The Impact of Insulin Resistance and Inflammation on the Association Between Sarcopenic Obesity and Physical Functioning

The prevalence of sarcopenic obesity is increasing worldwide, particularly amongst aging populations. Insulin resistance is the core mechanism of sarcopenic obesity and is also associated with variable cardiometabolic diseases such as cardiovascular disease, type 2 diabetes mellitus, and non-alcoholic fatty liver disease. Fat accumulation in muscle tissue promotes a proinflammatory cascade and oxidative stress, leading to mitochondrial dysfunction, impaired insulin signaling, and muscle atrophy. To compound the problem, decreased muscle mass aggravates insulin resistance. In addition, the crosstalk between myokines and adipokines leads to negative feedback, which in turn aggravates sarcopenic obesity and insulin resistance. In this review, we focus on the molecular mechanisms linking sarcopenic obesity and insulin resistance with various biological pathways. We also discuss the impact and mechanism of sarcopenic obesity and insulin resistance on cardiometabolic disease.

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Certain biological factors that may represent insulin resistance are associated with a decline in physical functioning

PsycEXTRA Dataset ◽

10.1037/e556332006-012 ◽

2004 ◽

Keyword(s):

Insulin Resistance ◽

Physical Functioning ◽

Biological Factors

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The impact of testosterone and the androgen receptor (AR) CAG length polymorphism on insulin resistance in men

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2007-972381 ◽

2007 ◽

Vol 115 (S 1) ◽

Author(s):

M Möhlig ◽

J Spranger ◽

MO Weickert ◽

AM Arafat ◽

AFH Pfeiffer ◽

...

Keyword(s):

Insulin Resistance ◽

Androgen Receptor ◽

Length Polymorphism ◽

The Impact

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Insulin Therapy in Pregnancy Hypertensive Diseases and its Effect on the Offspring and Mother Later in Life

Current Vascular Pharmacology ◽

10.2174/1570161117666181114125109 ◽

2019 ◽

Vol 17 (5) ◽

pp. 455-464 ◽

Cited By ~ 8

Author(s):

Alfonso Mate ◽

Antonio J. Blanca ◽

Rocío Salsoso ◽

Fernando Toledo ◽

Pablo Stiefel ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Insulin Therapy ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Insulin Resistant ◽

Hypertensive Disorders ◽

The Impact ◽

In Pregnancy

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.

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POS0291 THE IMPACT OF DRUG INDUCED AND OTHER RHEUMATIC MUSCULOSKELETAL DISORDERS (MD) ON THE QUALITY OF LIFE (QOL) OF CANCER PATIENTS RECEIVED ANTICANCER DRUG TREATMENT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2286 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 371.1-371

Author(s):

A. Koltakova ◽

A. Lila ◽

L. P. Ananyeva ◽

A. Fedenko

Keyword(s):

