Female Functional Constipation Is Associated with Overactive Bladder Symptoms and Urinary Incontinence.

This noninterventional cross-sectional study aims to assess the association between functional constipation (FC) and urinary symptoms in female patients with no treatment for urination and defecation. The Rome III criteria for evaluation of defecation, Overactive Bladder Symptom Score (OABSS) for evaluation of urinary symptoms, and clinical features were investigated in 145 female patients. Latent FC and moderate to severe overactive bladder (OAB) were defined on the basis of positivity for two or more of the Rome III criteria and an OABSS ≥ 6 with OABSS Q3 ≥ 2, respectively. In 60 latent FC patients, the OABSS was higher (5.0 versus 3.2, p = 0.001), and concurrent moderate to severe OAB symptoms and OAB with urinary incontinence were more frequent than those in 85 nonlatent FC patients (33.3 versus 10.6%, p = 0.001, and 31.7 versus 7.1%, p < 0.001). Multivariate analysis demonstrated that moderate to severe OAB symptoms were a significant associated factor of latent FC (odds ratio (OR) = 4.125, p = 0.005), while latent FC was the only associated factor of moderate to severe OAB and OAB with urinary incontinence (OR = 4.227, p = 0.005 and OR = 4.753, p = 0.004). In conclusion, moderate to severe OAB symptoms are correlated with FC. Moreover, FC is related to moderate to severe OAB symptoms and to OAB with urinary incontinence.

Diabetic Microangiopathy Is an Independent Predictor of Incident Diabetic Foot Ulcer.

AIM: To determine the diabetic foot ulcer incidence and examine its association with microangiopathy complications, including diabetic retinopathy (DR) and albuminuria (Alb), in type 2 diabetes patients. METHODS: This was a retrospective cohort study of 1,305 patients with type 2 diabetes who were assigned to the following groups: Category 1, normoalbuminuria without DR (n = 712); Category 2, Alb without DR (n = 195); Category 3, normoalbuminuria with DR (n = 185); and Category 4, Alb with DR (n = 213). Cox proportional hazard models were used to compare the risks of developing diabetic foot ulcers across the categories. RESULTS: During 14,249 person-years of follow-up, 50 subjects developed diabetic foot ulcers, with incidence rates of 1.6/1,000, 1.5/1,000, 3.4/1,000, and 12.5/1,000 person-years in Categories 1, 2, 3, and 4, respectively. After adjusting for the presence of diabetic neuropathy and macroangiopathy, the hazard ratios and 95% confidence intervals (CIs) for the risk of diabetic foot ulcer development were 0.66 (95% CI, 0.18-2.36), 1.72 (95% CI, 0.67-4.42), and 3.17 (95% CI, 1.52-6.61) in Categories 2, 3, and 4, respectively, compared with Category 1. CONCLUSION: The presence of DR and Alb significantly increases the risk of diabetic foot ulcer development.

Higher Body Mass Index and Increased Prevalence of Paranasal Sinus Disease.

BACKGROUND: We hypothesized that higher body mass index (BMI) was associated with increased prevalence of paranasal sinus disease and examined the hypothesis in Japanese adults. METHODS: This was a cross-sectional study including 1350 Japanese adults aged 40 years or more who participated in a health check-up program focusing on brain diseases and metabolic syndrome. Participants were divided into quartiles of BMI levels. Paranasal sinus disease was confirmed by a head MRI scan. The association between BMI and paranasal sinus disease was examined using logistic regression analysis, which was adjusted for age, sex, waist:hip ratio, hemoglobin A1c, systolic blood pressure, smoking status, alcohol intake, and white blood cell count. RESULTS: Of the 1350 participants, 151 (11.2%) had paranasal sinus disease. In relation to those in the lowest quartile of BMI, the odds ratios of having the disease among those in the 2nd, 3rd, and 4th quartiles of BMI were 1.89 (95% confidence interval [CI], 1.03-3.48), 2.26 (95% CI, 1.20-4.23) and 2.26 (95% CI, 1.14-4.51), respectively. When BMI was analysed as a continuous variable, an increase of one unit in BMI was significantly associated with increased odds of having the disease, with an OR of 1.08 (95% CI, 1.01-1.16). CONCLUSIONS: The present study suggests that patients with higher BMI are more likely to have paranasal sinus disease.

Clinical Background of Patients with Sperm in Their Urinary Sediment.

