Yoshimasa Igari

A CHINESE HERBAL MEDICINE, CHOTO‐SAN, IMPROVES COGNITIVE FUNCTION AND ACTIVITIES OF DAILY LIVING OF PATIENTS WITH DEMENTIA: A DOUBLE‐BLIND, RANDOMIZED, PLACEBO‐CONTROLLED STUDY

CASE REPORT This 81-year-old man presented in January 2004 at the emergency department for a first episode of acute abdominal distension. He had been hospitalized 8 years earlier for a myocardial infarction and atrial fibrillation. He lived at home with his wife. His treatment included aspirin (75 mg/d), an angiotensin-converting enzyme inhibitor, and digoxin. Initial electrolyte analysis showed severe hypokalemia, at 2.0 mmol/L. Natremia, urea nitrogen, and creatinemia were in the normal range. The electrocardiogram showed atrial fibrillation, with a ventricular rate of 92 beats per minute. A plain abdominal ray showed a gaseous distension of the right colon and of the rectum without sigmoid volvulus or fecal impaction. The diagnosis of acute colonic pseudoobstruction was made, and a colonoscopic exsufflation was performed. Kaliuresis was low (18 mmol/L). The patient was given 40 mEq potassium chloride intravenously. Because of the atrial fibrillation, thyroid function tests were performed, which showed latent hyperthyroidism with low thyroid-stimulating hormone (0.015 mUI/mL (normal range 0–15.4)) and normal peripheral hormones (T4, 19.4 pmol/L (normal range 10–25); T3, 5.23 pmol/L (normal range 4.5–9.2)). Clinically, the thyroid was normal. A second exsufflation was performed the day after admission. Kalemia was measured at 2.9 mm/L. The patient was given potassium supplementation orally (20 mEq/d). He was discharged on the tenth day. Kaliemia was 3.9 mmol/L. The abdomen was normal. A beta-blocker was added to his treatment because of the history of myocardial infarction, and potassium supplementation was stopped. The patient was rehospitalized 3 months later, in April 2004, with the same presentation: acute colonic pseudoobstruction and hypokalemia (1.9 mmol/L) with a low kaliuresis (11 mmol/L). Potassium supplementation was given intravenously initially and then orally. Two colonic exsufflations were necessary. The patient was discharged 10 days after admission. Kalemia was measured at 4.9 mmol/L. A third attack of acute colonic pseudoobstruction occurred 1.5 months later, in May 2004. Kalemia was measured at 2.5 mmol/L. The hypothesis of a relationship between hypokalemia and hyperthyroidism was formulated. Thyroid-stimulating hormone was undetectable (0.005 mUI/L (normal range 0.15–4), and free T4 was elevated (33 pmol/L (normal range 10–25)). Treatment with NeoMercazole (40 mg/d) was initiated. Radioactive iodine uptake was 30% at 4 hours, and the patient was treated with 7 milli Curie of 131 Iodine at the beginning of June 2004. Three months later, kalemia remained in the normal range, no colonic pseudoobstruction occurred, and thyroid function had normalized. DISCUSSION This observation of TPP is unusual in two aspects: the age of the patient and the type of paralysis. TPP usually occurs in young Asian men. To our knowledge, it has never been described in an elderly person. The most frequent clinical presentation is recurrent attacks of flaccid weakness, predominantly involving the lower limbs. Bulbar, ocular, cardiac, and respiratory muscles are rarely involved. Smooth-muscle paralysis has never been described. The cardinal biochemical abnormality during an attack is hypokalemia, which is the result of an intracellular shift of potassium, the total body potassium store being normal. The relationship between thyrotoxicosis and hypokalemia is based on the fact that thyroid hormone has been shown to increase sodium/potassium ATPase activity in skeletal muscle, the liver, and the kidneys, resulting in increased intracellular transport of potassium in the setting of hyperthyroidism, but the pathogenic mechanisms of TPP are not totally explained. A defect in the neuromuscular junction, classically suggested, may explain the colonic paralysis observed. As in classical TPP, recurrent attacks of colonic pseudoobstruction occurred until correction of the hyperthyroid status. Hyperthyroidism must be excluded in older people who present with a hypokalemic colonic pseudoobstruction.

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.

