Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal



Page Path
HOME > Diabetes Metab J > Volume 47(6); 2023 > Article
Lifestyle Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies
Jakub Mesinovic1,2orcid, Jackson J. Fyfe1, Jason Talevski1,3,4, Michael J. Wheeler1,5, Gloria K.W. Leung6, Elena S. George1, Melkamu T. Hunegnaw1,2, Costas Glavas1,2, Paul Jansons1,2, Robin M. Daly1, David Scott1,2
Diabetes & Metabolism Journal 2023;47(6):719-742.
Published online: September 14, 2023
  • 510 Download
  • 3 Web of Science
  • 4 Crossref
  • 4 Scopus

1Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia

2Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia

3Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St Albans, Australia

4School of Rural Health, Monash University, Warragul, Australia

5Baker Heart and Diabetes Institute, Melbourne, Australia

6Department of Nutrition, Dietetics and Food, Monash University, Notting Hill, Australia

Corresponding author: Jakub Mesinovic orcid Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia E-mail:
• Received: April 14, 2023   • Accepted: August 12, 2023

Copyright © 2023 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • Type 2 diabetes mellitus (T2DM) and sarcopenia (low skeletal muscle mass and function) share a bidirectional relationship. The prevalence of these diseases increases with age and they share common risk factors. Skeletal muscle fat infiltration, commonly referred to as myosteatosis, may be a major contributor to both T2DM and sarcopenia in older adults via independent effects on insulin resistance and muscle health. Many strategies to manage T2DM result in energy restriction and subsequent weight loss, and this can lead to significant declines in muscle mass in the absence of resistance exercise, which is also a first-line treatment for sarcopenia. In this review, we highlight recent evidence on established treatments and emerging therapies targeting weight loss and muscle mass and function improvements in older adults with, or at risk of, T2DM and/or sarcopenia. This includes dietary, physical activity and exercise interventions, new generation incretin-based agonists and myostatin-based antagonists, and endoscopic bariatric therapies. We also highlight how digital health technologies and health literacy interventions can increase uptake of, and adherence to, established and emerging treatments and therapies in older adults with T2DM and/or sarcopenia.
Globally, almost 500 million individuals have type 2 diabetes mellitus (T2DM) and prevalence is increasing [1]. Most adults with T2DM have overweight or obesity [2] and the hallmark characteristic of this disease, insulin resistance, leads to vascular complications and subsequent adverse outcomes [3,4]. T2DM is most prevalent in older adults [1] and associated with age-related conditions, including the skeletal muscle disease sarcopenia [5-7]. Sarcopenia is characterised as the age-related decline in skeletal muscle mass and function [8-10], and 10% to 27% of older adults have this condition [11]. Sarcopenia is associated with adverse outcomes including higher risk of falls, fractures, and premature mortality [12-14]. Sarcopenia has a bidirectional relationship with T2DM as components of both diseases worsen each other via positive feedback loops [5-7]. This review explores recent evidence on the relationship between T2DM and sarcopenia, including established and emerging treatments for managing these diseases, individually or concurrently.
There are several operational definitions of sarcopenia (Table 1) [8-10], resulting in inconsistent prevalence estimates and associations between sarcopenia and adverse outcomes. The most widely adopted is the revised European Working Group on Sarcopenia in Older People (EWGSOP) definition. The EWGSOP diagnoses sarcopenia as the presence of low muscle strength and mass, and determines severity based on physical performance [8]. Recently, the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) published a Delphi method-based consensus statement supporting the use of this definition in Australia and New Zealand [15]. The Asian Working Group for Sarcopenia’s (AWGS) revised definition requires low muscle mass in the presence of low muscle strength or poor physical performance to diagnose sarcopenia, with the presence of all three identifying severe cases [9]. The Sarcopenia Definitions and Outcomes Consortium (SDOC) [10] used statistical procedures to identify cut-points for sarcopenia based on clinical outcomes, resulting in the omission of low muscle mass as a requisite for the diagnosis of sarcopenia, and requiring only low muscle (hand grip) strength and poor physical performance (slow gait speed). The SDOC reported that low relative strength (i.e., low muscle strength scaled to measures of body size), was more consistently predictive of clinical outcomes compared with absolute muscle strength [12]. Overweight and obesity based on body mass index (BMI) are associated with higher absolute, but lower relative, muscle mass and strength [16-18], and it may therefore be appropriate to utilise relative muscle cut-points in populations with T2DM to ensure these individuals receive appropriate access to sarcopenia management interventions.
A link between T2DM and sarcopenia has been reported in several studies [19-22]. A recent cross-sectional study in 6,381 adults aged >50 years reported that the prevalence of sarcopenia in those with T2DM was 28% versus 16% in counterparts without T2DM [19]. Sarcopenia is also associated with two-fold higher odds of having diabetes (any subtype) [20]. Meta-analyses have identified associations between characteristics or components of T2DM and sarcopenia. Increased glycosylated hemoglobin (HbA1c) and the presence of vascular complications have been associated with increased odds for sarcopenia (1.2-fold and 2.4-fold, respectively) in people with diabetes [20,23], while those with T2DM have lower muscle strength and physical performance compared to counterparts without T2DM [21]. To date, few longitudinal studies have assessed the relationship between these diseases. The English Longitudinal Study of Ageing, including 5,953 older adults (mean age, 63 years), reported risk for incident T2DM over 6 years decreased by 2% for every 1-kg increase in grip strength [22]. In 824 Japanese older adults, individuals with T2DM had 2.5-fold higher odds of developing sarcopenia over 5 years compared to counterparts without T2DM [24]. Further longitudinal studies are required to clarify causality in what appears to be a bidirectional relationship, particularly since T2DM and sarcopenia share common risk factors including low physical activity, malnutrition, inflammation, mitochondrial dysfunction [25,26]. Myosteatosis may be a key mechanism linking many of these risk factors to the development of both sarcopenia and T2DM.
‘Myosteatosis’ describes adipose depots within skeletal muscle, including intermuscular adipose tissue (IMAT), extracellular adipose tissue found beneath the fascia and in-between muscle groups (known as intramuscular adipose tissue), and intramyocellular lipids (IMCLs) [27]. Myosteatosis, which increases with age and is caused by factors including cellular senescence, obesity, lower physical activity and mitochondrial dysfunction, is a key risk factor for both T2DM and sarcopenia and may mediate their bidirectional relationship [27,28]. Studies have shown that both IMAT and specific IMCL species are positively associated with skeletal muscle insulin resistance [29-35], a key defect in T2DM [36]. The speculated mechanisms explaining the link between myosteatosis and insulin resistance are complex and described elsewhere [37-41]. For example, the ‘athlete’s paradox’, describes the phenomenon whereby endurance-trained athletes have significantly higher IMCLs/diacylglycerol content compared with obese or lean sedentary counterparts, yet are markedly insulin-sensitive [37,38].
Although higher muscle lipid content is a beneficial adaptation in trained endurance athletes, higher IMAT is associated with poorer physical performance in older adults [42-45], which appears to be independent of muscle mass [43]. IMAT also appears to be a stronger predictor of mobility than muscle mass [42] and is associated with higher fall risk in older adults [46,47]. Muscle health may be adversely affected by IMAT through increased localised inflammation and impaired contractility [29,48], but further research is required to obtain additional mechanistic insights into these relationships. The links between myosteatosis, fatty acid (FA) metabolism, insulin resistance and muscle function may be crucial for understanding the etiology of, and relationship between, T2DM and sarcopenia (Fig. 1).
Diet and nutrition
Evidence-based dietary recommendations are available for the prevention and management of T2DM and sarcopenia. However, recommendations for these diseases can at times be conflicting, especially in older adults. Dietary recommendations are discussed below with consideration of how these can be implemented in older adults who have T2DM and/or sarcopenia.

Dietary approaches for weight loss

Weight loss achieved through lifestyle changes (i.e., diet and exercise) is a first-line treatment for T2DM in adults with overweight or obesity (BMI ≥25 kg/m2) [49]. However, the appropriateness of using BMI cut-offs for older adults aged ≥65 years has been disputed, as emerging evidence has suggested that a higher BMI may be protective against mortality in this population (the “obesity paradox”) [50]. This is supported by a meta-analysis (n=197,940; follow-up 5 years) showing that older adults with BMI between 24.0 and 30.9 kg/m2 had the lowest mortality risk [51]. This should be considered when prescribing weight loss to older adults with T2DM and overweight or obesity.
The effectiveness of hypocaloric diets (2,100 to 4,200 kJ/day deficit over 26 to 52 weeks) on weight loss in older adults with obesity (range, –2.3 to –10.7 kg) has been shown in a systematic review of randomised controlled trials (RCTs) [52]. However, both intentional and unintentional weight loss lead to muscle and bone loss [53,54], which exacerbates age-related declines in musculoskeletal health and physical function [55]. For this reason, the European Society for Clinical Nutrition and Metabolism (ESPEN) has recommended that for older adults with overweight (BMI ≥25 and <30 kg/m2), weight loss via hypocaloric diets should be avoided, and dietary strategies should be aimed at weight maintenance [56]. However, for older adults with obesity (BMI ≥30 kg/m2) and associated disorders (e.g., T2DM) weight loss via hypocaloric diets may be recommended depending on the risk-benefit profile for the person’s metabolic health, comorbidities, functioning, and quality of life [56].
Several dietary approaches can effectively induce weight loss for management of T2DM in adults. The recent Diabetes Remission Clinical Trial (DiRECT) using a ‘very low-calorie diet’ (VLCD; 3,500 kJ/day via total meal replacement for 3 months followed by structured food reintroduction) reported reductions in body weight (10.0 kg) and mean HbA1c (0.9%), with 46% of participants in the intervention group achieving T2DM remission at 12 months [57]. Despite their effectiveness, VLCDs are not recommended for older adults as they may lead to malnutrition and declines in muscle mass and physical function [56]. Accordingly, ESPEN guidelines advise that hypocaloric diets for older adults should not exceed a daily energy reduction of approximately 2,100 kJ/day and should maintain a minimum energy intake of 4,200 to 5,040 kJ/day. Importantly, diets should be well-balanced and ensure sufficient protein intake (at least 1 g/kg body weight/day) [56].
The Mediterranean diet may be a suitable weight loss dietary approach for older adults, as it is well-balanced and can be adapted to align with ESPEN’s recommended energy and protein requirements. The Mediterranean diet is characterised by high consumption of fruits, vegetables, legumes, and wholegrains; with olive oil as the main source of fat; and fish and poultry as the principal source of protein [58]. Meta-analyses of RCTs have suggested that the Mediterranean diet can induce weight loss and reduce HbA1c levels in adults with T2DM [58-60]. Further, emerging evidence suggests an association between greater adherence to the Mediterranean diet and protection against muscle mass loss and frailty [61,62].
Time-restricted eating (TRE) is a novel dietary approach that can achieve moderate energy intake restriction in older adults [57]. TRE can promote a small amount of weight loss in adults with overweight and obesity, by limiting eating, and therefore, energy intake, to a defined period of the 24-hour day (typically <12 hours) [63]. Qualitative studies have reported high satisfaction with TRE in adults with T2DM, noting it is relatively easy to follow as it does not require calorie counting nor changes to the types of food consumed [64,65]. A pilot study involving 10 older adults with overweight/obesity (mean age, 77.1 years; mean BMI, 34.1 kg/m2) reported high adherence (84%) to a 4-week TRE intervention with a self-selected 8-hour feeding window [66]. Mean weight loss over 4 weeks was 2.6 kg (no change in fasting glucose levels), with minor adverse events including decreased energy levels reported [66,67]. A major concern with prescribing TRE in individuals with T2DM is the risk of hypoglycemic events during fasting windows, especially in those taking sulfonylureas or exogenous insulin [68,69]. However, the few TRE trials to date that recruited participants taking sulfonylureas or insulin have reported no hypoglycemic events [70], and most reported reductions in body weight and improvements in glycemic indices [71-73]. TRE may therefore be safe and effective in individuals with T2DM, especially with frequent blood glucose monitoring, but additional clinical trials are needed including muscle mass as a primary endpoint.
The risks and benefits of weight loss need to be carefully evaluated in older adults with obesity and T2DM. If weight loss is warranted, prevention of malnutrition and preservation of muscle mass is integral when selecting a suitable dietary approach to reduce risk for sarcopenia. Supplementation of specific nutrients and performing exercise may therefore be important components of weight loss regimes for this population [56].

