Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments

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Diabetes is linked to impaired insulin secretion, impaired insulin action, or both.

“In the case of diabetes, it may be linked to impaired insulin secretion (insulin deficiency), impaired insulin action (insulin resistance), or both (71).”

• cites [71] Liu, 2020, Past, present and future of latent autoimmune diabetes in adults, Diabetes Metab Res Rev. sourceNot checked yet

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Aging is associated with a decrease in muscle mass and strength and an increase in body fat mass, leading to frailty, falls, disability, social isolation, and hospitalization.

“Aging is associated with the decrease in muscle mass and strength and the increase in body fat mass, which leads to frailty, falls, disability, social isolation, and hospitalization.”

• cites [1] Zamboni, 2019, Sarcopenia and obesity, Curr Opin Clin Nutr. sourceNot checked yet

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The diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms.

“Also, the diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms.”

Probably not a substantial claim: may not pass S4 (based).

The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes.

“The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes.”

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Compared to simple sarcopenia or obesity alone, the medical sequelae related to sarcopenic obesity are much greater, causing significantly higher healthcare costs.

“Compared to simple sarcopenia or obesity alone, the medical sequelae related to SO are much greater, causing significantly higher healthcare costs (4).”

• cites [4] Xie, 2019, Sarcopenic obesity: research advances in pathogenesis and diagnostic criteria, Aging Clin Exp Res sourceNot checked yet

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The percentage of diabetics rises with age.

“A study in America has suggested that the percentage of diabetics rises with age (9).”

• cites [9] Fang, 2018, Trends in the prevalence of diabetes among US adults: 1999-2016, Am J Prevent Med. sourceNot checked yet

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Insulin loses the function to enhance cellular glucose uptake and utilization in diabetics, which is defined clinically as insulin resistance which promotes obesity.

“On the one hand, insulin loses the function to enhance cellular glucose uptake and utilization in diabetics, which is defined clinically as insulin resistance which promotes obesity.”

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Aging and obesity are two risk factors of diabetes.

“Moreover, aging and obesity are two risk factors of diabetes as well. A variety of studies have the consensus that aging as well as obesity have positive associations with diabetes.”

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Due to the chronic progress of sarcopenic obesity, symptoms hardly draw attention, resulting in poor diagnosis, which causes negative consequences of quality of life and all-cause mortality.

“Due to the chronic progress of SO, the symptoms hardly draw people's attention, resulting in poor diagnosis, which causes negative consequences of quality of life and all-cause mortality (8).”

• cites [8] Stephen, 2009, Sarcopenic-obesity and cardiovascular disease risk in the elderly, J Nutr Health Aging. sourceNot checked yet

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Sarcopenic obesity and diabetes are two increasing health problems worldwide, and both share many common risk factors, such as aging and general obesity.

“Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging, and general obesity.”

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Sarcopenic obesity occurs in the old without increase of body weight, which could be due to the ectopic redistribution of fat.

“However, it is also common that SO occurs in the old without increase of body weight, which could be due to the ectopic redistribution of fat.”

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Elevated levels of IL-6 and C-reactive protein (CRP) are related to sarcopenic obesity, which in turn have suppressive effects on muscle strength.

“A study conducted in Italy has verified that elevated levels of IL-6 and C-reactive protein (CRP) are related to SO, which in turn have suppressive effects on muscle strength (26).”

• cites [26] Schrager, 2007, Sarcopenic obesity and inflammation in the InCHIANTI study, J Appl Physiol sourceNot checked yet

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With aging, the reduction of basal metabolic rates may lead to weight gain and muscle mass decrease, which are associated with sarcopenic obesity.

“With aging, the reduction of basal metabolic rates may lead to weight gain and muscle mass decrease, which are associated with SO.”

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Fat tends to move to viscera, muscle and abdomen with age, and ectopic fat causes disorders of inflammatory factors, insulin and hormones, thus resulting in sarcopenic obesity.

“Studies have found that fat tends to move to viscera, muscle and abdomen with age, and the ectopic fat cause disorders of inflammatory factors, insulin and hormones, thus resulting in SO (15).”

• cites [15] Polyzos, 2018, Sarcopenic obesity, Hormones. sourceNot checked yet

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Myostatin inhibits muscle cell growth and differentiation, and irisin stimulates the increase of muscle mass.

“It is believed that myostatin inhibits muscle cell growth and differentiation, and irisin stimulates the increase of muscle mass (42, 43).”

• cites [42] Huh, 2018, The role of exercise-induced myokines in regulating metabolism, Arch Pharm Res. sourceNot checked yet

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• cites [43] Díaz, 2018, Myokines, physical activity, insulin resistance and autoimmune diseases, Immunol Lett. sourceNot checked yet

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Obesity is related to a low-grade inflammation, and increased production and secretion of inflammatory factors including TNF-α and IL-6 modulate insulin sensitivity by altering key steps in the insulin signaling pathway, which is responsible for subsequent insulin resistance.

“Meanwhile, obesity is related to a low-grade inflammation, the increased production and secretion of multifarious inflammatory factors including TNF-α, IL-6 modulate insulin sensitivity by altering some key steps in the insulin signaling pathway, which is responsible for the subsequent insulin resistance (34–36).”

• cites [34] Mcternan, 2006, Recent advances in the relationship between obesity, inflammation, insulin resistance, Eur Cytokine Netw. sourceNot checked yet

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• cites [35] Shoelson, 2007, Inflammation, insulin resistance, Gastroenterology. sourceNot checked yet

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• cites [36] Matulewicz, 2016, Insulin resistance and chronic inflammation, Postepy Hig Med Dosw. sourceNot checked yet

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The content of myostatin is upregulated while irisin is downregulated in sarcopenia.

