Smoking and prevalence of nocturia in Japanese patients with type 2 diabetes mellitus: a post-hoc analysis of The Dogo Study.

AIMS: No evidence exists regarding the association between smoking status and nocturia among patients with type 2 diabetes mellitus. We evaluated this association among Japanese patients with type 2 diabetes mellitus by post-hoc analysis. METHODS: Study subjects were 817 Japanese patients with type 2 diabetes mellitus. Study subjects were considered to have nocturia if they answered "once or more" to the question: "Within one week, how many times do you typically wake up to urinate from sleeping at night until waking in the morning?" We used the following three outcomes: (1) nocturia was ≥1 voids per night; (2) moderate nocturia was ≥2 voids per night; and (3) severe nocturia was ≥3 voids per night. Adjustments were made for age, sex, body mass index, hypertension, dyslipidemia, stroke, glycated hemoglobin, current drinking, use of anti-hypertensive agent, use of insulin, use of oral anti-hyperglycemic agent, and diabetic retinopathy. RESULTS: The prevalence values of one void per night, two voids per night, and three or more voids per night were 39.5%, 27.1%, and 14.8%, respectively. Current smoking was independently inversely associated with severe nocturia compared with never or former smoking; the adjusted PR was 0.47 (95%CI: 0.25-0.89). Among the 443 patients who had ever smoked, compared with former smoking, current smoking was independently inversely related to severe nocturia; the adjusted PR was 0.44 (95%CI: 0.24-0.82). CONCLUSIONS: In Japanese patients with type 2 diabetes mellitus, current smoking may be independently inversely associated with severe nocturia.

B-type natriuretic peptide and renal function in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

Among patients with type 2 diabetes mellitus, the association between B-type natriuretic peptide (BNP) and renal function remains controversial. We therefore investigated this issue among Japanese patients with type 2 diabetes mellitus. This study included 687 Japanese patients with type 2 diabetes mellitus. BNP levels were divided at quartile points on the basis of the distribution. We used four outcomes regarding the renal function: 1) chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) < 60ml/min/1.72m2, 2) advanced CKD: eGFR < 30ml/min/1.72m2, 3) microalbuminuria: urinary albumin creatinine ratio (UACR) ≥ 30 mg/g creatinine, and 4) macroalbuminuria: UACR ≥ 300 mg/g creatinine. The prevalence values of CKD, advanced CKD, microalbuminuria, and macroalbuminuria were 27.4％, 2.5%, 31.4%, and 9.3%, respectively. Highest BNP (≥ 39.2 ng/ml) was independently positively associated with microalbuminuria and macroalbuminuria (adjusted ORs, 2.61 [95% CI: 1.53-4.49] and 3.45 [95% CI: 1.46-8.72], respectively). High BNP was not associated with advanced CKD or CKD. There was a statistically significant positive exposure-response relationships between the BNP level and advanced CKD, microalbuminuria, and macroalbuminuria (p for trend = 0.047, 0.001, and 0.003, respectively). BNP level may be independently positively associated with advanced CKD, microalbuminuria, and macroalbuminuria but not CKD in Japanese patients with type 2 diabetes mellitus.

Microvascular complications and prevalence of urgency incontinence in Japanese patients with type 2 diabetes mellitus: The dogo study.

AIMS: Diabetes was significantly positively associated with urgency incontinence in several epidemiological studies. We examine the association between diabetic neuropathy, which we defined based on neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception, and urgency incontinence among Japanese patients with type 2 diabetes mellitus. METHODS: Study subjects were 742 Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate ?". Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, the absence of the Achilles reflex, and/or abnormal vibration perception. Adjustment was made for sex, age, body mass index, duration of type 2 diabetes mellitus, current smoking, hypertension, dyslipidemia, glycated hemoglobin, stroke, coronary artery disease, insulin therapy, diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. RESULTS: The prevalence of urgency incontinence was 8.6%. Diabetic neuropathy was independently positively associated with urgency incontinence: the adjusted OR was 2.20 (95%CI: 1.16-4.36). Associations between diabetic retinopathy or nephropathy and the prevalence of urgency incontinence were not significant. CONCLUSIONS: In Japanese patients with type 2 diabetes mellitus, only diabetic neuropathy was independently positively associated with urgency incontinence. Neurourol. Urodynam. 35:1024-1027, 2016. © 2015 Wiley Periodicals, Inc.

Association between subclinical hypothyroidism and diabetic nephropathy in patients with type 2 diabetes mellitus.

