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Abstract

Sarcopenia, which is defined as an age-related decline in muscle mass and strength, has been found to have a strong bidirectional relationship with Type 2 diabetes. Both problems are associated with advancing age, and have now become of critical importance in view of increasing lifespan and a large increase in the elderly population. Sarcopenia significantly worsens the quality of life and increases morbidity and mortality in patients with Type 2 diabetes. Uncontrolled diabetes, on the other hand, predisposes to worsening sarcopenia. This review discusses the common risk factors and pathophysiology related to these two conditions. We also discuss pharmacological as well as non-pharmacological ways of combating this dual threat.

Keywords

Diabetes elderly ethnicity sarcopenia

Introduction

Type 2 diabetes mellitus (T2DM) is one of the most widespread metabolic diseases, and affects more than 500 million people worldwide.^[1] More than 90% of diabetes is Type 2 diabetes with an underlying mechanism characterised by insulin resistance. Sarcopenia, which is defined as an age-related decline in muscle strength and muscle function, is found to have a strong association with Type 2 diabetes.^[2] Risk factors for sarcopenia include age, dietary factors, systemic inflammation and physical inactivity. Sarcopenia is associated with various negative health outcomes such as increased risk of falls and fractures, cognitive impairment, and reduced overall survival. Sarcopenia is the result of a complex interaction of intrinsic and extrinsic factors. Sarcopenia has a bidirectional relationship with T2DM with each worsening the other. The course of T2DM is associated with declining muscle mass, which reduces physical activity and in turn accelerates the progress of disease. The bidirectional relationship between T2DM and sarcopenia may be related to the common underlying risk factors such as inactivity, inflammation, malnutrition and mitochondrial dysfunction.^[3]

The connection between T2DM and sarcopenia has been observed in a number of studies.^[4,5] Associations have also been found between complications of T2DM and sarcopenia. Uncontrolled diabetes (high haemoglobin A1c [HbA1c]) and the presence of vascular complications have been found to be associated with an increased prevalence of sarcopenia.^[5,6] Another study demonstrating a reciprocal relationship, reported a decrease in the risk of T2DM in older adults with increasing grip strength.^[7] Lower limb muscle mass was found to be lower in older adults with T2DM, compared to those without T2DM.^[5] Sarcopenia leads to a poor quality of life and increases mortality in T2DM. Patients with T2DM and sarcopenia have been shown to have higher mortality than those without sarcopenia.^[8] This review explores recent evidence on the connection between T2DM and sarcopenia, including established and emerging treatment strategies for managing these disorders.

Epidemiology

Population prevalence of sarcopenia in older adults depends on the patient population studied and the definition used. The prevalence among community dwelling older adults ranges between 9.9% and 40%^[9] and prevalence among those with T2DM ranges between 15% and 44%^[10] using various diagnostic criteria. The Longitudinal Aging Study in India (LASI) focused on adults aged more than 60 years, and using Asian Working Group on Sarcopenia (AWGS) definitions, reported a 27% prevalence of sarcopenia.^[11] Participants with diabetes were found to have a significantly higher odds ratio of 1.14 for sarcopenia. Lack of physical activity, physical disability, chronic health conditions and age more than 80 were the other significant risk factors in this study. A study by Sambashivaiah et al. found that muscle strength was significantly lower in patients with T2DM even after adjusting for age and other covariates.^[12]

Definition and Diagnosis of Sarcopenia

The diagnostic criteria for sarcopenia have been evolving over the past few years. Two of the most widely used definitions are the ones proposed by the AWGS, and the European Working Group on Sarcopenia in Older People (EWGSOP) (Table 1). They include measures of low muscle strength, low muscle mass and poor physical performance to define sarcopenia. The AWGS defines the condition as an ‘age related decline of skeletal muscle plus low muscle strength and /or physical performance’. It requires low muscle mass with either low muscle strength or poor physical performance to define sarcopenia. The EWGSOP requires both low muscle mass and strength and uses measures of physical performance to describe severity. The European working group recommends a stepwise process for diagnosis and stratification. Initial assessment of risk can be done by the SARC-F (Strength Assistance with walking Rise from a chair Climb stairs and Falls) questionnaire. Muscle strength is measured next using tests such as grip strength (for upper limbs) and chair stand strength (for lower limbs). Total skeletal muscle mass is quantified using methods such as computed tomography (CT), magnetic resonance imaging (MRI), dual energy X-ray absorptiometry (DXA) or bioelectrical impedance analysis (BIA). Measures of muscle function are necessary to quantify the severity of sarcopenia. Some of the commonly used tests include chair rising test (CRT), daily pace assessment and stand up and go test.

Table 1.