“However, several studies have documented that the content of myostatin is upregulated while irisin is downregulated in sarcopenia (44).”

• cites [44] Chang, 2017, Circulating irisin levels as a predictive biomarker for sarcopenia: a cross-sectional community-based study, Geriatr Gerontol Int sourceNot checked yet

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Old people tend to decrease physical activity, which contributes to the severe loss of muscle strength.

“In fact, old people tend to decrease physical activity, which contributes to the severe loss of muscle strength.”

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Atrophic muscles make it even more difficult for elderly people to exercise, further aggravating the sedentary lifestyle.

“Then atrophic muscles make even more difficult for elderly people to exercise, further aggravating the sedentary lifestyle.”

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Multiple factors cause sarcopenic obesity, such as aging, lack of physical activity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes, which lead to body composition changes (muscle mass and strength decline and fat mass increase).

“There are multiple factors that cause sarcopenic obesity, such as aging, lack of physical activity, malnutrition low-grade inflammation, insulin resistance and hormonal changes, which leads to body composition changes (muscle mass and strength decline and fat mass increase).”

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Dysfunctional insulin production occurs, gradually leading to insulin resistance.

“Thereby, dysfunctional insulin production occurs, gradually leading to insulin resistance (28).”

• cites [28] Michio, 2017, Leptin resistance and lipolysis of white adipose tissue: an implication to ectopic fat disposition and its consequences, J Atheroscler Thromb. sourceNot checked yet

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Physical activity is necessary to lose weight and improve muscle strength, which is beneficial to ameliorate the state of sarcopenic obesity.

“Numerous studies have proven that physical activity is necessary to lose weight and improve muscle strength, which is beneficial to ameliorate the state of SO (16, 17).”

• cites [16] Patel, 2018, Marrow adiposity and hematopoiesis in aging and obesity: exercise as an intervention, Curr Osteoporos Rep. sourceNot checked yet

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• cites [17] Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat Rev Endocrinol. sourceNot checked yet

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Either low-grade inflammation or ectopic fat distribution generates myokine imbalance and mitochondrial dysfunction.

“Moreover, either low-grade inflammation or ectopic fat distribution generates myokine imbalance and mitochondrial dysfunction (32, 33).”

• cites [32] Goya, 2015, Muscle loss and obesity: the health implications of sarcopenia and sarcopenic obesity, Proc Nutr Soc. sourceNot checked yet

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• cites [33] Kalinkovich, 2017, Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis, Ageing Res Rev. sourceNot checked yet

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A down-regulation of genes involving mitochondrial enzymes declines mitochondrial content, which has been found in insulin resistant states, augmenting accumulation of fat in muscle and liver.

“A down-regulation of genes involving mitochondrial enzymes declines mitochondrial content, which has been found in insulin resistant states (39, 40), augmenting accumulation of fat in muscle and liver.”

• cites [39] Mootha, 2003, PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes, Nat Genet. sourceNot checked yet

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• cites [40] Patti, 2003, Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1, Proc Natl Acad Sci USA. sourceNot checked yet

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Insulin resistance is essential for protein anabolism, thus directly concerns muscle fiber atrophy.

“Studies have elucidated that insulin resistance is essential for protein anabolism, thus directly concerns muscle fiber atrophy (37).”

• cites [37] Nomura, 2007, Muscle strength is a marker of insulin resistance in patients with type 2 diabetes: a pilot study, Endocr J. sourceNot checked yet

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The highest level of monocyte chemoattractant protein-1 (MCP-1) and the lowest level of appendicular lean mass are found in the sarcopenic obesity group.

“The study has found the highest level of monocyte chemoattractant protein-1 (MCP-1) and the lowest level of appendicular lean mass in SO group (27), which supports the theory that low-grade inflammation is linked to SO.”

• cites [27] Lim, 2015, Monocyte chemoattractant protein-1: a proinflammatory cytokine elevated in sarcopenic obesity, Clin Intervent Aging. sourceNot checked yet

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The production and efficiency of insulin decline in elderly and obese people.

“The production and efficiency of insulin decline in elderly and obese people.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Weight generally increases in elderly people.

“Therefore, weight generally increases in elderly people.”

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Increased level of leptin contributes to leptin resistance, resulting in accumulation of free fatty acids.

“Besides, the increased level of leptin contributes to leptin resistance, resulting in accumulation of free fatty acids.”

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The amount of bone mass and muscle mass peaks around 30 years old, and after that, a gradual loss of muscle mass is accompanied with a parallel gain of fat mass.

“Meanwhile, studies have validated that the amount of bone mass and muscle mass peak around 30 years old, and after that, a gradual loss of muscle mass is accompanied with a parallel gain of fat mass (14).”

• cites [14] Mourtzakis, 2008, A practical and precise approach to quantifica- tion of body composition in cancer patients using computed tomog- raphy images acquired during routine care, Appl Physiol Nutr Metab sourceNot checked yet

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Adipocytes promote macrophage recruitment, then adipocytes and immune cells secrete more adipokines such as leptin, chemerin, resistin, and more cytokines such as TNF-α, ILs, INF-γ, creating a circumstance of low-grade inflammation.

“Specifically, adipocytes promote macrophage recruitment (21), then adipocytes and immune cells secrete more adipokines such as leptin, chemerin, resistin, and more cytokines such as tumor necrosis factor-α (TNF-α), interleukins (ILs), interferon-γ (INF-γ) (22–25), creating a circumstance of low-grade inflammation.”

