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Objective: To compare the efficacy of romosozumab (ROMO) and denosumab (DEN) in prevalent long‐term glucocorticoid (GC) users. Methods: Adult patients receiving oral prednisolone (≥5 mg/day) with high risk of fracture were randomized to receive subcutaneous ROMO (210 mg monthly) or DEN (60 mg 6‐monthly) for 12 months, followed by DEN for two more doses. The primary end point was the change in spine bone mineral density (BMD) from Months 0 to 12. Secondary end points included changes in BMD of the spine/hip/femoral neck and bone turnover markers at various time points and adverse events. Results: Seventy patients (age 62.6 ± 9.1 years; 96% women; median prednisolone dose 5.0 mg/day; duration of therapy 10.7 ± 7.4 years) were enrolled, and 63 completed the study. At Month 12, the spine BMD increased significantly in both ROMO (+7.3% ± 4.5%; p < 0.001) and DEN (+2.3% ± 3.1%; p < 0.001) groups. The absolute spine BMD gain from Months 0 to 12 was significantly greater in ROMO‐treated patients (p < 0.001). Although the total hip BMD at Month 12 also increased significantly in the ROMO (+1.6% ± 3.3%; p = 0.01) and DEN groups (+1.6% ± 2.6%; p = 0.003), the absolute BMD gain was not significantly different between the groups. At Month 24, the spine BMD continued to increase in both the ROMO (+9.7% ± 4.8%; p < 0.001) and DEN group (+3.0% ± 3.0%; p < 0.001) compared to baseline, and the absolute BMD gain remained significantly greater in ROMO‐treated patients. The total hip BMD continued to increase in both groups (ROMO +2.9% ± 3.7%; p < 0.001; DEN +2.2% ± 3.4%; p = 0.001), but the changes from baseline were similar. Injection site reaction was more frequently reported in ROMO‐treated patients. Conclusion: ROMO was superior to DEN in raising the spine BMD at Month 12 in chronic GC users. After switching to DEN, ROMO‐treated patients continued to gain spine BMD to a greater extent than DEN until Month 24. [ABSTRACT FROM AUTHOR]

Aim: To develop 10‐year cardiovascular disease (CVD) risk prediction models in Chinese patients with type 2 diabetes mellitus (T2DM) managed in primary care using machine learning (ML) methods. Methods: In this 10‐year population‐based retrospective cohort study, 141 516 Chinese T2DM patients aged 18 years or above, without history of CVD or end‐stage renal disease and managed in public primary care clinics in 2008, were included and followed up until December 2017. Two‐thirds of the patients were randomly selected to develop sex‐specific CVD risk prediction models. The remaining one‐third of patients were used as the validation sample to evaluate the discrimination and calibration of the models. ML‐based methods were applied to missing data imputation, predictor selection, risk prediction modelling, model interpretation, and model evaluation. Cox regression was used to develop the statistical models in parallel for comparison. Results: During a median follow‐up of 9.75 years, 32 445 patients (22.9%) developed CVD. Age, T2DM duration, urine albumin‐to‐creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), systolic blood pressure variability and glycated haemoglobin (HbA1c) variability were the most important predictors. ML models also identified nonlinear effects of several predictors, particularly the U‐shaped effects of eGFR and body mass index. The ML models showed a Harrell's C statistic of >0.80 and good calibration. The ML models performed significantly better than the Cox regression models in CVD risk prediction and achieved better risk stratification for individual patients. Conclusion: Using routinely available predictors and ML‐based algorithms, this study established 10‐year CVD risk prediction models for Chinese T2DM patients in primary care. The findings highlight the importance of renal function indicators, and variability in both blood pressure and HbA1c as CVD predictors, which deserve more clinical attention. The derived risk prediction tools have the potential to support clinical decision making and encourage patients towards self‐care, subject to further research confirming the models' feasibility, acceptability and applicability at the point of care. [ABSTRACT FROM AUTHOR]