Diagnosis of sarcopenia

	Low Muscle Strength	Low Muscle Mass	Poor Physical Performance
Revised AWGS	HGS <28 kg (men) HGS <18 kg (women)	ALM/height 2 kg/m² - <7 kg/m² (men) <5.4 kg/m² (women)	Gait speed <1 m/sec SPPB score <9 points Chair stand time >12 sec
Revised EWGSOP	HGS <27 kg (men) HGS <16 kg (women) Chair stand time >15 sec	ALM <20 kg (men) ALM <15 kg (women) ALM/height 2 <7 kg/m² in men and <5.4 kg/m² in women	Gait speed 0.8 m/sec SPPB score <8 points TUG >20 sec 400 m walk >6 min or noncompletion

Source: Cruz-Jentoft et al. (2014)9 and Dhar et al. (2022)13.

Note: HGS: Hand grip strength; ALM: appendicular lean mass; SPPB: short physical performance battery; TUG: timed up and go.

The 2022 South Asian Working Group on SARCOpenia (SWAG SARCO) consensus focuses on the South Asian population, who have a smaller body size and adiposity as compared to western populations.^[13] Using AWGS guidelines also showed a spuriously high prevalence of sarcopenia in elderly South Asian individuals, in view of ethnic differences between the South Asian and South East Asian populations.^[14] The SWAG SARCO consensus defines sarcopenia as a syndrome where two of the following three parameters, of muscle mass, muscle strength and muscle function are suboptimal, without giving importance to any one parameter over the others. It also highlights secondary causes of sarcopenia in view of the increasing non-communicable disease burden. SWAG-SARCO proposes the 5-S pathway for screening and diagnosing sarcopenia: Suspect, Screening, Secondary sarcopenia (including concomitant therapy), Severity (muscle strength, function and/or mass), and Shared decision making. SARC F questionnaire, anthropometry, grip strength and/or chair stand test are recommended for screening. Severity is assessed by gait speed, SPPB (short physical performance battery), TUGT (timed up and go test) and 400 meter walk tests. The use of biomarkers and imaging modalities is also suggested as per requirement. Calf circumference is suggested as a simple parameter to measure muscle mass with cutoffs being 34 cm in men and 33 cm in women.

Sarcopenic Obesity

Sarcopenic obesity (SO) is the coexistence of obesity and sarcopenia. Loss of muscle mass is common in individuals with obesity due to metabolic changes seen with a sedentary lifestyle, comorbidities, adipose tissue derangements and the aging process. Sarcopenia may potentiate weight gain through reduced total energy expenditure. Sarcopenia and obesity both worsen each other by mechanisms such as insulin resistance, systemic inflammation and oxidative stress. Coexisting sarcopenia and obesity have been associated with higher cardiovascular risk than either disease alone.^[15] Obesity is associated with both sarcopenia and T2DM with more than 50% of patients being obese.

SO should be considered in individuals with an elevated body mass index (BMI)/waist circumference and indicators of impaired muscle mass or function. The European Society for Clinical Nutrition and Metabolism (ESPEN) and European Association for the Study of Obesity (EASO) consensus suggest diagnosis of SO following in high-risk individuals (e.g., elderly, presence of comorbids). They suggest diagnosis using a sequential assessment of muscle strength (e.g., hand grip strength, chair stand test), followed by body composition analysis using DXA, BIA or CT. Diagnosis of SO requires both altered skeletal muscle functional parameters and altered body composition. Additionally, diagnosis requires a relative reduction in skeletal mass adjusted to body weight.^[16] Anthropometric measurements such as calf circumference, when adjusted for BMI, can play a role in the rapid estimation of muscle mass.^[17] Weight-adjusted waist index (WWI), calculated as waist circumference divided by the square root of weight, showed significant correlation with standard measures of SO in male participants.^[18]

Osteosarcopenia

The term osteosarcopenia (OS) refers to the concurrent presence of sarcopenia and osteopenia/osteoporosis. Aging is associated with a chronic low-grade inflammation with a progressive fatty infiltration of bone and muscle tissue.^[19] Other factors commonly seen at an older age such as reduced physical activity, poor nutrition and a low vitamin D also predispose to OS. OS is more common in patients with T2DM and their co-occurrence may lead to an increase in falls and fractures. A study by Liu et al. showed that diabetic patients with OS have lower BMI and worse β-cell function, and surmised that better beta cell function could be protective against OS.^[20] Another study showed a higher prevalence of OS in patients with chronic complications of T2DM.^[21]

Pathophysiology

Aging is one of the most important factors contributing to both T2DM and sarcopenia. A decline in muscle mass starts in the fourth decade and is progressive.^[22] Aging is accompanied by an increase in the rate of muscle catabolism. An increase in fat deposition in the visceral as well as intramuscular depots is observed with aging. Impaired anabolic pathways mediated by growth hormone (GH) and insulin-like growth factor 1 (IGF-1), chronic inflammation and a reduced protein intake contribute to an age-related decline in muscle quality (Figure 1). A decrease in the regenerative capacity of skeletal muscle stem cells, which occurs with aging, contributes to muscle loss.

