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Background: Decisions on the frequency of physician encounters for patients with type 2 diabetes mellitus (T2DM) have significant impacts on both patients' health outcomes and burden on health systems, whereas definitive intervals for physician encounters are still lacking in most clinical guidelines. This study systematically reviewed the existing evidence evaluating different frequencies of physician encounters among T2DM patients., Methods: Systematic search of studies evaluating different visit frequencies for follow - up care in T2DM patients was performed in MEDLINE Ovid, Embase Ovid, and Cochrane library from database inception to 25 March 2022. Studies on the follow - up encounters driven by non - physicians and those on the episodic visits in the acute care settings were excluded in the screening. Citation searching was conducted via Google Scholar on the identified papers after screening. The risk of bias was assessed using Cochrane RoB2 tool for randomized controlled trials and Newcastle - Ottawa Scale for cohort studies. Findings were summarized narratively., Results: Among 6363 records from the database search and 231 references from the citation search, 12 articles were eligible for in - depth review. The results showed that for patients who had not achieved cardiometabolic control, intensifying encounter frequency could enhance medication adherence, shorten the time to achieve the treatment target, and improve the patients' quality of life. However, for the patients who had already achieved the treatment targets, less frequent encounters were equivalent to intensive encounters in maintaining their cardiometabolic control, and could save considerable healthcare costs without substantially lowering the quality of care and patients' satisfaction., Conclusion: Existing evidence suggested that the optimal frequency of physician encounters for patients with T2DM should be individualized, which can be stratified by patients' risk levels based on the cardiometabolic control to guide the differential scheduling of physician encounters in the follow - up. More research is needed to determine how to optimize the frequency of physician encounters for this large and heterogeneous population., (© 2024. The Author(s).)

Background: Continuity of care (COC) is associated with improved health outcomes in patients with hypertension. Team-based COC allows more flexibility in service delivery but there is a lack of research on its effectiveness for patients with hypertension., Aim: To investigate the effectiveness of team-based COC on the prevention of cardiovascular disease (CVD) and mortality in patients with hypertension., Design and Setting: A retrospective cohort study in a primary care setting in Hong Kong., Method: Eligible patients included those visiting public primary care clinics in Hong Kong from 2008 to 2018. The usual provider continuity index (UPCI) was used to measure the COC provided by the most visited physician team. Cox regression and restricted cubic splines were applied to model the association between the COC and the risk for CVDs and all-cause mortality., Results: This study included 421 640 eligible patients. Compared with participants in the lowest quartile of UPCI, the hazard ratios for overall CVD were 0.94 (95% CI = 0.92 to 0.96), 0.91(95% CI = 0.89 to 0.93), and 0.90 (95% CI = 0.88 to 0.92) in the second, third, and fourth quartiles, respectively. A greater effect size on CVD risk reduction was observed among the patients with unsatisfactory blood pressure control, patients aged <65 years, and those with a Charlson comorbidity index of <4 at baseline ( P interaction<0.05 in these subgroup analyses), but the effect was insignificant among the participants with an estimated glomerular filtration rate of <60 ml/ min/1.73 m 2 at baseline., Conclusion: Team-based COC via a coordinated physician team was associated with reduced risks of CVD and all-cause mortality among patients with hypertension, especially for the patients with unsatisfactory blood pressure control. Early initiation of team-based COC may also achieve extra benefits., (© The Authors.)

