Low Handgrip Strength (Possible Sarcopenia) With Insulin Resistance Is Associated With Type 2 Diabetes Mellitus.

Context: Older adults with sarcopenic obesity are at high risk for type 2 diabetes mellitus (T2DM). However, few East Asians have sarcopenic obesity. Since many East Asians have insulin resistance (IR) without obesity, it is possible that older East Asians with sarcopenia and IR might be at high risk for T2DM. However, this relationship has not been studied. Methods: This cross-sectional study included 1629 older adults aged 65 to 84 years registered in the Bunkyo Health Study. All underwent a 75-g oral glucose tolerance test and handgrip strength measurement. Participants were classified into 4 groups by possible sarcopenia (handgrip strength <28 kg in men and <18 kg in women) and IR status (triglyceride glucose [TyG] index ≥8.79 for men and ≥8.62 for women [third quartile]). Modified Poisson regression was used to estimate relative risk (RR) and 95% CIs for T2DM with adjustment for confounding factors. Results: The mean age was 73.1 ± 5.4 years. T2DM was diagnosed in 212 (13.0%) participants. After adjusting for age, sex, body mass index, use of lipid-lowering medications, hypertension, and cardiovascular disease, possible sarcopenia and IR were associated with T2DM, with their coexistence showing a notably stronger association (control: RR, 1.00 [Reference]; possible sarcopenia: RR, 1.55 [95% CI, 1.04-2.30]; IR: RR, 2.69 [95% CI, 1.99-3.65]; and IR possible sarcopenia: RR, 4.76 [95% CI, 3.34-6.79]). Conclusion: Possible sarcopenia based on low handgrip strength and IR based on the TyG index are independently associated with T2DM in older Japanese individuals. Their coexistence shows a particularly strong association with T2DM.

Fat Accumulation and Elevated Free Fatty Acid Are Associated With Age-Related Glucose Intolerance: Bunkyo Health Study.

Context: Older adults have a high prevalence of new-onset diabetes, often attributed to age-related decreases in insulin sensitivity and secretion. It remains unclear whether both insulin sensitivity and secretion continue to deteriorate after age 65. Objective: To investigate the effects of aging on glucose metabolism after age 65 and to identify its determinants. Methods: This cross-sectional study involved 1438 Japanese older adults without diabetes. All participants underwent a 75-g oral glucose tolerance test (OGTT). Body composition and fat distribution were measured with dual-energy X-ray absorptiometry and magnetic resonance imaging. Participants were divided into 4 groups by age (65-69, 70-74, 75-79, and 80-84 years) to compare differences in metabolic parameters. Results: Mean age and body mass index were 73.0 ± 5.4 years and 22.7 ± 3.0 kg/m2. The prevalence of newly diagnosed diabetes increased with age. Fasting glucose, fasting insulin, the area under the curve (AUC)-insulin/AUC-glucose and insulinogenic index were comparable between groups. AUC-glucose and AUC-insulin during OGTT were significantly higher and Matsuda index and disposition index (Matsuda index · AUC-insulin/AUC-glucose) were significantly lower in the age 80-84 group than in the age 65-69 group. Age-related fat accumulation, particularly increased visceral fat area (VFA), and elevated free fatty acid (FFA) levels were observed. Multiple regression revealed strong correlations of both Matsuda index and disposition index with VFA and FFA. Conclusion: Glucose tolerance declined with age in Japanese older adults, possibly due to age-related insulin resistance and ß-cell deterioration associated with fat accumulation and elevated FFA levels.

A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men.

