Reproducibility of glycaemic thresholds for activation of counterregulatory hormones and hypoglycaemic symptoms in healthy subjects

Two studies using a graded stepped hypoglycaemic clamp reported similar results.

“two studies using a graded stepped hypoglycaemic clamp reported similar results [18, 19].”

Two studies dating back to the 1990s that used a gradual glucose-lowering method to assess glycaemic thresholds in children with type 1 diabetes reported results in line with the systematic review's findings.

“Nevertheless, two studies dating back to the 1990s that used such a gradual glucose-lowering method to assess glycaemic thresholds in children with type 1 diabetes reported results that were in line with our findings [17, 18].”

A total of 25 studies (40%) provided data to either calculate or extract the glycaemic threshold for symptom responses to hypoglycaemia.

“A total of 25 studies (40%) provided data to either calculate or extract the glycaemic threshold for symptom responses to hypoglycaemia [6, 13, 16–18, 20, 23, 24, 26, 29, 31, 33–37, 46, 51–53, 56, 57, 58, 63, 68].”

The authors of the clamp reproducibility study concluded that the method produced reproducible results.

“indeed, the authors concluded that the method gave reproducible results [16].”

Intraindividual differences in the hyperinsulinaemic-euglycaemic and -hypoglycaemic clamp techniques are about 0.2 mmol/l (4 mg/dl).

“intraindividual differences of approximately 0.2 mmol/l (4 mg/dl) [16]”

It is controversial whether autonomic symptoms have a lower glycaemic threshold than neuroglycopenic symptoms.

“In addition, it is controversial as to whether the glycaemic threshold for appearance of autonomic symptoms is lower than that of neuroglycopenic symptoms (i.e. a smaller decrease in plasma glucose concentration is sufficient to elicit the autonomic as compared to neuroglycopenic symptoms) [2,3,6].”

If the glycaemic thresholds of neuroglycopenic and autonomic symptoms are identical, as indicated by Vea et al. and the present studies, then neuroglycopenic symptoms do not indicate more severe hypoglycaemia than autonomic symptoms.

“If the glycaemic thresholds of neuroglycopenic and autonomic symptoms are identical, as the studies of Vea et al. [6] and the present studies indicate, it can be concluded that the appearance of neuroglycopenic symptoms does not indicate a more severe hypoglycaemia, as compared to that inducing autonomic symptoms, as previously suggested [3].”

Vea et al. demonstrated that the glycaemic thresholds of autonomic and neuroglycopenic symptoms are identical (about 3.5 mmol/l) and reproducible on different days.

“These authors demonstrated that the glycaemic thresholds of autonomic and neuroglycopenic symptoms are identical (-3.5 mmol/1) and reproducible on different days.”

The present results agree with the majority of previous studies, including those of Vea et al.

“However, our results are in agreement with the majority of previous studies [1,2], including those of Vea et al. [6].”

Glycaemic thresholds differ between non-diabetic individuals, and accurate determination of thresholds is difficult in all individuals, irrespective of insulin-treated diabetes.

“Not only do glycaemic thresholds differ between non-diabetic individuals, but accurate determination of the thresholds is difficult in all individuals, irrespective of whether or not they have insulin-treated diabetes.”

Vea et al. showed mean intraindividual differences of 0.22 mmol/l for secretion of counter-regulatory hormones and 0.25 mmol/l for onset of symptoms.

“The reproducibility of the glycaemic thresholds was studied in normal individuals by Vea et al. [10], who showed mean intraindividual differences of 0.22 mmol/l for the secretion of counter-regulatory hormones and 0.25 mmol/l for the onset of symptoms.”