Figure 1

Pathophysiology-intrinsic versus extrinsic risk factors for sarcopenia

Loss of skeletal muscle mass contributes to increasing insulin resistance and increasing blood glucose. Impaired insulin action in skeletal muscle may interfere with protein synthesis, leading to a decrease in muscle mass.^[23] Elevated glucose levels may lead to muscle wasting via the ubiquitin proteasome activation.^[24] Insulin resistance inhibits the mammalian target of rapamycin (mTOR) pathway leading to an increase in muscle catabolism. Myostatin, which belongs to the transforming growth factor β (TGF-β) superfamily, decreases mTOR signalling. This leads to the activation of the AMPKα2 pathway, leading to proteolysis. Myostatin could also promote catabolism via the p38-caspase pathway. Insulin resistance in T2DM leads to hyperinsulinemia and increases myostatin activity, thereby causing muscle loss.^[25]

An increase in the adipose tissue depots within and surrounding skeletal muscle is called myosteatosis. Myosteatosis increases with aging, obesity and lower physical activity, which contribute to cellular senescence and mitochondrial dysfunction.^[26] It is a significant risk factor contributing to both sarcopenia and T2DM. Insulin resistance associated with myosteatosis is a key defected leading to T2DM. Higher intermuscular adipose tissue (IMAT) leads to increased local inflammation and impaired contractility in skeletal muscle.^[27] Increased insulin resistance per se increases ectopic fat accumulation, thereby promoting local inflammation.^[25]

T2DM is characterised by a chronic inflammatory state. This inflammation, acting via the PI3K-Akt pathway, leads to a decrease in protein anabolism combined with an increase in muscle catabolism. An increase in inflammatory markers such as interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α) is seen in patients with T2DM and insulin resistance. These inflammatory mediators adversely affect skeletal muscle.^[28] IL-6 acts on muscle cells directly and via the janus kinase-signal transducer and activator of transcription (JAK/STAT), nuclear factor kappa β (NF-κβ) pathways and leads to muscle catabolism. TNF-α, IL-1 and IL-10 act via other signalling pathways and induce mitophagy.^[29]

Hyperglycaemia in T2DM triggers the production of reactive oxygen species (ROS) leading to oxidative stress. ROS activates the ubiquitin proteasome pathway and leads to muscle catabolism.^[30] ROS inhibits the Akt/mTOR pathway and inhibits protein synthesis and muscle repair, thereby promoting muscle atrophy.^[31] Hyperglycaemia increases the production of advanced glycation end-products (AGEs), which accumulate in tissues such as muscles and bone. AGEs bind to the AGE receptor on muscle cells and increase inflammation, oxidative stress. AGEs can interfere with muscle contractility by increasing protein cross-linking.^[32]

The decline in exercise ability with age is a major contributor to muscle loss in the elderly. Muscle tissue needs constant stimulation and load bearing in order to maintain proper function. Lack of exercise, which is compounded by a fear of falling, will result in a decrease in muscle mass.^[33] Sedentary lifestyle with sedentary time exceeding two hours leads to a higher risk of sarcopenia.

Management

Dietary Interventions

There is evidence to suggest that increasing protein intake benefits both T2DM and sarcopenia. A high protein diet has been shown to improve insulin sensitivity.^[34] It also decreases postmeal glycaemic fluctuations in patients with T2DM by slowing down the absorption of glucose. Most guidelines for T2DM currently recommend protein intake of 0.8 g/kg-1.5 g/kg body weight per day in patients with normal kidney function.^[35] However, increasing the daily protein intake to 1.2 g/kg-1.6 g/kg of body weight may help maintain muscle mass and strength in older adults.^[36] Using protein elements to reach an intake of 1.2g/kg body weight per day is beneficial, especially in those with low basal protein intakes. An randomised controlled trial (RCT) studying whey protein supplementation found a significant increase in muscle mass, with no significant change in either upper or lower limb strength.^[37] However, the combination of protein supplementation and resistance exercise was found to increase both muscle mass and muscle strength.^[37] A meta-analysis of studies looking into the benefits of animal versus plant proteins did not find any difference between the two with regard to increase in total muscle mass or muscle strength, though animal protein was found to be produce a higher percentage gain in muscle mass.^[38,39] However, data about benefits of animal versus plant protein remain unclear and need further research.