Protein, vitamin D, and omega 3 fatty acids

Proteins contain amino acids essential for muscle protein synthesis and there is some evidence to suggest increasing protein intake improves blood glucose management [74-77]. A recent meta-analysis of 12 RCTs (n=1,138) reported that consuming a high-protein diet had no beneficial effects on fasting plasma glucose, but it had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) in individuals with T2DM [78]. Inconsistent findings in included RCTs could be related to factors such as differences in basal protein intake, types of protein consumed, or timing of intake. A subsequent meta-analysis of acute studies showed that whey protein supplementation decreased postprandial glycemia at 60 and 120 minutes compared with placebo [79]. This occurs due to the incorporation of protein into carbohydrate-containing meals delaying the release of glucose and may assist with managing blood glucose levels in this population [80]. Increasing protein intake to 1.2 to 1.6 g/kg of body weight promotes healthy aging, appetite regulation, weight management and helps maintain muscle mass and strength in older adults [81]. Protein supplementation supporting intakes exceeding approximately 1.2 g/kg of body weight may also enhance exercise-related improvements in muscle strength, mass and performance, particularly in those with low or inadequate basal intakes [82-85].
Vitamin D receptors are located within the pancreas and skeletal muscle and vitamin D deficiency is associated with poor metabolic and muscle health and physical performance [86-88]. However, these associations may be partly explained by confounding factors. For instance, obesity is common in T2DM, and it is a risk factor for vitamin D deficiency because a larger body size leads to greater volumetric dilution of vitamin D into tissues [89]. Low physical activity levels contribute to poor physical performance and sarcopenia, but they also lead to lower sunlight exposure, which is a risk factor for vitamin D deficiency. Nevertheless, there is some evidence from meta-analyses of RCTs showing that vitamin D supplementation improves glycemic indices in individuals with [90] and without T2DM [91], and also those with prediabetes [92,93], but not in populations with overweight or obesity [94]. With respect to improving muscle mass and function, older meta-analyses have reported beneficial effects, but only in individuals with 25-hydroxyvitamin D levels below 25 or 30 nmol/L [95,96]. Two recent meta-analyses showed no effect or adverse effects [97,98] on physical performance (short physical performance battery [SPPB] scores and timed up-and-go [TUG] times), which is supported by large vitamin D trials showing increased fall risk following high-dose supplementation [99,100]. Most studies identifying non-skeletal benefits following vitamin D supplementation reported them in populations with, or at risk of, moderate or severe vitamin D deficiency [90,95,96]. Thus, there appear to be very few benefits of vitamin D supplementation in populations with adequate vitamin D levels. Although there is some evidence that vitamin D holds promise as an adjunct therapy to enhance exercise-related improvements in physical function [101], recent RCTs have reported no benefits [102-104].
Long-chain omega-3 FA have anti-inflammatory benefits which may improve glycemic control and attenuate age-associated muscle loss, as both T2DM and sarcopenia are associated with chronic low-grade inflammation [105-108]. A meta-analysis of 45 RCTs showed that omega-3 FA supplementation led to significant improvements in lipid profile (decreased low-density lipoprotein and very low-density lipoprotein cholesterol and triglycerides) and reduced HbA1c, but changes in other glycemic indices such as fasting glucose, insulin levels and HOMA-IR were non-significant in individuals with T2DM [109]. Furthermore, the benefits on HbA1c became non-significant in a sensitivity analysis omitting two outliers showing very large treatment effects [109]. Other meta-analyses have shown no effect of omega-3 FA supplementation on glycemic indices [110,111]. The effects of omega-3 FA supplementation on muscle mass and function are also unclear. One of the largest meta-analyses conducted to date (66 studies) reported beneficial effects of omega-3 FA supplementation on some muscle mass and function outcomes (skeletal muscle mass and quadricep strength); however, other outcomes such as mid-arm muscle circumference and hand grip strength were unchanged [112]. Current evidence does not support the provision of omega-3 FA supplementation for managing T2DM or sarcopenia.
Given that older adults are at high risk of malnutrition and some individuals struggle with maintaining oral intake of food to sustain diet quality, multi-supplement interventions are promising in this population [113-115]. Multi-supplements may be beneficial if doses are not reduced for convenience (e.g., taking a single multi-supplement with several nutrients at low doses, as opposed to taking individual nutrients at recommended/higher doses). However, multi-supplement interventions are unlikely to be beneficial in those who have an adequate dietary intake from well-balanced diets.
Physical activity
Physical activity, defined as any bodily movement produced by skeletal muscles that results in energy expenditure [116], plays a significant role in the prevention and management of T2DM and sarcopenia. The World Health Organization (WHO) recommends that older adults with chronic conditions accumulate 150 to 300 minutes per week of moderate to vigorous intensity physical activity (MVPA) and limit sedentary time [117]. Canada has adopted 24-hour movement guidelines for older adults which include similar MVPA targets and additional guidance to limit sedentary time to 8 hours or less, and to break up periods of sitting as often as possible [118]. However, large observational studies using objective measures indicate approximately 80% to 95% of older adults do not achieve the minimum target for MVPA [119], and can spend up to 65% to 80% of their waking day sedentary [120]. Given low physical activity and high sedentary behavior are prospectively associated with worse health outcomes in older adults including development of T2DM [121], cardiovascular disease [122], lower muscle strength and power [123], and all-cause mortality [124], strategies to get older adults moving more and sitting less are of paramount importance.
Regular physical activity is recommended for management of glucose control in older adults with T2DM [125,126]. However, meta-analyses indicate that interventions aimed at changing people’s behavior to increase physical activity with limited focus on other interventions, such as consuming a hypocaloric diet, generally do not improve glycemic markers [127,128]. One meta-analysis demonstrated that physical activity interventions were more successful at improving glycemic control if they included structured/supervised exercise as opposed to behavioral intervention alone [127], and exercise will be discussed later in this review.
In recognition of the need to prevent frailty, falls, and fragility fractures in older adults, the WHO also recommends that: “As part of their weekly physical activity, older adults should do varied multicomponent physical activity that emphasizes functional balance and strength training at moderate or greater intensity, on 3 or more days a week, to enhance functional capacity and to prevent falls” [116]. A recent meta-analysis in older adults (112 studies; n=43,796) with and without chronic diseases showed that higher total physical activity levels and MVPA were associated with better hand grip strength and chair stand times [123]. Associations were also stronger between higher physical activity levels and higher lower-limb muscle strength and power measures, compared with upper-limb measures [123]. Physical activity interventions have both short- and long-term benefits for physical performance. In the Look Action for Health in Diabetes (AHEAD) trial, adults with T2DM and overweight or obesity (aged 45 to 76 at enrolment; BMI ≥25 kg/m2) were randomised to either intensive lifestyle intervention (ILI; individual weight loss goal of ≥10% and physical activity goal of ≥50 minutes per week in the first month and ≥175 minutes per week by the end of 6 months) or diabetes support and education (DSE; control) [129]. Between years 1–8, self-reported physical function remained significantly higher in the ILI group compared with DSE [130]. At 8-year post-randomisation, the ILI group had superior SPPB scores and gait speed compared with DSE [131]. At approximately 11 years post-randomisation and 1.5 years after the intervention ended, the ILI group still had 26% lower odds of having slow gait speed (<0.8 m/sec) compared with DSE [132]. Participants in the ILI group had considerable support from a lifestyle coach throughout the study, which likely contributed to long-term physical performance benefits.

Sedentary behavior

Interventions aimed at increasing MVPA alone can inadvertently lead to behavioral compensation whereby light-intensity activity is decreased and sedentary behavior is increased [133-135]. It is possible that metabolic and muscle health benefits of physical activity interventions can be blunted or eliminated by compensatory increases in sedentary behavior. High levels of MVPA (60 to 75 minutes per day) are required to offset the deleterious effect of sitting for >8 hours per day on all-cause mortality [136]. However, these levels of MVPA still may not be sufficient to offset the effects of sedentary behavior on metabolic health in older adults. A recent study of 54 extremely active older adults (mean age, 71 years) demonstrated that high volumes of sedentary behavior (9.4 hours/day) adversely influences metabolic health, even in the presence of high volumes of MVPA (2.6 hours/day) [136]. This suggests interventions should target both increasing MVPA and reducing sedentary behavior for optimal improvement in metabolic health in older adults.
Several short-term studies have investigated the acute metabolic effects of intermittent breaks in prolonged sitting in older adults (mean age ≥60 years) with T2DM [137-141]. These studies have reported reduced postprandial glucose and/or insulin levels [137,140,141], improved 22 to 24 hours continuous glucose monitoring profiles [138-140,142], and improved vascular function [143]. It is thought that intermittent activity improves glycemic control partly because it can be spread across multiple postprandial periods. Some of these studies even compared intermittent physical activity spread across the day to an energy-matched discrete bout of exercise demonstrating comparable [139], or superior glucose-lowering effects with intermittent physical activity [138,144]. This suggests that an effective intervention for improving glucose control in older adults with T2DM is to avoid prolonged periods of sitting and to spread physical activity across the day, particularly after meals. However, while there is evidence of small improvements in glycemic indices in some long-term studies [145-147], further RCTs are needed to confirm this.
Evidence from longitudinal observational studies with objective measures suggests that reducing sedentary behavior is associated with improved physical function and reduced falls risk in older adults [123,148]. However, other longitudinal observational studies in older adults have shown that higher amounts of MVPA are associated with a decreased likelihood of sarcopenia and/or its components (low appendicular lean mass and grip strength and slow TUG time), regardless of the amount of sedentary behavior [149,150]. Evidence from interventions specifically targeting sedentary behavior is inconclusive [151-153]. Some demonstrate improved physical function [151-153], even in the absence of observed reductions in sitting time [153], while others report reductions in sedentary time do not affect physical function [154]. Nevertheless, interventions specifically targeting reductions in sedentary behavior may be more acceptable to some older adults than interventions that increase MVPA [155].
Taken together, evidence suggests both increasing MVPA and reducing sedentary behavior improves metabolic and muscle health in older adults. Additional high-quality evidence from large RCTs is needed to better inform physical activity guidelines for those with T2DM and sarcopenia.