• cites [21] Neels, 2005, Inflamed fat: what starts the fire?, J Clin Invest. sourceNot checked yet

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• cites [22] Polyzos, 2016, Adipose tissue, obesity and nonalcoholic fatty liver disease, Minerva Endocrinologica. sourceNot checked yet

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• cites [23] Kim, 2013, Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean sarcopenic obesity study, Clin Endocrinol. sourceNot checked yet

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• cites [24] Dong, 2019, Molecular dynamics of the recruitment of immunoreceptor signaling module DAP12 homodimer to lipid raft boundary regulated by PIP2, J Phys Chem B. sourceNot checked yet

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• cites [25] Wei, 2017, Critical residues and motifs for homodimerization of the first transmembrane domain of the plasma membrane glycoprotein CD36, J Biol Chem. sourceNot checked yet

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Mitochondrial dysfunction causes more lipid peroxidation, which reinforces the collections of lipid intermediates and reactive oxygen metabolites, accelerating inflammation, insulin resistance, and oxidative stress.

“Also, mitochondrial dysfunction causes more lipid peroxidation, which reinforces the collections of lipid intermediates and reactive oxygen metabolites, accelerating inflammation, insulin resistance, and oxidative stress (33).”

• cites [33] Kalinkovich, 2017, Sarcopenic obesity or obese sarcopenia: a cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis, Ageing Res Rev. sourceNot checked yet

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The increase in myostatin and decrease in irisin are tightly associated with poor browning reaction of white fat, reducing energy expenditure, triggering fat gain.

“At the same time, the increase in myostatin and decrease in irisin are tightly associated with poor browning reaction of white fat, reducing energy expenditure, triggering fat gain (45).”

• cites [45] Colaianni, 2017, Irisin and musculoskeletal health, Ann N Y Acad Sci. sourceNot checked yet

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Both aging and physical inactivity contribute to weight gain, by which an increase in adipose cell size may be determined.

“Both aging and physical inactivity have contributions on weight gain, by which an increase in adipose cell size may be determined.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Each factor has independent impacts on the quality and quantity of muscle and fat, whereas the cross-talks of them have stronger influences.

“Moreover, each factor has independent impacts on the quality and quantity of muscle and fat, whereas, the cross-talks of them have stronger influences.”

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Obese individuals with insulin resistance have a higher rate of muscle catabolism, evidenced by a study that leg muscle strength and quality decrease distinctly in older diabetics.

“Obese individuals with insulin resistance have a higher rate of muscle catabolism, which has been evidenced in a study that leg muscle strength and quality decrease distinctly in older diabetics (38).”

• cites [38] Abbatecola, 2005, Insulin resistance and muscle strength in older persons, J Gerontol. sourceNot checked yet

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Testosterone and estrogen are essential for muscle health, but the production of these hormones decline naturally with aging.

“Moreover, testosterone and estrogen are essential for muscle health (47), but the production of these hormones decline naturally with aging.”

• cites [47] Choi, 2013, Sarcopenia and sarcopenic obesity, Endocrinol Metab (Seoul). sourceNot checked yet

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The inner mitochondrial membrane of islet β cells fails to protect, which increases the permeability of mitochondrial membrane, leading to β cells apoptosis.

“Thus, the inner mitochondrial membrane of islet β cells fails to protect, which increases the permeability of mitochondrial membrane, leading to β cells apoptosis (75, 76).”

• cites [75] Nolan, 2014, Lipotoxicity, β cell dysfunction, gestational diabetes, Cell Metab. sourceNot checked yet

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• cites [76] Farrell, 2018, Pathogenesis of NASH: how metabolic complications of overnutrition favour lipotoxicity and pro-inflammatory fatty liver disease, Adv Exp Med Biol. sourceNot checked yet

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Compared to non-sarcopenic-obesity participants, subjects with sarcopenic obesity have a 24% increased risk of all-cause mortality, especially in men.

“A meta-analysis of 12 prospective cohort studies has indicated that compare to non-SO participants, subjects with SO have a 24% increased risk of all-cause mortality, especially in men.”

• cites [52] Tian, 2016, Association of sarcopenic obesity with the risk of all-cause mortality: a meta-analysis of prospective cohort studies, Geriatr Gerontol Int. sourceNot checked yet

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Persistent elevated levels of glucose can swamp the glycolytic process and inhibit glyceraldehyde catabolism, which promotes reactive oxygen species (ROS) production and oxidative damage, inducing β cells apoptosis and inhibiting β cells secretion.

“Persistent elevated levels of glucose can swamp the glycolytic process and inhibit glyceraldehyde catabolism, which promotes reactive oxygen species (ROS) production and oxidative damage, inducing β cells apoptosis and inhibiting β cells secretion (73, 74).”

• cites [73] Mota, 2016, Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease, Metabolism. sourceNot checked yet

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• cites [74] Las, 2020, Emerging roles of β-cell mitochondria in type-2-diabetes, Mol Aspects Med. sourceNot checked yet

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Either low muscle mass and strength or obesity is an independent risk factor for reduced physical capacity and quality of life.

“It is acknowledged that either low muscle mass and strength or obesity is an independent risk factor for reduced physical capacity and quality of life.”

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Loss of muscle mass and strength makes a higher risk of osteoarthritis, which exacerbates physical inactivity, worsening both physical and mental health.

“As the loss of muscle mass and strength makes a higher risk of osteoarthritis (63, 64), this exacerbates physical inactivity, worsening both physical and mental health.”

• cites [63] Lee, 2012, Sarcopenic obesity is more closely associated with knee osteoarthritis than is nonsarcopenic obesity: a cross-sectional study, Arthritis Rheum. sourceNot checked yet

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• cites [64] Misra, 2019, Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia, Arthritis Rheumatol. sourceNot checked yet

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Classified as probably not a substantial claim.