Hypovitaminosis D is associated with a decrease in muscle mass and physical function.^[40] Vitamin D supplementation to maintain adequate vitamin D levels, especially in patients at risk for vitamin D deficiency, helps improve musculoskeletal health in this population.^[41] Combining a physical exercise programme, with whey protein and leucine supplementation, in addition to vitamin D optimisation showed significant improvement in muscle mass and function in a meta-analysis including 637 patients.^[37]

Observational and cross-sectional studies have shown a positive association between higher magnesium intake and muscle mass, muscle strength, especially in women.^[42] Similarly, cross-sectional studies of calcium intake found a correlation between lower calcium intake and the presence of sarcopenia.^[43]

Weight Management, Dietary Interventions in Older Adults with Type 2 DM

Weight loss achieved through hypocaloric diets and exercise is a first-line treatment approach in overweight patients with T2DM. On the other hand, higher mortality rate has been reported in older adults with lower BMIs. The lowest mortality risk was reported between BMI of 24 kg/m² and 30.9 kg/m².^[44] Weight loss, while effective for glycaemic control, leads to loss of muscle and bone mass, especially in older adults.^[45] Very low calorie diets are, therefore, not appropriate for older adults in the management of T2DM. Adequate energy and protein intake helps prevent muscle loss. It is important to maintain a balanced diet and adequate protein intake of at least 1g/kg body weight in older adults. Additionally, the daily negative calorie balance should not exceed 500 calories.^[46] The Mediterranean diet with an emphasis on whole grains, legumes, vegetables and lean sources of protein is a widely accepted approach. Essential amino acid supplementation has been studied in T2DM and sarcopenia. Supplementation with branched-chain amino acids such as leucine, isoleucine, valine has shown benefit in reducing muscle loss.^[47] Leucine also acts as an insulin secretagogue. Omega-3 fatty acid supplementation in combination with exercise shows benefit in some studies as well.^[48] Omega-3 fatty acids also reduce inflammation.

Combining exercise with dietary approaches increases insulin sensitivity and provides further improvement in glycaemic control.^[49] Exercise can also favourably influence changes in muscle mass that occur with dietary interventions. Studies in older overweight patients on weight-reducing diets have shown that the addition of exercise produces greater improvement in physical function.^[50] The addition of resistance exercise showed the most benefit in these patients.

Physical Activity

Physical activity plays an important role in the management of both T2DM and sarcopenia. Exercise can delay muscle loss by counteracting NF-κβ.^[51] The American Diabetes Association (ADA) recommends at least 150 minutes of moderate to vigorous intensity aerobic exercise per week, with no more than two consecutive days without exercise. The ADA also recommends resistance exercises at least two to three times per week. Aerobic exercise can improve insulin resistance, blood glucose levels and muscle strength. Resistance exercise decreases insulin resistance, improves mitochondrial function and increases muscle strength.^[52] Functional balance and strength training, reduce frailty, falls and fragility fractures in the elderly. Both the ADA and the World Health Organisation (WHO) guidelines for older adults with chronic conditions place an emphasis on the reduction in sedentary time, and to break up periods of sitting every 30 minutes.^[53] A majority of older adults spend up to 80% of their waking day sedentary and do not meet the minimum recommended goals for physical exercise. This pattern of behaviour is associated with declining muscle strength, incident T2DM and worse health outcomes.^[54]

In the look action for health in diabetes (look AHEAD) trial, adults with T2DM and overweight or obesity were randomised to either intensive lifestyle intervention (weight loss ≥10% and physical activity goal of ≥150 minutes per week in the first month, increasing to ≥175 minutes per week by the 6th month) or diabetes support and education.^[55] The intensive lifestyle group was supported by dedicated lifestyle coaches throughout the study. At one to eight years after randomisation, the intensive lifestyle intervention group had better subjective and objective scores of physical performance as compared to the controls.^[56] Reducing time spent sitting that is sedentary behaviour has also been shown to improve muscle health.

Exercise interventions can be either aerobic exercise or resistance exercise. Aerobic exercise is typically performed at moderate intensity for prolonged periods of time, with examples including walking, jogging and swimming. Resistance or muscle strengthening exercise involves repetitive muscle contractions against external resistance such as lifting weights. Several studies have investigated whether exercise interventions can improve metabolic health in older T2DM patients. The benefits of resistance training for improving muscle function in older adults with sarcopenia have been proven in a number of studies.^[57] The type of resistance training, intensity and frequency of exercise influences the benefits obtained. A meta-analysis of 15 studies involving older adults found that improvements in muscle strength tended to be greater when higher loads were used.^[58]

A practical and easy approach in sedentary older adults involves isolated short bouts of exercise, lasting ≤1 minute, performed multiple times throughout the day. The benefits of such an approach for glycaemic control have been demonstrated.^[59] A pilot study in older adults using short bouts (9 min) of body weight exercises reported significant improvements in muscle power and muscle mass.^[60] Positive changes in muscle strength were observed in frail patients, even with short bouts of less intense strength training.

Control of Blood Glucose Level

Uncontrolled blood glucose levels decrease mitochondrial activity, impair energy metabolism and predispose to sarcopenia. Impaired insulin signalling secondary to hyperglycaemia increases insulin resistance and predisposes to muscle atrophy.^[61] Stable insulin levels in people with well controlled T2DM contribute to muscle anabolism. Skeletal muscle in turn aids in glucose disposal and helps control diabetes.

