Redox-inflammatory synergy in the metabolic syndrome

Metabolic syndrome (MetS) comprises interrelated disease states including obesity, insulin resistance and type 2 diabetes (T2DM), dyslipidemia, and hypertension. Essential to normal physiological function, and yet massively damaging in excess, oxidative stress and inflammation are pivotal common threads among the pathologies of MetS. Increasing evidence indicates that redox and inflammatory dysregulation parallels the syndrome's physiological, biochemical, and anthropometric features, leading many to consider the pro-oxidative, pro-inflammatory milieu an unofficial criterion in itself. Left unchecked, cross-promotion of oxidative stress and inflammation creates a feed-forward cycle that can initiate and advance disease progression. Such redox-inflammatory integration is evident in the pathogenesis of obesity, insulin resistance and T2DM, atherogenic dyslipidemia, and hypertension, and is thus hypothesized to be the “common soil” from which they develop. The present review highlights the synergistic contributions of redox-inflammatory processes to each of the components of the MetS.

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“Obesity and Insulin Resistance” Is the Component of the Metabolic Syndrome Most Strongly Associated with Oxidative Stress

Antioxidants ◽

10.3390/antiox11010079 ◽

2021 ◽

Vol 11 (1) ◽

pp. 79

Author(s):

Grzegorz K. Jakubiak ◽

Kamila Osadnik ◽

Mateusz Lejawa ◽

Tadeusz Osadnik ◽

Marcin Goławski ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Blood Pressure ◽

Metabolic Syndrome ◽

Young Adults ◽

Anthropometric Parameters ◽

The Metabolic Syndrome ◽

Total Antioxidant ◽

History Of

Metabolic syndrome (MS) is not a homogeneous entity, but this term refers to the coexistence of factors that increase the risk for the development of type 2 diabetes and cardiovascular disease. There are different versions of the criteria for the diagnosis of MS, which makes the population of patients diagnosed with MS heterogeneous. Research to date shows that MS is associated with oxidative stress (OS), but it is unclear which MS component is most strongly associated with OS. The purpose of the study was to investigate the relationship between the parameters of OS and the presence of individual elements of MS in young adults, as well as to identify the components of MS by means of principal components analysis (PCA) and to investigate how the parameters of OS correlate with the presence of individual components. The study included 724 young adults with or without a family history of coronary heart disease (population of the MAGNETIC study). Blood samples were taken from the participants of the study to determine peripheral blood counts, biochemical parameters, and selected parameters of OS. In addition, blood pressure and anthropometric parameters were measured. In subjects with MS, significantly lower activity of superoxide dismutase (SOD), copper- and zinc-containing SOD (CuZnSOD), and manganese-containing SOD (MnSOD) were found, along with significantly higher total antioxidant capacity (TAC) and significantly lower concentration of thiol groups per gram of protein (PSH). We identified three components of MS by means of PCA: “Obesity and insulin resistance”, “Dyslipidemia”, and “Blood pressure”, and showed the component “Obesity and insulin resistance” to have the strongest relationship with OS. In conclusion, we documented significant differences in some parameters of OS between young adults with and without MS. We showed that “Obesity and insulin resistance” is the most important component of MS in terms of relationship with OS.

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Metabolic Syndrome During Menopause

Current Vascular Pharmacology ◽

10.2174/1570161116666180904094149 ◽

2019 ◽

Vol 17 (6) ◽

pp. 595-603 ◽

Cited By ~ 4

Author(s):

Sezcan Mumusoglu ◽

Bulent Okan Yildiz

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Central Obesity ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Natural Menopause ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

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Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging

Biology ◽

10.3390/biology10040253 ◽

2021 ◽

Vol 10 (4) ◽

pp. 253

Author(s):

Graciela Gavia-García ◽

Juana Rosado-Pérez ◽

Taide Laurita Arista-Ugalde ◽

Itzen Aguiñiga-Sánchez ◽

Edelmiro Santiago-Osorio ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Telomere Length ◽

Scientific Evidence ◽

Telomeric Dna ◽

Biochemical Alterations ◽

The Metabolic Syndrome ◽

Age Related ◽

And Function

A great amount of scientific evidence supports that Oxidative Stress (OxS) can contribute to telomeric attrition and also plays an important role in the development of certain age-related diseases, among them the metabolic syndrome (MetS), which is characterised by clinical and biochemical alterations such as obesity, dyslipidaemia, arterial hypertension, hyperglycaemia, and insulin resistance, all of which are considered as risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which are associated in turn with an increase of OxS. In this sense, we review scientific evidence that supports the association between OxS with telomere length (TL) dynamics and the relationship with MetS components in aging. It was analysed whether each MetS component affects the telomere length separately or if they all affect it together. Likewise, this review provides a summary of the structure and function of telomeres and telomerase, the mechanisms of telomeric DNA repair, how telomere length may influence the fate of cells or be linked to inflammation and the development of age-related diseases, and finally, how the lifestyles can affect telomere length.

