Physical Activity, Sedentary Behavior, and Type 2 Diabetes: Mendelian Randomization Analysis

Yuan, Shuai; Li, Xue; Liu, Qianwen; Wang, Zhe; Jiang, Xia; Burgess, Stephen; Larsson, Susanna C.

doi:10.1210/jendso/bvad090

Cited by 11 publications

(2 citation statements)

References 49 publications

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“…The history of smoking among diabetic patients in our study and the association with increased diabetes risk align with established research on the impact of smoking on insulin resistance and T2DM development [15]. Similarly, our findings regarding physical activity align with numerous studies demonstrating its inverse relationship with T2DM risk [16]. Modifiable risk factors like smoking and sedentary lifestyle significantly influence T2DM development.…”

Section: Discussionsupporting

confidence: 89%

Observational, Multicenter, Retrospective, Study on the Usage Patterns of the Fixed Dose Combination of Glimepiride, Metformin, and Voglibose in Type 2 Diabetes Management

Shamanna,

Jha,

Makwana

et al. 2024

Cureus

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Objective This study aimed to evaluate and analyze the characteristics of Indian patients with type 2 diabetes mellitus (T2DM) in relation to the usage patterns of a fixed-dose combination (FDC) of glimepiride, metformin, and voglibose. Methods This retrospective, observational, multicentric analysis was conducted from March 2021 to September 2022. It involved adult patients (aged ≥18 years) with T2DM from 424 sites including a combination of hospitals and privately owned clinics across India to ensure comprehensive representation of the patient population The study included patients who had been treated with FDC of glimepiride, metformin, and voglibose of varying strengths for T2DM management. Data were collected through a pre-designed electronic form, which captured demographic details, medical history, T2DM history, and drug usage patterns from medical records. The collected data were then analyzed using descriptive statistical methods. Results This analysis encompassed a final cohort of 8,587 patients out of which 5,840 were males with a mean age of 54.91 years and a BMI of 28.41 kg/m 2 . Newly diagnosed T2DM cases were 35.23%, 54.79% had a family history, and 61.21% had risk factors such as smoking, sedentary lifestyle, and others. Dyslipidemia (13.94%) and neuropathy (14.48%) were common comorbidities. The most prescribed FDC was 1 mg glimepiride, 500 mg metformin, 0.2 mg voglibose (40.14%), the most preferred dosing frequency was once daily (52.92%) and the most common duration of treatment was one to three months (48.78%). Conclusion In routine Indian clinical practice, the triple drug FDC of 1 mg glimepiride, 500 mg metformin, and 0.2 mg voglibose, taken once daily for one to three months, was the most common treatment for both newly diagnosed and long-standing diabetes patients.

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Section: Discussionsupporting

confidence: 89%

Observational, Multicenter, Retrospective, Study on the Usage Patterns of the Fixed Dose Combination of Glimepiride, Metformin, and Voglibose in Type 2 Diabetes Management

Shamanna,

Jha,

Makwana

et al. 2024

Cureus

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“…These alterations have adverse effects on local tissue function and metabolism, which in turn impacts systemic health. Inactivity diminishes physical performance (Brook et al, 2022;Manini et al, 2007), whole-body metabolic flexibility (Bergouignan et al, 2013), and is associated with reduced quality of life (Yerrakalva et al, 2023) and increased risk of non-communicable diseases like type 2 diabetes (Yuan et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of NR4A3 during inactivity alters glucose metabolism and impairs translation in human skeletal muscle

Smith,

Gabriel,

Abdelmoez

et al. 2024

Preprint

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Background: Physical activity promotes health, whereas inactivity is associated with metabolic impairment. The transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3) is a pleiotropic regulator of skeletal muscle exercise adaptation and metabolism. However, the consequence of lower NR4A3 expression remains largely unexplored. We investigated the impact of NR4A3 downregulation on human skeletal muscle metabolism. Methods: Published transcriptomic datasets from human bed rest and limb immobilisation studies were curated to meta-analyse the effect of physical inactivity on skeletal muscle NR4A3 levels. In primary human skeletal muscle myotubes, siRNA and lentivirus were used to silence and overexpress NR4A3, respectively. Basal and stimulated (insulin w/wo leucine) signal transduction was determined by immunoblot analysis. Effects on glucose, fatty acid, and protein metabolism were measured using radiolabelled substrate assays. Lactate production was assessed in culture supernatant by colourimetry. Cell morphology was analysed by immunocytochemistry and gene expression was quantified by RT-qPCR. Results: Physical inactivity decreased skeletal muscle NR4A3 (-27%), concomitant with pathways related to mitochondrial function, cytoskeleton organization, chromatin regulation, protein synthesis and degradation. Silencing of nuclear-localised NR4A3 protein (-38%) decreased glucose oxidation (-18%) and increased lactate production (+23%) in vitro. This coincided with greater signalling downstream of AMPK and elevated rates of basal (+26%) and FCCP-stimulated (+55%) fatty acid oxidation. NR4A3 downregulation lowered protein synthesis (-25%), and impaired mTORC1 signalling. Alternatively, overexpression of the canonical NR4A3 protein isoform (+290%) augmented translation (+152%) and total cellular protein content, while partial restoration of NR4A3 levels rescued glucose oxidation in NR4A3-silenced cells. NR4A3 depletion reduced myotube area (-48%) and further altered protein and gene expression of key contractile elements in skeletal muscle. Conclusions: Our study connects reduced NR4A3 expression with physical inactivity and indicates that NR4A3 downregulation in human skeletal muscle has adverse effects on glucose metabolism and protein synthesis. Thus, decrements in NR4A3 abundance could be causal in the deleterious health consequences resulting from sedentary lifestyles and targeting NR4A3 may offer new avenues for combating conditions such as disuse muscle atrophy.

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Atopic Dermatitis and Diabetes

Sendrea,

Salavastru

2024

Cutaneous Manifestations in Diabetes

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Physical Activity, Sedentary Behavior, and Type 2 Diabetes: Mendelian Randomization Analysis

Cited by 11 publications

References 49 publications

Observational, Multicenter, Retrospective, Study on the Usage Patterns of the Fixed Dose Combination of Glimepiride, Metformin, and Voglibose in Type 2 Diabetes Management

Observational, Multicenter, Retrospective, Study on the Usage Patterns of the Fixed Dose Combination of Glimepiride, Metformin, and Voglibose in Type 2 Diabetes Management

Downregulation of NR4A3 during inactivity alters glucose metabolism and impairs translation in human skeletal muscle

Atopic Dermatitis and Diabetes

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