Huey-Peir Wu

Investigation of urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in women with type 2 diabetes.

PURPOSE We studied urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in diabetic women. MATERIALS AND METHODS A total of 86 consecutive type 2 diabetic women with minimal confounders of voiding dysfunction followed at a diabetes clinic were prospectively enrolled and subjected to urodynamic studies. The sensory response of Adelta and C fibers of the bladder was measured by intravesical current perception threshold testing at frequencies of 250 and 5 Hz, respectively. RESULTS Of these 86 women 30 (34.9%) were classified as having detrusor underactivity, 12 (14.0%) presented signs of detrusor overactivity, 11 (12.8%) were referred to as having bladder outlet obstruction and 33 (38.4%) showed normal detrusor function on urodynamics. The normal detrusor function group was the reference group. The detrusor underactivity group showed impaired emptying function and decreased sensation on cystometry and intravesical current perception threshold testing. The detrusor overactivity group showed impaired storage and emptying function but had no significant changes in intravesical current perception threshold values. When the normal detrusor function group and detrusor underactivity group were pooled to perform multivariate analysis, an increase in current perception threshold values was associated with a decrease in bladder voiding efficiency on 5 and 250 Hz current perception threshold testing. CONCLUSIONS Our data provide the electrophysiological evidence that indicates an association between impaired Adelta as well as C fiber bladder afferent pathways and poor emptying function in diabetic women with detrusor underactivity. Diabetes can affect the bladder presumably via peripheral pathogenetic mechanisms to induce detrusor overactivity with impaired contractility.

Metabolic Syndrome Components Worsen Lower Urinary Tract Symptoms in Women with Type 2 Diabetes

CONTEXT Diabetic women are more susceptible to develop lower urinary tract symptoms (LUTS), especially overactive bladder (OAB). However, data regarding the effect of components of metabolic syndrome (MS) on this association are conflicting. OBJECTIVE The objective of the study was to examine the potential role of MS in the development of LUTS in diabetic women. DESIGN The study was a prevalence study conducted between 2005 and 2007. SETTING The study was conducted in a university hospital. PARTICIPANTS A total of 518 women with type 2 diabetes aged 50-75 yr were included. They were subgrouped as MS (47.5%) and non-MS (52.5%) groups according to whether they fulfilled the criteria of MS. MAIN OUTCOME MEASURE We used American Urological Association Symptom Index (AUA-SI) to evaluate LUTS and Indevus Urgency Severity Scale to evaluate OAB, respectively. RESULTS Women in the MS group had significantly higher storage and total AUA-SI scores as well as a higher prevalence of LUTS and OAB. Most intriguingly, the number of MS components was strongly associated with the LUTS severity because the AUA-SI scores increased in parallel to the number of components were present. Similar results were found between MS and OAB. Multivariate analysis revealed that peripheral neuropathy, but not MS, significantly predicted LUTS in diabetic women after age adjustment. However, MS remained significantly predictive for LUTS and OAB after additional adjustment for neuropathy. CONCLUSIONS Our results suggest that MS may especially influence LUTS and OAB in diabetic women, probably by compounding the effect of peripheral neuropathy.

QUANTITATIVE SENSORY TESTING AND RISK FACTORS OF DIABETIC SENSORY NEUROPATHY

Abstract The goal of this study was to identify risk factors for diabetic peripheral sensory neuropathy in type 2 diabetes mellitus in a Chinese population. Peripheral sensory neuropathy was detected by quantitative sensory testing (5.07/10 g monofilament, neurometer and 128-Hz Riedel Seiffert graduated tuning fork). Those who had two or more abnormal quantitative sensory testings were defined as having diabetic sensory neuropathy. Of the 558 non-insulin dependent diabetes mellitits subjects, 62 (11.1%) had peripheral neuropathy. In 59 (10.6%) detection was by monofilament testing, 45 (8.1%) by graduated tuning fork, and 189 (33.9%) by neurometer. In a multivariate logistic regression model, age and insulin therapy were significantly associated with peripheral neuropathy. Age, serum triglyceride, height, and fasting plasma glucose were independently associated with large fiber neuropathy. Our results confirm the previously identifed multiple risk factors of diabetic neuropathy. Different quantitative sensory testings detect different nerve fiber defects. The weak correlation between these tests indicates the need to use more than one test in screening for diabetic neuropathy.

