Hung-Yuan Li

Common Variation in the Fat Mass and Obesity-Associated ( FTO ) Gene Confers Risk of Obesity and Modulates BMI in the Chinese Population

OBJECTIVE— Genetic variants in the fat mass and obesity-associated (FTO) gene have been linked with obesity and type 2 diabetes in European populations. We aimed to test the role of FTO genetic variants in obesity and type 2 diabetes in the Chinese population. RESEARCH DESIGN AND METHODS— We genotyped 19 single-nucleotide polymorphisms (SNPs) spanning from the 3′ end of the neighboring RPGRIP1L gene to the 5′ flanking region of the FTO gene. We analyzed their associations with obesity (638 case and 1,610 control subjects), type 2 diabetes (759 case and 784 control subjects), and obesity-related traits in nondiabetic subjects. RESULTS— Among the 19 SNPs, the rs9939609 A allele was strongly associated with obesity (P = 7.0 × 10−4) and BMI (P = 0.0024) in the Chinese population. The odds ratio for obesity was 2.60 (95% CI 1.24–5.46) (P = 0.011) for the AA genotype and 1.32 (1.05–1.66) (P = 0.018) for the AT genotype compared with the TT genotype. Each additional copy of the rs9936609 A allele was associated with a BMI increase of ∼0.37 kg/m2. The rs9939609 A allele was substantially less common in the Chinese population than in the European population (12.6 vs. 45%). We did not find significant associations of the 19 SNPs with type 2 diabetes or other obesity-related traits. CONCLUSIONS— Genetic variation in the FTO gene is strongly associated with obesity and BMI in the Chinese population. The risk variant is less common in the Chinese population, but its effect size on BMI is comparable with that in the European population.

Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999–2004: a national health insurance data set study

Diabet. Med. 27, 636–643 (2010)

Cross-Sectional Validation of Diabetes Risk Scores for Predicting Diabetes, Metabolic Syndrome, and Chronic Kidney Disease in Taiwanese

OBJECTIVE To validate the performance of current diabetes risk scores (DRSs) based on simple clinical information in detecting type 2 diabetes, metabolic syndrome (MetSyn), and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS The performance of 10 DRSs was evaluated in a cross-sectional population screening of 2,759 Taiwanese subjects. RESULTS All DRSs significantly correlated with measures of insulin resistance, estimated glomerular filtration rate, and urine albumin excretion. The prevalence of screening-detected diabetes (SDM), MetSyn, and CKD increased with higher DRSs. For prediction of SDM, the Cambridge DRS by Griffin et al. and the Finnish DRS outperformed other DRSs in terms of discriminative power and model fit. For prediction of MetSyn and CKD, the Atherosclerosis Risk in Community Study score by Schmidt et al. outperformed other DRSs. CONCLUSIONS Risk scores based on simple clinical information are useful to identify individuals at high risk for diabetes, MetSyn, and CKD in different ethnic populations.

Birth Weight Correlates Differently with Cardiovascular Risk Factors in Youth

Objective: Childhood obesity has become prevalent, resulting in a greater risk of hypertension, diabetes, and dyslipidemia. However, the relationship between these comorbid conditions and birth weight remains uncertain. We conducted this study to evaluate the relationship between birth weight and cardiovascular risk factors in children and adolescents.

Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia

BACKGROUND Primary aldosteronism (PA) is a common curable disease of secondary hypertension. Most such patients have either idiopathic bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA). Bilateral APAs are reportedly extremely rare. AIM To compare the distinctive characteristics, clinical course, and outcomes of bilateral APA vs. BAH. DESIGN Retrospective record review. METHODS From July 1994 to Jan 2007, 190 patients diagnosed with PA underwent surgical intervention at our hospital. Bilateral APA was diagnosed in 7/164 patients with histologically-proven APA. Twenty-one patients diagnosed as BAH, and 21 randomly selected of unilateral APA patients, matched by age and sex served as controls. RESULTS Patients with bilateral APA had similar blood pressure, arterial blood gas analysis, spot urinary potassium to creatinine ratio and clinical symptoms to those with BAH, but lower serum potassium levels (p = 0.027), lower plasma renin activity (p = 0.037), and higher plasma aldosterone concentrations (p = 0.029). Aldosterone-renin ratio (ARR) after administration of 50 mg captopril was higher in bilateral APA than in BAH patients (p = 0.023), but not different between unilateral APA and BAH (p = 0.218). A cut-off of ARR >100 ng/dl per ng/ml/h and plasma aldosterone >20 ng/dl after captopril significantly differentiated bilateral APA from BAH. Bilateral subtotal adrenalectomy normalized blood pressure and biochemistry in all patients with bilateral APA. DISCUSSION Bilateral APA, presenting simultaneously or sequentially, may not be a rare disease, accounting for 4.3% of APA in this sample. The clinical presentations of bilateral functional adenoma are not different from BAH, but patients with low serum potassium and ARR >100 after captopril should be carefully evaluated for bilateral adenoma.

