Tomomi Shiiya

Fasting plasma ghrelin levels in subtypes of anorexia nervosa.

Ghrelin has a role in regulating eating behavior and energy metabolism in the central nervous system, and has been reported to play an important role in the pathophysiology of anorexia nervosa (AN). The aim of the present study was to compare fasting plasma ghrelin levels in different subtypes of untreated AN patients. The subjects included 39 female AN patients and 11 female controls. The patients were then divided into two subtypes as follows: 19 AN patients with restricting (AN-R) and 20 AN patients with binge-eating/purging (AN-BP) form of the illness. Blood samples from subjects after an overnight fast were used to analyze plasma ghrelin concentrations. Plasma ghrelin concentrations in both AN-R and AN-BP were negatively correlated with body mass index (BMI). The mean plasma ghrelin levels in both AN-R and AN-BP were significantly higher than that in controls. The mean ghrelin level in AN-BP was significantly higher than that in AN-R. However, mean BMI and serum potassium in both groups were not significantly different. These results suggest that both BMI and the presence of binge-eating/purging may have some influence on fasting plasma ghrelin levels in patients with AN.

Habitual binge/purge behavior influences circulating ghrelin levels in eating disorders

Previous studies have reported that fasting plasma ghrelin concentrations play an important role in the pathophysiology of eating disorders. The purpose of this study was to examine the relationship between plasma ghrelin levels and frequency of abnormal eating behaviors, nutritional parameters in eating disorders. Fasting blood samples were obtained in 40 female anorexia nervosa (AN) patients, 21 restricting type (AN-R) and 19 binge-eating/purging type (AN-BP), in 31 bulimia nervosa (BN) patients, 18 purging type (BN-P) and 13 non-purging type (BN-NP), in 15 female healthy volunteers (control) before the initiation of active treatment. The fasting plasma ghrelin concentrations in all subjects were negatively correlated with nutritional parameters such as body mass index, percent body fat and serum cholinesterase concentration. The mean plasma ghrelin level in BN-P was higher than that in both BN-NP and controls despite similar nutritional parameters. The plasma ghrelin levels in both AN-R and AN-BP did not differ from BN-P despite difference of nutritional parameters. For both AN-BP and BN-P patients with habitual binge/purge behavior, there were significant correlations among plasma ghrelin values, frequencies of binge/purge cycles and serum amylase values. In BN-NP, there were no significant correlations among plasma ghrelin values, frequencies of binge-eating episodes and serum amylase values. These results suggest that habitual binge/purge behavior may have some influence on circulating plasma ghrelin levels in both BN-P and AN-BP. Habitual binge/purge cycles with vomiting as opposed to binge-eating episodes without vomiting may have a greater influence on fasting plasma ghrelin concentration in eating disorders.

Changes in plasma ghrelin levels, gastric ghrelin production, and body weight after Helicobacter pylori cure

BackgroundGhrelin is a body weight-regulating peptide produced and secreted primarily by the gastric mucosa. Helicobacter pylori infection impairs gastric ghrelin production, leading to a lower plasma ghrelin concentration. However, the effect of H. pylori eradication on plasma ghrelin levels and its relation to body weight change after H. pylori cure are still uncertain. We examined the association of plasma ghrelin levels with gastric ghrelin production and body weight change before and after H. pylori eradication.MethodsPlasma ghrelin concentrations, gastric ghrelin expression, and body weight were determined in a total of 134 consecutive individuals before and 12 weeks after successful H. pylori eradication. Gastric ghrelin expression was evaluated by determining mRNA expression levels and the number of ghrelin-producing cells in gastric mucosa biopsy specimens by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively.ResultsPlasma ghrelin concentration increased in 50 patients and decreased in 84 patients after H. pylori eradication. After H. pylori cure, however, gastric preproghrelin mRNA expression was increased nearly fourfold (P < 0.0001), and the number of ghrelin-positive cells was increased or unchanged. In contrast, plasma ghrelin changes after H. pylori cure were inversely correlated with both body weight change (P < 0.0001) and initial plasma ghrelin levels (P < 0.0001).ConclusionsChanges in plasma ghrelin concentrations before and after H. pylori cure were inversely correlated with body weight change and initial plasma ghrelin levels but not with gastric ghrelin production in Japanese patients.

