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.

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.

Substituent dependence on the spin crossover behaviour of mononuclear Fe(ii) complexes with asymmetric tridentate ligands.

Three mononuclear iron(ii) complexes of the formula [FeII(H2L1-3)2](BF4)2·x(solv.) (H2L1-3 = 2-[5-(R-phenyl)-1H-pyrazole-3-yl] 6-benzimidazole pyridine; H2L1: R = 4-methylphenyl, H2L2, R = 2,4,6-trimethylphenyl, H2L3, R = 2,3,4,5,6-pentamethylphenyl) (1, H2L1; 2, H2L2; 3, H2L3) with asymmetric tridentate ligands (H2L1-3) were synthesized and their structures and magnetic behaviour investigated. Significant structural distortions of the dihedral angles between phenyl and pyrazole groups were observed and found to depend on the nature of the substituent groups. Cryomagnetic studies reveal that 1 and 2 show gradual spin crossover behavior, while 3 remains in the high spin state between 1.8 and 300 K.

A Brønsted-Ligand-Based Iron Complex as a Molecular Switch with Five Accessible States.

A mononuclear FeII complex, prepared with a Brønsted diacid ligand, H2 L (H2 L=2-[5-phenyl-1H-pyrazole-3-yl] 6-benzimidazole pyridine), shows switchable physical properties and was isolated in five different electronic states. The spin crossover (SCO) complex, [FeII (H2 L)2 ](BF4 )2 (1A ), exhibits abrupt spin transition at T1/2 =258 K, and treatment with base yields a deprotonated analogue [FeII (HL)2 ] (1B ), which shows gradual SCO above 350 K. A range of FeIII analogues were also characterized. [FeIII (HL)(H2 L)](BF4 )Cl (1C ) has an S=5/2 spin state, while the deprotonated complexes [FeIII (L)(HL)], (1D ), and (TEA)[FeIII (L)2 ], (1E ) exist in the low-spin S=1/2 state. The electronic properties of the five complexes were fully characterized and we demonstrate in situ switching between multiple states in both solution and the solid-state. The versatility of this simple mononuclear system illustrates how proton donor/acceptor ligands can vastly increase the range of accessible states in switchable molecular devices.

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.

Alcohol flushing is independently associated with lesser degree of carotid atherosclerosis in Japanese type 2 diabetic patients.

BACKGROUND: Type 2 diabetes mellitus is a well-known risk factor for atherosclerosis. Intima media thickness (IMT) of the carotid arteries has been widely used for assessing atherosclerotic changes representing cerebro-cardiovascular disease risk. Previous studies have associated the presence of inactive aldehyde dehydrogenase with progression of atherosclerosis and alcohol flushing. However, reports conflict on whether alcohol flushing could potentially modify the degree of atherosclerosis in type 2 diabetic patients. METHODS: We retrospectively assessed the relationships among alcohol flushing, IMT, and clinical characteristics in 123 consecutive Japanese type 2 diabetic patients. Alcohol flushing was assessed by standardized questionnaires. RESULTS: Patients with alcohol flushing had lower mean IMT [0.7 (0.65-0.80) vs. 0.8 (0.73-0.90) mm, p < 0.05], despite having higher triglycerides [132 (94-169) vs. 98 (70-139) mg/dL, p < 0.01] and lower high-density lipoprotein cholesterol [52 (44-60) vs. 59 (49-67) mg/dL, p < 0.05] concentration. Patients with alcohol flushing had lower frequency of alcohol intake (45 vs. 76%, p < 0.0001). Mean IMT was positively associated with age and low-density lipoprotein cholesterol concentration, and negatively with alcohol flushing according to stepwise multiple regression analysis. Alcohol flushing was also independently associated with mean IMT by multivariate analysis. CONCLUSIONS: These findings suggest that alcohol flushing is independently associated with lesser degree of carotid atherosclerosis in Japanese type 2 diabetic patients.

Oxalate-bridged heterometallic chains with monocationic dabco derivatives.

A series of bimetallic oxalate-bridged one-dimensional chains with monocationic dabco derivatives, ({R-dabco}[M(solv)2][Cr(ox)3]·n(solv)) (dabco = 1,4-diazabicyclo[2.2.2]octane, H2ox = oxalate; R = H, M = Co (1); R = H, M = Zn (2); R = Bu, M = Co (3); R = Bu, M = Zn (4)) were synthesized. All compounds have one-dimensional zig-zag chain structures with R-dabco cations located between chains. Cryomagnetic studies reveal that 1 and 3 showed intrachain ferromagnetic interactions between Co(ii) and Cr(iii) ions and metamagnetic behaviour due to interchain antiferromagnetic interactions. Permittivity measurements on compound 4 indicate specific paraelectronic relaxation behaviour originating from the rotational motion of the dabco alkyl substituent.

A case of painless thyroiditis in a very early stage of pregnancy.

We report a case of painless thyroiditis detected during the first trimester of pregnancy. A 29-year-old Japanese woman was hospitalized because of thyrotoxicosis and she was confirmed to be pregnant. The gestational age was 4 weeks. Blood examinations revealed negative TSH receptor antibodies, however, we started potassium iodide because we were unable to rule out Graves' disease. Thyroid hormone levels were normalized in 3 weeks and remained low even after discontinuation of medication. She received replacement therapy with levothyroxine sodium hydrate till 3 months after delivery. Painless thyroiditis can be one of the differential diagnoses of thyrotoxicosis in a very early stage of pregnancy.

Effects of pioglitazone on increases in visceral fat accumulation and oxidative stress in spontaneously hypertensive hyperlipidemic rats fed a high-fat diet and sucrose solution.

We examined oxidative stress and metabolic characteristics of the spontaneously hypertensive hyperlipidemic rat (SHHR) when it was fed a high-fat diet and sucrose solution (HFDS) after N(G)-nitro-L-arginine methyl ester ingestion to develop a rat model of metabolic syndrome. This study was carried out to assess the effects of pioglitazone on levels of lipid peroxide (LPO), Cu,Zn superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), and non-esterified fatty acids (NEFA) in the plasma and liver tissue in HFDS-SHHR compared with Sprague-Dawley rats (SD). In the HFDS-treated groups, levels of LPO, CAT, GPx, and NEFA were elevated and levels of Cu,Zn-SOD were reduced in the plasma and liver tissue, with a marked accumulation of visceral fat. The changes induced by HFDS feeding were severe in the SHHR model that had essential hypertension and hyperlipidemia, when compared with SD that did not have these essential risk factors. Subcutaneous injection of 10 mg/kg per day of pioglitazone for 2 months significantly restored levels of LPO, CAT, GPx, Cu,Zn-SOD, and NEFA in the HFDS-SHHR group, and visceral fat accumulation was reduced. These results suggest that HFDS-SHHR is a suitable model of metabolic syndrome and that pioglitazone treatment can improve oxidative dysregulation in this rat model.