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

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 HbA1 [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.