Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2 Diabetes: The Hong Kong Diabetes Database.

OBJECTIVE: Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time. RESULTS: Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%. CONCLUSIONS: From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period.

Control of exciton confinement in quantum dot-organic complexes through energetic alignment of interfacial orbitals.

This paper describes a method to control the quantum confinement, and therefore the energy, of excitonic holes in CdSe QDs through adsorption of the hole-delocalizing ligand phenyldithiocarbamate, PTC, and para substitutions of the phenyl ring of this ligand with electron-donating or -withdrawing groups. These substitutions control hole delocalization in the QDs through the energetic alignment of the highest occupied orbitals of PTC with the highest density-of-states region of the CdSe valence band, to which PTC couples selectively.

Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3.

Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of thyrotoxicosis. We conducted a genome-wide association study (GWAS) and a replication study with a total of 123 southern Chinese with TPP (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (rs312691: odds ratio (OR) = 3.3; P(meta-analysis) = 1.8 × 10(-14)). All subjects with TPP also had Graves' disease, and subsequent TPP versus Graves' disease comparison confirmed that the association at 17q24.3 was specific to TPP. The area under the curve (AUC) of rs312691 genotype for risk prediction of TPP in subjects with Graves' disease was 0.73. Expression quantitative trait locus (eQTL) analysis identified SNPs in the region flanking rs312691 (±10 kb) that could potentially affect KCNJ2 expression (P = 0.0001). Our study has identified a susceptibility locus associated with TPP and provides insight into the causes of TPP.

Determinants of peak bone mineral density and bone area in young women.

Osteoporosis is a disease caused by compromised bone strength, and individuals with a high peak bone mass at a young age are likely to have a high bone mass in old age. To identify the clinical determinants of peak bone mass in young adult women, 418 southern Chinese women, aged 20-39 years, were studied. Low bone mass was defined as areal bone mineral density (aBMD) Z-score < -1 at either the spine or total hip. Within the cohort, 62 (19.0%) and 86 (26.4%) women had low aBMD at the spine and hip, respectively. Regression model analysis revealed that low body weight (<44 kg) was associated with an 8.3-fold (95% CI, 3.7-18.9) and a 6.8-fold (95% CI, 3.0-15.6) risk of having low aBMD at the spine and hip, respectively. Low body weight was also predictive of low volumetric BMD (vBMD) at the spine (odds ratio (OR) 7.8, 95% CI, 3.1-20.1) and femoral neck (OR 3.0, 95% CI, 1.3-7.1). A body height below 153 cm was associated with a 4.8-fold risk in the small L2-4 bone area (95% CI, 2.3-9.8) and a 3.9-fold risk in the small femoral neck area (95% CI, 1.9-8.1). Delayed puberty (onset of menstruation beyond 14 years) was associated with a 2.2-fold (95% CI, 1.0-4.9) increased risk of having low aBMD at the hip. Physical inactivity was associated with a 2.8-fold risk of low spine vBMD (OR 2.8, 95% CI, 1.1-6.7) and a 3.3-fold risk of low hip aBMD (95% CI, 1.0-10.0). Pregnancy protected against low spine aBMD (OR 0.4, 95% CI, 0.1-1.2) and spine vBMD (OR 0.1, 95% CI, 0.0-1.0), low femoral neck vBMD (OR 0.3, 95% CI, 0.1-1.1) and small L2-4 bone area vBMD (OR 0.3, 95% CI, 0.1-1.1). In conclusion, this study identified a number of modifiable determinants of low peak bone mass in young adult women. Maintaining an ideal body weight, engaging in an active lifestyle, and diagnosing late menarche may enable young women to maximize their peak bone mass and so reduce their risk of osteoporosis in later life.

Efficacy and tolerability of alendronate once weekly in Asian postmenopausal osteoporotic women.

BACKGROUND: Osteoporosis has become a major health problem worldwide, and the incidence is rising in Asian countries. The aminobisphosphonates are potent inhibitors of bone resorption and are currently the mainstay of treatment for postmenopausal osteoporosis. Dosing frequency will likely affect tolerability and adherence to treatment. OBJECTIVE: To assess the tolerability and efficacy of a once-weekly aminobisphosphonate preparation in improving bone mineral density (BMD) and bone turnover markers in osteoporotic Asian women. METHODS: Chinese postmenopausal women with osteoporosis were randomized to receive either alendronate 70 mg once weekly plus calcium carbonate 500 mg daily (n = 29) or calcium carbonate 500 mg daily (n = 29) for one year. BMD was measured by dual energy X-ray absorptiometry. Markers of bone formation and bone resorption included plasma total alkaline phosphatase and urine N-telopeptides. RESULTS: Treatment with alendronate 70 mg once weekly for one year resulted in significant BMD improvement of 6.1% at the spine, 5.6% at the femoral neck, and 3.5% at the total hip. There was no significant change in the BMD values in the calcium group (spine 1.4%, femoral neck -0.2%, total hip 0%). The BMD response in the alendronate group was significantly different from that in the calcium group at all time points, and the difference was detectable as early as after 3 months of treatment (ANOVA p < 0.001). The changes remained significant after adjusting for age, age at menarche, and years since menopause (p < 0.001). Similarly, the reductions in bone markers at 12 months were significantly different between the 2 treatment groups (plasma total alkaline phosphatase: alendronate 27.9%, calcium 5.4%; urine N-telopeptide: alendronate 55.6%, calcium 11.2%; both p < 0.001). The alendronate regimen was well tolerated, without significant adverse events. CONCLUSIONS: The results confirmed that once-weekly alendronate was efficacious in increasing BMD and reducing bone turnover and was well tolerated in Asian women.