When muscle damage and obesity coexist, they act synergistically on the risk of mortality, metabolic disorders, and quality of life.

“Therefore, it is reasonable to speculate when muscle damage and obesity coexist, they act synergistically on the risk of mortality, metabolic disorders, and quality of life (47, 51).”

• cites [47] Choi, 2013, Sarcopenia and sarcopenic obesity, Endocrinol Metab (Seoul). sourceNot checked yet

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• cites [51] Stenholm, 2008, Sarcopenic obesity: definition, cause and consequences, Curr Opin Clin Nutr Metab Care. sourceNot checked yet

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The reduction of IGF-1 is accompanied by the downregulation of irisin, and high level of free fatty acids in obese people inhibits both IGF-1 and growth hormone, which lowers the mass and strength of muscle, leading to muscle impairment and thus to sarcopenic obesity.

“The reduction of IGF-1 is accompanied by the downregulation of irisin (45), and high level of free fatty acids in obese people inhibits both IGF-1 and growth hormone (48), which lowers the mass and strength of muscle, leading to muscle impairment and thus to SO (49).”

• cites [45] Colaianni, 2017, Irisin and musculoskeletal health, Ann N Y Acad Sci. sourceNot checked yet

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• cites [48] Weltman, 2001, Body composition, physical exercise, growth hormone and obesity, Eat Weight Disord.Not checked yet

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• cites [49] Waters, 2008, Altered growth hormone, cortisol, and leptin secretion in healthy elderly persons with sarcopenia and mixed body composition phenotypes, J Gerontol. sourceNot checked yet

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Impaired insulin secretion is multifactorial, the exact mechanism is still unclear, but commonly develops from glucose toxicity, lipid toxicity, immunoinflammatory response, and oxidative stress, leading to the dysfunction of islet β cells.

“Impaired insulin secretion is multifactorial, the exact mechanism is still unclear, but commonly develops from glucose toxicity, lipid toxicity, immunoinflammatory response, and oxidative stress, leading to the dysfunction of islet β cells (72).”

• cites [72] Zhang, 2018, Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link, Behav Brain Res. sourceNot checked yet

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The highest fall risk and the lowest muscle function test results are in the sarcopenic obesity group, confirming an inverse association with health-related quality of life scores.

“Therefore, these factors, which significantly affect the quality of life for elderly people, have been illustrated in another study that the highest fall risk and the lowest muscle function test results in the SO group, confirming an inverse association with health-related quality of life scores (66).”

• cites [66] Öztürk, 2018, Health-related quality of life and fall risk associated with age-related body composition changes; sarcopenia, obesity and sarcopenic obesity, Inter Med J. sourceNot checked yet

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In a Japanese study, all-cause mortality increases in men with sarcopenic obesity defined by waist circumference (HR, 1.19; 95% CI, 1.02-1.38), but not body mass index (BMI) or percent body fat (BF%).

“Moreover, in a Japanese study, all-cause mortality increases in men with SO defined by waist circumference (HR, 1.19; 95% CI, 1.02–1.38), but not body mass index (BMI) or percent body fat (BF%) (53).”

• cites [53] Sanada, 2017, Association of sarcopenic obesity predicted by anthropometric measurements and twenty-four year all-cause mortality in elderly men: the kuakini honolulu heart program, Nutrition. sourceNot checked yet

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Prolonged as well as elevated levels of glucose blood, high free fatty acids, and chronic inflammatory environment, all increase the levels of ROS, activating the mechanism of oxidative stress.

“As mentioned above, prolonged as well as elevated levels of glucose blood, high free fatty acids, and chronic inflammatory environment, all increase the levels of ROS, activating the mechanism of oxidative stress (81).”

• cites [81] Rendra, 2019, Reactive oxygen species (ROS) in macrophage activation and function in diabetes, Immunobiology. sourceNot checked yet

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Both obesity and hyperglycemia promote the release of inflammatory mediators, like TNF-α or IL-6, and released mediators stimulate macrophages and other innate immune cells, as well as some apoptosis-related signaling pathways, such as Fas/FasL signaling pathway.

“Both obesity and hyperglycemia promote the release of inflammatory mediators, like TNF-α, or IL-6, released mediators stimulate macrophages and other innate immune cells, as well as some apoptosis-related signaling pathways, such as Fas/FasL signaling pathway (78, 79).”

• cites [78] Acharjee, 2013, Understanding type 1 diabetes: etiology and models, Can J Diabetes. sourceNot checked yet

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• cites [79] DeFronzo, 2004, Pathogenesis of type 2 diabetes mellitus, Med Clin North Am. sourceNot checked yet

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Chronic inflammatory environment is also beneficial for the formation of free radicals such as reactive oxygen species (ROS), exacerbating β cells damage and yielding a positive feedback circle with the secretion of more detrimental cytokines to trigger further damage to β cells.

“Besides, chronic inflammatory environment is also beneficial for the formation of free radicals such as reactive oxygen species (ROS), exacerbating β cells damage and yielding a positive feedback circle with the secretion of more detrimental cytokines to trigger further damage to β cells (80).”

• cites [80] Blaser, 2016, TNF and ROS crosstalk in inflammation, Trends Cell Biol. sourceNot checked yet

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ROS is capable to directly damage β cells, promoting apoptosis, or it can indirectly regulate insulin signaling pathway to inhibit the function of β cells.

“Therefore, ROS is capable to directly damage β cells, promoting apoptosis, or it can indirectly regulate insulin signaling pathway to inhibit the function of β cells (82, 83).”

