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.
Postprandial hyperglycemia is an independent risk factor for cardiovascular disease-related morbidity and mortality, not only in diabetes mellitus (DM) but also in impaired glucose tolerance. ...Postprandial glycemic levels have been difficult to monitor, but recently 1,5-anhydroglucitol (1,5-AG) levels have proven to be beneficial for this purpose. In humans, 1,5-AG, a 1-deoxy-glucopyranose, is a major and abundant polyol, of which 90% is derived from ingested food, and little is produced from glycogen in the liver. Nearly all 1,5-AG is reabsorbed in normoglycemia, but the reabsorption rate decreases in proportion to the degree of hyperglycemia above the renal threshold for glucosuria, which is 160 to 180 mg/dL. Glucosuria appears if the level of blood glucose rises above this level. The renal reabsorption of 1,5-AG is competitively inhibited by glucosuria. The 1,5-AG level appears to be well suited for monitoring glucose homeostasis in subjects with near-normoglycemia or with postprandial hyperglycemia without fasting hyperglycemia.
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.
Background: An anion exchange resin has been reported to lower blood glucose levels in patients with type 2 diabetes. Aim: To examine, in comparison with an α-glucosidase inhibitor, the usefulness of ...colestimide in lowering blood glucose levels in patients with type 2 diabetes and hypercholesterolemia. Methods: Thirty-three patients with type 2 diabetes and hypercholesterolemia were more or less randomly assigned to receive either colestimide (17 patients) or acarbose (16 patients). At 10 time points before and after administration, plasma glucose levels and serum lipid concentrations were measured in all subjects, and the J-index and M-value were calculated. Results: Patients receiving colestimide showed significant decreases in glucose levels 2 hours after breakfast (from 216.9 ± 37.2 mg/dl before treatment to 191.1 ± 40.9 mg/dl after treatment; p=0.008), in the J-index (from 42.6 ± 14.5 to 32.6 ± 9.8; p<0.001), and in the M-value (from 23.1 ± 12.1 to 14.6 ± 7.1; p<0.001). Conclusion: In patients with type 2 diabetes and hyperlipidemia, colestimide was suggested to have blood glucose-lowering activity as does acarbose.
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.
Background: The present study sought to investigate the relationship between asymptomatic leukocyturia (ASL) and autonomic nervous function by power spectral analysis of the R‐R intervals in women.
...Methods: One hundred and forty‐two female outpatients aged 23–91 years were studied. We regarded ASL to be present if two consecutive samples were found to have 10 or more leukocytes/high‐power field at ×400 magnification in a centrifuged midstream urine sample. The R‐R intervals of all subjects were measured by the wavelet transform analysis system. This system detected R‐R variation data distributed in two bands: low‐frequency power (LF) (0.04–0.15 Hz) and high‐frequency power (HF) (0.15–0.40 Hz). The ratio of LF to HF (LF/HF) was also determined. Post‐void residual urine volume was measured using an automated, compact 3‐D ultrasound device.
Results: The patients with ASL had diabetes mellitus more frequently than those without ASL. Residual urine volume was significantly higher in the former than in the latter, while the HF values in both a recumbent position and a standing position were significantly lower in the former than in the latter (P = 0.003, P = 0.001, respectively). However, there were no significant differences in LF or LF/HF values in either a recumbent or a standing position between the two groups. The HF values in both a recumbent position and in a standing position were independent indicators of ASL, even after adjustment for age, diabetes mellitus and residual urine volume.
Conclusion: The present study reveals the relationship between ASL and impairment of the parasympathetic nervous system in women.
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