The role of blink reflex R1 latency as an electrophysiological marker in diabetic distal symmetrical polyneuropathy.

OBJECTIVE: Studies showed a relatively prolonged blink R1 latency in patients with diabetic distal symmetrical polyneuropathy (DSPN) compared to that without DSPN. We tested the hypothesis that blink R1 latency would provide a diagnostic alternative to nerve conduction studies (NCS) in DSPN and act as a marker of the severity of NCS abnormalities in DSPN. METHOD: A total of 109 patients with type 2 diabetes underwent blink reflex studies and NCS. We used the composite amplitude scores of nerve conductions (CAS), which consisted of motor (tibial, peroneal and ulnar) and sensory (sural and ulnar) amplitudes for estimating the severity of NCS. RESULTS: Patients with DSPN had longer blink R1, R2, and contralateral R2 latencies (P < 0.0001, P = 0.001, and P = 0.031, respectively) and higher CAS (P < 0.0001). Area under curve on receiver operating characteristic curve analysis in diagnosing occurrence of DSPN in blink R1 latency was 0.772 (P < 0.0001). Multiple linear regression analysis showed that blink R1 latency was independently associated with CAS. CONCLUSION: Blink R1 latency may be valuable in auxiliary diagnosis and in determining the severity of NCS abnormalities in DSPN. SIGNIFICANCE: Blink R1 latency can be added as a supplemental marker of severity of NCS in DSPN, especially if the patient's sural amplitudes has a floor effect.

Sural nerve sensory response in diabetic distal symmetrical polyneuropathy.

INTRODUCTION: The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS: Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS: Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P < .0001), and changes in sural SNAP amplitudes were negatively correlated with those of CAS after controlling for follow-up duration (r = -.531, P = .028). DISCUSSION: When a patient's baseline sural SNAP amplitude is above zero, it can be used as one measure of DSPN in screening, severity evaluation, and follow-up. However, if the patient's sural SNAP value is zero, CAS can be used as a follow-up measure.

Close relationship between cardiovagal function and sural sensory nerve action potential in type 2 diabetes.

OBJECTIVE: Both diabetic distal symmetrical polyneuropathy (DSPN) and cardiac autonomic neuropathy (CAN) indicate the length-dependent pattern of disease. Decreased parasympathetic activity has been found in the early phase of CAN and sural sensory nerve action potential (SNAP) imply axonal loss in DSPN. METHOD: All patients with type 2 diabetes underwent cardiovascular autonomic function and nerve conduction studies (NCS). We constructed modified composite autonomic scoring scale (CASS) and composite score of NCS to measure the severity of CAN and DSPN, respectively. RESULTS: Patients with a longer duration of diabetes had a lower heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS), higher CASS, a higher percentage of CAN, lower sural SNAP, higher composite score of NCS, and a higher percentage of DSPN. Multiple linear regression analysis showed that only sural SNAPs were independently associated with mean HR_DB. CONCLUSION: Sural SNAP was closely correlated with parameters of cardiovagal functions in patients with different durations of diabetes. The percentage and severity of CAN and DSPN increase with longer duration of diabetes. SIGNIFICANCE: The independent association of sural sensory nerve action potential amplitude and heart rate response to deep breathing with type 2 diabetes is important because combined testing increases diagnostic sensitivity and specificity.

HbA1C Variability Is Strongly Associated With the Severity of Cardiovascular Autonomic Neuropathy in Patients With Type 2 Diabetes After Longer Diabetes Duration.

