Changing the glucose cut-off values that define hypoglycaemia has a major effect on reported frequencies of hypoglycaemia

Abstract

Aims/hypothesis The aim of this analysis was to quantify the relationship between the frequency of hypoglycaemia and various glucose cut-off points for the definition of hypoglycaemia, within a range of HbA 1c strata. Methods Data from two trials examining insulin glargine dose titration in 12,837 type 2 diabetic participants starting insulin therapy were combined. Curves for hypoglycaemia frequency plotted against endpoint HbA 1c level were constructed, using a range of glucose cut-off points for hypoglycaemia. Results During the 12-week study period, 3,912 patients recorded 21,592 hypoglycaemic episodes, comprising 242 severe, 8,871 symptomatic and 12,479 asymptomatic events, corresponding to hypoglycaemia event rates of 0.10, 3.8 and 5.3 events per patient year. Increasing the hypoglycaemia cutoff point from, for instance, <3.1 to <3.9 mmol/l more than doubled the percentage of affected patients, e.g. from 17.7 to 43.3% at HbA 1c 7.0-7.2%. At higher hypoglycaemia cut-off points the proportion of patients having only asymptomatic hypoglycaemia increased, e.g. from 30.7% at <3.1 mmol/l to 61.7% of patients at a cut-off point of <3.9 mmol/l. In sensitivity analysis, 121 of 1,756 patients with at least one self-monitored blood glucose value <3.1 mmol/l experienced severe hypoglycaemia, compared with 149 of 3,912 patients with a self-monitored blood glucose level of <3.9 mmol/l. Thus, to identify 28 more patients with severe hypoglycaemia, the number of patients experiencing only non-severe hypoglycaemia more than doubled. Conclusions/interpretation The glucose cut-off point defining hypoglycaemia greatly affects the reported frequency of hypoglycaemia. When hypoglycaemia is to be defined by a predetermined glucose level, to have clinical relevance the cut-off should be set at a lower level than the threshold of 3.9 mmol/l proposed by the American Diabetes Association.

Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies

“…Similarly, in the international Addison's survey of the UK Addison's Disease Self-Help Group, 47% of the participants reported that they had needed emergency treatment at a hospital since their diagnosis, and of these 10% reported that they had needed emergency hospital treatment on four or more occasions (17). Thus, AC is relatively common in patients with PAI or SAI with a frequency in the same order of magnitude as severe hypoglycaemia requiring assistance in patients with diabetes mellitus (about 10 per 100 patient years) (18,19).…”

Defining hypoglycaemia: what level has clinical relevance?

“…This is an important consideration as it is evident that the glucose level that is selected to define hypoglycaemia can influence estimates of the frequency of this therapeutic side effect-a choice that could have important clinical and commercial implications. To illustrate this, Swinnen et al [3] applied a range of different glucose levels defining hypoglycaemia to the blood glucose data from two large prospective trials of people with type 2 diabetes who had commenced treatment with insulin. As reported in this issue of Diabetologia, they unequivocally demonstrate how changing the glucose cut-off level can profoundly influence the estimated frequency of hypoglycaemia.…”

“…Although these responses may be preceded by some release of counter-regulatory hormones in non-diabetic individuals, the absence of glucagon secretion in insulin-deficient diabetes negates the clinical importance of defining hypoglycaemia on this basis. While the difference between 3.5 and 3.9 mmol/l may appear to be insignificant, Swinnen et al [3] have clearly illustrated how a small change in the cut-off level can magnify the prevalence of asymptomatic hypoglycaemia. Ironically, an arterialised venous glucose level of 3.9 mmol/l is probably equivalent to a capillary blood glucose level of 3.5 mmol/l.…”

Preventing hypoglycaemia: what is the appropriate glucose alert value?

“…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 identifies a higher percentage of patients who suffer severe hypoglycaemia, i.e.…”