Are strategies to increase muscle mass and strength as effective in people with type 2 diabetes?

Abstract

People with type 2 diabetes (T2D) have a 2–3-time higher risk of developing sarcopenia, a musculoskeletal disease marked by a progressive loss of skeletal muscle mass and strength, compared to people without T2D. This narrative review examines the effectiveness of lifestyle interventions in enhancing muscle mass and strength in people with T2D, emphasizing their growing importance with advancements in obesity treatments. PubMed and Google Scholar were utilized to identify the most relevant published studies based on the authors’ knowledge. The maintenance of skeletal muscle strength and mass in people with T2D is becoming more prominent due to the advent of weight loss therapies such as low-energy diets, bariatric surgery and pharmacotherapies. Although the weight loss is to be commended, a large proportion (20–50%) of the weight loss comes from lean mass, indicative of a loss in muscle mass. There are currently no pharmacotherapies to increase, or mitigate the loss of, lean mass, with lifestyle strategies prominent in this arena. Resistance exercise is the most effective method to increase muscle mass and strength in people with T2D, but there is some evidence of an anabolic resistance. Aerobic exercise and increased dietary protein intake may result in small increases in muscle mass and strength, with no evidence of an anabolic resistance to these stimuli. Exercise and protein supplementation can increase, or aid in the retention of, muscle strength and mass in individuals with T2D, but further research is needed to explore their benefits in patients undergoing concomitant pharmaceutical and surgical treatments.

Introduction

In 2021, the International Diabetes Federation reported that 537 million individuals worldwide are living with diabetes, with 90% of them having type 2 diabetes (T2D). This number is projected to increase by 1.7-fold by 2045 [1]. The Middle East and North Africa (MENA) region has the highest diabetes prevalence globally, with 73 million affected individuals, and it is projected to see the second-fastest increase, rising by 86% to 136 million by 2045 [1]. The highest prevalence is found among older adults, with 25% of people over the age of 65 years living with the condition [2]. T2D is one of the biggest challenges facing healthcare systems globally due to its considerable burden on patients and medical costs [3, 4]. The global medical expenses related to diabetes for people aged 20 to 79 years have increased dramatically, from USD 232 billion in 2007 to USD 966 billion in 2021. By 2030, it is anticipated to reach 1 trillion USD [1]. T2D is a progressive disorder that often coexists with microvascular, including diabetic retinopathy, nephropathy, and neuropathy, and macrovascular, including peripheral vascular, cerebrovascular, and cardiovascular diseases (CVD), complications [3, 4]. For example, CVD affects 32.2% of people with T2D [5], increasing the risk of physical disability [6] and results in early death for at least 50% of people with T2D [7]. There is also evidence that T2D results in an accelerated loss of skeletal muscle mass and strength, although this comparatively receives relatively little attention [8–10].

Cohort studies with prospective data indicate that T2D accelerates the loss of muscle mass and strength by 26% and 33%, respectively [8, 9, 11–13]. For this reason, sarcopenia has been considered a new complication of T2D [8, 14, 15], suggesting a close pathological relationship between both conditions [16]. Sarcopenia is a musculoskeletal disease marked by a progressive loss of skeletal muscle mass and strength and people with T2D have a 2–3 time higher risk of developing sarcopenia, compared to people without T2D [17–19]. Data from meta-analyses revealed that individuals with T2D had a pooled prevalence of sarcopenia of 18%, and that sarcopenia was significantly associated with poor glycaemic control and older age [17, 20]. Poor glycaemic control can lead to declines in muscle mass and strength due to increased muscle protein breakdown and reduced muscle protein synthesis, especially in people with uncontrolled T2D who have greater glucose variability [21, 22]. Other studies have revealed that, depending on the population characteristics and the methods employed to evaluate the strength and quality of the muscles, the prevalence of sarcopenia in people withT2D varies from 7–29.3% [14, 19, 23, 24]. The precise mechanisms underlying the accelerated loss of muscle mass and strength and T2D remains unclear but is multifactorial in nature involving accumulation of advanced glycation end products (AGEs) [25, 26], inflammation and excess reactive oxygen species (ROS) [25, 27, 28], and insulin resistance [29–38], which can negatively influence muscle protein metabolism. In addition, insulin resistance in people with T2D can accelerate muscle loss and weakness by disrupting insulin’s anabolic signalling pathways, reducing glucose transporter type 4 (GLUT4) translocation, and impairing mitochondrial function [33, 39].

