Preventing hypoglycaemia: what is the appropriate glucose alert value?

Contrary to the assertions of Swinnen et al. [1], Frier [2] and Amiel et al. [3], the American Diabetes Association (ADA) Workgroup on Hypoglycemia [4] defined hypoglycaemia in diabetes as ‘all episodes of an abnormally low plasma glucose concentration that expose the individual to potential harm’. It is not possible to state a single plasma glucose concentration that defines hypoglycaemia because the glycaemic thresholds for responses to falling glucose levels, including those for symptoms, are dynamic. The ADA Workgroup recommended that people with diabetes (implicitly those with insulin secretagogueor insulin-treated diabetes) should become concerned about the possibility of developing hypoglycaemia at a self-monitored plasma glucose concentration of ≤3.9 mmol/l (70 mg/dl) [4]. Given the limited accuracy of monitoring devices [5], this conservative lower limit for individuals with diabetes approximates the lower limit of the postabsorptive plasma glucose concentration range (approximately 3.9–6.1 mmol/l [70–110 mg/dl] [6]) and the glycaemic threshold for activation of glucose counter-regulatory systems (approximately 3.6–3.9 mmol/l [65–70 mg/dl] [6–9]), and is low enough to cause reduced glucose counter-regulatory responses to subsequent hypoglycaemia [10] in non-diabetic individuals. It is higher than the glucose levels required to produce symptoms in non-diabetic individuals (approximately 2.8–3.1 mmol/l [50–55 mg/dl] [6–9]) and substantially higher than those that do so in people with well-controlled diabetes [11], although individuals with poorly controlled diabetes sometimes have symptoms at higher glucose levels [11, 12]. Thus, the recommended glucose alert level of ≤3.9 mmol/l (70 mg/dl) is data-driven, generally gives the patient time to take action to prevent a clinical hypoglycaemic episode, and provides some margin for the limited accuracy of glucose monitoring devices at low plasma glucose concentrations [5]. The ADA Workgroup-recommended alert value does not, of course, mean that people with diabetes should always self-treat at an estimated plasma glucose concentration of ≤3.9 mmol/l (70 mg/dl). Rather, it suggests that they should consider actions ranging from repeating the measurement in the short term, through behavioural changes such as avoiding exercise or driving, to carbohydrate ingestion and adjustments of the treatment regimen. The data reported by Swinnen et al. [1] nicely document that a higher plasma glucose cut-off value increases the percentage of affected patients and increases the proportion of patients who are asymptomatic; but those are predictable findings. Their data also indicate that a higher cut-off value Diabetologia (2009) 52:35–37 DOI 10.1007/s00125-008-1205-7