BACKGROUND: Variability in the glycated hemoglobin (HbA1c) level is associated with a higher risk of microvascular complications in patients with type 2 diabetes. We tested the hypothesis that HbA1c variability is not only strongly associated with the presence but also the degree of severity of cardiovascular autonomic neuropathy (CAN) in patients with long diabetes durations (more than 10 years). METHODS: For each patient, the intrapersonal mean, standard deviation (SD), and coefficient of variation (CV) for HbA1c were calculated using all measurements obtained 3 years before the study. We constructed the composite autonomic scoring scale (CASS) as a measure of the severity of cardiovascular autonomic functions. Stepwise logistic regression and linear regression analyses were performed to evaluate the presence of CAN and the influence of independent variables on the mean CASS, respectively. RESULTS: Those with CAN had a higher mean age, a higher low-density lipoprotein cholesterol (LDL-C), HbA1c-SD, HbA1c-CV, mean HbA1c, and index HbA1c, higher prevalence of retinopathy as the underlying disease, and lower high-density lipoprotein (HDL) levels. Stepwise logistic regression showed that HbA1c-SD and retinopathy were risk factors that were independently associated with the presence of CAN. Mean HbA1c, HbA1c-CV, HbA1c-SD, and index HbA1c were positively correlated with mean CASS, and a multiple linear regression analysis revealed that HbA1c-SD was independently associated with the mean CASS. CONCLUSION: HbA1c variability is strongly associated with not only the presence but also the degree of severity of CAN. A longitudinal study is required to confirm whether controlling blood glucose level is effective in reducing CAN progression.

IRAK1, a Target of miR-146b, Reduces Cell Aggressiveness of Human Papillary Thyroid Carcinoma.

CONTEXT: MicroRNA (miR)-146b is overexpressed in papillary thyroid carcinoma (PTC) and is associated with extrathyroidal invasion, advanced tumor stage, and poor prognosis. However, the underlying mechanism of miR-146b in relation to its oncogenic behavior in PTC and its putative targets remain unknown. OBJECTIVE: The purpose was to investigate IL-1 receptor-associated kinase 1 (IRAK1) as the potential miR-146b target gene and its involvement in PTC. DESIGN: We used genome-wide microarray, computational analysis, and 3' UTR reporter gene assays to identify IRAK1 as a miR-146b target gene. In vitro gain/loss-of-function experiments were further performed to determine the effects of IRAK1 on proliferation, colony formation, and wound-healing in PTC cancer cell lines. Expression levels of miR-146b and IRAK1 of 50 cases of PTC and its adjacent normal thyroid specimens were assessed via qRT-PCR. RESULTS: Microarray expression profile revealed that the mRNA level of IRAK1 gene was down-regulated by miR-146b. The 3' UTR of IRAK1 mRNA was found to be a molecular target of miR-146b posttranscriptional repression in BCPAP cells by reporter gene assays. MiR-146b promoted the migration and proliferation of PTC cells by down-regulating IRAK1 expression, whereas restoration of IRAK1 expression reversed this effect. In addition, the expression of IRAK1 mRNA was significantly lower in PTC clinical tissue samples than normal adjacent thyroid specimens and showed a strong inverse correlation with the expression of miR-146b in PTC specimens. CONCLUSION: Our results demonstrated that IRAK1 is a direct target of miR-146b and has functional roles to inhibit various aggressive PTC cell activities. In conjunction with current therapeutic regimens, targeting the miR-146b-IRAK1 axis may provide a potential approach for PTC management.

Nocturia indicates a poor health status and increases mortality in male patients with type 2 diabetes mellitus.

OBJECTIVES: To investigate the association between nocturia and erectile dysfunction, androgen deficiency, overactive bladder and systemic diseases in men with type 2 diabetic mellitus. METHODS: A self-administered questionnaire containing overactive bladder symptom score and sexual health inventory for men was obtained from subjects with type 2 diabetic mellitus. Nocturia and severe nocturia were defined as rising ≥2 or ≥3 per night to void, respectively. Patient characteristics and diabetes-related complications to risk of nocturia were evaluated. RESULTS: Of 632 consecutive subjects, 56.0 and 24.2 % reported having nocturia and severe nocturia, respectively. After adjustment of age, diabetic mellitus duration, and overactive bladder, the presence of erectile dysfunction, stroke, hypertension, and higher serum creatinine level was associated with nocturia and severe nocturia. The patients with the lowest quartile of testosterone level (2.21 ± 0.51 ng/mL) had higher prevalence of nocturia (65.1 %) and severe nocturia (32.9 %) than the sum of the other three quartiles. The patients with severe nocturia had threefold higher mortality than the other group after 3.5-year follow-up. CONCLUSIONS: The presence of nocturia was associated with erectile dysfunction, systemic vascular events, higher mortality, and indicated poor health in male with type 2 diabetic mellitus.

Diabetic Retinopathy Is Strongly Predictive of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes.