Low levels of high‐density lipoprotein‐cholesterol (HDL‐C) is considered a major cardiovascular risk factor. However, recent studies have suggested a more U‐shaped association between HDL‐C and cardiovascular disease. It has been shown that the cardioprotective effect of HDL is related to the functions of HDL particles rather than their cholesterol content. HDL particles are highly heterogeneous and have multiple functions relevant to cardiometabolic conditions including cholesterol efflux capacity, anti‐oxidative, anti‐inflammatory, and vasoactive properties. There are quantitative and qualitative changes in HDL as well as functional abnormalities in both type 1 and type 2 diabetes. Non‐enzymatic glycation, carbamylation, oxidative stress, and systemic inflammation can modify the HDL composition and therefore the functions, especially in situations of poor glycemic control. Studies of HDL proteomics and lipidomics have provided further insights into the structure–function relationship of HDL in diabetes. Interestingly, HDL also has a pleiotropic anti‐diabetic effect, improving glycemic control through improvement in insulin sensitivity and β‐cell function. Given the important role of HDL in cardiometabolic health, HDL‐based therapeutics are being developed to enhance HDL functions rather than to increase HDL‐C levels. Among these, recombinant HDL and small synthetic apolipoprotein A‐I mimetic peptides may hold promise for preventing and treating diabetes and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Objective: Baseline circulating thrombospondin‐2 (TSP2) level was identified as a potential novel hepatic fibrosis biomarker that associates with development and progression of hepatic fibrosis in patients with nonalcoholic fatty liver disease and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver stiffness (LS), which reflects liver fibrosis on transient elastography. Design: Serum TSP2 levels were measured in participants from a randomized, open‐label intervention study, at baseline and after 24‐weeks treatment of either dapagliflozin 10 mg (N = 30) or sitagliptin 100 mg daily (N = 30). Vibration‐controlled transient elastography was performed to evaluate the severity of hepatic fibrosis and steatosis using LS and controlled attenuation parameter (CAP), respectively. Patients and Measurements: Among all 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.8 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (p =.012), CAP (p =.015) and LS (p =.011) after 24 weeks. Results: Serum TSP2 level decreased significantly from baseline in dapagliflozin‐treated participants (p =.035), whereas no significant change was observed with sitagliptin. In correlation analysis, change in serum TSP2 levels only positively correlated with change in LS (r =.487, p =.006), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment. Conclusions: Serum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and hepatic steatosis, further supporting the potential of serum TSP2 level as a novel hepatic fibrosis biomarker in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the long‐term associations between coronavirus disease 2019 (COVID‐19) and diabetes complications and mortality, in patients with diabetes. Materials and Methods: People with diabetes diagnosed with COVID‐19 infection (exposed group), from 16 March 2020 to 31 May 2021 from the UK Biobank (UKB cohort; n = 2456), and from 1 April 2020 to 31 May 2022 from the electronic health records in Hong Kong (HK cohort; n = 80 546), were recruited. Each patient was randomly matched with participants with diabetes but without COVID‐19 (unexposed group), based on age and sex (UKB, n = 41 801; HK, n = 391 849). Patients were followed for up to 18 months until 31 August 2021 for UKB, and up to 28 months until 15 August 2022 for HK. Characteristics between cohorts were further adjusted with Inverse Probability Treatment Weighting. Long‐term association of COVID‐19 with multi‐organ disease complications and all‐cause mortality after 21 days of diagnosis was evaluated by Cox regression. Results: Compared with uninfected participants, patients with COVID‐19 infection with diabetes were consistently associated with higher risks of cardiovascular diseases (coronary heart disease [CHD]: hazard ratio [HR] [UKB]: 1.6 [95% confidence interval {CI}: 1.0, 2.4], HR [HK]: 1.2 [95% CI: 1.0, 1.5]; and stroke: HR [UKB]: 2.0 [95% CI: 1.1, 3.6], HR [HK]: 1.5 [95% CI: 1.3, 1.8]), microvascular disease (end stage renal disease: HR [UKB]: 2.1 [95% CI: 1.1, 4.0], HR [HK]: 1.2 [95% CI: 1.1, 1.4]) and all‐cause mortality (HR [UKB]: 4.6 [95% CI: 3.8, 5.5], HR [HK]: 2.6 [95% CI: 2.5, 2.8]), in both cohorts. Conclusions: COVID‐19 infection is associated with long‐term increased risks of diabetes complications (especially cardiovascular complications, and mortality) in people with diabetes. Monitoring for signs/symptoms of developing these long‐term complications post‐COVID‐19 infection in the infected patient population of people with diabetes may be beneficial in minimizing their morbidity and mortality. [ABSTRACT FROM AUTHOR]