From a lifestyle point of view, behavioural factors such as physical inactivity and unhealthy dietary habits among people with T2D, have been implicated in the accelerated loss of muscle mass and strength [40–46]. It has been reported that 27.5% of people with T2D are physically inactive [47]. The high levels of physical inactivity in individuals with T2D remove the anabolic stimulus of activity, resulting in skeletal muscle atrophy and strength loss [48]. Combined with obesity and insulin resistance, elevated intramyocellular lipid droplets (IMCLs), oxidative stress, and inflammation are induced, further contributing to muscle decline [49]. Unhealthy dietary habits, especially insufficient protein intake, are also known to accelerate muscle loss and are considered key lifestyle risk factors for sarcopenia in people with T2D [42, 43].

Regardless of the underlying mechanisms, this loss of muscle mass and strength is deleterious due to skeletal muscles wide ranging roles in health. Skeletal muscles primary role is in the maintenance of physical mobility but it also has important metabolic roles, as it is most insulin-sensitive tissue responsible for whole body insulin-mediated glucose disposal [50–52]. It is also the major amino acid store in the body providing substrates for hepatic gluconeogenic precursors and protein synthesis [53]. This amino acid store is critical in the preservation of plasma glucose levels during metabolic crises like starvation and in many clinical conditions [54]. It is perhaps not surprising, therefore, that low muscle strength, and to a lesser extent muscle mass, is associated with an increased risk of falls [55], reduced independence [56], impaired quality of life, and increased mortality and morbidity from various diseases including CVD, cancer [57, 58], and T2D [59, 60]. On top of this, we have shown that in people with T2D a low grip strength is associated with an ~ 4 fold higher risk of CVD mortality [61] and all-cause mortality [6, 62].

It is clear, therefore, that strategies to attenuate the decline in, or even increase, muscle mass and strength are needed, and the current narrative review will explore the efficacy of lifestyle interventions to increase muscle mass and strength in people with T2D and how these interventions are becoming more important with advances in the pharmaceutical/surgical treatment of obesity and T2D. In a small number of studies data indicates that lifestyle interventions, like nutrition counselling and individualized medical nutrition therapy, may be associated with a reduced incidence of sarcopenia and improved muscle health in people with T2D [63, 64]. There is, however, a lack of robust randomized controlled trial (RCT) evidence in this area and previous reviews have reported minimal or no impact of these interventions on muscle health in T2D [38]. Thus, the primary lifestyle interventions we will consider in this review are physical exercise and nutrition, which have been shown to be effective to increase muscle mass and strength in other populations. We will explore whether T2D is associated with a further exacerbation of the age-related anabolic resistance, i.e. the reduction of sensitivity in muscle protein metabolism and the gains in muscle mass and strength in response to anabolic stimuli such as exercise and dietary protein intake [65].

Physical exercise

Exercise is crucial in the management of T2D due to its wide ranging beneficial effects, including stimulating insulin-dependent glucose disposal in skeletal muscle [37, 66]. Indeed it is well established that exercise can reduce HbA1c levels (ranged from 0.71 to 0.84% following aerobic exercise [67, 68], 0.39–0.63% following resistance exercise [69–71], and 0.37–0.48% following combined exercises [72, 73]) in people with T2D [74–76]. The American Diabetes Association (ADA), therefore, recommended that people with T2D should engage in 150 min of moderate-intensity physical exercise every week (such as brisk walking, cycling, and swimming), with at least three days of activity and no more than two days without activity in between [77]. In addition, international guidelines suggest that this patient group should engage in resistance training at least twice a week [78, 79]. Regular exercise has been shown to prevent the age-related loss of muscle mass, strength [80–82], and functional disability in older adults [83]. But whether aerobic and resistance exercises can increase muscle mass and strength in people with T2D, to the same extent as in people without T2D, is rarely explored.