A well-established, comprehensive, and simple test battery was used here to re-evaluate risk factors for cardiovascular autonomic neuropathy (CAN) in type 2 diabetes. One hundred and seventy-four patients with type 2 diabetes were evaluated through the methods of deep breathing and Valsalva maneuver for correlation with factors that might influence the presence and severity of CAN. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment, and CAN was defined as a CASS score ≥2. Results showed that nephropathy, duration of diabetes, blood pressure, uric acid, and the presence of retinopathy and metabolic syndrome significantly correlated with the CASS score. Age may not be a risk factor for diabetic CAN. However, the effects of diabetes on CAN are more prominent in younger patients than in older ones. Diabetic retinopathy is the most significant risk factor predictive of the presence of CAN in patients with type 2 diabetes.

Genetic disposition and modifiable factors independently associated with anemia in patients with type 2 diabetes mellitus.

AIMS: Anemia is prevalent but under-recognized in patients with diabetes mellitus (DM). Genetic variants in angiotensin-converting enzyme (ACE), tumor necrosis factor-alpha (TNF-α) and erythropoietin (EPO) have been associated with diabetic nephropathy. In the present study, we investigated the associations between anemia and polymorphisms in EPO promoter (rs1617640), TNF-α G-308A and ACE Insertion/Deletion in Chinese patients with type 2 diabetes. METHODS: Polymorphisms in ACE, TNF-α and EPO were genotyped in 1142 patients. Anemia was defined as hemoglobin (Hb) levels below 12 g/dL for women and 13 g/dL for men. RESULTS: 286 (25%) patients had anemia. Patients with anemia were older, had longer duration of diabetes, worse renal function and more albuminuria. ACE Insertion/Deletion and TNF-a G-308A were not associated with anemia. The frequencies of EPO polymorphism (rs1617640) were significantly different between anemic and nonanemic patients. Patients with TT genotype had higher prevalence of anemia than those with TG and GG. Regression analysis identified EPO SNP, duration of DM, serum albumin, albuminuria and renal function independently associated with anemia. After adjusting for multiple variables, TT and TG genotypes were associated with 3-5-fold increased risk for anemia compared to GG. CONCLUSIONS: The EPO genotype in Chinese patients with type 2 diabetes is associated with anemia and may help to identify those at risk. Further evaluation of its effect on clinical outcomes in prospective studies may be useful to predict the outcomes of erythropoiesis stimulating therapy, and to individualize anemia management.

Differentiation of type 2 diabetes mellitus with different complications by proteomic analysis of plasma low abundance proteins.

BACKGROUND: Few biomarkers of type 2 diabetes mellitus (T2DM) are replicable in the differentiation of T2DM with different complications. We aimed to identify proteomic biomarkers among T2DM patients with nephropathy or retinopathy. METHODS: Plasma low abundance proteins were enriched by depletion of 14 high abundance proteins using an affinity removal system, and subjected to nanoflow liquid chromatography electrospray ionization (nano LC-ESI) mass spectrometry after a gel electrophoresis with in-gel digestion. The plasma differential proteomes between normal adults and diabetic patients were validated by another cohort of 149 T2DM patients. RESULTS: A total of 826 proteins in plasma were consistently identified from 8 plasma samples of normal adults, and 817 proteins were consistently identified in 8 plasma samples of T2DM patients. Using the MetaCore analysis, low abundance proteins in plasma between normal adults and T2DM patients were significantly different in 5 functional pathways. Moreover, plasma prolactin-induced protein (PIP), thrombospondin-2 (THBS2), L1 cell adhesion molecule (L1CAM) and neutrophil gelatinase-associated lipocalin (NGAL) levels were higher in T2DM patients. Further, PIP, THBS2 and NGAL were significantly higher in T2DM patients with nephropathy (albuminuria) but not in those with retinopathy, while L1CAM levels were higher in T2DM patients with retinopathy. CONCLUSIONS: This study identified that higher PIP, THBS2 and/or NGAL levels were significantly associated with nephropathy of T2DM, and higher L1CAM but normal PIP, THBS2 or NGAL was significantly associated with retinopathy of T2DM.

Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan--a 3-year prospective study.

