Hypoglycaemic counter-regulation at normal blood glucose concentrations in patients with well controlled type-2 diabetes

Lancet. 2000 Dec 9;356(9246):1970-4. doi: 10.1016/s0140-6736(00)03322-5.


Background: Intensive treatment to achieve good glycaemic control in diabetic patients is limited by a high frequency of hypoglycaemia. The glucose concentrations at which symptoms and release of counter-regulatory hormones takes place have not been studied in patients with well controlled type-2 diabetes.

Methods: We studied seven well controlled, non-insulin treated, type-2 diabetic patients (mean HbA1c [corrected according to Diabetes Control and Complications Trial] 7.4%, SD 1.0) and seven healthy controls matched for age, sex, and body mass index with a stepped hyperinsulinaemic hypoglycaemic glucose clamp. Symptoms, cognitive function, and counter-regulatory hormone concentrations were measured at each glucose plateau, and the glucose value at which there was a significant change from baseline was calculated.

Findings: Symptom response took place at higher whole-blood glucose concentrations in diabetic patients than in controls. Counter-regulatory release of epinephrine, norepinephrine, growth hormone, and cortisol showed a similar pattern--eg, at blood glucose concentrations of 3.8 mmol/L [SD 0.4] vs 2.6 [0.3] for epinephrine.

Interpretation: Glucose thresholds for counter-regulatory hormone secretion are altered in well controlled type-2 diabetic patients, so that both symptoms and counter-regulatory hormone release can take place at normal glucose values. This effect might protect type-2 diabetic patients against episodes of profound hypoglycaemia and make the achievement of normoglycaemia more challenging in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Epinephrine / blood
  • Epinephrine / metabolism
  • Female
  • Glucagon / blood
  • Glucagon / metabolism
  • Human Growth Hormone / blood
  • Human Growth Hormone / metabolism
  • Humans
  • Hydrocortisone / blood
  • Hydrocortisone / metabolism
  • Hypoglycemia / blood*
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Norepinephrine / metabolism
  • Pancreatic Polypeptide / blood
  • Pancreatic Polypeptide / metabolism


  • Blood Glucose
  • Human Growth Hormone
  • Pancreatic Polypeptide
  • Glucagon
  • Hydrocortisone
  • Norepinephrine
  • Epinephrine