Glucose Effectiveness Decreases in Relationship to a Subtle Worsening of Metabolic Parameters in Young Japanese with Normal Glucose Tolerance.

Background: The aim of the study was to investigate the relationship between glucose effectiveness (Sg) and some metabolic parameters in male and female young Japanese. Methods: We measured plasma glucose and immunoreactive insulin levels in 1309 young Japanese persons (age <40 years) with normal glucose tolerance (NGT) before and at 30, 60, and 120 min during a 75 gram oral glucose tolerance test. We also measured serum adiponectin and high-sensitivity C-reactive protein (hsCRP) levels and oral glucose effectiveness (SgIO), and investigated factors related to SgIO. Results: The results of Spearman correlation analysis revealed that high-density lipoprotein cholesterol (HDL) and adiponectin were positively correlated with SgIO, whereas the proportion of males, body mass index, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure, triglycerides (TG), and hsCRP were inversely correlated with SgIO. The results of multiple regression analysis indicated negative correlations between SgIO and the proportion of males, WC, and SBP and a positive correlation with HDL. The results of multiple regression analysis excluding WC indicated negative correlations between SgIO and the proportion of males, SBP, and TG and positive correlations with HDL and adiponectin. Conclusions: Sg decreased with a subtle worsening of metabolic parameters, even in young persons with NGT. Decreased Sg may be involved in the development of glucose intolerance in individuals with worse metabolic parameters.

Analysis of the Relationships between Multiple Endocrine Hormones and Return of Spontaneous Circulation (ROSC) in Cardiac Arrest Patients: Possible Association of the Serum Free T4 Level with ROSC.

BACKGROUND: Endocrine hormones are closely associated with homeostasis, so it is important to clarify hormone secretion dynamics in shock. Few reports, however, have examined the dynamics of endogenous hormone secretion relative to prognosis in cardiac arrest patients. Therefore, to clarify the roles of endocrine hormones in out-of-hospital cardiac arrest (OHCA) patients, the concentrations of anterior pituitary, thyroid, and adrenocortical hormones were measured, and their associations with return of spontaneous circulation (ROSC) were examined. METHODS: The subjects were OHCA patients transported to our Emergency Department. In addition to conventional clinical laboratory tests, the following were measured: serum TSH, serum free T3, serum free T4 (F-T4), plasma ACTH, serum cortisol, serum GH, serum IGF-1, plasma aldosterone concentration (PAC), and plasma renin activity. The primary endpoint was the presence or absence of ROSC, and the secondary endpoint was 24-hour survival. RESULTS: A total of 29 patients, 17 in the ROSC group and 12 in the non-ROSC group, were studied. There were associations between ROSC and low serum potassium, high F-T4, low cortisol, and low PAC on bivariate analyses. There were associations between ROSC and serum potassium, F-T4, and GH using the step-wise method. On multiple logistic regression analysis, a relationship between ROSC and high serum F-T4 level was identified by both methods. There were also associations between 24-hour survival and both low serum potassium and elevated blood glucose levels. CONCLUSIONS: The present findings suggest a possible relationship between the serum F-T4 level and ROSC in OHCA patients. A higher serum F-T4 level might cause an increase in the ß-adrenergic response in cardiomyocytes and increased responsiveness to catecholamines and was possibly associated with ROSC.

Insulin and Proinsulin Dynamics Progressively Deteriorate From Within the Normal Range Toward Impaired Glucose Tolerance.