Subclinical hypothyroidism (SCH) has been associated with type 2 diabetes mellitus. However, it is unknown whether common complications of type 2 diabetes, such as diabetic nephropathy, are also present with SCH. Here, we investigated the association between SCH and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. In this multicenter cross-sectional study, we recruited 414 such patients who had no previous history of thyroid disease. Serum thyroid hormone levels and the urinary albumin:creatinine ratio were measured. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (>4.0 mIU/L), and diabetic nephropathy was defined as urinary albumin/creatinine ratio ≥300 mg/g. The prevalence of SCH was 8.7% (n = 36) among patients with type 2 diabetes mellitus. The SCH group had a higher prevalence of dyslipidemia (p = 0.008) and diabetic nephropathy (p = 0.014) than the euthyroid group. Multivariate analysis identified significant positive associations between diabetic nephropathy and SCH (odds ratio [OR], 3.51; 95% confidence interval [CI], 1.10-10.0; p = 0.034), hypertension (OR, 4.56; 95% CI, 1.69-14.7; p = 0.001), and smoking (OR, 3.02; 95% CI, 1.14-7.91; p = 0.026). SCH may be independently associated with diabetic nephropathy in Japanese patients with type 2 diabetes mellitus.

Interleukin-18 induces insulin resistance in the hyperthyroid state.

We previously reported that serum interleukin-18 (IL-18) levels were significantly increased in hyperthyroid Graves' disease patients. The development of insulin resistance in hyperthyroidism has been documented. We investigated the relationship between IL-18 and insulin resistance in patients with hyperthyroid Graves' disease and in experimental hyperthyroid mice. Then, we examined whether IL-18 induces insulin resistance in mice injected with IL-18 for a week. A significant positive correlation was observed between serum IL-18 levels and parameters such as thyroid functions and homeostasis model assessment for insulin resistance in hyperthyroid Graves' disease. In experimental hyperthyroid mice, IL-18 was significantly elevated. Insulin resistance increased in experimental hyperthyroid mice and IL-18-injected mice. These findings suggest IL-18 to be an important factor inducing insulin resistance in hyperthyroidism.

Suicide attempt by an overdose of sitagliptin, an oral hypoglycemic agent: a case report and a review of the literature.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of oral hypoglycemic agents for the management of diabetes that elevate the plasma concentration of active glucagon-like peptide-1 via inhibition of DPP-4. They effectively lower not only glycosylated hemoglobin levels, but also fasting and postprandial plasma glucose levels. Patients with diabetes occasionally consume an overdose of oral hypoglycemic agents in suicide attempts: the prevalence of depression is high in patients with diabetes, and depression is a strong risk factor for suicide. We encountered an 86-year-old woman with type 2 diabetes and depression, who was transferred to the emergency room 4h after ingestion of 1,700 mg of the DPP-4 inhibitor sitagliptin (1,700 mg is 17 times greater than the approved maximum dose). Upon arrival, she was fully conscious, plasma glucose was 124 mg/dL, and serum immunoreactive insulin level was 5.81 µU/mL. Thereafter, the plasma concentration of sitagliptin rose to 3,793 nM, which is 4.5 times higher than the value found under regular treatment with the maximum dose. The patient did not suffer from hypoglycemia, suggesting that a single oral overdose of sitagliptin is unlikely to cause hypoglycemia. A literature review of oral anti-diabetic agents revealed that overdose of biguanides is occasionally fatal when immediate intensive care is not provided. In summary, sitagliptin is a good treatment option for diabetic elderly patients or patients with psychiatric disorders who are suicidal and do not require insulin.

Physical activity and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

AIMS/INTRODUCTION: To date, there is no evidence regarding the association between physical activity (PA) and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. We investigated this issue among Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Study participants were 460 male Japanese patients with type 2 diabetes mellitus. The definitions of exercise habit, walking habit and fast walking were based on a self-administered questionnaire regarding PA behavior. Participants were classified into one of four PA levels based on the number of 'Yes' answers to the three questions in the questionnaire: (i) lowest; (ii) lower; (iii) moderate; and (iv) higher. Severe ED and moderate-to-severe ED were based on Sexual Health Inventory for Men score <8 and <12, respectively. RESULTS: The prevalence of moderate-to-severe ED, severe ED, exercise habit, walking habit, and fast walking was 64.6, 51.1, 36.3, 41.3 and 37.6%, respectively. Walking habit was independently inversely associated with moderate-to-severe ED and severe ED. Exercise habit was independently inversely associated with severe ED, but not moderate-to-severe ED. Higher PA was independently inversely associated with moderate-to-severe ED and severe ED (adjusted odds ratio 0.42, 95% confidence interval 0.21-0.85; and adjusted odds ratio 0.38, 95% CI: 0.19-0.73, respectively). There was a statistically significant inverse exposure-response relationship between the PA level and moderate-to-severe ED and severe ED (P for trend = 0.02 and 0.005), respectively. CONCLUSIONS: PA might be inversely associated with ED in Japanese patients with type 2 diabetes mellitus.