A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and gut microbiota before and after 6-day HCHFD consisting of a regular diet plus a 45% energy excess with dairy fat supplementation. We evaluated tissue-specific insulin sensitivity and metabolic clearance rate of insulin (MCRI) using a two-step hyperinsulinemic euglycemic clamp, glucose tolerance using the glucose tolerance test, and measured ectopic fat in muscle and the liver using ¹H-magnetic resonance spectroscopy. The primary outcome of this study was insulin sensitivity measured by the clamp study. The secondary/exploratory outcomes were other metabolic changes. After HCHFD, levels of circulating lipopolysaccharide binding protein (LBP), a marker of endotoxemia, increased by 14%. In addition, intramyocellular lipid levels in the tibialis anterior and soleus and intrahepatic lipid levels increased by 47%, 31%, and 200%, respectively. Insulin sensitivity decreased by 4% in muscle and 8% in liver. However, even with reduced insulin sensitivity, glucose metabolism was maintained by increased serum insulin concentrations due to lower MCRI and higher endogenous insulin secretion during the clamp. Glucose levels during the meal tolerance test were comparable before and after HCHFD. In conclusion, short-term HCHFD impaired insulin sensitivity in the muscle and livers of non-obese Japanese men with increased LBP and ectopic fat accumulation. Elevated insulin levels from modulated insulin secretion and clearance might contribute to the maintenance of normal glucose metabolism during the clamp and meal tolerance test.

Prediabetes is an independent risk factor for sarcopenia in older men, but not in older women: the Bunkyo Health Study.

BACKGROUND: Sarcopenia is a major cause of disability in the elderly. Although type 2 diabetes is a risk factor for increased sarcopenia, the relationship between prediabetes and sarcopenia has not been elucidated. We aimed to examine the relationship between sarcopenia and prediabetes. METHODS: The design of this study is a cross-sectional study. We evaluated glucose metabolism using the 75-g oral glucose tolerance test and glycated haemoglobin, appendicular skeletal muscle mass, and hand grip strength in 1629 older adults living in an urban area of Tokyo, Japan. We investigated the frequency of sarcopenia in participants with normal glucose tolerance (NGT), prediabetes and diabetes. A multivariable logistic regression model was used to analyse the association between glucose tolerance and the prevalence of sarcopenia. RESULTS: The mean age of participants was 73.1 ± 5.4 years. In men, 44.3% had NGT, 26.6% had prediabetes, and 29.1% had diabetes. In women, the distribution was 56.1%, 28.8% and 15.2%. The prevalence of sarcopenia was 12.7% in men and 11.9% in women. Logistic regression revealed that prediabetes and diabetes are independent risk factors for sarcopenia in men (prediabetes, odds ratio [OR] = 2.081 [95% confidence interval {CI}: 1.031-4.199]; diabetes, OR = 2.614 [95% CI: 1.362-5.018]) and diabetes, but not prediabetes, is an independent risk factor for sarcopenia in women (prediabetes, OR = 1.036 [95% CI: 0.611-1.757]; diabetes, OR = 2.099 [95% CI: 1.146-3.844]). In both sexes, higher age (men, OR = 1.086 [95% CI: 1.028-1.146]; women, OR = 1.195 [95% CI: 1.142-1.251]), higher body fat percentage (men, OR = 1.346 [95% CI: 1.240-1.461]; women, OR = 1.218 [95% CI: 1.138-1.303]) and lower body mass index (men, OR = 0.371 [95% CI: 0.299-0.461]; women, OR = 0.498 [95% CI: 0.419-0.593]) were independent risk factors for sarcopenia. CONCLUSIONS: Although we confirmed that diabetes mellitus is associated with sarcopenia in both sexes, prediabetes is associated with sarcopenia in men, but not in women.

Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes.

BACKGROUND: Decreased insulin clearance could be a relatively upstream abnormality in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Previous studies have shown that sodium-glucose cotransporter 2 inhibitor (SGLT2i) increases insulin-C-peptide ratio, a marker of insulin clearance, and improves metabolic parameters. We evaluated the effects of the SGLT2i tofogliflozin on metabolic clearance rate of insulin (MCRI) with a hyperinsulinemic euglycemic clamp study, the gold standard for measuring systemic insulin clearance. METHODS: Study participants were 12 Japanese men with type 2 diabetes. We evaluated MCRI and tissue-specific insulin sensitivity with a hyperinsulinemic euglycemic clamp (insulin infusion rate, 40 mU/m2·min) before and immediately after a single dose (n = 12) and 8 weeks (n = 9) of tofogliflozin. We also measured ectopic fat in muscle and liver and the abdominal fat area using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively, before and after 8 weeks of tofogliflozin. RESULTS: MCRI did not change after a single dose of tofogliflozin (594.7 ± 67.7 mL/min·m2 and 608.3 ± 90.9 mL/min·m2, p = 0.61) or after 8 weeks (582.5 ± 67.3 mL/min·m2 and 602.3 ± 67.0 mL/min·m2, p = 0.41). The 8-week treatment significantly improved glycated hemoglobin and decreased body weight (1.7%) and the subcutaneous fat area (6.4%), whereas insulin sensitivity and ectopic fat in muscle and liver did not change significantly. CONCLUSIONS: MCRI did not change after a single dose or 8 weeks of tofogliflozin. Increased MCRI does not precede a decrease in body fat or improved glycemic control.

Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men.

CONTEXT: Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians. DESIGN AND SETTING: To investigate the relationships between decreased AN level, impaired ATIS, and metabolic abnormalities, we studied 94 Japanese men whose body mass index was less than 25 kg/m2. We divided the subjects into 4 groups based on their median AN level and ATIS, the latter calculated as the degree of insulin-mediated suppression of free fatty acids during hyperinsulinemic euglycemic clamp, and compared the metabolic parameters in the 4 groups. RESULTS: The High-ATIS/High-AN group (n = 29) showed similar anthropometric data to the High-ATIS/Low-AN group (n = 18). In contrast, both the Low-ATIS/High-AN (n = 18) and Low-ATIS/Low-AN (n = 29) groups showed significantly lower muscle insulin sensitivity than the High-ATIS groups. The intrahepatic lipid level in the Low-ATIS/Low-AN group was significantly higher than that in the High-ATIS groups. In addition, the Low-ATIS/Low-AN group had a significantly higher fasting serum triglyceride level and significantly lower high-density lipoprotein cholesterol level than the other 3 groups. CONCLUSIONS: In nonobese Japanese men with high ATIS, the AN level was not associated with metabolic characteristics. On the other hand, subjects with low ATIS showed reduced muscle insulin sensitivity, and those with a decreased AN level demonstrated multiple metabolic abnormalities, represented by fatty liver and dyslipidemia.

Prevalence and Features of Impaired Glucose Tolerance in Young Underweight Japanese Women.

OBJECTIVE: In Japan, while it is known that underweight women over the age of 40 years have a high risk for type 2 diabetes, there is a lack of clarity on the association between glucose tolerance and underweight in younger women. Accordingly, we investigate the prevalence and features of impaired glucose tolerance (IGT) in young underweight Japanese women. DESIGNS AND METHODS: In this cross-sectional study, we recruited 56 normal weight and 98 underweight young Japanese women and evaluated their glucose tolerance levels using an oral glucose tolerance test. Then, we compared the clinical characteristics associated with normal glucose tolerance (NGT) and IGT in the underweight women. Insulin secretion, whole-body insulin sensitivity, and adipose tissue insulin resistance values were measured using the insulinogenic index, whole-body insulin sensitivity index (Matsuda index), and adipose insulin resistance index (Adipo-IR), respectively. Fitness level (peak VO2) was measured using an ergometer. RESULTS: The prevalence of IGT was higher in the underweight women than the normal weight women (13.3% vs 1.8%). The underweight women with IGT showed a lower insulinogenic index, lower peak VO2, and Matsuda index and a higher fasting free fatty acid level and Adipo-IR than those with NGT. The whole-body composition was comparable between the NGT and IGT groups. CONCLUSIONS: The prevalence of IGT was higher in young Japanese women with underweight than those with a normal weight. The underweight women with IGT showed impaired early-phase insulin secretion, low fitness levels, and reduced whole-body and adipose tissue insulin sensitivity levels.

A decrease in plasma glucose levels is required for increased endogenous glucose production with a single administration of a sodium-glucose co-transporter-2 inhibitor tofogliflozin.

