Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments

In the paper

“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).”

What the sources say

• Partly supported

  The Results report increased all-cause mortality for waist-circumference-defined sarcopenic obesity (HR 1.19; 95% CI 1.02–1.38), but not for the BMI- or percent-body-fat-defined groups. The population is misstated: the Methods describe 2,309 Japanese-American men aged 71–93, not a study of men in Japan. (LLM, conf=0.90)

  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. sourceExperimental — accuracy not yet measured

In the paper

“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).”

What the sources say

• Partly supported

  The Results report a loss of total lean mass with resistance training plus caloric restriction, alongside improvements in strength and physical function; the Discussion says those gains were not compromised by the lean-mass loss. The combined group had a better 400-m walk time than the resistance-training-only group, but no greater improvement in knee extensor strength. The trial had no caloric-restriction-only group, so it cannot establish that adding resistance training is more beneficial than caloric restriction alone. (LLM, conf=0.85)

  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. sourceExperimental — accuracy not yet measured

In the paper

“Acupuncture has been used in diabetes for a long time in Asian countries and recent studies have also suggested that acupuncture may alleviate SO (197–199).”

What the sources say

• Not checked yetcites [197] Zhou, 2018, The effects of electrical acupuncture and essential amino acid supplementation on sarcopenic obesity in male older adults: a randomized control study, Obes Facts. source
• ?Could not verify

  The Summary describes historical uses of heat-producing acupuncture for cold limbs, abdominal pain, and diarrhea, while the Selection of Participants section describes healthy volunteers. Searches for diabetes and sarcopenic obesity found no passage addressing either the claimed long-standing use for diabetes in Asian countries or a possible benefit for sarcopenic obesity. (LLM, conf=0.75)

  cites [198] Liao, 2018, Effect of heat-producing needling technique on the local skin temperature: clinical dataset, Data. sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page unavailable) says traditional Chinese medicine, including acupuncture, has been used in China for thousands of years and practiced as an adjunctive treatment for diseases such as diabetes. It does not specifically establish long-standing acupuncture use for diabetes, and the paper’s acupuncture section addresses knee osteoarthritis, not whether acupuncture alleviates sarcopenic obesity. (LLM, conf=0.84)

  cites [199] Wang, 2020, Mechanism of traditional chinese medicine in treating knee osteoarthritis, J Pain Res. sourceExperimental — accuracy not yet measured

In the paper

“Meanwhile, they can reduce plasma free fatty acid and intramyocellular lipid content to increase insulin sensitivity and redistribute fats from visceral to subcutaneous adipose to alleviate diabetes.”

What the sources say

• Partly supported

  The “Peroxisome Proliferator-Activated Receptors and Diabetes” section describes TZDs as insulin-sensitizing, and the PPAR-γ mechanism section says PPAR-γ agonists improve insulin resistance. Neither section states that TZDs reduce plasma free fatty acids or intramyocellular lipids, or redistribute fat from visceral to subcutaneous tissue. Page numbers are not available in our copy. (LLM, conf=0.88)

  cites [185] Tyagi, 2011, The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases, J Adv Pharmac Technol Res. sourceExperimental — accuracy not yet measured
• Partly supported

  Section 6.1 says thiazolidinediones improve insulin sensitivity and that pioglitazone treats type 2 diabetes. It also reports reduced intramuscular lipid accumulation with constitutive PPARγ activation in mouse muscle, but does not establish that thiazolidinediones cause that reduction. The cited passages do not support reduced plasma free fatty acids or redistribution of fat from visceral to subcutaneous tissue. Page numbers were not provided. (LLM, conf=0.85)

  cites [186] Wendy, 2018, An aPPARent functional consequence in skeletal muscle physiology via peroxisome proliferator-activated receptors, Int J Mol Sci. sourceExperimental — accuracy not yet measured

In the paper

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

What the sources say

• Not checked yetcites [71] Liu, 2020, Past, present and future of latent autoimmune diabetes in adults, Diabetes Metab Res Rev. source

In the paper

“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.”

What the sources say

• Not checked yetcites [1] Zamboni, 2019, Sarcopenia and obesity, Curr Opin Clin Nutr. source

In the paper

“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.”

In the paper

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

In the paper

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

What the sources say

• Not checked yetcites [4] Xie, 2019, Sarcopenic obesity: research advances in pathogenesis and diagnostic criteria, Aging Clin Exp Res source

In the paper

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

What the sources say

• Not checked yetcites [9] Fang, 2018, Trends in the prevalence of diabetes among US adults: 1999-2016, Am J Prevent Med. source

In the paper

“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.”

In the paper

“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.”

In the paper

“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).”

What the sources say

• Not checked yetcites [8] Stephen, 2009, Sarcopenic-obesity and cardiovascular disease risk in the elderly, J Nutr Health Aging. source

In the paper

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

In the paper

“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.”