Drug Treatment ◽

Cancer Patients ◽

Anticancer Drug ◽

Physical Functioning ◽

Role Functioning ◽

Drug Induced ◽

Significant Difference ◽

Eortc Qlq C30 ◽

Eortc Qlq ◽

The Impact

Background:Pts with cancer may have MD that can be caused by neoplastic/paraneoplastic disease, rheumatic diseases or be induced by anticancer drug treatment. There is no data about MD influence on the QoL of cancer patients. The EORTC QoL questionnaire (QLQ)-C30 is a valid questionnaire designed to assess different aspects (Global health (GH), Functional (FS) and symptoms (SS) scales) that define the QoL of cancer patients [1].Objectives:The objective of the study was to assess the impact of drug induced and other types of MD on the QoL of cancer patients that received anticancer drug treatment by using of EORTC QLQ-C30 v3.0.Methods:The sampling of 123 pts (M/F – 40/83; mean age 54.4±12.8) with breast (32,5%), gastrointestinal (17%), ovary (8%), lung (7%) and other cancer was observed by rheumatologist in the oncology outpatient clinic. All pts received anticancer drug treatment: chemotherapy (104 pts), target therapy (16 pts) checkpoint-inhibitors (14 pts), hormone therapy (13 pts) in different combinations. 102(82.9%) of 123pts had MD include arthritis (12 pts), synovitis (5 pts), arthralgia (66 pts), periarthritis (34 pts), osteodynia (13 pts). There were 58 pts (group 1; M/F – 14/44; mean age 52.5±12.2) with anticancer drug treatment induced MD and 44 pts (group 2; M/F – 16/27; mean age 57.6±13.5) with other type of MD include 26 pts with skeletal metastasis. The were 21 pts (group 3; M/F – 10/11; mean age 52.9±11.1) without MD. All pts fulfilled EORTC QLQ-C30 v3.0 (tab.1).Table 1.The median [Q1;Q3] of results of GH, SS and SS of EORTC QLQ-C30ScaleSubscaleGroup1Group2Group3GH58.3[50;58]58.3[41.7;83.3]50[50;66.7]FS*Physical functioning73.3[60;86.7]73.3[66.7;86.7]86.7[80;93]Role functioning66.7[66.7;100]83.3[50;100]100[83;100]Emotional functioning83.3[66.7;100]75[66.7;91.7]91.6[83.3;100]Social functioning83.3[66.7;100]83.3[50;100]100[83.3;100]SS*Pain33.3[0;50]16.7[0;33.3]0[0;16.7]*There are only the scores that had got a statistical difference between the groups.Kruskal-Wallis H and post-hoc (Dwass-Steel-Critchlow-Fligner (DSCF) pairwise comparisons) tests for data analysis were performed.Results:A Kruskal-Wallis H test has shown a statistically significant difference in physical (χ2(2)=7.54; p=0.023), role (χ2(2)=9.87; p=0.007), emotion (χ2(2)=7.69; p=0.021) functioning and pain (χ2(2)=8.44; p=0.015) scores between the different groups. A post-hoc test with DSCF pairwise comparisons of median has shown a statistically significant difference between 1 and 3 groups (W=3.904; p=0.016) for physical functioning, between 2 and 3 groups (W=3.35; p=0.004) for role functioning, between 2 and 3 groups (W=4.03; p=0.012) for emotional functioning, between 1 and 3 groups (W=-3.97; p=0.014) for pain scale.Conclusion:The study has shown that MD associated with anticancer drug treatment adversely affected the QoL of cancer patients received anticancer drug treatment by reducing a physical functioning and by increasing pain scores. Presence of other types of MD adversely affect the QoL by reducing emotional and role functioning.References:[1]Aaronson NK,et al.The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst.1993;85(5):365-376. doi:10.1093/jnci/85.5.365Disclosure of Interests:None declared

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The Impact of Differentiation on Cytotoxicity and Insulin Sensitivity in Streptozotocin Treated SH-SY5Y Cells

Neurochemical Research ◽

10.1007/s11064-021-03269-2 ◽

2021 ◽

Vol 46 (6) ◽

pp. 1350-1358

Author(s):

Fruzsina Bagaméry ◽

Kamilla Varga ◽

Kitti Kecsmár ◽

István Vincze ◽

Éva Szökő ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Insulin Signaling ◽