Medication

There are no approved pharmacological therapies for the management of sarcopenia. Inhibitors of myostatin have been found to increase muscle mass in animal models.^[62] However, they have shown no effect on physical function. Testosterone treatment improves muscle mass and glycaemic control in hypogonadal men.^[63] There is no definite evidence to support the use of testosterone in men without hypogonadism. Selective androgen receptor modulators (SARMs) have recently been investigated in the management of muscle wasting. SARMs are non-steroidal ligands that bind to androgen receptors with tissue selective androgen signalling. However, clinical efficacy of this group of drugs remains to be seen.

Nandrolone is a synthetic anabolic androgen with a higher myotropic: androgenic ratio. Nandrolone has been shown to increase lean body mass in chronic conditions such as HIV and chronic renal failure.^[64] Nandrolone combined with resistance training was found to improve insulin sensitivity and lipid parameters in a study involving HIV-infected men.^[65] However, there is currently insufficient evidence to recommend its use in the elderly with sarcopenia.

The drugs used to treat T2DM can have different types of effects on muscle function. Metformin, which is one of the oldest drugs used in the management of diabetes, has shown beneficial effects on skeletal muscle.^[66] Thiazolidinediones improve insulin sensitivity, decrease intramuscular fat and may be beneficial to muscle.^[67] However, they increase the risk of fractures and congestive cardiac failure in high-risk populations. Sulfonylureas can aggravate muscle loss in T2DM and should be used with caution in sarcopenic patients.^[68] dipeptidyl peptidase 4 (DPP-4) inhibitors act on the incretin pathway and have some minor beneficial effects on muscle mass. The effects of sodium glucose co-transporter 2 (SGLT-2) inhibitors on muscle mass are inconclusive and need further study. One study of dapagliflozin significantly decreased skeletal muscle mass (−2.1%) compared to placebo over 24 weeks.^[69] Two studies with Luseogliflozin showed significant reduction in skeletal muscle indices (−1.9% and −2.9%).^[70,71] However, other trials did not report any changes.^[72,73] A six-month study of glucagon like peptide -1 (GLP-1) analogue dulaglutide, in patients on haemodialysis showed a significant (−3.8%) decrease in skeletal muscle mass.^[74] Studies of liraglutide attributed 33%-77% weight loss to loss of fat free mass.^[75] The newest generation of incretin-based medications such as semaglutide (GLP-1 analogue) and tirzepatide (dual GIP and GLP-1 agonist) have shown a lot of promise in the management of T2DM as well as obesity. However, a decrease in absolute lean mass, with preservation of relative muscle mass, has been observed with this group of medications. Studies of semaglutide, reported fat-free mass to comprise 40% of weight lost(6.92 kg lean mass in 68 weeks or 13.2%), which correlates with the loss seen in diet induced weight loss or bariatric surgery.^[76] The pivotal study of tirzepatide also showed a loss 10.9% of lean mass during the 72 weeks of the study.^[77] Measures to preserve muscle mass and function should, therefore, be taken while initiating treatment with these agents.

Conclusion

Sarcopenia represents a progressive degenerative muscle disease affecting a significant number of older adults in the community. Type 2 diabetes is a metabolic disorder which has increasing prevalence with age. There is a complex interaction between these two conditions with each potentiating the other. Lifestyle factors, age, insulin resistance and elevated blood glucose can decrease muscle mass in diabetic patients. Sarcopenia leads to a poor quality of life with an increased morbidity and mortality in diabetic patients. Early detection helps initiate measures to address sarcopenia and improve quality of life.

Muscle health can be preserved by paying attention to nutrition, physical exercise and hormonal considerations. A diet rich in protein, essential amino acids, vitamin D, calcium and omega-3 fatty acids with adequate calories needs to be encouraged. A customised exercise plan encompassing aerobic and resistance exercises needs to be given to each patient. While prescribing diabetic medications, the impact of the drug on skeletal muscle also needs to considered in addition to efficacy of glycaemic control.

Footnotes

Declaration of conflicting interests

The author declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author received no financial support for the research, authorship and/or publication of this article.

Institutional ethical committee approval number

Not applicable.

Informed consent

Not applicable.

Credit author statement

SS conceived the article and designed the layout. SS wrote the original draft and revised and edited the final manuscript.

Data availability

Not applicable.

Use of artificial intelligence

Not applicable.

References

Magliano

, Boyko

. IDF Diabetes Atlas 10th edition scientific committee. IDF DIABETES ATLAS [Internet]. 10th ed. Brussels: International Diabetes Federation; 2021 [cited 2024 Dec 20]. (IDF Diabetes Atlas). Available from: http://www.ncbi.nlm.nih.gov/books/NBK581934/

Izzo

, Massimino

, Riccardi

, Della Pepa

. A narrative review on sarcopenia in Type 2 diabetes mellitus: prevalence and associated factors. Nutrients. 2021;13(1):183.

