Causal associations between cardiorespiratory fitness and type 2 diabetes

Cai, Lina; Gonzales, Tomas I.; Wheeler, Eleanor; Kerrison, Nicola D.; Day, Felix R.; Langenberg, Claudia; Perry, John R. B.; Brage, Sören; Wareham, Nick

doi:10.1038/s41467-023-38234-w

Cited by 16 publications

(7 citation statements)

References 76 publications

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“…While there is substantial evidence on how galectin-1 modulates inflammation, studies are needed to further elucidate the direct effects of galectin-1 in healthy muscle physiology [40]. High intensity training increases CRF, which in turn is causally associated with lower risk of T2D in genetic studies [41][42][43]. As galectin-1 is a proposed biomarker in T2D, future studies should examine the potential biomarkers capabilities of serum galectin-1 in exercise interventions in patients with T2D.…”

Section: Plos Onementioning

confidence: 99%

Cardiorespiratory fitness and the association with galectin-1 in middle-aged individuals

Arvidsson,

Rodrigues Silva,

Ekblom

et al. 2024

PLoS ONE

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Galectin-1 plays a functional role in human metabolism and the levels are altered in obesity and type 2 diabetes (T2D). This study investigates the association of cardiorespiratory fitness (CRF) with galectin-1 and the interconnection with body fatness. Cross-sectional data from the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot was analyzed, including a sample of 774 middle-aged individuals. A submaximal cycle ergometer test was used to estimate CRF as an indirect measure of the physical activity (PA) level. Serum-galectin-1 concentration was determined from venous blood collected after an overnight fast. Body mass index (BMI) was used as an indirect measure of body fatness. CRF was significantly associated with galectin-1, when controlled for age and sex (regression coefficient (regr coeff) = -0.29, p<0.001). The strength of the association was attenuated when BMI was added to the regression model (regr coeff = -0.09, p = 0.07), while the association between BMI and galectin-1 remained strong (regr coeff = 0.40, p<0.001). CRF was associated with BMI (regr coeff = -0.50, p<0.001). The indirect association between CRF and galectin-1 through BMI (-0.50 x 0.40) contributed to 69% of total association (mediation analysis). In group comparisons, individuals with low CRF-high BMI had the highest mean galectin-1 level (25 ng/ml), while individuals with high CRF-low BMI had the lowest level (21 ng/ml). Intermediate levels of galectin-1 were found in the low CRF-low BMI and high CRF-high BMI groups (both 22 ng/ml). The galectin-1 level in the low CRF-high BMI group was significantly different from the other three groups (P<0.001). In conclusion, galectin-1 is associated with CRF as an indirect measure of the PA level through interconnection with body fatness. The size of the association is of clinical relevance.

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Section: Plos Onementioning

confidence: 99%

Cardiorespiratory fitness and the association with galectin-1 in middle-aged individuals

Arvidsson,

Rodrigues Silva,

Ekblom

et al. 2024

PLoS ONE

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“…The innovation of our approach is contextualized by a rich history of approaches targeting CRF prediction to ease clinical translation. Indeed, previous work to develop nonexercise prediction models of CRF has spanned physical activity questionnaires [51][52][53][54][55][56][57][58][59][60] , resting heartrate 53,58,60 , BMI/body composition [51][52][53][54][55][56][57][58][59][60][61][62][63] , genetics 64 , proteomics 16 , metabolomics 13 and activity monitor data [61][62][63]65 . However, most previous studies have been conducted in healthy or trained individuals and lack a demonstration of strong relations with to multisystem clinical outcomes.…”

Section: Articlementioning

confidence: 99%

Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks

Perry,

Farber-Eger,

Gonzales

et al. 2024

Nat Med

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Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48–0.52) per 1 s.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable.

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“…Moreover, reducing glucose entry into β-cells for aerobic metabolism directly reduces ROS production and attenuates oxidative stress [176]. A recent large cohort study showed that appropriate exercise increases cardiorespiratory fitness, and that a higher cardiorespiratory fitness reduces T2DM risk [177]. The American College of Sports Medicine updated the Consensus Statement on exercise in patients with T2DM in 2022 [178].…”

Section: Diet-and Exercise-based Therapymentioning

confidence: 99%

Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

Su,

Luo,

et al. 2023

IJMS

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Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh leading cause of death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists and SGLT-2 inhibitors, single-target drugs are gradually failing to meet the therapeutic requirements owing to the individual variability, diversity of pathogenesis, and organismal resistance. Therefore, there remains a need to investigate the pathogenesis of T2DM in more depth, identify multiple therapeutic targets, and provide improved glycemic control solutions. This review presents an overview of the mechanisms of action and the development of the latest therapeutic agents targeting T2DM in recent years. It also discusses emerging target-based therapies and new potential therapeutic targets that have emerged within the last three years. The aim of our review is to provide a theoretical basis for further advancement in targeted therapies for T2DM.

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Causal associations between cardiorespiratory fitness and type 2 diabetes

Cited by 16 publications

References 76 publications

Cardiorespiratory fitness and the association with galectin-1 in middle-aged individuals

Cardiorespiratory fitness and the association with galectin-1 in middle-aged individuals

Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks

Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

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