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>

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>

scholarly journals Association of extracellular heat shock protein 70 and insulin resistance in type 2 diabetes; independent of obesity and C-reactive protein

2018 ◽  
Vol 24 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Hamid Alemi ◽  
Pegah Khaloo ◽  
Soghra Rabizadeh ◽  
Mohammad Ali Mansournia ◽  
Hossein Mirmiranpour ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
C Reactive Protein ◽  
Reactive Protein

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.

Abstract 020: C-reactive Protein As A Moderator And Insulin Resistance As A Mediator For The Association Between Endothelin-1 And Type 2 Diabetes Progression Among African Americans In The Jackson Heart Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Xiang Gao ◽  
Steven R Horbal ◽  
Hao Fan ◽  
Le Su ◽  
Solomon K Musani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
African Americans ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Heart Study ◽  
Diabetes Progression ◽  
Adjusted Model ◽  
Multivariable Adjusted Model

Objective: Little is known about the moderation and mediation factors among the association between endothelin-1 (ET-1) level and type 2 diabetes progression in African Americans. We explored the role of high sensitivity C-reactive protein (hsCRP) as a moderator and homeostatic model assessment of insulin resistance (HOMA-IR) as a mediator for the association between ET-1 level and type 2 diabetes progression among African Americans enrolled in the Jackson Heart Study (JHS). Methods: We included 1,692 participants free of prediabetes and diabetes at baseline, who attended Exam 1 of the JHS in 2000-2004 and Exam 3 in 2009-2013, and with measured ET-1 level at Exam 1. Incident prediabetes and diabetes were ascertained at Exam 3. We used a sequential regression model procedure. Zou’s modified Poisson multivariable models were used to calculate risk ratios (RR) and 95% confidence intervals (CI) for prediabetes and diabetes. Effect modification was assessed in the multivariable adjusted model. Valeri and VanderWeele’s mediation analysis approach was utilized to evaluate mediation. Results: A higher log-transformed ET-1 level was detected when comparing non-diabetes versus prediabetes and diabetes participants (p-value for trend = 0.03). Compared to quartile 1 (<0.9 pg/mL) of ET-1, quartile 2 (0.9-1.2 pg/mL) of ET-1 was significantly associated with higher risk of prediabetes (RR=1.19 [95% CI 1.02, 1.38]) and diabetes (RR=1.19 [95% CI 1.02, 1.40]). This association only remained significant for diabetes in the multivariable adjusted model (RR=1.20 [95% CI 1.02, 1.40]) and was not attenuated after adjusted for hsCRP (RR=1.20 [95% CI 1.03, 1.40]), HOMA-IR (RR=1.20 [95% CI 1.02, 1.40]), and both hsCRP and HOMA-IR (RR=1.20 [95% CI 1.03, 1.40]) in quartile 2 of ET-1.The risk of elevated ET-1 level on diabetes was higher in participants with increased hsCRP level in the multivariable adjusted model (RR=1.06 [95% CI 1.02, 1.09]), and further adjusted for HOMA-IR (RR=1.06 [95% CI 1.02, 1.09]. The indirect effect of ET-1 on prediabetes through HOMA-IR is 0.96 (P<0.01), but not found for hsCRP (p=0.26). The total effect of ET-1 on prediabetes mediated by HOMA-IR is 47%. No such mediation effect of HOMA-IR was found among diabetes participants. Conclusions: African Americans with higher ET-1 levels have a higher risk of prediabetes and diabetes. Additionally, the risk of diabetes is elevated among those African Americans with increased hsCRP levels. The mediation analysis result supports that ET-1 is involved in the stage of glucose metabolism imbalances leading to diabetes progression.

Does high dietary protein intake contribute to the increased risk of developing prediabetes and type 2 diabetes?

2021 ◽  
Vol 46 (1) ◽  
pp. 1-9
Author(s):  
Oana Ancu ◽  
Monika Mickute ◽  
Nicola D. Guess ◽  
Nicholas M. Hurren ◽  
Nicholas A. Burd ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Amino Acids ◽  
Amino Acid ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Protein Intake ◽  
High Protein Diets ◽  
Protein Diets

Insulin resistance is a complex metabolic disorder implicated in the development of many chronic diseases. While it is generally accepted that body mass loss should be the primary approach for the management of insulin resistance-related disorders in overweight and obese individuals, there is no consensus among researchers regarding optimal protein intake during dietary restriction. Recently, it has been suggested that increased plasma branched-chain amino acids concentrations are associated with the development of insulin resistance and type 2 diabetes. The exact mechanism by which excessive amino acid availability may contribute to insulin resistance has not been fully investigated. However, it has been hypothesised that mammalian target of rapamycin (mTOR) complex 1 hyperactivation in the presence of amino acid overload contributes to reduced insulin-stimulated glucose uptake because of insulin receptor substrate (IRS) degradation and reduced Akt-AS160 activity. In addition, the long-term effects of high-protein diets on insulin sensitivity during both weight-stable and weight-loss conditions require more research. This review focusses on the effects of high-protein diets on insulin sensitivity and discusses the potential mechanisms by which dietary amino acids can affect insulin signalling. Novelty: Excess amino acids may over-activate mTOR, resulting in desensitisation of IRS-1 and reduced insulin-mediated glucose uptake.

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