Lee

, Boyko

, Strotmeyer

, . Association between insulin resistance and lean mass loss and fat mass gain in older men without diabetes mellitus. J Am Geriatr Soc. 2011;59(7):1217–24.

Kim

, Park

, Yang

, . Prevalence and determinant factors of sarcopenia in patients with Type 2 diabetes: the Korean Sarcopenic Obesity Study (KSOS). Diabetes Care. 2010;33(7):1497–9.

Park

, Goodpaster

, Lee

, . Excessive loss of skeletal muscle mass in older adults with Type 2 diabetes. Diabetes Care. 2009;32(11):1993–7.

, Liu

, Chi

VTQ

, . Handgrip strength is inversely associated with metabolic syndrome and its separate components in middle aged and older adults: a large-scale population-based study. Metabolism. 2019;93:61–7.

Son

, Lee

, Kim

, . Low muscle mass and risk of Type 2 diabetes in middle-aged and older adults: findings from the KoGES. Diabetologia. 2017;60(5):865–72.

Lin

, Hou

, Wu

. Effect of sarcopenia on mortality in Type 2 diabetes: a long-term follow-up propensity score-matched diabetes cohort study. J Clin Med. 2022;11(15):4424.

Cruz-Jentoft

, Landi

, Schneider

, . Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–59.

10.

Kaur

, Bansal

, Bhargava

, Mishra

, Gill

, Mithal

. Decreased handgrip strength in patients with Type 2 diabetes: a cross-sectional study in a tertiary care hospital in north India. Diabetes Metab Syndr. 2021;15(1):325–9.

11.

Das

, Prasad

. Gender differences in determinants of the components of the frailty phenotype among older adults in India: findings from LASI Wave-1. Int J Environ Res Public Health. 2023;20(4):3055.

12.

Sambashivaiah

, Harridge

SDR

, Sharma

, Selvam

, Rohatgi

, Kurpad

. Asian Indians with prediabetes have similar skeletal muscle mass and function to those with Type 2 diabetes. Front Nutr. 2019;6:179.

13.

Dhar

, Kapoor

, Suastika

, . South Asian working action group on SARCOpenia (SWAG-SARCO)—a consensus document. Osteoporos Sarcopenia. 2022;8(2):35–57.

14.

Singhal

, Bansal

, Dewangan

, . Low one-repetition-maximum knee extension is significantly associated with poor grip strength, female sex, and various aging-related syndromes. Aging Med Milton NSW. 2020;3(2):125–31.

15.

Roh

, Choi

. Health consequences of sarcopenic obesity: a narrative review. Front Endocrinol. 2020;11:332.

16.

Donini

, Busetto

, Bischoff

, . Definition and diagnostic criteria for sarcopenic obesity: ESPEN and EASO consensus statement. Obes Facts. 2022;15(3):321–35.

17.

Gonzalez

, Mehrnezhad

, Razaviarab

, Barbosa-Silva

, Heymsfield

. Calf circumference: cutoff values from the NHANES 1999–2006. Am J Clin Nutr. 2021;113(6):1679–87.

18.

Kim

, Choi

, Kim

, Won

. Assessment of existing anthropometric indices for screening sarcopenic obesity in older adults. Br J Nutr. 2023;129(5):875–87.

19.

Ferrucci

, Baroni

, Ranchelli

, . Interaction between bone and muscle in older persons with mobility limitations. Curr Pharm Des. 2014;20(19):3178–97. Available from: https://pubmed.ncbi.nlm.nih.gov/24050165/

20.

Liu

, Yu

, Xu

, . β-Cell function is associated with osteosarcopenia in middle-aged and older nonobese patients with Type 2 diabetes: a cross-sectional study. Open Med Wars Pol. 2021;16(1):1583–90.

21.

Pechmann

, Petterle

, Moreira

, Borba

VZC

. Osteosarcopenia and trabecular bone score in patients with Type 2 diabetes mellitus. Arch Endocrinol Metab. 2021;65(6):801–10.

22.

McCormick

, Vasilaki

. Age-related changes in skeletal muscle: changes to life-style as a therapy. Biogerontology. 2018;19(6):519–36.

23.

Russell

, Rajani

, Dhadda

, Tisdale

. Mechanism of induction of muscle protein loss by hyperglycaemia. Exp Cell Res. 2009;315(1):16–25.

24.

Purnamasari

, Tetrasiwi

, Kartiko

, Astrella

, Husam

, Laksmi

. Sarcopenia and chronic complications of Type 2 diabetes mellitus. Rev Diabet Stud RDS. 2022;18(3):157–65.

25.

Buch

, Carmeli

, Boker

, . Muscle function and fat content in relation to sarcopenia, obesity and frailty of old age—an overview. Exp Gerontol. 2016;76:25–32.