• cites [82] Robertson, 2004, Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes, J Biol Chem. sourceNot checked yet

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• cites [83] Panigrahy, 2017, Reactive oxygen species: sources, consequences and targeted therapy in type 2 diabetes, J Drug Target. sourceNot checked yet

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Studies have estimated 10-years risk of cardiovascular disease in the sarcopenic obesity group, non-sarcopenic group, and non-obese group, and a significant increase has been found in the sarcopenic obesity group.

“In addition, studies have also estimated 10-years risk of CVD in SO group, non-sarcopenic group, and non-obese group, and a significant increase has been found in the SO group (58).”

• cites [58] Jeong-Hyeon, 2015, Relationship between sarcopenic obesity and cardiovascular disease risk as estimated by the framingham risk score, J Korean Med Sci. sourceNot checked yet

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Individuals with sarcopenic obesity are associated with increased waist circumference, elevated fasting blood glucose, insulin resistance, higher blood pressure, and abnormal blood lipids as compared to sarcopenia or obesity alone.

“Several Korean studies have indicated that individuals with SO are associated with increased waist circumference, elevated fasting blood glucose, insulin resistance, higher blood pressure, and abnormal blood lipids as compared to sarcopenia or obesity alone (13, 23, 56).”

• cites [13] Baek, 2014, Sarcopenia and sarcopenic obesity and their association with dyslipidemia in Korean elderly men: the 2008–2010 Korea National health and nutrition examination survey, J Endocrinol Invest. sourceNot checked yet

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• cites [23] Kim, 2013, Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean sarcopenic obesity study, Clin Endocrinol. sourceNot checked yet

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• cites [56] Kim, 2009, Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study, Int J Obes (Lond). sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Diabetes is considered as an independent risk factor for coronary heart diseases.

“Moreover, recent studies have shown that diabetes is considered as an independent risk factor for coronary heart diseases (114).”

• cites [114] Leon, 2015, Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research, World J Diabetes. sourceNot checked yet

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There is 1-2% of diabetic patients who will develop pancreatic cancer in 3 years.

“It has been proven that there is 1–2% of diabetic patients who will develop pancreatic cancer in 3 years (118).”

• cites [118] Magruder, 2016, Diabetes and pancreatic cancer: chicken or egg? sourceNot checked yet

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Individuals with diabetes suffer from a higher risk of cardiovascular diseases compared to those without diabetes, which is associated with a number of common risk factors such as age, obesity, smoking, hypertension, and dyslipidemia.

“Individuals with diabetes suffer from a higher risk of cardiovascular diseases compared to those without diabetes, which is associated with a number of common risk factors such as age, obesity, smoking, hypertension, and dyslipidemia (113).”

• cites [113] de Matheus, 2013, Impact of diabetes on cardiovascular disease: an update, Int J Hypertens. sourceNot checked yet

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GSK3β is one of the few protein kinases of which the activity can be inhibited by phosphorylation.

“GSK3β is one of the few protein kinases of which the activity can be inhibited by phosphorylation (94).”

• cites [94] Yaribeygi, 2019, Insulin resistance: review of the underlying molecular mechanisms, J Cell Physiol. sourceNot checked yet

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Neuropathy is associated with a 1.7-fold increase in the risk of amputation, and even higher when coupled with other problems.

“It has been reported that neuropathy is associated with a 1.7-fold increase in the risk of amputation, and even higher when coupled with other problems (107).”

• cites [107] Vinik, 2013, Diabetic neuropathy, Endocrinol Metab Clin North Am. sourceNot checked yet

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Recent studies have regarded Alzheimer's disease as type 3 diabetes because of insulin signaling pathways damage.

“Recent studies have regarded Alzheimer's disease as type 3 diabetes because of insulin signaling pathways damage (123).”

• cites [123] Kandimalla, 2017, Is alzheimer's disease a type 3 diabetes? a critical appraisal, Biochim Biophys Acta Mol Basis Dis. sourceNot checked yet

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Sexual dysfunction becomes more and more popular in both men and women with diabetes.

“Moreover, sexual dysfunction becomes more and more popular in both men and women with diabetes (124).”

• cites [124] Bak, 2017, Relationships of sexual dysfunction with depression and acceptance of illness in women and men with type 2 diabetes mellitus, Int J Environ Res Public Health. sourceNot checked yet

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Patients with type 2 diabetes in Asian countries have a lower risk of coronary diseases than those from eastern Europe or Established Market Economies.

“Interestingly, a study has indicated that patients with T2D in Asian countries have a lower risk of coronary diseases than those from eastern Europe or Established Market Economies (100).”

• cites [100] Clarke, 2010, Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis, PLoS Med. sourceNot checked yet

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When the insulin signaling pathway fails, the expression of GSK3β improves, which reduces the insulin sensitivity and increases the levels of blood glucose, thus subsequently leading to type 2 diabetes.

“When the insulin signaling pathway fails, the expression of GSK3β improves, which reduces the insulin sensitivity and increases the levels of blood glucose, thus subsequently leading to T2D (72, 96, 97).”

• cites [72] Zhang, 2018, Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link, Behav Brain Res. sourceNot checked yet

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• cites [96] Arneth, 2019, Metabolomics of type 1 and type 2 diabetes, Int J Mol Sci. sourceNot checked yet

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• cites [97] Gao, 2011, GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease, Rev Neurosci. sourceNot checked yet

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May combine two claims.

Diabetes contributes a 27% increased risk of breast cancer in women and predisposes to more aggressive cancer stages.