In the paper

“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).”

What the sources say

• Not checked yetcites [26] Schrager, 2007, Sarcopenic obesity and inflammation in the InCHIANTI study, J Appl Physiol source

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [15] Polyzos, 2018, Sarcopenic obesity, Hormones. source

In the paper

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

What the sources say

• Not checked yetcites [42] Huh, 2018, The role of exercise-induced myokines in regulating metabolism, Arch Pharm Res. source
• Not checked yetcites [43] Díaz, 2018, Myokines, physical activity, insulin resistance and autoimmune diseases, Immunol Lett. source

In the paper

“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).”

What the sources say

• Not checked yetcites [34] Mcternan, 2006, Recent advances in the relationship between obesity, inflammation, insulin resistance, Eur Cytokine Netw. source
• Not checked yetcites [35] Shoelson, 2007, Inflammation, insulin resistance, Gastroenterology. source
• Not checked yetcites [36] Matulewicz, 2016, Insulin resistance and chronic inflammation, Postepy Hig Med Dosw. source

In the paper

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

What the sources say

• Not checked yetcites [44] Chang, 2017, Circulating irisin levels as a predictive biomarker for sarcopenia: a cross-sectional community-based study, Geriatr Gerontol Int source

In the paper

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

In the paper

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

In the paper

“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).”

In the paper

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

What the sources say

• Not checked yetcites [28] Michio, 2017, Leptin resistance and lipolysis of white adipose tissue: an implication to ectopic fat disposition and its consequences, J Atheroscler Thromb. source

In the paper

“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).”

What the sources say

• Not checked yetcites [16] Patel, 2018, Marrow adiposity and hematopoiesis in aging and obesity: exercise as an intervention, Curr Osteoporos Rep. source
• Not checked yetcites [17] Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat Rev Endocrinol. source

In the paper

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

What the sources say

• Not checked yetcites [32] Goya, 2015, Muscle loss and obesity: the health implications of sarcopenia and sarcopenic obesity, Proc Nutr Soc. source
• Not checked yetcites [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. source

In the paper

“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.”

What the sources say

• Not checked yetcites [39] Mootha, 2003, PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes, Nat Genet. source
• Not checked yetcites [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. source

In the paper

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

What the sources say

• Not checked yetcites [37] Nomura, 2007, Muscle strength is a marker of insulin resistance in patients with type 2 diabetes: a pilot study, Endocr J. source

In the paper

“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.”

What the sources say

• Not checked yetcites [27] Lim, 2015, Monocyte chemoattractant protein-1: a proinflammatory cytokine elevated in sarcopenic obesity, Clin Intervent Aging. source

In the paper

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

In the paper

“Therefore, weight generally increases in elderly people.”

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [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 source

In the paper

“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.”

What the sources say

• Not checked yetcites [21] Neels, 2005, Inflamed fat: what starts the fire?, J Clin Invest. source
• Not checked yetcites [22] Polyzos, 2016, Adipose tissue, obesity and nonalcoholic fatty liver disease, Minerva Endocrinologica. source
• Not checked yetcites [23] Kim, 2013, Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean sarcopenic obesity study, Clin Endocrinol. source
• Not checked yetcites [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. source
• Not checked yetcites [25] Wei, 2017, Critical residues and motifs for homodimerization of the first transmembrane domain of the plasma membrane glycoprotein CD36, J Biol Chem. source

In the paper

“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).”

What the sources say

• Not checked yetcites [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. source

In the paper

“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).”

What the sources say

• Not checked yetcites [45] Colaianni, 2017, Irisin and musculoskeletal health, Ann N Y Acad Sci. source

In the paper

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

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [38] Abbatecola, 2005, Insulin resistance and muscle strength in older persons, J Gerontol. source

In the paper

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

What the sources say

• Not checked yetcites [47] Choi, 2013, Sarcopenia and sarcopenic obesity, Endocrinol Metab (Seoul). source

In the paper

“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).”

What the sources say

• Not checked yetcites [75] Nolan, 2014, Lipotoxicity, β cell dysfunction, gestational diabetes, Cell Metab. source
• Not checked yetcites [76] Farrell, 2018, Pathogenesis of NASH: how metabolic complications of overnutrition favour lipotoxicity and pro-inflammatory fatty liver disease, Adv Exp Med Biol. source

In the paper

“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.”

What the sources say

• Not checked yetcites [52] Tian, 2016, Association of sarcopenic obesity with the risk of all-cause mortality: a meta-analysis of prospective cohort studies, Geriatr Gerontol Int. source

In the paper

“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).”