The efficacy and tolerability of risedronate on bone mineral density and bone turnover markers in osteoporotic Chinese women: a randomized placebo-controlled study.

Osteoporosis has become an important health problem in postmenopausal Asian populations as the prevalence of hip and vertebral fractures in some Asian countries has risen to approach that of Caucasian populations. Risedronate, a pyridinyl-bisphosphonate agent, is a potent inhibitor of bone resorption. Risedronate increases bone mineral density (BMD), reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. To determine the efficacy and tolerability of risedronate in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in Hong Kong. Sixty-five (65) postmenopausal osteoporotic Southern Chinese women, aged 67+/-6 years, were randomly assigned to receive either risedronate 5 mg daily (n=31) or placebo (n=34) for 12 months. All women received calcium carbonate 500 mg daily and vitamin D 400 IU daily. Mean baseline BMD T-score at the spine and total hip was -3.4 and -2.6, respectively. A significant increase in spine BMD was already evident at month 3 of risedronate treatment (P<0.001). Risedronate significantly increased BMD and reduced bone turnover markers as compared with placebo. The risedronate group had significant increase in BMD at 12 months at both the spine and hip when compared with the placebo group (L1-4 6.6% vs. 0.4%, P<0.001; total hip 2.7% vs. 0.3, P<0.0001; femoral neck 1.8% vs. 1.1%, P<0.02; trochanter 4% vs. 1.1%, P<0.0001, respectively). Significant changes in urine N-telopeptide (NTx) and serum osteocalcin were evident as early as 1 and 3 months, respectively, with risedronate treatment. No significant changes were seen in both BMD and bone markers in the placebo group. Risedronate was well tolerated without major adverse effects. We conclude that risedronate is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Asian population.

Development of a clinical assessment tool in identifying Asian men with low bone mineral density and comparison of its usefulness to quantitative bone ultrasound.

Osteoporosis in men is a largely neglected condition in Asia (and elsewhere), despite the fact that one-third of hip fractures occur in men. Moreover, access to bone mineral density (BMD) measurements is limited in many areas of Asia, and inexpensive methods of targeting high risk patients for BMD measurements would be valuable. We have developed a simple clinical assessment tool to identify high risk Asian men for BMD measurements. Information on risk factors was collected from 420 community-dwelling adult Chinese men aged 50 years and above using a structured questionnaire, and the ability of these risk factors to identify subjects with femoral neck BMD T score < or = -2.5 was assessed. Multiple regression analysis and item reduction yielded a final clinical risk assessment tool based on only age and weight, similar to the Osteoporosis Self-assessment Tool for Asians (OSTA), described previously for Asian women. The OSTA values of < or = -1 had a sensitivity of 81% and specificity of 66%, and the area under the receiver operating characteristics curve was 0.83. The index was validated in another sample of 356 men with a sensitivity of 82% and specificity of 67 %, and an AUC of 0.85. The usefulness of OSTA was further compared to calcaneal quantitative bone ultrasound (QUS) in the validation sample of 356 men. The optimal cutoff T score of -1.2 for QUS yielded sensitivity and specificity values of 75 and 67%, respectively. The AUC for QUS was 0.79. Combining OSTA and QUI gave a sensitivity of 88% and specificity of 66% to identify men with low BMD at the femoral neck, and an AUC of 0.86 which was statistically not different from either OSTA or QUI alone. We conclude that OSTA is a simple and effective clinical risk assessment tool for identifying not only female but also male subjects at increased risk of osteoporosis, and its use could facilitate the appropriate and more cost-effective use of bone densitometry in developing countries.

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial.

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.

Comparison of a simple clinical risk index and quantitative bone ultrasound for identifying women at increased risk of osteoporosis.

Osteoporosis is a growing problem in Asia, and early identification of at risk subjects for preventive measures is likely the most cost-effective method for managing this disease in developing countries. Patients with low bone mineral density (BMD) have a high risk of future fracture. However, access to BMD measurements is limited in many areas of Asia, and inexpensive methods of targeting high-risk patients for BMD measurements would be valuable. We compared two methods, a simple clinical risk assessment tool, the Osteoporosis Self-assessment Tool for Asians (OSTA), and quantitative bone ultrasound (QUS) in identifying subjects with low BMD by DXA in 722 southern Chinese postmenopausal women recruited from the community in Hong Kong. Using the published cutoff value of -1 (versus 0 or higher) for OSTA to identify subjects with femoral neck BMD T-score < or =-2.5, basing on our local population peak young mean value, the sensitivity and specificity was 88% and 54% respectively. The optimal cutoff T-score of -2.35 for QUS yielded sensitivity and specificity values of 81% and 65%, respectively. The AUC for QUS was 0.78, which was not significantly different from that of 0.80 for OSTA. Both OSTA and QUS correlated significantly with BMD at the femoral neck (0.62 and 0.36, respectively, P both <0.001). When these cut-off values were used to identify subjects with either lumbar spine or femoral neck BMD T-score < or =-2.5, the sensitivity and specificity was 79% and 60%, respectively, for OSTA, and 69% and 70%, respectively, for QUS. Combining QUS with OSTA improved the sensitivity to 91%, but the specificity was reduced to 44%. We conclude that the simple clinical risk assessment tool OSTA is a free and effective method for identifying subjects at increased risk of osteoporosis, and its use could facilitate the appropriate and more cost-effective use of bone densitometry in developing countries.