Comparing hormonal and symptomatic responses to experimental hypoglycaemia in insulin‐ and sulphonylurea‐treated Type 2 diabetes

Aims  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.