AIM: To investigate whether changes in endogenous glucose production (EGP) and insulin and glucagon levels are elicited by the decrease in plasma glucose (PG) levels induced by the sodium-glucose co-transporter-2 (SGLT2) inhibitor tofogliflozin. MATERIALS AND METHODS: We evaluated EGP in 12 Japanese patients with type 2 diabetes under the conditions of no drugs administered (CON), single administration of the SGLT2 inhibitor tofogliflozin (TOF), and single administration of TOF with adjustment of PG levels with exogenous glucose infusion to mimic changes in PG levels observed with CON (TOF + G). We evaluated changes in EGP and levels of C-peptide and glucagon from baseline to 180 minutes after drug administration. RESULTS: Endogenous glucose production decreased in the CON (-0.22 ± 0.11 mg/kg·min) and TOF + G experiments (-0.31 ± 0.24 mg/kg·min), but not in the TOF experiment (+0.08 ± 0.19 mg/kg·min). The decrease in C-peptide was significantly greater in the TOF experiment (-0.11 ± 0.06 nmol/L) than in the CON (-0.03 ± 0.06 nmol/L) and the TOF + G experiments (-0.01 ± 0.11 nmol/L), while the increase in glucagon was significantly greater in the TOF experiment (+11.1 ± 6.3 pmol/L), but not in the TOF + G experiment (+8.6 ± 7.6 pmol/L) compared to the CON experiment (+5.1 ± 4.3 pmol/L). CONCLUSIONS: These results indicate that the decrease in PG levels induced by SGLT2 inhibitor administration is required for the increase in EGP and decrease in insulin secretion.

Ingestion of an exogenous ketone monoester improves the glycemic response during oral glucose tolerance test in individuals with impaired glucose tolerance: A cross-over randomized trial.

AIMS/INTRODUCTION: As a low-carbohydrate diet and the use of sodium-glucose transporter-2 inhibitors are both known to increase D-beta-hydroxybutyrate levels, the effect of these levels on glucose metabolism has attracted attention. We investigated the acute effects of ketone monoester (KM) ingestion on blood glucose levels during the 75-g oral glucose tolerance test (OGTT) in participants with impaired glucose tolerance. MATERIALS AND METHODS: Nine Japanese adults aged 48-62 years (4 men, 5 women) with impaired glucose tolerance participated in this study. After participants fasted overnight, we carried out OGTT for 180 min with and without KM ingestion on two separate days in a randomized cross-over design. We compared the area under the curve (AUC) of D-beta-hydroxybutyrate, glucose, insulin, C-peptide, glucagon and free fatty acids during OGTT. RESULTS: The AUC of D-beta-hydroxybutyrate during OGTT was significantly higher with KM than without KM (KM 5995.3 ± 1257.1 mmol/L·h; without KM 116.1 ± 33.9 mmol/L·h, P < 0.0001), and the AUC of glucose with KM was significantly lower than that without KM (KM 406.6 ± 70.6 mg/dL·h; without KM 483.2 ± 74.3 mg/dL·h, P < 0.0001). This improved glucose excursion was associated with enhanced AUC of insulin during the first half (0-90 min) of OGTT, even though the AUC of C-peptide during this period was unchanged. In contrast, the AUC of insulin, C-peptide, glucagon and free fatty acids during 180 min of OGTT were similar in both conditions. CONCLUSION: The ingestion of KM decreased the AUC of glucose during 75-g OGTT in Japanese individuals with impaired glucose tolerance, and the mechanism might involve elevated levels of circulating early phase insulin.

Characteristics associated with elevated 1-h plasma glucose levels during a 75-g oral glucose tolerance test in non-obese Japanese men.

Elevated 1-h plasma glucose (1h-PG; ≥155 mg/dL) during an oral glucose tolerance test is a risk factor for type 2 diabetes. However, the metabolic characteristics of non-obese Asians with elevated 1h-PG are unknown. Thus, we studied 59 non-obese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h-PG group (<155 mg/dL) and the High 1h-PG group (≥155 mg/dL). We compared the metabolic characteristics of the groups, including tissue-specific insulin sensitivity measured using a two-step hyperinsulinemic-euglycemic clamp. Insulinogenic index and adiponectin levels were significantly lower in the High 1h-PG group than in the Low 1h-PG group. Other characteristics, including insulin sensitivity, adiposity and ectopic fat accumulation, were similar between the groups. In conclusion, non-obese Japanese men with high 1h-PG have impaired early-phase insulin secretion and lower adiponectin levels. Insulin resistance and abnormal fat distribution were not evident in this population.