Serum Vascular Adhesion Protein-1 Predicts 10-Year Cardiovascular and Cancer Mortality in Individuals With Type 2 Diabetes

OBJECTIVE Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 correlates positively with both acute hyperglycemia and diabetes. We conducted a cohort study to evaluate whether serum VAP-1 predicts 10-year survival in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Between July 1996 and June 2003, we enrolled 661 type 2 diabetic subjects at National Taiwan University Hospital. Serum VAP-1 in the samples obtained at enrollment was measured by time-resolved immunofluorometric assay. The vital status of all subjects was ascertained by linking their data with computerized death certificates in Taiwan. RESULTS The medium follow-up period was 10.4 years. Subjects with serum VAP-1 in the highest tertile had a hazard ratio (HR) of 2.19 (95% CI 1.17–4.11) for all-cause mortality adjusted for age, sex, smoking, history of cardiovascular disease, obesity, hypertension, hemoglobin A1c, diabetes duration, total cholesterol, use of statins, abnormal ankle-brachial index, estimated glomerular filtration rate (eGFR), and proteinuria. The adjusted HRs for logarithmically transformed serum VAP-1 were 5.83 (95% CI 1.17–28.97) for cardiovascular mortality, 6.32 (95% CI 1.25–32.00) for mortality from cardiovascular and diabetic causes, and 17.24 (95% CI 4.57–65.07) for cancer mortality. There were four variables, including age, serum VAP-1, proteinuria, and eGFR, which could enhance mortality prediction significantly. CONCLUSIONS Serum VAP-1 can predict 10-year all-cause mortality, cardiovascular mortality, and cancer mortality independently in type 2 diabetic subjects. Serum VAP-1 is a novel biomarker that improves risk prediction over and above established risk factors.

Serum vascular adhesion protein-1 is increased in acute and chronic hyperglycemia

BACKGROUND The relationship between serum vascular adhesion protein-1 (VAP-1) and plasma glucose in normal and drug-naïve type 2 diabetes subjects is unclear. We examined if serum VAP-1 changed acutely to oral glucose loading and analyzed the relationship between serum VAP-1, fasting plasma glucose (FPG), hemoglobin A1c, and type 2 diabetes. METHODS Adults without history of diabetes were included. Subjects taking anti-diabetic drugs were excluded. Serum VAP-1 was analyzed by time-resolved immunofluorometric assay. RESULTS We recruited 333 subjects (186 females and 147 males), aged 56.1 +/- 11.6 y. After glucose challenge, serum VAP-1 rose significantly at 30 min (p < 0.0001) and lasted until 2 h (p < 0.0001). The change of serum VAP-1 between fasting and 30-min postload correlated inversely to the change of plasma insulin (r = -0.21, p = 0.049). Fasting serum VAP-1 was associated with FPG in those with FPG > or = 5.55 mmol/l (p = 0.025) but not in those with FPG < 5.55 mmol/l (p = NS). Fasting serum VAP-1 were higher in diabetic subjects (p = 0.04) and correlated positively to hemoglobin A1c (r = 0.18, p = 0.002) after adjusting for age, gender, and waist circumference. CONCLUSIONS Serum VAP-1 is increased in both acute and chronic hyperglycemia. Whether serum VAP-1 is a good biomarker for hyperglycemia-associated complications merits further investigation.

Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease

OBJECTIVES An increased level of serum vascular adhesion protein-1 (VAP-1) has been found in patients with diabetes mellitus and vascular disorders. This study examined whether serum VAP-1 levels are associated with chronic kidney disease (CKD). DESIGN AND METHODS We included 262 subjects aged 30 and above with fasting plasma glucose level <7 mmol/L checked within 1 year. First morning urine specimens were collected. Microalbuminuria was defined if urinary albumin-to-creatinine ratio > or =30 microg/mg creatinine. The glomerular filtration rate (GFR) was estimated. CKD stages were defined according to the suggestions of the National Kidney Foundation. Serum VAP-1 levels were analyzed by immunofluorometric assay. RESULTS Serum VAP-1 levels were positively associated with the urinary albumin-to-creatinine ratio (r=0.29, p<0.0001) and negatively associated with estimated GFR (r=-0.24, p=0.0001). Subjects with CKD stage 2 (N=51) and stage 3 (N=91) had significantly higher levels of serum VAP-1 than those without CKD (p=0.0003 and p=0.035, adjusted for age and gender, respectively). A high serum VAP-1 level was associated with the presence of CKD (OR 1.63 for 1 SD increase of VAP-1, p=0.018), adjusting for age, sex, and smoking. Ordered logit models revealed that high serum VAP-1 levels correlated with advanced stages of CKD. CONCLUSIONS Serum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. The true mechanism which links the serum VAP-1 and CKD remains to be elucidated in further studies.

Procedural Safety and Potential Vascular Complication of Endovascular Recanalization for Chronic Cervical Internal Carotid Artery Occlusion

Background—Patients with chronic cervical internal carotid artery occlusion (ICAO) and cerebral ischemia may benefit from revascularization. The feasibility of endovascular recanalization for chronic ICAO has been reported recently, but its safety is still unproven. We report the follow-up results of 54 chronic ICAO patients who underwent endovascular recanalization, focusing on potential vascular complications and corresponding management. Methods and Results—Endovascular recanalization for chronic ICAO was attempted in 54 consecutive patients (48 men; 69.2±9.8 years old) with either recurrent neurological deficit or objective ipsilateral hemisphere ischemia. Mean duration from occlusion documentation to the procedure was 237±327 days (range, 56 to 1424 days). Adverse events while in the hospital and during the 3-month follow-up were recorded. Successful recanalization was achieved in 35 of 54 patients (65%). Three-month cumulative stroke and death rate was 4% (2 of 54), including 1 in-hospital fatal nonipsilateral stroke and 1 in-hospital minor ipsilateral stroke secondary to systemic hypotension. Vascular complications developed in 3 of 54 patients (6%), including 1 late pseudoaneurysm formation 3 months after recanalization, 1 immediate carotid-cavernous fistula after recanalization, and 1 minor extravasation at carotid bifurcation after failed recanalization. However, no clinical sequela was noted with close follow-up and adequate management. Conclusion—Certain immediate or delayed vascular complications may develop during or after the endovascular recanalization for chronic ICAO. Although periprocedural death and stroke rate is limited in our study, further study combining neuroimaging tools and cognitive function evaluation is mandatory to assess its utility and appropriateness in patients with chronic ICAO.

Neurocognitive Improvement After Carotid Artery Stenting in Patients With Chronic Internal Carotid Artery Occlusion and Cerebral Ischemia

Background and Purpose— Chronic cerebral hypoperfusion may lead to impairment in neurocognitive performance in patients with chronic internal carotid artery occlusion, and the effects of carotid artery stenting on neurocognitive function have been unclear. Methods— We prospectively enrolled 20 chronic internal carotid artery occlusion patients with objective ipsilateral hemisphere ischemia, in whom carotid artery stenting was attempted. Functional assessments, including the National Institutes of Health Stroke Scale, Barthel Index, and a battery of neuropsychological tests, including the Mini-Mental State Examination, Alzheimer Disease Assessment Scale–Cognitive Subtest, verbal fluency, and Color Trail Making A and B, were administered before and 3 months after intervention. Results— Successful recanalization was achieved in 12 of 20 patients (60%). There was no procedural or new cerebral ischemic event, except for 1 intracranial hemorrhage, which occurred during the procedure and had neurologic sequelae; this case was excluded from analysis. The demographics and baseline cognitive performance were similar between the group with a successful outcome (group 1, n=12) and patients who did not (group 2, n=7). Ten of 12 patients in group 1 had improvement in ipsilateral brain perfusion after the procedure, but none in group 2 had improvement. Significant improvement in the scores on the Alzheimer Disease Assessment Scale–Cognitive Subtest (before, 7.7±8.9 versus after, 5.7±7.1; P=0.024), Mini-Mental State Examination (before, 25.8±3.8 versus after, 27.7±2.7; P=0.015), and Color Trail Making A (before, 123.2±68.6 versus after, 99.3±51.5; P=0.017) were found in group 1 but not in group 2. Conclusions— Successful carotid artery stenting improves global cognitive function as well as attention and psychomotor processing speed in patients with chronic internal carotid artery occlusion.