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Prediabetes and diabetes burden become the strong challenge in the Western Pacific region. Prediabetes with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and the mixed status (IFG + IGT) are considered as risk factors for the development of diabetes. Effective early intervention for prediabetes can significantly delay the progression of the onset of diabetes, even if reverse blood glucose to normal. Increasing evidence shows that without targeted intervention, the progression from prediabetes to diabetes occurs more frequently in Asians compared with Caucasians. Consequently, it is essential to timely detect the populations at higher risk and effectively implement intervention and management to prevent diabetes. Significant evidence also supports the effectiveness of adjusting lifestyle in combination with medication to delay the onset of diabetes. A working group of Western Pacific expertise in diabetes conducted to develop evidence-based consensus recommendations to guide the management of patients with prediabetes. These consensual recommendations are intended to provide a clear and concise approach to the management of individuals with prediabetes. [ABSTRACT FROM AUTHOR]

Objective: Existing studies reported the potential prognostic role of non‐thyroidal illness syndrome (NTIS), characterized by low triiodothyronine (T3) with normal/low thyroid‐stimulating hormone (TSH), mainly in severe COVID‐19. None considered the significant impact of SARS‐CoV‐2 viral load on adverse outcomes. We aimed to clarify the prognostic role of NTIS among predominantly mild‐to‐moderate COVID‐19 patients. Design: A prospective study of COVID‐19 patients. Patients and Measurements: Consecutive adults admitted to Queen Mary Hospital for confirmed COVID‐19 from July to December 2020 were prospectively recruited. SARS‐CoV‐2 viral load was represented by cycle threshold (Ct) values from real‐time reverse transcription‐polymerase chain reaction of the respiratory specimen on admission. Serum TSH, free thyroxine and free T3 were measured on admission. The outcome was deterioration in clinical severity, defined as worsening in ≥1 category of clinical severity according to the Chinese National Health Commission guideline. Results: We recruited 367 patients. At baseline, 75.2% had mild disease, and 27 patients (7.4%) had NTIS. Fifty‐three patients (14.4%) had clinical deterioration. Patients with NTIS were older, had more comorbidities, worse symptomatology, higher SARS‐CoV‐2 viral loads and worse profiles of inflammatory and tissue injury markers. They were more likely to have clinical deterioration (p <.001). In multivariable stepwise logistic regression analysis, NTIS independently predicted clinical deterioration (adjusted odds ratio 3.19, p =.017), in addition to Ct value <25 (p <.001), elevated C‐reactive protein (p =.004), age >50 years (p =.011) and elevated creatine kinase (p =.017). Conclusions: Non‐thyroidal illness syndrome was not uncommon even in mild‐to‐moderate COVID‐19 patients. NTIS on admission could predict clinical deterioration in COVID‐19, independent of SARS‐CoV‐2 viral load, age and markers of inflammation and tissue injury. [ABSTRACT FROM AUTHOR]

