Abstract

Approximately 65% of patients with T2DM die as a result of cardiovascular disease with hyperglycemia and hyperlipidemia being important risk factors for cardiovascular diseases. Both T2DM and atherosclerosis are considered to be inflammatory processes Human T-lymphocytes (T-cells) and aortic endothelial cells (HAEC) have been shown to be components of plaque formation in atherosclerosis. T cells and HAEC are unique in that in their naive state they have no insulin receptors responsive to insulin but become activated in vitro hyperglycemia and in vivo hyperglycemic conditions such as diabetic ketoacidosis and non-ketotic hyperglycemic conditions. Our studies show that T-cells and HAEC in the presence of high concentrations of glucose /and or the saturated fatty acid (SFA) palmitic acid become activated and express insulin receptors, reactive oxygen species (ROS), cytokine elevation, and lipid peroxidation in a time and concentration-dependent manner. Whereas, the unsaturated fatty acid α-linoleic, was not able to activate these cells and had a salutary effect on the activation by glucose and palmitic acid. We have demonstrated that unsaturated fatty acids (UFA) may provide a protective mechanism against the prooxidant effects of hyperglycemia and high SFA such as palmitic acid. Therefore, diet alternations may be beneficial for decreasing hyperglycemia and cardiovascular risks. Studies have shown that lifestyle changes of diet and exercise can reduce the risk of developing diabetes by 58%. Hyperglycemia and hyperlipidemia are important risk factors of developing diabetes and cardiovascular disease. Therefore, we studied the effects of a High Protein diet versus a High Carbohydrate diet in obese non-diabetic, prediabetic and diabetic subjects for effects on weight loss, blood sugar, lipid levels, inflammation, and oxidative stress.

Highlights

  • Greater than 65% of patients with Type 2 Diabetes Mellitus (T2DM) die as a result of cardiovascular disease with hyperglycemia and hyperlipidemia being important risk factors for cardiovascular diseases [1]

  • Our studies have shown that reactive oxygen species (ROS) along with proinflammatory cytokines such as: Tumor Necrosis Factor α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β) and Interleukin-8 (IL-8); cardiovascular risk markers such as: PAI-1, CRP and Free Fatty Acids (FFA); and counterregulatory hormones such as: IGF-1 and cortisol were all elevated two to three fold above normal with hyperglycemia and returned to normal levels after resolution of hyperglycemia with treatment with insulin and hydration [12]

  • Linolenic acid may serve as a protective mechanism against the deleterious effects of high glucose and palmitate in human T-cells and HAEC and reduce the inflammatory process observed with high blood glucose and high saturated fatty acid foods as observed in diabetes, prediabetes, cardiovascular disease and other health conditions

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Summary

Introduction

Greater than 65% of patients with Type 2 Diabetes Mellitus (T2DM) die as a result of cardiovascular disease with hyperglycemia and hyperlipidemia being important risk factors for cardiovascular diseases [1]. Unsaturated fatty acids such as linoleic, oleic, linolenic, and arachidonic acids were not able to activate these cells These studies showed that palmitic acid, but not oleic, linoleic, linolenic or arachidonic acids, exhibited dose and time dependent responses of deleterious effects of palmitic acid by demonstrating increased levels of ROS and lipid peroxidation (malondialdehyde- MDA), emergence of receptors for insulin, IGF-1, IL-2, GLUT 4, inflammatory and proinflammatory effects detected by the emergence of interleukin (IL) cytokines IL-1B, IL-6, IL-8, IL-2, IL-10, and TNFα. Linolenic acid may serve as a protective mechanism against the deleterious effects of high glucose and palmitate in human T-cells and HAEC and reduce the inflammatory process observed with high blood glucose and high saturated fatty acid foods as observed in diabetes, prediabetes, cardiovascular disease and other health conditions. ∆p < 0.05 from glucose (15 mM) + palmitate (100 uM)

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