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Background: The relationship between ankle blood pressure (BP) and cardiovascular disease remains unclear. We examined the relationships between known and new ankle BP indices and major cardiovascular outcomes in people with and without type 2 diabetes. Methods: We used data from 3 large trials with measurements of ankle systolic BP (SBP), ankle-brachial index (ABI, ankle SBP divided by arm SBP), and ankle-pulse pressure difference (APPD, ankle SBP minus arm pulse pressure). The primary outcome was a composite of cardiovascular mortality, myocardial infarction, hospitalization for heart failure, or stroke. Secondary outcomes included death from cardiovascular causes, total (fatal and non-fatal) myocardial infarction, hospitalization for heart failure, and total stroke. Results: Among 42,929 participants (age 65.6 years, females 31.3%, type 2 diabetes 50.1%, 53 countries), the primary outcome occurred in 7230 (16.8%) participants during 5 years of follow-up (19.4% in people with diabetes, 14.3% in those without diabetes). The incidence of the outcome increased with lower ankle BP indices. Compared with people whose ankle BP indices were in the highest fourth, multivariable-adjusted hazard ratios (HRs, 95% CI) of the outcome for each lower fourth were 1.05 (0.98–1.12), 1.17 (1.08–1.25), and 1.54 (1.54–1.65) for ankle SBP; HR 1.06 (0.99–1.14), 1.26 (1.17–1.35), and 1.48 (1.38–1.58) for ABI; and HR 1.02 (0.95–1.10), 1.15 (1.07–1.23), and 1.48 (1.38–1.58) for APPD. The largest effect size was noted for ankle SBP (HRs 1.05 [0.90–1.21], 1.21 [1.05–1.40], and 1.93 [1.68–2.22]), and APPD (HRs 1.08 [0.93–1.26], 1.30 [1.12–1.50], and 1.97 [1.72–2.25]) with respect to hospitalization for heart failure, while only a marginal association was observed for stroke. The relationships were similar in people with and without diabetes (all p for interaction > 0.05). Conclusions: Inverse and independent associations were observed between ankle BP and cardiovascular events, similarly in people with and without type 2 diabetes. The largest associations were observed for heart failure and the smallest for stroke. Including ankle BP indices in routine clinical assessments may help to identify people at highest risk of cardiovascular outcomes. Ankle blood pressure indices and incidence of major cardiovascular outcomes. Expanded MACE, a composite of death from cardiovascular causes, myocardial infarction,hospitalization for heart failure, or stroke. BP, blood pressure; CV, cardiovascular; HHF, hospitalization for heart failure; HR, Hazard ratio (for the lowest fourth of blood pressure indice compared to the highest); MACE, major adverse cardiovascular events; MI, myocardial infarction; Total, fatal and non-fatal MI or stroke. [ABSTRACT FROM AUTHOR]

Aims: To describe the development and report the first‐stage validation of a digital version of the digit symbol substitution test (DSST), for assessment of cognitive function in older people with diabetes. Materials and Methods: A multidisciplinary team of experts was convened to conceptualize and build a digital version of the DSST and develop a machine‐learning (ML) algorithm to analyse the inputs. One hundred individuals with type 2 diabetes (aged ≥ 60 years) were invited to participate in a one‐time meeting in which both the digital and the pencil‐and‐paper (P&P) versions of the DSST were administered. Information pertaining to demographics, laboratory measurements, and diabetes indices was collected. The correlation between the digital and P&P versions of the test was determined. Additionally, as part of the validation process, the performance of the digital version in people with and without known risk factors for cognitive impairment was analysed. Results: The ML model yielded an overall accuracy of 89.1%. A strong correlation was found between the P&P and digital versions (r = 0.76, p < 0.001) of the DSST, as well as between the ML model and the manual reading of the digital DSST (r = 0.99, p < 0.001). Conclusions: This study describes the development of and provides first‐stage validation data for a newly developed digital cognitive assessment tool that may be used for screening and surveillance of cognitive function in older people with diabetes. More studies are needed to further validate this tool, especially when self‐administered and in different clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Red and processed meat is considered risk factors of gestational diabetes mellitus (GDM), but the evidence is inconclusive. We aimed to examine the association between red and processed meat intake and odds of GDM among South Asian and White European women living in Canada. Methods: This is a cross-sectional analysis of pregnant women from two birth cohorts: SouTh Asian biRth cohorT (START; n = 976) and Family Atherosclerosis Monitoring In earLY life (FAMILY; n = 581). Dietary intake was assessed using a validated 169-item semi-quantitative food-frequency questionnaire (FFQ). Multivariate logistic regression models were used to examine the associations between gestational diabetes and: 1) total red and processed meat; 2) unprocessed red meat; 3) processed meat and GDM after adjustment for potential confounders. Results: There were 241 GDM cases in START and 91 in FAMILY. The median total red and processed meat intake were 1.5 g/d (START) and 52.8 g/d (FAMILY). In START, the multivariable-adjusted odds ratio (OR) showed neither lower nor higher intakes of unprocessed red meat (p-trend = 0.68), processed meat (p-trend = 0.90), or total red and processed meat (p-trend = 0.44), were associated with increased odds of GDM, when compared with medium intake. Similar results were observed in FAMILY except for processed meat intake [OR = 0.94 (95% CI 0.47–1.91), for medium versus low and OR = 1.51 (95% CI 0.77–2.29) for medium versus high; p-trend = 0.18] after adjusting for additional dietary factors such as the diet quality score, total fiber, saturated fat and glycemic load. Conclusion: Medium compared with low or high red and processed meat intake is not associated with GDM in White Europeans and South Asians living in Canada. [ABSTRACT FROM AUTHOR]

It has long been known that some patients with type 2 diabetes (T2DM) can experience sustained metabolic improvement to near-normal levels of glycemia either spontaneously or after medical intervention. Now recognized as remission of diabetes, this intriguing state is currently more feasible than ever before due to profound advances in metabolic surgery, pharmacologic therapy, and regimens of lifestyle modification. This enhanced capacity to induce remission has revealed new pathophysiologic insights, including the presence of a reversible component of the pancreatic beta-cell dysfunction that otherwise drives the chronic progressive nature of T2DM. In doing so, it has changed the therapeutic landscape by offering new potential management objectives and considerations for patients and providers. However, the excitement around these developments must also be tempered by the sobering realities of our current understanding of remission, including the recognition that this condition may not be permanent (resulting in glycemic relapse over time) and that beta-cell function may not be normalized in the setting of remission. These limitations highlight both the many gaps in our current understanding of remission and the caution with which clinical discussions must be handled for clear patient-directed communication of the pros and cons of targeting this outcome in practice. In this mini-review, we consider this rapidly growing literature, including its implications and its limitations, and thereby seek to provide objective balanced perspectives on targeting remission of T2DM in current clinical care. [ABSTRACT FROM AUTHOR]

Aims: To estimate the incidence of a major adverse cardiovascular event (MACE) and a composite kidney outcome across estimated glomerular filtration rate (eGFR) and urine albumin‐to‐creatinine ratio (UACR) levels, and to determine whether efpeglenatide's effect varies with these indices. Materials and Methods: AMPLITUDE‐O trial data were used to estimate the relationship of eGFR, UACR, and Kidney Disease Improving Global Outcomes (KDIGO) category to the hazard of MACE and the kidney composite. Interactions on these outcomes between eGFR and the UACR, and between each of these variables and efpeglenatide were also assessed. Results: Baseline eGFR and UACR were available for 3983 participants (mean age 64.5 years). During a median follow‐up of 1.8 years, the hazards of MACE and the kidney composite for the lowest versus highest eGFR third were 1.6 (95% confidence interval [CI] 1.2, 2.2) and 2.3 (95% CI 1.9, 2.8), respectively. The hazards for the highest versus the lowest UACR third were 2.3 (95% CI 1.8, 3.1) and 18.0 (95% CI 12.7, 25.5), respectively, and for the high‐ versus low‐risk KDIGO categories the hazards were 2.4 (95% CI 1.8, 3.1) and 16.0 (95% CI 11.6, 22.0), respectively. eGFR and UACR were independent determinants of both outcomes, but negatively interacted with each other for the kidney outcome. Efpeglenatide's effect on both outcomes did not vary with any kidney disease measure (all interaction p values ≥0.26). Conclusions: In high‐risk people with diabetes, eGFR, UACR, and KDIGO category have different relationships to incident cardiovascular and kidney outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of kidney‐related risk category. [ABSTRACT FROM AUTHOR]