26.

Abbatecola

, Ferrucci

, Ceda

, . Insulin resistance and muscle strength in older persons. J Gerontol A Biol Sci Med Sci. 2005;60(10):1278–82.

27.

Yoon

, Ha

, Kim

, . Hyperglycemia is associated with impaired muscle quality in older men with diabetes: the Korean longitudinal study on health and aging. Diabetes Metab J. 2016;40(2):140–6.

28.

Visser

, Pahor

, Taaffe

, . Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the health ABC study. J Gerontol A Biol Sci Med Sci. 2002;57(5):M326–32.

29.

Giha

, Alamin

OAO

, Sater

. Diabetic sarcopenia: metabolic and molecular appraisal. Acta Diabetol. 2022;59(8):989–1000.

30.

Matsuo

, Gleitsmann

, Mangner

, . Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines. J Cachexia Sarcopenia Muscle. 2015;6(1):62–72.

31.

Zhang

, Kimball

, Jefferson

, Shenberger

. Hydrogen peroxide impairs insulin-stimulated assembly of mTORC1. Free Radic Biol Med. 2009;46(11):1500–9.

32.

Suzuki

, Yabu

, Nakamura

. Advanced glycation end products in musculoskeletal system and disorders. Methods San Diego Calif. 2022;203:179–86.

33.

Ibata

, Terentjev

. Why exercise builds muscles: titin mechanosensing controls skeletal muscle growth under load. Biophys J. 2021;120(17):3649–63.

34.

Collins

, Foley

, Gilbertson

, Chen

. United States renal data system public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl. 2015;5(1):2–7.

35.

American Diabetes Association Professional Practice Committee. 5. Facilitating positive health behaviors and well-being to improve health outcomes: standards of care in diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S77–110.

36.

Souza

VA de

, Oliveira

, Barbosa

, . Sarcopenia in patients with chronic kidney disease not yet on dialysis: analysis of the prevalence and associated factors. PloS One. 2017;12(4):e0176230.

37.

Chang

, Choo

. Effects of whey protein, leucine, and vitamin D supplementation in patients with sarcopenia: a systematic review and meta-analysis. Nutrients. 2023;15(3):521.

38.

Gielen

, Beckwée

, Delaere

, . Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Nutr Rev. 2021;79(2):121–47.

39.

Lim

, Pan

, Toh

DWK

, Sutanto

, Kim

. Animal protein versus plant protein in supporting lean mass and muscle strength: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2021;13(2):661.

40.

Conzade

, Grill

, Bischoff-Ferrari

, . Vitamin D in relation to incident sarcopenia and changes in muscle parameters among older adults: the KORA-age study. Calcif Tissue Int. 2019;105(2):173–82.

41.

Marcus

, Addison

, Dibble

, Foreman

, Morrell

, Lastayo

. Intramuscular adipose tissue, sarcopenia, and mobility function in older individuals. J Aging Res. 2012;2012:629637.

42.

Welch

, Skinner

, Hickson

. Dietary magnesium may be protective for aging of bone and skeletal muscle in middle and younger older age men and women: cross-sectional findings from the UK Biobank Cohort. Nutrients. 2017;9(11):1189.

43.

Seo

, Kim

, Park

, . The association between daily calcium intake and sarcopenia in older, non-obese Korean adults: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV) 2009. Endocr J. 2013;60(5):679–86.

44.

Zacarías-Flores

, Sánchez-Rodríguez

, García-Anaya

, Correa-Muñoz

, Mendoza-Núñez

. Relationship between oxidative stress and muscle mass loss in early postmenopause: an exploratory study. Endocrinol Diabetes Nutr. 2018;65(6):328–34.

45.

Short

, Bigelow

, Kahl

, . Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A. 2005;102(15):5618–23.

46.

Conley

, Jubrias

, Esselman

. Oxidative capacity and ageing in human muscle. J Physiol. 2000;526(Pt 1):203–10.

47.

Hamarsland

, Aas

, Nordengen

, . Native whey induces similar post exercise muscle anabolic responses as regular whey, despite greater leucinemia, in elderly individuals. J Nutr Health Aging. 2019;23(1):42–50.

48.

Madison

, Belury

, Andridge

, . Omega-3 supplementation and stress reactivity of cellular aging biomarkers: an ancillary substudy of a randomized, controlled trial in midlife adults. Mol Psychiatry. 2021;26(7):3034–42.

49.

Dunstan

, Daly

, Owen

, . High-intensity resistance training improves glycemic control in older patients with Type 2 diabetes. Diabetes Care. 2002;25(10):1729–36.

50.

Villareal

, Chode

, Parimi

, . Weight loss, exercise, or both and physical function in obese older adults. N Engl J Med. 2011;364(13):1218–29.

51.

Zhao

, Cheng

, Song

, . The effect of resistance training on the rehabilitation of elderly patients with sarcopenia: a meta-analysis. Int J Environ Res Public Health. 2022;19(23):15491.

