Shoko Futami-Suda

Oral glucose loading attenuates endothelial function in normal individual.

Eur J Clin Invest 2011; 41 (5): 465–473

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

BackgroundPrevious studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals.MethodsThirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.ResultPercentage decreases from FMD0 to FMD60 were significantly greater in the TM group (−21.19% ± 17.90%; P < 0.001) and the OG group (−17.59% ± 26.64%) than in the control group (6.46% ± 9.17%; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group (−18.91% ± 16.58%) than in the control group (6.78% ± 11.43%; P < 0.001) or the TM group (5.22% ± 37.22%; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = −0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = −0.462; P < 0.05) and the AUC of IRI (r = −0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables.ConclusionDifferences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.

Effects of bile-acid-binding resin (colestimide) on blood glucose and visceral fat in Japanese patients with type 2 diabetes mellitus and hypercholesterolemia: an open-label, randomized, case-control, crossover study.

OBJECTIVE The objective was to examine the effects of colestimide on blood glucose, visceral fat, adipocytokines, and bile acid conjugate fractions in Japanese patients. METHODS This study was an open-label, randomized, case-control, crossover study of colestimide 3 g/day in 40 Japanese patients with type 2 diabetes mellitus (T2D) and hypercholesterolemia. Patients were assigned to the colestimide group in which pravastatin and colestimide were administered orally and to the statin group in which pravastatin alone was administered orally. The principal outcome measures were serum lipid levels, fasting plasma glucose level in the early morning, hemoglobin A1c (HbA(1c)), visceral fat area (VFA), and serum 1,5-anhydroglucitol (1,5-AG) level. RESULTS Serum low-density lipoprotein cholesterol levels significantly decreased from 113±38 mg/dl at baseline to 90±20 mg/dl (P=.009) at week 12 of colestimide administration. HbA(1c) significantly decreased from 7.4%±0.9% at baseline to 6.9%±0.9% (P=.001) at week 12 of colestimide administration. Serum 1,5-AG levels increased from 9.4±10.1 μg/ml to 12.4±9.5 μg/ml (P=.05) at week 12 of colestimide administration. The statin group showed no significant changes in lipids and 1,5-AG. However, ΔVFA was inversely correlated with Δcholic acid, and multivariate analysis revealed that ΔVFA was a significant explanatory variable. CONCLUSIONS Colestimide holds promise not only for the treatment of hypercholesterolemia but also for the possible improvement of T2D and visceral fat obesity.

Low-molecular-weight lipoprotein (a) and low relative lymphocyte concentration are significant and independent risk factors for coronary heart disease in patients with type 2 diabetes mellitus: Lp(a) phenotype, lymphocyte, and coronary heart disease

BackgroundThe aim of the present prospective study was to examine whether lipoprotein (a) [Lp(a)] phenotypes and/or low relative lymphocyte concentration (LRLC) are independently associated with coronary heart disease (CHD) in patients with type 2 diabetes mellitus (T2DM).MethodsSerum Lp(a) concentration, Lp(a) phenotypes, and RLC were analyzed in 214 subjects. Lp(a) phenotypes were classified into 7 subtypes according to sodium dodecyl sulfate-agarose gel electrophoresis by Western blotting. Subjects were assigned to the low-molecular-weight (LMW (number of KIV repeats: 11–22) ) and high-molecular-weight (HMW( number of KIV repeats: >22 )) Lp(a) groups according to Lp(a) phenotype and to the LRLC (RLC: <20.3%) and normal RLC (NRLC; RLC: ≥20.3%) groups according to RLC. A CHD event was defined as the occurrence of angina pectoris or myocardial infarction during the follow-up period.ResultsDuring the follow-up period, 30 cases of CHD events were verified. Neutrophil count showed no correlation with CHD, while relative neutrophil concentration and RLC showed positive and negative correlations, respectively, with CHD. The Cox proportional hazard model analysis revealed the following hazard ratios adjusted for LMW Lp(a), LRLC, and LMW Lp(a) + LRLC: (4.31; 95% confidence interval [CI], 1.99-9.32; P < 0.01, 3.621; 95% CI, 1.50-8.75; P < 0.05, and 7.15; 95% CI, 2.17-23.56; P < 0.01, respectively).ConclusionsOur results suggest that both LMW Lp(a) and LRLC are significant and independent risk factors for CHD and that the combination thereof more strongly predicts CHD in patients with T2DM.

