Rate of fall of blood glucose and physiological responses of counterregulatory hormones, clinical symptoms and cognitive function to hypoglycaemia in Type I diabetes mellitus in the postprandial state

Diabetologia. 2003 Jan;46(1):53-64. doi: 10.1007/s00125-002-0948-9. Epub 2002 Nov 9.


Aims/hypothesis: The aim of this study was to establish the effect of a rate of decreasing plasma glucose concentrations on responses to hypoglycaemia, i.e. release of counterregulatory hormones, perception of symptoms, deterioration of cognitive function, and rates of forearm noradrenaline spillover, in the postprandial condition and in the sitting position.

Methods: We studied 11 subjects with Type I (insulin-dependent) diabetes mellitus, twice during clamped insulin-induced hypoglycaemia (2.4 mmol/l) after eating in the sitting position. On one occasion, plasma glucose was decreased at the rate of 0.1+/-0.003 mmol x min(-1) x l(-1) (fast fall), on the other at the rate of 0.03+/-0.001 mmol x min(-1) x l(-1) (slow fall). Subjects underwent a control euglycaemic clamp study as well.

Results: In response to fast-fall as compared to slow-fall hypoglycaemia, which was about 30 min longer, cognitive tasks were performed as follows: Trail-Making B, PASAT 2 s, Digit Vigilance Test and Verbal Memory deteriorated more, adrenaline increased less (2.8+/-0.5 vs 3.5+/-0.7 nmol/l, p=0.03), forearm noradrenaline spillover was greater (6.5+/-1.0 vs 5.2+/-0.4 pmol x min(-1) x 100 ml(-1), p=0.04), and symptoms were no different. After recovery from hypoglycaemia, cognitive function was still deteriorated compared to the baseline with no difference between fast and slow-fall hypoglycaemia. The evident response of glucagon to postprandial hypoglycaemia contrasted with the blunted or absent response in the fasting state.

Conclusion/interpretation: In the postprandial condition and sitting position, fast-fall hypoglycaemia is more dangerous than slow-fall, because it deteriorates cognitive function more, and activates responses of counterregulatory hormones less than slow-fall hypoglycaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Cognition*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Female
  • Forearm / blood supply
  • Hormones / blood
  • Hormones / metabolism*
  • Humans
  • Hypoglycemia / physiopathology*
  • Hypoglycemia / psychology*
  • Insulin / analogs & derivatives*
  • Insulin / blood
  • Insulin / pharmacology
  • Insulin Lispro
  • Male
  • Norepinephrine / metabolism
  • Osmolar Concentration
  • Postprandial Period*
  • Posture / physiology
  • Regional Blood Flow
  • Vascular Resistance


  • Blood Glucose
  • Hormones
  • Insulin
  • Insulin Lispro
  • Norepinephrine