In this study, when compared to healthy controls; T2DM - either under the treatment of OAD or insulin - was found to have negative associations with the presence of OP (about 2 to 3 times lower, respectively). Additionally, the duration of T2DM had a positive association with the presence of sarcopenia and a negative association with balance.
A recent meta-analysis has shown that sarcopenia was frequent in T2DM patients with a pooled prevalence of 18% [28]. In our study, we also found a similar frequency (20.9%) in our DM population. The meta-analysis reported that different diagnostic criteria and tests, definition of sarcopenia and the population (e.g. postmenopausal women as in our study) may affect the prevalence of sarcopenia. Similar to the relevant literature [29, 30], we found that all sarcopenia-related parameters (i.e., SARC-F, anterior thigh MT, handgrip strength, CST and gait speed values) were worse in diabetic patients than non-diabetic subjects. Other than older age, and increased weight and duration of DM had positive and independent impact concerning the presence of sarcopenia. Recently, it has been shown that the presence of DM was negatively related with handgrip strength values [17]. Moreover, a longitudinal study has also reported that chronic conditions such as cardiovascular disease, hypertension and DM were associated with a rapid decline of handgrip strength [31]. Although hyperinsulinemia might have an anabolic effect in the skeletal system, uncontrolled or progressive T2DM might negatively affect the skeletal muscle mass and physical function. Herein, possible mechanisms of sarcopenia and balance problems in T2DM comprise increased levels of reactive oxygen radc, loss of alpha motor neurons, central, peripheral and autonomic neuropathies, hyperglycemia, insulin resistance, chronic inflammation, and declines in the number of radicals, neuromuscular junctions, and hormonal changes (i.e., estrogen, insulin, and adrenocorticotropic hormone) [28]. Needless to say, the deleterious effects of DM on the peripheral nervous system are well-known - although not assessed in our study.
Osteoporosis (OP) can develop with aging, especially after menopause. The pertinent risk factors include - but not confined to - older age, low body weight, physical inactivity, and smoking [32]. On the other hand, while overweight and obesity are positively correlated with BMD (i.e. protective against the OP); together with hyperinsulinemia, they are also risk factors for T2DM [33]. A study including 313 postmenopausal women has found that DM patients had higher BMD values than non-diabetic women [12]. A meta-analysis has also shown that T2DM patients had higher BMD levels (about 25–50% SD) than non-diabetic subjects - independent of the age, gender, BMI, skeletal site measurement or medication use [9]. It is noteworthy that higher BMD in DM patients - probably independent of increased skeletal loading - can be caused by hormonal changes such as hyperinsulinemia, adipokines, leptin, and drug use (thiazide, exogenous statin, insulin, etc.) [9]. Moreover, higher weight or BMI, hyperinsulinemia, performing less exercise or physical inactivity, smoking and use of diuretics and statins are more common in diabetic patients, and they might influence the bone metabolism (9). In our study, DM patients had similar age, body weight and BMI, and lower frequency of OP, whereas they had higher waist circumferences, and higher frequency of sarcopenia and lower balance test values when compared to non-diabetics.
Although BMD increases in T2DM patients even after adjustment for BMI in numerous cohort studies [9], paradoxical increase in the risk of fracture (independent of BMD values) has been demonstrated in T2DM [34, 35]. In some studies, this increased fracture risk has been attributed to the deterioration of bone quality in T2DM [11, 36]. Notably, despite the preserved BMD in T2DM, sarcopenia and balance problems can - for sure - increase the risk of falls and fractures [30]. The mechanism is multifactorial, including bone fragility and extra-skeletal factors such as peripheral neuropathy, retinopathy and microvascular complications of diabetes, and usage of other medications (e.g. insulin and diuretics), and presence of comorbidities (e.g. obesity, sarcopenia and frailty) [30]. According to our results, presence of T2DM under the treatment of insulin was found to be at least three times protective against the OP, but increased duration of DM was related with sarcopenia and negatively impacted the balance. Therefore, the increased fracture risk might stem from the presence of sarcopenia and balance problems in T2DM.
While the abdominal subcutaneous fat tissue was found thinner in DM patients, the waist circumference was wider than the controls. These findings might imply that DM affects intraabdominal (rather than subcutaneous) fat deposition in postmenopausal women with aging [12]. Patients with T2DM are more prone to sarcopenia and frailty than non-diabetics, and they have decreased extremity muscle strength, balance and aerobic endurance [29]. Interestingly, we found that frailty scores were found higher in DM patients, while their nutritional and cognition statuses were found similar to non-diabetic subjects. These may actually indicate that T2DM affects skeletal muscle mass and function, and physical performance (including balance, endurance, and gait speed) which accelerates sarcopenia, frailty and balance problems in DM - eventually increasing falls and fractures [29]. Likewise, poor walking speed and CST performance were shown to be related with higher risk of falls and fractures [37]. The CST evaluates muscle power and strength, and balance and endurance of the lower extremity muscles, which are closely associated with power required daily life activities such as speed walking, standing from a chair and climbing stairs [4, 17].
Studies have shown that the risk of hip fracture is increased in T2DM patients [38], which may be due to increased falls caused by age- and chronic disease related loss of skeletal muscle mass (i.e., sarcopenia) and deterioration in balance [5, 8, 25]. In addition, poor glycemic control and/or longer duration of DM can increase fracture risk due to microstructural changes of the bone in DM patients with microvascular complications [39]. It has been shown that the fracture risk is not increased within the first five years of T2DM [40], and that high risk of fracture is observed only in patients with at least 10 years of DM [41]. In our study, we found that the duration of DM was positively related with the presence of sarcopenia and negatively related with balance, which may increase the risk of falls and fractures. On the other hand, we found that DM patients had lower 10-year probability of fracture risk calculated with FRAX tool, which could be perceived as a limitation or underestimation of the FRAX. Of note, it was found that the fracture risk in T2DM calculated with FRAX is equal to adding 10 years of age or decreasing the BMD T-score by 0.5 SD [42].
There are a few limitations of this study. The frequency of sarcopenia (15.8%) was found lower than the frequency of OP (44.6%) in our relatively young postmenopausal population. Therefore, the association of DM was found to be more prominent on OP than on sarcopenia. Although the age range of our subjects (around 61.5 years) was compatible with OP, sarcopenia, falls and fractures, and balance problems are more likely to ensue in older (geriatric) postmenopausal DM patients. Additionally, the lack of electrophysiological studies for peripheral neuropathy or the absence of any history taking for microvascular complications related to T2DM would be other limitations of this study. Lastly, our study design was cross-sectional and further larger and longitudinal studies are indisputably needed to examine the effects of DM and other medications on the risk of sarcopenia, OP, balance, and falls and fractures.