Hyperglycemia-triggered lipid peroxidation destabilizes STAT4 and impairs anti-viral Th1 responses in type 2 diabetes.

Patients with type 2 diabetes (T2D) are more susceptible to severe respiratory viral infections, but the underlying mechanisms remain elusive. Here, we show that patients with T2D and coronavirus disease 2019 (COVID-19) infections, and influenza-infected T2D mice, exhibit defective T helper 1 (Th1) responses, which are an essential component of anti-viral immunity. This defect stems from intrinsic metabolic perturbations in CD4 T cells driven by hyperglycemia.

Phenome-Wide Analysis of Coffee Intake on Health over 20 Years of Follow-Up Among Adults in Hong Kong Osteoporosis Study.

Background/objectives: There has been limited evidence on the long-term impacts of coffee intake on health. We aimed to investigate the association between coffee intake and the incidence of diseases and mortality risk over 20 years among community-dwelling Chinese adults.

Methods: Participants were from the Hong Kong Osteoporosis Study who attended baseline assessments during 1995-2010.

External validation of the Hong Kong Chinese non-laboratory risk models and scoring algorithm for case finding of prediabetes and diabetes mellitus in primary care.

Aims/introduction: Two Hong Kong Chinese non-laboratory-based prediabetes/diabetes mellitus (pre-DM/DM) risk models were developed using logistic regression (LR) and machine learning, respectively. We aimed to evaluate the models' validity in case finding of pre-DM/DM in a Chinese primary care (PC) population. We also evaluated the validity of a risk-scoring algorithm derived from the LR model.

Hip fracture is associated with a reduced risk of type 2 diabetes: A retrospective cohort study.

Objectives: Type 2 diabetes mellitus (T2DM) shares a complex relationship with bone metabolism and few studies investigated the effect of impaired bone health on the risk of T2DM. This study was conducted to investigate the association between hip fractures and the risk of incident T2DM

Methods: This is a retrospective cohort study using data from the real-world hip fracture cohort. Hong Kong Chinese patients aged ≥ 65 years without T2DM who were admitted to public hospitals due to a fall between 2008 and 2015 were included in the study.

Development and validation of 10-year risk prediction models of cardiovascular disease in Chinese type 2 diabetes mellitus patients in primary care using interpretable machine learning-based methods.

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.

Serum thrombospondin-2 level changes with liver stiffness improvement in patients with type 2 diabetes.

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).

Illicit drug use is associated with lower bone mineral density and bone strength.

Objectives: To evaluate the association of illicit drug use with bone mineral density (BMD) and hip geometric parameters at the narrow neck.

Methods: This is a cross-sectional matched cohort study conducted in the Hong Kong Chinese population. Associations with illicit drug use were estimated using linear regression for BMD (lumbar spine and femoral neck) and hip geometrical parameters (cross-sectional area [CSA], cross-sectional moment of inertia [CSMI], section modulus [SM], average cortical thickness [ACT] and BMD at the narrow neck) after adjusting for age, body mass index (BMI), smoking status, drinking status, physical activity, and history of antipsychotic and antidepressant use.

Association of Bone Mineral Density and Bone Turnover Markers with the Risk of Diabetes: Hong Kong Osteoporosis Study and Mendelian Randomization.

Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS).

Development and validation of the Chinese osteoporosis screening algorithm (COSA) in identification of people with high risk of osteoporosis.

Objectives: To enhance the public awareness and facilitate diagnosis of osteoporosis, we aim to develop a new Chinese Osteoporosis Screening Algorithm (COSA) to identify people at high risk of osteoporosis.

Methods: A total of 4747 postmenopausal women and men aged ≥ 50 from the Hong Kong Osteoporosis Study were randomly split into a development (N = 2373) and an internal validation cohort (N = 2374). An external validation cohort comprising 1876 community-dwelling subjects was used to evaluate the positive predictive value (PPV).

Development and validation of sex-specific hip fracture prediction models using electronic health records: a retrospective, population-based cohort study.

Background: Hip fracture is associated with immobility, morbidity, mortality, and high medical cost. Due to limited availability of dual-energy X-ray absorptiometry (DXA), hip fracture prediction models without using bone mineral density (BMD) data are essential. We aimed to develop and validate 10-year sex-specific hip fracture prediction models using electronic health records (EHR) without BMD.

Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease.

Background: Non-diabetic overweight/obese metabolic dysfunction-associated fatty liver disease (MAFLD) represents the largest subgroup with heterogeneous liver fibrosis risk. Metabolic dysfunction promotes liver fibrosis. Here, we investigated whether incorporating additional metabolic risk factors into clinical evaluation improved liver fibrosis risk stratification among individuals with non-diabetic overweight/obese MAFLD.

Comparing the B and T cell-mediated immune responses in patients with type 2 diabetes receiving mRNA or inactivated COVID-19 vaccines.