CONTEXT: Slight elevations in plasma glucose (PG) manifest in advance of diabetes onset, but abnormalities in immunoreactive insulin (IRI), proinsulin (Pro), and adiponectin dynamics during this stage remain poorly understood. OBJECTIVE: The objective of this work is to investigate whether IRI and Pro dynamics become abnormal as glucose tolerance deteriorates from within the normal range toward impaired glucose tolerance (IGT), as well as the relationship between PG, and these dynamics and serum adiponectin levels. DESIGN: A cross-sectional study was designed. SETTING: This study took place at Jichi Medical University in Japan. PARTICIPANTS AND MEASUREMENTS: PG, IRI, and Pro levels were determined in 1311 young Japanese individuals (age < 40 years) with normal or IGT before and at 30, 60, and 120 minutes during a 75-g oral glucose tolerance test. Participants were assigned to 4 groups according to glucose tolerance, and then background factors, adiponectin levels, insulin sensitivity (SI), and insulin secretion (ß) indexes were determined. RESULTS: PG levels as well as IRI and Pro levels 60 and 120 minutes after glucose-loading increased incrementally with deteriorating glucose tolerance. All measures of ß and the SI measure index of insulin sensitivity (ISI)-Matsuda decreased incrementally. Serum adiponectin levels were not significantly different among the glucose tolerance groups, but were independently and negatively correlated with fasting glucose. CONCLUSIONS: Early ß decreased and postloading Pro levels became excessive in a progressive manner as glucose tolerance deteriorated from within the normal range toward IGT.

Factors involved in body weight loss and its maintenance in morbidly obese inpatients.

BACKGROUND: Body weight loss in patients with obesity improves abnormal glucose tolerance, dyslipidemia and hypertension; however, it is difficult to maintain this loss of body weight. The objective of this study was to examine factors involved in body weight loss and its maintenance in morbidly obese inpatients. METHOD: The subjects were 31 patients (11 males and 20 females) who were admitted to hospital for obesity management. Factors involved in body weight changes during hospitalization and after discharge were examined retrospectively. The mean age was 58.1 ± 13.6 years and body mass index (BMI) was 40.2 ± 10.2 kg/m2. Twenty-four patients were complicated with type 2 diabetes mellitus. Diet therapy was 23.8 ± 3.9 kcal/kg ideal body weight/day. RESULTS: Excess weight loss (EWL) during hospitalization varied from 4.2 to 61.7%. Since EWL was affected by duration of hospital stay, the subjects were divided by the median of EWL per day. The subjects with greater EWL per day had lower body weight, BMI and fat mass on admission in the entire (n = 31), diabetic (n = 24), and non-diabetic subjects (n = 7), respectively. EWL per day was not different between diabetic and non-diabetic subjects. Follow-up data revealed that BMI remained unchanged 3 months after discharge but modestly increased 1 year after discharge, irrespective of EWL per day during hospitalization. In diabetic subjects followed up 1 year after discharge (n = 15), the increase in body weight was smaller than that in non-diabetic subjects (n = 3). CONCLUSION: These results suggest that EWL in morbidly obese inpatients is greater than those with lower baseline BMI and fat mass. The presence of diabetes had no effects on EWL during hospitalization. EWL during hospitalization was not correlated with its maintenance after discharge. Diabetic patients displayed lesser degree of body weight gain after discharge, possibly due to the effects of anti-diabetic medications.

Association of ghrelin dynamics with beta cell function in Japanese subjects with normal glucose tolerance.

BACKGROUND: Ghrelin is involved in feeding regulation and energy metabolism and is also known to inhibit insulin secretion (ß). However, few clinical studies have demonstrated the relationship between ß and ghrelin dynamics. This study tested the hypothesis that, in oral glucose tolerance tests (OGTT), ghrelin dynamics are associated with ß. METHODS: Subjects were 1145 healthy individuals <40 years old who tested normal on the 75-g OGTT. The following indicators and the ghrelin suppression ratio (GSR) during OGTT were calculated: insulin sensitivity (SI) [1/homoeostasis model assessment of insulin resistance, insulin sensitivity index-Matsuda and 1/fasting insulin (1/FIRI)]; and ß [Stumvoll first-phase index (Stumvoll-1), Stumvoll second-phase index and insulinogenic index]. From nine combinations of SI and ß, combinations that produce hyperbolic relationships were identified. RESULTS: Stumvoll-1 and 1/FIRI showed a hyperbolic relationship in nonobese subjects, and the product of Stumvoll-1 and 1/FIRI was used as the disposition index (DI). When analyzed by BMI quartiles, post-loading glucose and insulin levels at each time point increased from Q1 (low BMI) through Q4 (high BMI), whereas the DI, ghrelin levels at each time point, and GSR decreased from Q1 to Q4. On multivariate and bivariate analysis, GSR and DI were positive and independent, and fasting ghrelin and FIRI were negatively and independently correlated. CONCLUSIONS: Ghrelin dynamics were associated with beta cell function in subjects with normal glucose tolerance. Glucose intolerance in obesity may be due not only to insulin resistance but also to impaired beta cell function associated with abnormalities of ghrelin dynamics.