Glycogen Synthase ◽

Insulin Metabolism ◽

Relative Significance ◽

Differentiated Cells ◽

Mature Neuron ◽

The Right ◽

The Impact

AbstractRecently neuronal insulin resistance was suggested playing a role in Alzheimer’s disease. Streptozotocin (STZ) is commonly used to induce impairment in insulin metabolism. In our previous work on undifferentiated SH-SY5Y cells the compound exerted cytotoxicity without altering insulin sensitivity. Nevertheless, differentiation of the cells to a more mature neuron-like phenotype may considerably affect the significance of insulin signaling and its sensitivity to STZ. We aimed at studying the influence of STZ treatment on insulin signaling in SH-SY5Y cells differentiated by retinoic acid (RA). Cytotoxicity of STZ or low serum (LS) condition and protective effect of insulin were compared in RA differentiated SH-SY5Y cells. The effect of insulin and an incretin analogue, exendin-4 on insulin signaling was also examined by assessing glycogen synthase kinase-3 (GSK-3) phosphorylation. STZ was found less cytotoxic in the differentiated cells compared to our previous results in undifferentiated SH-SY5Y cells. The cytoprotective concentration of insulin was similar in the STZ and LS groups. However, the right-shifted concentration–response curve of insulin induced GSK-3 phosphorylation in STZ-treated differentiated cells is suggestive of the development of insulin resistance that was further confirmed by the insulin potentiating effect of exendin-4. Differentiation reduced the sensitivity of SH-SY5Y cells for the non-specific cytotoxicity of STZ and enhanced the relative significance of development of insulin resistance. The differentiated cells thus serve as a better model for studying the role of insulin signaling in neuronal survival. However, direct cytotoxicity of STZ also contributes to the cell death.

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The Role of Visceral Obesity, Sarcopenia and Sarcopenic Obesity on Surgical Outcomes After Liver Resections for Colorectal Metastases

World Journal of Surgery ◽

10.1007/s00268-021-06073-9 ◽

2021 ◽

Author(s):

M. Runkel ◽

T. D. Diallo ◽

S. A. Lang ◽

F. Bamberg ◽

M. Benndorf ◽

...

Keyword(s):

Risk Factors ◽

Postoperative Complications ◽

Visceral Obesity ◽

The Body ◽

Postoperative Outcomes ◽

Sarcopenic Obesity ◽

Colorectal Metastases ◽

Complication Rates ◽

The Impact ◽

Body Compositions

Abstract Background The impact of body compositions on surgical results is controversially discussed. This study examined whether visceral obesity, sarcopenia or sarcopenic obesity influence the outcome after hepatic resections of synchronous colorectal liver metastases. Methods Ninety-four consecutive patients with primary hepatic resections of synchronous colorectal metastases were identified from a single center database between January 2013 and August 2018. Patient characteristics and 30-day morbidity were retrospectively analyzed. Body fat and skeletal muscle were calculated by planimetry from single-slice CT images at the level of L3. Results Fifty-nine patients (62.8%) underwent minor hepatectomies, and 35 patients underwent major resections (37.2%). Postoperative complications occurred in 60 patients (62.8%) including 35 patients with major complications (Clavien–Dindo grade III–V). The mortality was nil at 30 days and 2.1% at 90 days. The body mass index showed no influence on postoperative outcomes (p = 1.0). Visceral obesity was found in 66 patients (70.2%) and was significantly associated with overall and major complication rates (p = .002, p = .012, respectively). Sarcopenia was observed in 34 patients (36.2%) without a significant impact on morbidity (p = .461), however, with longer hospital stay. Sarcopenic obesity was found in 18 patients (19.1%) and was significantly associated with postoperative complications (p = .014). Visceral obesity, sarcopenia and sarcopenic obesity were all identified as significant risk factors for overall postoperative complications. Conclusion Visceral obesity, sarcopenic obesity and sarcopenia are independent risk factors for overall complications after resections of CRLM. Early recognition of extremes in body compositions could prompt to perioperative interventions and thus improve postoperative outcomes.

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Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages

Mediators of Inflammation ◽

10.1155/2010/219583 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 51

Author(s):

Lucía Fuentes ◽

Tamás Rőszer ◽

Mercedes Ricote

Keyword(s):

Insulin Resistance ◽

Nuclear Receptor ◽

Cytokine Production ◽

Current Knowledge ◽

Liver Steatosis ◽

Visceral Obesity ◽

M2 Macrophage ◽

Low Grade ◽

The Impact

Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.

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Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

Hormone and Metabolic Research ◽

10.1055/a-0594-2404 ◽

2018 ◽

Vol 50 (05) ◽

pp. 408-413 ◽

Cited By ~ 1

Author(s):

Sema Dogansen ◽

Gulsah Yalin ◽

Seher Tanrikulu ◽

Sema Yarman

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Glucose Metabolism Disorders ◽

Insulin Resistant ◽

Normal Glucose ◽

Resistant Group ◽

The Impact

AbstractIn this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.

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