Exercise is a planned, structured, and repetitive subset of physical activity with the objective to improve or maintain physical fitness [116]. Exercise interventions have well-established benefits for multiple health outcomes, including metabolic and musculoskeletal health markers such as insulin sensitivity [156,157], glycemic control [158], skeletal muscle mass [159], strength [160,161], and bone mass [162].
The benefits of exercise interventions may be influenced by various factors, including the mode/type of exercise performed (e.g., aerobic vs. resistance exercise) and prescription-related factors such as frequency, intensity, and duration of exercise sessions. Aerobic exercise is a form of repetitive/rhythmic structured physical activity that uses large muscle groups and can be maintained continuously, it includes activities such as jogging, cycling and swimming. Resistance or muscle-strengthening exercise involves repetitive muscular contractions against ex-ternal resistance, such as lifting weights or body weight alone. Short- and long-term physiological adaptations to aerobic and resistance exercise are somewhat distinct, with aerobic exercise primarily associated with improvements in cardiometabolic health markers (such as cardiorespiratory fitness, insulin sensitivity, and glycemic control), and resistance exercise mainly targeting aspects of musculoskeletal health (such as skeletal muscle mass, strength, and bone mineral density). There is, however, some cross-over in the specificity of responses and adaptations to aerobic and resistance exercise, particularly following shorter-term interventions and in those with lower baseline fitness levels [158,163,164]. Understanding the role of exercise prescription-related factors in addressing consequences of T2DM and/or sarcopenia can inform practical guidelines for management of these diseases.
Several RCTs have investigated whether exercise interventions (up to 96 weeks), involving either aerobic or resistance training alone, or in combination, can improve markers of metabolic health in older adults with T2DM [165-170]. Overall, these studies provide evidence that in those with T2DM, both supervised aerobic and resistance training are effective for improving HbA1c and fasting blood glucose levels [171]. In a RCT of 100 adults aged ≥55 years with T2DM, the effects of three different 16-week exercise interventions (aerobic exercise, resistance exercise, or a combination of both [same intensity but half the volume of other exercise groups]) on various metabolic health markers were compared with a control group encouraged to perform low-to-moderate intensity aerobic activities (e.g., brisk walking, cycling) for 150 minutes per week [165]. At follow-up, all exercise conditions showed improved metabolic health markers from baseline, including reduced fasting plasma glucose, HbA1c, fasting plasma insulin, and HOMA-IR, with no differences between conditions (including vs. the control condition, which showed no within-group changes in these outcomes). These improvements occurred independent of weight loss. Although both aerobic and resistance training appear to independently improve glycemic control, a network meta-analysis showed that the combination of both is more effective for reducing HbA1c than either mode alone in individuals with T2DM [172].
The benefits of resistance training for improving muscle mass and function in older adults with sarcopenia are well-established and it is a first-line treatment for this condition [173,174]. A recent systematic review and meta-analysis of 26 studies in 1,191 older individuals with sarcopenia (age range, 60.6 to 89.5years) [173] found resistance training was effective for improving knee extensor strength and measures of physical function (gait speed, TUG test, but not chair stand test performance). Resistance training prescription factors, such as frequency, intensity, and dose, may influence the effectiveness of such interventions. Indeed, a meta-analysis of 15 studies found that in older adults (mean age, 67.8 years), improvements in muscle strength and size following resistance training tended to be greater when involving higher loads (approximately 80% one-repetition maximum [1-RM]) compared with lower loads (approximately 45% 1-RM) [175]. However, these effects were substantially smaller in studies that work-matched both higher- and lower-load resistance training protocols [175].
Pragmatic and time-efficient approaches including “exercise snacking” may be effective for improving markers of glycemic control [176]. “Exercise snacks” may be considered as isolated bouts of exercise lasting ≤1 minute and performed multiple times throughout the day [177]. Various studies have shown the efficacy of exercise snacking approaches [176,178-180] for interrupting short-term sedentary behavior patterns and improving cardiometabolic health markers in preclinical and clinical populations. While some studies have found shortterm benefits of exercise snacking for improving indices of metabolic health and glycemic control [176,178-180], there is less evidence for the long-term efficacy of this approach.
A few studies have also explored the effects of exercise snacking on musculoskeletal health in older adults [181-183]. A pilot study in older adults (age range, 65 to 80 years) showed that twice-daily “exercise snacks” (five bodyweight exercises performed for 1 minute with 1-minute passive recovery between exercises; 9 minutes total session duration) performed for 28 consecutive days improved 60-second sit-to-stand performance, and large effect sizes were noted for the difference in the change in leg press power and thigh muscle cross-sectional area versus control [182]. Another pilot study [181] using a similar resistance-based “exercise snacking” protocol in older adults (mean age, 70 years) noted positive findings regarding the feasibility and acceptability of this exercise approach, but there was little evidence of physical function benefits versus control (no exercise; study was not powered to detect differences in physical function) when assessed remotely after 4 weeks. Overall, while the limited available evidence has shown mixed benefits of exercise snacking approaches for improving measures of metabolic and musculoskeletal health, the positive findings regarding the feasibility and acceptability of these approaches highlight the need for further work to determine and improve their efficacy in older adults, particularly those with sarcopenia and/or T2DM [181-184].
Combined exercise and hypocaloric diet interventions
As described earlier, weight loss may lead to muscle mass losses, but is beneficial for metabolic health in older adults with T2DM, and exercise can augment weight loss-related metabolic health improvements [169]. In sedentary older adults (aged 60 to 80 years) with overweight and T2DM consuming a hypocaloric diet, performing supervised and structured high-intensity resistance training (nine exercises; eight to 10 repetitions; 75% to 85% 1-RM) further reduced HbA1c levels after both 3 and 6 months (–0.5% and –0.8%, respectively) [169]. In 160 older adults with obesity consuming a hypocaloric diet, completing concurrent combined aerobic and resistance training led to an 86% improvement in insulin sensitivity index, which was significantly better than completing either exercise mode alone [185].
Exercise also influences changes in muscle mass, IMAT and physical function that occur following hypocaloric diet interventions. In 107 older adults with obesity consuming a hypocaloric diet for 12 months, combined resistance and aerobic exercise led to greater improvements in a composite physical performance score compared with no exercise (21% vs. 12%, P<0.001) [186]. Another study in older adults with obesity (n=160) comparing different exercise modes during a hypocaloric diet intervention showed that combined resistance and aerobic exercise led to greater improvements in a composite physical function score (21%) compared with aerobic (14%) and resistance exercise (14%), although this may be attributed to the higher training dose in this group [187]. Interestingly, those completing aerobic exercise had significantly greater lean mass losses (–5%) than the resistance exercise (–2%) and combined resistance and aerobic exercise (–3%) groups [187]. In support of the abovementioned findings, a recent meta-analysis showed that resistance exercise attenuates muscle mass losses that occur following weight loss [53]. Only one RCT has compared changes in IMAT between older adults with obesity undertaking a hypocaloric diet intervention alone, or in combination with resistance or aerobic exercise for 18 months [188]. The greatest decreases in trunk and thigh IMAT area were observed in the group performing concurrent aerobic training, followed by the resistance training group, and then the no exercise training group (between-group differences were significant but post-hoc tests were non-significant). All groups had significant improvements in trunk and thigh IMAT area relative to baseline [188]. More studies are required to determine optimal exercise prescriptions for improving metabolic and muscle health in older adults with T2DM and/or sarcopenic obesity consuming a hypocaloric diet.
T2DM is managed using several types of medications (e.g., biguanides, dipeptidyl peptidase inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, insulin) and their mixed effects on muscle health and function have been described previously [6,189]. However, use of new generation incretin-based medications has increased recently due to their ability to treat both poor glycemic control and obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists are the most common incretin-based medications, which lower glucose levels by stimulating insulin secretion from pancreatic β-cells [190]. They also suppress appetite, delay gastric emptying, improve satiety, and decrease glucagon secretion [190]. In a recent RCT of 1961 adults with overweight and obesity, once-weekly subcutaneous semaglutide (2.4 mg) led to a 15% decrease in body weight over 68 weeks compared with a 2.4% reduction in placebo (both groups also underwent a lifestyle intervention involving 500 kcal/day energy restriction and increased physical activity [150 minutes per week] was encouraged) [191]. Approximately 86% of participants had clinically significant weight loss (≥5%) in the semaglutide group versus 32% in placebo and these participants also had improvements in fasting glucose, HbA1c, and self-reported physical function [191]. While a significant decrease in absolute lean (muscle) mass was observed, percentage lean mass increased, relative to placebo [191]. Another incretin-based medication, tirzepatide, is a dual glucose-dependent insulinotropic peptide and GLP-1 agonist. Tirzepatide leads to similar improvements in the abovementioned outcomes in individuals with overweight and obesity over a similar timeframe [192]. In a recent head-to-head study, tirzepatide led to greater reductions in body mass and HbA1c compared with semaglutide in individuals with T2DM, although the semaglutide dose was 1 mg (once-weekly) [193]. Dual-agonists appear to confer additional benefits over mono-agonists, and other dual- and tri-agonists currently in clinical trials show great promise (NCT04478708 [194,195]). Future studies on these medications would benefit from comprehensively measuring physical function outcomes and prescribing targeted exercise to attenuate weight loss-related declines in muscle mass.
Currently there are no approved pharmacological treatments for sarcopenia; however, several medications have shown potential efficacy in recent clinical trials. Myostatin-based medications are of great interest given the inhibition of this myokine significantly increases muscle mass in animal knockout/loss-of-function models [196,197]. Myostatin propeptides, soluble receptors, antibodies, and endogenous antagonists have been developed and some have undergone testing in clinical trials [198-200]; myostatin-based treatments consistently increase muscle mass, but they have limited or no benefits for physical function, which is a more clinically relevant outcome for patients [198-200]. Recent trials demonstrated that bimagrumab can decrease fat mass and improve insulin sensitivity and HbA1c in individuals with insulin resistance and T2DM [201,202], but larger trials are required to establish the safety and efficacy of this treatment. Testosterone treatment is effective for increasing muscle mass and to a lesser degree, muscle strength, but similar to myostatin-based agonists there is inconsistent evidence supporting beneficial effects on physical performance in older populations with and without T2DM [203,204]. There are no clinical trials assessing efficacy of testosterone for improving muscle health in older adults with diagnosed sarcopenia. Testosterone also decreases risk of incident T2DM in middle-aged and older men [205], with glycemic improvements being mediated to the greatest degree by treatment-related changes in fat mass [206]. Despite these positive findings, there is still insufficient evidence to support routine use of this treatment in older adults with T2DM without pathological hypogonadism [205,207]. To overcome adverse androgenic/virilising side effects associated with testosterone [208,209], selective androgen receptor modulators (SARMs) have been developed to stimulate anabolic effects in skeletal muscle and other tissues (e.g., bone) while minimising adverse effects on other tissues (e.g., prostate) [210,211]. Only one study has explored the effects of a SARM in a population with sarcopenia [212]. In 170 postmenopausal women (aged >65 years), a SARM (MK-0773) taken for 6 months led to a 0.6 kg increase in appendicular lean mass relative to placebo, but it did not lead to any improvements in muscle strength or performance [212]. SARMs have shown some promise in other populations with respect to increasing muscle mass, but effects on physical function are unclear [213,214]. Increasing muscle mass via pharmacological treatments provides limited functional benefits, so the addition of targeted exercise (particularly resistance training), will likely be key in achieving physical function-related endpoints in future clinical trials.
Endoscopic bariatric therapies
Bariatric surgery (BS) is the most effective intervention for long-term weight loss for individuals with obesity and its comorbidities [215]. BS-induced weight loss improves glycemic control with T2DM remission rates ranging from 69% to 90% depending on the type of surgery [216,217]. Achievement of T2DM remission following BS is multi-factorial but largely driven by weight loss-related improvements in insulin sensitivity and β-cell function, and there are also documented changes in gut physiology, bile acid metabolism, and gut microbiota that appear to have benefits on glycemia [218]. Although the beneficial effects of BS on metabolic health are well-established, its effect on muscle health is unclear.
A prospective cohort study in 47 adults (mean age, 42 years) who underwent Roux-en-Y gastric bypass (RYGB) showed that total lean mass decreased by 13% and absolute hand grip strength decreased by 9%, however, relative hand grip strength (normalized to BMI) increased by 32% [219]. The same study reported an increase in gait speed (0.1 m/s) and improved 400 m walk time [219]. A recent meta-analysis showed that RYGB results in greater 12-month body weight and fat loss, but similar losses in lean mass, compared with adjustable gastric band, although this was based on only two RCTs [220]. Non-surgical intragastric balloons, involving endoscopic insertion of a silicon fluid-filled balloon into the stomach causing earlier feelings of satiety [221], also lead to lean mass losses [222], despite improving glycemic control [223]. Maintaining muscle mass should therefore be a key focus following BS.
Exercise augments BS-related metabolic, body composition and physical function improvements. A recent RCT showed that 62 adults with obesity (age range, 18 to 55 years) randomised to combined resistance and aerobic training following RYGB had greater improvements in insulin sensitivity (Matsuda index, 325%) than those randomised to standard care following RYGB [224]. A meta-analysis showed that exercise training (aerobic and/or resistance exercise and/or high-intensity interval training) led to greater total body mass (mean difference [MD], –1.8 kg) and fat mass (MD, –2.1 kg) losses, but similar lean mass losses (MD, 0.7 kg), compared with controls receiving standard care, following BS [225]. Exercise also improved muscle strength (based on different strength tests) and endurance (based on different walking tests) [225]. Although performing any type of exercise following BS is likely to be beneficial, performing resistance training is particularly important for attenuating losses in muscle mass and function, especially in older patients.
Digital health technologies
The WHO describes digital health as “the field of knowledge and practice associated with the development and use of digital technologies to improve health.” Digital health technologies are an effective and valued tool for delivering and monitoring remote diet and exercise interventions targeting glycemic control in older adults with and without T2DM [226,227]. These interventions use delivery approaches such as video-conferencing, phone calls, text messages, smartphone and tablet-based applications and other digital inputs [228], and improve practitioner-patient communication and support, as well as access to medical services [229]. The Weight Achievement and Intensive Treatment (Why WAIT) 12-week multidisciplinary weight management program was delivered via a smartphone application and video-conferencing during the coronavirus disease 2019 (COVID-19) pandemic [230]. This intervention for individuals with obesity (BMI, 30 to 45 kg/m2) and diabetes (type 1 or 2) [231] involved a hypocaloric diet and exercise, as well as a cognitive-behavioral intervention and group education. The 16 participants who completed the digital health program had similar changes in body weight (–6.8 kg vs. –7.4 kg), HbA1c (–1.0% vs. –1.03%) and other metabolic outcomes compared with 22 participants who completed the in-person program before the pandemic [230]. Several other studies involving web-based dietary interventions have also reported improvements in HbA1c after 4 months (–0.30%) [232], 12 months (–0.24%) [233], and 5 years (–0.29%) [234] in adults and older adults with T2DM. A recent systematic review found that 20 out of 21 studies that delivered digital interventions for the management and prevention of T2DM showed significant within-group improvements in at least one key T2DM-related outcome (e.g., HbA1c, blood glucose levels, weight loss) and 85% (11/13) of parallel-group studies showed a significant improvement compared with control [235].
Only a few studies have explored effects of digital health interventions on muscle mass and/or function in older adults. A recent 12-month RCT explored the feasibility, acceptability and efficacy of the successful Lifestyle integrated Functional Exercise (LiFE) intervention (involving the incorporation of strength and balance exercises into daily activities) [236] in older adults aged between 61 and 70 years, delivered via smartphone and smartwatch [237]. The program appeared to be feasible with 58 out of 61 participants in the virtual group using the application for an average of 180 days, but had no benefits on hand grip strength or gait speed [237]. Another 12-week RCT assessed the effects of a home-based exercise (resistance band-based exercises, 10 repetitions and five sets, performed 3 days per week) and hypocaloric dietary intervention (1,200 kcal/day) delivered via digital communication applications (e.g., LINE, FaceTime) on muscle mass and function, in older adults (≥55 years) with overweight or obesity (BMI range, 27 to 35 kg/m2) and knee osteoarthritis [238]. Participants were randomised into three groups; diet alone, exercise alone, and combined exercise and diet. Lower-limb muscle mass increased in the exercise alone group and decreased in the other two groups (losses were attenuated in combined exercise and diet) [238]. TUG times improved in all groups and significantly more in the combined exercise and diet group compared with exercise alone [238]. It is currently unclear how digital health interventions affect muscle health and function in older adults with T2DM and/or sarcopenia.
Collectively, the above studies demonstrate that digital health interventions can have similar efficacy compared to in-person interventions; however, digital health technologies can be challenging for patients, and may require resource-intensive training and support by a health professional [234,239]. A recent scoping review evaluated barriers to digital health in 14 qualitative studies of older adults (≥60 years) and identified that small screens and text size, reduction of fine motor control and cognitive concerns related to memory, remembering passwords and logging in were commonly cited concerns [240]. However, older adults can overcome barriers to engaging with digital technology. An observational study (n=2,169) analysing data from a fully automated digital health platform reported that older adults had significantly more digital coaching conversations, logged more meals, and recorded more device measurements than younger users (35 to 64 years) over 12 months [241]. Further research is required to determine the efficacy and feasibility of multicomponent digital health interventions, using different technologies, and how these can enhance older adults’ self-management of sarcopenia and/or T2DM.
Health literacy
T2DM and sarcopenia are both chronic diseases where self-management is the primary means of treatment. Individuals often need to make major lifestyle changes to adhere to dietary and physical activity recommendations and follow new medication regimens. These behavior changes can be difficult to initiate and maintain [242], and individuals require health literacy (HL) skills to self-manage their health [243]. HL is a multidimensional concept defined as ‘the personal characteristics needed for an individual to access, understand, appraise and use information about health and health care services to make decisions about health’ [244]. The risk of developing T2DM is increased in individuals with low or inadequate HL [245,246]. A meta-analysis of 29 observational studies (n=13,457 participants) reported that almost 33% of patients with T2DM have low HL [247]. This is problematic because higher HL is associated with greater T2DM health knowledge and glucose control [248,249] and increased uptake of positive self-management behaviors such as medication adherence, physical activity and healthy diet [250-253].
In a recent systematic review of 14 RCTs [254], HL-focused interventions led to significant improvements in T2DM health knowledge, quality of life, physical activity levels, and health-related self-efficacy, although inconsistent results were seen across self-management strategies such as glycemic control, foot care, diet management, and medication adherence [254]. However, this review was highly education-focused and included studies that interchangeably used the terms ‘health literacy’ with ‘health education.’ While education often plays an important role in HL interventions, providing education alone is not considered a ‘HL approach’ and is rarely sufficient to facilitate behavior change to sustain optimal health outcomes [255].
The ‘teach-back method’ can be considered a HL intervention because it aims to improve patient-provider interactions by repeatedly checking and clarifying health information given to patients until the patient can correctly recall the information given [256]. Teach-back is effective across a wide range of settings, populations, and outcome measures, including patients with T2DM [256]. Clinical trials have reported significant improvements in medication adherence, diet changes, and foot self-care in populations with T2DM after implementation of the ‘teach-back method’ compared with usual care control groups [257-259]. More recent RCTs assessing HL-based counselling and/or behavior change interventions have shown positive results for patient activation (an individual’s knowledge, skills, and confidence for managing their health) [260], diabetes self-management behaviors [260,261], and self-efficacy [261,262]. The evidence supporting the effectiveness of HL-oriented interventions on physical activity and exercise in patients with T2DM is limited, although a systematic review of six interventional studies (n=980) reported generally positive findings across several physical activity behaviors in individuals with T2DM [263].
Two RCTs of a HL-oriented behavior change program for exercise, diet and nutrition reported significant improvements in components of sarcopenia (TUG test; gait speed; grip strength), as well as improvements in physical activity levels and dietary variety scores for older adults compared to a standard control group [264,265]. No studies have investigated associations between HL and sarcopenia, although, one longitudinal study [266] found that older adults with lower socioeconomic factors (education, occupation), which influence HL levels, were more likely to have lower grip strength and lean mass. Another cross-sectional study in the same cohort also reported that lower educational attainment, but not occupation, was associated with increased likelihood for both obesity and sarcopenic obesity in community-dwelling older adults [267]. There is a need for further research regarding the effectiveness of HL interventions, and whether they can enhance other treatments and therapies, in older adults with metabolic and musculoskeletal diseases [268].
There is considerable cross-sectional data highlighting the bidirectional relationship between T2DM and sarcopenia, but longitudinal data are lacking. Myosteatosis is likely a significant contributor to this relationship via direct effects on insulin resistance and physical function. Increasing physical activity and decreasing sedentary behavior have independent benefits on metabolic and muscle health, and may be achieved in by breaking up prolonged sedentary periods with brief activity or exercise bouts (e.g., activity breaks or ‘exercise snacks’). Nevertheless, structured exercise has the most pronounced effect on these aspects of health, and different modalities have distinct but overlapping benefits, so multi-modal interventions should be prioritised with a key focus on resistance training in this population. Weight loss is the most effective method for improving metabolic health and can be achieved via hypocaloric diets, using pharmacotherapies and/or undergoing surgical or non-surgical endoscopic bariatric procedures. However, in the absence of exercise, weight loss can have detrimental effects on muscle mass, potentially increasing risk for sarcopenia. As described in Fig. 2, uptake of, and adherence to, the abovementioned treatments and therapies for improving metabolic and muscle health may be facilitated or enhanced via the use of digital health interventions or targeting individual or system-level HL barriers.