Development of Macrovascular Diseases in NIDDM Patients in Northern Taiwan: A 4-yr follow-up study

Objective— To assess the development of macrovascular diseases and explore major associative factors in NIDDM. Research Design and Methods— A total of 479 NIDDM patients ≥ 40 yr of age were recruited from four community primary care health centers of northern Taiwan in July 1986 for a cohort study with a 4-yr follow-up. No patient required insulin therapy within 1 yr of diagnosis nor had a history of diabetic ketoacidosis. All were able to participate independently in the activities of daily living. BP and ECG were measured, and a structured questionnaire was asked of each patient. Venous blood after overnight fasting was collected every year to measure cholesterol, HDL cholesterol, plasma glucose, and HbA1c. Results— The duration of diabetes was associated with the development of stroke with a relative risk of 1.063 for every 1-yr increment (P = 0.07). As for HVDs, the significant risk factors were serum cholesterol and HbA1c. For every 1-mg/dl increase in mean total cholesterol level, the relative risk of developing HVD increased 1.016-fold (P = 0.04). For every 1% increase in HbA1c, the relative risk of developing HVD increased 1.170-fold (P = 0.01). With regard to leg VDs, sex and cigarette smoking were significant risk factors. Women diabetic subjects had a higher relative risk than men. Cigarette smoking was significantly associated with leg VD with a relative risk of 6.9 for smokers compared with nonsmokers. The most significant risk factor for LVD was the total cholesterol level. For every 1-mg/dl increase in mean serum cholesterol level, the relative risk of LVD increased 1.013-fold. Conclusions— In the prevention of macrovascular diseases, effective intervention of the nondiabetic cardiovascular risk factors may be as important as or even more important than the good control of diabetes.

No association between the Gly971Arg variant of the insulin receptor substrate 1 gene and NIDDM in the Taiwanese population.

OBJECTIVE To study the role of the Gly971 Arg variant of the insulin receptor substrate 1 (IRS-1) gene in the development of NIDDM in the Chinese population living in Taiwan. RESEARCH DESIGN AND METHODS A total of 82 unrelated normal control subjects, 89 subjects with NIDDM, and 23 multiplex families were recruited in Taiwan. All of them were Han Chinese. Pedigree members without a history of diabetes were studies by the standard 75-g oral glucose tolerance test. Detection of the Gly971 Arg variant of the IRS-1 gene was performed by polymerase chain reaction and restriction fragment-length polymorphism analysis. RESULTS The frequency of Gly971 Arg variant of the IRS-1 gene in the normal population was 1.2% which was lower than frequencies reported in white populations. The prevalence of the Gly971 Arg variant was not significantly increased in both the nonselected NIDDM population (1.1%) and the probands of the multiplex families (4.3%). More importantly, the Gly971 Arg variant of the IRS-1 gene did not cosegregate with BMI and NIDDM in these families, CONCLUSIONS The Gly971 Arg variant of the IRS-1 gene is an infrequent normal allele among Taiwanese. This variant is neither associated nor cosegregated with NIDDM in the Taiwanese population and families. Gly971 Arg of IRS-1 gene does not play an important role in the development of NIDDM in this population.

Anti‐GAD65 autoantibody in Taiwanese patients with insulin‐dependent diabetes mellitus: effect of HLA on anti‐GAD65 positivity and clinical characteristics

Anti‐GAD65 antibody has been studied widely in patients with insulin‐dependent diabetes mellitus (IDDM) in many different populations. However, the prevalence of GAD65 autoantibody has not been assessed in Taiwanese patients with IDDM. We therefore characterized GAD65 antibody and investigated the effect of HLA‐DR phenotypes on GAD65 autoimmunity and other clinical characteristics in Taiwanese subjects with IDDM.

A rapid method to study heat shock protein 70-2 gene polymorphism in insulin-dependent diabetes mellitus

To examine the role of DNA loci within the human leukocyte antigen (HLA) region and insulin-dependent diabetes mellitus (IDDM), we studied fine mapping of HSP70-2 gene. Polymerase chain reaction (PCR)-based genotyping was then developed and applied to type HSP70-2 in 59 patients with IDDM and 83 unrelated controls recruited from the inhabitants of northern Taiwan. Southern blot analysis revealed a diallelic PstI polymorphism of the HSP 70-2 gene, i.e., 9.6- and 8.5-kb alleles. The polymorphic site was mapped in the intragenic PstI sequences (nucleotides 1051-1056) of the HSP70-2 gene. PCR-based restriction fragment length polymorphism studies revealed that the frequency of the 8.5-kb allele was increased in IDDM (56.8%, vs. 40.4% in controls; p < 0.009), with a relative risk of 1.93 (95% confidence interval = 1.20-3.11). The genotypic frequencies of 9.6/9.6, 9.6/8.5, and 8.5/8.5 were 17.0, 52.5, and 30.5% for IDDM were different from those of controls (36.1, 47.0, and 16.9%, respectively; the homozygous 9.6/ 9.6 genotype was significantly decreased in the IDDM group, p < 0.02). In conclusion, we provide a simple, rapid, and nonradioactive method for HSP70-2 genotyping. Our data confirmed that the 8.5-kb allele of HSP70-2 was associated with IDDM susceptibility in the Taiwanese population.