Translational research of ghrelin

Gastrointestinal peptides play important roles regulating feeding and energy homeostasis. Most gastrointestinal peptides including glucagon like peptide‐1, peptide YY, amylin, and oxytomodulin are anorectic, and only ghrelin is an orexigenic peptide. Ghrelin increases appetite, modulates energy balance, suppresses inflammation, and enhances growth hormone secretion. Given its diversity of functions, ghrelin is expected be an effective therapy for lean patients with cachexia caused by chronic heart failure, chronic respiratory disease, anorexia nervosa, functional dyspepsia, and cancer. Clinical trials have demonstrated that ghrelin effectively increases lean body mass and activity in cachectic patients. Ghrelin interrupts the vicious cycle of the cachectic paradigm through its orexigenic, anabolic, and anti‐inflammatory effects, and ghrelin administration may improve the quality of life of cachectic patients. We discuss the significant roles of ghrelin in the pathophysiology of cachectic diseases and the possible clinical applications of ghrelin.

Exploratory Trial of Intranasal Administration of Glucagon-like Peptide-1 in Japanese Patients With Type 2 Diabetes

OBJECTIVE This study aimed to assess the efficacy and safety of our newly developed nasal glucagon-like peptide-1 (GLP-1) compound and injector. RESEARCH DESIGN AND METHODS Twenty-six patients with type 2 diabetes were enrolled in this double-blind placebo-controlled study. The nasal compound containing 1.2 mg of human GLP-1 (7–36) amide or placebo was administered immediately before every meal for 2 weeks. RESULTS The plasma peak concentration of active GLP-1 was 47.2 pmol/L, and its Tmax was 8.1 min. The early phase of insulin and glucagon secretion were recovered and suppressed, respectively, in the GLP-1 group. Glycoalbumin levels became significantly lower and 1,5-anhydroglucitol levels significantly higher after GLP-1 administration. No marked adverse events were observed after using nasal GLP-1. CONCLUSIONS The newly developed nasal GLP-1 compound may be a potential treatment for type 2 diabetes. The long-term application of the drug should be evaluated in future trials.

Fenofibrate ameliorates insulin resistance, hypertension and novel oxidative stress markers in patients with metabolic syndrome.

SUMMARY OBJECTIVE The benefits of fenofibrate, a peroxisome proliferator-activated receptor α agonist, against cardiovascular risk factors have been established. To clarify the underlying mechanisms of these benefits, we examined the effects of fenofibrate on insulin resistance, hypertension, inflammation, oxidative stress and coagulation markers in patients with metabolic syndrome. METHODS Eleven Japanese patients with metabolic syndrome underwent physical examinations and blood tests before and after treatment with fenofibrate 200 mg daily for 8 weeks. RESULTS Fenofibrate significantly decreased systolic blood pressure, pulse wave velocity, serum insulin, insulin resistance (calculated from the homeostasis model assessment), total cholesterol, triglyceride, remnant-like particles cholesterol, uric acid, D-dimer, fibrinogen, serum amyloid A/low-density lipoprotein (LDL) and apoA1/LDL levels. It also significantly increased levels of high molecular weight adiponectin, thrombomodulin and high-density lipoprotein cholesterol in these patients. Plasminogen activator inhibitor-1, C-reactive protein, fasting plasma glucose and thrombin-antithrombin complex levels did not change. LIMITATION Small sample size. CONCLUSION Short-term fenofibrate administration not only improved lipid profiles, but also ameliorated insulin resistance, hypertension and oxidative stress markers in patients with metabolic syndrome, suggesting that fenofibrate can decrease the risk of arteriosclerosis through various pathways.

Clinical application of ghrelin for diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, and its progression significantly worsens the patients quality of life. Although several drugs are available for DPN, all of these provide only symptomatic relief. We investigated the therapeutic effects of ghrelin for DPN, based on its various physiological functions. Seven patients with type 2 diabetes with typical clinical signs and symptoms of DPN were hospitalized. Synthetic human ghrelin (1.0 μg/kg) was administered intravenously for 14 days. Motor nerve conduction velocity (MCV) of the posterior tibial nerve improved significantly after the treatment, compared to that at baseline (35.1 ± 1.8 to 38.6 ± 1.8 m/s, p < 0.0001), while the MCV in six untreated patients did not change throughout hospitalization. The subjective symptoms assessed based on the total symptom score also significantly improved (15.6 ± 3.1 to 11.1 ± 2.2, p = 0.047). Although sensory nerve conduction velocity (SCV) of the sural nerve could not be detected in three patients at baseline, it was detected in two of the three patients after 14 days of ghrelin administration. Overall, SCV did not change significantly. Plasma glucose, but not serum C peptide, levels during a liquid meal tolerance test significantly improved after treatment. These results suggest that ghrelin may be a novel therapeutic option for DPN; however, a double-blind, placebo-controlled trial is needed in the future.