Nocturia and Prevalence of Depressive Symptoms in Japanese Adult Patients With Type 2 Diabetes Mellitus: The Dogo Study.

OBJECTIVES: No studies have investigated the association between nocturia and depressive symptoms in patients with type 2 diabetes mellitus. Because nocturia and depressive symptoms are common in patients with type 2 diabetes, we examined this association in Japanese patients with type 2 diabetes. METHODS: We studied 762 Japanese patients with type 2 diabetes. A self-administered questionnaire was used to collect information about the variables under study. The subjects were divided into 3 groups according to their nocturnal micturition: 1) no nocturia; 2) mild nocturia (1 void per night) and 3) moderate to severe nocturia (2 or more voids per night). Depressive symptoms were defined as being present when a subject had a Self-Rating Depression Scale score higher than 49. RESULTS: The prevalence values of mild nocturia, moderate to severe nocturia and depressive symptoms were 39.5%, 41.9% and 16.8%, respectively. Both mild nocturia and moderate to severe nocturia were independently positively associated with depressive symptoms in all patients; the adjusted ORs were 1.96 (95% CI 1.06 to 3.77) and 2.58 (95% CI 1.38 to 5.04). In female patients, both mild nocturia and moderate to severe nocturia were independently associated with depressive symptoms; the adjusted ORs were 5.26 (95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15 to 28.54), respectively. In male patients, neither mild nocturia nor moderate to severe nocturia was significantly related to depressive symptoms. CONCLUSIONS: In Japanese female patients with type 2 diabetes, nocturia may be positively associated with depressive symptoms.

Dietary intake habits and the prevalence of nocturia in Japanese patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: No reports have been published on the association between dietary intake habits and nocturia in the diabetes population. We therefore evaluated this issue among Japanese patients with diabetes mellitus. MATERIALS AND METHODS: Study participants in the present study were 785 Japanese patients with type 2 diabetes mellitus. Self-administered questionnaires were used to assess each type of dietary intake habit. Vegetable intake habit was assessed by the following question: "Do you have vegetables or seaweed every day?" We used the following two outcomes: (i) nocturia: ≥2 voids per night; and (ii) severe nocturia: ≥3 voids per night. Adjustment was made for age, sex, body mass index, glycated hemoglobin, hypertension, dyslipidemia, smoking, drinking, exercise habit, stroke, ischemic artery disease, diabetic nephropathy, diabetic neuropathy and diabetic retinopathy. RESULTS: The prevalence of nocturia, severe nocturia, and vegetable intake habit was 39.9%, 14.4% and 67.3%, respectively. After adjusting for confounding factors, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted odds ratios were 0.67 (95% confidence interval [CI] 0.48-0.94) and 0.46 (95% CI 0.30-0.71), respectively. Among male patients, vegetable intake habit was independently inversely associated with severe nocturia, but not nocturia: the adjusted OR was 0.51 (95% CI 0.29-0.88). Among female patients, vegetable intake habit was independently inversely associated with nocturia and severe nocturia: the adjusted ORs were 0.44 (95% CI 0.24-0.79) and 0.34 (95% CI 0.15-0.78), respectively. CONCLUSIONS: We found an inverse association between vegetable intake habit and nocturia in Japanese patients with type 2 diabetes mellitus.

Clinical usefulness of quantitative evaluation of visceral fat by ultrasonography.

PURPOSE: The aim of this work was to evaluate the usefulness of a proposed method for visceral fat volume assessment by ultrasonography (US) in identifying those at risk of metabolic syndrome, and also to establish the most suitable cutoff level of waist circumference for the diagnosis of visceral adiposity. METHODS: One hundred and fifty-two outpatients with metabolic diseases such as hypertension, diabetes, or dyslipidemia were studied. The total visceral fat volume (total-VFA) was measured by computed tomography (CT), the visceral fat area at the level of the umbilicus was measured by CT (CT-VFA), and the visceral fat area was also measured by US (US-VFA), as we recently proposed. RESULTS: Significant correlation coefficients were found between total-VFA and CT-VFA, US-VFA, and waist circumference in men but not in women. The correlation co-efficient between US-VFA and waist circumference was significantly positive in men and weakly positive in women. According to receiver-operator characteristic curves, the cutoff value of waist circumference yielding the maximal sensitivity plus specificity for predicting more than 100 cm(2) of US-VFA was 85 cm in men and 84 cm in women. The change in US-VFA was significantly larger than that in waist circumference after a 6-month interval. CONCLUSION: The US-measured visceral fat area is more useful than waist circumference in a clinical setting.