Aerobic exercise

Although aerobic exercise is more widely known for its cardiometabolic benefits there is evidence that it may also influence muscle mass and strength in people with T2D. In one RCT involving 43 people with T2D (aged 50–70 years), a 12-week continuous versus interval aerobic exercise program (30 to 40-minute walking, 3 times/ week), increased leg extension muscle strength by 6.1 kg (continuous) and 7.0 kg (interval) compared to the sedentary control group (-0.9 kg) (all p < 0.05) [84]. Another study of 43 women (mean age 67.7) showed significant improvements of ~ 10% in hand grip strength, mobility (timed up-and-go, 10-meter walk), and sit-to-stand tests after a 10-week aerobic program (40 min walking, 3 time/week), although muscle mass was not assessed [85]. Similarly, Kwon HR, et al. [86] found that women with T2D (aged 45–65) maintained quadriceps mass (measured by computed tomography scan) and muscle strength with aerobic exercise (60 min walking, 5 times per week), while the control group experienced significant declines in both. Whilst these studies involved more moderate intensity walking-based interventions, recently there has been a growing interest in high-intensity interval training (HIIT) in people with T2D [67]. Data from these studies are mixed, demonstrating that HIIT has superior effects (~ 10%), compared to moderate intensity aerobic exercise, on muscle strength [87] and similar effects (0.5-2%) on appendicular lean mass (measured by Dual-Energy X-ray Absorptiometry; DXA) [88] with no effect on whole body lean mass [88, 89] in people with T2D. It is worth noting that uptake and adherence to any form of exercise is a challenge and there is a debate about whether this is more challenging with HIIT [90], potentially limiting its public health utility– although this is a somewhat contentious issue. In addition, although HIIT has the potential to benefit muscle health in people with T2D, there are risks associated with it, including an increased risk of musculoskeletal injuries, the possibility of adverse cardiac events in high-risk individuals, and the possibility of overtraining and burnout [91]. Consequently, modifications to the HIIT protocols and safety measures are necessary for individuals with chronic conditions to guarantee both efficacy and safety.

Overall while these studies show that aerobic exercise may have a low-moderate benefits on muscle mass and strength in people with T2D, no trials have been conducted to compare the effects of such exercise on muscle mass and strength between people with and without T2D and so it is unclear, therefore, if there is an anabolic resistance to aerobic exercise in people with T2D.

Resistance exercise

While moderate benefits were seen with aerobic exercise, resistance exercise is the most effective way to increase muscle mass and strength, with several trials in people with T2D. The evidence is nicely summarised in a recent meta-analysis which demonstrated that resistance exercise training significantly increased muscle strength in patients with T2D when compared to aerobic (standardised mean difference (SMD): 1.44, 95% CI 0.83 to 2.05, I2 0% ) and no exercise (SMD: 0.95, 95% CI 0.58 to 1.31, I2 34%) [92]. This highlights the superiority of resistance exercise to aerobic exercise for muscle strength, although caution must be applied due to low number of participants in these comparisons (n = 135 for comparison with no exercise and n = 44 for comparison with aerobic exercise). In support of these findings, another meta-analysis in older adults with T2D (n = 193) found that resistance exercise improved muscle strength, with mean effect size of 1.05 [95% CI = 0.26 to 1.84, p = 0.01], with no effect on lean body mass [93]. Although data is limited it indicates that resistance exercise increases muscle strength in people with T2D, to a greater extent than aerobic exercise, although its effects on muscle mass are less clear. Although more effective than aerobic exercise, we know that there are many unique barriers to performing resistance exercise (fear of injury, lack of knowledge, access to equipment, dislike of gyms) [94] and participation is much lower [95, 96] and this should be taken into account in developing public health guidance. To overcome many of these barriers recent work has developed a home-based resistance exercise programme, in people with T2D, and found that 32 weeks of the intervention significantly increased arm and leg lean muscle mass measured by DXA (by 1.58%, and 1.2%, respectively) as well as the number of push-ups (3.6 push-ups [95%CI 0.8, 6.4]) although other measures such as grip strength were not increased [97]. Such work, we contend, must be built upon to increase the potential effectiveness of resistance exercise in people with T2D, to prevent the development of sarcopenia, or to treat those with T2D and sarcopenia.

