Long sleep duration and cardiovascular disease: Associations with arterial stiffness and blood pressure variability

Although short and long sleep duration are both risk factors of cardiovascular disease (CVD), the recent meta‐analyses have been shown that long sleep duration was closely associated with CVD mortality. While the specific mechanism underlying the association between long sleep duration and CVD remains unclear, long sleep duration was shown to be associated with arterial stiffness and blood pressure variability (BPV) in many Asian populations. This review article will focus on the pathophysiology of long sleep duration, arterial stiffness, BPV and their effects on CVD. To set the stage for this review, we first summarize the current insights for the relationship between long sleep duration and CVD in relation to arterial stiffness and BPV.     

Multiple bone fractures found in a young sarcoidosis patient with long stable disease

A 22-year-old Japanese man was found to have bilateral hilar lymphadenopathy (BHL), and was diagnosed with sarcoidosis in 1995. He was followed without treatment until 2002, when a bone fracture due to osseous sarcoidosis was found in his left thumb. Despite systemic treatment with corticosteroid and methotrexate, a new bone lesion developed in his right foot and his right middle finger was fractured. The patient also suffered multiple organ involvements including brain and muscle lesions. This is the first report of a sarcoidosis patient who presented with BHL, and developed bone fractures after a long stable period of more than 5 years.     

Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia

OBJECTIVE: Vasopressin (AVP) is reported to be an important factor for regulating cortisol secretion in patients with Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia (AIMAH). Recently, there have been several case reports of subclinical Cushing's syndrome due to AIMAH, in which the pathophysiological role of AVP has been unknown. The aim was to conduct an extensive investigation of AVP in the autonomous secretion of cortisol in subclinical Cushing's syndrome due to AIMAH. PATIENTS AND MEASUREMENTS: Five cases of AIMAH with subclinical Cushing's syndrome underwent prospective study including physical examination, imaging (MRI, CT and 131I-adosterol scintigraphy) and endocrinological evaluation that comprised basal plasma cortisol levels and urinary excretions of steroid metabolites, a dexamethasone suppression test and an AVP stimulation test. In case 1, left adrenalectomy was performed and the pathological diagnosis of AIMAH was established. An in vitro experiment using the cultured AIMAH adrenal cells was conducted to investigate cortisol secretion and expression of the V1-AVP receptor, mRNA by RT-PCR. RESULTS: All five cases were discovered incidentally to have bilateral adrenal nodules. Imaging by MRI and CT revealed large multinodular lesions in both adrenal glands, which showed positive uptake on 131I-adosterol scintigraphy. Although the basal values of plasma cortisol and urinary excretions of steroid metabolites were within normal limits, autonomous secretion of cortisol was assumed to occur because of lack of suppression during dexamethasone suppression. The five patients had no overt signs of Cushing's syndrome, and they were therefore diagnosed with subclinical Cushing's syndrome due to AIMAH. In all five patients, AVP stimulated cortisol secretion in vivo, whereas desmopressin acetate failed to affect cortisol secretion. In case 1, AVP stimulated cortisol secretion from cultured AIMAH adrenal cells, but this secretion had no relationship with cAMP production. In addition, over-expression of V1-AVP receptor mRNA in AIMAH tissue was determined by RT-PCR. CONCLUSION: Patients with subclinical Cushing's syndrome due to AIMAH commonly exhibit cortisol responsiveness to AVP, and this is probably mediated through activation of overexpressed V1-AVP receptors.     

Institutional indications for islet transplantation after total pancreatectomy

Background/Purpose

This study was designed to establish institutional indications for pancreatic islet transplantation by examining patients with total pancreatectomy as candidates for islet allotransplantation.

Methods

In 12 patients who underwent total pancreatectomy, we compared pre-and postoperative plasma glucose level, body mass index, HbA1c, and daily insulin use; we examined candidacy for islet allotransplantation based on the guidelines of Japan’s islet transplantation registry.

Results

Eight of the 12 patients with total pancreatectomy were operated for intraductal papillary mucinous neoplasm. At our institution, the 5-year survival of patients with intraductal papillary mucinous neoplasm was far better (76.3%) than that of patients with pancreatic cancer. Postoperatively, plasma glucose level, HbA1c, and daily insulin use were increased in all patients with total pancreatectomy. Of the 12 patients treated with total pancreatectomy, 4 (intraductal papillary mucinous neoplasm, n = 2; islet cell tumor, n = 1; and acute pancreatitis due to arteriovenous malformation, n = 1) showed deteriorated diabetic control and therefore were considered to be candidates for islet allotransplantation according to the guidelines.

Conclusions

Islet allotransplantation could be indicated for patients with favorable postoperative survival who have had a total pancreatectomy for either benign or neoplastic disease.     

Low serum bilirubin concentration is a novel risk factor for the development of albuminuria in patients with type 2 diabetes

Objective

Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes.

Materials and Methods

We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria.

Results

During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93).

Conclusions

Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes.     

Associations Between hOGG1 Ser326Cys Polymorphism and Increased Body Mass Index and Fasting Glucose Level in the Japanese General Population

Background

Evidence suggests that Ser326Cys, a genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1), is associated with insulin resistance and type 2 diabetes; however, the underlying mechanism is unclear. Recently, an animal study showed a significant association between the hOGG1 genotype and obesity, although evidence for such an association in humans is limited. The purpose of this study was to examine the association between the hOGG1 genotype and body mass index (BMI) and fasting blood glucose (FBG) levels.

Methods

Cross-sectional analysis was conducted using the baseline survey data from a Japan Multi-Institutional Collaborative Cohort Study, which included 1793 participants aged 40–69 years. The hOGG1 polymorphism was detected using a multiplex polymerase chain reaction-based invader assay. Multiple linear regression, analysis of covariance, and logistic regression were used to control for confounding variables.

Results

The Cys allele was significantly associated with increased BMI, FBG level, and total cholesterol (TC) level, even after adjustment for gender, age, energy intake, alcohol, smoking, physical activity, and family history of diabetes. An association with BMI was still observed after further adjustment for FBG and TC, but not for the study area (Amami or the mainland). The Cys/Cys genotype was significantly more prevalent in the participants with higher BMI (>27.5 kg/m²). However, the impact of genotype decreased and significance disappeared after adjusting for the study area.

Conclusions

The present results suggest that the study area being inside Japan confounds the association between hOGG1 genotype and obesity.Key words: human 8-oxoguanine glycosylase 1 (hOGG1), obesity, body mass index (BMI), fasting blood glucose (FBG), polymorphism, study area