What the sources say

• Not checked yetcites [73] Mota, 2016, Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease, Metabolism. source
• Not checked yetcites [74] Las, 2020, Emerging roles of β-cell mitochondria in type-2-diabetes, Mol Aspects Med. source

In the paper

“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.”

In the paper

“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.”

What the sources say

• Not checked yetcites [63] Lee, 2012, Sarcopenic obesity is more closely associated with knee osteoarthritis than is nonsarcopenic obesity: a cross-sectional study, Arthritis Rheum. source
• Not checked yetcites [64] Misra, 2019, Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia, Arthritis Rheumatol. source

In the paper

“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).”

What the sources say

• Not checked yetcites [47] Choi, 2013, Sarcopenia and sarcopenic obesity, Endocrinol Metab (Seoul). source
• Not checked yetcites [51] Stenholm, 2008, Sarcopenic obesity: definition, cause and consequences, Curr Opin Clin Nutr Metab Care. source

In the paper

“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).”

What the sources say

• Not checked yetcites [45] Colaianni, 2017, Irisin and musculoskeletal health, Ann N Y Acad Sci. source
• Not checked yetcites [48] Weltman, 2001, Body composition, physical exercise, growth hormone and obesity, Eat Weight Disord.
• Not checked yetcites [49] Waters, 2008, Altered growth hormone, cortisol, and leptin secretion in healthy elderly persons with sarcopenia and mixed body composition phenotypes, J Gerontol. source

In the paper

“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).”

What the sources say

• Not checked yetcites [72] Zhang, 2018, Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link, Behav Brain Res. source

In the paper

“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).”

What the sources say

• Not checked yetcites [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. source

In the paper

“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).”

What the sources say

• Not checked yetcites [81] Rendra, 2019, Reactive oxygen species (ROS) in macrophage activation and function in diabetes, Immunobiology. source

In the paper

“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).”

What the sources say

• Not checked yetcites [78] Acharjee, 2013, Understanding type 1 diabetes: etiology and models, Can J Diabetes. source
• Not checked yetcites [79] DeFronzo, 2004, Pathogenesis of type 2 diabetes mellitus, Med Clin North Am. source

In the paper

“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).”

What the sources say

• Not checked yetcites [80] Blaser, 2016, TNF and ROS crosstalk in inflammation, Trends Cell Biol. source

In the paper

“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).”

What the sources say

• Not checked yetcites [82] Robertson, 2004, Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes, J Biol Chem. source
• Not checked yetcites [83] Panigrahy, 2017, Reactive oxygen species: sources, consequences and targeted therapy in type 2 diabetes, J Drug Target. source

In the paper

“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).”

What the sources say

• Not checked yetcites [58] Jeong-Hyeon, 2015, Relationship between sarcopenic obesity and cardiovascular disease risk as estimated by the framingham risk score, J Korean Med Sci. source

In the paper

“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).”

What the sources say

• Not checked yetcites [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. source
• Not checked yetcites [23] Kim, 2013, Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean sarcopenic obesity study, Clin Endocrinol. source
• Not checked yetcites [56] Kim, 2009, Prevalence of sarcopenia and sarcopenic obesity in Korean adults: the Korean sarcopenic obesity study, Int J Obes (Lond). source

In the paper

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

What the sources say

• Not checked yetcites [114] Leon, 2015, Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research, World J Diabetes. source

In the paper

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

What the sources say

• Not checked yetcites [118] Magruder, 2016, Diabetes and pancreatic cancer: chicken or egg? source

In the paper

“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).”

What the sources say

• Not checked yetcites [113] de Matheus, 2013, Impact of diabetes on cardiovascular disease: an update, Int J Hypertens. source

In the paper

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

What the sources say

• Not checked yetcites [94] Yaribeygi, 2019, Insulin resistance: review of the underlying molecular mechanisms, J Cell Physiol. source

In the paper

“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).”

What the sources say

• Not checked yetcites [107] Vinik, 2013, Diabetic neuropathy, Endocrinol Metab Clin North Am. source

In the paper

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

What the sources say

• Not checked yetcites [123] Kandimalla, 2017, Is alzheimer's disease a type 3 diabetes? a critical appraisal, Biochim Biophys Acta Mol Basis Dis. source

In the paper

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

What the sources say

• Not checked yetcites [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. source

In the paper

“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).”

What the sources say

• Not checked yetcites [100] Clarke, 2010, Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis, PLoS Med. source

In the paper

“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).”

What the sources say

• Not checked yetcites [72] Zhang, 2018, Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link, Behav Brain Res. source
• Not checked yetcites [96] Arneth, 2019, Metabolomics of type 1 and type 2 diabetes, Int J Mol Sci. source
• Not checked yetcites [97] Gao, 2011, GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease, Rev Neurosci. source

In the paper

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

What the sources say

• Not checked yetcites [120] Boyle, 2012, Diabetes and breast cancer risk: a meta-analysis, Br J Cancer. source

In the paper

“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).”