Correlation between postprandial bile acids and body fat mass in healthy normal-weight subjects☆

BACKGROUND Bile acids (BAs) play important roles in glucose regulation and energy homeostasis via G protein-coupled receptors, such as enteroendocrine L cell TGR5. The aim of the present study was to investigate the relationship between postprandial BA levels and body composition after ingestion of a standard test meal. METHODS Eleven healthy subjects of normal weight (body-mass index, 22.0 ± 1.6 kg/m(2) [mean ± SD]), ingested a 400-kcal test meal, and blood samples were obtained from them before ingestion and every 30 min for 120 min after ingestion. The BA fractions were measured with high-performance liquid chromatography. To evaluate body composition, body impedance analysis was performed 1h before ingestion of the test meal. RESULTS Concentrations of both total BA and total glycine-conjugated BA (GCBA) at 30, 60, 90, and 120 min after test-meal ingestion were significantly higher than those at baseline. The body-mass index was correlated with total GCBA at baseline. Moreover, body fat mass was correlated with total GCBA at 30 min (r=-0.688, P=0.019) and 60 min (r=-0.642, P=0.033) and with total BA at 30 min (r=-0.688, P=0.019) and 60 min (r=-0.642, P=0.033). CONCLUSION The postprandial BA response is inversely related with body fat mass in healthy subjects of normal weight.

Change in urinary N-acetyl-β-d-glucosaminidase levels relevant to postprandial glycemic control conditions in subjects without diabetes mellitus.

BACKGROUND To assess the relationship between the serum level of 1,5-anhydroglucitol (1,5-AG), a marker of postprandial hyperglycemia, and the ratio of the urinary activity of N-acetyl-β-d-glucosaminidase to creatinine (NAG index) in subjects without diabetes mellitus (DM). METHODS This was a cross-sectional study with 495 subjects without DM who had an estimated glomerular filtration rate≥30ml/min/1.73m(2). Subjects were divided into tertiles based on serum 1,5-AG levels: high (>21.0μg/ml), middle (14.0-21.0μg/ml), and low (<14.0μg/ml). Adjusted odds ratios for an elevated urinary NAG index (>5.8U/g creatinine) according to the HbA1c (≤5.4%, 5.5%-5.9%, and 6.0%-6.4%) and 1,5-AG tertiles were calculated. RESULTS The NAG index was negatively correlated with the serum 1,5-AG level in all subjects. The slopes of the regression lines for these variables did not differ significantly between elderly (≥65y) and nonelderly subjects. As compared with high 1,5-AG and HbA1c≤5.4%, the odds ratios for an elevated urinary NAG index increased progressively to 7.71 across the categories of low 1,5-AG and HbA1c of 6.0% to 6.4%. CONCLUSION Poor control of postprandial glucose is related to an elevated urinary NAG index in persons without DM.

Daily blood glucose profiles of glibenclamide and gliclazide taken once or twice daily in elderly type 2 diabetic patients

Aim:  The aim of this study was to evaluate the difference in daily blood glucose profiles between once‐ and twice‐daily regimens of a moderate daily dose of glibenclamide or gliclazide in elderly patients with type 2 diabetes.

The Effect of Colestimide on Visceral Fat Mass and Cytokine Levels in Patients with Metabolic Syndrome

The Effect of Colestimide on Visceral Fat Mass and Cytokine Levels in Patients with Metabolic Syndrome Bile acid–binding resins (BABRs) improve hyperglycemia in patients with type 2 diabetes, and the BABR colesevelam has been approved by the U.S. Food and Drug Administration for use as an antihyperglycemic agent. Colestimide (colestilan) is a new type of anion resin that increases the number of hepatic low-density lipoprotein receptors and decreases serum cholesterol levels by promoting the excretion of bile acids and inhibiting the absorption of cholesterol in the intestine; with these changes, the serum level of low-density lipoprotein cholesterol decreases.