No potential conflict of interest relevant to this article was reported.



Fig. 1.
Major causes and outcomes of myosteatosis in older adults with type 2 diabetes mellitus and sarcopenia.
Fig. 2.
Proposed relationships between emerging and established treatments for type 2 diabetes mellitus and sarcopenia.
Table 1.
Current operational definitions of sarcopenia
Low muscle strength Low muscle mass Poor physical performance
Revised EWGSOP HGS: <27 kg (men) and <16 kg (women) ALM: <20 kg (men) and <15 kg (women) Gait speed: 0.8 m/sec (4‐m course)
SPPB score: <8 points
Chair stand time: >15 sec (5 rises) ALM/Height2: <7.00 kg/m2 (men) <5.5 kg/m2 (women) TUG: >20 sec
400 m walk: ≥6 min or non-completion
Revised AWGS HGS: <28 kg (men) and <18 kg (women) ALM/Height2: <7.0 kg/m2 (men) <5.4 kg/m2 (women) Gait speed: <1 m/sec (6‐m course)
SPPB score: ≤9 points
Chair stand time: ≥12 sec (5 rises)
SDOC HGS: <35.5 kg (men) and <20 kg (women) - Gait speed: ≤0.8 m/sec
HGS/BMI: <1.05 kg/body weight (kg)/height (m2) (men) and <0.79 kg/body weight (kg)/height (m2) (women)
HGS/TBF: <1.66 kg/TBF (kg) (men) and <0.65 kg/TBF (kg) (women)
HGS/arm lean mass: <6.08 kg/arm lean mass (kg) (men) and <3.26 kg/arm lean mass (kg) (women)
HGS/body weight: <0.45 kg/body weight (kg) (men) and <0.34 kg/body weight (kg) (women)

EWGSOP, European Working Group on Sarcopenia in Older People; HGS, hand grip strength; ALM, appendicular lean mass; SPPB, short physical performance battery; TUG, timed up-and-go; AWGS, Asian Working Group for Sarcopenia; SDOC, Sarcopenia Definitions and Outcomes Consortium; BMI, body mass index; TBF, total body fat.

