OBJECTIVE: The social environment (SE), that is, the social relationships and social context in which groups of people live and interact, is an understudied element of the broader living environment which impacts health. We aim to summarise the available evidence on the associations between SE and cardiometabolic disease (CMD) outcomes.
METHODS: Systematic review and meta-analysis.
METHODS: PubMed, Scopus and Web of Science Core Collection were searched from inception to 28 February 2024.
METHODS: We included studies for which determinants were SE factors such as area-level deprivation and social network characteristics and outcomes were type 2 diabetes mellitus and cardiovascular diseases incidence and prevalence.
METHODS: Titles and abstracts and full text were screened in duplicate. Data appraisal and extraction were based on the study protocol published in PROSPERO. Methodological quality was assessed with the Newcastle-Ottawa Scale. We synthesised the data through vote counting and meta-analyses.
RESULTS: From 10 143 records screened, 281 studies reporting 1108 relevant associations are included in this review. Of the 384 associations included in vote counting, 271 (71%) suggested that a worse SE is associated with a higher risk of CMD. 14 meta-analyses based on 180 associations indicated that worse SE was associated with increased odds of CMD outcomes, with 4 of them being statistically significant. For example, more economic and social disadvantage was associated with higher heart failure risk (OR 1.58, 95% CI 1.08 to 1.61; n=18; I2=95%). With the exception of two meta-analyses for men, meta-analysed sex-specific associations consistently showed results in the same direction as the overall meta-analyses.
CONCLUSIONS: Worse SE seems to be associated with increased odds of CMD outcomes, although certain SE dimensions are underexplored in relation to CMD.
UNASSIGNED: CRD42021223035.

BACKGROUND: Novel strategies are needed to address the rising burden of osteoporosis and fragility fractures. High-intensity resistance and impact (HiRIT) exercise has shown benefit in improving bone density in postmenopausal women with osteoporosis/osteopenia. Whether HiRIT can enhance the therapeutic effects of osteoporosis pharmacotherapy has not been established. ROLEX-DUO is a randomised controlled trial designed to assess the efficacy of romosozumab on various bone and muscle outcomes in combination with different exercise interventions in women with postmenopausal osteoporosis/osteopenia.
METHODS: ROLEX-DUO is an 8-month randomised placebo-controlled trial conducted at two tertiary referral centres for patients with osteoporosis/osteopenia in Sydney, New South Wales, Australia. The study is implementing the combination of romosozumab or placebo with different forms of exercise in postmenopausal women with osteoporosis/osteopenia without recent fragility fracture (n=102). Eligible women will be randomised 1:1:1 into one of three groups: (1) romosozumab with supervised HiRIT, (2) romosozumab with unsupervised low-intensity exercise or (3) placebo with unsupervised low-intensity exercise. Co-primary outcomes are the mean percentage change in lumbar spine bone mineral density (BMD), and mean change in five times sit-to-stand test performance (seconds) at 8 months. Secondary/exploratory outcomes include BMD changes at the femoral neck, total hip and distal radius, three-dimensional dual-energy X-ray absorptiometry (DXA) hip outcomes, DXA-derived lean and fat mass, serum markers of bone turnover (procollagen type 1 peptide, C-telopeptide of type 1 collagen) and bone biomarkers (dickkopf-1), serum extracellular vesicle analyses, 36-Item Short Form Survey (SF-36) quality-of-life scores, Menopause-Specific Quality Of Life (MENQOL) Questionnaire menopause symptom burden scores, number of falls and fractures. Mixed-effects models will be performed to compare longitudinal outcome results between groups using intention-to-treat analysis.
BACKGROUND: The trial was approved by the Northern Sydney Local Health District Human Research Ethics Committee (2022/ETH01794, protocol V.8, dated 03 July 2024). Participants will provide written informed consent prior to inclusion. Findings will be disseminated via peer-reviewed journals, scientific conferences and summary reports to funding bodies.
BACKGROUND: ACTRN12623000867695.