Continuous Hemodiafiltration for Pheochromocytoma Crisis with a Positive Outcome.

A 38-year-old woman who consulted a local doctor with chief complaints of sudden palpitations, headaches, and chest pain is herein presented. After admission, pheochromocytoma crisis was suspected. Since the patient had a history of acute heart failure and had once survived an episode of cardiac arrest, a rapid decrease in the catecholamine levels was needed. After resuscitation, pharmacological therapy with agents such as phentolamine and landiolol was administered, and continuous hemodiafiltration (CHDF) was performed to reduce the catecholamine levels. Elective surgery was then performed, and a positive outcome was achieved. This case suggests that the preoperative use of CHDF to control pheochromocytoma crisis may therefore be effective.

A case of pheochromocytoma with a marked decrease in catecholamine levels after rupture in which a good outcome was achieved by elective surgery.

Changes in imaging findings and hormone levels before and after pheochromocytoma rupture, as well as detailed histopathology of resected tumors, have rarely been reported. A 52-year-old woman developed hypertension and diabetes mellitus in 2014, but despite treatment with antihypertensive and hypoglycemic drugs, good control was not achieved. On April 2, 2016, the patient started to have headaches and palpitations, and on April 6, she visited our hospital. Plain computed tomography (CT) of the abdomen showed a 4-cm, isodense mass in the left adrenal gland, and the patient was hospitalized for further examination. Because the patient had hypertension, tachycardia, and hyperglycemia on admission, therapies for those were started. Catecholamine levels were markedly elevated. However, after the patient developed left flank pain on Day 4, antihypertensive and insulin therapies were no longer required. Plain CT then showed heterogeneous high density areas in the left adrenal mass. On Day 7, 3 meta-iodobenzylguanidine scintigraphy showed no abnormal uptake. On Day 8, contrast CT showed low density areas within the left adrenal tumor and contrast enhancement of the tumor margins, and catecholamine levels were markedly decreased. Elective left adrenal tumor resection was performed on Day 49. The capsule of the resected tumor was ruptured. Histopathology showed widespread hemorrhagic necrosis and viable cell components in the tumor margins. Positive chromogranin A staining of the tumor cells confirmed a diagnosis of pheochromocytoma. This patient displayed remarkable changes in imaging findings and hormone levels before and after pheochromocytoma rupture. Pheochromocytoma rupture and hemorrhagic necrosis were confirmed histopathologically.

Efficacy of Adalimumab in a Girl with Refractory Intestinal Behcet's Disease.

We describe our experience with a juvenile patient who had refractory intestinal Behcet's disease that responded to adalimumab, a fully humanized antibody against soluble TNF-α and its receptor. The patient, a 13-year-old girl, presented with oral aphthous ulcers, vulvar pain, and rashes on the lower extremities. She gradually developed a low-grade fever, abdominal pain, diarrhea, and hematochezia. Lower gastrointestinal endoscopy revealed ulcers in the terminal ileum, consistent with intestinal Behcet's disease. Methylprednisolone pulse therapy was initiated, after which the symptoms transiently improved, but, during the corticosteroid taper, the abdominal pain recurred. The symptoms resolved soon after the administration of adalimumab. Of importance, the dose of corticosteroids was successfully reduced without exacerbation during 8 months of observation. This is the first reported case in which adalimumab was used for pediatric gastrointestinal Behcet's disease. Adalimumab is a good choice for intestinal Behcet's disease refractory to conventional treatment.