  • 1. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 2022;183:109119.ArticlePubMed
  • 2. Daousi C, Casson IF, Gill GV, MacFarlane IA, Wilding JP, Pinkney JH. Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors. Postgrad Med J 2006;82:280-4.ArticlePubMedPMCPDF
  • 3. Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010;375:2215-22.ArticlePubMedPMC
  • 4. Mesinovic J, Scott D, Seibel MJ, Cumming RG, Naganathan V, Blyth FM, et al. Risk factors for incident falls and fractures in older men with and without type 2 diabetes mellitus: the concord health and ageing in men project. J Gerontol A Biol Sci Med Sci 2021;76:1090-100.ArticlePubMedPDF
  • 5. Liu ZJ, Zhu CF. Causal relationship between insulin resistance and sarcopenia. Diabetol Metab Syndr 2023;15:46.ArticlePubMedPMCPDF
  • 6. Mesinovic J, Zengin A, De Courten B, Ebeling PR, Scott D. Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship. Diabetes Metab Syndr Obes 2019;12:1057-72.PubMedPMC
  • 7. Scott D, de Courten B, Ebeling PR. Sarcopenia: a potential cause and consequence of type 2 diabetes in Australia’s ageing population? Med J Aust 2016;205:329-33.ArticlePubMedPDF
  • 8. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019;48:16-31.ArticlePubMedPMCPDF
  • 9. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, et al. Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc 2020;21:300-7.ArticlePubMed
  • 10. Bhasin S, Travison TG, Manini TM, Patel S, Pencina KM, Fielding RA, et al. Sarcopenia definition: the position statements of the Sarcopenia Definition and Outcomes Consortium. J Am Geriatr Soc 2020;68:1410-8.ArticlePubMedPDF
  • 11. Petermann-Rocha F, Balntzi V, Gray SR, Lara J, Ho FK, Pell JP, et al. Global prevalence of sarcopenia and severe sarcopenia: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2022;13:86-99.ArticlePubMedPMCPDF
  • 12. Cawthon PM, Manini T, Patel SM, Newman A, Travison T, Kiel DP, et al. Putative cut-points in sarcopenia components and incident adverse health outcomes: an SDOC analysis. J Am Geriatr Soc 2020;68:1429-37.PubMedPMC
  • 13. Gandham A, Mesinovic J, Jansons P, Zengin A, Bonham MP, Ebeling PR, et al. Falls, fractures, and areal bone mineral density in older adults with sarcopenic obesity: a systematic review and meta-analysis. Obes Rev 2021;22:e13187.ArticlePubMedPDF
  • 14. Yeung SS, Reijnierse EM, Pham VK, Trappenburg MC, Lim WK, Meskers CG, et al. Sarcopenia and its association with falls and fractures in older adults: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2019;10:485-500.ArticlePubMedPMCPDF
  • 15. Zanker J, Scott D, Reijnierse EM, Brennan-Olsen SL, Daly RM, Girgis CM, et al. Establishing an operational definition of sarcopenia in Australia and New Zealand: Delphi method based consensus statement. J Nutr Health Aging 2019;23:105-10.ArticlePubMedPDF
  • 16. Keevil VL, Luben R, Dalzell N, Hayat S, Sayer AA, Wareham NJ, et al. Cross-sectional associations between different measures of obesity and muscle strength in men and women in a British cohort study. J Nutr Health Aging 2015;19:3-11.ArticlePubMedPMC
  • 17. Stenholm S, Sallinen J, Koster A, Rantanen T, Sainio P, Heliovaara M, et al. Association between obesity history and hand grip strength in older adults: exploring the roles of inflammation and insulin resistance as mediating factors. J Gerontol A Biol Sci Med Sci 2011;66:341-8.ArticlePubMedPMC
  • 18. Janssen I, Heymsfield SB, Wang ZM, Ross R. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol (1985) 2000;89:81-8.ArticlePubMed
  • 19. Dai S, Shu D, Meng F, Chen Y, Wang J, Liu X, et al. Higher risk of sarcopenia in older adults with type 2 diabetes: NHANES 1999-2018. Obes Facts 2023;16:237-48.ArticlePubMedPDF
  • 20. Veronese N, Pizzol D, Demurtas J, Soysal P, Smith L, Sieber C, et al. Association between sarcopenia and diabetes: a systematic review and meta-analysis of observational studies. Eur Geriatr Med 2019;10:685-96.ArticlePubMedPDF
  • 21. Anagnostis P, Gkekas NK, Achilla C, Pananastasiou G, Taouxidou P, Mitsiou M, et al. Type 2 diabetes mellitus is associated with increased risk of sarcopenia: a systematic review and meta-analysis. Calcif Tissue Int 2020;107:453-63.ArticlePubMedPDF
  • 22. Cuthbertson DJ, Bell JA, Ng SY, Kemp GJ, Kivimaki M, Hamer M. Dynapenic obesity and the risk of incident type 2 diabetes: the English Longitudinal Study of Ageing. Diabet Med 2016;33:1052-9.ArticlePubMed
  • 23. Feng L, Gao Q, Hu K, Wu M, Wang Z, Chen F, et al. Prevalence and risk factors of sarcopenia in patients with diabetes: a meta-analysis. J Clin Endocrinol Metab 2022;107:1470-83.ArticlePubMedPDF
  • 24. Nakamura K, Yoshida D, Honda T, Hata J, Shibata M, Hirakawa Y, et al. Midlife and late-life diabetes and sarcopenia in a general older Japanese population: the Hisayama Study. J Diabetes Investig 2021;12:1899-907.ArticlePubMedPMCPDF
  • 25. Bellou V, Belbasis L, Tzoulaki I, Evangelou E. Risk factors for type 2 diabetes mellitus: an exposure-wide umbrella review of meta-analyses. PLoS One 2018;13:e0194127.ArticlePubMedPMC
  • 26. Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull 2010;95:139-59.ArticlePubMed
  • 27. Correa-de-Araujo R, Addison O, Miljkovic I, Goodpaster BH, Bergman BC, Clark RV, et al. Myosteatosis in the context of skeletal muscle function deficit: an Interdisciplinary Workshop at the National Institute on Aging. Front Physiol 2020;11:963.ArticlePubMedPMC
  • 28. Addison O, Marcus RL, Lastayo PC, Ryan AS. Intermuscular fat: a review of the consequences and causes. Int J Endocrinol 2014;2014:309570.ArticlePubMedPMCPDF
  • 29. Sachs S, Zarini S, Kahn DE, Harrison KA, Perreault L, Phang T, et al. Intermuscular adipose tissue directly modulates skeletal muscle insulin sensitivity in humans. Am J Physiol Endocrinol Metab 2019;316:E866-79.ArticlePubMedPMC
  • 30. Boettcher M, Machann J, Stefan N, Thamer C, Haring HU, Claussen CD, et al. Intermuscular adipose tissue (IMAT): association with other adipose tissue compartments and insulin sensitivity. J Magn Reson Imaging 2009;29:1340-5.ArticlePubMed
  • 31. Goodpaster BH, Krishnaswami S, Resnick H, Kelley DE, Haggerty C, Harris TB, et al. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 2003;26:372-9.ArticlePubMedPDF
  • 32. Goodpaster BH, Thaete FL, Kelley DE. Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr 2000;71:885-92.ArticlePubMed
  • 33. Bergman BC, Brozinick JT, Strauss A, Bacon S, Kerege A, Bui HH, et al. Muscle sphingolipids during rest and exercise: a C18:0 signature for insulin resistance in humans. Diabetologia 2016;59:785-98.ArticlePubMedPDF
  • 34. Bergman BC, Hunerdosse DM, Kerege A, Playdon MC, Perreault L. Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans. Diabetologia 2012;55:1140-50.ArticlePubMedPMCPDF
  • 35. Goodpaster BH. CrossTalk proposal: intramuscular lipid accumulation causes insulin resistance. J Physiol 2020;598:3803-6.ArticlePubMedPDF
  • 36. DeFronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care 2009;32(Suppl 2):S157-63.ArticlePubMedPMCPDF
  • 37. Amati F, Dube JJ, Alvarez-Carnero E, Edreira MM, Chomentowski P, Coen PM, et al. Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Diabetes 2011;60:2588-97.PubMedPMC
  • 38. Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 2001;86:5755-61.ArticlePubMedPDF
  • 39. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev 2018;98:2133-223.ArticlePubMedPMC
  • 40. Bosma M, Kersten S, Hesselink MK, Schrauwen P. Re-evaluating lipotoxic triggers in skeletal muscle: relating intramyocellular lipid metabolism to insulin sensitivity. Prog Lipid Res 2012;51:36-49.ArticlePubMed
  • 41. Li X, Li Z, Zhao M, Nie Y, Liu P, Zhu Y, et al. Skeletal muscle lipid droplets and the athlete’s paradox. Cells 2019;8:249.ArticlePubMedPMC
  • 42. Marcus RL, Addison O, Dibble LE, Foreman KB, Morrell G, Lastayo P. Intramuscular adipose tissue, sarcopenia, and mobility function in older individuals. J Aging Res 2012;2012:629637.ArticlePubMedPMCPDF
  • 43. Scott D, Trbojevic T, Skinner E, Clark RA, Levinger P, Haines TP, et al. Associations of calf inter- and intra-muscular adipose tissue with cardiometabolic health and physical function in community-dwelling older adults. J Musculoskelet Neuronal Interact 2015;15:350-7.PubMedPMC
  • 44. Santanasto AJ, Zmuda JM, Cvejkus RK, Gordon CL, Nair S, Carr JJ, et al. Thigh and calf myosteatosis are strongly associated with muscle and physical function in african caribbean men. J Gerontol A Biol Sci Med Sci 2023;78:527-34.ArticlePubMedPMCPDF
  • 45. Scott D, Shore-Lorenti C, McMillan LB, Mesinovic J, Clark RA, Hayes A, et al. Calf muscle density is independently associated with physical function in overweight and obese older adults. J Musculoskelet Neuronal Interact 2018;18:9-17.PubMedPMC
  • 46. Scott D, Johansson J, McMillan LB, Ebeling PR, Nordstrom A, Nordstrom P. Mid-calf skeletal muscle density and its associations with physical activity, bone health and incident 12-month falls in older adults: the Healthy Ageing Initiative. Bone 2019;120:446-51.ArticlePubMed
  • 47. Frank-Wilson AW, Farthing JP, Chilibeck PD, Arnold CM, Davison KS, Olszynski WP, et al. Lower leg muscle density is independently associated with fall status in community-dwelling older adults. Osteoporos Int 2016;27:2231-40.ArticlePubMedPDF
  • 48. Biltz NK, Collins KH, Shen KC, Schwartz K, Harris CA, Meyer GA. Infiltration of intramuscular adipose tissue impairs skeletal muscle contraction. J Physiol 2020;598:2669-83.ArticlePubMedPMCPDF
  • 49. The Royal Australian College of General Practitioners. Management of type 2 diabetes: a handbook for general practice East Melbourne: RACGP; 2020.
  • 50. Villani A. Lifestyle strategies for the management of obesity in older adults: from controversies to alternative interventions. Healthcare (Basel) 2022;10:2107.ArticlePubMedPMC
  • 51. Winter JE, MacInnis RJ, Wattanapenpaiboon N, Nowson CA. BMI and all-cause mortality in older adults: a meta-analysis. Am J Clin Nutr 2014;99:875-90.ArticlePubMed
  • 52. Batsis JA, Gill LE, Masutani RK, Adachi-Mejia AM, Blunt HB, Bagley PJ, et al. Weight loss interventions in older adults with obesity: a systematic review of randomized controlled trials since 2005. J Am Geriatr Soc 2017;65:257-68.ArticlePubMedPMCPDF
  • 53. Sardeli AV, Komatsu TR, Mori MA, Gaspari AF, Chacon-Mikahil MP. Resistance training prevents muscle loss induced by caloric restriction in obese elderly individuals: a systematic review and meta-analysis. Nutrients 2018;10:423.ArticlePubMedPMC
  • 54. Mesinovic J, Jansons P, Zengin A, de Courten B, Rodriguez AJ, Daly RM, et al. Exercise attenuates bone mineral density loss during diet-induced weight loss in adults with overweight and obesity: a systematic review and meta-analysis. J Sport Health Sci 2021;10:550-9.ArticlePubMedPMC
  • 55. Goisser S, Kiesswetter E, Schoene D, Torbahn G, Bauer JM. Dietary weight-loss interventions for the management of obesity in older adults. Rev Endocr Metab Disord 2020;21:355-68.ArticlePubMedPDF
  • 56. Volkert D, Beck AM, Cederholm T, Cruz-Jentoft A, Goisser S, Hooper L, et al. ESPEN guideline on clinical nutrition and hydration in geriatrics. Clin Nutr 2019;38:10-47.ArticlePubMed
  • 57. Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, clusterrandomised trial. Lancet 2018;391:541-51.ArticlePubMed
  • 58. Esposito K, Kastorini CM, Panagiotakos DB, Giugliano D. Mediterranean diet and weight loss: meta-analysis of randomized controlled trials. Metab Syndr Relat Disord 2011;9:1-12.ArticlePubMed
  • 59. Esposito K, Maiorino MI, Bellastella G, Chiodini P, Panagiotakos D, Giugliano D. A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses. BMJ Open 2015;5:e008222.ArticlePubMedPMC
  • 60. Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr 2013;97:505-16.ArticlePubMed
  • 61. Isanejad M, Sirola J, Mursu J, Rikkonen T, Kroger H, Tuppurainen M, et al. Association of the Baltic Sea and Mediterranean diets with indices of sarcopenia in elderly women, OSPTRE-FPS study. Eur J Nutr 2018;57:1435-48.ArticlePubMedPDF
  • 62. Silva R, Pizato N, da Mata F, Figueiredo A, Ito M, Pereira MG. Mediterranean diet and musculoskeletal-functional outcomes in community-dwelling older people: a systematic review and meta-analysis. J Nutr Health Aging 2018;22:655-63.ArticlePubMedPDF
  • 63. Davis R, Rogers M, Coates AM, Leung GK, Bonham MP. The impact of meal timing on risk of weight gain and development of obesity: a review of the current evidence and opportunities for dietary intervention. Curr Diab Rep 2022;22:147-55.ArticlePubMedPMCPDF
  • 64. O’Connor SG, Boyd P, Bailey CP, Nebeling L, Reedy J, Czajkowski SM, et al. A qualitative exploration of facilitators and barriers of adherence to time-restricted eating. Appetite 2022;178:106266.ArticlePubMedPMC
  • 65. Bjerre N, Holm L, Quist JS, Færch K, Hempler NF. Watching, keeping and squeezing time to lose weight: implications of time-restricted eating in daily life. Appetite 2021;161:105138.ArticlePubMed
  • 66. Lee SA, Sypniewski C, Bensadon BA, McLaren C, Donahoo WT, Sibille KT, et al. Determinants of adherence in time-restricted feeding in older adults: lessons from a pilot study. Nutrients 2020;12:874.ArticlePubMedPMC
  • 67. Anton SD, Lee SA, Donahoo WT, McLaren C, Manini T, Leeuwenburgh C, et al. The effects of time restricted feeding on overweight, older adults: a pilot study. Nutrients 2019;11:1500.ArticlePubMedPMC
  • 68. Chaudhury A, Duvoor C, Reddy Dendi VS, Kraleti S, Chada A, Ravilla R, et al. Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Front Endocrinol (Lausanne) 2017;8:6.ArticlePubMedPMC
  • 69. Corley BT, Carroll RW, Hall RM, Weatherall M, Parry-Strong A, Krebs JD. Intermittent fasting in type 2 diabetes mellitus and the risk of hypoglycaemia: a randomized controlled trial. Diabet Med 2018;35:588-94.ArticlePubMedPDF
  • 70. Uldal S, Clemmensen KK, Persson F, Faerch K, Quist JS. Is time-restricted eating safe in the treatment of type 2 diabetes?: a review of intervention studies. Nutrients 2022;14:2299.ArticlePubMedPMC
  • 71. Arnason TG, Bowen MW, Mansell KD. Effects of intermittent fasting on health markers in those with type 2 diabetes: a pilot study. World J Diabetes 2017;8:154-64.ArticlePubMedPMC
  • 72. Che T, Yan C, Tian D, Zhang X, Liu X, Wu Z. Time-restricted feeding improves blood glucose and insulin sensitivity in overweight patients with type 2 diabetes: a randomised controlled trial. Nutr Metab (Lond) 2021;18:88.ArticlePubMedPMCPDF
  • 73. Kahleova H, Belinova L, Malinska H, Oliyarnyk O, Trnovska J, Skop V, et al. Eating two larger meals a day (breakfast and lunch) is more effective than six smaller meals in a reduced-energy regimen for patients with type 2 diabetes: a randomised crossover study. Diabetologia 2014;57:1552-60.ArticlePubMedPMCPDF
  • 74. Huang JH, Cheng FC, Tsai LC, Lee NY, Lu YF. Appropriate physical activity and dietary intake achieve optimal metabolic control in older type 2 diabetes patients. J Diabetes Investig 2014;5:418-27.ArticlePubMedPMCPDF
  • 75. Borsheim E, Bui QU, Tissier S, Kobayashi H, Ferrando AA, Wolfe RR. Effect of amino acid supplementation on muscle mass, strength and physical function in elderly. Clin Nutr 2008;27:189-95.ArticlePubMedPMC
  • 76. Tieland M, van de Rest O, Dirks ML, van der Zwaluw N, Mensink M, van Loon LJ, et al. Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2012;13:720-6.ArticlePubMed
  • 77. van Loon LJ, Kruijshoop M, Menheere PP, Wagenmakers AJ, Saris WH, Keizer HA. Amino acid ingestion strongly enhances insulin secretion in patients with long-term type 2 diabetes. Diabetes Care 2003;26:625-30.ArticlePubMedPDF
  • 78. Yu Z, Nan F, Wang LY, Jiang H, Chen W, Jiang Y. Effects of high-protein diet on glycemic control, insulin resistance and blood pressure in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Clin Nutr 2020;39:1724-34.ArticlePubMed
  • 79. Chiang SW, Liu HW, Loh EW, Tam KW, Wang JY, Huang WL, et al. Whey protein supplementation improves postprandial glycemia in persons with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Nutr Res 2022;104:44-54.ArticlePubMed
  • 80. Gannon MC, Nuttall FQ, Saeed A, Jordan K, Hoover H. An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes. Am J Clin Nutr 2003;78:734-41.ArticlePubMed
  • 81. Phillips SM, Chevalier S, Leidy HJ. Protein “requirements” beyond the RDA: implications for optimizing health. Appl Physiol Nutr Metab 2016;41:565-72.ArticlePubMed
  • 82. Yoshimura Y, Wakabayashi H, Yamada M, Kim H, Harada A, Arai H. Interventions for treating sarcopenia: a systematic review and meta-analysis of randomized controlled studies. J Am Med Dir Assoc 2017;18:553.Article
  • 83. Wu PY, Huang KS, Chen KM, Chou CP, Tu YK. Exercise, nutrition, and combined exercise and nutrition in older adults with sarcopenia: a systematic review and network meta-analysis. Maturitas 2021;145:38-48.ArticlePubMed
  • 84. Naseeb MA, Volpe SL. Protein and exercise in the prevention of sarcopenia and aging. Nutr Res 2017;40:1-20.ArticlePubMed
  • 85. Phillips SM. Nutritional supplements in support of resistance exercise to counter age-related sarcopenia. Adv Nutr 2015;6:452-60.ArticlePubMedPMC
  • 86. Dang M, Shore-Lorenti C, McMillan LB, Mesinovic J, Hayes A, Ebeling PR, et al. Associations of serum 25-hydroxyvitamin D with physical performance and bone health in overweight and obese older adults. Int J Environ Res Public Health 2019;16:509.ArticlePubMedPMC
  • 87. Scott D, Blizzard L, Fell J, Ding C, Winzenberg T, Jones G. A prospective study of the associations between 25-hydroxy-vitamin D, sarcopenia progression and physical activity in older adults. Clin Endocrinol (Oxf) 2010;73:581-7.ArticlePubMed
  • 88. Zhu A, Kuznia S, Niedermaier T, Holleczek B, Schottker B, Brenner H. Consistent inverse associations of total, “bioavailable”, free, and “non-bioavailable” vitamin D with incidence of diabetes among older adults with lower baseline HbA1c (≤6%) levels. Nutrients 2022;14:3282.ArticlePubMedPMC
  • 89. Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring) 2012;20:1444-8.ArticlePubMedPDF
  • 90. Hu Z, Chen J, Sun X, Wang L, Wang A. Efficacy of vitamin D supplementation on glycemic control in type 2 diabetes patients: a meta-analysis of interventional studies. Medicine (Baltimore) 2019;98:e14970.PubMedPMC
  • 91. Tang H, Li D, Li Y, Zhang X, Song Y, Li X. Effects of vitamin D supplementation on glucose and insulin homeostasis and incident diabetes among nondiabetic adults: a meta-analysis of randomized controlled trials. Int J Endocrinol 2018;2018:7908764.ArticlePubMedPMCPDF
  • 92. Mirhosseini N, Vatanparast H, Mazidi M, Kimball SM. Vitamin D supplementation, glycemic control, and insulin resistance in prediabetics: a meta-analysis. J Endocr Soc 2018;2:687-709.ArticlePubMedPMC