On this latter point there has also been some work in people (> 50 years) with T2D and sarcopenia demonstrating that, in a 12-week RCT, progressive resistance exercise training (3 times/week) resulted in improved HbA1c levels (7.7% vs. 7.4%, p < 0.004), skeletal muscle mass (17.1 kg versus. 16.6 kg, p < 0.001), muscle mass index (7.1 kg versus. 6.8 kg, p < 0.001) and five times sit-to-stand test (13.4 s versus. 17.1 s, p < 0.001) in comparison to the non-exercising control group [98]. There is also a recent meta-analysis in people with T2D and sarcopenia, including a mix of different aerobic and resistance exercises. In this work, exercise appears to be beneficial in enhancing physical performance (mean difference in the sit-to-stand test: -1.57[95%CI: -2.26 to -0.87], p = 0.0001) and in the timed up and go test: -0.61[95%CI: -1.21 to -0.01], p = 0.05). It is worth noting, however, that only three studies on T2D and sarcopenia were pooled into this meta-analysis [99].

Resistance exercise and anabolic resistance in T2D

It is apparent, therefore, that resistance exercise can effectively increase muscle strength, with less certainty for muscle mass, in people with T2D, but whether it is as effective as it is in people without T2D remains to be established. In an RCT, after 12-weeks of resistance exercise comparable improvements in muscle strength were seen in both people with T2D (n = 17) and healthy volunteers (n = 198) [100]. However, lean body mass (measured by DXA) was significantly increased by + 1.34 kg (p < 0.001) in healthy volunteers but not in those with T2D (+ 0.83 kg, p = 0.54) [100] indicative of a potential partial anabolic resistance to exercise in muscle mass in people with T2D. This is supported by other work where an attenuated increase in lean mass (measured by DXA), and also in muscle strength, were observed following 13 weeks of resistance exercise training in people with T2D compared to age and sex matched controls [101]. Notably, prior to the intervention, basal muscle protein synthesis was lower in people with T2D and did not increase, as it did in the control group, in response to resistance exercise training [101] which strongly supports the notion of an anabolic resistance to exercise in people with T2D. Overall, whilst resistance exercise is effective in people with T2D there does appear to be an anabolic resistance in muscle mass, and potentially muscle strength, to resistance exercise in people with T2D. Strategies to overcome this anabolic resistance are needed, and there is a clear need for studies in this area (Table 1), and it is also important to understand if there is also an anabolic resistance to the other primary anabolic stimuli - protein.

Table 1.

Summary of the available evidence on the effects of exercise on muscle mass and strength in people with T2D versus those without T2D

