyperglycemia is associated with an increased risk of cardiovascular disease (CVD). The present study was conducted in order to compare the effects of acarbose and glimepiride treatment on serum lipoprotein profiles in patients with type 2 diabetes. METHODS A total of 37 patients with newly diagnosed type 2 diabetes were studied. The patients were assigned randomly to treatment for 12 weeks with either acarbose (n=13, 100 mg x 3/day, group A), glimepiride (n=13, 2 mg/day, group G) or diet only (n=11, group D). Lipid and lipoprotein profiles before and after each treatment were evaluated. RESULTS A significant reduction in the net electronegative charge of low-density lipoprotein (emLDL) was observed in group A (-1.8, P<0.01), whereas no significant change in emLDL was observed in groups G and D. In group A, small VLDL and very small LDL levels were also decreased significantly (P<0.05). The change in emLDL levels correlated significantly with changes in very small LDL (r=0.751, P<0.01) and oxidized LDL levels (r=0.623, P<0.05). CONCLUSION These results suggest that measurement of serum emLDL may be a sensitive and clinically useful marker for determining qualitative lipoprotein abnormalities in diabetes, and that acarbose treatment lowers CVD risk by decreasing production of emLDL.