Both higher fitness level and higher current physical activity level may be required for intramyocellular lipid accumulation in non-athlete men.

Accumulation of intramyocellular lipid (IMCL) is observed in individuals with insulin resistance as well as insulin-sensitive endurance athletes with high peak oxygen consumption (VO2peak), which is called the athlete's paradox. It remains unclear whether non-athletes with higher fitness levels have IMCL accumulation and higher insulin sensitivity in general. In this study, we investigated the association between IMCL accumulation and muscle insulin sensitivity (M-IS) in subjects with high or low VO2peak. We studied 61 nonobese (BMI, 23 to 25 kg/m2), non-athlete Japanese men. We divided the subjects into four groups based on the median value of VO2peak and IMCL in the soleus muscle. We evaluated M-IS using a two-step hyperinsulinemic-euglycemic clamp. Among subjects with higher VO2peak (n = 32), half of those (n = 16) had lower IMCL levels. Both High-VO2peak groups had higher M-IS than the Low-VO2peak groups. On the other hand, M-IS was comparable between the High-VO2peak/High-IMCL and High-VO2peak/Low-IMCL groups, whereas the High-VO2peak/High-IMCL group had IMCL levels that were twice as high as those in the High-VO2peak/Low-IMCL group. On the other hand, the High-VO2peak/High-IMCL group had significantly higher physical activity levels (approximately 1.8-fold) than the other three groups. In conclusion, in nonobese, non-athlete Japanese men, subjects with higher VO2peak and higher IMCL had higher physical activity levels. IMCL accumulation is not associated with insulin resistance in individuals with higher or lower fitness levels.

Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study.

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369.

Simple and non-invasive assessment of the accommodation reflex of the proximal stomach.

BACKGROUND: Impaired gastric accommodation of the proximal stomach is one of the major pathophysiological mechanisms in functional dyspepsia (FD). However, no useful method exists for the clinical evaluation of this phenomenon. AIM: The aim of the present study was to establish a simple and non-invasive method for evaluating the accommodation reflex of the proximal stomach. METHODS: Nine healthy subjects received up to 1,700 mL water (stepwise administration in 100-mL increments) using a nasogastric tube while they were in a supine position. To assess the meal-induced gastric accommodation reflex, we measured the cross-sectional area of the proximal stomach via ultrasonography (US) at 3-min intervals after administration of water. We also measured the pressure of the water column using the same tube. Then, we administrated up to 400 mL of water in 100-mL increments and measured the area of the proximal stomach in 44 FD patients with early satiation (the measurements were performed at intervals of 3-min), and we compared the results with those for 44 healthy subjects. RESULTS: The incremental changes in the area of the proximal stomach corresponded well with the amount of water administered. The area of the proximal stomach increased, but the antral area and the intragastric pressure remained relatively stable. After administration of more than 100 ml water, the area of the proximal stomach in healthy subjects was significantly greater than that in FD patients. CONCLUSION: US can be used to assess the isotonic expansion of the proximal stomach. We were able to distinguish FD patients with impaired accommodation reflex from healthy individuals by using this simple and easy method.

Evaluation of duodenal hypersensitivity induced by duodenal acidification using transnasal endoscopy.

BACKGROUND AND AIM: Although duodenal hypersensitivity has been suggested as one of the causes of functional dyspepsia (FD), a practical method to clarify this has not yet been established. The aim of this study was to evaluate whether patients with FD have duodenal hypersensitivity to acid, using transnasal endoscopy. METHODS: In all, 44 patients with FD and 16 healthy volunteers were enrolled, and all the subjects received transnasal endoscopy in the morning after overnight fasting. After ordinary transnasal endoscopy, an infusion tube was introduced into the duodenal bulb by transnasal endoscopy and acid (20 mL, 0.1 N HCl, 20 mL/min, 36.5 degrees C) was injected via the infusion tube. The severity of 12 symptoms was assessed by each subject using a 100-mm visual analogue scale. The maximum severity scale was defined as the maximum score of the symptom severity scale. The total score was defined as the aggregate score of the maximum severity scale of the 12 symptoms. The maximum severity scales and the total scores between patients with FD and healthy volunteers were evaluated. RESULTS: The maximum severity scales of nine symptoms increased significantly more after acid infusion in patients with FD than in healthy volunteers (P < 0.05). There were significant differences in the total scores (patients with FD vs healthy volunteers 233.8 +/- 37.8 vs 63.9 +/- 14.6, mean +/- standard error of the mean, P < 0.001). CONCLUSIONS: Duodenal acidification using transnasal endoscopy enabled the evaluation of duodenal hypersensitivity to acid in healthy volunteers and patients with FD.