  • 93. Zhang Y, Tan H, Tang J, Li J, Chong W, Hai Y, et al. Effects of vitamin D supplementation on prevention of type 2 diabetes in patients with prediabetes: a systematic review and meta-analysis. Diabetes Care 2020;43:1650-8.ArticlePubMedPDF
  • 94. Jamka M, Wozniewicz M, Jeszka J, Mardas M, Bogdanski P, Stelmach-Mardas M. The effect of vitamin D supplementation on insulin and glucose metabolism in overweight and obese individuals: systematic review with meta-analysis. Sci Rep 2015;5:16142.ArticlePubMedPMCPDF
  • 95. Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, et al. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2014;99:4336-45.ArticlePubMed
  • 96. Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL. Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 2011;22:859-71.ArticlePubMed
  • 97. Bislev LS, Grove-Laugesen D, Rejnmark L. Vitamin D and muscle health: a systematic review and meta-analysis of randomized placebo-controlled trials. J Bone Miner Res 2021;36:1651-60.ArticlePubMedPDF
  • 98. Prokopidis K, Giannos P, Katsikas Triantafyllidis K, Kechagias KS, Mesinovic J, Witard OC, et al. Effect of vitamin D monotherapy on indices of sarcopenia in community-dwelling older adults: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2022;13:1642-52.ArticlePubMedPMCPDF
  • 99. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med 2016;176:175-83.ArticlePubMed
  • 100. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010;303:1815-22.ArticlePubMed
  • 101. Antoniak AE, Greig CA. The effect of combined resistance exercise training and vitamin D3 supplementation on musculoskeletal health and function in older adults: a systematic review and meta-analysis. BMJ Open 2017;7:e014619.ArticlePubMedPMC
  • 102. Mesinovic J, Rodriguez AJ, Cervo MM, Gandham A, Xu CL, Glavas C, et al. Vitamin D supplementation and exercise for improving physical function, body composition and metabolic health in overweight or obese older adults with vitamin D deficiency: a pilot randomized, double-blind, placebo-controlled trial. Eur J Nutr 2023;62:951-64.ArticlePubMedPMCPDF
  • 103. Mølmen KS, Hammarstrom D, Pedersen K, Lian Lie AC, Steile RB, Nygaard H, et al. Vitamin D3 supplementation does not enhance the effects of resistance training in older adults. J Cachexia Sarcopenia Muscle 2021;12:599-628.ArticlePubMedPMCPDF
  • 104. Savolainen L, Timpmann S, Mooses M, Maestu E, Medijainen L, Tonutare L, et al. Vitamin D supplementation does not enhance resistance training-induced gains in muscle strength and lean body mass in vitamin D deficient young men. Eur J Appl Physiol 2021;121:2077-90.ArticlePubMedPDF
  • 105. Sinclair AJ, Abdelhafiz AH, Rodriguez-Manas L. Frailty and sarcopenia: newly emerging and high impact complications of diabetes. J Diabetes Complications 2017;31:1465-73.ArticlePubMed
  • 106. Chow LS, Nair KS. Sarcopenia of male aging. Endocrinol Metab Clin North Am 2005;34:833-52.ArticlePubMed
  • 107. Johns N, Stephens NA, Fearon KC. Muscle wasting in cancer. Int J Biochem Cell Biol 2013;45:2215-29.ArticlePubMed
  • 108. Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov 2015;14:58-74.ArticlePubMedPDF
  • 109. O’Mahoney LL, Matu J, Price OJ, Birch KM, Ajjan RA, Farrar D, et al. Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials. Cardiovasc Diabetol 2018;17:98.ArticlePubMedPMCPDF
  • 110. Akinkuolie AO, Ngwa JS, Meigs JB, Djousse L. Omega-3 polyunsaturated fatty acid and insulin sensitivity: a meta-analysis of randomized controlled trials. Clin Nutr 2011;30:702-7.ArticlePubMedPMC
  • 111. Chen C, Yu X, Shao S. Effects of omega-3 fatty acid supplementation on glucose control and lipid levels in type 2 diabetes: a meta-analysis. PLoS One 2015;10:e0139565.ArticlePubMedPMC
  • 112. Bird JK, Troesch B, Warnke I, Calder PC. The effect of long chain omega-3 polyunsaturated fatty acids on muscle mass and function in sarcopenia: a scoping systematic review and meta-analysis. Clin Nutr ESPEN 2021;46:73-86.ArticlePubMed
  • 113. Norman K, Hab U, Pirlich M. Malnutrition in older adults-recent advances and remaining challenges. Nutrients 2021;13:2764.ArticlePubMedPMC
  • 114. Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 2015;16:740-7.ArticlePubMed
  • 115. Lin CC, Shih MH, Chen CD, Yeh SL. Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: an open-label, parallel-group study. Clin Nutr 2021;40:1323-9.ArticlePubMed
  • 116. Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep 1985;100:126-31.PubMedPMC
  • 117. Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med 2020;54:1451-62.ArticlePubMedPMC
  • 118. Ross R, Chaput JP, Giangregorio LM, Janssen I, Saunders TJ, Kho ME, et al. Canadian 24-hour movement guidelines for adults aged 18-64 years and adults aged 65 years or older: an integration of physical activity, sedentary behaviour, and sleep. Appl Physiol Nutr Metab 2020;45(10 Suppl 2):S57-102.PubMed
  • 119. Berkemeyer K, Wijndaele K, White T, Cooper AJ, Luben R, Westgate K, et al. The descriptive epidemiology of accelerometer-measured physical activity in older adults. Int J Behav Nutr Phys Act 2016;13:2.ArticlePubMedPMC
  • 120. Harvey JA, Chastin SF, Skelton DA. How sedentary are older people?: a systematic review of the amount of sedentary behavior. J Aging Phys Act 2015;23:471-87.ArticlePubMed
  • 121. Ballin M, Nordstrom P, Niklasson J, Alamaki A, Condell J, Tedesco S, et al. Daily step count and incident diabetes in community-dwelling 70-year-olds: a prospective cohort study. BMC Public Health 2020;20:1830.ArticlePubMedPMCPDF
  • 122. Yerramalla MS, McGregor DE, van Hees VT, Fayosse A, Dugravot A, Tabak AG, et al. Association of daily composition of physical activity and sedentary behaviour with incidence of cardiovascular disease in older adults. Int J Behav Nutr Phys Act 2021;18:83.ArticlePubMedPMCPDF
  • 123. Ramsey KA, Rojer AG, D’Andrea L, Otten RH, Heymans MW, Trappenburg MC, et al. The association of objectively measured physical activity and sedentary behavior with skeletal muscle strength and muscle power in older adults: a systematic review and meta-analysis. Ageing Res Rev 2021;67:101266.ArticlePubMed
  • 124. Ekelund U, Tarp J, Steene-Johannessen J, Hansen BH, Jefferis B, Fagerland MW, et al. Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis. BMJ 2019;366:l4570.ArticlePubMedPMC
  • 125. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 diabetes, 2022: a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022;45:2753-86.ArticlePubMedPMCPDF
  • 126. Kanaley JA, Colberg SR, Corcoran MH, Malin SK, Rodriguez NR, Crespo CJ, et al. Exercise/physical activity in individuals with type 2 diabetes: a consensus statement from the American College of Sports Medicine. Med Sci Sports Exerc 2022;54:353-68.ArticlePubMedPMC
  • 127. Mosalman Haghighi M, Mavros Y, Fiatarone Singh MA. The effects of structured exercise or lifestyle behavior interventions on long-term physical activity level and health outcomes in individuals with type 2 diabetes: a systematic review, meta-analysis, and meta-regression. J Phys Act Health 2018;15:697-707.ArticlePubMed
  • 128. Tan KH, Siah CJ. Effects of low-to-moderate physical activities on older adults with chronic diseases: a systematic review and meta-analysis. J Clin Nurs 2022;31:2072-86.ArticlePubMedPDF
  • 129. Look AHEAD Research Group, Wadden TA, West DS, Delahanty L, Jakicic J, Rejeski J, et al. The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obesity (Silver Spring) 2006;14:737-52.ArticlePubMedPMC
  • 130. Rejeski WJ, Bray GA, Chen SH, Clark JM, Evans M, Hill JO, et al. Aging and physical function in type 2 diabetes: 8 years of an intensive lifestyle intervention. J Gerontol A Biol Sci Med Sci 2015;70:345-53.ArticlePubMedPMC
  • 131. Houston DK, Leng X, Bray GA, Hergenroeder AL, Hill JO, Jakicic JM, et al. A long-term intensive lifestyle intervention and physical function: the look AHEAD Movement and Memory Study. Obesity (Silver Spring) 2015;23:77-84.PubMed
  • 132. Houston DK, Neiberg RH, Miller ME, Hill JO, Jakicic JM, Johnson KC, et al. Physical function following a long-term lifestyle intervention among middle aged and older adults with type 2 diabetes: the look AHEAD study. J Gerontol A Biol Sci Med Sci 2018;73:1552-9.ArticlePubMedPMC
  • 133. Gray P, Murphy M, Gallagher A, Simpson EE. A qualitative investigation of physical activity compensation among older adults. Br J Health Psychol 2018;23:208-24.ArticlePubMedPDF
  • 134. Careau V, Halsey LG, Pontzer H, Ainslie PN, Andersen LF, Anderson LJ, et al. Energy compensation and adiposity in humans. Curr Biol 2021;31:4659-66.ArticlePubMedPMC
  • 135. Melanson EL. The effect of exercise on non-exercise physical activity and sedentary behavior in adults. Obes Rev 2017;18(Suppl 1):40-9.ArticlePubMedPMCPDF
  • 136. Madden KM, Feldman B, Chase J. Sedentary time and metabolic risk in extremely active older adults. Diabetes Care 2021;44:194-200.ArticlePubMedPMCPDF
  • 137. Homer AR, Taylor FC, Dempsey PC, Wheeler MJ, Sethi P, Townsend MK, et al. Frequency of interruptions to sitting time: benefits for postprandial metabolism in type 2 diabetes. Diabetes Care 2021;44:1254-63.ArticlePubMedPMCPDF
  • 138. Duvivier BM, Schaper NC, Hesselink MK, van Kan L, Stienen N, Winkens B, et al. Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes. Diabetologia 2017;60:490-8.ArticlePubMedPMCPDF
  • 139. DiPietro L, Gribok A, Stevens MS, Hamm LF, Rumpler W. Three 15-min bouts of moderate postmeal walking significantly improves 24-h glycemic control in older people at risk for impaired glucose tolerance. Diabetes Care 2013;36:3262-8.ArticlePubMedPMCPDF
  • 140. van Dijk JW, Venema M, van Mechelen W, Stehouwer CD, Hartgens F, van Loon LJ. Effect of moderate-intensity exercise versus activities of daily living on 24-hour blood glucose homeostasis in male patients with type 2 diabetes. Diabetes Care 2013;36:3448-53.ArticlePubMedPMCPDF
  • 141. Dempsey PC, Larsen RN, Sethi P, Sacre JW, Straznicky NE, Cohen ND, et al. Benefits for type 2 diabetes of interrupting prolonged sitting with brief bouts of light walking or simple resistance activities. Diabetes Care 2016;39:964-72.ArticlePubMedPDF
  • 142. Dempsey PC, Blankenship JM, Larsen RN, Sacre JW, Sethi P, Straznicky NE, et al. Interrupting prolonged sitting in type 2 diabetes: nocturnal persistence of improved glycaemic control. Diabetologia 2017;60:499-507.ArticlePubMedPDF
  • 143. Taylor FC, Dunstan DW, Homer AR, Dempsey PC, Kingwell BA, Climie RE, et al. Acute effects of interrupting prolonged sitting on vascular function in type 2 diabetes. Am J Physiol Heart Circ Physiol 2021;320:H393-403.ArticlePubMed
  • 144. Blankenship JM, Chipkin SR, Freedson PS, Staudenmayer J, Lyden K, Braun B. Managing free-living hyperglycemia with exercise or interrupted sitting in type 2 diabetes. J Appl Physiol (1985) 2019;126:616-25.ArticlePubMed
  • 145. Eriksen L, Dahl-Petersen I, Haugaard SB, Dela F. Comparison of the effect of multiple short-duration with single long-duration exercise sessions on glucose homeostasis in type 2 diabetes mellitus. Diabetologia 2007;50:2245-53.ArticlePubMedPDF
  • 146. Reynolds AN, Mann JI, Williams S, Venn BJ. Advice to walk after meals is more effective for lowering postprandial glycaemia in type 2 diabetes mellitus than advice that does not specify timing: a randomised crossover study. Diabetologia 2016;59:2572-8.ArticlePubMedPDF
  • 147. Chastin S, Gardiner PA, Harvey JA, Leask CF, Jerez-Roig J, Rosenberg D, et al. Interventions for reducing sedentary behaviour in community-dwelling older adults. Cochrane Database Syst Rev 2021;6:CD012784.ArticlePubMedPMC
  • 148. Ramsey KA, Zhou W, Rojer AG, Reijnierse EM, Maier AB. Associations of objectively measured physical activity and sedentary behaviour with fall-related outcomes in older adults: a systematic review. Ann Phys Rehabil Med 2022;65:101571.ArticlePubMed
  • 149. Johansson J, Morseth B, Scott D, Strand BH, Hopstock LA, Grimsgaard S. Moderate-to-vigorous physical activity modifies the relationship between sedentary time and sarcopenia: the Tromsø Study 2015-2016. J Cachexia Sarcopenia Muscle 2021;12:955-63.ArticlePubMedPMCPDF
  • 150. Scott D, Johansson J, Gandham A, Ebeling PR, Nordstrom P, Nordstrom A. Associations of accelerometer-determined physical activity and sedentary behavior with sarcopenia and incident falls over 12 months in community-dwelling Swedish older adults. J Sport Health Sci 2021;10:577-84.ArticlePubMedPMC
  • 151. Grant D, Tomlinson D, Tsintzas K, Kolic P, Onambele-Pearson G. Minimizing sedentary behavior (without increasing medium-to-vigorous exercise) associated functional improvement in older women is somewhat dependent on a measurable increase in muscle size. Aging (Albany NY) 2020;12:24081-100.ArticlePubMedPMC
  • 152. Harvey JA, Chastin SF, Skelton DA. Breaking sedentary behaviour has the potential to increase/maintain function in frail older adults. J Frailty Sarcopenia Falls 2018;3:26-31.ArticlePubMedPMC
  • 153. Barone Gibbs B, Brach JS, Byard T, Creasy S, Davis KK, McCoy S, et al. Reducing sedentary behavior versus increasing moderate-to-vigorous intensity physical activity in older adults. J Aging Health 2017;29:247-67.ArticlePubMedPDF
  • 154. Rosenberg DE, Anderson ML, Renz A, Matson TE, Lee AK, Greenwood-Hickman MA, et al. Reducing sitting time in obese older adults: the I-STAND randomized controlled trial. J Aging Phys Act 2020;28:864-74.ArticlePubMedPMC
  • 155. Greenwood-Hickman MA, Renz A, Rosenberg DE. Motivators and barriers to reducing sedentary behavior among overweight and obese older adults. Gerontologist 2016;56:660-8.ArticlePubMedPMCPDF
  • 156. Bird SR, Hawley JA. Update on the effects of physical activity on insulin sensitivity in humans. BMJ Open Sport Exerc Med 2017;2:e000143.ArticlePubMedPMC
  • 157. Ismail AD, Alkhayl FF, Wilson J, Johnston L, Gill JM, Gray SR. The effect of short-duration resistance training on insulin sensitivity and muscle adaptations in overweight men. Exp Physiol 2019;104:540-5.ArticlePubMedPDF
  • 158. Evans PL, McMillin SL, Weyrauch LA, Witczak CA. Regulation of skeletal muscle glucose transport and glucose metabolism by exercise training. Nutrients 2019;11:2432.ArticlePubMedPMC
  • 159. Grgic J, Mcllvenna LC, Fyfe JJ, Sabol F, Bishop DJ, Schoenfeld BJ, et al. Does aerobic training promote the same skeletal muscle hypertrophy as resistance training?: a systematic review and meta-analysis. Sports Med 2019;49:233-54.ArticlePubMedPDF
  • 160. Suchomel TJ, Nimphius S, Bellon CR, Stone MH. The importance of muscular strength: training considerations. Sports Med 2018;48:765-85.ArticlePubMedPDF
  • 161. Farup J, Kjolhede T, Sorensen H, Dalgas U, Moller AB, Vestergaard PF, et al. Muscle morphological and strength adaptations to endurance vs. resistance training. J Strength Cond Res 2012;26:398-407.ArticlePubMed
  • 162. Santos L, Elliott-Sale KJ, Sale C. Exercise and bone health across the lifespan. Biogerontology 2017;18:931-46.ArticlePubMedPMCPDF
  • 163. Konopka AR, Harber MP. Skeletal muscle hypertrophy after aerobic exercise training. Exerc Sport Sci Rev 2014;42:53-61.ArticlePubMedPMC
  • 164. Frank P, Andersson E, Ponten M, Ekblom B, Ekblom M, Sahlin K. Strength training improves muscle aerobic capacity and glucose tolerance in elderly. Scand J Med Sci Sports 2016;26:764-73.ArticlePubMed
  • 165. Kadoglou NP, Fotiadis G, Kapelouzou A, Kostakis A, Liapis CD, Vrabas IS. The differential anti-inflammatory effects of exercise modalities and their association with early carotid atherosclerosis progression in patients with type 2 diabetes. Diabet Med 2013;30:e41-50.ArticlePubMed
  • 166. Castaneda C, Layne JE, Munoz-Orians L, Gordon PL, Walsmith J, Foldvari M, et al. A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with type 2 diabetes. Diabetes Care 2002;25:2335-41.ArticlePubMedPDF
  • 167. Terada T, Friesen A, Chahal BS, Bell GJ, McCargar LJ, Boule NG. Feasibility and preliminary efficacy of high intensity interval training in type 2 diabetes. Diabetes Res Clin Pract 2013;99:120-9.ArticlePubMed
  • 168. Miller EG, Nowson CA, Dunstan DW, Kerr DA, Menzies D, Daly RM. Effects of whey protein plus vitamin D supplementation combined with progressive resistance training on glycaemic control, body composition, muscle function and cardiometabolic risk factors in middle-aged and older overweight/obese adults with type 2 diabetes: a 24-week randomized controlled trial. Diabetes Obes Metab 2021;23:938-49.PubMed
  • 169. Dunstan DW, Daly RM, Owen N, Jolley D, De Courten M, Shaw J, et al. High-intensity resistance training improves glycemic control in older patients with type 2 diabetes. Diabetes Care 2002;25:1729-36.ArticlePubMedPDF
  • 170. Loimaala A, Groundstroem K, Rinne M, Nenonen A, Huhtala H, Parkkari J, et al. Effect of long-term endurance and strength training on metabolic control and arterial elasticity in patients with type 2 diabetes mellitus. Am J Cardiol 2009;103:972-7.ArticlePubMed
  • 171. Hou L, Wang Q, Pan B, Li R, Li Y, He J, et al. Exercise modalities for type 2 diabetes: a systematic review and network meta-analysis of randomized trials. Diabetes Metab Res Rev 2023;39:e3591.ArticlePubMedPDF
  • 172. Pan B, Ge L, Xun YQ, Chen YJ, Gao CY, Han X, et al. Exercise training modalities in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis. Int J Behav Nutr Phys Act 2018;15:72.ArticlePubMedPMCPDF
  • 173. Lu L, Mao L, Feng Y, Ainsworth BE, Liu Y, Chen N. Effects of different exercise training modes on muscle strength and physical performance in older people with sarcopenia: a systematic review and meta-analysis. BMC Geriatr 2021;21:708.ArticlePubMedPMCPDF
  • 174. Vlietstra L, Hendrickx W, Waters DL. Exercise interventions in healthy older adults with sarcopenia: a systematic review and meta-analysis. Australas J Ageing 2018;37:169-83.ArticlePubMedPDF
  • 175. Csapo R, Alegre LM. Effects of resistance training with moderate vs heavy loads on muscle mass and strength in the elderly: a meta-analysis. Scand J Med Sci Sports 2016;26:995-1006.ArticlePubMed
  • 176. Rafiei H, Omidian K, Myette-Cote E, Little JP. Metabolic effect of breaking up prolonged sitting with stair climbing exercise snacks. Med Sci Sports Exerc 2021;53:150-8.ArticlePubMed
  • 177. Islam H, Gibala MJ, Little JP. Exercise snacks: a novel strategy to improve cardiometabolic health. Exerc Sport Sci Rev 2022;50:31-7.ArticlePubMed
  • 178. Wolfe AS, Burton HM, Vardarli E, Coyle EF. Hourly 4-s sprints prevent impairment of postprandial fat metabolism from inactivity. Med Sci Sports Exerc 2020;52:2262-9.ArticlePubMed
  • 179. Little JP, Langley J, Lee M, Myette-Cote E, Jackson G, Durrer C, et al. Sprint exercise snacks: a novel approach to increase aerobic fitness. Eur J Appl Physiol 2019;119:1203-12.ArticlePubMedPDF
  • 180. Jenkins EM, Nairn LN, Skelly LE, Little JP, Gibala MJ. Do stair climbing exercise “snacks” improve cardiorespiratory fitness? Appl Physiol Nutr Metab 2019;44:681-4.ArticlePubMed
