scholarly journals Effects of n−3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation

2006 ◽  
Vol 84 (3) ◽  
pp. 540-550 ◽  
Author(s):  
Ingrid L Mostad ◽  
Kristian S Bjerve ◽  
Marit R Bjorgaas ◽  
Stian Lydersen ◽  
Valdemar Grill
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Fat Oxidation ◽  
Time Dependent

scholarly journals Risk of diabetes associated with fatty acids in the de novo lipogenesis pathway is independent of insulin sensitivity and response: the Insulin Resistance Atherosclerosis Study (IRAS)

2019 ◽  
Vol 7 (1) ◽  
pp. e000691 ◽  
Author(s):  
Waqas Qureshi ◽  
Ingrid D Santaren ◽  
Anthony J Hanley ◽  
Steven M Watkins ◽  
Carlos Lorenzo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Palmitic Acid ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Diabetes Incidence ◽  
Incident Type ◽  
Insulin Resistance Atherosclerosis Study

ObjectiveTo examine the associations of fatty acids in the de novo lipogenesis (DNL) pathway, specifically myristic acid (14:0), palmitic acid (16:0),cis-palmitoleic acid (c16:1 n-7),cis-myristoleic acid (c14:1n5), stearic acid (18:0) andcis-oleic acid (c18:1 n-9), with 5-year risk of type 2 diabetes. We hypothesized that DNL fatty acids are associated with risk of type 2 diabetes independent of insulin sensitivity.Research design and methodsWe evaluated 719 (mean age 55.1±8.5 years, 44.2% men, 42.3% Caucasians) participants from the Insulin Resistance Atherosclerosis Study. Multivariable logistic regression models with and without adjustment of insulin sensitivity were used to assess prospective associations of DNL fatty acids with incident type 2 diabetes.ResultsType 2 diabetes incidence was 20.3% over 5 years. In multivariable regression models, palmitic, palmitoleic, myristic, myristoleic and oleic acids were associated with increased risk of type 2 diabetes (p<0.05). Palmitic acid had the strongest association (OR per standard unit of palmitic acid 1.46; 95% CI 1.23 to 1.76; p<0.001), which remained similar with addition of insulin sensitivity and acute insulin response (AIR) to the model (OR 1.36; 95% CI 1.09 to 1.70, p=0.01). Oleic and palmitoleic acids were also independently associated with incident type 2 diabetes. In multivariable models, ratios of fatty acids corresponding to stearoyl CoA desaturase-1 and Elovl6 enzymatic activity were significantly associated with risk of type 2 diabetes independent of insulin sensitivity and AIR.ConclusionsWe observed associations of DNL fatty acids with type 2 diabetes incidence independent of insulin sensitivity.

scholarly journals Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort

2021 ◽  
Author(s):  
Eleni Rebelos ◽  
Marco Bucci ◽  
Tomi Karjalainen ◽  
Vesa Oikonen ◽  
Alessandra Bertoldo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
C Reactive Protein ◽  
Brain Glucose ◽  
Reactive Protein ◽  
Wide Range

<b>Objective</b> Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of subjects across a wide range of age and insulin sensitivity. <p><b>Research Design and Methods</b> [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 subjects scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acids levels, C-reactive protein, HbA<sub>1c,</sub> and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. </p> <p><b>Results</b> Insulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin resistant subjects BGU is enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with a further increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein, free fatty acids, sex, and HbA<sub>1c</sub> were not associated with BGU.</p> <p><b>Conclusions </b>In this large cohort of subjects of either sex across a wide range of age and insulin sensitivity,<b> </b>insulin sensitivity is the best predictor of brain glucose uptake. <b></b></p>

From Obesity to Diabetes

2006 ◽  
Vol 76 (4) ◽  
pp. 172-177 ◽  
Author(s):  
Keller
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Free Fatty Acids ◽  
Vegetable Consumption ◽  
Prediabetic State ◽  
The Metabolic Syndrome ◽  
Life Style Changes

The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide – reaching a prevalence in adults of approx. 5–6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-α and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic β-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 β-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-γ) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjecs, and an increase in physical activity. There are now three published randomized controlled trials demonstrating that in high risk individuals, life style changes with modest weight lost, associated with diminished fat intake and an increase in fruit and vegetable consumption result in marked inhibition of the transition from the prediabetic state to manifest type 2 diabetes.

Redox regulation of insulin sensitivity due to enhanced fatty acid utilization in the mitochondria

2013 ◽  
Vol 305 (5) ◽  
pp. H634-H643 ◽  
Author(s):  
Paul M. Rindler ◽  
Clair L. Crewe ◽  
Jolyn Fernandes ◽  
Michael Kinter ◽  
Luke I. Szweda
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Redox Regulation ◽  
Acid Oxidation ◽  
Glucose Accumulation ◽  
Intracellular Glucose

Obesity enhances the risk for the development of type 2 diabetes and cardiovascular disease. Loss in insulin sensitivity and diminished ability of muscle to take up and use glucose are characteristics of type 2 diabetes. Paradoxically, regulatory mechanisms that promote utilization of fatty acids appear to initiate diet-induced insulin insensitivity. In this review, we discuss recent findings implicating increased mitochondrial production of the prooxidant H2O2 due to enhanced utilization of fatty acids, as a signal to diminish reliance on glucose and its metabolites for energy. In the short term, the ability to preferentially use fatty acids may be beneficial, promoting a metabolic shift that ensures use of available fat by skeletal muscle and heart while preventing intracellular glucose accumulation and toxicity. However, with prolonged consumption of high dietary fat and ensuing obesity, the near exclusive dependence on fatty acid oxidation for production of energy by the mitochondria drives insulin resistance, diabetes, and cardiovascular disease.

The effect of exercise, training, and inactivity on insulin sensitivity in diabetics and their relatives: what is new?

2007 ◽  
Vol 32 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Torben Østergård ◽  
Niels Jessen ◽  
Ole Schmitz ◽  
Lawrence J. Mandarino
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Large Scale ◽  
High Energy ◽  
First Degree Relatives ◽  
Type 2 Diabetics

Insulin resistance is a hallmark characteristic of type 2 diabetes. However, in healthy first-degree relatives of type 2 diabetics, insulin resistance is often present years before glucose intolerance or diabetes becomes clinically manifest. The mechanisms of insulin resistance involve conditions leading to an increased supply of fatty acids (e.g., high energy intake, obesity) and conditions in which the degradation/oxidation of muscular fatty acids is impaired. Several large-scale studies have documented the fact that increased physical activity can reduce or at least postpone the development of type 2 diabetes, and low physical fitness is a clear independent risk factor for the development of type 2 diabetes. The mechanisms responsible for the improvement in insulin sensitivity after exercise training have been studied extensively, but are not fully understood. This review focuses on insulin resistance in skeletal muscle and, in particular, its relation to changes in aerobic fitness in type 2 diabetics and their first-degree relatives.

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