Background: The effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection., Methods: PubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity., Results: Eleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI -0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI -0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators; most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3); two studies reported an increase in total cholesterol and triglyceride., Conclusions: This review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research., Systematic Review Registration: PROSPERO CRD42022360433., Competing Interests: Declaration of Competing Interest ICKW reports research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, the European Commission, and the National Health and Medical Research Council in Australia, outside the submitted work; and is a non-executive director of Jacobson Medical in Hong Kong and a consultant to IQVIA and World Health Organization. Other authors declare that they have no competing interests., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Diabetes mellitus-related characteristics, including available medications, onset ages, and newly-introduced management program, have been changing recently in Hong Kong, especially after the introduction of the Risk Assessment and Management Program-Diabetes Mellitus in all outpatient clinics in 2009. To understand the plural change and improve the management of patients with Type 2 Diabetes Mellitus (T2DM) based on the latest data, we examined the trends of clinical parameters, T2DM complications and mortality in patients with T2DM in Hong Kong from 2010 to 2019., Methods: In this retrospective cohort study, we acquired data from the Clinical Management System of the Hospital Authority in Hong Kong. Among adults with T2DM diagnosed on or before Sept 30, 2010, and with at least one attendance in general outpatient clinics between Aug 1, 2009, to Sept 30, 2010, we investigated the age-standardised trends of clinical parameters including haemoglobin A1c, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C), body mass index and estimated glomerular filtration rate (eGFR), complications including cardiovascular disease (CVD), peripheral vascular disease (PVD), sight-threatening diabetic retinopathy (STDR), neuropathy, eGFR<45 mL/min/1.73 m 2 and end-stage renal disease (ESRD), and all-cause mortality from 2010 to 2019 and tested the statistical significance of the trends using generalised estimating equation by sex, level of clinical parameters and age groups., Findings: In total, 82,650 males and 97,734 females with T2DM were identified. LDL-C decreased from 3 to 2 mmol/L in both males and females, while other clinical parameters changed within 5% over the full decade from 2010 to 2019. CVD, PVD, STDR, and neuropathy had declining incidences, while ESRD and all-cause mortality had increasing incidences from 2010 to 2019. The incidence of eGFR<45 mL/min/1.73 m 2 increased in males but decreased in females. The odds ratio (OR) of ESRD (1.13, 95% CI [1.12, 1.15]) was highest in both males and females while the ORs of STDR (0.94, 95% CI [0.92, 0.96]) and neuropathy (0.90, 95% CI [0.88, 0.92]) were lowest in males and females, respectively. Complications and all-cause mortality trends varied among baseline HbA1c, eGFR, and age subgroups. In contrast to the findings in other age groups, the incidence of any outcomes did not decrease in younger patients (<45 years) from 2010 to 2019., Interpretation: Improvements were observed in LDL-C and incidences of most complications from 2010 to 2019. Worse performance in the younger age group and increasing incidence of renal complications and mortality need more attention in managing patients with T2DM., Funding: The Health and Medical Research Fund, the Health Bureau, and Government of the Hong Kong Special Administrative Region., Competing Interests: EYFW has received research grants from the Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grant Council, outside the submitted work. EYTY has received research grants from the Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. CLKL has received research grants from the Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, the Hong Kong College of Family Physicians, and Kerry Group Kuok Foundation, outside the submitted work. All other authors declare no competing interests., (© 2023 The Authors.)

