Related Experiment Video
Updated: May 2, 2026
Measuring Frailty in HIV-infected Individuals. Identification of Frail Patients is the First Step to Amelioration and Reversal of Frailty
Published on: July 24, 2013
The Impact of SGLT1 Inhibition on Frailty and Sarcopenia: A Mediation Mendelian Randomization Study
Bang-Bang Huang1,2,3,4,5, Yu-Jie Zhang6, Guang-Feng Ruan7
1Department of Geriatrics, First Affiliated Hospital of Fujian Medical University, Institute of Neuroscience, Fujian Medical University, Fuzhou, China.
Background:
Although pharmacological effects of SGLT2 inhibitors on the development of frailty and sarcopenia were known, the role of SGLT1 remained less clear. The present study investigated the possible effect of SGLT1 inhibition on these conditions and explored potential mediators.
Methods:
A two-sample Mendelian randomization (MR) analysis was performed to assess the effect of SGLT1 inhibition on frailty index (FI) and low grip strength in individuals aged 60 years and older using both the FNIH and EWGSOP criteria. Subsequently, a two-step MR analysis was conducted to investigate the mediating role of insulin resistance phenotype and identify potential mediators of the effect of SGLT1 inhibition on the FI and low grip strength from 1558 plasma proteins and 1352 metabolites.
Results:
Genetically predicted SGLT1 inhibition was associated with decreased FI (β: -0.290 [95% CI: -0.399, -0.181]) and reduced risk of low grip strength in individuals aged 60 years and older under both FNIH (β: -0.796 [95% CI: -1.216, -0.376]) and EWGSOP criteria (β: -0.287 [95% CI: -0.532, -0.041]). The two-step MR analysis demonstrated the role of insulin resistance phenotype in mediating SGTL1 inhibition on alleviating frailty (mediation proportion = 19.56% [95% CI: 8.42%, 30.70%]). After screening, 24 proteins and 16 metabolites were identified as mediators of the impact of SGLT1 inhibition on FI. Additionally, 13 proteins and 16 metabolites were found to mediate the effect of SGLT1 inhibition on low grip strength according to FNIH criteria while 22 proteins and 6 metabolites were shown to mediate the impact of SGLT1 inhibition on low grip strength under EWGSOP criteria.
Conclusions:
SGLT1 inhibition potentially mitigated frailty and sarcopenia through several biological mediators, shedding new light for therapeutic intervention.
Insights
Sodium-glucose cotransporter 1 (SGLT1) inhibition may reduce frailty and sarcopenia in older adults. This effect is partly mediated by insulin resistance and involves various proteins and metabolites.
Area of Science:
- Gerontology
- Metabolic Medicine
- Pharmacology
Background:
- The role of Sodium-glucose cotransporter 1 (SGLT1) in frailty and sarcopenia is less understood compared to SGLT2 inhibitors.
- This study investigates the potential impact of SGLT1 inhibition on these age-related conditions.
Purpose of the Study:
- To assess the effect of SGLT1 inhibition on frailty index (FI) and low grip strength in individuals aged 60 years and older.
- To explore potential mediators, including insulin resistance, plasma proteins, and metabolites, involved in this process.
Main Methods:
- A two-sample Mendelian randomization (MR) analysis was employed to evaluate the genetic association between SGLT1 inhibition and frailty/sarcopenia.
- A two-step MR analysis was used to identify mediating factors, such as insulin resistance, 1558 plasma proteins, and 1352 metabolites.
Main Results:
- Genetically predicted SGLT1 inhibition was linked to a decreased FI and a reduced risk of low grip strength.
- Insulin resistance phenotype mediated 19.56% of the effect of SGLT1 inhibition on alleviating frailty.
- Numerous proteins and metabolites were identified as potential mediators for the effects of SGLT1 inhibition on frailty and grip strength.
Conclusions:
- SGLT1 inhibition shows potential in mitigating frailty and sarcopenia in older adults.
- The findings highlight several biological mediators, offering new avenues for therapeutic interventions targeting age-related decline.
