Physical activity and weight loss among adults with type 2 diabetes and overweight or obesity: a post hoc analysis of the Look AHEAD trial

Importance: Prior findings from the Look AHEAD trial showed no significant reduction in the risk of cardiovascular events by lifestyle-induced weight loss among individuals with type 2 diabetes (T2D) and overweight or obesity. However, physical activity (PA) may modify the changes in cardiovascular risk associated with weight loss. Objective: To examine the joint association of weight loss and PA with the risk of adverse cardiovascular events in patients with T2D and overweight or obesity. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Look AHEAD randomized clinical trial, which compared the cardiovascular effects of weight loss by intensive lifestyle intervention vs diabetes support and education among individuals with T2D and overweight or obesity. The study was conducted from June 2001 to September 2012, and participants were patients in the substudy of accelerometry-measured PA from 8 locations in the United States. Data were analyzed from June to August 2023. Exposures: Body weight change and accelerometer-derived PA volume across the first 4 years. Main Outcomes and Measures: The primary outcome was a composite cardiovascular outcome including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina. Results: Among a total of 1229 participants (mean [SD] age, 60 [7] years; 533 male [43%]), 333 (27%) achieved and maintained weight loss for the first 4 years. Among the individuals who maintained weight loss, 105 (32%) maintained high PA volume. During a median of 9.5 years of follow-up, 198 participants (16.1%) experienced the primary outcome. Compared with those with low PA volume and no weight loss (105 [15.8%]), maintaining high PA volume and weight loss was associated with a 61% lower risk of the primary end point (hazard ratio, 0.39; 95% CI, 0.19-0.81; P = .01). However, there was no significant difference in the risk of the primary end point among those with either weight loss only or high PA only. The multiplicative interaction between weight loss and PA for the risk of cardiovascular events was also significant (P for interaction = .01). Conclusions and Relevance: In this cohort study, maintaining weight loss and higher PA volume was associated with a lower risk of the composite cardiovascular outcome. The findings suggest that the cardiovascular benefits of PA may vary and be enhanced by weight loss among individuals with T2D and overweight or obesity

Changes in Cardiovascular Health during Young Adulthood and Subclinical Atherosclerosis in Middle Age: The CARDIA Study

Background and aims: The benefits of reaching ideal cardiovascular health (CVH) are well known, but it is unclear whether positive CVH changes from young adulthood to middle age reduce subclinical atherosclerosis risk. This study examined associations of changes in CVH from young adulthood to middle age and CVH in young adulthood with subclinical atherosclerosis. Methods: Data was analyzed from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CVH was examined at years 0 and 20 using Life Simple 7 metrics from AHA guideline. Coronary artery calcium (CAC) was identified at years 20 and 25. Carotid intima-media thickness (IMT) was identified at year 20. Results: Among 2,935 participants (56.2% women, 46.7% black), the change of CVH score was –1.26 (2.13). For per 1-unit increase in CVH at baseline, the adjusted odds ratios (ORs) of presence of CAC and IMT were 0.81 (95% CI 0.78, 0.86) and 0.85 (95% CI 0.76, 0.94), respectively. For per 1-unit increase in CVH changes, the adjusted ORs of CAC and IMT were 0.86 (95% CI 0.82, 0.90) and 0.81 (95% CI 0.73, 0.90). Compared with stable moderate CVH, improvement from moderate to high was associated with a lower risk of CAC (0.64 [95% CI 0.43, 0.96]), while retrogression from moderate to low was associated with a higher risk of CAC (1.45 [95% CI 1.19, 1.76]). Conclusions: Positive changes of CVH during young adulthood are associated with negative subclinical atherosclerosis risk in middle age, indicating the importance of reaching an ideal cardiovascular health status through young adulthood

Association between the insulin resistance and all-cause mortality in patients with moderate and severe aortic stenosis: a retrospective cohort study

Abstract Background The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance (IR). However, whether the TyG index has prognostic value in patients with moderate to severe aortic stenosis (AS) remains unclear. Methods This study enrolled 317 patients with moderate to severe AS at the First Affiliated Hospital of Sun Yat-Sen University. The patients were grouped according to the cut-off value of the TyG index. Cox regression with Firth’s penalized maximum likelihood method and restricted cubic splines regression were conducted to assess the association between the TyG index and all-cause mortality. The added value of the TyG index included in the traditional risk factors model for outcome prediction was also analyzed. Results Among 317 patients (mean age 67.70 years, 62.8% male), there was 84 all-cause mortality during a median 38.07 months follow-up. After fully adjusting for confounders, a per-unit increase in the TyG index was associated with a 62% higher all-cause mortality risk (HR 1.622, 95% CI 1.086–2.416, p = 0.018). The restricted cubic splines regression model revealed a linear association between the TyG index and the risk of all-cause mortality (p for nonlinearity = 0.632). The addition of the TyG index in the basic risk model has an incremental effect on the prediction of mortality [C-statistic change from 0.755 to 0.768; continuous net reclassification improvement (95% CI): 0.299 (0.051–0.546), p = 0.017; integrated discrimination improvement: 0.017 (0.001–0.033), p = 0.044]. Conclusions Higher IR assessed by the TyG index was associated with a higher risk of all-cause mortality in patients with moderate and severe AS

New Insights into Rate Control: Time in Target Range of Resting Heart Rate and Major Adverse Outcomes in Atrial Fibrillation

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation

Protective effects of astragaloside IV on db/db mice with diabetic retinopathy.

ObjectivesDiabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the potential biological functions of astragaloside IV (AS IV) have long been described in traditional system of medicine, its protective effect on DR remains unclear. This study aims to investigate the function and mechanism of AS IV on type 2 diabetic db/db mice.MethodsDb/db mice were treated with AS IV (4.5 mg/kg or 9 mg/kg) or physiological saline by oral gavage for 20 weeks along with db/m mice. In each group, retinal ganglion cell (RGC) function was measured by pattern electroretinogram (ERG) and apoptosis was determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Blood and retina aldose reductase (AR) activity were quantified by chemiluminescence analysis. The expressions of phosporylated-ERK1/2, NF-κB were determined by Western blot analysis. Furthermore, the expression of related downstream proteins were quantified by Label-based Mouse Antibody Array.ResultsAdministration of AS IV significantly improved the amplitude in pattern ERG and reduced the apoptosis of RGCs.in db/db mice. Furthermore, downregulation of AR activity, ERK1/2 phosphorylation, NF-κB and related cytokine were observed in AS IV treatment group.ConclusionsOur study indicated that AS IV, as an inhibitor of AR, could prevent the activation of ERK1/2 phosporylation and NF-kB and further relieve the RGCs disfunction in db/db mice with DR. It has provided a basis for investigating the clinical efficacy of AR inhibitors in preventing DR

Animal general situations (collected every 4 weeks).

<p>A: body weight in all groups during treatment. B: Blood glucose in all groups during treatment.</p

The effect of astragaloside IV on the apoptosis of retina cells.

<p>Apoptotic cells were marked with green fluorescence, the nuclei of cells are stained by blue fluorescence (DAPI). A: LC, B: NC, C: AL, D: AH. GCL, retinal ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer. Original magnification: ×20; scale bar, 100 mm. Triangles: Apoptotic cells.</p

Pattern ERGs derived from each eye in response to pattern reversal of horizontal gratings in a population of 48 mice aged 28 weeks.

<p>Individual waveforms of each eye are shown superimposed in each group. Mean amplitude in each group is regarded as a consult. A: LC, B: NC, C: AL, D: AH.</p