Importance: There is a lack of information regarding the impact of implementing a protocol-driven, team-based, multicomponent intervention in public primary care settings on hypertension-related complications and health care burden over the long term., Objective: To compare hypertension-related complications and health service use at 5 years among patients managed with Risk Assessment and Management Program for Hypertension (RAMP-HT) vs usual care., Design, Setting, and Participants: In this population-based prospective matched cohort study, patients were followed up until the date of all-cause mortality, an outcome event, or last follow-up appointment before October 2017, whichever occurred first. Participants included 212 707 adults with uncomplicated hypertension managed at 73 public general outpatient clinics in Hong Kong between 2011 and 2013. RAMP-HT participants were matched to patients receiving usual care using propensity score fine stratification weightings. Statistical analysis was conducted from January 2019 to March 2023., Interventions: Nurse-led risk assessment linked to electronic action reminder system, nurse intervention, and specialist consultation (as necessary), in addition to usual care., Main Outcomes and Measures: Hypertension-related complications (cardiovascular diseases, end-stage kidney disease), all-cause mortality, public health service use (overnight hospitalization, attendances at accident and emergency department, specialist outpatient clinic, and general outpatient clinic)., Results: A total of 108 045 RAMP-HT participants (mean [SD] age: 66.3 [12.3] years; 62 277 [57.6%] female) and 104 662 patients receiving usual care (mean [SD] age 66.3 [13.5] years; 60 497 [57.8%] female) were included. After a median (IQR) follow-up of 5.4 (4.5-5.8) years, RAMP-HT participants had 8.0% absolute risk reduction in cardiovascular diseases, 1.6% absolute risk reduction in end-stage kidney disease, and 10.0% absolute risk reduction in all-cause mortality. After adjusting for baseline covariates, the RAMP-HT group was associated with lower risk of cardiovascular diseases (hazard ratio [HR], 0.62; 95% CI, 0.61-0.64), end-stage kidney disease (HR, 0.54; 95% CI, 0.50-0.59), and all-cause mortality (HR, 0.52; 95% CI, 0.50-0.54) compared with the usual care group. The number needed to treat to prevent 1 cardiovascular disease event, end-stage kidney disease, and all-cause mortality was 16, 106, and 17, respectively. RAMP-HT participants had lower hospital-based health service use (incidence rate ratios ranging from 0.60 to 0.87) but more general outpatient clinic attendances (IRR, 1.06; 95% CI, 1.06-1.06) compared with usual care patients., Conclusions and Relevance: In this prospective matched cohort study involving 212 707 primary care patients with hypertension, participation in RAMP-HT was associated with statistically significant reductions in all-cause mortality, hypertension-related complications, and hospital-based health service use after 5 years.

Aim: To evaluate the association between the number of co-morbidities, all-cause mortality and public health system expenditure in patients with type 2 diabetes (T2D) across different age groups., Materials and Methods: A retrospective observational study of T2D patients using electronic health records in Hong Kong was conducted. Patients were stratified by age (< 50, 50-64, 65-79, ≥ 80 years) and the number of co-morbidities (0, 1, 2, 3, ≥ 4), defined using the Charlson Comorbidity Index and prevalent chronic diseases identified in local surveys. The association between the number of co-morbidities, all-cause mortality and direct medical costs was examined using Cox proportional hazard regression and the gamma generalized linear model with log link function., Results: A total of 262 212 T2D patients with a median follow-up of 10 years were included. Hypertension and dyslipidaemia were the most common co-morbidities in all age groups. After age stratification, cardiovascular diseases dominated the top pair of co-morbidities in the older age groups (65-79 and ≥ 80 years), while inflammatory and liver disease were predominant among younger individuals. Compared with co-morbidity-free T2D patients, the hazard ratios (95% CI) of death for patients aged younger than 50 and 80 years or older with two co-morbidities were 1.31 (1.08-1.59) and 1.25 (1.15-1.36), respectively, and increased to 3.08 (2.25-4.21) and 1.98 (1.82-2.16), respectively, as the number of co-morbidities increased to four or more. Similar trends were observed for medical costs., Conclusions: Age-specific co-morbidity patterns were observed for patients with T2D. A greater number of co-morbidities was associated with increased mortality and healthcare costs, with stronger relationships observed among younger patients., (© 2022 John Wiley & Sons Ltd.)