52.

Porter

, Reidy

, Bhattarai

, Sidossis

, Rasmussen

. Resistance exercise training alters mitochondrial function in human skeletal muscle. Med Sci Sports Exerc. 2015;47(9):1922–31.

53.

Bull

, Al-Ansari

, Biddle

, . World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54(24):1451–62.

54.

Ramsey

, Rojer

AGM

, D’Andrea

, . 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.

55.

Look AHEAD Research Group, Wadden

, West

, . The look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obes Silver Spring Md. 2006;14(5):737–52.

56.

Houston

, Neiberg

, Miller

, . 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(11):1552–9.

57.

, Mao

, Feng

, Ainsworth

, Liu

, Chen

. 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(1):708.

58.

Csapo

, Alegre

. 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(9):995–1006.

59.

Wolfe

, Burton

, Vardarli

, Coyle

. Hourly 4-s sprints prevent impairment of postprandial fat metabolism from inactivity. Med Sci Sports Exerc. 2020;52(10):2262–9.

60.

Perkin

, McGuigan

, Stokes

. Exercise snacking to improve muscle function in healthy older adults: a pilot study. J Aging Res. 2019;2019:7516939.

61.

Basiri

, Spicer

, Ledermann

, Arjmandi

. Effects of nutrition intervention on blood glucose, body composition, and phase angle in obese and overweight patients with diabetic foot ulcers. Nutrients. 2022;14(17):3564.

62.

Latres

, Pangilinan

, Miloscio

, . 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.

63.

Wittert

, Bracken

, Robledo

, . 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(1):32–45.

64.

Pan

, Kovac

. Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness. Transl Androl Urol. 2016;5(2):213–9.

65.

Sattler

, Schroeder

, Dube

, . Metabolic effects of nandrolone decanoate and resistance training in men with HIV. Am J Physiol Endocrinol Metab. 2002;283(6):E1214-22.

66.

, Tien

. The impact of antidiabetic agents on sarcopenia in Type 2 diabetes: a literature review. J Diabetes Res. 2020;2020:9368583.

67.

Takada

, Hirabayashi

, Kinugawa

, . Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in Type 2 diabetic mice. Eur J Pharmacol. 2014;740:690–6.

68.

Cetrone

, Mele

, Tricarico

. Effects of the antidiabetic drugs on the age-related atrophy and sarcopenia associated with diabetes type, II. Curr Diabetes Rev. 2014;10(4):231–7.

69.

Shimizu

, Suzuki

, Kato

, . Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with Type 2 diabetes and non-alcoholic fatty liver disease. Diabetes Obes Metab. 2019;21(2):285–92.

70.

Sasaki

, Sugawara

, Fukuda

. Sodium-glucose cotransporter 2 inhibitor-induced changes in body composition and simultaneous changes in metabolic profile: 52-week prospective LIGHT (Luseogliflozin: the components of weight loss in Japanese patients with Type 2 diabetes mellitus) study. J Diabetes Investig. 2019;10(1):108–17.

71.

Bouchi

, Terashima

, Sasahara

, . Luseogliflozin reduces epicardial fat accumulation in patients with Type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017;16(1):32.

72.

Inoue

, Hayashi

, Taguchi

, . Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non-alcoholic fatty liver disease. J Diabetes Investig. 2019;10(4):1004–11.

73.

Yamakage

, Tanaka

, Inoue

, Odori

, Kusakabe

, Satoh-Asahara

. Effects of dapagliflozin on the serum levels of fibroblast growth factor 21 and myokines and muscle mass in Japanese patients with type 2 diabetes: a randomized, controlled trial. J Diabetes Investig. 2020;11(3):653–61.

74.

Yajima

, Yajima

, Takahashi

, Yasuda

. The effect of dulaglutide on body composition in Type 2 diabetes mellitus patients on hemodialysis. J Diabetes Complications. 2018;32(8):759–63.

75.

Jendle

, Nauck

, Matthews

, . Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for Type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes Obes Metab. 2009;11(12):1163–72.

76.

Wilding

JPH

, Batterham

, Calanna

, . Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002.

77.

Jastreboff

, Aronne

, Ahmad

, . Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205–16.

Type 2 Diabetes and Sarcopenia

Abstract

Keywords

Introduction

Epidemiology

Definition and Diagnosis of Sarcopenia

Sarcopenic Obesity

Osteosarcopenia

Pathophysiology

Pathophysiology-intrinsic versus extrinsic risk factors for sarcopenia

Management

Dietary Interventions

Weight Management, Dietary Interventions in Older Adults with Type 2 DM

Physical Activity

Control of Blood Glucose Level

Medication

Conclusion

Footnotes

Declaration of conflicting interests

Funding

Institutional ethical committee approval number

Informed consent

Credit author statement

Data availability

Use of artificial intelligence

References