Source of Hypoglycaemia

{{Infobox concept | name = Hypoglycaemia | subtitle = Adverse effect | Common threshold = Below 3.9 mmol/L (70 mg/dL) | Level 2 = Below 3.0 mmol/L (54 mg/dL) | Level 3 = Severe: requires assistance | Risk with incretin monotherapy = Low }} '''Hypoglycaemia''' is abnormally low blood glucose. It is classified by level: below 3.9 mmol/L as an alert value, below 3.0 mmol/L as clinically significant, and any episode requiring assistance as severe regardless of the measured value.{{r|ada2024}} Incretin agonists carry a low intrinsic risk because their action on [[Insulin secretion|insulin secretion]] is glucose-dependent: they amplify a response that glucose has initiated rather than initiating one. Below the glucose threshold for triggering, there is nothing to amplify.{{r|nauck2016}} Risk arises when they are combined with agents that are not glucose-dependent — insulin and sulfonylureas — and the usual response on initiating an incretin agonist alongside either is to reduce the background agent.{{r|ada2024}} == Why glucose dependence matters == The beta cell distinguishes a triggering signal from an amplifying one. Glucose metabolism raises the ATP:ADP ratio, closes potassium channels and admits calcium — the trigger. Incretin signalling raises cAMP, which increases the amount of insulin released per unit of calcium — the amplifier.{{r|nauck2016}} Sulfonylureas act on the trigger, closing the potassium channel pharmacologically regardless of glucose, which is why they cause hypoglycaemia. Injected insulin bypasses the beta cell entirely. This is a mechanistic argument rather than a guarantee. Reported hypoglycaemia rates on incretin monotherapy are low but not zero, and the residual reflects other contributors — missed meals, alcohol, renal impairment, and concurrent agents.{{r|drucker2018}} == Recognition and classification == | Level | Threshold | Interpretation | |---|---|---| | 1 | 3.0–3.9 mmol/L | Alert value; action advised | | 2 | Below 3.0 mmol/L | Clinically significant | | 3 | Any, with impaired cognition requiring assistance | Severe | Level 3 is defined by the need for assistance rather than by a number, because the glucose concentration at which cognition is impaired varies with prior exposure. Repeated hypoglycaemia lowers the threshold at which symptoms appear, a phenomenon termed impaired awareness.{{r|ada2024,seaquist2013}} Symptoms are conventionally divided into adrenergic — tremor, sweating, palpitation — and neuroglycopenic — confusion, difficulty concentrating, visual change. Adrenergic symptoms are the warning, and it is those that impaired awareness removes.{{r|ada2024}} == In the context of this wiki == Compounds discussed here that are sold for research use are not approved for human administration, and this article describes hypoglycaemia as it appears in the clinical literature rather than as advice for any use.{{r|ada2024}} The relevant general point is that the glucose-dependence argument is a property of receptor pharmacology and does not extend to a preparation of unknown identity or content. A material whose actual peptide mass is unknown — see [[Peptide content]] and [[Underfilling]] — cannot be reasoned about pharmacologically at all, because the exposure is unknown.{{r|drucker2018}} Nothing on this wiki is medical advice.{{r|nauck2016}} == References == {{reflist}} <ref name="ada2024">American Diabetes Association. "Standards of Care in Diabetes." ''Diabetes Care'' 47(Suppl 1) (2024).</ref> <ref name="nauck2016">Nauck MA, Meier JJ. "The incretin effect in healthy individuals and those with type 2 diabetes." ''The Lancet Diabetes & Endocrinology'' 4(6):525–536 (2016). PMID 26876794.</ref> <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> <ref name="seaquist2013">Seaquist ER, Anderson J, Childs B, et al. "Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society." ''Diabetes Care'' 36(5):1384–1395 (2013). PMID 23589542.</ref> == See also == * [[Insulin secretion]] * [[Beta cell function]] * [[GLP-1 receptor agonist]] * [[Adverse effects of GLP-1 receptor agonists]] * [[Baseline laboratory panel]] {{DEFAULTSORT:Hypoglycaemia}} [[Category:Adverse effects]] [[Category:Clinical practice]] [[Category:Metabolic biomarkers]]