AIMS: To explore the role of serum uric acid (SUA) concentration in diabetic retinopathy (DR) for patients with type 2 diabetes mellitus (T2DM). METHODS: A 3-year prospective study in 749 patients with T2DM and without proliferative diabetic retinopathy (PDR) was conducted at a medical center. Baseline SUA concentration and parameters of glycemic control, blood pressure, kidney disease, and lipid profiles were analyzed to determine their contribution to DR. RESULTS: Fundus examination showed that 184 patients (24.6%) had non-proliferative retinopathy and 565 (75.4%) without DR at baseline. After 3 years, increase in the severity of DR was recognized in 103 patients (13.8%), including 81 patients with newly developed DR. Patients with increase in severity of DR positively associated with duration of DM (11.9 vs. 9.4 years, p = 0.001), HbA1c (7.6 vs. 7.2%, p = 0.001), albuminuria (45.5 vs. 31.0%, p = 0.006), and SUA (6.47 vs. 5.87 mg/dl, p<0.001) than did those without change in DR stage. Cox regression showed that patients with SUA in the 3rd (5.9-6.9 mg/dl) and 4th (≥ 7.0mg/dl) quartiles had hazard ratios for DR worsening of 2.57 and 3.66 (95% C.I. 1.30-5.08 and 1.92-7.00) when compared with patients with SUA in the 1st quartile (<4.9 mg/dl). CONCLUSIONS: SUA concentration is associated with the increase in severity of DR over a 3-year period in patients with T2DM. Further study is required to define the exact role of SUA in DR.

Long-term outcomes of extracorporeal shockwave therapy for chronic foot ulcers.

BACKGROUND: Recent studies showed that extracorporeal shockwave therapy (ESWT) is effective in the treatment of chronic foot ulcers in short term. However, the long-term effects of ESWT in chronic foot ulcers are unknown. The purpose of this study was to evaluate the long-term outcomes of ESWT in chronic foot ulcers with 5-y follow-up. METHODS: The study cohort consisted of 67 patients with 72 ulcers including 38 patients with 40 ulcers in the diabetes mellitus (DM) group and 29 patients with 32 ulcers in the non-diabetes mellitus (non-DM) group. Each patient received ESWT to the affected foot twice per week for 3 wk for a total of six treatments. The evaluations included clinical assessment for the ulcer status, local blood flow perfusion, and analysis of mortality and morbidity. RESULTS: The results showed completely healed ulcers in 55.6% and 57.4% of total series, 48% and 43% of DM group, and 66% and 71% of non-DM group at 1 and 5 y (P = 0.022 and P = 0.027), respectively. The mortality rate was 15% in total series, 24% in DM group, and 3% in non-DM group (P = 0.035). The rate of amputation was 11% in total series, 17% in DM group, and 3.6% in non-DM group (P = 0.194). The blood flow perfusion rate significantly increased after ESWT for up to 1 yr but decreased from 1-5 y in both groups. However, the non-DM group showed significantly better blood flow perfusion than the DM group at 5 y (P = 0.04). CONCLUSIONS: ESWT appears effective in chronic diabetic and nondiabetic foot ulcers. However, the effects decreased from 1-5 y after treatment.

Prevalence and associated risk factors of nocturia and subsequent mortality in 1,301 patients with type 2 diabetes.

OBJECTIVE: To evaluate the correlates of nocturia and subsequent mortality in patients with type 2 diabetes mellitus (T2DM). METHODS: A self-administered questionnaire containing overactive bladder symptom score was obtained from subjects with T2DM. Nocturia and severe nocturia were defined as rising ≥2 or ≥3 per night to void, respectively. Patient characteristics and diabetes-related complications to risk of nocturia were evaluated. RESULTS: Of 1,301 consecutive subjects, 59.6 and 25.3% reported having nocturia and severe nocturia, respectively. The presence and severity of nocturia increased with age and overactive bladder (OAB). The presence of OAB was 28.8% in patients with nocturia and was significantly associated with nocturia (OR 2.26) after adjustment for age and duration of DM. The presence of stroke, calcium channel blocker use, hypertension, waist circumference greater than standard, albuminuria, and higher serum creatinine level, and high-sensitivity C-reactive protein was associated with nocturia and severe nocturia after adjustment for age, duration of DM, and the presence of OAB. Higher estimated glomerular filtration rate, hemoglobin, serum albumin, and male gender were less likely to have nocturia (OR <1). Severe nocturia increased mortality (OR 1.93) independent of age and DM duration and has a higher mortality rate compared to those without severe nocturia (6.1 vs. 2.4%, P = 0.001) in 2.5 years follow-up. CONCLUSIONS: While OAB is an important predictor of nocturia in T2DM patients, systemic issues, including stroke, hypertension, obesity, and chronic kidney disease, have further impact on nocturia independent of OAB. Severe nocturia is a marker for increased mortality.