Self-reported sitting time and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

AIMS: No evidence exists regarding the association between sitting time and erectile dysfunction (ED) among patients with type 2 diabetes mellitus. The aim of this study was to evaluate the association between self-reported sitting time and ED among patients with type 2 diabetes mellitus. METHODS: Study subjects were 430 male Japanese patients with type 2 diabetes mellitus (mean age, 60.5years). A self-administered questionnaire was used to collect information on the variables under study. The study subjects were asked about time spent sitting during typical 24-hour periods over the past 12months. Subjects were divided into four groups according to self-reported sitting time: 1) <5hours, 2) 5-7hours, 3) 7-9hours, and 4) ≥9hours. ED was defined as present when a subject had a Sexual Health Inventory for Men score <8. Adjustment was made for age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, coronary artery disease, stroke, glycated hemoglobin, walking habit, and diabetic neuropathy. RESULTS: The prevalence values of moderate to severe ED and severe ED were 36.1% and 49.8%. At least 9hours sitting was independently positively associated with severe ED but not moderate to severe ED; the adjusted OR was 1.84 (95% CI: 1.06-3.33). In the multivariate model, there was a statistically significant inverse exposure-response relationship between the self-reported sitting time and severe ED (p for trend=0.029). CONCLUSIONS: Self-reported sitting time may be positively associated with ED in Japanese patients with type 2 diabetes mellitus.

Obesity and the prevalence of nocturia in Japanese elderly patients with type 2 diabetes mellitus: The Dogo study.

AIM: Nocturia is common among patients with type 2 diabetes mellitus, but limited evidence regarding the association between body mass index (BMI) and nocturia exists among such patients. The aim of the present study, therefore, was to evaluate the association between BMI and nocturia among Japanese patients with type 2 diabetes mellitus. METHODS: Study participants were 809 Japanese patients with type 2 diabetes mellitus. Study participants were considered to have nocturia if they answered "two or more" to the question: "How many times do you typically wake up to urinate from sleeping at night until waking in the morning?" We used the following two outcomes: (i) moderate nocturia was defined as ≥2 voids per night; and (ii) severe nocturia was defined as ≥3 voids per night. Participants were categorized into four groups according to their BMI: (i) BMI <18.5; (ii) 18.5 ≤ BMI < 25; (iii) 25 ≤ BMI < 30; and (iv) BMI ≥30. Multiple logistical regression analysis for nocturia in relation to BMI was used, with the category of 18.5 ≤ BMI < 25 as the reference. RESULTS: Obesity (BMI ≥30) was independently positively associated with severe nocturia among elderly patients (age ≥65 years) with type 2 diabetes mellitus, but not among young and middle-aged patients: the adjusted OR was 2.96 (95% CI 1.10-7.83). BMI was not associated with moderate nocturia in all patients. CONCLUSIONS: In Japanese elderly patients with type 2 diabetes mellitus, obesity was independently positively associated with severe nocturia. Geriatr Gerontol Int 2017; 17: 2460-2465.

Macrovascular Complications and Prevalence of Urgency Incontinence in Japanese Patients with Type 2 Diabetes Mellitus: The Dogo Study.

Objective Macrovascular diseases and urgency incontinence are common among Japanese patients with type 2 diabetes mellitus. However, little evidence exists regarding the association between stroke and urgency incontinence among patients with type 2 diabetes mellitus. We examined the associations between macrovascular complications and urgency incontinence among Japanese patients with type 2 diabetes mellitus. Methods The study subjects were 818 Japanese patients with type 2 diabetes mellitus. Urgency incontinence was defined as present when a subject answered "once a week or more" to the question: "Within one week, how often do you leak urine because you cannot defer the sudden desire to urinate?" We adjusted our analyses for sex, age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, glycated hemoglobin, diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy. Results The prevalence of urgency incontinence was 9.2%. Stroke was independently positively associated with urgency incontinence, with an adjusted odds ratio of 2.34 (95% confidence interval: 1.03-4.95). The associations between ischemic heart disease or peripheral artery disease and the prevalence of urgency incontinence were not significant. Conclusion In Japanese patients with type 2 diabetes mellitus, stroke, but not ischemic heart diseases or peripheral artery disease, was independently positively associated with urgency incontinence.