“Moreover, diabetes contributes a 27% increased risk of breast cancer in women and predisposes to more aggressive cancer stages (120).”

• cites [120] Boyle, 2012, Diabetes and breast cancer risk: a meta-analysis, Br J Cancer. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Diabetes serves as an independent risk factor for colorectal cancer; there is a 49% increased risk of colorectal cancer in men with diabetes.

“Also, diabetes serves as an independent risk factor for colorectal cancer as a study has found that there is a 49% increased risk of colorectal cancer in men with diabetes (119).”

• cites [119] Larsson, 2005, Diabetes and colorectal cancer incidence in the cohort of Swedish men, Diabetes Care. sourceNot checked yet

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May combine two claims.

High prevalence of depression as one of psychological complications that result from diabetes, makes it harder for diabetics to manage blood glucose, thus leading to further complications.

“Besides, high prevalence of depression as one of psychological complications that result from diabetes, makes it harder for diabetics to manage blood glucose, thus leading to further complications (125).”

• cites [125] Semenkovich, 2015, Depression in type 2 diabetes mellitus: prevalence, impact, and treatment, Drugs. sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Diabetic neuropathy involves various syndromes, such as mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy, among which distal symmetric polyneuropathy is very prevalent.

“Diabetic neuropathy involves various syndromes, such as mono- and polyneuropathies, plexopathies, radiculopathies and autonomic neuropathy, among which distal symmetric polyneuropathy is very prevalent (108).”

• cites [108] Feldman, 2019, Diabetic neuropathy, Nat Rev Dis Primers. sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

One of the structural changes in diabetic retinopathy is widened retinal arteriolar caliber which might be an early sign of microvascular dysfunction.

“One of the structural changes in diabetic retinopathy is widened retinal arteriolar caliber which might be an early sign of microvascular dysfunction.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The true prevalence of diabetic neuropathy is unclear but it varies from 10 to 90% in diabetics, according to the different standards and approaches used to define diabetic neuropathy.

“The true prevalence is unclear but it varies from 10 to 90% in diabetics, according to the different standards and approaches used to define diabetic neuropathy (107).”

• cites [107] Vinik, 2013, Diabetic neuropathy, Endocrinol Metab Clin North Am. sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Diabetic neuropathy is one of the most prominent complications of diabetes.

“Diabetic neuropathy is one of the most prominent complications of diabetes.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Another change is widened retinal venular caliber which might be independently related to the prevalence and progression in diabetic retinopathy, as well as an indicator of developing retinopathy.

“Also, another change is widened retinal venular caliber which might be independently related to the prevalence and progression in diabetic retinopathy, as well as an indicator of developing retinopathy (105, 106).”

• cites [105] Cheung, 2010, Diabetic retinopathy, Lancet. sourceNot checked yet

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• cites [106] Sosna, 2016, History of diagnosis and therapy of diabetic retinopathy, Vnitr Lek.Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Unmanaged diabetes can cause multiple complications, most common of which are microvascular complications: nephropathy, retinopathy, and neuropathy, and macrovascular complications: cardiovascular diseases.

“Unmanaged diabetes can cause multiple complications, most common of which are microvascular complications: nephropathy, retinopathy, and neuropathy, and macrovascular complications: cardiovascular diseases.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Cancer is a class of diseases resulted from external factors such as environment, diet and radiation as well as internal factors including obesity and diabetes.

“Cancer is a class of diseases resulted from external factors such as environment, diet and radiation as well as internal factors including obesity and diabetes (31, 116, 117).”

• cites [31] Liao, 2019, Reactive oxygen species: a volatile driver of field cancerization and metastasis, Mol Cancer. sourceNot checked yet

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• cites [116] Yang, 2019, Concentrated ambient PM2. 5 exposure affects mice sperm quality and testosterone biosynthesis, PeerJ. sourceNot checked yet

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• cites [117] Stone, 2018, Obesity and cancer: existing and new hypotheses for a causal connection, EBioMedicine. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

There are many diabetes-related ocular diseases, such as cataract, glaucoma, ischemic optic neuropathy, cranial nerve palsies, and recurrent corneal erosion syndrome.

“There are many diabetes-related ocular diseases, such as cataract, glaucoma, ischemic optic neuropathy, cranial nerve palsies, and recurrent corneal erosion syndrome (102).”

• cites [102] Henriques, 2015, Diabetic eye disease, Acta Med Port. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The transduction of the insulin PI3K/AKT signaling pathway is weakened, which may be the major manifestation of insulin resistance, impacting the downstream mediator-glycogen synthase kinase-3β (GSK3β).

“Meanwhile, the transduction of the insulin PI3K/AKT signaling pathway is weakened, which may be the major manifestation of insulin resistance, impacting the downstream mediator—glycogen synthase kinase-3β (GSK3β).”

May combine two claims.

With the destruction of β cells, the peak of insulin secretion will be delayed, intensifying the fluctuation of blood glucose, resulting in further severe damage of β cells.

“With the destruction of β cells, the peak of insulin secretion will be delayed, intensifying the fluctuation of blood glucose, resulting in further severe damage of β cells (85).”

• cites [85] Newsholme, 2016, Molecular mechanisms of ROS production and oxidative stress in diabetes, Biochem J. sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The risk of diabetic kidney disease is much higher in Asian countries than in Western countries due to different economic outcomes.

“A study has found that the risk of diabetic kidney disease is much higher in Asian countries than in Western countries due to different economic outcomes (100).”

• cites [100] Clarke, 2010, Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis, PLoS Med. sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Cardiovascular diseases, involving coronary heart disease, peripheral vascular disease and cerebrovascular disease, are the primary contributors of death and disability in diabetic people.