Introduction: Type 2 diabetes mellitus (T2DM) has traditionally been considered a coronary heart disease 'risk equivalent' for future mortality, but significant heterogeneity exists across people with T2DM. This study aims to determine the risk of all-cause mortality of patients with cardiovascular disease (CVD) and T2DM in UK and Hong Kong, with stratifications for hemoglobin A1 (HbA1c) concentrations, compared with those without CVD and diabetes mellitus., Research Design and Methods: This is a retrospective cohort study of 3 839 391 adults from Hong Kong and a prospective cohort study of 497 779 adults from the UK Biobank. Individuals were divided into seven disease groups: (1) no T2DM and CVD, (2) T2DM only with HbA1c <7%, (3) T2DM only with HbA1c 7%-7.9%, (4) T2DM only with HbA1c 8%-8.9%, (5) T2DM only with HbA1c ≥9%, (6) CVD only, and (7) T2DM and CVD. Differences in all-cause mortality between groups were examined using Cox regression., Results: After around 10 years of median follow-up, 423 818 and 19 844 deaths were identified in the Hong Kong cohort and UK Biobank, respectively. Compared with individuals without T2DM and CVD, the adjusted HR for all-cause mortality in the other six disease groups for the Hong Kong cohort was 1.25 (95% CI 1.23 to 1.27) for T2DM only with HbA1c <7%, 1.21 (95% CI 1.19 to 1.23) for T2DM only with HbA1c 7%-7.9%, 1.36 (95% CI 1.33 to 1.39) for T2DM only with HbA1c 8%-8.9%, 1.82 (95% CI 1.78 to 1.85) for T2DM only with HbA1c ≥9%, 1.37 (95% CI 1.36 to 1.38) for CVD only, and 1.83 (95% CI 1.81 to 1.85) for T2DM and CVD, and for the UK Biobank the HR was 1.45 (95% CI 1.33 to 1.58), 1.50 (95% CI 1.32 to 1.70), 1.72 (95% CI 1.43 to 2.08), 2.51 (95% CI 2.05 to 3.08), 1.67 (95% CI 1.59 to 1.75) and 2.62 (95% CI 2.42 to 2.83), respectively. This indicates that patients with T2DM had an increased risk of mortality compared with those without T2DM and CVD, and in those with HbA1c ≥9% an even higher risk than people with CVD., Conclusions: Patients with T2DM with poor HbA1c control (8%-8.9% and ≥9%) were associated with similar and higher risk of mortality compared with patients with CVD, respectively. Optimal HbA1c, controlled for risk reduction and prevention of mortality and complications in diabetes management, remains important., Competing Interests: Competing interests: EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR and the Hong Kong Research Grant Council, outside the submitted work. CLKL has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, the Hong Kong College of Family Physicians and Kerry Group Kuok Foundation, outside the submitted work. EYTY has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. EWYC has received research grants from the Hong Kong Research Grant Council, Narcotics Division of the Security Bureau of the Government of the Hong Kong SAR, Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, National Health and Medical Research Council in Australia, Wellcome Trust, Bayer, Bristol Myers Squibb, Pfizer, Janssen, Amgen and Takeda, outside the submitted work. ICKW has received research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Hong Kong Research Grant Council and Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, and National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice, outside the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Few family-centered lifestyle interventions (FCLIs) for children with overweight or obesity (OW/OB) have assessed regional adiposity and bone health. This study assessed changes in adiposity in 9- to 12-year olds with OW/OB in a 1-year FCLI. Methods: Children were randomized to FCLI (six registered dietitian-led sessions) or no intervention (Control, CTRL). The FCLI focused on physical activity, nutrition education, and behavioral counseling children with families present. Assessments occurred at baseline and every 3 months for 1 year to assess changes in waist circumference (WC), body mass index for age-and-sex Z-scores (BAZ), body composition (dual-energy x-ray absorptiometry), and cardiometabolic biomarkers. Mixed models were used to determine the effects of group and time or group-by-time interactions for all outcomes. Results: Sixty children (age: 11.1 ± 1.1 years, BAZ: 2.7 ± 0.6) were enrolled; 55 participants ( n  = 28 CTRL, n  = 27 FCLI) completed the study. There were no between group differences from baseline to follow-up for any measure. The FCLI group had significant decreases in BAZ over 12 months (-0.18 ± 0.27, p  = 0.03) but not CTRL (-0.05 ± 0.32, p  = 0.92). WC and android fat mass did not change in FCLI ( p  > 0.20) but increased in CTRL ( p  < 0.02). Whole body bone area, content, and areal bone mineral density (aBMD) increased in both groups ( p  < 0.010); whole body aBMD Z-score decreased by 5.8% and 1.6% in CTRL and FCLI, respectively ( p  < 0.001). There were no significant within group changes in biomarkers. Conclusion: The FCLI resulted in small reductions in BAZ and a plateau in android fat mass, which suggest that FCLIs are suitable as an intervention for 9- to 12-year-old children with OW/OB. Clinical Trial Registration number: NCT01290016.

