title: Comparing hormonal and symptomatic responses to experimental hypoglycaemia in insulin- and sulphonylurea-treated Type 2 diabetes.
abstract: OBJECTIVE
  Patients with diabetes rely on symptoms to identify hypoglycaemia. Previous data suggest patients with Type 2 diabetes develop greater symptomatic and hormonal responses to hypoglycaemia at higher glucose concentrations than non-diabetic controls and these responses are lowered by insulin treatment. It is unclear if this is as a result of insulin therapy itself or improved glucose control. We compared physiological responses to hypoglycaemia in patients with Type 2 diabetes patients treated with sulphonylureas (SUs) or insulin (INS) with non-diabetic controls (CON).
  
  
  METHODS
  Stepped hyperinsulinaemic hypoglycaemic clamps were performed on 20 subjects with Type 2 diabetes, 10 SU-treated and 10 treated with twice-daily premixed insulin, and 10 age- and weight-matched non-diabetic controls. Diabetic subjects were matched for diabetes duration, glycated haemoglobin (HbA(1c)) and hypoglycaemia experience. We measured symptoms, counterregulatory hormones and cognitive function at glucose plateaux of 5, 4, 3.5, 3 and 2.5 mmol/l.
  
  
  RESULTS
  Symptomatic responses to hypoglycaemia occurred at higher blood glucose concentrations in SU-treated than INS-treated patients [3.5 (0.4) vs. 2.6 (0.5) mmol/l SU vs. INS; P = 0.001] or controls [SU vs. CON 3.5 (0.4) vs. 3.0 (0.6) mmol/l; P = 0.05]. They also had a greater increase in symptom scores at hypoglycaemia [13.6 (11.3) vs. 3.6 (6.1) vs. 5.1 (4.3) SU vs. INS vs. CON; P = 0.017]. There were no significant differences in counterregulatory hormone responses or impairment of cognitive function among groups.
  
  
  CONCLUSIONS
  Sulphonylurea-treated subjects are more symptomatic of hypoglycaemia at a higher glucose level than insulin-treated subjects. This may protect them from severe hypoglycaemia but hinder attainment of glycaemic goals.
authors: Diabetes Research Group, King's College London School of Medicine, London, UK.
authors: P
authors: P
authors: Choudhary
authors: K
authors: K
authors: Lonnen
authors: C J
authors: CJ
authors: Emery
authors: I A
authors: IA
authors: MacDonald
authors: K M
authors: KM
authors: MacLeod
authors: S A
authors: SA
authors: Amiel
authors: S R
authors: SR
authors: Heller
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D016022:Case-Control Studies; D003071:Cognition; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000523:psychology; D004837:Epinephrine / Q000378:metabolism; D005215:Fasting; D005934:Glucagon / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced* / Q000378:metabolism / Q000523:psychology; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D014202:Tremor
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine