Postprandial glycemic control conditions in relation to urinary N-acetyl-ß-D-glucosaminidase in patients with type 2 diabetes mellitus without low glomerular filtration rate.

BACKGROUND: This study assessed 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-ß-D-glucosaminidase (NAG) to creatinine (NAG index) in patients with type 2 diabetes mellitus. SUBJECTS AND METHODS: This was a cross-sectional study with 153 patients who had an estimated glomerular filtration rate of ≥60 mL/min/1.73 m(2) and no proteinuria and who had never been treated with oral hypoglycemic agents or insulin. On the basis of 1,5-AG levels, the patients were divided into a High 1,5-AG group (>14.0 µg/mL) and a Low 1,5-AG group (≤14.0 µg/mL). RESULTS: The logarithmically transformed NAG index was significantly higher in the Low 1,5-AG group than in the High 1,5-AG group when all glycated hemoglobin (HbA1c) levels were included. The logarithmically transformed NAG index was lowest in the High 1,5-AG group with an HbA1c level of ≤6.4% and was highest in the Low 1,5-AG group with an HbA1c level of ≥7.5%. Multivariate regression analysis showed that the NAG index had a higher independent association with 1,5-AG than with HbA1c or the fasting plasma glucose level. In all models, multivariate regression analyses showed that the NAG index was correlated with age. CONCLUSIONS: These results suggest that postprandial hyperglycemia correlates with early renal tubule injury in type 2 diabetes mellitus.

Improving in the fasting, but not the postprandial, glucose level is associated with reduction of plasma d-ROMs level in patients with type 2 diabetes.

AIMS: This study aimed to evaluate the relationship between improvement of glucose metabolism and plasma levels of diacron-reactive oxygen metabolites (d-ROMs) in patients with type 2 diabetes. METHODS: As the first daily profile, the plasma levels of glucose and d-ROMs were determined on admission. Then, after treatment to lower plasma glucose levels, the second daily profile of these levels was evaluated. Fasting plasma glucose (FPG), the total area under the curve (AUC) of the daily plasma glucose profile (AUCDP), the AUC of the postprandial plasma glucose levels (AUCPP), the AUC of the daily plasma d-ROMs profile (AUCd-ROMs), the coefficient of variation (CV) of plasma glucose (CVPG), and the mean amplitude of glycemic excursions (MAGE) were calculated. The relationship between the improvement of glucose metabolism and that of oxidative stress in patients with type 2 diabetes was evaluated. RESULTS: The second determinations of FPG, AUCDP, AUCPP, MAGE, and AUCd-ROMs were significantly lower than those of the first determinations, but no significant difference was observed in CVPG. Linear regression analysis demonstrated significant associations between the changes in AUCd-ROMs and the changes in both FPG and AUCDP, whereas no significant association was observed between the change in AUCd-ROMs and the change in AUCPP, CVPG, or MAGE. CONCLUSIONS: This study has demonstrated that improvement of the FPG level, but not of the postprandial glucose level, is associated with a reduction of the plasma level of d-ROMs in patients with type 2 diabetes.

Serum uric acid in relation to serum 1,5-anhydroglucitol levels in patients with and without type 2 diabetes mellitus.

OBJECTIVES: The aim of this study was to examine the relationship between serum levels of uric acid (UA) and 1,5-anhydroglucitol (1,5-AG) in elderly subjects (60 years or older; mean age, 73.0±7.2 years) with and without type 2 diabetes mellitus (DM). METHODS: Subjects with DM (n=97) and without DM (n=360) were recruited from among our outpatients (estimated glomerular filtration rate≥45 mL min⁻¹ 1.73 m⁻², and urine protein equivalent to <1.0 g/L), and a cross-sectional study was performed with simple linear regression and stepwise multiple linear regression analyses. RESULTS: The mean serum UA levels of men were significantly higher than those of women in both groups. The mean serum 1,5-AG levels of men were significantly higher than those of women in the non-DM group. There were positive correlations (indicated by Pearson's correlation coefficients) between serum UA levels and 1,5-anhydroglucitol levels in all patients and in both men and women. Simple linear regression and multiple linear regression analyses showed that the serum 1,5-AG levels were significantly and positively correlated with the serum UA level in both the non-DM group and the DM group. In the non-DM group, HbA1c levels, as well as 1,5-AG levels, were positively correlated with serum UA levels. Furthermore, the correlation between 1,5-AG and UA levels was stronger in subjects with DM than in subjects without DM. CONCLUSIONS: These results suggest that the serum 1,5-AG level is an independent factor associated with serum UA levels in the nondiabetic state, as in DM.

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.

BACKGROUND: The 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). METHODS: Serum 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. RESULTS: During 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). CONCLUSIONS: Our 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 asymptomatic leukocyturia and urinary N-acetyl-ß-d-glucosaminidase in women.

Urinary N-acetyl-ß-d-glucosaminidase (NAG) has been suggested as a marker for early diabetic nephropathy. This study aimed to prospectively investigate the relationship between asymptomatic leukocyturia (ASL) and NAG in women. One hundred and five female outpatients aged 31-86 years were selected for a 10-year follow-up study. We regarded ASL to be present if two consecutive samples were found to have 10 or more leukocytes/high-power field at 400× magnifications in a centrifuged midstream urine sample both at baseline and 10 years later. The urinary activities of NAG to creatinine ratios (NAG index) were measured in random spot urine samples. Patients without ASL at the beginning of the study were followed. The patients with ASL had diabetes mellitus more frequently than those without ASL at baseline and after 10 years. Residual urine volume and the NAG index were significantly higher in the former than in the latter (p = 0.014 and p = 0.002, respectively) at baseline. During the observation period, 15 patients had ASL (30.6%). Although a gradual increase in the NAG index was found during the study in both patients who had ASL and those who did not, the mean NAG index was significantly higher in the latter during study period (6.4 ± 3.0 vs. 9.8 ± 5.5, p = 0.004, 9.4 ± 5.2 vs. 11.5 ± 6.4, p = 0.328, respectively). On multiple logistic regression analysis, the NAG index at the beginning of the study was an independent predictor of ASL. These results demonstrate that the NAG index may serve as an indicator of ASL in women.

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.

[A case of ileus caused by a fecalith in an elderly patient with severe dementia].

An 82-year-old woman with severe dementia, living in a nursing home, had severe chronic constipation, possibly due to the presence of multiple risk factors for constipation such as a past history of abdominal open surgery, diabetes, hypothyroidism, and bedridden status. She visited our department accompanied by nursing staff with complaints of nausea and vomiting. Abdominal X-ray films and computed tomography (CT) images showed ileus. We diagnosed strangulation ileus, and performed an emergency laparotomy. There was a mobile cystic lesion located 180 cm from the ileocecal junction which was causing the intestinal obstruction. The cystic lesion was surgically removed via an enterotomy. The greatest dimensions of the cystic lesion were 5 × 3 cm, and it was histologically diagnosed as a fecalith. We report a rare case of ileus caused by a fecalith in an elderly patient.

Oral glucose loading attenuates endothelial function in normal individual.

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.

Lack of relationship between blood glucose-lowering activity of colestimide and serum cholecystokinin (CCK) concentrations in patients with type 2 diabetes.

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.