Acquiring protective immunity through vaccination is essential, especially for patients with type 2 diabetes who are vulnerable for adverse clinical outcomes during coronavirus disease 2019 (COVID-19) infection. Type 2 diabetes (T2D) is associated with immune dysfunction. Here, we evaluated the impact of T2D on the immunological responses induced by mRNA (BNT162b2) and inactivated (CoronaVac) vaccines, the two most commonly used COVID-19 vaccines.

Osteoporosis is a novel risk factor of infections and sepsis: A cohort study.

Background: Accumulating evidence suggests the interaction of bone metabolism and the immune system, but how bone health is associated with the risk of infections remains unknown.

Methods: This study aimed to investigate the relationship of bone mineral density (BMD) with the risk of common infections and sepsis in Hong Kong Osteoporosis Study (HKOS). A prospective cohort study, initiated in 1995 and followed until 31 December 2020, of 5,717 participants examined the association of BMD at three skeletal sites (lumbar spine, femoral neck, and total hip) with common infections - pneumonia, urinary tract infection (UTI), skin infection, and sepsis.

Cholesterol efflux capacity of high-density lipoprotein was not associated with cognitive decline and brain structures in older people with diabetes mellitus.

Aims/introduction: To examine the association between cholesterol efflux capacity (CEC) of serum high-density lipoprotein (HDL) and cognitive function and brain structures in older people with diabetes mellitus.

Materials And Methods: Participants of a randomized placebo-controlled trial of 27-month vitamin B supplementation in older people with diabetes mellitus, which showed no effect on cognition, were further followed up at month 72. Cognitive tests included the Clinical Dementia Rating scale, Neuropsychological Test Battery in memory, executive function and psychomotor speed.

Effect of type 2 diabetes on A disintegrin and metalloprotease 10.

Background: As a type 1 transmembrane protein, a disintegrin and metalloprotease 10 (ADAM10) is responsible for the cleavage of a variety of cell surface molecules and has been implicated in the pathogenesis of Alzheimer disease, atherosclerosis, and inflammatory and neoplastic disorders. It has been suggested that systemic ADAM10 concentration may potentially be used as a prognostic biomarker. Since high glucose can upregulate ADAM10 expression in vitro, we investigated whether serum levels of ADAM10 and its substrate, the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), can be influenced by type 2 diabetes.

Effects of statins on the inducible degrader of low-density lipoprotein receptor in familial hypercholesterolemia.

The inducible degrader of low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase involved in the post-transcriptional regulation of LDL receptor (LDLR). Statins lower plasma LDL by activating transcription of hepatic LDLR expression, and we have determined whether statins modulate IDOL expression and influence LDLR protein abundance. IDOL expression in monocytes and serum IDOL level was determined in statin-treated familial hypercholesterolemia (FH) patients and compared with control subjects.

Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus.

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.

Genetically Determined TSH Level Within Reference Range Is Inversely Associated With Alzheimer Disease.

Context: Contradictory findings were reported in observational studies on the association of thyroid function (thyrotropin [TSH] and free thyroxine [FT4] levels) with Alzheimer disease (AD).

Objective: This work aims to determine whether genetically determined TSH/FT4 levels within reference range are causally associated with AD.

Methods: A bidirectional, 2-sample mendelian randomization (MR) study was conducted.

Association of Genetic Variants Related to Serum Calcium Levels with Reduced Bone Mineral Density.

Context: The role of serum calcium in bone metabolism is unknown, even though calcium/vitamin D supplementations have been widely used and are expected to improve bone health. We aim to determine the independent role of serum calcium in bone mineral density (BMD).

Design And Setting: Two epidemiological analyses with 5478 and 5556 participants from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2006 and the Hong Kong Osteoporosis Study (HKOS) to evaluate the cross-sectional association of serum calcium with BMD.

Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian randomization study.

Background: Low-density lipoprotein cholesterol (LDL-C) is suggested to play a role in osteoporosis but its association with bone metabolism remains unclear. Effects of LDL-C-lowering drugs on bone are also controversial. We aim to determine whether LDL-C is linked causally to bone mineral density (BMD) and assess the effects of LDL-C-lowering drugs on BMD.

25-Hydroxyvitamin D and the risk of incident diabetes in Hong Kong Chinese.

Objective: To investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and risk of incident diabetes in Hong Kong Chinese, after accounting for the effect of multiple bone- and mineral-related markers.

Design: We conducted a retrospective study on the Hong Kong Osteoporosis Study cohort. Incident diabetes was ascertained using electronic medical records.

Glycogenic hepatopathy as an unusual etiology of deranged liver function in a patient with type 1 diabetes: A case report.

Rationale: Deranged liver function is a common finding among patients with diabetes mellitus. We report a case of liver biopsy-proven glycogenic hepatopathy (GH) in a patient with long-standing poorly controlled type 1 diabetes (DM1), presented with recurrent transaminitis.

Patient Concerns: A 28-year-old Chinese woman was noted to have deranged liver function with transaminases elevated to more than 15 times the upper limit of normal.