Alcohol consumption and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: Baseline data from the Dogo Study.

Diabetes mellitus and heavy alcohol consumption are both associated with vascular disease, a category that includes erectile dysfunction (ED). However, the association between alcohol consumption and ED among patients with type 2 diabetes mellitus remains unclear. The aim of the present multicenter cross-sectional study was to investigate the relationship between drinking frequency, weekly alcohol consumption, daily alcohol consumption, and ED among Japanese patients with type 2 diabetes mellitus. Study subjects were 340 male Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. ED was defined as present when a subject had a Sexual Health Inventory for Men score <8. Adjustment was made for age, body mass index, duration of type 2 diabetes mellitus, current smoking, hypertension, dyslipidemia, glycated hemoglobin, stroke, coronary artery disease, diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. The prevalence of ED was 43.2% (147/340). The frequency of alcohol consumption and weekly alcohol consumption were independently inversely associated with ED (p for trend p = 0.001 and 0.004, respectively). The relationship between daily alcohol consumption and ED was an inverted J-shaped curve: alcohol consumption of less than 60 g, but not 60 g or more, per day was independently related to a lower prevalence of ED (p for quadratic trend = 0.003). In Japanese men with type 2 diabetes mellitus, an inverted J-shaped relationship between daily alcohol consumption and ED was observed, while frequency of alcohol consumption and weekly alcohol consumption were significantly inversely associated with ED.

Microvascular Complications and Prevalence of Nocturia in Japanese Patients With Type 2 Diabetes Mellitus: The Dogo Study.

OBJECTIVE: To evaluate the association between microvascular complications and nocturia among Japanese patients with type 2 diabetes mellitus. METHODS: Study subjects were 731 Japanese patients with type 2 diabetes mellitus. A self-administered questionnaire was used to collect information on the variables under study. Study subjects were considered to have nocturia if they answered "once or more" to the question: "How many times do you typically wake up to urinate from sleeping at night until waking in the morning?" Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, the absence of the Achilles reflex, or abnormal vibration perception. Diabetic nephropathy was defined as positive when the estimated glomerular filtration rate was <30 mL/min/1.73 m(2) and/or the urine albumin-to-creatinine ratio was ≥34 mg/mmol creatinine. Several ophthalmology specialists were responsible for evaluating diabetic retinopathy. Adjustment was made for sex, age, body mass index, duration of diabetes mellitus, current smoking, current drinking, hypertension, stroke, ischemic heart disease, and glycated hemoglobin. RESULTS: The prevalence of nocturia was 80.4%. Diabetic retinopathy was independently positively associated with nocturia (adjusted odds ratio 2.39 [95% confidence interval: 1.08-6.11]). In contrast, diabetic nephropathy or diabetic neuropathy was not associated with nocturia. CONCLUSION: In Japanese patients with type 2 diabetes mellitus, only diabetic retinopathy was independently positively associated with nocturia.

Serum lipoprotein(a) levels and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus.

AIMS: We aimed to evaluate the association between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. METHODS: This study included 581 patients with type 2 diabetes mellitus. Serum Lp(a) levels were divided into four groups; the cut-off points were at the 30th, 60th, and 90th percentile values on the basis of the distribution for all subjects. Diabetic nephropathy was defined as present when the urinary albumin-creatinine ratio was ≥33.9mg/mmol creatinine and/or the estimated glomerular filtration rate was <30ml/min/1.72m(2). Adjustment was made for age, sex, body mass index, hemoglobin A1c, duration of diabetes mellitus, current drinking, current smoking, hypertension, dyslipidemia, coronary heart disease, and stroke. RESULTS: Higher serum Lp(a) levels were significantly associated with a higher prevalence of diabetic nephropathy: the adjusted odds ratios (95% confidence intervals) for diabetic nephropathy in relation to serum Lp(a) levels of ≤6, 7-15, 16-38, and ≥39mg/dl were 1.00 (reference), 2.74 (1.08-7.00), 3.31 (1.28-8.54), and 4.80 (1.57-14.60), respectively (P for trend=0.004). CONCLUSIONS: The results suggest that serum Lp(a) levels may be positively associated with diabetic nephropathy among Japanese patients with type 2 diabetes mellitus.