Clinical Characteristics of Endogenous Cushing's Syndrome at a Medical Center in Southern Taiwan.

From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing's syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing's disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 µ g, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days, P < 0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy.

The prevalence and predictors of androgen deficiency in Taiwanese men with type 2 diabetes.

OBJECTIVE: To evaluate the prevalence and predictors of androgen deficiency (AD) in Taiwanese men with type 2 diabetes mellitus (T2DM). METHODS: A recent hospital-based series of Western populations showed that 30%-50% of men with T2DM have low testosterone, and AD links to DM and obesity bidirectionally. However, data of AD from other ethnicities with character of less obesity are rarely reported. AD was defined as having a total testosterone level less than 300 ng/dL. The clinical variables and diabetes-associated complications of the risk of AD were evaluated. RESULTS: Of 766 consecutive subjects (mean age 62.2 years, mean body mass index [BMI] 26.0) attending out-patient diabetic clinics, 32.5% have AD. The AD group was older, had higher BMI, waist circumference, higher proportion of metabolic syndrome and stroke, higher levels of triglyceride, high sensitivity C-reactive protein (hsCRP), uric acid, and lower levels of total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) than the normal testosterone group. After age adjustment, AD was positively associated with metabolic syndrome (odds ratio [OR] = 2.142), serum high sensitivity C-reactive protein (OR = 1.120), uric acid (OR = 1.118), BMI (OR = 1.083), waist circumference (OR = 1.038), triglyceride (OR = 1.028), and inversely associated with serum low-density lipoprotein (OR = 0.931) and high-density lipoprotein (OR = 0.826) in logistic regression analysis. There were no significant differences in retinopathy, neuropathy, nephropathy, or coronary artery disease between patients with or without AD. CONCLUSION: One third of Taiwanese men with T2DM have AD. The major predictors of AD are linked to obesity, which is a potentially modifiable risk factor, and may represent an important avenue for intervention.

Prognostic implications of miR-146b expression and its functional role in papillary thyroid carcinoma.

CONTEXT: Recent studies suggest that miR-146b deregulation in papillary thyroid carcinoma (PTC) was associated with advanced tumor characteristics. However, the influence of miR-146b expression on the prognosis of PTC remains unknown. We sought to correlate tumor expression levels of miR-146b with the prognosis of a previously reported PTC cohort and reveal the underlying mechanisms via a PTC cell line model. METHODOLOGY: Expression levels of miR-146b were assessed via quantitative real-time PCR in 71 cases of PTC with distinct clinico-pathogenetic characteristics. All patients were classified into the disease-free or active disease group, based on their medical records at the end of the follow-up period. In vitro gain-of-function experiments were performed in a BCPAP human papillary thyroid cancer cell line model, which harbored the homozygous mutation of BRAF. BCPAP cells were transfected with a mimic-miR-146b and nonspecific microRNA (miRNA) control to determine whether miR-146b overexpression promotes cell migration and invasion. Proliferation assay, colony formation assay, and chemotherapy-induced apoptosis were also determined. RESULTS: Multivariate logistic regression analysis demonstrated advanced tumor stage, presence of cervical lymph node metastasis, and miR-146b expression were independent risk factors for poor prognosis in PTC. Patients with higher miR-146b expression levels had significantly poorer overall survival compared with those with lower miR-146b levels. The associated hazard ratio was 3.92 (95% confidence interval, 1.73-8.86, log-rank P < .05). Overexpression of miR-146b significantly increased cell migration and invasiveness. Furthermore, miR-146b also increased resistance to chemotherapy-induced apoptosis. CONCLUSIONS: Our results suggest that miR-146b is a novel prognostic factor of PTC. Furthermore, in vitro functional studies provided the mechanistic explanation for miR-146b in tumor aggressiveness. These results enhance understanding of the molecular mechanisms involved in tumor aggressiveness in PTC, provide new prognostic biomarkers, and ultimately offer new leads for developing therapies for PTC.