BACKGROUND: The cornerstone in the management of type 2 diabetes (T2D) is lifestyle modification including a healthy diet, typically one in which carbohydrate provides 45%-60% of total energy intake (E%). Nevertheless, systematic reviews and meta-analyses of trials with low carbohydrate diets (which are increased in protein and/or fat) for T2D have found improved glycaemic control in the first months relative to comparator diets with higher carbohydrate content. Studies lasting ≥1 year are inconclusive, which could be due to decreased long-term dietary adherence. We hypothesise that glucometabolic benefits can be achieved following 12 months of carbohydrate-restricted dieting, by maximising dietary adherence through delivery of meal kits, containing fresh, high-quality ingredients for breakfast, dinner and snacks, combined with nutrition education and counselling.
METHODS: This protocol describes a 12-month investigator-initiated randomised controlled, open-label, superiority trial with two parallel groups that will examine the effect of a carbohydrate-reduced high-protein (CRHP) diet compared with a conventional diabetes (CD) diet on glucometabolic control (change in glycated haemoglobin being the primary outcome) in 100 individuals with T2D and body mass index (BMI) >25 kg/m2. Participants will be randomised 1:1 to receive either the CRHP or the CD diet (comprised 30/50 E% from carbohydrate, 30/17 E% from protein and 40/33 E% from fat, respectively) for 12 months delivered as meal kits, containing foods covering more than two-thirds of the participants\' estimated daily energy requirements for weight maintenance. Adherence to the allocated diets will be reinforced by monthly sessions of nutrition education and counselling from registered clinical dietitians.
BACKGROUND: The trial has been approved by the National Committee on Health Research Ethics of the Capital Region of Denmark. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be submitted for publication in international peer-reviewed scientific journals.
BACKGROUND: NCT05330247.
METHODS: The trial protocol was approved on 9 March 2022 (study number: H-21057605). The latest version of the protocol, described in this manuscript, was approved on 23 June 2023.

OBJECTIVE: To assess the prevalence of metabolic syndrome (MS) and association of central obesity measures such as body mass index (BMI), visceral fat adiposity (VFA) and superficial fat adiposity (SFA) with MS, diabetes (DM) and hypertension (HTN).
METHODS: Cross-sectional study design.
METHODS: Tertiary care hospital in Pakistan.
METHODS: 165 participants. There were 124 male participants and 41 female participants of Pakistani population. All participants above 18 years, who had unenhanced CT abdomen examination and relevant blood workup, were included. Patients with a known clinical history of coronary artery disease, HTN and DM as well as pregnant patients were excluded.
METHODS: VFA and SFA were estimated, at the level of the umbilicus. Data of BMI, MS, DM and HTN were extracted from patient files. Data for MS, DM and HTN were recorded as binary variables.
METHODS: The primary outcome measures were the prevalence of MS and the association of MS, DM and HTN with gender, VFA, SFA and BMI. P value of <0.05 was taken as significant with CI of 95%.
RESULTS: The prevalence of MS was 29.7%. There was a significant association of MS, DM and HTN with VFA, SFA and BMI. In gender-based analysis 48.7% of the female participants had MS. In subset analysis, 47% of male subjects in the third tertile of VFA revealed significant association with MS (p value <0.05) while only 32.7% of subjects in the obesity category of BMI had MS. SFA revealed a significant association with DM only (p value <0.5).
CONCLUSIONS: In conclusion, VFA shows a significant association with MS, DM and HTN. Considering these results, further studies with a larger sample size are warranted to generate gender-based cut-offs for VFA for obesity screening purposes.

BACKGROUND: Even with recent treatment advances, type 2 diabetes (T2D) remains poorly controlled for many patients, despite the best efforts to adhere to therapies and lifestyle modifications. Although estimates vary, studies indicate that in >10% of individuals with difficult-to-control T2D, hypercortisolism may be an underlying contributing cause. To better understand the prevalence of hypercortisolism and the impact of its treatment on T2D and associated comorbidities, we describe the two-part Hyper c ortisolism in P at ients with Difficult to Control Type 2 Di a betes Despite Receiving Standard-of-Care Therapies: Preva l ence and Treatment with Korl y m® (Mifepri st one) (CATALYST) trial.
METHODS: In part 1, approximately 1000 participants with difficult-to-control T2D (haemoglobin A1c (HbA1c) 7.5%-11.5% despite multiple therapies) are screened with a 1 mg dexamethasone suppression test (DST). Those with post-DST cortisol >1.8 µg/dL and dexamethasone level ≥140 ng/dL are identified to have hypercortisolism (part 1 primary endpoint), have morning adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) measured and undergo a non-contrast adrenal CT scan. Those requiring evaluation for elevated ACTH are referred for care outside the study; those with ACTH and DHEAS in the range may advance to part 2, a randomised, double-blind, placebo-controlled trial to evaluate the impact of treating hypercortisolism with the competitive glucocorticoid receptor antagonist mifepristone (Korlym®). Participants are randomised 2:1 to mifepristone or placebo for 24 weeks, stratified by the presence/absence of an abnormal adrenal CT scan. Mifepristone is dosed at 300 mg once daily for 4 weeks, then 600 mg daily based on tolerability and clinical improvement, with an option to increase to 900 mg. The primary endpoint of part 2 assesses changes in HbA1c in participants with hypercortisolism with or without abnormal adrenal CT scan. Secondary endpoints include changes in antidiabetes medications, cortisol-related comorbidities and quality of life.
BACKGROUND: The study has been approved by Cleveland Clinic IRB (Cleveland, Ohio, USA) and Advarra IRB (Columbia, Maryland, USA). Findings will be presented at scientific meetings and published in peer-reviewed journals.
BACKGROUND: NCT05772169.

