Eur J Clin Invest 2011; 41 (5): 465–473
Background We evaluated the relationship between glucose fluctuation and vascular endothelial function.
Material and methods We recruited 25 healthy ...individuals with no family history of diabetes (14 subjects and 11 controls). Brachial artery flow‐mediated dilation (FMD) and elapsed time when the after‐hyperaemia maximum brachial artery diameter is reached; the peak times (PT) of each study subject were measured before and at 60, 120, and 180 min after 75‐g oral glucose loading. FMD and PT of controls were measured for four consecutive hours in the fasting state from morning. Also, brachial‐ankle pulse wave velocity (baPWV) of each subject was measured at 180 min after 75‐g oral glucose loading.
Results Flow‐mediated dilation of the study subjects was significantly lower at 60, 120 and 180 min than at pre‐load, and significantly lower than that of the controls at 60 and 120 min, but not significantly different at 0 and 180 min. There was no significant difference between the PT of the subjects and the controls during 75‐g oral glucose loading. In contrast, the PT of the subjects was significantly shorter than that of the controls at 120 and 180 min, but showed no significant difference at 0 and 60 min. Moreover, baPWV had no significant relationship with FMD.
Conclusions Our study showed that oral glucose loading attenuates FMD and shortens elapsed time at the maximum after‐hyperaemia diameter, and the effect of glucose fluctuation on atherosclerosis in individuals with normal glucose tolerance remains despite only the attenuation of endothelial function.
Background: Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes complicated by hypercholesterolemia. Aim: To examine the mechanism by which colestimide ...decreases plasma glucose levels in the above patients. Methods: A total of 16 inpatients with type 2 diabetes complicated by hypercholesterolemia received colestimide for 1 week after their plasma glucose levels stabilized. We measured plasma glucose, serum immunoreactive insulin (IRI), serum lipid, plasma glucagon, and plasma glucagon-like peptide-1 (GLP-1) levels. These variables at baseline and 1 week of colestimide administration were compared. Results: Preprandial plasma glucose levels (baseline: 132 ± 33 mg/dL vs. completion: 118 ± 43 mg/dL, P=0.073) tended to decrease after colestimide administration, while 1-hr postprandial plasma glucose levels (baseline: 208 ± 49 mg/dL vs. completion: 166 ± 30 mg/dL, P<0.001) and 2-hr postprandial plasma glucose levels (baseline: 209 ± 56 mg/dL vs. completion: 178 ± 39 mg/dL, P=0.015) decreased significantly at 1 week of colestimide administration. The 2-hr postprandial plasma GLP-1 level was significantly (P=0.015) higher at 1 week of colestimide administration as compared with the baseline level, while there were no significant changes in preprandial and 1-hr postprandial plasma GLP-1 levels. Conclusions: The GLP-1-increasing activity of colestimide may explain, at least in part, the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes complicated by hypercholesterolemia.
Previous 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.
Thirty-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.
Percentage 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.
Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.
Colestimide, an anion exchange resin, reportedly improves glycemic control in patients with type 2 diabetes. However, no studies of the glucose-lowering effect of colestimide have identified ...responders and nonresponders. In the present study, we compared glycemic control, lipids, and body-mass index (BMI) among patients with type 2 diabetes receiving colestimide (n=59) until 24 weeks after the start of treatment. Subjects were classified as responders to treatment (n=40), who showed a 15% or greater decrease in glycated hemoglobin (HbA1c) or a 20% or greater decrease in plasma glucose level or both after 24 weeks of colestimide treatment as compared with baseline; nonresponders showed HbA1c>11.5% or fasting plasma glucose (FPG)>250 mg/dL during the course of the study and <15% decrease in HbA1c levels or <20% decrease in FPG levels or both after 24 weeks of colestimide treatment as compared with baseline. In responders, FPG decreased significantly from 196 ± 91 mg/dL to 125 ± 47 mg/dL after 24 weeks (P<0.001), and HbA1c decreased from 9.1% ± 2.0% to 7.0% ± 0.9% (P<0.001). In nonresponders, HbA1c decreased significantly from 7.7% ± 2.9% to 7.6% ± 1.2% (P<0.05). Multiple logistic regression analysis revealed that baseline HbA1c and the presence of cholelithiasis were significant determinants of the response to colestimide treatment when corrected for sex, age, triglyceride levels, and BMI at baseline and the presence of fatty liver. In conclusion, baseline HbA1c and the presence of cholelithiasis have strong and independent influences on the glucose-lowering effect of colestimide.
Ultrasonography is widely used to evaluate atherosclerosis. Therefore, many ultrasound parameters exist, each with its own clinical implications. Many reports have shown that these ultrasound ...parameters are useful for evaluating the progression of atherosclerosis or the risk of cardiovascular disease in healthy persons and in persons with cardiovascular risk factors. Ultrasound parameters are categorized as either structural or functional parameters. Particularly in the early stage of atherosclerosis, functional parameters are useful for evaluating the risk of the further development of atherosclerosis. We have also reported that the pulsatility index of the brachial artery is related to atherothrombotic infarctions in high-risk elderly subjects1. Next, we studied flow-mediated dilation (FMD) as a functional parameter in the early stage of atherosclerosis. FMD is believed to be associated with endothelial nitric oxide (NO) synthesis. Furthermore, NO has the ability to prevent progression in the early stage of atherosclerosis. Guideline for FMD measurement have already been established2. FMD has been defined as the rate of brachial artery vasodilation 60 seconds after a sphygmomanometric cuff is deflated after being inflated for 5 minutes to a pressure 50mmHg greater than the systolic blood pressure.