“Cardiovascular diseases, involving coronary heart disease, peripheral vascular disease and cerebrovascular disease, are the primary contributors of death and disability in diabetic people (112).”

• cites [112] Henning, 2018, Type-2 diabetes mellitus and cardiovascular disease, Future Cardiol. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

A vegetarian diet demonstrated better weight loss and insulin sensitivity.

“The macrobiotic and vegan diets were beneficial to glycemic control, while the vegetarian diet demonstrated better weight loss and insulin sensitivity.”

• cites [159] Papamichou, 2019, Dietary patterns and management of type 2 diabetes: a systematic review of randomised clinical trials, Nutr Metab Cardiovasc Dis. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The benefits of Mediterranean diets were greater than low-fat diets in diabetic retinopathy, but no significant differences were found in diabetic nephropathy.

“In addition, a study has also found that the benefits of Mediterranean diets were greater than low-fat diets in diabetic retinopathy, but no significant differences were found in diabetic nephropathy (160).”

• cites [160] Díaz-López, 2015, Mediterranean diet, retinopathy, nephropathy, and microvascular diabetes complications: a post hoc analysis of a randomized trial, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

DXA is recommended to estimate the lean and fat mass of the whole body or certain regions of body.

“Therefore, another relatively inexpensive and low radiation method called dual-energy-X-ray absorptiometry (DXA) is recommended to estimate the lean and fat mass of the whole body or certain regions of body.”

May combine two claims.

Even caloric restriction might cause loss of muscle mass, but it is still more beneficial to mobility and strength when accompanied by resistance training.

“Moreover, another study has demonstrated that even caloric restriction might cause loss of muscle mass, and hence, it is still more beneficial to mobility and strength when accompanying with resistance training (148).”

• cites [148] Nicklas, 2015, Effects of resistance training with and without caloric restriction on physical function and mobility in overweight and obese older adults: a randomized controlled trial, Am J Clin Nutr. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Knee flexion/extension is strongly related with certain functional activities.

“Furthermore, keen flexion/extension is strongly related with certain functional activities.”

May combine two claims.

DXA manifests strength in assessment of bone mass and density, thus simultaneously providing the conditions of bone, muscle, and fat.

“Moreover, it also manifests strength in assessment of bone mass and density, thus simultaneously providing the conditions of bone, muscle, and fat (130, 131).”

• cites [130] Ilich, 2016, Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed?, Curr Gerontol Geriatr Res. sourceNot checked yet

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• cites [131] Berger-Groch, 2020, Assessment of bone quality at the lumbar and sacral spine using CT scans: a retrospective feasibility study in 50 comparing CT and DXA data, Eur Spine J. sourceNot checked yet

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May combine two claims.

Physical activity has multiple biological effects: promoting insulin sensitivity, improving anabolic response to endogenous amino acids, activating skeletal muscle satellite cells and triggering their proliferation and differentiation, amplifying irisin production, adjusting hormonal milieu, increasing mitochondrial biogenesis, ameliorating inflammation, and reducing oxidative stress.

“Indeed, there are multiple biological effects of physical activity: promote insulin sensitivity, improve anabolic response to endogenous amino acids, activate skeletal muscle satellites cells and trigger the proliferation and differentiation of them, amplify irisin production, adjust hormonal milieu, increase mitochondrial biogenesis, ameliorate inflammation and reduce oxidative stress (162–164).”

• cites [162] Barazzoni, 2018, Sarcopenic obesity: time to meet the challenge, Obesity Facts. sourceNot checked yet

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• cites [163] Joseph, 2016, Beneficial effects of exercise on age-related mitochondrial dysfunction and oxidative stress in skeletal muscle, J Physiol. sourceNot checked yet

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• cites [164] Mooren, 2015, Exercise autophagy, and apoptosis, Prog Mol Biol Transl Sci. sourceNot checked yet

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May combine two claims.

Older people have anabolic resistance, so a higher protein intake is needed to promote muscle protein synthesis.

“While in older people, a higher protein intake should be provided in order to promote muscle protein synthesis due to anabolic resistance.”

• cites [149] Deutz, 2014, Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group, Clin Nutr. sourceNot checked yet

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• cites [150] Bauer, 2013, Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group, J Am Med Direct Assoc. sourceNot checked yet

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• cites [151] Paddon-Jones, 2009, Dietary protein recommendations and the prevention of sarcopenia, Curr Opin Cin Nutr Metab Care. sourceNot checked yet

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May combine two claims.

A high-protein diet improves muscle strength in sarcopenic obesity patients and prevents weight loss-induced sarcopenia.

“A similar result has been shown in another study that high-protein diet improves muscle strength in SO patients and prevent weight loss-induced sarcopenia (152).”

• cites [152] Sammarco, 2017, Evaluation of hypocaloric diet with protein supplementation in middle-aged sarcopenic obese women: a pilot study, Obesity Facts. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

Handgrip strength is a great predictor of extremity muscle power and mobility.

“Handgrip strength is a great predictor of extremity muscle power and mobility.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The American Diabetes Association recognizes four approaches to diagnose diabetes: fasting plasma glucose test, two-hour oral glucose tolerance test, glycated hemoglobin, and random plasma glucose coupled with symptoms.

“According to American Diabetes Association (ADA), there are four approaches to diagnosis diabetes: Fasting plasma glucose test (FPG), Two-Hour Oral Glucose Tolerance Test (OGTT), Glycated Hemoglobin (A1C), and Random plasma glucose coupled with symptoms (67).”

• cites [67] 2015, (2) Classification and diagnosis of diabetes, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

A1C reflects average blood glucose over the last 2-3 months and is relatively accurate because it is less influenced by acute illness or stress.