INTRODUCTION: The detection rate and associated factors of at least one sperm in urinary sediment is not well-known in real clinical practice. AIMS: The aim of the present study was to evaluate the clinical features associated with the presence of sperm in urinary sediment in a large number of samples. METHODS: We conducted a cross-sectional study at Tokyo Saiseikai Central Hospital. We identified 5,005 males who were aged ≥20 years in whom urinary sedimentation had been performed at least twice between May 2011 and June 2012. The sperm group included patients in whom at least one urinary sediment test performed under a microscope had detected at least one sperm. We evaluated the associations between the presence of at least one sperm in urinary sediment and clinical parameters such as various diseases and the use of particular oral medicines. MAIN OUTCOMES: In total, 1.6% (339/20,937) of urinary sediment samples contained at least one sperm. The sperm group consisted of 282 subjects (5.6%), and the no-sperm group included 4,723 subjects (94.3%). RESULTS: Multivariate analysis demonstrated that younger age (<65) (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 1.32-2.21), the total number of examinations (≥4) (OR: 1.46, 95%CI: 1.11-1.92), diabetes (OR: 1.72, 95%CI: 1.31-2.25), a history of pelvic surgery for colon cancer (OR: 4.89, 95%CI: 2.38-10.02), alpha-1 blocker use (OR: 1.55, 95%CI: 1.16-2.08), a history of trans-urethral resection of the prostate (OR: 2.77, 95%CI: 1.46-5.13), and selective serotonin reuptake inhibitor use (OR: 2.12, 95%CI: 1.07-4.19) were independent predictors of the presence of at least one sperm in urinary sediment. CONCLUSION: There is considerable overlap between the factors associated with the presence of at least one sperm in urinary sediment and those that are strongly associated with ejaculatory disorders.

Association between diabetes and increased prevalence of paranasal sinus disease: a cross-sectional study in Japanese adults.

BACKGROUND: The association between diabetes and paranasal sinus disease has not been thoroughly investigated. METHODS: We cross-sectionally investigated the association between diabetes and the presence of paranasal sinus disease, which was confirmed by a head MRI scan in 1350 adults who underwent a health screening program focusing on brain diseases and metabolic syndrome. Logistic regression, which was adjusted for age, sex, body mass index, waist-to-hip ratio, hypertension, smoking status, alcohol intake, and white blood cell count, was performed to calculate the odds ratio (OR) of having paranasal sinus disease among adults with diabetes in relation to those without. The dose-response relationship between hemoglobin A1c (HbA1c) levels and the presence of paranasal sinus disease was also investigated. RESULTS: Of the 1350 participants (mean age, 61.6 ± 10.0 years; 71.6% men), 220 diabetes cases were identified. Paranasal sinus disease was diagnosed in 151 adults. The adjusted OR of having paranasal sinus disease was 1.74 (95% confidence interval [CI], 1.12-2.71) in those with diabetes. The odds of having paranasal sinus disease increased with HbA1c levels. Compared to those with HbA1c of ≤5.4%, those with HbA1c of 5.5%-6.4%, 6.5%-7.9%, and ≥8.0% were more likely to have paranasal sinus disease, with adjusted ORs of 1.32 (95% CI, 0.88-1.98), 1.63 (95% CI, 0.86-3.09) and 2.71 (95% CI, 1.12-6.61), respectively (P for trend = 0.019). CONCLUSIONS: Diabetes may be significantly associated with higher prevalence of paranasal sinus disease in Japanese adults. We should keep this increased risk in mind when a diabetic patient is suspected of having paranasal sinus disease.

Association of glycemic status with impaired lung function among recipients of a health screening program: a cross-sectional study in Japanese adults.

BACKGROUND: The dose-response relationship between glycemic status and lung function has not been thoroughly investigated. We hypothesized that there are continuous and inverse associations between glycemic measures and lung function tests and examined the hypothesis in Japanese adults. METHODS: We cross-sectionally investigated associations of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) with forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 3161 adults who participated in a health screening from 2008 to 2011. The study participants included both diabetic and non-diabetic adults. Multiple linear regression analyses were performed to examine the associations. RESULTS: Inverse associations were observed in both sexes, which were attenuated in women after adjustment for multiple variables. A 1% absolute increase in HbA1c was associated with a -52-mL (95% confidence interval [CI] -111 to 8 mL) difference in FVC and a -25-mL (95% CI -75 to 25 mL) difference in FEV1 in women, and a -128-mL (95% CI -163 to -94 mL) difference in FVC and a -73-mL (95% CI -101 to -44 mL) difference in FEV1 in men. A 10-mg/dL increase in FPG was associated with a -11-mL (95% CI -29 to 8 mL) difference in FVC and a -8-mL (95% CI -24 to 7 mL) difference in FEV1 in women, and a -32-mL (95% CI -44 to -21 mL) difference in FVC and a -19-mL (95% CI -28 to -9 mL) difference in FEV1 in men. CONCLUSIONS: Inverse associations between glycemic measures and lung function were observed. Men seem more susceptible to the alteration in FVC and FEV1 than women.

Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus.

Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (n = 133, 115 men and 18 women; age 64.7 ± 11.5 years; HbA1c 8.1 ± 1.6%). Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was 71.2 ± 22.3 ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (r = -0.450, P < 0.01), triglyceride (r = 0.445, P < 0.01), and high sensitive C-reactive protein (r = 0.316, P < 0.01) but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (ß = -0.411, P < 0.01) and high sensitive C-reactive protein (ß = 0.193, P < 0.05). Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus.

Past Obesity as well as Present Body Weight Status Is a Risk Factor for Diabetic Nephropathy.

Aims. We analyzed the prevalence of nephropathy according to past body weight status in Japanese subjects with type 2 diabetes because the influence of past obesity on diabetic complications is not certain. Methods. We examined the prevalence of nephropathy in 2927 subjects with type 2 diabetes mellitus according to current BMI and maximum BMI in the past. We defined "current obesity" as BMI on hospitalization of 25 or more, "previous obesity" as BMI on hospitalization of less than 25 and self-reported maximum BMI in the past of 25 or more, and "continuously lean" as maximum BMI of less than 25. Results. The prevalence of nephropathy was significantly higher in subjects with current obesity (40.6%) or previous obesity (35.6%) than in those who were continuously lean (24.3%) (P < 0.017). In logistic regression analysis, previous obesity, as well as current obesity, was a significant risk factor for nephropathy, independent of sex, age, disease duration, hypertension, dyslipidemia, HbA1c, and diabetic retinopathy. Conclusions. Obesity in the past, as well as the present body weight status, was a risk factor for diabetic nephropathy.

Severe hyponatremia caused by secondary adrenal insufficiency in a patient with giant pituitary prolactinoma.

A 55-year-old-man was admitted to Saiseikai Central Hospital, Tokyo, Japan, complaining of nausea and appetite loss, and was found to have severe hyponatremia. Despite severe hyponatremia and plasma hypo-osmolarity, urinary sodium excretion was not reduced. A brain magnetic resonance imaging (MRI) scan revealed a giant pituitary prolactinoma, and endocrinological tests showed a markedly increased prolactin level. Despite the observation that the basal plasma ACTH level was normal, serum cortisol and urinary cortisol excretion levels were low. Rapid ACTH loading sufficiently stimulated an increase in serum cortisol levels, suggesting secondary adrenal insufficiency. Notably, loading of CRH induced a good ACTH response; however, the serum cortisol response remained low. In contrast, the continuous daily administration of exogenous ACTH dramatically increased serum cortisol levels. These discrepant responses may have been caused by the low biological activity of innate ACTH. Following partial resection of the prolactinoma, postoperative adjuvant therapy with cabergoline effectively reduced prolactin levels, but did not improve the hyponatremia. In contrast, hydrocortisone replacement therapy recovered the serum sodium level to the normal range. The present case is the first report describing a link between severe hyponatremia and biologically inactive circulating ACTH as a likely result of giant prolactinoma.

Risk for future diabetes among individuals with high-normal glycemia at 40 years of age.

OBJECTIVE: The present study investigated the risk for future diabetes among individuals with high-normal glycemia (fasting plasma glucose (FPG) of 100-109 mg/dL) in an early middle-aged population. METHODS: We retrospectively observed a workplace cohort all aged 40 and followed the incidence of diabetes according to the FPG levels at baseline. A total of 901 non-diabetic males were included in the analysis. The 10-year cumulative incidence of diabetes was calculated. The hazard ratios of developing diabetes were calculated using a Cox proportional hazards regression. RESULTS: The proportions of those with high-normal glycemia and impaired fasting glucose (IFG) (FPG of 110-125 mg/dL) at baseline were 21.5% and 4.7%. The 10-year cumulative incidence of diabetes was 14.7% and 48.9%, respectively, in these individuals. After adjustment for possible confounders, the hazard ratios of developing diabetes among individuals with high-normal glycemia and IFG were 5.2 (95% CI=2.4-11.2) and 21.3 (95% CI=9.2-49.5) relative to those with an FPG of <90 mg/dL. CONCLUSION: High-normal glycemia is a risk for future diabetes even in the relatively young and healthy workplace population. Although the relative risk is much higher in those with IFG, the absolute number of incident diabetes developing from those with high-normal glycemia seems to be considerable given the prevalence of this condition.