HLA-DQB1 Codon 57 and IDDM in Chinese Living in Taiwan

OBJECTIVE To study the human leukocyte antigen (HLA)-DQB1 genetic background in the Chinese population in Taiwan and its association with the low incidence of insulin-dependent diabetes mellitus (IDDM) in this population. RESEARCH DESIGN AND METHODS Forty-eight IDDM patients and 59 nondiabetic unrelated control subjects were recruited from the population in Taiwan. HLA-DQB1 exon 2 was enzymatically amplified by polymerase chain reaction. HLA-DQBl alleles were diagnosed by dot blotting and hybridization with 16 sequence-specific oligonucleotide probes. RESULTS DQB1*0201 and DQB1*0302 alleles were more frequent and DQB1*0301 and DQB1*0601 were less frequent in Chinese with IDDM than in control subjects. Genotypes for homozygous non-aspartic acid residue (NA/NA) at position 57 were positively associated with IDDM at a relative risk of 4.34 (P < 0.001), and those for homozygous aspartic acid (A/A) were negatively associatedwith IDDM at a relative risk of 0.14 (P < 0.001). Among the NA/A heterozygotes, only DQB1*0201/ DQB1*0303 was significantly increased in IDDM subjects. CONCLUSIONS The amino acid residue at position 57 of HLA-DQ β3-chain is significantly associated with the development or prevention of IDDM in Chinese subjects living in Taiwan. Other genetic and environmental factors may also play important roles in pathogenesis of IDDM.

Mitochondrial gene mutations in familial non-insulin-dependent diabetes mellitus in Taiwan

Mitochondrial gene mutations are found to cause certain forms of diabetes mellitus and related syndromes. To study the prevalence of mitochondrial gene mutations in subjects with non‐insulin‐dependent diabetes mellitus (NIDDM) in Taiwan, 23 pedigrees with multiple siblings affected with NIDDM were consecutively collected from patients living in northern Taiwan. The A‐to‐G mutation at position 3243 np in the tRNALeu gene and the mutation at position 8344 were screened by PCR‐RFLP methods and confirmed by direct DNA sequence analysis. Among 23 NIDDM pedigrees, one pedigree was found to carry the 3243 np mutation. There was no 8344 np mutation in this series. Clinical features of this pedigree were consistent with mitochondrial disease in terms of maternal transmission, relatively early onset, non‐obesity, insulin‐requirement and association with hearing impairment. There was no correlation between the degree of heteroplasmy of mitochondrial gene mutation in leukocyte DNA and clinical severity. We conclude that a mitochondrial gene defect is an important genetic factor in familial cases with NIDDM in Taiwan.

Inhibitory effect of islet amyloid polypeptide of glucose-induced proinsulin biosynthesis in rat insulinoma cells

Islet amyloid polypeptide (IAPP) has been recently identified as the principal constituent of amyloid deposits in pancreatic islets of patients with type 2 (non-insulin-dependent) diabetes mellitus and causes insulin resistance in some target cells. In addition, glucose-induced insulin secretion is inhibited by IAPP. We studied the effect of IAPP on proinsulin biosynthesis in rat insulinoma (RINr) cells. Glucose at concentrations of 0, 15, 30, 60, 100, and 300 mg/dl stimulated proinsulin biosynthesis in a dose-responsive and actino-mycin D-inhibitable manner after 6 h of incubation. At a glucose concentration of 300 mgldl, IAPP decreased the mean responses of proinsulin biosynthesis to 61.2 and 29% at concentrations of 0.1 and 1 μM, respectively, compared with the IAPP-free control. In conclusion, IAPP inhibits glucose-induced proinsulin biosynthesis in RINr cells. IAPP might play an important role in the pathogenesis of type 2 diabetes mellitus.