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  1. Article ; Online: Obesity, insulin resistance, Type 2 diabetes and free fatty acids.

    Boden, Guenther

    Expert review of endocrinology & metabolism

    2018  Volume 1, Issue 4, Page(s) 499–505

    Abstract: High levels of free fatty acids have emerged as a major link between obesity and insulin resistance/Type 2 diabetes. In pancreatic β cells, free fatty acids potentiate glucose-stimulated insulin secretion precisely to the extent needed to compensate for ... ...

    Abstract High levels of free fatty acids have emerged as a major link between obesity and insulin resistance/Type 2 diabetes. In pancreatic β cells, free fatty acids potentiate glucose-stimulated insulin secretion precisely to the extent needed to compensate for the free fatty acid-induced insulin resistance. It is postulated that this prevents the development of Type 2 diabetes mellitus in the majority of obese, insulin-resistant individuals who have free fatty acid-mediated insulin resistance. In individuals with inherited defects of β-cell function (prediabetics), this compensation fails and hyperglycemia develops. Elevated levels of free fatty acids also activate the proinflammatory and proatherogenic nuclear factor κB pathway. Thus, elevated plasma levels of free fatty acid in obese people can produce a low-grade inflammatory state, which may contribute to accelerated atherosclerosis (coronary artery disease, strokes and peripheral arterial disease) and to nonalcoholic steatohepatitis; these conditions are increased in obesity.
    Language English
    Publishing date 2018-10-05
    Publishing country England
    Document type Journal Article
    ISSN 1744-8417
    ISSN (online) 1744-8417
    DOI 10.1586/17446651.1.4.499
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Does inhibition of β-cell proliferation by free fatty acid in mice explain the progressive failure of insulin secretion in type 2 diabetes?

    Boden, Guenther

    Diabetes

    2012  Volume 61, Issue 3, Page(s) 560–561

    MeSH term(s) Animals ; Cell Proliferation/drug effects ; Cyclin-Dependent Kinase Inhibitor p16/physiology ; Cyclin-Dependent Kinase Inhibitor p18/physiology ; Fatty Acids, Nonesterified/physiology ; Glucose/pharmacology ; Insulin-Secreting Cells/physiology ; Male
    Chemical Substances Cyclin-Dependent Kinase Inhibitor p16 ; Cyclin-Dependent Kinase Inhibitor p18 ; Fatty Acids, Nonesterified ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2012-02-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db11-1613
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Obesity, insulin resistance and free fatty acids.

    Boden, Guenther

    Current opinion in endocrinology, diabetes, and obesity

    2011  Volume 18, Issue 2, Page(s) 139–143

    Abstract: Purpose of review: To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people.: Recent findings: Elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. ...

    Abstract Purpose of review: To describe the role of free fatty acid (FFA) as a cause for insulin resistance in obese people.
    Recent findings: Elevated plasma FFA levels can account for a large part of insulin resistance in obese patients with type 2 diabetes. Insulin resistance is clinically important because it is closely associated with several diseases including type 2 diabetes, hypertension, dyslipidemia and abnormalities in blood coagulation and fibrinolysis. These disorders are all independent risk factors for cardiovascular disease (heart attacks, strokes and peripheral arterial disease). The mechanisms by which FFA can cause insulin resistance, although not completely known, include generation of lipid metabolites (diacylglycerol), proinflammatory cytokines (TNF-α, IL-1β, IL-6, MCP1) and cellular stress including oxidative and endoplasmic reticulum stress.
    Summary: Increased plasma FFA levels are an important cause of obesity-associated insulin resistance and cardiovascular disease. Therapeutic application of this knowledge is hampered by the lack of readily accessible methods to measure FFA and by the lack of medications to lower plasma FFA levels.
    MeSH term(s) Animals ; Fatty Acids, Nonesterified/blood ; Humans ; Insulin Resistance ; Obesity/blood ; Obesity/complications ; Obesity/physiopathology ; Risk Assessment ; Risk Factors ; Up-Regulation
    Chemical Substances Fatty Acids, Nonesterified
    Language English
    Publishing date 2011-02-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2272017-0
    ISSN 1752-2978 ; 1752-296X
    ISSN (online) 1752-2978
    ISSN 1752-296X
    DOI 10.1097/MED.0b013e3283444b09
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Increased insulin resistance in young adults born with very low birth weight.

    Boden, Guenther

    Current diabetes reports

    2008  Volume 8, Issue 3, Page(s) 231–232

    Language English
    Publishing date 2008-07-15
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2065167-3
    ISSN 1539-0829 ; 1534-4827
    ISSN (online) 1539-0829
    ISSN 1534-4827
    DOI 10.1007/s11892-008-0039-5
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  5. Article ; Online: Endoplasmic reticulum stress: another link between obesity and insulin resistance/inflammation?

    Boden, Guenther

    Diabetes

    2009  Volume 58, Issue 3, Page(s) 518–519

    MeSH term(s) Adipose Tissue/physiology ; Endoplasmic Reticulum/physiology ; Gastric Bypass ; Humans ; Inflammation/physiopathology ; Insulin Resistance/physiology ; Liver/physiology ; Muscle, Skeletal/physiology ; Obesity/physiopathology ; Stress, Physiological
    Language English
    Publishing date 2009-02-26
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db08-1746
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  6. Article: Pioglitazone and nonalcoholic steatohepatitis.