Duodenal hypersensitivity to acid in patients with functional dyspepsia-pathogenesis and evaluation.

Functional dyspepsia (FD) is a subcategory of the functional gastrointestinal disorders according to the Rome III classification of functional gastroduodenal disorders. FD is characterized by the presence of symptoms that are believed to be associated with gastroduodenal lesions, particularly epigastric pain or burning, postprandial fullness, or early satiation, without the evidence of organic disease likely to explain the onset of these symptoms. Generally, multiple factors are considered to be involved in the onset of dyspeptic symptoms in patients with FD. Among these factors, acid is thought to be more important because proton pump inhibitors (PPIs) and histamine 2 (H2)-receptor antagonists have been proposed to be effective therapies for a subset of patients with FD. Although manometric methods, scintigraphic methods, electrogastrography and ultrasonography have been used to evaluate enterokinesis, a practical method for evaluating duodenal hypersensitivity to acid has not been reported. Recently, we attempted to evaluate duodenal hypersensitivity to acid and gastric motility by duodenal acidification using transnasal endoscopy. Using this method, we could simultaneously evaluate both dyspeptic symptoms and gastric motility in healthy volunteers. Furthermore, we evaluated duodenal hypersensitivity to acid in healthy volunteers and in patients with FD, and we reported that duodenal acidification induced dyspeptic symptoms more significantly in patients with FD than in healthy volunteers.

Effect of irsogladine maleate on NSAID-induced reduction of gastric mucosal blood flow in anesthetized dogs.

BACKGROUND AND AIM: Although mucoprotective agents are commonly used against gastric and duodenal lesions in Japan, their availability as agents for non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal damage has not been clarified. To investigate the effect of irsogladine maleate (IM) on gastric mucosal blood flow (GMBF) reduction induced by diclofenac sodium, a NSAID commonly used in Japan, by laser Doppler flowmetry (LDF) and ultrasonography (US) in canine stomach. METHODS: GMBF was measured by LDF and contrast-enhanced US in 15 beagles. US was performed employing real-time harmonic imaging under low acoustic power after intravenous contrast injection using Definity (60 mg/kg). 60 min after insertion of a diclofenac sodium suppository (1.0 mg/kg) into the rectum, LDF and contrast-enhanced US were repeated. The examination was done in a crossover, single-blinded fashion. RESULTS: The mean extent of the change in GMBF in the IM group and in the placebo group was +29.3 and -38%, respectively. CONCLUSIONS: IM alleviates the reduction of GMBF induced by diclofenac sodium.

Real-time evaluation of dyspeptic symptoms and gastric motility induced by duodenal acidification using noninvasive transnasal endoscopy.

BACKGROUND: Although different pathophysiological mechanisms have been suggested to be involved in functional dyspepsia, a practical method to clarify them has not been established. The aim of this study was to evaluate dyspeptic symptoms and gastric motility induced by duodenal acidification using transnasal endoscopy. METHODS: Fourteen healthy volunteers (mean age, 32 years) were enrolled. Transnasal endoscopy was performed on all fasting volunteers. Dyspeptic symptoms and antral contractions were evaluated before and after duodenal infusions of pure water (20 ml/min for 5 min) and acid (0.1 N HCl, 20 ml/min for 5 min). The severity of various symptoms was assessed by each subject using a 10-cm visual analog scale every 2 min. The maximum severity scale was calculated as the mean of the individual maximum values. The motility number was defined as the mean number of antral contractions in 1 min. RESULTS: The maximum severity score for a heavy feeling in the stomach and other symptoms significantly increased after the acid infusion compared with after the pure water infusion. During pure water infusion, there were no changes in the motility number. On the other hand, the motility number significantly decreased after duodenal acidification (before vs. after, 2.93 +/- 0.12 times vs. 1.11 +/- 0.23 times, P < 0.0001). CONCLUSIONS: Duodenal acid exposure induces dyspeptic symptoms and inhibits antral motility. Transnasal endoscopy enabled us to evaluate both dyspeptic symptoms and gastric motility simultaneously.