OBJECTIVE: The association between the Triglyceride-Glucose (TyG) Index and mortality rates in patients with cardiovascular disease (CVD) remains unclear. This study investigates the association between the TyG index and the incidence of all-cause and CVD-specific mortality among individuals with a history of CVD.
METHODS: Population-based cohort study.
METHODS: Data were sourced from the US National Health and Nutrition Examination Survey (2007-2018) and linked mortality data, with follow-up continuing until 31 December 2019.
METHODS: The study population comprised 3422 individuals aged 20 years or older with a documented history of CVD.
METHODS: We examined the association between the TyG index and the risk of all-cause and cardiovascular mortality.
RESULTS: Over a median follow-up of 5.79 years, 1030 deaths occurred, including 339 due to CVD. Cox regression analysis, adjusted for multiple confounders, showed that individuals in the highest TyG index quartile, compared with those in the lowest, had HRs of 0.76 (95% CI: 0.60 to 0.96) for all-cause mortality and 0.58 (95% CI: 0.39 to 0.89) for CVD mortality. There was a significant inverse relationship between higher TyG index levels and lower mortality risks. For each unit increase in the TyG index, the adjusted HRs for all-cause and CVD mortality decreased by 18% (HR 0.82; 95% CI: 0.71 to 0.94) and 27% (HR 0.73; 95% CI: 0.57 to 0.92), respectively.
CONCLUSIONS: TyG index values are negatively associated with all-cause and CVD mortality risks among individuals with previous CVD. Further interventional studies are needed to clarify the impact of TyG levels on cardiovascular health.

OBJECTIVE: To evaluate the association between type 1 diabetes (T1D)/type 2 diabetes (T2D) and periodontitis and assess the influence of periodontitis on diabetes-related complications.
METHODS: Observational study; longitudinal analysis of register data.
METHODS: Swedish primary care centres, hospitals and dental clinics reporting to nationwide healthcare registers (2010-2020).
METHODS: 28 801 individuals with T1D (13 022 women; mean age 42 years) and 57 839 individuals without diabetes (non-T1D; 26 271 women; mean age 43 years). 251 645 individuals with T2D (110 627 women; mean age 61 years) and 539 805 individuals without diabetes (non-T2D; 235 533 women; mean age 60 years). Diabetes and non-diabetes groups were matched for age, gender and county of residence.
METHODS: Prevalent periodontitis, diabetes-related complications (retinopathy, albuminuria, stroke and ischaemic heart disease) and mortality.
RESULTS: Periodontitis was more common among T2D (22%) than non-T2D (17%). Differences were larger in younger age groups (adjusted RR at age 30-39 years 1.92; 95% CI 1.81 to 2.03) and exacerbated by poor glycaemic control. Periodontitis prevalence was 13% in T1D and 11% in non-T1D; only the subgroup with poor glycaemic control was at higher risk for periodontitis. Periodontitis was associated with a higher incidence of retinopathy (T1D: HR 1.08, 95% CI 1.02 to 1.14; T2D: HR 1.08, 95% CI 1.06 to 1.10) and albuminuria (T1D: HR 1.14, 95% CI 1.06 to 1.23; T2D: HR 1.09, 95% CI 1.07 to 1.11). Periodontitis was not associated with a higher risk for stroke, cardiovascular disease or higher mortality in T1D/T2D.
CONCLUSIONS: The association between T2D and periodontitis was strong and exacerbated by poor glycaemic control. For T1D, the association to periodontitis was limited to subgroups with poor glycaemic control. Periodontitis contributed to an increased risk for retinopathy and albuminuria in T1D and T2D.