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Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001425 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001425

Author(s):

Cornelia Then ◽

Christina Gar ◽

Barbara Thorand ◽

Cornelia Huth ◽

Holger Then ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Waist Circumference ◽

Vascular Complications ◽

Model Assessment ◽

Incident Type ◽

The Metabolic Syndrome ◽

Incident Type 2 Diabetes

IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study (2006–2008)/FF4 study (2013–2014).Research design and methodsThe analyses included 1514 participants of the KORA F4 study at baseline and 1132 participants of the KORA FF4 study after a median follow-up time of 6.6 years. All-cause and cardiovascular mortality as well as cardiovascular events were analyzed after a median time of 9.1 and 8.6 years, respectively. The association of PIR with T2D, renal and cardiovascular characteristics and mortality were assessed using logistic regression models. Linear regression analyses were used to assess the association of PIR with components of the metabolic syndrome.ResultsAfter adjustment for sex, age, body mass index (BMI), and physical activity, PIR was associated with prevalent (OR: 2.24; 95% CI 1.81 to 2.77; p<0.001) and incident T2D (OR: 1.66; 95% CI 1.26 to 2.17; p<0.001). PIR was associated with fasting glucose (β per SD: 0.11±0.02; p<0.001) and HbA1c (β: 0.21±0.02; p<0.001). However, PIR was not positively associated with other components of the metabolic syndrome and was even inversely associated with waist circumference (β: −0.22±0.03; p<0.001), BMI (β: −0.11±0.03; p<0.001) and homeostatic model assessment of insulin resistance (β: −0.22±0.02; p<0.001). PIR was not significantly associated with the intima-media thickness (IMT), decline of kidney function, incident albuminuria, myocardial infarction, stroke, cardiovascular or all-cause mortality.ConclusionsIn the KORA F4/FF4 cohort, PIR was positively associated with prevalent and incident T2D, but inversely associated with waist circumference, BMI and insulin resistance, suggesting that PIR might serve as a biomarker for T2D risk independently of the metabolic syndrome, but not for microvascular or macrovascular complications.

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A szexuális funkciózavar és a metabolikus szindróma kapcsolata

Orvosi Hetilap ◽

10.1556/650.2019.31235 ◽

2019 ◽

Vol 160 (3) ◽

pp. 98-103 ◽

Cited By ~ 3

Author(s):

Márta Zsoldos ◽

Attila Pajor ◽

Henriette Pusztafalvi

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Sexual Dysfunction ◽

The Metabolic Syndrome ◽

Atherogenic Lipid Profile ◽

Arousal Response ◽

Atherogenic Lipid

Abstract: The prevalence of the metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, obesity and depression have increased during the recent years. As the sexual dysfunction is also frequent, we aimed to search for the associations between sexual dysfunction and the metabolic syndrome and its components, respectively, by reviewing the literature. The clinical and biochemical components of the metabolic syndrome included cardiovascular disease, type 2 diabetes mellitus, visceral obesity and depression, furthermore, insulin resistance, atherogenic lipid profile, hypogonadism, chronic systemic inflammation and endothelial dysfunction were all demonstrated to affect adversely the sexual function. The dysfunction of the sexual arousal response shows a strong association in men and a milder one in women with the cardiovascular diseases and depression. Sexual function in diabetes mellitus is mostly impaired by microvascular injury, polyneuropathy and autonomic neuropathy. Erectile dysfunction and disorder of the female sexual arousal response and the orgasm, respectively, are associated with insulin resistance, atherogenic lipid profile and systemic inflammatory condition in overweight or obese patients. Sexual dysfunction particularly in men can be an early sign of the severe complications of metabolic syndrome. The pathogenetic link between the metabolic syndrome and the sexual dysfunction seems to be the insulin resistance. Both metabolic syndrome and sexual dysfunction can be restored by altering the lifestyle. Orv Hetil. 2019; 160(3): 98–103.

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Insulin Resistance is the Best Predictor of the Metabolic Syndrome in Subjects With a First-Degree Relative With Type 2 Diabetes

Obesity ◽

10.1038/oby.2010.77 ◽

2010 ◽

Vol 18 (9) ◽

pp. 1781-1787 ◽

Cited By ~ 19

Author(s):

Kristina M. Utzschneider ◽

Anne Van de Lagemaat ◽

Mirjam V. Faulenbach ◽

Julia H. Goedecke ◽

Darcy B. Carr ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Degree Relative ◽

The Metabolic Syndrome

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Galantamine alleviates oxidative stress alongside anti-inflammatory and cardio-metabolic effects in subjects with the metabolic syndrome in a randomized trial

10.1101/2019.12.30.19016105 ◽

2020 ◽

Author(s):

Carine Teles Sangaleti ◽

Keyla Yukari Katayama ◽

Kátia De Angelis ◽

Tércio Lemos de Moraes ◽

Amanda Aparecida Araújo ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Autonomic Regulation ◽

Metabolic Effects ◽

Antioxidant Enzyme Activities ◽

Low Grade ◽

The Metabolic Syndrome ◽

Inflammatory State ◽

Anti Inflammatory

AbstractBackgroundThe metabolic syndrome (MetS) is an obesity-driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA-approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.MethodsThe effects of galantamine treatment, 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n=22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.ResultsGalantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, [95% CI 0.39 to 2.92], P=0.004) and CAT (+0.93 nmol/mg, [95% CI 0.34 to 1.51], P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, -5.45 pmol/mg, [95% CI -10.97 to 0.067], P=0.053) and systemic nitrite levels (-0.05 nit/mg protein, [95% CI -0.21 to 0.10], P=0.038) compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.ConclusionLow-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.