Objective: To evaluate surgical outcomes of patients with aldosterone‐producing adenoma (APA) over a 6‐year period from 2009 to 2014 in Hong Kong, and to derive a new scoring system to predict cure of hypertension after surgery. Methodology: This was a retrospective multi‐centre study evaluating 104 APA patients from five major hospitals in Hong Kong. These patients were retrieved using database from Surgical Outcomes Monitoring and Improvement Programme (SOMIP). Their clinical characteristics and surgical outcomes were evaluated. Results: Over a median follow‐up period of 5 years, APA patients who had undergone adrenalectomy had an average decrease in systolic and diastolic blood pressure of 16.9 and 4.8 mm Hg respectively. Cure of hypokalaemia, cure of hypertension and improvement in hypertension occurred in 100%, 48.5% and 40% respectively. When a patient had two of the following three parameters, namely, female sex, duration of hypertension ≤5 years and number of anti‐hypertensives ≤2, the sensitivity and specificity in achieving cure in hypertension was 79.6% and 70.6%, respectively. Surgical complications were uncommon. Conclusions: Adrenalectomy resulted in resolution of hypokalaemia for all and cure of hypertension in half of the patients with APA. It was safe and effective in curing hyperaldosteronism. [ABSTRACT FROM AUTHOR]

Aims: To develop and validate 10‐year risk prediction models, nomograms and charts for end‐stage renal disease (ESRD) in Chinese patients with type 2 diabetes mellitus (T2DM) in primary care, in order to guide individualized treatment. Materials and Methods: This was a 10‐year population‐based observational cohort study. A total of 141 516 Chinese T2DM patients without history of cardiovascular disease or ESRD who were managed in public primary care clinics in 2008 were included and followed up until December 2017. Two‐thirds of these patients were randomly selected to develop sex‐specific ESRD risk prediction models using Cox regressions. The validity and accuracy of the models were tested on the remaining third of patients using Harrell's C‐index. We selected variables based on their clinical and statistical importance to construct the nomograms and charts. Results: The median follow‐up period was 9.75 years. The cumulative incidence of ESRD was 6.0% (men: 6.1%, women: 5.9%). Age, diabetes duration, systolic blood pressure (SBP), SBP variability, diastolic blood pressure, triglycerides, glycated haemoglobin (HbA1c), HbA1c variability, urine albumin to creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) were significant predictors for both sexes. Smoking and total cholesterol to HDL cholesterol ratio were additional significant predictors for men and women, respectively. The models showed Harrell's C‐statistics of 0.889/0.889 (women/men). Age, eGFR, UACR, SBP and HbA1c were selected for both sexes to develop nomograms and charts. Conclusions: Using routinely available variables, the 10‐year ESRD risk of Chinese T2DM patients in primary care can be predicted with approximately 90% accuracy. We have developed different tools to facilitate routine ESRD risk prediction in primary care, so that individualized care can be provided to prevent or delay ESRD in T2DM patients. [ABSTRACT FROM AUTHOR]

Background: The skeletal indication for parathyroidectomy for primary hyperparathyroidism (PHPT) is based on bone mineral density (BMD) T-score < − 2.5. Whether trabecular bone score (TBS) additionally identifies patients who benefit from parathyroidectomy in terms of bone health is unknown. We aimed to study changes in BMD and TBS among Chinese who underwent curative parathyroidectomy for PHPT, in relation to their preoperative parameters, especially in those with worst site BMD T-score ≥ − 2.5 (non-osteoporotic range). Methods: We included consecutive Chinese individuals who underwent curative parathyroidectomy during 2002–2015 for PHPT and completed preoperative and postoperative BMD and TBS measurements in Queen Mary Hospital. Correlations between preoperative parameters and changes in densitometric parameters were studied. Results: 45 Chinese individuals (13 men, 32 women) were included (mean age 62.0 ± 10.0 years and BMI 24.6 ± 4.7 kg/m2). After parathyroidectomy, BMD at lumbar spine (LS) improved by 6.7% (p < 0.001) while TBS did not change. Among women, peak preoperative parathyroid hormone and calcium levels independently predicted LS BMD gain. Among women with BMD in non-osteoporotic range, LS BMD also improved after parathyroidectomy, where preoperative TBS was the only significant variable inversely correlating with percentage change in LS BMD (ρ − 0.775, p = 0.005). Particularly, those with preoperative TBS ≤ 1.25 gained 7.1% LS BMD post-parathyroidectomy (p = 0.003). Conclusions: LS BMD, but not TBS, improved after parathyroidectomy. Among non-osteoporotic PHPT women, preoperative TBS inversely correlated with postoperative BMD improvement. Hence, low preoperative TBS may be an additional indication for surgical benefit with parathyroidectomy in non-osteoporotic PHPT women, as those with worse preoperative TBS tend to benefit more from surgery. [ABSTRACT FROM AUTHOR]

