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Hypoglycaemia (revision 4)

Old revision·10:26, 5 Sep 2024·MTC_Marisol

This is an old revision of this page, as it stood at 10:26, 5 Sep 2024, saved by MTC_Marisol with the summary add the interaction with the mechanism that explains it. It may differ substantially from the current revision, and any error it contains may since have been corrected.
Hypoglycaemia
Common thresholdBelow 3.9 mmol/L (70 mg/dL)
Level 2Below 3.0 mmol/L (54 mg/dL)
Level 3Severe: requires assistance
Risk with incretin monotherapyLow
Topic infobox · conventions

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.[1]

Incretin agonists carry a low intrinsic risk because their action on 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.[2]

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.[1]

Why glucose dependence matters

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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.[2]

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.

References

  1. ^ a b American Diabetes Association. "Standards of Care in Diabetes." Diabetes Care 47(Suppl 1) (2024).
  2. ^ a b 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.