Exercise Type	Studies Characteristics					Overall benefit on muscle mass and strength in T2D	Evidence on people with T2D compared to no exercise	Evidence on people with T2D compared to people without T2D
	Author/s (Year)	Study Design	Sample Size and Population	Exercise Frequency and Duration	Assessment Measures
Aerobic exercise (moderate intensity)	Mitranun et al. (2014) [85]	Randomized Trial	45 adults with T2D (50–70 years)	12-weeks, 3x/week	Muscle strength: 1-RM with Nautilus-type machines, Sit-and-reach box test.	low-moderate benefit on muscle mass and strength.	Increased leg extension muscle strength [85] hand grip strength, mobility (timed up-and-go, 10-meter walk), and sit-to-stand tests [86]. Maintained quadriceps mass and muscle strength [87].	None
	Dos Anjos et al. (2016) [86]	Quasi-experimental study (pre-test, intervention, and post-test)	43 elderly women with T2DM (65 years or older)	10-weeks, 3x/week	Muscle strength: Timed Up and Go test, timed 10-meter walk test, Five-repetition sit-to-stand test, Handgrip strength test, One-legged stance test.
	Kwon HR, et al. (2010) [87]	Randomized Trial	27 obese women with T2D (45–65 years)	12-weeks, 5x/week	Muscle Mass: CT scan Muscle strength: Chest and leg press test.
Aerobic exercise (high intensity)	Marcotte-Chénard et al. (2021a) [88]	Randomized parallel group (High vs. Moderate Intensity)	30 inactive older women with T2D (60–85 years)	12-weekd, 3x/week	Muscle Strength: 6-min walking test, 30-s Chair Stand test, single-leg balance test, handgrip dynamometer, Sit and Reach test.	low-moderate benefit on muscle mass and strength.	Increased muscle strength [88] Increased appendicular lean mass [89] No effect on whole body lean mass [89, 90]	None
	Marcotte-Chénard et al. (2021b) [89]	Randomized two-arm parallel study with no control group (High vs. Moderate Intensity)	30 older women with T2D (60–85 years)	12-weeks, 3x/week	Muscle mass: DXA.
	Winding et al., (2017) [90]	Randomized Trial	29 adults with T2D	11-weeks, 3x/week	Muscle mass: DXA.
Resistance exercise	Irvine and Taylor (2009) [93]	Meta-analysis of Randomized Trial	9 Trials (372 people with T2D, 46–68 years)	Ranged from 8 to 26 weeks, 3x/week	Muscle mass: skin fold measurements, DXA and BIA. Muscle strength: 1-RM, dynamometry.	High benefit on muscle strength. Moderate benefit on muscle mass.	Increased muscle strength[93,94], the number of push-ups [98] and sit-to-stand test [99]. Increased arm and leg lean muscle mass [98]. Improved skeletal muscle mass and muscle mass index [99].	Comparable improvements in muscle strength with no effect on lean body mass [101] Diminished increase in lean mass, and muscle strength [102].
	Lee et al., (2017) [94]	Meta-analysis of Randomized Trial	4 Trials (193 people with T2D, + 60 years)	> 8 weeks, 3x/week	Muscle strength: 1-RM
	Al Ozairi et al., (2023) [98]	Three-arm RCT	120 adults with T2D (+ 21 years)	36 weeks, 3x/week	Muscle mass: DXA Muscle strength: Grip strength dynamometer, SPPB test.
	Chein et al., (2022) [99]	Randomized Trial	40 adults with T2D and possible sarcopenia (+ 50 years)	12-weeks, 3x/week	Muscle mass: BIA. Muscle strength: Electronic digital grip strength dynamometer, Five times sit-to-stand test.
	Geirsdottir et al., (2012) [101]	RCT	213 adults, 65 years or older (healthy = 198 prediabetic = 20, and T2D = 17)	12-weeks, 3x/week	Muscle mass: DXA. Muscle strength: grip strength dynamometer, and knee extensor muscle strength isokinetic dynamometer, timed up and go test, 6-minute walk for distance
	Randolph et al., (2020) [102]	RCT	30 adults with T2D, 65 years or older (T2D = 15 and age- and sex- matched controls = 15)	13-weeks, 3x/week	Muscle mass: DXA Muscle strength: SPPB test, dynamometry of the tibiofemoral joint.

1-RM; 1-repetition maximum testing, CT; computed tomography, DXA; Dual-Energy X-ray Absorptiometry, BIA; bioimpedance analysis, SPPB; short physical performance battery

Protein

Sufficient protein intake plays a vital role in the synthesis of muscle proteins [102] and it is recommended that older adults consume 1.2–1.6 g/kg/day to maintain muscle mass and strength [103–105]. However, socioeconomic factors, such as food insecurity and financial constraints, along with a lack of knowledge about healthy dietary practices and protein sources, both plant- and animal-based, are identified as potential barriers to achieving adequate protein intake in this age group [105, 106]. In people without T2D, evidence on the efficacy of protein supplements to increase muscle mass and strength is mixed, with no effect generally seen in the absence of concomitant resistance exercise [107] and a small increase in muscle mass and strength when taken alongside resistance exercise training [108]. There is a paucity of data in people with T2D investigating the effects of protein and protein/resistance exercise interactions on muscle mass and strength, but findings are broadly similar to those without T2D. Data from acute physiological studies demonstrated that in response to ingested or infused protein there were similar increases in muscle protein synthesis and decreases in muscle protein breakdown in people with and without T2D [101, 109, 110], suggesting that an anabolic resistance to protein intake is unlikely to exist in people with T2D (Fig. 1).

