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[...]most NAFLD guidelines recommend the early identification of those at risk of AF, although none has specifically issued recommendations on the best strategy to screen for AF in patients with type 2 diabetes, despite their high propensity for NAFLD progression. 1 TableCommonly used serum‐based fibrosis panels for detection of advanced fibrosis in non‐alcoholic fatty liver disease Variables AUROC reported in general NAFLD population † NFS Age, BMI, hyperglycemia, platelet count, albumin and AST/ALT ratio 0.84 FIB‐4 Age, platelet count, AST and ALT 0.84 APRI Platelet count and AST 0.77 BARD BMI, diabetes, AST and ALT 0.76 †Data from Xiao et al. 5 ALT, alanine aminotransferase; APRI, aspartate aminotransferase to platelet ratio index; AST, aspartate aminotransferase; AUROC, area under the receiver operating curve; BMI, body mass index; FIB‐4, Fibrosis‐4 index; NAFLD, non‐alcoholic fatty liver disease; NFS, non‐alcoholic fatty liver disease fibrosis score. [...]there is still a long road before these adipokines or hepatokines can be used outside the research laboratories as commercially available fibrosis markers in clinical practice. [...]to avoid a flood of referrals to hepatology clinics for TE or further investigations, a simple and cost‐effective strategy is eagerly awaited to facilitate AF risk stratification in patients with type 2 diabetes and NAFLD.

Aims/Introduction To develop a new non‐invasive risk score for undiagnosed diabetes in Chinese people, and to evaluate the incident diabetes risk in those with high‐risk scores, but no diabetes on initial testing. Materials and Methods A total of 2,609 participants with no known diabetes (aged 25–74 years) who underwent oral glucose tolerance tests in Hong Kong (HK) were investigated for independent risk factors of diabetes to develop a categorization point scoring system, the Non‐invasive Diabetes Score (NDS). This NDS was validated in a cross‐sectional study of 2,746 participants in Shaanxi, China. HK participants tested to not have diabetes at baseline were assessed for subsequent incident diabetes rates. Results In the HK cohort, hypertension, age and body mass index were the key independent risk factors selected to develop the NDS, with ≥28 out of 50 NDS points considered as high risk. The area under the receiver operating characteristic curve for undiagnosed diabetes was 0.818 and 0.720 for the HK and Shaanxi cohort, respectively. The negative predictive value was 97.4% (HK) and 95.8% (Shaanxi); the number needed to screen to identify one case of diabetes was five (HK) and 11 (Shaanxi), respectively. Among those that tested non‐diabetes at baseline, individuals with NDS ≥28 had a threefold risk of incident diabetes during the subsequent 20.9 years, compared with those with NDS <28 (P < 0.001), with a steeper rise in incident diabetes observed in those with NDS at higher tertiles. Conclusions This new three‐component risk score is a user‐friendly tool for diabetes screening, and might inform the subsequent testing interval for high‐risk non‐diabetes individuals. We described the development, validation and longitudinal evaluation of a simple diabetes risk score with the fewest number of variables for undiagnosed diabetes in Chinese people. This risk score might help in opportunistic screening of diabetes, and inform subsequent testing interval for high‐risk individuals after initial testing.

Background In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). Methods Patients with severe RHPT (defined by PTH ≥ 100 pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00 mmol/L. Results Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n  = 27; Group II, n  = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49 pmol/L vs Group II: 154 ± 45, p  = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60 pmol/L vs 154 ± 45, p  < 0.001), higher post-operative calcium ( p  < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p  = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels ( p  < 0.05). Cinacalcet use for > 1 year resulted in fewer severe post-operative hypocalcemia than non-users ( p  = 0.022, OR 0.242, 95% CI 0.068–0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17–7.77, p  = 0.022). Conclusion In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1 year reduced severe post-operative hypocalcemia.

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. The study consisted of two parts. In Part 1, the sera titres of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) alpha receptor binding domain ( RBD), their neutralizing capacity, and antigen-specific CD4 + T and CD8 + T cell responses at 3-6 months after vaccination were compared between BNT162b2 (n=60) and CoronaVac (n=50) vaccinees with or without T2D. Part 2 was a time-course study investigating the initial B and T cell responses induced by BNT162b2 among vaccinees (n=16) with or without T2D. Our data showed that T2D impaired both cellular and humoral immune responses induced by CoronaVac. For BNT162b2, T2D patients displayed a reduction in CD4 + T-helper 1 (Th1) differentiation following their first dose. However, this initial defect was rectified by the second dose of BNT162b2, resulting in comparable levels of memory CD4 + and CD8 + T cells, anti-RBD IgG, and neutralizing antibodies with healthy individuals at 3-6 months after vaccination. Hence, T2D influences the effectiveness of COVID-19 vaccines depending on their platform. Our findings provide a potential mechanism for the susceptibility of developing adverse outcomes observed in COVID-19 patients with T2D and received either CoronaVac or just one dose of BNT162b2.