Genotype and phenotype predictors of relapse of graves' disease after antithyroid drug withdrawal.

BACKGROUND: For patients with Graves' disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. METHODS: To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. RESULTS: FOUR SNPS WERE SIGNIFICANTLY ASSOCIATED WITH DISEASE RELAPSE: rs231775 (OR 1.96, 95% CI 1.18-3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01-62.7), rs11569309 (OR 8.09, 95% CI 1.03-63.7), and rs3765457 (OR 2.60, 95% CI 1.08-6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09-1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05-1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15-2.35), and smoking habit (HR 1.60, 95% CI 1.05-2.42). CONCLUSION: Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.

Inertia on hypoglycemia: highlight from a Taiwan subgroup analysis of Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) study.

Type 2 diabetes mellitus is a global health issue. Patients with poor glycemic control often suffer from cardiovascular, cerebrovascular, neuropathic, and nephropathic complications as well as other chronic conditions. Therapeutic guidelines recommend that diabetic patients should maintain their HbA(1c) level below a certain target in order to minimize the risk of developing complications. However, hypoglycemia is recognized as a major impediment to the adequate control of type 2 diabetes. Hypoglycemia can manifest symptoms of varying degrees of severity. Moreover, an association between hypoglycemia and cardiovascular morbidity and mortality has been reported. Here, we present a post hoc Taiwan subgroup analysis of these data collected in the RECAP-DM study to indicate probably more emphasis and concern on hypoglycemia in type 2 diabetic patients in Taiwan. In this analysis, we found no significant difference was observed in treatment-related satisfaction between Taiwanese patients with or without hypoglycemia. Another finding of our study further shows that varying order of hypoglycemic symptoms or severity has no effect on patients' assessment of health-related quality of life scores. We need to pay more attention to this issue because of its enduring impact on compliance and concerns about hypoglycemia in type 2 diabetic patients. Nevertheless, socio-demographic characteristics are also important factors influencing glycemic control and patients' health-related quality of life. Future interventions and therapeutic algorithms should emphasize the probable patients' unawareness or neglect on hypoglycemia in diabetic patients.

The presence of overactive bladder wet increased the risk and severity of erectile dysfunction in men with type 2 diabetes.

INTRODUCTION: Diabetes is a common risk factor for overactive bladder (OAB) syndrome and erectile dysfunction (ED). AIM: The study evaluated the risk factors of OAB and association of OAB and ED in type 2 diabetic men. METHODS: The diagnosis of ED and OAB was based on a self-administered questionnaire containing Sexual Health Inventory for Men (SHIM) and OAB symptom score (OABSS, 0-15, indicating increasing severity of symptoms), respectively. MAIN OUTCOME MEASURES: The clinical variables and diabetes-associated complications, including ED, which are risk factors for OAB, were evaluated. RESULTS: Of 453 consecutive subjects attending outpatient diabetic clinic with a mean age of 60.6 years, 25.4%, 10.2%, 81.9%, and 28.3% reported having OAB, OAB wet, ED, and severe ED, respectively. The OABSS is inversely associated with SHIM (correlation coefficient-0.275). The patients with OAB have significantly lower SHIM score, testosterone level, and serum albumin level, have more proportion of severe ED, were older, and have longer duration of diabetes mellitus (DM). After adjustment for age and duration of DM, the presence of severe ED was associated with OAB (odds ratio [OR] = 1.58), and severe ED (OR = 2.36), SHIM score (OR = 0.92), and serum albumin level (OR = 0.24) were risk factors for OAB wet (patients with urgency incontinence, once a week or more). The OR of ED in patients with OAB or OAB wet compared with no OAB was 1.82, and 3.61, respectively. Among the OAB components, urgency incontinence has the strongest impact on ED (OR = 4.06), followed by nocturia, urgency, and frequency. About 15.1% (N = 68) without OAB and ED are younger and have shorter DM duration, lower systolic BP, and higher serum albumin level after multivariate analysis compared with patients with OAB or ED. CONCLUSION: The presence of severe ED was significantly associated with OAB, especially OAB wet. The presence of OAB wet increased the risk and severity of ED.

