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 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.


RESULTS
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.


CONCLUSIONS
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.
Spyer
G
G
Department of Vascular Medicine and Diabetes Research, School of Postgraduate Medicine and Health Sciences, Exeter, Devon, UK.
Hattersley
A T
AT
MacDonald
I A
IA
Amiel
S
S
MacLeod
K M
KM
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism; D007003:Hypoglycemia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D019382:Human Growth Hormone; D010191:Pancreatic Polypeptide; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine