The Clash of Two Epidemics: the Relationship Between Opioids and Glucose Metabolism

Abstract

Purpose of Review We are currently in the midst of a global opioid epidemic. Opioids affect many physiological processes, but one side effect that is not often taken into consideration is the opioid-induced alteration in blood glucose levels. Recent Findings This review shows that the vast majority of studies report that opioid stimulation increases blood glucose levels. In addition, plasma levels of the endogenous opioid β-endorphin rise in response to low blood glucose. In contrast, in hyperglycaemic baseline conditions such as in patients with type 2 diabetes mellitus (T2DM), opioid stimulation lowers blood glucose levels. Furthermore, obesity itself alters sensitivity to opioids, changes opioid receptor expression and increases plasma β-endorphin levels. Summary Thus, opioid stimulation can have various side effects on glycaemia that should be taken into consideration upon prescribing opioid-based medication, and more research is needed to unravel the interaction between obesity, glycaemia and opioid use.

Acute severe hypoglycemia immediately after induction of anesthesia in an elderly patient with type 2 diabetes mellitus: A case report

“…[ 13 ] A recent review indicates that while opioid stimulation often elevates blood glucose levels, it can reduce levels in patients with type 2 diabetes. [ 14 ] Diabetes appears to be a risk factor. Additionally, a case report described fasting hypoglycemia with acute, transient, opioid-induced secondary hypoadrenalism.…”

Effects of the POMC System on Glucose Homeostasis and Potential Therapeutic Targets for Obesity and Diabetes

“…110,111 In contrast, the β-endorphin levels increase during hypoglycemia, consequently inducing an increase in the blood glucose levels. 108 Dynorphin-A, an endogenous κ-opioid receptor agonist, can increase food intake and body weight when acting on the POMC neurons, while directly inhibiting the POMC neurons by activating the G-protein-coupled inwardly-rectifying K+ Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2022:15 https://doi.org/10.2147/DMSO.S380577 DovePress 2945 channels. 112 Additionally, obesity affects opioid sensitivity and the expression of its receptors and increases β-endorphin levels.…”

“…Similarly, opioid receptors can also be expressed in tissues and cells throughout the body. 108 The regulation of blood glucose by opioids is affected by glucose concentration. 106 , 109 In the case of hyperglycemia, the injection of β-endorphin and µ-opioid receptor agonists can reduce hypoglycemia without affecting food intake.…”

“… 110 , 111 In contrast, the β-endorphin levels increase during hypoglycemia, consequently inducing an increase in the blood glucose levels. 108 …”

“… 112 Additionally, obesity affects opioid sensitivity and the expression of its receptors and increases β-endorphin levels. 108 However, the mechanisms by which these processes occur must be explored to identify their therapeutic viability against obesity and type 2 diabetes.…”