The influence of self-monitoring blood glucose frequency on the oscillation of hemoglobin A1c and chronic complications.

BACKGROUND: A fluctuating blood glucose level is one of the risks of chronic complications in diabetes. Previous studies indicated that hemoglobin A1c (HbA1c) values apparently improved after initiation of self-monitoring blood glucose (SMBG). The purpose of this study is to investigate the relationship between the frequency of SMBG, long-term fluctuatation of HbA1c, and risks of chronic complications in diabetes. METHODS: We enrolled 1052 patients with type 2 diabetes. The mean follow-up was 4.7 years. The HbA1c level and frequency of SMBG were recorded every 3 months. Non-mydriatic retinal photography, semiquantitative neuropathy assessment, the lipid profile, serum creatinine level, and urine protein were measured at the beginning of the study and then every year. The fluctuation in HbA1c throughout the period was expressed as the standard deviations (SDs) of all measurements of the HbA1c. RESULTS: The frequency of SMBG was significantly and negatively correlated with the SDs of the HbA1c (r = -0.553, p < 0.001) but not with the average HbA1c. After controlling for age, sex, body mass index, duration of diabetes and comorbidities (dyslipidemia and hypertension), the correlation was still apparent (r = -0.511, p = 0.008). Patients with progression of nephropathy, neuropathy, and retinopathy, exhibited greater fluctuation of HbA1cs (2.38 ± 0.99 vs. 0.93 ± 1.16, p-value 0.002; 0.97 ± 1.59 vs. 0.90 ± 0.56, p-value 0.04; 0.99 ± 1.33 vs. 0.90 ± 0.56, p-value 0.04, respectively) and less frequent SMBG (3.2 ± 2.6 vs. 4.3 ± 3.1, p-value 0.02; 3.2 ± 2.6 vs. 4.1 ± 3.9, p-value 0.05; 3.0 ± 3.1 vs. 4.2 ± 2.8, p-value 0.01, respectively) than patients without progression of these complications. CONCLUSION: This study shows that frequent SMBG decreased the fluctuation of HbA1c and decreased microvascular complications. Decreasing fluctuation of HbA1c may play an important role in diabetes treatment.

Albuminuria is an independent risk factor of erectile dysfunction in men with type 2 diabetes.

INTRODUCTION: Erectile dysfunction (ED) is a frequent comorbidity in men with diabetes and is frequently overlooked in routine clinical evaluation. Albuminuria, a marker of endothelial dysfunction, may link to ED. AIM: The study evaluated the association of albuminuria with risk factors of ED in men with type 2 diabetes. METHODS: The diagnosis of ED was based on a self-administered questionnaire containing Sexual Health Inventory for Men. Urinary albumin excretion rate was determined by urine albumin-to-creatinine ratio (UACR) in spot urine. MAIN OUTCOME MEASURES: The clinical variables and diabetes-associated complications to risk of ED were evaluated. RESULTS: Of 666 patients who received the questionnaire, 455 patients completed it. Among them, 82.0%, 28.1%, and 35.8% reported having ED, severe ED, and albuminuria, respectively. The UACR level was significantly higher in ED (0.20 ± 0.83) and severe ED (0.34 ± 1.18) groups compared with non-ED group (0.07 ± 0.33). The presence of albuminuria adjusted for age and duration of diabetes was significantly associated with ED (OR = 2.76), and macroalbuminuria has stronger impact (OR = 4.49) than microalbuminuria (OR = 2.48). The other associated risk factors included hypertension, higher level of systolic blood pressure, lower level of serum hemoglobin, and estimated glomerular filtration rate. The presence of retinopathy, neuropathy, insulin therapy, using calcium channel blocker, and higher level of HbA1c further correlated with severe ED. Men with severe ED have higher prevalence of subnormal testosterone than the no ED patients. The high sensitivity C-reactive protein level, and the presence of metabolic syndrome were not risk factors. The 211 nonrespondents to the questionnaire had similar or worse risk profiles compared with the ED patients. CONCLUSION: Albuminuria is an important independent risk factor of ED in men with diabetes after adjustment of age and diabetes mellitus duration. Identification and control of albuminuria and other associated risk factors might play a role in the prevention or reversal of ED.