Urinary N-acetyl-β-d-Glucosaminidase Levels are Positively Correlated With 2-Hr Plasma Glucose Levels During Oral Glucose Tolerance Testing in Prediabetes

Urinary N‐acetyl‐β‐D‐glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT). This study investigated when during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose, and insulin levels correlate most strongly with urinary N‐acetyl‐β‐d‐glucosaminidase (NAG) levels in prediabetic subjects.

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.

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 Pearsons 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.

Four-year prospective study of the influence of elevated serum lipoprotein (a) concentration on ischemic heart disease and cerebral infarction in elderly patients with type-2 diabetes

Background:  The purpose of the present paper was to elucidate the influence of an elevated serum lipoprotein (a) (Lp(a)) concentration on the incidence of ischemic heart disease (IHD) and perforating artery occlusion‐type cerebral infarction (CI) in elderly patients with type‐2 diabetes.

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.

Bile duct hamartomas (von Meyenburg complexes) associated with a bacterial infection: Case report of elderly diabetic patient

Bile duct hamartomas (BDH), also known as von Meyenburg complexes, are rare, benign neoplasms of the liver, which contain cystic dilated bile ducts embedded in a fibrous stroma. They occur at all ages but are seen more frequently in older people. An increasing number of cases have been reported along with the recent development of diagnostic imaging technology. However, BDH associated with an infection are uncommon and are therefore very difficult to differentiate from multiple bacterial liver abscesses. We experienced a 75-year-old man with BDH suspected of complicating a cystic infection. He was admitted to our hospital because of high fever and disturbance of consciousness in late October 2008. He was first seen in our department in December 2006 as an Alzheimer’s disease patient with type 2 diabetes mellitus and atrial fibrillation. In February 2008, abdominal ultrasonography (US) performed for screening purposes showed multiple hyperechoic and hypoechoic lesions less than 1 cm in diameter with both multiple comettail echoes in the liver and gallstones. Subsequent findings of magnetic resonance cholangiopancreatography (MRCP) were highly suggestive of BDH. On admission, his body temperature was 39.1°C, blood pressure 118/68 mmHg and pulse 108 b.p.m. (irregular). The chest radiograph identified no significant findings, and the electrocardiogram revealed tachycardic atrial fibrillation. Laboratory findings included C-reactive protein (CRP) of 32.07 mg/dL, white blood cell count of 10 900/mL, aspartate aminotransferase level of 42 IU/L, alanine aminotransferase of 41 IU/L, alkaline phosphatase of 344 IU/L and gglutamyltransferase of 184 IU/L. Blood culture, urine culture, sputum culture and stool culture were all performed on admission, but only the blood culture revealed growth of Escherichia coli. Abdominal US (Fig. 1a) showed multiple hyperechoic and hypoechoic lesions less than 1 cm in diameter with multiple, scattered comet-tail echoes and localized dilation of the bile ducts in the liver. There were multiple strong echoes with acoustic shadows in the gallbladder, suggesting gallstones, but no obvious abnormalities were found in the common bile duct or the main pancreatic duct. Plain abdominal computed tomography (CT) showed multiple small cystic lesions in the liver. Non-contrast abdominal magnetic resonance imaging (MRI) was performed and confirmed the presence of multiple hepatic nodules, hypointense on T1-weighted images and hyperintense on T2-weighted images. MRCP showed multiple irregularly delineated hyperintense nodules, not communicating with the biliary tree (Fig. 2). These results of the laboratory and imaging findings suggested that the patient was suffering from a biliary tract infection. Therefore, administration of a thirdgeneration cephem (ceftriaxone 2 g/day) was started. On hospital day 3, his fever subsided. He showed satisfactory progress thereafter, and CRP was normalized on hospital day 17. Abdominal US findings after improvement of the inflammatory process (Fig. 1b) showed that the intensity of echo levels in multiple hyperechoic lesions and comet-tail sign echoes had decreased in a similar way to findings obtained in February 2008. Furthermore, follow-up non-contrast abdominal MRI examination after 2 months revealed no remarkable changes of distribution, size and number of the cystic lesions when compared with the findings of MRI images at the time of admission. Multiple bacterial liver abscesses were not considered according to these imaging findings. Therefore, on the basis of the clinical course and imaging findings, we suspected the cystic Geriatr Gerontol Int 2011; 11: 534–536