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.
Methods: Daily blood glucose profile data were evaluated in 18 elderly type 2 diabetic patients treated with 80 mg/day gliclazide or 5 mg/day glibenclamide as monotherapy. The first daily blood glucose profile of the twice‐daily regimen was performed approximately 1 week before hospital discharge, and the second was performed after taking a once‐daily regimen for 4–7 days. Plasma glucose and plasma immunoreactive insulin (IRI) concentrations were measured daily at 12 time points: 08.00 (before breakfast); 10.00; 12.00 (before lunch); 14.00; 18.00 (before dinner); 20.00; 0.00; 02.00; 03.00; 04.00; 06.00; and 08.00 hours the next morning.
Results: Daily blood glucose profiles and plasma IRI profiles did not differ between the once‐ and twice‐daily regimen groups in either the gliclazide group or the glibenclamide group. Plasma glucose values between midnight and early morning tended to be lower than the 08.00 hours plasma glucose value in the glibenclamide group, but not in the gliclazide group.
Conclusion: These results suggest that the blood glucose‐lowering effects of a once‐ and twice‐daily moderate daily dose of glibenclamide or gliclazide do not differ in elderly type 2 diabetic patients. However, glibenclamide, regardless of the dosage schedule, tends to lower the plasma glucose values between midnight and early morning.
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.
Eleven healthy subjects of normal weight (body-mass index, 22.0±1.6kg/m2 mean±SD), ingested a 400-kcal test meal, and blood samples were obtained from them before ingestion and every 30min for 120min 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.
Concentrations of both total BA and total glycine-conjugated BA (GCBA) at 30, 60, 90, and 120min 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 30min (r=–0.688, P=0.019) and 60min (r=–0.642, P=0.033) and with total BA at 30min (r=–0.688, P=0.019) and 60min (r=–0.642, P=0.033).
The postprandial BA response is inversely related with body fat mass in healthy subjects of normal weight.
Abstract Colestimide, an anion exchange resin, reportedly improves glycemic control in patients with type 2 diabetes. However, no studies of the glucose-lowering effect of colestimide have identified ...responders and nonresponders. In the present study, we compared glycemic control, lipids, and body-mass index (BMI) among patients with type 2 diabetes receiving colestimide (n=59) until 24 weeks after the start of treatment. Subjects were classified as responders to treatment (n=40), who showed a 15% or greater decrease in glycated hemoglobin (HbA1c) or a 20% or greater decrease in plasma glucose level or both after 24 weeks of colestimide treatment as compared with baseline; nonresponders showed HbA1c>11.5% or fasting plasma glucose (FPG)>250mg/dL during the course of the study and <15% decrease in HbA1c levels or <20% decrease in FPG levels or both after 24 weeks of colestimide treatment as compared with baseline. In responders, FPG decreased significantly from 196 ± 91 mg/dL to 125 ± 47 mg/dL after 24 weeks (P<0.001), and HbA1c decreased from 9.1% ± 2.0% to 7.0% ± 0.9% (P<0.001). In nonresponders, HbA1c decreased significantly from 7.7% ± 2.9% to 7.6% ± 1.2% (P<0.05). Multiple logistic regression analysis revealed that baseline HbA1c and the presence of cholelithiasis were significant determinants of the response to colestimide treatment when corrected for sex, age, triglyceride levels, and BMI at baseline and the presence of fatty liver. In conclusion, baseline HbA1c and the presence of cholelithiasis have strong and independent influences on the glucose-lowering effect of colestimide.
Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes and hypercholesterolemia. We investigated the mechanism of the hypoglycemic activity of colestimide by ...examining changes in serum cholecystokinin (CCK) and insulin concentrations before and after its 2-week oral administration. A total of seven type 2 diabetes inpatients with hypercholesterolemia received colestimide after their blood glucose levels had stabilized. We daily measured plasma glucose levels and serum lipid concentrations, calculated Body Mass Index (BMI), and determined whole-day changes in serum immunoreactive insulin (IRI) and CCK concentrations in all study subjects. We daily measured plasma glucose levels, as well as serum IRI and CCK concentrations at 10 time points for measurement. Plasma glucose levels, as well as serum IRI and CCK concentrations before and after the 2-week oral administration of colestimide were compared. The means of total cholesterol levels and BMI decreased significantly after administration. At time points for measurement (10 : 00 and 12 : 00), plasma glucose levels decreased significantly after administration (P=0.026 and P=0.009, respectively). Diurnal changes in serum IRI and CCK concentrations were not observed after administration, except for the IRI concentration at 20: 00. The effect of colestimide on CCK may not explain the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes and hypercholesterolemia.
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