Fig. 1.

An illustration of the anabolic resistance to anabolic stimuli in muscle of people with T2D. Muscle growth is seen with all the three stimuli, with the greatest increase with resistance exercise. Existing evidence suggests that people with T2D are unlikely to exhibit anabolic resistance to protein intake. However, they exhibit a potential anabolic resistance to resistance exercise with no available data on aerobic exercise

The muscle anabolic response to protein ingestion is influenced by amino acid bioavailability and intracellular signalling pathways, like mechanistic target of rapamycin complex 1 (mTORC1), with branched chain amino acids, particularly leucine, playing a crucial role in initiating this signalling cascade that drives muscle protein synthesis [111]. In one RCT, Leenders et al. [112] found that leucine supplementation (7.5 g/day), in the absence of resistance exercise training, for 24-weeks in older men (age 71±1 years) with T2D did not affect glycaemic control, muscle mass (measured by DXA) or strength (measured by 1-repetition maximum testing; 1-RM). A 13-week RCT found that resistance exercise combined with a protein drink enriched with leucine (3 g) significantly improved gains in total lean mass (+ 0.92 kg, 95%CI: 0.19–0.97) and appendicular muscle mass (+ 0.36 kg, 95%CI: 0.005–0.71), measured by DXA, when compared to resistance exercise alone in people with T2D [113]. There were no differences, however, between the groups in muscle strength (based on 10-RM leg press strength test), which significantly increased in both groups when compared to the baseline [113]. Supporting that, a further RCT found that while resistance exercise by itself markedly improved muscle strength (measured by 1-RM and handgrip strength), consuming 20 g of whey protein in combination with resistance exercise did not further increase this effect after 12-weeks period in older men with T2D (aged 68.5±11.5 years) [114].

Protein intake and anabolic resistance in T2D

Whilst there doesn’t appear to be an anabolic resistance to protein intake in muscle, it remains uncertain whether increasing protein intake is an effective strategy to increase muscle mass and strength, either with or without concomitant resistance exercise, in people with T2D. This is due to a limited number of robust RCTs. There are also no longer-term studies comparing the effects of increasing protein intake on muscle mass and strength in people with, to people without, T2D to allow us to confirm if people with T2D do, or do not, have an exacerbated anabolic resistance to protein. Furthermore, whether increasing protein intake may be a strategy to attenuate the aforementioned anabolic resistance to resistance exercise in people with T2D, this has yet to be investigated. Overall, therefore, the potential for increases to protein intake to be a useful public health strategy to increase muscle mass and strength in people with T2D remains to be established.

Pharmacotherapy and bariatric surgery

Pharmacotherapy

One area that has received little attention, thus far, is the potential role for lifestyle changes to mitigate some of the deleterious effects of the current and developing pharmacological/surgical strategies for the treatment of obesity/T2D. One of the major advances in this field is the development of glucose-lowering drugs glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2Is), which are the preferred second-line treatment for T2D [115]. As well as improving glycaemic control both groups of drugs have shown a reduction in the risk of cardiovascular events [116–120]. Also, both have been shown to result in clinically relevant levels of weight loss [115], which is clearly a further desirable effect. There is also recent evidence that the combining GLP1-RAs with glucose dependent insulinotropic polypeptide (GIP) may enhance benefits. For example, Tirzepatide, a once-weekly GIP/GLP-1RA, has been shown to result in greater reductions in both body weight and HbA1c in people with T2D [121]. However, as with weight loss via dietary restriction, whilst the majority of weight lost is fat mass a considerable amount is lean tissue, including muscle mass. Indeed, in a recent review of the literature on this topic, it was shown that 20–50% of the total weight lost with GLP-1RA and SGLT2Is was lean body mass [122]. Specifically, with Tirzepatide (15 mg) in people with T2D after 28 weeks of treatment there was a loss of body mass of 11.2 kg with a 1.6 kg loss of fat-free mass [123]. This is similar to data from the SURMOUNT-1 trials where in people with obesity, but not diabetes, Tirzepatide treatment resulted in a 26% greater fat mass loss and 8% greater lean mass loss compared to placebo [124]. It is clear therefore that these medications result in substantial decreases in lean tissue. Whilst the beneficial effects of these novel medications on body mass are to be celebrated, it is prudent to consider developing strategies to limit the loss of muscle tissue, during such weight loss. This is due to muscles wide ranging health role and even though physical function is not attenuated but is often increased with weight loss we would content that maximizing muscle strength and mass is always the preferred outcome. Furthermore, the maintenance of muscle is particularly important in an older population as loss of lean mass accelerates with aging. Based on the literature included in the current review we contend that a combination of resistance exercise alongside dietary protein supplements are worthy of investigating in this context, the latter of importance due to reductions in appetite and food intake that occurs with these medications. To our knowledge, there are currently no such studies.