“A1C shows the average of blood glucose over last 2–3 months, and it is relative accurate since less influence by acute illness or stress.”

• cites [67] 2015, (2) Classification and diagnosis of diabetes, Diabetes Care. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

BIA is used to measure muscle mass, but the inaccuracy makes it unrecommended to diagnose sarcopenia.

“In addition, as an affordable and available tool, bioelectrical impedance analysis (BIA) is used to measure muscle mass as well, whereas, the inaccuracy makes it unrecommended to diagnose sarcopenia (132).”

• cites [132] Bosy-Westphal, 2017, Quantification of whole-body and segmental skeletal muscle mass using phase-sensitive 8-electrode medical bioelectrical impedance devices, Eur J Clin Nutr sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The diagnosis of sarcopenic obesity varies with the changes of the diagnosis of obesity and sarcopenia.

“However, the diagnosis of SO varies with the changes of the diagnosis of obesity and sarcopenia.”

May combine two claims.

It is hard to generalize CT and MRI due to the high cost, and the risk of radiation (for CT).

“However, it is hard to generalize CT and MRI due to the high cost, and the risk of radiation (for CT) (129).”

• cites [129] Donini, 2020, Critical appraisal of definitions and diagnostic criteria for sarcopenic obesity based on a systematic review, Clin Nutr. sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Many professional organizations recommend that a combination of resistance training and aerobic training is the most practical way to improve physical performance.

“many professional organizations recommend that a combination of resistance training and aerobic training seems to be the most practical way to improve physical performance (165, 166).”

• cites [165] Lombardo, 2019, Sarcopenic obesity: etiology and lifestyle therapy, Eur Rev Med Pharmacol Sci. sourceNot checked yet

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• cites [166] Batsis, 2018, Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies, Nat Rev Endocrinol. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Vitamin D deficiency is associated with lower muscle strength, greater body instability, falls, and disability in the geriatric population.

“several studies have suggested that vitamin D deficiency is associated with lower muscle strength, greater body instability, falls and disability in geriatric population (153).”

• cites [153] Bellia, 2013, Serum 25-hydroxyvitamin D levels are inversely associated with systemic inflammation in severe obese subjects, Inter Emerg Med. sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Peak expiratory flow manifests the strength of respiratory muscles, but it is not considered as a separated method.

“Although peak expiratory flow manifests the strength of respiratory muscles, it is not considered as a separated method.”

May combine two claims.

Major RCTs in non-sarcopenic women with obesity suggest that caloric restriction with a 500 kcal deficit and at least 0.8 g/kg protein intake can effectively lose fat and improve physical function.

“Major RCTs in non-sarcopenic women with obesity have suggested that caloric restriction (500 kcal deficit) with at least 0.8 g/kg of protein intake can effectively lose fat and improve physical function (146, 147).”

• cites [146] Backx, 2016, Protein intake and lean body mass preservation during energy intake restriction in overweight older adults, Int J Obesity. sourceNot checked yet

  Not checked in the free run.

• cites [147] Petroni, 2019, Prevention and treatment of sarcopenic obesity in women, Nutrients. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

CT and MRI are deemed as the gold standard to distinguish fat from other soft tissues, thereby effectively estimating fat mass and muscle mass.

“Various techniques emerge for assessing muscle mass, among which, computed tomography (CT) and magnetic resonance imaging (MRI) are deemed as the gold standard to distinguish fat from other soft tissues, thereby, effectively estimating fat mass and muscle mass.”

May combine two claims.

Vegan, vegetarian, and Mediterranean diets are better strategies to control glycemic markers in diabetics.

“Therefore, the study has concluded that vegan, vegetarian and Mediterranean diets are better strategies to control glycemic marker in diabetics (159).”

• cites [159] Papamichou, 2019, Dietary patterns and management of type 2 diabetes: a systematic review of randomised clinical trials, Nutr Metab Cardiovasc Dis. sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Thiazolidinediones can promote insulin sensitivity, increase glucose metabolism, and preserve β-cell function through activating PPAR-γ.

“Also, thiazolidinediones can promote insulin sensitivity, increase glucose metabolism, and preserve the β-cell function through activating PPAR-γ (185, 186).”

• cites [185] Tyagi, 2011, The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases, J Adv Pharmac Technol Res. sourceNot checked yet

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• cites [186] Wendy, 2018, An aPPARent functional consequence in skeletal muscle physiology via peroxisome proliferator-activated receptors, Int J Mol Sci. sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Metformin is considered one of the most prevalent medications for diabetes management.

“Metformin is considered as one of the most prevalent medications for diabetes management (179).”

• cites [179] Vallianou, 2019, Metformin and gut microbiota: their interactions and their impact on diabetes, Hormones (Athens). sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Metformin decreases fasting plasma glucose concentration and hemoglobin A1c by conserving β-cell function or by decreasing liver glucose production (hepatic gluconeogenesis).

“A considerable number of studies have also found that metformin decreases fasting plasma glucose (PG) concentration and hemoglobin A1c by conserving the β-cell function or by decreasing liver glucose production (hepatic gluconeogenesis) (181–184).”

• cites [181] DeFronzo, 1991, Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects, J Clin Endocrinol Metab. sourceNot checked yet

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• cites [182] DeFronzo, 1995, Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. the multicenter metformin study group, N Engl J Med. sourceNot checked yet

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• cites [183] Foretz, 2019, Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus, Nat Rev Endocrinol. sourceNot checked yet

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• cites [184] Turner, 1999, Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) group, JAMA. sourceNot checked yet

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