Objective: The Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) is a protocol-driven, risk-stratified, and individualized management program offered by a multidisciplinary team in addition to usual care for primary care patients with diabetes. This study aimed to evaluate the effectiveness of RAMP-DM for preventing complications and mortality over 10 years., Research Design and Methods: A population-based, prospective cohort study of adult patients with type 2 diabetes managed in the Hong Kong public primary health care system between 2009 and 2010 was conducted. RAMP-DM participants and usual care patients were matched using one-to-one propensity score matching and followed for 10 years. Risks of macrovascular and microvascular complications and all-cause mortality were estimated by Cox proportional hazards regression., Results: A total of 36,746 patients (18,373 in each group) were included after propensity score matching, with a median follow-up of 9.5 years and 306,802 person-years. RAMP-DM participants had significantly lower risks of macrovascular (hazard ratio [HR] 0.52, 95% CI 0.50-0.54) and microvascular (HR 0.68, 95% CI 0.64-0.72) complications and all-cause mortality (HR 0.45, 95% CI 0.43-0.47) than patients who received usual care only. However, the effect of RAMP-DM on macrovascular and microvascular complications attenuated after the 9th and 8th year of follow-up, respectively. RAMP-DM participants also showed better control of hemoglobin A1c, blood pressure, triglycerides, and BMI and a slower decline in renal function., Conclusions: Significant reductions in diabetes-related complications and all-cause mortality were observed among RAMP-DM participants over a 10-year follow-up, yet the effect of preventing complications attenuated after 8 years., (© 2022 by the American Diabetes Association.)

Introduction: The COVID-19 pandemic has a significant spill-over effect on people with non-communicable diseases (NCDs) over the long term, beyond the direct effect of COVID-19 infection. Evaluating changes in health outcomes, health service use and costs can provide evidence to optimise care for people with NCDs during and after the pandemic, and to better prepare outbreak responses in the future., Methods and Analysis: This is a population-based cohort study using electronic health records of the Hong Kong Hospital Authority (HA) CMS, economic modelling and serial cross-sectional surveys on health service use. This study includes people aged ≥18 years who have a documented diagnosis of diabetes mellitus, hypertension, cardiovascular disease, cancer, chronic respiratory disease or chronic kidney disease with at least one attendance at the HA hospital or clinic between 1 January 2010 and 31 December 2019, and without COVID-19 infection. Changes in all-cause mortality, disease-specific outcomes, and health services use rates and costs will be assessed between pre-COVID-19 and-post-COVID-19 pandemic or during each wave using an interrupted time series analysis. The long-term health economic impact of healthcare disruptions during the COVID-19 pandemic will be studied using microsimulation modelling. Multivariable Cox proportional hazards regression and Poisson/negative binomial regression will be used to evaluate the effect of different modes of supplementary care on health outcomes., Ethics and Dissemination: The study was approved by the institutional review board of the University of Hong Kong, the HA Hong Kong West Cluster (reference number UW 21-297). The study findings will be disseminated through peer-reviewed publications and international conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Cardiovascular diseases (CVD) are a long-term sequela of diabetes. Better individual-based continuity of care has been reported to reduce the risk of chronic complications among patients with diabetes. Maintaining a one-to-one patient-physician relationship is often challenging, especially in public health care settings. This study aimed to evaluate the relationship between higher team-based continuity of care, defined as consultations provided by the same physician team, and CVD risks in patients with diabetes from public primary care clinics., Research Design and Methods: This was a retrospective cohort study in Hong Kong of 312,068 patients with type 2 diabetes and without any history of CVD at baseline (defined as the earliest attendance at a doctor's consultation in a public-sector clinic between 2008 and 2018). Team-based continuity of care was measured using the usual provider continuity index (UPCI), calculated by the proportion of consultations provided by the most visited physician team in the 2 years before baseline. Patients were divided into quartiles based on their UPCI, and the characteristics of the quartiles were balanced using propensity score fine stratification weights. Multivariable Cox regression was applied to assess the effect of team-based continuity of care on CVD incidence. Patient demographics, smoking status, physiological measurements, number of attendances, comorbidities, and medications were adjusted for in the propensity weightings and regression analyses., Results: After an average follow-up of 6.5 years, the total number of new CVD events was 52,428. Compared with patients in the 1st quartile, patients in the 2nd, 3rd, and 4th quartiles of the UCPI had a CVD hazard ratio (95% CI) of 0.95 (0.92-0.97), 0.92 (0.89-0.94), and 0.87 (0.84-0.89), respectively, indicating that higher continuity of care was associated with lower CVD risks. The subtypes of CVD, including coronary heart disease and stroke, also showed a similar pattern. Subgroup analyses suggested that patients <65 years of age had greater benefits from higher team-based continuity of care., Conclusions: Team-based continuity of care was associated with lower CVD risk among individuals with type 2 diabetes, especially those who were younger. This suggests a potential flexible alternative implementation of continuity of care in public clinics., (© 2022 by the American Diabetes Association.)