What the sources say

• Not checked yetcites [119] Larsson, 2005, Diabetes and colorectal cancer incidence in the cohort of Swedish men, Diabetes Care. source

In the paper

“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).”

What the sources say

• Not checked yetcites [125] Semenkovich, 2015, Depression in type 2 diabetes mellitus: prevalence, impact, and treatment, Drugs. source

In the paper

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

What the sources say

• Not checked yetcites [108] Feldman, 2019, Diabetic neuropathy, Nat Rev Dis Primers. source

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [107] Vinik, 2013, Diabetic neuropathy, Endocrinol Metab Clin North Am. source

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [105] Cheung, 2010, Diabetic retinopathy, Lancet. source
• Not checked yetcites [106] Sosna, 2016, History of diagnosis and therapy of diabetic retinopathy, Vnitr Lek.

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [31] Liao, 2019, Reactive oxygen species: a volatile driver of field cancerization and metastasis, Mol Cancer. source
• Not checked yetcites [116] Yang, 2019, Concentrated ambient PM2. 5 exposure affects mice sperm quality and testosterone biosynthesis, PeerJ. source
• Not checked yetcites [117] Stone, 2018, Obesity and cancer: existing and new hypotheses for a causal connection, EBioMedicine. source

In the paper

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

What the sources say

• Not checked yetcites [102] Henriques, 2015, Diabetic eye disease, Acta Med Port. source

In the paper

“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).”

In the paper

“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).”

What the sources say

• Not checked yetcites [85] Newsholme, 2016, Molecular mechanisms of ROS production and oxidative stress in diabetes, Biochem J. source

In the paper

“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).”

What the sources say

• Not checked yetcites [100] Clarke, 2010, Event rates, hospital utilization, and costs associated with major complications of diabetes: a multicountry comparative analysis, PLoS Med. source

In the paper

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

What the sources say

• Not checked yetcites [112] Henning, 2018, Type-2 diabetes mellitus and cardiovascular disease, Future Cardiol. source

In the paper

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

What the sources say

• Not checked yetcites [159] Papamichou, 2019, Dietary patterns and management of type 2 diabetes: a systematic review of randomised clinical trials, Nutr Metab Cardiovasc Dis. source

In the paper

“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).”

What the sources say

• Not checked yetcites [160] Díaz-López, 2015, Mediterranean diet, retinopathy, nephropathy, and microvascular diabetes complications: a post hoc analysis of a randomized trial, Diabetes Care. source

In the paper

“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.”

In the paper

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

In the paper

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

What the sources say

• Not checked yetcites [130] Ilich, 2016, Osteosarcopenic obesity syndrome: what is it and how can it be identified and diagnosed?, Curr Gerontol Geriatr Res. source
• Not checked yetcites [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. source

In the paper

“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).”

What the sources say

• Not checked yetcites [162] Barazzoni, 2018, Sarcopenic obesity: time to meet the challenge, Obesity Facts. source
• Not checked yetcites [163] Joseph, 2016, Beneficial effects of exercise on age-related mitochondrial dysfunction and oxidative stress in skeletal muscle, J Physiol. source
• Not checked yetcites [164] Mooren, 2015, Exercise autophagy, and apoptosis, Prog Mol Biol Transl Sci. source

In the paper

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

What the sources say

• Not checked yetcites [149] Deutz, 2014, Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group, Clin Nutr. source
• Not checked yetcites [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. source
• Not checked yetcites [151] Paddon-Jones, 2009, Dietary protein recommendations and the prevention of sarcopenia, Curr Opin Cin Nutr Metab Care. source

In the paper

“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).”

What the sources say

• Not checked yetcites [152] Sammarco, 2017, Evaluation of hypocaloric diet with protein supplementation in middle-aged sarcopenic obese women: a pilot study, Obesity Facts. source

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [67] 2015, (2) Classification and diagnosis of diabetes, Diabetes Care. source

In the paper

“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.”

What the sources say

• Not checked yetcites [67] 2015, (2) Classification and diagnosis of diabetes, Diabetes Care. source

In the paper

“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).”

What the sources say

• Not checked yetcites [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 source

In the paper

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

In the paper

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

What the sources say

• Not checked yetcites [129] Donini, 2020, Critical appraisal of definitions and diagnostic criteria for sarcopenic obesity based on a systematic review, Clin Nutr. source

In the paper

“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).”

What the sources say

• Not checked yetcites [165] Lombardo, 2019, Sarcopenic obesity: etiology and lifestyle therapy, Eur Rev Med Pharmacol Sci. source
• Not checked yetcites [166] Batsis, 2018, Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies, Nat Rev Endocrinol. source