BACKGROUND: Almonds have prebiotic potential to maintain gut health and regulate glycaemia. Western studies have shown their positive effects on preventing non-communicable diseases like diabetes and cardiovascular diseases. However, there is a lack of research involving Asian Indians, who have a higher predisposition to diabetes due to their unique \'Asian phenotype\'. Therefore, this study aims to evaluate the impact of almond supplementation on glycaemic control and gut health in adults with pre-diabetes in rural India through a randomised clinical trial.
METHODS: A parallel cluster randomised controlled trial with 178 participants with pre-diabetes (assigned 1:1) aged 20-50 years, of both genders, with a body mass index of 18.9-25 kg/m2, will be conducted in rural areas of Chikkaballapur, Kolar and Rural Bangalore districts in India. The intervention group will receive 56 g of almonds as mid-morning snacks for 16 weeks, while the control group will receive cereal/pulse-based traditional isocaloric snacks under the closed supervision of the study investigators. The primary outcome of the study is HbA1c measured at the 16th week. The secondary outcomes-anthropometry, clinical and other biochemical parameters-will be measured at 0th, 8th and 16th weeks, and a subgroup of 120 participants will undergo gut health analysis. Glucagon-like peptide 1 analysis will be conducted on 30 participants at 0th and 16th weeks. Statistical analysis will be performed using SPSS for Windows V.27.0, and both intention-to-treat and per-protocol analyses will be conducted.
BACKGROUND: Ethics approval was obtained from the Institutional Ethics Committee at Ramaiah Medical College, Bangalore, Karnataka, India (DRPEFP7672021). We will obtain the informed written consent of the participants prior to screening and enrolling them in the study. Results from this trial will be disseminated through publication in peer-reviewed journals and scientific gatherings.
BACKGROUND: Clinical Trial Registry of India (CTRI/2023/03/050421).

OBJECTIVE: Novel antidiabetes medications with proven cardiovascular or renal benefit, such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA), have been introduced to the market. This study explored the 4-year trends of antidiabetes medication use among medical hospitalisations with type 2 diabetes (T2D).
METHODS: Retrospective cohort study.
METHODS: Tertiary care hospital in Switzerland.
METHODS: 4695 adult hospitalisations with T2D and prevalent or incident use of one of the following antidiabetes medications (metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), sulfonylureas, GLP-1 RA, SGLT-2i, short-acting insulin or long-acting insulin), identified using electronic health record data. Quarterly trends in use of antidiabetes medications were plotted overall and stratified by cardiovascular disease (CVD) and chronic kidney disease (CKD).
RESULTS: We observed a stable trend in the proportion of hospitalisations with T2D who received any antidiabetes medication (from 77.6% during 2019 to 78% in 2022; p for trend=0.97). In prevalent users, the largest increase in use was found for SGLT-2i (from 7.4% in 2019 to 21.8% in 2022; p for trend <0.01), the strongest decrease was observed for sulfonylureas (from 11.4% in 2019 to 7.2% in 2022; p for trend <0.01). Among incident users, SGLT-2i were the most frequently newly prescribed antidiabetes medication with an increase from 26% in 2019 to 56.1% in 2022 (p for trend <0.01). Between hospital admission and discharge, SGLT-2i also accounted for the largest increase in prescriptions (+5.1%; p<0.01).
CONCLUSIONS: These real-world data from 2019 to 2022 demonstrate a significant shift in antidiabetes medications within the in-hospital setting, with decreased use of sulfonylureas and increased prescriptions of SGLT-2i, especially in hospitalisations with CVD or CKD. This trend aligns with international guidelines and indicates swift adaptation by healthcare providers, signalling a move towards more effective diabetes management.

OBJECTIVE: Diabetes care remains unavailable and unaffordable for many people. Adapting models of care to low-income and middle-income country contexts is a priority. Digital technology offers substantial potential yet must surmount health system, technological and acceptability issues. This formative research aimed to identify the potential for a digital technology solution (Diabetes Compass) to address diabetes care gaps in primary healthcare.
METHODS: Qualitative research was conducted in selected districts of Sri Lanka and Tanzania with practitioners, patients and family members. In-depth interviews assessed how digital solutions may improve diabetes care, acceptability and usability; contextual and clinical observations identified practitioner clinical competencies, strengths and weaknesses, and the influence of the care environment on service delivery; and workshop discussions explored strategies to encourage digital solution uptake and sustain use.
METHODS: The research was undertaken in 2022 at nine health facilities in Sri Lanka\'s Southern Province (Galle), and 16 health facilities in Tanzania\'s Lindi and Pwani Regions.
METHODS: Participants included primary and secondary care practitioners, facility managers, patients and family members.
RESULTS: There was striking concordance in the diabetes care gaps and potential for digital solutions in the two countries, and between practitioners, patients and family members. Five main gaps were practitioner training; health information systems and data; service delivery; infrastructure, equipment and medication; and community awareness and knowledge. Practitioners, patients and family members saw strong potential for digital solutions to improve early detection, diagnosis, secondary prevention of complications and improve patients\' and families\' experience of living with diabetes. They identified specific design and implementation considerations to enable the Diabetes Compass to realistically meet these needs and overcome challenges.
CONCLUSIONS: There was a strong appetite among practitioners, patients and family members for a digital solution to strengthen diabetes care. Their experience of challenges and practical recommendations informed the Diabetes Compass design.