Objectives: The coronavirus-19 (COVID-19) pandemic has claimed more than 5 million lives worldwide by November 2021. Implementation of lockdown measures, reallocation of medical resources, compounded by the reluctance to seek help, makes it exceptionally challenging for people with non-communicable diseases (NCD) to manage their diseases. This review evaluates the spill-over impact of the COVID-19 pandemic on people with NCDs including cardiovascular diseases, cancer, diabetes mellitus, chronic respiratory disease, chronic kidney disease, dementia, mental health disorders, and musculoskeletal disorders. Methods: Literature published in English was identified from PubMed and medRxiv from January 1, 2019 to November 30, 2020. A total of 119 articles were selected from 6,546 publications found. Results: The reduction of in-person care, screening procedures, delays in diagnosis, treatment, and social distancing policies have unanimously led to undesirable impacts on both physical and psychological health of NCD patients. This is projected to contribute to more excess deaths in the future. Conclusion: The spill-over impact of COVID-19 on patients with NCD is just beginning to unravel, extra efforts must be taken for planning the resumption of NCD healthcare services post-pandemic., Competing Interests: EW, CC, and EC were affiliated with, and worked as co-investigators without payment at the Laboratory of Data Discovery for Health Limited (D24H). IW was partly funded by the Laboratory of Data Discovery for Health Limited (D24H). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mak, Wan, Wong, Lee, Chan, Choi, Chui, Ip, Lau, Lau, Lee, Wong, Yu and Lam.)

Introduction: Cardiometabolic risk factors and renal function are monitored regularly for patients with diabetes mellitus (DM)/ hypertension (HT). In addition to risk factor levels at a single time point, their trajectory (changes over time) can also be differentially related to the risk of cardiovascular diseases (CVD) and mortality. This study aimed to systematically examine the evidence regarding the association between risk factor trajectories and risk of CVD/mortality in patients with DM/HT., Method: PubMed, MEDLINE, and Embase were searched for articles from January 1963 to April 2021. Inclusion criteria: studies that 1) analyzed trajectories of risk factors including haemoglobin A1c (HbA1c), blood pressure, estimated glomerular filtration rate (eGFR), body mass index (BMI), and blood lipids; 2) were performed in the DM/HT population and, 3) included risk of CVD/mortality as outcomes. Study quality was assessed using the Newcastle-Ottawa quality assessment scale., Results: A total of 22,099 articles were identified. After screening by title and abstract, 22,027 articles were excluded by irrelevant outcomes, exposure, population, or type of articles. Following full-text screening, 11 articles investigating the trajectories of HbA1c (N = 7), systolic blood pressure (SBP) (N = 3), and eGFR (N = 1) were included for data extraction and analysis. No studies were identified examining the association of BMI or lipid trajectories with CVD/mortality. All included studies were of good quality based on the NOS criteria. In general, stable trajectories within optimal ranges of the risk factors (HbA1c: <7%, SBP: 120-139mmHg, eGFR: >60mL/min/1.73m2) had the lowest CVD/mortality risk compared to an increasing HbA1c trajectory (from 8% to 10%), an increasing SBP trajectory (from 120-139 to ≥140mmHg), or a decreasing eGFR trajectory (from 90 to 70mL/min/1.73m2)., Conclusion: A relatively stable and well-controlled trajectory for cardiometabolic risk factors was associated with the lowest risk of CVD/mortality. Risk factor trajectories have important clinical implications in addition to single time point measurements. More attention should be given to patients with suboptimal control and those with unstable trends of cardiometabolic risk factors., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Eric Wan has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grant Council, outside the submitted work. Esther Yu has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. Professor Cindy Lam has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, the Hong Kong College of Family Physicians, and Kerry Group Kuok Foundation, outside the submitted work.