Aim: The outcomes reduction with an initial glargine intervention (ORIGIN) trial reported that, allocation to insulin glargine‐mediated normoglycaemia versus standard care, and to omega 3 fatty acids versus placebo had a neutral effect on cognitive test scores when analysed as continuous variables. Analyses of these scores as standardized categorical variables using a previously validated strategy may yield different results. Materials and Methods: The ORIGIN trial recruited participants with dysglycaemia and additional cardiovascular risk factors from 573 sites in 40 countries. They completed a mini mental state examination and a subset completed the digit symbol substitution test at baseline and up to three subsequent visits. The effect of the interventions on country‐standardized substantive cognitive impairment, defined as the first occurrence of a baseline‐adjusted follow‐up mini mental state examination or digit symbol substitution test score ≥1.5 standard deviations below the baseline mean score in each participant's country was assessed using Cox proportional hazards models. Results: During a median follow‐up of 6.2 years, 2627 of 11 682 people (22.5%) developed country‐standardized substantive cognitive impairment. The hazard of this outcome was reduced by 9% (hazard ratio 0.91, 95% confidence interval 0.85, 0.99; p =.023) in participants assigned to insulin glargine (21.6%) versus standard care (23.3%). Conversely, the hazard of this outcome was not affected by assignment to omega 3 fatty acid versus placebo (hazard ratio 0.93, 95% confidence interval 0.86, 1.01; p =.074). Conclusions: In this post hoc exploratory analysis, insulin glargine‐mediated normoglycaemia but not omega 3 fatty acids reduced the hazard of substantive cognitive impairment in people with dysglycaemia and additional cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Background: The Acarbose Cardiovascular Evaluation (ACE) trial (ISRCTN91899513) evaluated the alpha‐glucosidase inhibitor acarbose, compared with placebo, in 6522 patients with coronary heart disease and impaired glucose tolerance in China and showed a reduced incidence of diabetes. We assessed the within‐trial medical resource use and costs, and quality‐adjusted life years (QALYs). Methods: Resource use data were collected prospectively within the ACE trial. Hospitalizations, medications, and outpatient visits were valued using Chinese unit costs. Medication use was measured in drug days, with cardiovascular and diabetes drugs summed across the trial by participant. Health‐related quality of life was captured using the EuroQol‐5 Dimension‐3 Level questionnaire. Regression analyses were used to compare resource use, costs, and QALYs, accounting for regional variation. Costs and QALYs were discounted at 3% yearly. Results: Hospitalizations were 6% higher in the acarbose arm during the trial (rate ratio 1.06, p =.009), but there were no significant differences in total inpatient days (rate ratio 1.04, p =.30). Total costs per participant, including study drug, were significantly higher for acarbose (¥ [Yuan] 56 480, £6213), compared with placebo (¥48 079, £5289; mean ratio 1.18, p < 0.001). QALYs reported by participants in the acarbose arm (3.96 QALYs) were marginally higher than in the placebo arm (3.95 QALYs), but the difference was not statistically significant (0.01 QALYs; p =.58). Conclusions: Acarbose, compared with placebo, participants cost more due to study drug costs and reported no statistically significant difference in QALYs. These higher within‐trial costs could potentially be offset in future by savings from the acarbose‐related lower incidence of diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether adiposity depots modulate vaspin levels and whether vaspin predicts type 2 diabetes (T2D) risk, through epidemiological and genetic analyses. RESEARCH DESIGN AND METHODS: We assessed the relationship of plasma vaspin concentration with incident and prevalent T2D and adiposity-related variables in 1) the Prospective Urban and