Associations of insulin resistance and glycemic control with the risk of kidney stones.

OBJECTIVE: The associations of insulin resistance and glycemic control with the risk of kidney stones were explored. METHODS: Generally healthy Japanese (n=2,171) who visited Saiseikai Central Hospital (Tokyo, Japan) for a health check were included in a cross-sectional study. We calculated odds ratios (OR) of having kidney stones in terms of four measures: fasting serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), adjusting for possible risk factors for kidney stones. RESULTS: Fasting serum insulin and HOMA-IR were non-significantly associated with the risk of kidney stones, whereas FPG and HbA1c were significantly associated. Compared with those with an FPG of <100 mg/dL, the ORs in those with an FPG of 100 to <126 mg/dL and ≥126 mg/dL were 1.38 (95% confidence interval [CI] =0.95-2.00) and 1.83 (95% CI =1.09-3.06) (p for trend =0.016). In relation to those with an HbA1c of <5.5%, the ORs in those with an HbA1c of 5.5 to <6.0%, 6.0% to <6.5% and ≥6.5% were 1.16 (95% CI =0.76-1.79), 1.25 (95% CI =0.70-2.23) and 1.98 (95% CI =1.11-3.52), respectively (p for trend =0.027). The significant associations between glycemic control measures and the risk of kidney stones were preserved even after the adjustment for factors related to insulin resistance. CONCLUSION: Glycemic control could be an independent risk factor for kidney stones.

Factors Associated with the Decline of Kidney Function Differ among eGFR Strata in Subjects with Type 2 Diabetes Mellitus.

Introduction. There is no report about risk factors for renal deterioration according to the clinical stage, divided by the estimated glomerular filtration rate (eGFR) in type 2 diabetes. Materials and Methods. We evaluated the factors correlated with the annual eGFR decline in 1303 subjects with type 2 diabetes whose eGFR was ≥30 mL/min/1.73 m(2). eGFR strata were defined by baseline eGFR value as follows: stratum 1: ≥90, stratum 2: ≥60, <90, and stratum 3: ≥30, <60. Results. The annual eGFR decline was 2.3 ± 5.4 mL/min/1.73 m(2) in overall subjects. Multiple linear regression analysis demonstrated that age, male sex, systolic blood pressure, logarithmically transformed albumin excretion rate (AER), eGFR strata, and hemoglobin concentration were significantly correlated with the annual eGFR decline. When stratified by eGFR, the factors that showed a significant correlation were different among eGFR strata. AER was significantly correlated with annual eGFR decline in all eGFR strata. Hemoglobin concentration showed a significant correlation only in the advanced eGFR stratum. Conclusion. The factors correlated with the annual eGFR decline were different among eGFR strata in type 2 diabetes mellitus, and hemoglobin concentration and AER were important factors for renal deterioration, especially in the advanced eGFR stratum.

Plasma 25-hydroxyvitamin d is independently associated with hemoglobin concentration in male subjects with type 2 diabetes mellitus.

Introduction. It was reported that 25-hydroxyvitamin D level was independently associated with anemia in chronic kidney diseases, but the relation between vitamin D and anemia in diabetes mellitus is not still certain. We analyzed the relation between plasma 25-hydroxyvitamin D level and hemoglobin concentration. Materials and Methods. A cross-sectional study in male patients with type 2 diabetes was performed. Correlation coefficients and standardized partial regression coefficient for the hemoglobin concentration were evaluated. Results. Hemoglobin concentration was positively correlated with body mass index, HbA1c, estimated glomerular filtration rate, cholinesterase, and 25-hydroxyvitamin D level and negatively correlated with age, duration of diabetes mellitus, serum creatinine, and urinary albumin creatinine ratio. Multiple regression analysis revealed the independent relation of 25-hydroxyvitamin D to hemoglobin concentration. Conclusions. Plasma circulating form of vitamin D is significantly associated with hemoglobin concentration in diabetes mellitus independent of the clinical markers for kidney function or nutrition.

Determinants of an optimal response to pioglitazone in terms of HDL-cholesterol.

OBJECTIVE: The effect of pioglitazone on high-density lipoprotein cholesterol (HDL-C) has been attracting attention. However, there are limited data on the characteristics of patients who are likely to respond to pioglitazone in terms of the improvement in HDL-C levels (lipid responders). In the present study, the characteristics of lipid responders were investigated. METHODS: Five hundred and sixty-three patients with type 2 diabetes who started pioglitazone treatment were followed for six months. They were divided into two groups according to the response to pioglitazone. Subjects whose HDL-C levels increased by 10% or more from the baseline were defined as lipid responders. The odds ratios (OR) for becoming lipid responders were calculated using logistic regression. RESULTS: Significant patients' characteristics of lipid responders were age, HbA1c, HDL-C and low-density lipoprotein cholesterol (LDL-C), yielding adjusted ORs of 0.76 [95% confidence interval (CI)=0.61-0.93] for an increment of 10 years, 0.79 (95% CI=0.66-0.95) for an increment of 1%, 0.83 (95% CI=0.72-0.96) for an increment of 10 mg/dL and 0.93 (95% CI=0.87-1.00) for an increment of 10 mg/dL, respectively. Patients with sulfonylurea treatment and those with both sulfonylurea and metformin treatment were less likely to become lipid responders than diet-treated patients with ORs of 0.32 (95% CI=0.15-0.69) and 0.41 (95% CI=0.19-0.87), respectively. CONCLUSION: Pioglitazone could be beneficial especially for patients with young age, low HbA1c, low HDL-C or low LDL-C levels at baseline in terms of the improvement in HDL-C levels. Use of sulfonylureas at baseline could attenuate the effect of pioglitazone on HDL-C.

Increased risk of renal deterioration associated with low e-GFR in type 2 diabetes mellitus only in albuminuric subjects.

OBJECTIVE: The significance of estimated glomerular filtration rate (e-GFR) in diabetic nephropathy has yet to be clearly determined. We therefore compared albuminuria and e-GFR for usefulness in predicting progressive decline in renal function. METHODS: A total of 1,303 subjects with type 2 diabetes mellitus whose e-GFR was more than 30 mL/min/1.73 m(2) were followed for three years. Associations of clinical staging based on AER and that based on e-GFR with progression of renal insufficiency (e-GFR <30 mL/min/1.73 m(2)) were evaluated. RESULTS: On univariate analysis, both clinical stages based on e-GFR and AER were significant variables (p<0.05). On multiple logistic regression analysis, the odds ratio for macroalbuminuria was 132.3, and that for microalbuminuria was 10.3 while that for e-GFR less than 60 mL/min/1.73 m(2) was 9.0 for further deterioration of renal function. On the other hand, subjects without albuminuria exhibited a rate of disease progression of less than 1% irrespective of e-GFR level. CONCLUSIONS: Both albuminuria and reduced e-GFR are significant and independent risk factors for further deterioration of diabetic nephropathy, though albuminuria had a greater odds ratio than reduced e-GFR for deterioration of renal function over a three-year period. e-GFR exhibited additive risk for deterioration of diabetic nephropathy within three years only when albuminuria was present.

[Syndrome of inappropriate ADH secretion (SIADH) induced by pramipexole in a patient with Parkinson's disease].

An 85-year-old woman with Parkinson's disease was admitted to our hospital to conduct a further work-up for progressive gait disturbance. She had been on medications for the disease for more than a decade prior to admission. In order to improve her condition, she was newly administered pramipexole, a dopamine agonist, from day 3 in addition to the preceding anti-Parkinson's therapy. However, on day 10, her consciousness level was rapidly deteriorated into delirium(JCS II-10), which was not accompanied by neurological signs and symptoms. Laboratory tests showed severe hyponatoremia with relatively increased urinary sodium excretion, and severe low serum osmolarity with an increased urinary osmolarity. Brain CT and brain MRI showed no specific abnormalities except for those related to aging. Blood concentration of ADH measured at the onset was substantially higher(39.5 pg/ml) than normal (0.3-3.5 pg/ml under normal osmolarity). Diseases causing hyponatremia, such as liver cirrhosis, congestive heart failure, hypotonic dehydration, and malignancy-associated inappropriate ADH secretion (SIADH), were all excluded. Under the suspicion of SIADH due to pramipexole, the drug was discontinued and as a result, her consciousness level improved rapidly together with a prompt reduction in ADH level (9.2 pg/ml). To the best of our knowledge, the present case is the first that demonstrates pramipexole-induced SIADH. Since pramipexole is classified as a dopaminergic receptor agonist, this case may provide new insight into a link between ADH and the dopaminergic receptor in the central nervous system.