  • 181. Fyfe JJ, Dalla Via J, Jansons P, Scott D, Daly RM. Feasibility and acceptability of a remotely delivered, home-based, pragmatic resistance ‘exercise snacking’ intervention in community-dwelling older adults: a pilot randomised controlled trial. BMC Geriatr 2022;22:521.ArticlePubMedPMCPDF
  • 182. Perkin OJ, McGuigan PM, Stokes KA. Exercise snacking to improve muscle function in healthy older adults: a pilot study. J Aging Res 2019;2019:7516939.ArticlePubMedPMCPDF
  • 183. Jansons P, Dalla Via J, Daly RM, Fyfe JJ, Gvozdenko E, Scott D. Delivery of home-based exercise interventions in older adults facilitated by amazon alexa: a 12-week feasibility trial. J Nutr Health Aging 2022;26:96-102.ArticlePubMedPDF
  • 184. Liang IJ, Perkin OJ, McGuigan PM, Thompson D, Western MJ. Feasibility and acceptability of home-based exercise snacking and Tai Chi snacking delivered remotely to self-isolating older adults during COVID-19. J Aging Phys Act 2022;30:33-43.ArticlePubMed
  • 185. Waters DL, Aguirre L, Gurney B, Sinacore DR, Fowler K, Gregori G, et al. Effect of aerobic or resistance exercise, or both, on intermuscular and visceral fat and physical and metabolic function in older adults with obesity while dieting. J Gerontol A Biol Sci Med Sci 2022;77:131-9.ArticlePubMedPMCPDF
  • 186. Villareal DT, Chode S, Parimi N, Sinacore DR, Hilton T, Armamento-Villareal R, et al. Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med 2011;364:1218-29.ArticlePubMedPMC
  • 187. Villareal DT, Aguirre L, Gurney AB, Waters DL, Sinacore DR, Colombo E, et al. Aerobic or resistance exercise, or both, in dieting obese older adults. N Engl J Med 2017;376:1943-55.ArticlePubMedPMC
  • 188. Madrid DA, Beavers KM, Walkup MP, Ambrosius WT, Rejeski WJ, Marsh AP, et al. Effect of exercise modality and weight loss on changes in muscle and bone quality in older adults with obesity. Exp Gerontol 2023;174:112126.ArticlePubMedPMC
  • 189. Massimino E, Izzo A, Riccardi G, Della Pepa G. The impact of glucose-lowering drugs on sarcopenia in type 2 diabetes: current evidence and underlying mechanisms. Cells 2021;10:1958.ArticlePubMedPMC
  • 190. Lee YS, Jun HS. Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells. Metabolism 2014;63:9-19.ArticlePubMed
  • 191. Wilding JP, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384:989-1002.ArticlePubMed
  • 192. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022;387:205-16.ArticlePubMed
  • 193. Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 2021;385:503-15.ArticlePubMed
  • 194. Wharton S, Blevins T, Connery L, Rosenstock J, Raha S, Liu R, et al. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med 2023;389:877-88.ArticlePubMed
  • 195. Jastreboff AM, Kaplan LM, Frias JP, Wu Q, Du Y, Gurbuz S, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med 2023;389:514-26.ArticlePubMed
  • 196. Latres E, Pangilinan J, Miloscio L, Bauerlein R, Na E, Potocky TB, et al. Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice. Skelet Muscle 2015;5:34.ArticlePubMedPMC
  • 197. Lv Q, Yuan L, Deng J, Chen M, Wang Y, Zeng J, et al. Efficient generation of myostatin gene mutated rabbit by CRISPR/Cas9. Sci Rep 2016;6:25029.ArticlePubMedPMCPDF
  • 198. Becker C, Lord SR, Studenski SA, Warden SJ, Fielding RA, Recknor CP, et al. Myostatin antibody (LY2495655) in older weak fallers: a proof-of-concept, randomised, phase 2 trial. Lancet Diabetes Endocrinol 2015;3:948-57.ArticlePubMed
  • 199. Rooks D, Swan T, Goswami B, Filosa LA, Bunte O, Panchaud N, et al. Bimagrumab vs optimized standard of care for treatment of sarcopenia in community-dwelling older adults: a randomized clinical trial. JAMA Netw Open 2020;3:e2020836.ArticlePubMedPMC
  • 200. Hanna MG, Badrising UA, Benveniste O, Lloyd TE, Needham M, Chinoy H, et al. Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol 2019;18:834-44.ArticlePubMed
  • 201. Heymsfield SB, Coleman LA, Miller R, Rooks DS, Laurent D, Petricoul O, et al. Effect of bimagrumab vs placebo on body fat mass among adults with type 2 diabetes and obesity: a phase 2 randomized clinical trial. JAMA Netw Open 2021;4:e2033457.ArticlePubMedPMC
  • 202. Garito T, Roubenoff R, Hompesch M, Morrow L, Gomez K, Rooks D, et al. Bimagrumab improves body composition and insulin sensitivity in insulin-resistant individuals. Diabetes Obes Metab 2018;20:94-102.ArticlePubMedPDF
  • 203. De Spiegeleer A, Beckwee D, Bautmans I, Petrovic M; Sarcopenia Guidelines Development Group of the Belgian Society of Gerontology and Geriatrics (BSGG). Pharmacological interventions to improve muscle mass, muscle strength and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Drugs Aging 2018;35:719-34.ArticlePubMedPDF
  • 204. Skinner JW, Otzel DM, Bowser A, Nargi D, Agarwal S, Peterson MD, et al. Muscular responses to testosterone replacement vary by administration route: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle 2018;9:465-81.ArticlePubMedPMCPDF
  • 205. Wittert G, Bracken K, Robledo KP, Grossmann M, Yeap BB, Handelsman DJ, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol 2021;9:32-45.ArticlePubMed
  • 206. Robledo KP, Marschner IC, Handelsman DJ, Bracken K, Stuckey BG, Yeap BB, et al. Mediation analysis of the testosterone treatment effect to prevent type 2 diabetes in the Testosterone for Prevention of Type 2 Diabetes Mellitus trial. Eur J Endocrinol 2023;188:613-20.ArticlePubMedPDF
  • 207. Grossmann M, Hoermann R, Wittert G, Yeap BB. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Clin Endocrinol (Oxf) 2015;83:344-51.ArticlePubMed
  • 208. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 2005;60:1451-7.ArticlePubMed
  • 209. Shufelt CL, Braunstein GD. Safety of testosterone use in women. Maturitas 2009;63:63-6.ArticlePubMed
  • 210. Narayanan R, Coss CC, Dalton JT. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol 2018;465:134-42.ArticlePubMedPMC
  • 211. Xie Y, Tian Y, Zhang Y, Zhang Z, Chen R, Li M, et al. Overview of the development of selective androgen receptor modulators (SARMs) as pharmacological treatment for osteoporosis (1998-2021). Eur J Med Chem 2022;230:114119.ArticlePubMed
  • 212. Papanicolaou DA, Ather SN, Zhu H, Zhou Y, Lutkiewicz J, Scott BB, et al. A phase IIA randomized, placebo-controlled clinical trial to study the efficacy and safety of the selective androgen receptor modulator (SARM), MK-0773 in female participants with sarcopenia. J Nutr Health Aging 2013;17:533-43.ArticlePubMedPDF
  • 213. Dobs AS, Boccia RV, Croot CC, Gabrail NY, Dalton JT, Hancock ML, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol 2013;14:335-45.ArticlePubMedPMC
  • 214. Dalton JT, Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle 2011;2:153-61.ArticlePubMedPMCPDF
  • 215. Lee DY, Lee CM. Surgical treatment for obesity. J Korean Med Assoc 2022;65:417-22.ArticlePDF
  • 216. Hollanda A, Lecube A, Rubio MA, Sanchez E, Vilarrasa N, Oliva JG, et al. New metrics to assess type 2 diabetes after bariatric surgery: the “time-within-remission range”. J Clin Med 2020;9:1070.ArticlePubMedPMC
  • 217. Chumakova-Orin M, Vanetta C, Moris DP, Guerron AD. Diabetes remission after bariatric surgery. World J Diabetes 2021;12:1093-101.ArticlePubMedPMC
  • 218. Basu R. Precision medicine in diabetes: a multidisciplinary approach to an emerging paradigm. Cham: Springer; 2022. Chapter 11, Surgical management for diabetes remission. p. 217-31.
  • 219. Alba DL, Wu L, Cawthon PM, Mulligan K, Lang T, Patel S, et al. Changes in lean mass, absolute and relative muscle strength, and physical performance after gastric bypass surgery. J Clin Endocrinol Metab 2019;104:711-20.ArticlePubMedPMC
  • 220. Sylivris A, Mesinovic J, Scott D, Jansons P. Body composition changes at 12months following different surgical weight loss interventions in adults with obesity: a systematic review and meta-analysis of randomized control trials. Obes Rev 2022;23:e13442.ArticlePubMedPMCPDF
  • 221. Staudenmann DA, Sui Z, Saxena P, Kaffes AJ, Marinos G, Kumbhari V, et al. Endoscopic bariatric therapies for obesity: a review. Med J Aust 2021;215:183-8.ArticlePubMedPDF
  • 222. Gazdzinska AP, Mojkowska A, Zielinski P, Gazdzinski SP. Changes in resting metabolic rate and body composition due to intragastric balloon therapy. Surg Obes Relat Dis 2020;16:34-9.ArticlePubMed
  • 223. Shah RH, Vedantam S, Kumar S, Amin S, Pearlman M, Bhalla S. Intragastric balloon significantly improves metabolic parameters at 6 months: a meta-analysis. Obes Surg 2023;33:725-32.ArticlePubMedPDF
  • 224. Dantas WS, Roschel H, Murai IH, Gil S, Davuluri G, Axelrod CL, et al. Exercise-induced increases in insulin sensitivity after bariatric surgery are mediated by muscle extracellular matrix remodeling. Diabetes 2020;69:1675-91.ArticlePubMedPMCPDF
  • 225. Bellicha A, van Baak MA, Battista F, Beaulieu K, Blundell JE, Busetto L, et al. Effect of exercise training before and after bariatric surgery: a systematic review and meta-analysis. Obes Rev 2021;22(Suppl 4):e13296.ArticlePubMedPMCPDF
  • 226. Hunsaker A, Hargittai E. A review of Internet use among older adults. New Media Soc 2018;20:3937-54.ArticlePDF
  • 227. Jones RB, Ashurst EJ, Atkey J, Duffy B. Older people going online: its value and before-after evaluation of volunteer support. J Med Internet Res 2015;17:e122.ArticlePubMedPMC
  • 228. Kruse CS, Krowski N, Rodriguez B, Tran L, Vela J, Brooks M. Telehealth and patient satisfaction: a systematic review and narrative analysis. BMJ Open 2017;7:e016242.ArticlePubMedPMC
  • 229. Flodgren G, Rachas A, Farmer AJ, Inzitari M, Shepperd S. Interactive telemedicine: effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2015;2015:CD002098.ArticlePubMedPMC
  • 230. Al-Badri M, Kilroy CL, Shahar JI, Tomah S, Gardner H, Sin M, et al. In-person and virtual multidisciplinary intensive lifestyle interventions are equally effective in patients with type 2 diabetes and obesity. Ther Adv Endocrinol Metab 2022;13:20420188221093220.ArticlePubMedPMCPDF
  • 231. Hamdy O, Mottalib A, Morsi A, El-Sayed N, Goebel-Fabbri A, Arathuzik G, et al. Long-term effect of intensive lifestyle intervention on cardiovascular risk factors in patients with diabetes in real-world clinical practice: a 5-year longitudinal study. BMJ Open Diabetes Res Care 2017;5:e000259.ArticlePubMedPMC
  • 232. Hansel B, Giral P, Gambotti L, Lafourcade A, Peres G, Filipecki C, et al. A fully automated web-based program improves lifestyle habits and HbA1c in patients with type 2 diabetes and abdominal obesity: randomized trial of patient e-coaching nutritional support (The ANODE Study). J Med Internet Res 2017;19:e360.ArticlePubMedPMC
  • 233. Murray E, Sweeting M, Dack C, Pal K, Modrow K, Hudda M, et al. Web-based self-management support for people with type 2 diabetes (HeLP-Diabetes): randomised controlled trial in English primary care. BMJ Open 2017;7:e016009.ArticlePubMedPMC
  • 234. Shea S, Weinstock RS, Teresi JA, Palmas W, Starren J, Cimino JJ, et al. A randomized trial comparing telemedicine case management with usual care in older, ethnically diverse, medically underserved patients with diabetes mellitus: 5 year results of the IDEATel study. J Am Med Inform Assoc 2009;16:446-56.ArticlePubMedPMC
  • 235. Gershkowitz BD, Hillert CJ, Crotty BH. Digital coaching strategies to facilitate behavioral change in type 2 diabetes: a systematic review. J Clin Endocrinol Metab 2021;106:e1513-20.ArticlePubMedPDF
  • 236. Clemson L, Fiatarone Singh MA, Bundy A, Cumming RG, Manollaras K, O’Loughlin P, et al. Integration of balance and strength training into daily life activity to reduce rate of falls in older people (the LiFE study): randomised parallel trial. BMJ 2012;345:e4547.ArticlePubMedPMC
  • 237. Taraldsen K, Mikolaizak AS, Maier AB, Mellone S, Boulton E, Aminian K, et al. Digital technology to deliver a lifestyle-integrated exercise intervention in young seniors: the PreventIT Feasibility Randomized Controlled Trial. Front Digit Health 2020;2:10.ArticlePubMedPMC
  • 238. Hsu YI, Chen YC, Lee CL, Chang NJ. Effects of diet control and telemedicine-based resistance exercise intervention on patients with obesity and knee osteoarthritis: a randomized control trial. Int J Environ Res Public Health 2021;18:7744.ArticlePubMedPMC
  • 239. Waki K, Fujita H, Uchimura Y, Omae K, Aramaki E, Kato S, et al. DialBetics: a novel smartphone-based self-management support system for type 2 diabetes patients. J Diabetes Sci Technol 2014;8:209-15.ArticlePubMedPMCPDF
  • 240. Wilson J, Heinsch M, Betts D, Booth D, Kay-Lambkin F. Barriers and facilitators to the use of e-health by older adults: a scoping review. BMC Public Health 2021;21:1556.ArticlePubMedPMCPDF
  • 241. Graham SA, Stein N, Shemaj F, Branch OH, Paruthi J, Kanick SC. Older adults engage with personalized digital coaching programs at rates that exceed those of younger adults. Front Digit Health 2021;3:642818.ArticlePubMedPMC
  • 242. King DE, Mainous AG 3rd, Carnemolla M, Everett CJ. Adherence to healthy lifestyle habits in US adults, 1988-2006. Am J Med 2009;122:528-34.ArticlePubMed
  • 243. Bailey SC, Oramasionwu CU, Wolf MS. Rethinking adherence: a health literacy-informed model of medication selfmanagement. J Health Commun 2013;18(Suppl 1):20-30.ArticlePubMedPMC
  • 244. World Health Organization; Regional Office for South-East Asia. Health literacy toolkit for low- and middle-income countries: a series of information sheets to empower communities and strengthen health systems. New Delhi: WHO; 2015.
  • 245. O’Meara L, Williams SL, Ames K, Lawson C, Saluja S, Vandelanotte C. Low health literacy is associated with risk of developing type 2 diabetes in a nonclinical population. Diabetes Educ 2019;45:431-41.ArticlePubMedPDF
  • 246. Tajdar D, Luhmann D, Fertmann R, Steinberg T, van den Bussche H, Scherer M, et al. Low health literacy is associated with higher risk of type 2 diabetes: a cross-sectional study in Germany. BMC Public Health 2021;21:510.ArticlePubMedPMCPDF
  • 247. Abdullah A, Liew SM, Salim H, Ng CJ, Chinna K. Prevalence of limited health literacy among patients with type 2 diabetes mellitus: a systematic review. PLoS One 2019;14:e0216402.ArticlePubMedPMC
  • 248. Chin J, Wang H, Awwad AW, Graumlich JF, Wolf MS, Morrow DG. Health literacy, processing capacity, illness knowledge, and actionable memory for medication taking in type 2 diabetes: cross-sectional analysis. J Gen Intern Med 2021;36:1921-7.ArticlePubMedPMCPDF
  • 249. de Abreu IR, Baia C, Silva JM, Santos AM, Oliveira M, Castro F, et al. LitKDm2 study: the impact of health literacy and knowledge about the disease on the metabolic control of type 2 diabetes mellitus. Acta Diabetol 2022;59:819-25.ArticlePubMedPDF
  • 250. Fan JH, Lyons SA, Goodman MS, Blanchard MS, Kaphingst KA. Relationship between health literacy and unintentional and intentional medication nonadherence in medically underserved patients with type 2 diabetes. Diabetes Educ 2016;42:199-208.ArticlePubMedPMCPDF
  • 251. Hussain N, Said AS, Khan Z. Influence of health literacy on medication adherence among elderly females with type 2 diabetes in Pakistan. Int Q Community Health Educ 2020;41:35-44.ArticlePubMedPDF
  • 252. Friis K, Vind BD, Simmons RK, Maindal HT. The relationship between health literacy and health behaviour in people with diabetes: a Danish population-based study. J Diabetes Res 2016;2016:7823130.ArticlePubMedPMCPDF
  • 253. McCleary-Jones V. Health literacy and its association with diabetes knowledge, self-efficacy and disease self-management among African Americans with diabetes mellitus. ABNF J 2011;22:25-32.PubMed
  • 254. Dahal PK, Hosseinzadeh H. Association of health literacy and diabetes self-management: a systematic review. Aust J Prim Health 2019;25:526-33.ArticlePubMed
  • 255. Beauchamp A, Talevski J, Niebauer J, Gutenberg J, Kefalianos E, Mayr B, et al. Health literacy interventions for secondary prevention of coronary artery disease: a scoping review. Open Heart 2022;9:e001895.ArticlePubMedPMC
  • 256. Talevski J, Wong Shee A, Rasmussen B, Kemp G, Beauchamp A. Teach-back: a systematic review of implementation and impacts. PLoS One 2020;15:e0231350.ArticlePubMedPMC
  • 257. George NE, Sunny SM, Sam AM, Sabu AS, Rodrigues PA. Effect of medication related educational interventions on improving medication adherence in patients with type 2 diabetes mellitus. Asian J Pharm Clin Res 2018;11:167-70.ArticlePDF
  • 258. Mahmoudirad G, Hoseini MS, Madarshahian F. The effect of teach-back education on foot self-care among patients with type II diabetes mellitus. Mod Care J 2015;12:1-7.
  • 259. Negarandeh R, Mahmoodi H, Noktehdan H, Heshmat R, Shakibazadeh E. Teach back and pictorial image educational strategies on knowledge about diabetes and medication/dietary adherence among low health literate patients with type 2 diabetes. Prim Care Diabetes 2013;7:111-8.ArticlePubMed
  • 260. Kim SH, Utz S. Effectiveness of a social media-based, health literacy-sensitive diabetes self-management intervention: a randomized controlled trial. J Nurs Scholarsh 2019;51:661-9.ArticlePubMedPDF
  • 261. Zeidi IM, Morshedi H, Alizadeh Otaghvar H. A theory of planned behavior-enhanced intervention to promote health literacy and self-care behaviors of type 2 diabetic patients. J Prev Med Hyg 2021;61:E601-13.PubMedPMC
  • 262. Agrali H, Akyar I. The effect of health literacy-based, health belief-constructed education on glycated hemoglobin (HbA1c) in people with type 2 diabetes: a randomized controlled study. Prim Care Diabetes 2022;16:173-8.ArticlePubMed
  • 263. Lam MH, Leung AY. The effectiveness of health literacy oriented programs on physical activity behaviour in middle aged and older adults with type 2 diabetes: a systematic review. Health Psychol Res 2016;4:5595.ArticlePubMedPMCPDF
  • 264. Uemura K, Yamada M, Okamoto H. Effects of active learning on health literacy and behavior in older adults: a randomized controlled trial. J Am Geriatr Soc 2018;66:1721-9.ArticlePubMedPDF
  • 265. Uemura K, Yamada M, Okamoto H. The effectiveness of an active learning program in promoting a healthy lifestyle among older adults with low health literacy: a randomized controlled trial. Gerontology 2021;67:25-35.ArticlePubMedPDF
  • 266. Brennan-Olsen SL, Vogrin S, Balogun S, Wu F, Scott D, Jones G, et al. Education, occupation and operational measures of sarcopenia: six years of Australian data. Australas J Ageing 2020;39:e498-505.ArticlePubMedPDF
  • 267. Gandham A, Zengin A, Bonham MP, Brennan-Olsen SL, Aitken D, Winzenberg TM, et al. Associations between socioeconomic status and obesity, sarcopenia, and sarcopenic obesity in community-dwelling older adults: the Tasmanian Older Adult Cohort Study. Exp Gerontol 2021;156:111627.ArticlePubMed
  • 268. Talevski J, Daly RM. Additional insights on the osteoporosis care gap. J Bone Miner Res 2023;38:615-6.ArticlePubMedPDF