Real-time assessment of gastroduodenal motility by ultrasonography.

Functional dyspepsia (FD) is a clinical syndrome involving upper abdominal symptoms, the causes of which cannot be identified by conventional diagnostic evaluation. Many pathophysiological factors, such as gastric acid, gastroduodenal motility, gastric accommodation, sensory disturbance, stress and Helicobacter pylori infection, may play a role in the pathogenesis of FD. Dysmotility of the upper gastrointestinal tract has been implicated in the symptoms of FD. In previous studies, antral hypomotility and delayed gastric emptying have been reported as major pathogenetic factors in patients with FD. Although a number of methods have been applied to evaluate gastroduodenal motility in humans, many of them have technical limitations and are too expensive or complex to use in daily clinical practice. Recent technical developments enable one to evaluate gastroduodenal motility by using ultrasonography. Ultrasonography is a simple, noninvasive modality for the assessment of gastric emptying and antral motility in either a liquid or solid meal, along with the examination of duodenogastric reflux.

Stepped assessment of gastric emptying of a solid meal using the (13)C-octanoic acid breath test.

The (13)C-octanoic acid breath test is widely used for evaluating gastric emptying of solids. Since the results of this test are influenced by multiple factors such as the time required to grind the solid meal into smaller particles, the gastroduodenal transport time of the ground meal, and the time required for bowel drug absorption and drug dispersion, the administration of a test meal by the oral route alone cannot result in an accurate measurement of the complicated process of emptying the stomach of solids. The aim of the present study was to evaluate each phase of gastric emptying of solids by varying the administration route of the test meal. Six healthy male volunteers (mean age: 33.2 yr) participated in the study. The test meal consisted of a bowl of rice topped with a mixture of boiled chicken and eggs admixed with 100 mg of (13)C-octanoic acid (total: 273 kcal). All subjects were given the test meal by each of the following three methods: 1. Normal oral intake of the test meal, 2. Feeding of the ground test meal through a nasogastric tube, 3. Feeding of the ground test meal through a duodenal tube. For each set of examinations, the mean residence time (MRT), half-emptying time (T(1/2)), gastric emptying coefficient (GEC), lag phase (L-breath), and measured maximum (13)C excretion time (Tmax-measured) were calculated. The data was analyzed to determine the time for each phase of gastric emptying as follows: mean grinding time (MGT) = MRT(oral) - MRT(nasogastric), mean gastroduodenal transport time (MGDTT) = MRT(nasogastric) - MRT (nasoduodenal). Data was expressed as the mean +/- SE. The values of the parameters of MGT were 0.82 +/- 0.50 hr (MRT), 0.64 +/- 0.18 hr (T(1/2)), 0.51 +/- 0.24 hr (L-breath), -0.45 +/- 0.30 hr (GEC), and 49.2 +/- 8.0 min (Tmax-measured). The values of the parameters of MGDTT were 0.87 +/- 0.38 hr (MRT), 0.26 +/- 0.29 hr (T(1/2)), 0.92 +/- 0.36 hr (L-breath), 0.55 +/- 0.23 hr (GEC), and 63.33 +/- 8.16 min (Tmax-measured). The times required for the drug absorption and disposition were 1.60 0.20 hr (MRT), 1.03 +/- 0.24 hr (T(1/2)), 0.10 +/- 0.08 hr (L-breath), 3.72 +/- 0.46 hr (GEC), and 19.67 +/- 2.11 min (Tmax-measured). By varying the administration route of a test meal containing (13)C-octanoic acid, we may be able to assess each phase of the emptying of gastric solids in detail, thus leading to a better understanding of gastroduodenal motility.