Rural Epidemiology (PURE) biomarker substudy (N = 10,052) and 2) the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (N = 7,840), using regression models. We then assessed whether vaspin is causally associated with T2D and whether genetic variants associated with MRI-measured adiposity depots modulate vaspin levels, using two-sample Mendelian randomization (MR). RESULTS: A 1-SD increase in circulating vaspin levels was associated with a 16% increase in incident T2D in the PURE cohort (hazard ratio 1.16; 95% CI 1.09–1.23; P = 4.26 × 10−7) and prevalent T2D in the ORIGIN cohort (odds ratio [OR] 1.16; 95% CI 1.07–1.25; P = 2.17 × 10−4). A 1-unit increase in BMI and triglyceride levels was associated with a 0.08-SD (95% CI 0.06–0.10; P = 2.04 × 10−15) and 0.06-SD (95% CI 0.04–0.08; P = 4.08 × 10−13) increase, respectively, in vaspin in the PURE group. Consistent associations were observed in the ORIGIN cohort. MR results reinforced the association between vaspin and BMI-adjusted T2D risk (OR 1.01 per 1-SD increase in vaspin level; 95% CI 1.00–1.02; P = 2.86 × 10−2) and showed that vaspin was increased by 0.10 SD per 1-SD decrease in genetically determined gluteofemoral adiposity (95% CI 0.02–0.18; P = 2.01 × 10−2). No relationships were found between subcutaneous or visceral adiposity and vaspin. CONCLUSIONS: These findings support that higher vaspin levels are related to increased T2D risk and reduced gluteofemoral adiposity, positioning vaspin as a promising clinical predictor for T2D. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To evaluate the effect on type 2 diabetes remission of short‐term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed‐ratio insulin degludec/liraglutide.In a multicentre open‐label randomized controlled trial, insulin‐naïve participants within 5 years of diabetes diagnosis were assigned to a 16‐week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose‐lowering drugs.A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m2, and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16‐week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period.An intensive remission‐induction intervention including fixed‐ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors both improve cardiovascular and kidney outcomes in persons with type 2 diabetes. We conducted a systematic review and meta-analysis to assess the effects of GLP-1 receptor agonists on clinical outcomes with and without SGLT2 inhibitors. Methods: We searched MEDLINE and Embase databases from inception until July 12, 2024 for randomized, double-blind, placebo-controlled outcome trials of GLP-1 receptor agonists in type 2 diabetes that reported treatment effects by baseline use of SGLT2 inhibitors, with findings supplemented by unpublished data. We estimated treatment effects by baseline SGLT2 inhibitor use using inverse variance weighted meta-analysis. The main cardiovascular outcomes were major adverse cardiovascular events ([MACE] nonfatal myocardial infarction, stroke or cardiovascular death) and hospitalization for heart failure. Kidney outcomes included a composite of ≥50 % reduction in estimated glomerular filtration rate (eGFR ), kidney failure or death due to kidney failure, and annualized rate of decline in eGFR (eGFR slope). Serious adverse events and severe hypoglycemia were also evaluated. This meta-analysis was registered on PROSPERO (CRD42024565765). Results: We identified three trials with 1,743/17,072 (10.2%) participants with type 2 diabetes receiving an SGLT2 inhibitor at baseline. GLP-1 receptor agonists reduced the risk of MACE by 21% (HR 0.79, 95% CI 0.71-0.87), with consistent effects in those receiving and not receiving SGLT2 inhibitors at baseline (HR 0.77, 95% CI 0.54-1.09 and HR 0.79, 95% CI 0.71-0.87, respectively; P-heterogeneity=0.78). The effect on hospitalization for heart failure was similarly consistent regardless of SGLT2 inhibitor use (HR 0.58, 95% CI 0.36-0.93 and HR 0.73, 95% CI 0.63-0.85; P-heterogeneity=0.26). Effects on the composite kidney outcome (RR 0.79, 95% CI 0.66-0.95 ) and eGFR slope (0.78 mL/min/1.73m 2 /year, 95% CI 0.57-0.98) also did not vary according to SGLT2 inhibitor use (P-heterogeneity=0.53 and 0.94, respectively). Serious adverse effects and severe hypoglycemia were also similar regardless of SGLT2 inhibitor use (P-heterogeneity=0.29 and 0.50, respectively). Conclusions: In persons with type 2 diabetes, the cardiovascular and kidney benefits of GLP-1 receptor agonists are consistent regardless of SGLT2 inhibitor use.