Molecular mechanisms for myocardial mitochondrial dysfunction in the metabolic syndrome

The metabolic syndrome represents a cluster of abnormalities, including obesity, insulin resistance, dyslipidaemia and Type 2 diabetes, that increases the risk of developing cardiovascular diseases, such as coronary artery disease and heart failure. The heart failure risk is increased even after adjusting for coronary artery disease and hypertension, and evidence is emerging that changes in cardiac energy metabolism might contribute to the development of contractile dysfunction. Recent findings suggest that myocardial mitochondrial dysfunction may play an important role in the pathogenesis of cardiac contractile dysfunction in obesity, insulin resistance and Type 2 diabetes. This review will discuss potential molecular mechanisms for these mitochondrial abnormalities.

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Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

Diabetologia ◽

10.1007/s00125-007-0743-8 ◽

2007 ◽

Vol 50 (9) ◽

pp. 1930-1937 ◽

Cited By ~ 118

Author(s):

M. von Eynatten ◽

P. M. Lepper ◽

D. Liu ◽

K. Lang ◽

M. Baumann ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Metabolic Syndrome ◽

Coronary Artery ◽

Retinol Binding Protein ◽

Retinol Binding Protein 4 ◽

The Metabolic Syndrome ◽

Artery Disease

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The metabolic syndrome phenotype is associated with raised circulating Big endothelin-1 independently of coronary artery disease in type 2 diabetes

Diabetes & Metabolic Syndrome Clinical Research & Reviews ◽

10.1016/j.dsx.2007.09.001 ◽

2007 ◽

Vol 1 (4) ◽

pp. 229-237 ◽

Cited By ~ 8

Author(s):

Michel P. Hermans ◽

Sylvie A. Ahn ◽

Damien Gruson ◽

Michel F. Rousseau

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Metabolic Syndrome ◽

Coronary Artery ◽

Endothelin 1 ◽

The Metabolic Syndrome ◽

Artery Disease

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Fetuin-A in patients with metabolic syndrome

Current Issues in Pharmacy and Medical Sciences ◽

10.12923/j.2084-980x/26.3/a.14 ◽

2013 ◽

Vol 26 (3) ◽

pp. 305-308

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Coronary Artery Disease ◽

Metabolic Syndrome ◽

Coronary Artery ◽

Ldl Cholesterol ◽

Fetuin A ◽

Artery Disease

Metabolic syndrome is a common disorder the prevalence of which is estimated to be about 20% in Polish adult population. Abdominal obesity and insulin resistance are important pathogenetic factors. Metabolic syndrome plays a role as a risk factor for type 2 diabetes and cardiovascular disease. Fetuin-A is a multifunctional plasma glycoprotein. It is a physiological inhibitor of insulin receptor tyrosine kinase and thus associated with insulin resistance, metabolic syndrome and an increased risk for type 2 diabetes. The study was conducted in 62 patients with metabolic syndrome (34F and 28M) aged 35-83. In 47 persons type 2 diabetes was a component of metabolic syndrome, 62% of diabetics had coronary artery disease as a macrovascular complication. Determinations of biochemical parameters and anthropometric measurements were performed in the studied group. We analysed a relationship between serum fetuin-A concentration and components of metabolic syndrome and total cholesterol, LDL-cholesterol, HbA1C, BMI as well. Diabetics had lower fetuin-A concentrations than patients without diabetes (0.550 g/l vs 0.600 g/l). Fetuin-A levels in patients with diabetes and coronary artery disease were significantly lower (0.535 g/l) than in those without macrovascular complications (0.590 g/l) (Z=1.969; p=0.048). Furthermore the correlation between fetuin-A serum concentration and fasting plasma glucose, LDL-cholesterol and triglycerides levels were observed. Patients with higher fasting glucose had lower fetuin-A levels. However, fetuin-A concentration was positive correlated with LDL-cholesterol and triglycerides levels. No association between fetuin-A and waist circumference, blood pressure, HDL-cholesterol, HbA1C and BMI were found. In summary, serum fetuin-A level has a correlation with some components of metabolic syndrome. We concluded that fetuin-A could be used not only as a marker, but also plays some role in pathogenesis of metabolic syndrome, type 2 diabetes and higher risk of cardiovascular disease.

