Abstract
BackgroundPrediabetes is characterized by a hemoglobin A1c of 5.7–6.4% and fasting blood glucose of 100–125 mg/dl. A high percentage of prediabetes subjects develop type 2 diabetes mellitus in the next years. The effects of opioid peptides and their receptors, in addition to immunological cytokines, on prediabetes are not well understood. Therefore, molecular, physiological, and clinical studies are required to link the opioid system, immune system, and insulin resistance (IR) in prediabetes. We hypothesize that opioid peptides (endomorphin-2 (EM2), and β-endorphin (βEP)), and their receptors (µ-opioid receptors (MOR) and κ-opioid receptors (KOR)), in addition to the inflammatory cytokines (IL-6) and anti-inflammatory cytokine (IL-10), affect IR parameters in patients with prediabetes.MethodsSixty prediabetes patients with IR (prediabetes+IR) and sixty prediabetes patients without IR (prediabetes-IR), in addition to 58 controls, have participated in the study. IL-6, IL-10, EM2, βEP, MOR, and KOR were measured by the ELISA technique.ResultsIn general, most prediabetes subjects have dyslipidemia. The IL-6, IL-10, β-endorphin, MOR, and endomorphin-2 were higher in the prediabetes subgroups than the control group. The immune system was activated in the prediabetes in an IR-dependent manner. Prediabetes+IR can be predicted by the increased levels of IL-10, βEP, and EM2 and by the combination of IL-10 and EM2/KOR with good sensitivity and specificity.ConclusionOpioid peptides and their receptors were upregulated in patients with prediabetes, depending on the significance of IR and the immune cytokines. The intercorrelation between the immune system, EOS, and insulin in prediabetes was confirmed.
Highlights
Prediabetes is characterized by a hemoglobin A1c of 5.7–6.4% and fasting blood glucose of 100–125 mg/dl
About 34.5% of American adults over 18 years of age (88 million people) have prediabetes experience prediabetes, a disorder associated with higher hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) levels than average but not significantly elevated to be grouped as diabetes mellitus [2]
A large percentage of prediabetes patients showed a rise in IR index, and they labeled as insulin-resistant patients when the value of the homeostasis model assessment of the insulin resistance (HOMA2IR) reaches the cut-off value (> 2.5) [7, 8]
Summary
Prediabetes is characterized by a hemoglobin A1c of 5.7–6.4% and fasting blood glucose of 100–125 mg/dl. Impaired fasting blood glucose (FBG) or glucose tolerance develops years before evolving into a strong type 2 diabetes mellitus (T2DM), and this disorder is known as prediabetes, a major risk factor for diabetes development [1]. About 34.5% of American adults over 18 years of age (88 million people) have prediabetes experience prediabetes, a disorder associated with higher hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) levels than average but not significantly elevated to be grouped as diabetes mellitus [2]. At formation, Aβ oligomers exhaust insulin receptors from the neuronal surface membrane, leading to IR and producing abnormal phosphorylation of the insulin receptor substrate (IRS) [13] This state reduces the neurons’ normal pro-survival signaling and promotes apoptosis to their death [14]. Elevated IR that occurs during midlife may increase the risk of cognitive impairment later in life, demonstrated by reduced verbal fluency and sluggish basic response time [16]
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