Diabetes is a risk factor for the severity of coronavirus disease 2019 (COVID‐19). Little is known how the COVID‐19 pandemic has disrupted diabetes‐related acute care. We compared hospitalization rates for severe hyperglycemia or hypoglycemia during the COVID‐19 outbreak in Hong Kong (study period: 25 January to 24 April 2020) with those during 25 January to 24 April 2019 (inter‐year control) and 25 October 2019 to 24 January 2020 (intra‐year control), using Poisson regression analysis. Hospitalization rates abruptly decreased after the first confirmed local COVID‐19 case on 23 January 2020, by 27% and 23% compared with the inter‐year and intra‐year control periods, respectively (incidence rate ratio 0.73 and 0.77, P < 0.001). Hospitalizations were reduced for severe hyperglycemia and hypoglycemia, but not diabetic ketoacidosis. This significant reduction in hospitalization rates should alert endocrinologists to take proactive measures to optimize glycemic control of individuals with diabetes. [ABSTRACT FROM AUTHOR]

There is a bidirectional relationship between coronavirus disease 2019 (COVID-19) and diabetes. Future research is required to assess the impact of COVID-19 on new-onset diabetes and the influence of diabetes on responses to COVID-19 vaccines. One year into the clash of pandemics of diabetes and COVID-19: Lessons learnt and future perspectives. [Extracted from the article]

Two Chinese studies of COVID-19 patients with diabetes from Wuhan in the early stage of the pandemic suggested potential beneficial effects of metformin. Is metformin a miracle or a menace in COVID-19 patients with type 2 diabetes? Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic since March 2020. [Extracted from the article]

Background: Familial hypercholesterolemia (FH) is a monogenic disorder of lipoprotein metabolism leading to an increased risk of premature cardiovascular disease. Genetic testing for FH is not commonly used in Asian countries. We aimed to define the genetic spectrum of FH in Hong Kong and to test the feasibility of cascade genetic screening. Methods: Ninety‐six Chinese subjects with a clinical diagnosis of FH were recruited, and family‐based cascade screening incorporating genetic testing results was performed. Results: Forty‐two distinct mutations were identified in 67% of the index FH cases. The majority of causative mutations were in the LDLR gene. The three commonest mutations in the LDLR gene were NM_000527.4(LDLR): c.1241 T>G, NM_000527.4(LDLR): c.1474G>A, and NM_000527.4(LDLR): c. 682G>A, and nine novel variants were identified. The NM_000384.2(APOB): c.10579 C>T variant of the APOB gene was found in 5% of the index subjects. The presence of causative mutation significantly increased the odds of successful family recruitment for screening with an OR of 3.7 (95% CI: 1.53–9.11, p = 0.004). Conclusion: Approximately two‐third of the subjects in this clinically ascertained sample of patients with FH had a discrete genetic basis. Genetic identification improves the response rate and efficiency of family screening. This study investigated the genetic spectrum in a clinically ascertained cohort of Chinese patients with familial hypercholesterolemia in Hong Kong. The three most common mutations altogether accounted for a combined frequency of 21% among the cohort. We assessed the feasibility of cascade screening to identify untreated patients and showed that having an identifiable genetic cause increases the performance of systematic family tracing. [ABSTRACT FROM AUTHOR]