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

Abstract

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 SUtreated 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 INStreated 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 insulintreated subjects. This may protect them from severe hypoglycaemia but hinder attainment of glycaemic goals. Diabet. Med. 26, 665-672 (2009)

Glucose concentrations of less than 3.0 mmol/l (54 mg/dl) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the Europian Association for the Study of Diabetes

“…They approximate the upper and lower limits, respectively, of the non-diabetic glycaemic threshold for symptoms of insulin-induced hypoglycaemia [8][9][10]. The generic non-diabetic glycaemic threshold for impairment of cognitive function is <2.8 mmol/l [8][9][10], but higher glucose levels have been reported for some tests [11][12][13][14]. Glucose concentrations of both <3.0 mmol/l and <2.8 mmol/l cause defective glucose counterregulation and impaired awareness of hypoglycaemia, the core components of hypoglycaemia-associated autonomic failure in diabetes [5].…”

Relationship Between Interstitial and Blood Glucose During Hypoglycemia in Subjects with Type 2 Diabetes

“…The counterregulatory hormone data in the present study, published in detail elsewhere, found no significant differences in counterregulatory hormone responses between the diabetes groups. 17 These findings are relevant to the increasing use of CGM in both research and clinical practice, particularly in type 2 diabetes. 15 Similar sensors and software are used in CGM systems such as the Medtronic Paradigm Ò , Abbott Navigator Ò , and Dexcom Ô (San Diego, CA) Seven Ò used therapeutically.…”

“…17 Baseline blood samples were taken before starting a primed infusion of Actrapid insulin made up in 0.9% NaCl containing 2 mL of autologous blood maintained at a rate of 1.5 U/kg/min. Glucose (20%) (Clintec Nutrition, Slough, UK) was infused through the same intravenous catheter at a variable rate to maintain BG at plateaus of 5.0, 4.0, 3.5, 3.0, and 2.5 mmol/L for 40 min each.…”

Diabetes and Cardiovascular Disease: Is intensive glucose control beneficial or deadly? Lessons from ACCORD, ADVANCE, VADT, UKPDS, PROactive, and NICE-SUGAR

“…A recent study demonstrated that hormonal and symptomatic responses to hypoglycemia seem to be different for insulin and SUs. Interestingly, SU-treated subjects are more symptomatic of hypoglycemia at a higher glucose level than insulin-treated subjects [17]. This may protect them from severe hypoglycemia but hinder attainment of glycemic goals.…”