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Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease

Cardiovascular Diabetology ◽

10.1186/1475-2840-10-80 ◽

2011 ◽

Vol 10 (1) ◽

pp. 80 ◽

Cited By ~ 28

Author(s):

Duncan J Campbell ◽

Jithendra B Somaratne ◽

Alicia J Jenkins ◽

David L Prior ◽

Michael Yii ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Metabolic Syndrome ◽

Coronary Artery ◽

The Metabolic Syndrome ◽

Myocardial Structure ◽

Artery Disease

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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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Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type 2 diabetes mellitus: Sub-study of a randomized control trial

Diabetes and Vascular Disease Research ◽

10.1177/1479164119836922 ◽

2019 ◽

Vol 16 (4) ◽

pp. 360-368

Author(s):

Hani Zaidi ◽

Rune Byrkjeland ◽

Ida U Njerve ◽

Sissel Åkra ◽

Svein Solheim ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Type 2 Diabetes Mellitus ◽

Adipose Tissue ◽

Coronary Artery ◽

Exercise Training ◽

Artery Disease

Background: Adipose tissue produces pro-inflammatory mediators involved in the atherosclerotic process. We investigated whether 12-month exercise training in patients with type 2 diabetes mellitus and coronary artery disease would reduce circulating levels and genetic expression of mediators in the interleukin-18, Caspase-1 and NLR pyrin domain containing 3 pathways. Correlations to glucometabolic variables; fasting glucose, HbA1c, duration of diabetes, insulin, C-peptide, insulin resistance (measured by homeostatic model assessment indexes – insulin resistance) and body mass index at baseline were further assessed. Methods: 137 patients (aged 41–81 years, 17.2% female participants) were included and randomized to a 12-month exercise programme or to a control group. Fasting blood and adipose tissue samples were taken at inclusion and after 12 months. Results: No statistically significant difference in changes of any variable between the intervention and the control group was found. At baseline, a positive correlation between insulin and homeostatic model assessment indexes – insulin resistance, interleukin-18 expression in adipose tissue and an inverse correlation between some glucometabolic variables and leukocyte expression of NLR pyrin domain containing 3 and Caspase-1 were observed. Conclusion: No significant effects of long-term exercise training were observed on the inflammasome-related mediators in our patients with combined coronary artery disease and type 2 diabetes mellitus. The observed correlations may indicate a pro-inflammatory state in adipose tissue by overweight and a compensatory downregulation of these mediators in circulating leucocytes.

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Potential Biomarkers of Insulin Resistance and Atherosclerosis in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

International Journal of Endocrinology ◽

10.1155/2013/698567 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 38

Author(s):

Sharifah Intan Qhadijah Syed Ikmal ◽

Hasniza Zaman Huri ◽

Shireene Ratna Vethakkan ◽

Wan Azman Wan Ahmad

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Type 2 Diabetes Mellitus ◽

Coronary Artery ◽

Endothelial Dysfunction ◽

Biological Marker ◽

Artery Disease

Type 2 diabetes mellitus patients with coronary artery disease have become a major public health concern. The occurrence of insulin resistance accompanied with endothelial dysfunction worsens the state of atherosclerosis in type 2 diabetes mellitus patients. The combination of insulin resistance and endothelial dysfunction leads to coronary artery disease and ischemic heart disease complications. A recognized biological marker, high-sensitivity C-reactive protein, has been used widely to assess the progression of atherosclerosis and inflammation. Along with coronary arterial damage and inflammatory processes, high-sensitivity C-reactive protein is considered as an essential atherosclerosis marker in patients with cardiovascular disease, but not as an insulin resistance marker in type 2 diabetes mellitus patients. A new biological marker that can act as a reliable indicator of both the exact state of insulin resistance and atherosclerosis is required to facilitate optimal health management of diabetic patients. Malfunctioning of insulin mechanism and endothelial dysfunction leads to innate immune activation and released several biological markers into circulation. This review examines potential biological markers, YKL-40, alpha-hydroxybutyrate, soluble CD36, leptin, resistin, interleukin-18, retinol binding protein-4, and chemerin, as they may play significant roles in insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease.

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