Low free triiodothyronine levels are associated with risk of frailty in older adults with type 2 diabetes mellitus

Highlights

• The association between thyroid hormone concentrations and frailty in older adults with T2DM was investigated.

• The free triiodothyronine (FT3) FT3 level was the lowest among frail people

• Low levels of FT3 were associated with an increased risk of frailty

Abstract

Objectives

With aging populations around the world, frailty is becoming more prevalent increasing the need to early identify those at risk of frailty. The association between thyroid hormone levels and frailty in subjects with type 2 diabetes mellitus (T2DM) remains unclear. The objective of the study was to evaluate the relationship between thyroid hormone concentrations and frailty in older adults with T2DM.

Methods

A total of 240 older adults with T2DM were divided into three groups according to the frailty phenotype criteria: robust group (n = 94), pre-frail (n = 110) and frail group (n = 36). Concentrations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH), 25-hydroxyvitamin D₃ [25(OH) D₃], highly sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were determined. Handgrip strength was measured using a Jamar hand dynamometer. Physical function was assessed by gait speed and the timed go and up (TUG) test. Logistic regression analysis was performed to evaluate the association between FT3 and frailty.

Results

The FT3 level was the lowest among frail people (2.56 ± 0.42 pg/mL), followed by pre-frail participants (2.73 ± 0.38 pg/mL), with the highest among the robust subjects (2.83 ± 0.43 pg/mL). FT3 level was positively correlated with handgrip strength and gait speed (R = 0.313, P < 0.001; R = 0.250, P < 0.001, respectively), while negatively correlated with TUG time (R = −0.276, P < 0.001). After adjusting for age, sex, TSH, 25(OH) D₃ and estimate glomerular filtration rate (eGFR), logistic regression showed that low FT3 was significantly associated with an increased risk of frailty (odds ratio (OR): 4.53; 95% confidence interval (CI): 1.89–10.83; P = 0.001).

Conclusion

Low levels of FT3 were associated with an increased risk of frailty in older adults with T2DM. Measuring FT3 might be useful for identifying those at high risk of frailty.

Introduction

Frailty is a state characterized by reduced physiological reserves, decreased resistance to stressful events, and vulnerability to adverse outcomes, such as falls, disability, hospitalization and mortality (Clegg et al., 2013). Type 2 diabetes mellitus (T2DM) and frailty are two highly prevalent conditions of late life. Several studies have shown that diabetes has been associated with an increased risk of developing frailty (Thein et al., 2018; Jang, 2016; Assar et al., 2019). Furthermore, frail people with diabetes had a higher mortality than non-frail people (Cacciatore et al., 2013; Castro-Rodríguez et al., 2016). Thus, it is crucial to identify those at risk of frailty in old adults with diabetes and facilitate early multimodal intervention so as to avoid the negative health outcomes.

Accumulating evidence has shown that the endocrine system has a crucial role in the regulation of aging and frailty. The endocrine system involved in the pathogenesis of frailty includes insulin-like growth factor signaling, aberrant regulation of glucocorticoid secretion, androgen production, vitamin D and insulin resistance (Clegg and Hassan-Smith, 2018). However, the role of thyroid hormones in the pathogenesis of frailty is still under debate (Clegg and Hassan-Smith, 2018). Few studies have reported the association between frailty and thyroid function (subclinical thyroid dysfunction (Virgini et al., 2015), thyroid-stimulating hormone (TSH) levels (Veronese et al., 2017), serum free thyroxin (FT4) concentrations (Bano et al., 2018), thyroglobulin and TPO antibodies (Wang et al., 2010)). However, most previous studies didn't have data available on serum free triiodothyronine (FT3) levels. To our knowledge, only one study has investigated the relation between FT3 and frailty, which reported an inverse correlation between FT3 and frailty in a cohort of 112 participants aged 65 years or above (Bertoli et al., 2017). While another study has shown that FT3 concentrations were positively correlated to muscle mass and muscle function in elderly Chinese euthyroid subjects (Sheng et al., 2019).

There has been controversy about the changes of serum TSH concentrations with aging. Most studies showed a higher mean TSH concentration in older participants (Chaker et al., 2018), while another study reported serum TSH concentrations decreased gradually with age throughout life (Hoogendoorn et al., 2006). With advancing age, T3 concentrations decrease, while FT4 concentrations remain stable (Mitrou et al., 2011). The prevalence of thyroid dysfunction is higher in older adults as compared to the younger adults. Furthermore, it is reported that the prevalence of thyroid diseases in diabetic patients is 2–3 times higher than in non-diabetic subjects (Vondra et al., 2005). To date, the association of FT3 and frailty in individuals with T2DM has not yet been investigated.

Therefore, the aim of our study was to investigate if the levels of TSH, FT3 and FT4 in T2DM older adults with frailty differed to those in T2DM older adults without frailty and whether low FT3 was an independent risk factor for frailty in this population.