The association between total dietary fat intake and measures of body fatness in children with obesity remains inconsistent. This study aimed to determine whether dietary long-chain polyunsaturated fatty acids (LCPUFA) and LCPUFA status relate to body composition in children with obesity. Children (n = 63, 9.0 ± 0.2 year, BMI Z-score 3.1 ± 0.2) were divided into tertiles of percentage body fat assessed by dual-energy X-ray absorptiometry. Diet was assessed 3-days food diaries. Fatty acid proportions in red blood cells (RBC) were measured by gas chromatography. Data stratified by sex and Tanner stages were compared with a MIXED model ANOVA. Associations between RBC fatty acid status and dietary intakes were examined with Spearman correlation. Moderate correlations were observed between RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) proportions, dietary EPA and DHA (r = 0.39, P < .05) as well as fish servings (r = 0.33, P < .05). Dietary LCPUFA did not differ among tertiles. Children in tertile 3 had lower RBC α-linolenic acid (-40%) and EPA + DHA (-15%) proportions adjusted for age, Tanner stages and race compared with tertile 1. The lower omega-3 LCPUFA status in children with greater adiposity is consistent with suboptimal intakes of omega-3 LCPUFA and fish in the diet., (© 2020 World Obesity Federation.)

Long-chain polyunsaturated fatty acids are implicated in musculoskeletal health in adults. This study examined whether fatty acid status relates to bone health outcomes in children with overweight condition or obesity (body mass index z score, 3.1 ± 0.1; age, 9.0 ± 0.2 years; n = 108). Nondominant forearm bone density (distal one-third), geometry (4% site), and soft tissue composition (66%) were assessed using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Red blood cell (RBC) fatty acid profile and indices of glucose homeostasis were measured. Differences in outcomes among RBC arachidonic acid (AA, C20:4n-6) tertiles were tested using mixed-model ANOVA. Ultra-, mid-, and total-distal forearm bone mineral content, adjusted for sex, age, percentage body fat, race, and forearm length, were 10% to 13% greater in children in the first AA tertile relative to the third. Children in the second tertile had the highest bone cross-sectional area and estimated strength at the 66% radius. Muscle cross-sectional area was 15% lower in the third tertile compared with the first, along with higher fasting insulin concentrations (27%) and homeostasis model of assessment estimate of insulin resistance (31%). Higher RBC AA status aligns with deficits in forearm bone mass, geometry, and muscle mass in children with excess adiposity and early signs of insulin resistance. Novelty Higher arachidonic acid status is associated with lower forearm bone mass in children with overweight condition or obesity. Children with higher arachidonic acid status had increased fasting insulin concentrations and indices of insulin resistance.

Long-chain polyunsaturated fatty acids modulate bone mass and adipocyte metabolism. Arachidonic acid (AA, C20:4 n-6) is elevated in obesity and postulated to stimulate bone resorption. This study aimed to determine the effect of AA on bone mass, quality, and adiposity in diet-induced obesity during growth. Male Sprague-Dawley rats (n=42, 4-week) were randomized into groups fed a control diet (CTRL, AIN-93G), high-fat diet (HFD, 35% kcal fat) or HFD + AA (1% w/w diet) for 6 weeks. Body composition, bone mineral density and microarchitecture were measured using dual-energy X-ray absorptiometry and micro-computed tomography. Red blood cell fatty acid profile was measured with gas chromatography. Group differences were evaluated using repeated measures two-way analysis of variance with Tukey-Kramer post hoc testing. Total energy intake did not differ among diet groups. At week 6, HFD + AA had significantly greater body fat % (12%), body weight (6%) and serum leptin concentrations (125%) than CTRL, whereas visceral fat (mass and %, assessed with micro-computed tomography) was increased in both HFD and HFD + AA groups. HFD + AA showed reduced whole body bone mineral content and femur mid-diaphyseal cortical bone cross-sectional area than HFD and CTRL, without impairment in