Background Both glucagon-like peptide 1 receptor agonist (GLP1RA) and pioglitazone are associated with cardiovascular and hepatic benefits in patients with type 2 diabetes (T2D). However, studies that directly compare their cardio-hepatic effects are lacking. We emulated a target trial to compare their effects on adverse liver and cardiovascular outcomes in T2D patients. Methods We adopted an “active comparator, new user” design involving T2D patients newly prescribed GLP1RA or pioglitazone between January 2008 and December 2022. The primary outcomes were major adverse liver outcomes (MALO) and cardiovascular events (MACE), with their individual outcomes and heart failure (HF) as secondary outcomes. Cox proportional hazards models were used to estimate hazard ratios (HRs) via intention-to-treat (ITT) and per-protocol (PP) analyses. Results A total of 8922 patients (N = 4461 each group) were included. Compared to pioglitazone users, GLP1RA users had comparable risks of incident MALO (ITT: HR 0.94, 95% CI 0.66–1.34; PP: HR 1.13, 95% CI 0.60–2.15) and MACE (ITT: HR 0.99, 95% CI 0.80–1.22; PP: HR 1.10, 95% CI 0.77–1.58). The risk of HF was significantly lower in GLP1RA users in ITT analysis (HR 0.65, 95% CI 0.51–0.83). The results were consistent across most subgroup and sensitivity analyses. Conclusions The effects on incident major adverse liver and cardiovascular outcomes were comparable between GLP1RA and pioglitazone, although the risk of incident HF was lower with GLP1RA. Treatment decisions for T2D patients at risk of adverse cardio-hepatic events should be individualized, considering HF risk and the need for weight loss, which if present, GLP1RA may be preferred.

There is a bidirectional relationship between coronavirus disease 2019 (COVID‐19) and diabetes. Furthermore, the COVID‐19 pandemic has catalyzed the use of technology in diabetes care. 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.

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. Diabetes is a risk factor contributing to the severity of COVID‐19 infection. However, little is known about the collateral effect of the COVID‐19 pandemic on diabetes‐related acute care. We have quantified the impact in a territory‐wide study and shown an abrupt drop in hospitalization rates for severe hyperglycemia or hypoglycemia after the onset of the COVID‐19 outbreak on 23 January 2020.

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.Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).Conclusion: Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

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. HDL particles are highly heterogeneous, and there are quantitative and qualitative changes as well as functional abnormalities of HDL particles in both type 1 and type 2 diabetes. HDL dysfunction is common in diabetes and contributes to the increased cardiovascular risk in people with diabetes.

Background In view of accumulating case reports of thyroid dysfunction following COVID-19 vaccination, we evaluated the risks of incident thyroid dysfunction following inactivated (CoronaVac) and mRNA (BNT162b2) COVID-19 vaccines using a population-based dataset. Methods We identified people who received COVID-19 vaccination between 23 February and 30 September 2021 from a population-based electronic health database in Hong Kong, linked to vaccination records. Thyroid dysfunction encompassed anti-thyroid drug (ATD)/levothyroxine (LT4) initiation, biochemical picture of hyperthyroidism/hypothyroidism, incident Graves’ disease (GD), and thyroiditis. A self-controlled case series design was used to estimate the incidence rate ratio (IRR) of thyroid dysfunction in a 56-day post-vaccination period compared to the baseline period (non-exposure period) using conditional Poisson regression. Results A total of 2,288,239 people received at least one dose of COVID-19 vaccination (57.8% BNT162b2 recipients and 42.2% CoronaVac recipients). 94.3% of BNT162b2 recipients and 92.2% of CoronaVac recipients received the second dose. Following the first dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.864, 95% CI 0.670–1.114; CoronaVac: IRR 0.707, 95% CI 0.549–0.912), LT4 initiation (BNT162b2: IRR 0.911, 95% CI 0.716–1.159; CoronaVac: IRR 0.778, 95% CI 0.618–0.981), biochemical picture of hyperthyroidism (BNT162b2: IRR 0.872, 95% CI 0.744–1.023; CoronaVac: IRR 0.830, 95% CI 0.713–0.967) or hypothyroidism (BNT162b2: IRR 1.002, 95% CI 0.838–1.199; CoronaVac: IRR 0.963, 95% CI 0.807–1.149), GD, and thyroiditis. Similarly, following the second dose of COVID-19 vaccination, there was no increase in the risks of ATD initiation (BNT162b2: IRR 0.972, 95% CI 0.770–1.227; CoronaVac: IRR 0.879, 95%CI 0.693–1.116), LT4 initiation (BNT162b2: IRR 1.019, 95% CI 0.833–1.246; CoronaVac: IRR 0.768, 95% CI 0.613–0.962), hyperthyroidism (BNT162b2: IRR 1.039, 95% CI 0.899–1.201; CoronaVac: IRR 0.911, 95% CI 0.786–1.055), hypothyroidism (BNT162b2: IRR 0.935, 95% CI 0.794–1.102; CoronaVac: IRR 0.945, 95% CI 0.799–1.119), GD, and thyroiditis. Age- and sex-specific subgroup and sensitivity analyses showed consistent neutral associations between thyroid dysfunction and both types of COVID-19 vaccines. Conclusions Our population-based study showed no evidence of vaccine-related increase in incident hyperthyroidism or hypothyroidism with both BNT162b2 and CoronaVac.