    Boden, Guenther

    Current diabetes reports

    2007  Volume 7, Issue 3, Page(s) 221–222

    Language English
    Publishing date 2007-05-16
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2065167-3
    ISSN 1534-4827
    ISSN 1534-4827
    DOI 10.1007/s11892-007-0034-2
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  7. Article ; Online: High- or low-carbohydrate diets: which is better for weight loss, insulin resistance, and fatty livers?

    Boden, Guenther

    Gastroenterology

    2009  Volume 136, Issue 5, Page(s) 1490–1492

    MeSH term(s) Dietary Carbohydrates/administration & dosage ; Energy Intake ; Fatty Liver/diet therapy ; Female ; Humans ; Insulin Resistance ; Male ; Obesity/diet therapy ; Weight Loss
    Chemical Substances Dietary Carbohydrates
    Language English
    Publishing date 2009-03-21
    Publishing country United States
    Document type Comment ; Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2009.03.019
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  8. Article: Obesity and free fatty acids.

    Boden, Guenther

    Endocrinology and metabolism clinics of North America

    2008  Volume 37, Issue 3, Page(s) 635–46, viii–ix

    Abstract: Plasma free fatty acid (FFA) levels are elevated in obesity. FFAs cause insulin resistance in all major insulin target organs (skeletal muscle, liver, endothelial cells) and have emerged as a major link between obesity, the development of the metabolic ... ...

    Abstract Plasma free fatty acid (FFA) levels are elevated in obesity. FFAs cause insulin resistance in all major insulin target organs (skeletal muscle, liver, endothelial cells) and have emerged as a major link between obesity, the development of the metabolic syndrome, and atherosclerotic vascular disease. FFAs also produce low-grade inflammation in skeletal muscle, liver, and fat, which may contribute to cardiovascular events. The challenges for the future include the prevention or correction of obesity and elevated plasma FFA levels through methods that include decreased caloric intake and increased caloric expenditure, the development of methods to measure FFAs in small blood samples, and the development of efficient pharmacologic approaches to normalize increased plasma FFA levels.
    MeSH term(s) Animals ; Atherosclerosis/etiology ; Fatty Acids, Nonesterified/blood ; Fatty Acids, Nonesterified/physiology ; Humans ; Inflammation/etiology ; Insulin Resistance ; Matrix Metalloproteinases/physiology ; Metabolic Syndrome/etiology ; Obesity/metabolism
    Chemical Substances Fatty Acids, Nonesterified ; Matrix Metalloproteinases (EC 3.4.24.-)
    Language English
    Publishing date 2008-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 92116-6
    ISSN 1558-4410 ; 0889-8529
    ISSN (online) 1558-4410
    ISSN 0889-8529
    DOI 10.1016/j.ecl.2008.06.007
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  9. Article: New benefits of statin treatment.

    Boden, Guenther

    Current diabetes reports

    2005  Volume 5, Issue 3, Page(s) 165; discussion 165–6

    MeSH term(s) Anticholesteremic Agents/therapeutic use ; Cholesterol, LDL/blood ; Cholesterol, LDL/drug effects ; Diabetes Complications/blood ; Diabetes Complications/drug therapy ; Diabetes Mellitus/blood ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hypercholesterolemia/blood ; Hypercholesterolemia/drug therapy
    Chemical Substances Anticholesteremic Agents ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Language English
    Publishing date 2005-05-25
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2065167-3
    ISSN 1534-4827
    ISSN 1534-4827
    DOI 10.1007/s11892-005-0003-6
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  10. Article: Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver.

    Boden, Guenther

    Current diabetes reports

    2006  Volume 6, Issue 3, Page(s) 177–181

    Abstract: Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty ...

    Abstract Plasma free fatty acid (FFA) levels are elevated in obesity. FFA, by causing insulin resistance in muscle, liver, and endothelial cells, contributes to the development of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). The mechanism through which FFA induces insulin resistance involves intramyocellular and intrahepatocellular accumulation of triglycerides and diacylglycerol, activation of several serine/threonine kinases, reduction in tyrosine phosphorylation of the insulin receptor substrate (IRS)-1/2, and impairment of the IRS/phosphatidylinositol 3-kinase pathway of insulin signaling. FFA also produces low-grade inflammation in skeletal muscle and liver through activation of nuclear factor-kappaB, resulting in release of several proinflammatory and proatherogenic cytokines. Thus, elevated FFA levels (due to obesity or to high-fat feeding) cause insulin resistance in skeletal muscle and liver, which contributes to the development of T2DM, and produce low-grade inflammation, which contributes to the development of atherosclerotic vascular diseases and NAFLD.
    MeSH term(s) Diabetes Mellitus, Type 2/physiopathology ; Fatty Acids, Nonesterified/blood ; Fatty Acids, Nonesterified/physiology ; Humans ; Inflammation/etiology ; Insulin Resistance/physiology ; Liver/physiology ; Muscle, Skeletal/physiology ; Obesity/complications
    Chemical Substances Fatty Acids, Nonesterified
    Language English
    Publishing date 2006-08-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2065167-3
    ISSN 1534-4827
    ISSN 1534-4827
    DOI 10.1007/s11892-006-0031-x
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