bone strength. Contrarily, HFD + AA had greater femur metaphyseal trabecular vBMD (35%) and bone volume fraction (5%) compared to controls. Inclusion of AA elevated leptin concentrations in male rats. The early manifestations of diet-induced obesity on bone mass were accelerated with AA. Studies of longer duration are needed to clarify the effect of AA on peak bone mass following growth cessation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This study aims to examine agreement among bone mineral content (BMC) and density (BMD) estimates obtained using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and micro-computed tomography (μCT) against high-resolution μCT and bone ash of the guinea pig femur. Middle-aged (n = 40, 86 weeks) male guinea pigs underwent in vivo followed by ex vivo DXA (Hologic QDR 4500A) scanning for intact and excised femur BMC and areal density. To assess bone architecture and strength, excised femurs were scanned on pQCT (Stratec XCT 2000L) as well as on two μCT scanners (LaTheta LCT-200; Skyscan 1174), followed by three-point bending test. Reproducibility was determined using triplicate scans; and agreement assessed using Bland-Altman plots with reference methods being high-resolution μCT (Skyscan) for BMD and bone ashing for BMC. All techniques showed satisfactory ex vivo precision (CV 0.05-4.3 %). However, bias compared to the reference method was highest (207.5 %) in trabecular bone volume fraction (BV/TV) measured by LaTheta, and unacceptable in most total femur and cortical bone measurements. Volumetric BMD (vBMD) and BV/TV derived by LaTheta and pQCT at the distal metaphysis were biased from the Skyscan by an average of 49.3 and 207.5 %, respectively. Variability of vBMD, BV/TV and cross-sectional area at the diaphysis ranged from -5.5 to 30.8 %. LaTheta best quantified total femur BMC with an upper bias of 3.3 %. The observed differences among imaging techniques can be attributable to inherent dissimilarity in construction design, calibration, segmentation and scanning resolution used. These bone imaging tools are precise but are not comparable, at least when assessing guinea pig bones.

Age-related osteoporosis and sarcopenia are ascribed in part to reductions in anabolic hormones. Dietary conjugated linoleic acid (CLA) improves lean and bone mass, but its impact during androgen deficiency is not known. This study tested if CLA would attenuate the effects of orchidectomy (ORX)-induced losses of bone and lean tissue. Male guinea pigs (n=40; 70-72 weeks), were randomized into four groups: (1) SHAM+Control diet, (2) SHAM+CLA diet, (3) ORX+Control diet, (4) ORX+CLA diet. Baseline blood sampling and dual-energy X-ray absorptiometry (DXA) scans were conducted, followed by surgery 4 days later with the test diets started 7 days after baseline sampling. Serial blood sampling and DXA scans were repeated 2, 4, 8 and 16 weeks on the test diets. Body composition and areal BMD (aBMD) of whole body, lumbar spine, femur and tibia were measured using DXA. At week 16, muscle protein fractional synthesis rate (FSR), volumetric BMD (vBMD), microarchitecture and bone strength were assessed. Body weight declined after SHAM and ORX surgery, with slower recovery in the ORX group. Dietary CLA did not affect weight or lean mass, but attenuated gains in fat mass. Lean mass was stable in SHAM and reduced in ORX by 2 weeks with whole body and femur bone mineral content (BMC) reduced by 4 weeks; CLA did not alter BMC. By week 16 ORX groups had lower free testosterone and myofibrillar FSR, yet higher cortisol, osteocalcin and ionized calcium with no alterations due to CLA. ORX+Control had higher prostaglandin E2 (PGE2) and total alkaline phosphatase compared to SHAM+Control whereas ORX+CLA were not different from SHAM groups. Femur metaphyseal vBMD was reduced in ORX+CTRL with the reduction attenuated by CLA. Femur cortical thickness (Ct.Th.) and biomechanical strength were reduced and cortical porosity (Ct.Po.) elevated by ORX and attenuated by CLA. This androgen deficient model with a sarcopenic-osteoporotic phenotype similar to aging men responded to dietary CLA with significant benefits to femur density and strength., (Copyright © 2014 Elsevier Inc. All rights reserved.)