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Pericytopathy: Oxidative Stress and Impaired Cellular Longevity in the Pancreas and Skeletal Muscle in Metabolic Syndrome and Type 2 Diabetes

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.3.5.13653 ◽

2010 ◽

Vol 3 (5) ◽

pp. 290-303 ◽

Cited By ~ 25

Author(s):

Melvin R. Hayden ◽

Ying Yang ◽

Javad Habibi ◽

Sarika V. Bagree ◽

James R. Sowers

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Metabolic Syndrome ◽

Screening Method ◽

Lifestyle Changes ◽

Pancreatic Stellate Cells ◽

Rodent Models ◽

The Metabolic Syndrome

The pericyte's role has been extensively studied in retinal tissues of diabetic retinopathy; however, little is known regarding its role in such tissues as the pancreas and skeletal muscle. This supportive microvascular mural cell plays an important and novel role in cellular and extracellular matrix remodeling in the pancreas and skeletal muscle of young rodent models representing the metabolic syndrome and type 2 diabetes mellitus (T2DM). Transmission electron microscopy can be used to evaluate these tissues from young rodent models of insulin resistance and T2DM, including the transgenic Ren2 rat, db/db obese insulin resistantߞT2DM mouse, and human islet amyloid polypeptide (HIP) rat model of T2DM. With this method, the earliest pancreatic remodeling change was widening of the islet exocrine interface and pericyte hypercellularity, followed by pericyte differentiation into islet and pancreatic stellate cells with early fibrosis involving the islet exocrine interface and interlobular interstitium. In skeletal muscle there was a unique endothelial capillary connectivity via elongated longitudinal pericyte processes in addition to pericyte to pericyte and pericyte to myocyte cellcell connections allowing for paracrine communication. Initial pericyte activation due to moderate oxidative stress signaling may be followed by hyperplasia, migration and differentiation into adult mesenchymal cells. Continued robust oxidative stress may induce pericyte apoptosis and impaired cellular longevity. Circulating antipericyte autoantibodies have recently been characterized, and may provide a screening method to detect those patients who are developing pericyte loss and are at greater risk for the development of complications of T2DM due to pericytopathy and rarefaction. Once detected, these patients may be offered more aggressive treatment strategies such as early pharmacotherapy in addition to lifestyle changes targeted to maintaining pericyte integrity. In conclusion, we have provided a review of current knowledge regarding the pericyte and novel ultrastructural findings regarding its role in metabolic syndrome and T2DM.

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Fetal origins of insulin resistance and obesity

Proceedings of The Nutrition Society ◽

10.1079/pns2005417 ◽

2005 ◽

Vol 64 (2) ◽

pp. 143-151 ◽

Cited By ~ 116

Author(s):

Claire J. Stocker ◽

Jonathan R. S. Arch ◽

Michael A. Cawthorne

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

G Protein ◽

High Fat Diet ◽

High Fat ◽

Fetal Origins ◽

Thrifty Phenotype ◽

The Metabolic Syndrome ◽

Increased Susceptibility

A number of epidemiological studies worldwide have demonstrated a relationship between poor early growth and an increased susceptibility to insulin resistance, visceral obesity, type 2 diabetes and other features of the metabolic syndrome in adulthood. However, the mechanistic basis of this relationship and the relative roles of genes and the environment remain a subject of debate. The ‘thrifty phenotype’ hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. The maternal reduced-protein rat model has been used to examine the importance of the maternal environment in determining susceptibility to adult disease. Pregnant and lactating rat dams are fed a diet containing 80 g protein/kg as compared with 200 g protein/kg, which leads to growth restriction in utero. Offspring of low-protein dams have increased susceptibility to diabetes, insulin resistance and hypertension when fed a palatable high-fat diet that promotes obesity. Administration of leptin during pregnancy and lactation to these protein-restricted dams produces offspring that have increased metabolic rate and do not become obese or insulin resistant when fed on a high-fat diet. Increased glucocorticoid exposure, particularly during late gestation, has been linked with insulin resistance in adulthood. High levels of fetal glucocorticoids may result from a decreased activity of placental 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2, which normally protects the fetus from high maternal glucocorticoid levels. Leptin administration to protein-restricted dams inhibits the suppression of 11β-HSD-2 and may be one mechanism by which the metabolic syndrome is prevented.

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