Bariatric surgery

Bariatric surgery is another treatment method frequently employed in T2D and has been shown to increase T2D remission rate [125], improve diabetes-specific cardiovascular outcomes and reduce all-cause mortality in patients with T2D and obesity [126]. However, accumulating evidence suggests that patients with T2D who underwent bariatric surgery are at higher risk of osteoporosis and fractures compared to those without T2D [127, 128]. Furthermore, as this procedure results in a significant weight loss, of which around 31.3(± 12.2) % is muscle mass [129–132]. An analysis of the long-term consequences of bariatric surgery showed that patients lost an average of 17% of their lean mass after a year, with 10% lost in the first month [133]. As with diet and pharmaceutical weight loss physical function is not negatively affected, but similarly to those cases we would suggest that the beneficial effects of all these methods of weight loss could be enhanced with the preservation of muscle mass. There are some studies which have investigated the effects of exercise on muscle mass and strength following bariatric surgery.

In a recent RCT found that at 6 and 12 months post-bariatric surgery, patients who followed a multicomponent exercise program (n = 41; 24.6% with T2D), 3-session per week, 75-minutes per session, significantly outperformed the control group (n = 20) in terms of relative muscular strength (measured by knee flexion at 60°/s and 180°/s relative to body weight) [134]. Improvements in physical function, such as the intermittent shuttle walk test performance, have also been shown when exercise training (a mix of aerobic and resistance exercise) was performed post-surgery [135]. This data highlights some of the potential benefits that can be achieved by exercise training applied alongside large levels of weight loss, and some of this learning can be applied to mitigate the effects of pharmaceutically derived weight loss.

Conclusion and future directions

In conclusion, T2D results in an accelerated loss of muscle mass and function which can be mitigated by the application of resistance exercise, with a potential role of aerobic exercise and increases to dietary protein intake, although there is some evidence of an anabolic resistance to exercise (Fig. 2). With advances in pharmaceutical and surgical approaches to the management of T2D large levels of weight loss are widely achievable, but these come with a concomitant decline in muscle mass which we contend is important to mitigate. Work is needed, therefore, to explore the potential effectiveness of exercise (resistance and aerobic) and nutritional (protein) strategies to mitigate this and enhance the benefits of these treatments. Future research should also explore other nutritional strategies like omega-3 polyunsaturated fatty acids and vitamin D, combined with physical exercise. Based on preliminary data, these strategies have some potential for preserving muscle mass and strength in older adults [136–138] and in people with T2D [139–141]. Furthermore, future interventional studies should explore the effectiveness of individualized medical nutrition therapy on muscle health in people with T2D [38, 63, 64]. Such approaches should be conducted under the supervision of registered dietitians/nutritionists to tailor the dietary intervention for each patient considering their activity level, stress level, and specific energy and protein requirements.

Fig. 2.

The relationship between muscular health and T2D and the most effective lifestyle therapeutic strategies to increase muscle mass and strength

Author contributions

A.A-A wrote the first draft after S.R.G and E.A-O shared key articles to facilitate the writing process. A.A-A prepared the figures. S.R.G and E.A-O critically reviewed the manuscript. All authors have read and agreed with the final version of the manuscript.

Funding

None.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.