Nocturia and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

AIMS/INTRODUCTION: Several epidemiological studies have reported a positive association between nocturia and erectile dysfunction (ED). Yet only limited evidence exists regarding the association between nocturia and ED among patients with type 2 diabetes mellitus, although nocturia and ED are common among type 2 diabetes mellitus patients. MATERIAL AND METHODS: Study participants were 332 male Japanese patients with type 2 diabetes mellitus, aged 19-70 years, who had undergone blood tests at our institutions. A self-administered questionnaire was used to collect information on the variables under study. Adjustment was made for age, body mass index, hypertension, stroke, ischemic heart disease, glycated hemoglobin and diabetic neuropathy. ED, moderate to severe ED and severe ED were defined as present when a participant had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Study participants were considered to have nocturia if they answered 'once or more' to the question: 'Within 1 week, how many times do you typically wake up to urinate from sleeping at night until waking in the morning?' RESULTS: The prevalence of nocturia was 79.8%. Nocturia was independently positively associated with ED and moderate to severe ED: the adjusted odds ratios were 7.86 (95% confidence interval 2.11-33.56) and 2.17 (95% confidence interval 1.16-4.12), respectively. The positive association between nocturia and severe ED fell just short of significance. CONCLUSIONS: In Japanese men with type 2 diabetes mellitus, nocturia might be associated with ED and moderate to severe ED.

Fully automated micro- and nanoscale one- or two-dimensional high-performance liquid chromatography system for liquid chromatography-mass spectrometry compatible with non-volatile salts for ion exchange chromatography.

A one- or two-dimensional high performance liquid chromatography system for electrospray ionization mass spectrometers has been developed that is optimized for ion exchange and reversed phase separations. A unique and simple valve configuration permits the use of a variety of non-volatile salts; ammonium sulfate was used in an example of strong cation exchange separations. The system was designed and evaluated for both micro- and nanoflow chromatography. The peptide detection limit was approximately 100 fmol for micro- and 20 fmol for nanoflow, demonstrating the concentration and mass sensitivity improvements expected with nanoelectrospray ionization. The 1D/2D-HPLC MS system is fully automated for routine peptide analyses, compatible with direct injection of proteolytic digests, and exhibits chromatographic reproducibility and sensitivity. Software permits operator selection of either a 1D or 2D configuration with corresponding system parameters as required for individual samples. The hardware elements and resulting performance are described in this paper.

Drug-induced hepatitis due to repeated use of hair dye.

A 27-year-old Japanese man with no past history of liver disease was admitted to our hospital due to liver abnormalities. The patient was diagnosed with drug-induced hepatitis, as the three episodes of hepatitis occurred just after repeated use of hair dye. After cessation of the hair dye use, abnormal liver function tests improved to within the normal range. Although hair dyes contain various hepatotoxic compounds, hair dye is not known to cause drug-induced hepatitis. Thus, in cases of liver abnormality of unknown origin, the history of hair dye use should be investigated.

Critical residues in the transmembrane helical bundle domains of the human motilin receptor for erythromycin binding and activity.

The motilin receptor belongs to a family of Class I G protein-coupled receptors, and is an important endogenous regulator of gastrointestinal motor function. Motilin and erythromycin, two chemically distinct full agonists of the motilin receptor, are known to bind to distinct regions of this receptor, based on previous systematic mutagenesis of extracellular regions that dissociated the effects on these two agents. The action of these different chemical classes of agonists likely yields a common activation state of the cytosolic face of this receptor that is responsible for interaction with its G protein. In the current work, we studied the predicted transmembrane (TM) domains of this receptor for functional responses to motilin and erythromycin. Motilin receptor constructs were prepared in which each residue in the TM domains was mutated to alanine or valine. Each construct was expressed in COS cells and characterized for motilin and erythromycin binding and intracellular calcium responses stimulated by both agonists. Constructs with mutations of residues, Asp94, Leu95, Arg97 and Trp99 in TM2, Ser169 in TM4, and Tyr321 and Glu325 in TM6, were responsible for the negative impact on biological activity stimulated by erythromycin, but had no effect on motilin responses. On the other hand, constructs with mutations of residues, Leu113 in TM3, Pro172 in TM4, Trp250 and Tyr255 in TM5, and Gln334 in TM7, were negatively responsive to both erythromycin and motilin. These data support important roles of new regions in the TM domains of the motilin receptor for erythromycin action, suggesting differential mechanisms of actions by peptidyl and non-peptidyl ligands.