Figure & Data



    Citations to this article as recorded by  
    • Fucoidan ameliorates diabetic skeletal muscle atrophy through PI3K/Akt pathway
      Caixia Li, Yaping Liu, Mingzhi Yang, Haoyue Huang, Lulu Tang, Yufan Miao, Wenjie Li, Xing Li
      Journal of Functional Foods.2024; 114: 106076.     CrossRef
    • Evaluation of the effect of testosterone replacement therapy with a transdermal testosterone on glycemic control in men with type 2 diabetes mellitus
      R. V. Rozhivanov, M. O. Chernova, V. A. Ioutsi, G. A. Mel’nichenko, M. V. Shestakova, E. R. Rozhivanova, E. N. Andreeva, N. G. Mokrysheva
      Diabetes mellitus.2024; 27(2): 120.     CrossRef
    • Higher dietary live microbe intake is associated with a lower risk of sarcopenia
      Kemin Yan, Xiaoyi Ma, Chen Li, Xiang Zhang, Manxuan Shen, Sai Chen, Jia Zhao, Wen He, Hua Hong, Yingying Gong, Gang Yuan
      Clinical Nutrition.2024; 43(7): 1675.     CrossRef
    • d-Pinitol Improves Diabetic Sarcopenia by Regulation of the Gut Microbiome, Metabolome, and Proteome in STZ-Induced SAMP8 Mice
      Xin Yu, Pei Li, Baoying Li, Fei Yu, Wenqian Zhao, Xue Wang, Yajuan Wang, Haiqing Gao, Mei Cheng, Xiaoli Li
      Journal of Agricultural and Food Chemistry.2024; 72(25): 14466.     CrossRef

    • PubReader PubReader
    • ePub LinkePub Link
    • Cite this Article
      Cite this Article
      export Copy Download
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      • Citation for the content below
      Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies
      Diabetes Metab J. 2023;47(6):719-742.   Published online September 14, 2023
    • XML DownloadXML Download
    Mesinovic J, Fyfe JJ, Talevski J, Wheeler MJ, Leung GK, George ES, Hunegnaw MT, Glavas C, Jansons P, Daly RM, Scott D. Type 2 Diabetes Mellitus and Sarcopenia as Comorbid Chronic Diseases in Older Adults: Established and Emerging Treatments and Therapies. Diabetes Metab J. 2023;47(6):719-742.
    Received: Apr 14, 2023; Accepted: Aug 12, 2023

    Diabetes Metab J : Diabetes & Metabolism Journal
    Close layer