Oral Azelaic Acid Ester Decreases Markers of Insulin Resistance in Overweight Human Male Subjects

Abstract

Background/Aim: Insulin resistance (IR) is linked to increased risk of cardiovascular disease and cancer. We examined safety and efficacy of the natural product diethyl azelate (DEA) in overweight males with a varying degree of IR. Patients and Methods: Seventeen subjects [age 18-42, hemoglobin A1c (A1c) of 5.2-6.2%] received orally 1 mg/kg DEA daily for 21 days. Blood plasma glucose, insulin and lipid levels were assessed before and after treatment. Results: DEA was well tolerated without hypoglycemia or adverse effects except transient diarrhea (n=1). DEA significantly reduced fasting glucose by 6.06 mg/dl (n=8) and insulin by 37.8% (n=8) in subjects with IR and/or A1c ≥5.6%. Furthermore, it improved cholesterol/HDL, LDL/HDL, and non-cholesterol HDL/HDL by 5.4, 6.5, and 6.6%, respectively in all subjects, and by 8.0, 9.8, and 9.8%, respectively in 9 subjects with A1c ≥5.6%. Conclusion: DEA efficacy correlates with the degree of IR. DEA holds promise as a novel treatment for the management of IR.Azelaic acid and its esters, azelates, occur naturally in plants, animals, and humans. We discovered that the naturally occurring fatty acid ester, diethyl azelate (DEA) (1), can be used for the treatment of diet-and ethanol-induced insulin resistance (IR), the hallmark of metabolic syndrome, prediabetes and Type 2 diabetes (T2D). A number of studies (2-4) have shown a correlation of metabolic diseases with increased risk of cancer, especially liver, pancreatic and endometrial (5-7).The Western diet combined with a sedentary lifestyle results in chronic metabolic inflammation (8,9). A diet 1173 This article is freely accessible online.

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System and Target for Pharmacological Intervention

“…Azelates as potential drugs, membrane active immunomodulators. We have demonstrated clinical activity of DEA on mitigation of insulin resistance in obese individuals (31). Examples of in vivo activity of DEA against PVL(+)MRSA and anthrax toxin suggest that DEA may be useful for the treatment of these diseases.…”

“…We have previously conducted a clinical study that demonstrated health benefits of oral diethyl azelate (DEA) on surrogate markers of insulin resistance, such as blood plasma glucose, insulin and lipids, when administered to overweight or obese adult male volunteers (31)(32)(33). We also Isolation of human peripheral blood mononuclear cells.…”

Adaptive Membrane Fluidity Modulation: A Feedback Regulated Homeostatic System Hiding in Plain Sight

“…Intentional pharmacological tuning of membrane fluidity with drugs has received little attention but on closer examination there is a significant amount of data suggesting the "druggability" of the fluidity of cell membranes. The hypothesis that one can affect the activities of membrane-associated proteins through alterations in plasma membrane fluidity using lipid-soluble molecules with application in the treatment of human and animal diseases is supported by our experimental data on the effects of esters of azelaic acid (azelates) that act as membrane fluidizers and exert immunomodulatory effects in vitro and in vivo (1, [21][22][23]. Unlike targeted therapies that usually focus on single molecular entities, the target for azelates is the entire plasma membrane.…”

“…For example, the fatty acid azelaic acid has been used in the treatment of dermatological diseases for decades (25,26). Diethyl azelate, a natural product made by plants and animals and unwittingly used by humanity over many millennia (27)(28)(29)(30)(31)(32)(33)(34), is also a promising drug candidate (21).…”

“…Elevated risk for perioperative hyperglycemia observed in non-diabetic subjects but not in diabetic patients (120) was referred to as paradoxical. For us the effect is akin to improved control of glucose by DEA in subjects with higher levels of hemoglobin A1c (21).…”