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However, the clinical consequence of improving glycaemic control is an increase in the frequency of
hypoglycaemia 2, 3 which is a concern in the risk assessment of diabetic aircrew. The relative risk of
severe hypoglycaemia (requiring the assistance of another) is greater for intensively treated (to achieve
lower HbA1C levels) patients with Type 1 diabetes (about 27 per cent per year according to the Disease
Control and Complications Trial [DCCT]) 3 than for those with Type 2 (2 per cent per year according to
the UK Prospective Diabetes Study [UKPDS]) 2 despite similar glycaemic control.
Several factors may explain why patients with Type 2 diabetes are less prone to severe hypoglycaemia.
Normally, as plasma glucose concentrations fall, there is a hierarchy of defence responses. The first is an
increase in the release of counter-regulatory hormones as plasma glucose falls to approximately
3.8 mmol/L, which is designed to prevent glucose concentrations from falling further. The second is an
awareness of warning symptoms, predominantly autonomic (sweating, hunger, anxiety, tachycardia, etc.),
which begin as plasma concentration decreases to approximately 3.4 mmol/L. In patients well educated
in diabetic management, such symptoms will prompt preventive steps, i.e. ingestion of carbohydrate,
which will prevent neuroglycopaenia, which commences at approximately 3.0 mmol/L.
In people who have had Type 1 diabetes for over five years, counter-regulatory hormone responses to
hypoglycaemia are generally impaired. Initially, most patients lose their glucagon response to
hypoglycaemia, thereby becoming dependent on catecholamine responses to prevent or reverse
hypoglycaemia. Sometimes even that response becomes impaired and the risk of severe hypoglycaemia
increases several fold. Additionally, episodes of mild hypoglycaemia, even if symptomless, can further
impair glucose counter regulation and may reduce ß-adrenergic sensitivity leading to a situation of
“hypoglycaemic unawareness”. In this situation, patients may not recognize impending hypoglycaemia
until it is too late to institute preventive measures (Gerich J F) 4. The situation is somewhat different in
Type 2 diabetes. Firstly, although glucagon responses are commonly impaired, catecholamine responses
are usually normal or increased. Secondly, the patients are insulin resistant; and thirdly, they have
persistent ß-cell function. The ability to modulate insulin secretion can act as a buffer, since endogenous
insulin secretion will decrease as plasma glucose falls. This opportunity is not available in Type 1 patients
whose insulin availability is pre-determined by the amount already injected. Fourthly, most Type 2
patients are not on intensive insulin regimes so they are less at risk of hypoglycaemic unawareness as a
result of insulin induced hypoglycaemia.
This differing rate of hypoglycaemia has been confirmed by Heller et. al.5 who found no differences in
the rate of severe hypoglycaemia in Type 2 diabetic patients treated with sulphonylureas or insulin for
less than 2 years (0.1 and 0.2 episodes per subject – year) and this frequency was far less than that
encountered in Type 1 diabetes (< 5 years 1.1; > 15 years 3.2 episodes per subject – year).
From a number of studies including Akram et. al.6, the risk factors for severe hypoglycaemia include
previous hypoglycaemia, long duration of diabetes, and impaired hypoglycaemic awareness.
From the literature review, the risk of hypoglycaemia in Type 1 diabetes is outside that which would be
acceptable in terms of the “1 per cent rule”. States using different risk criteria should make their own
assessment of risk.
ICAO Preliminary Unedited Version — November 2009 III-4A2-2
For aircrew with Type 2 diabetes, whether taking insulin or not, individuals should be at low risk of
hypoglycaemia. What follows is a cautious protocol that may assist States to determine fitness in
applicants who present with Type 2 diabetes. It provides guidance and may be adjusted by individual
States to suit their own requirements.
PROTOCOL
Initial assessment
• Stimulated C-peptide levels* > 25 per cent of normal;
• No previous hypoglycaemic episodes requiring the intervention of another person;
• Stable blood glucose control: satisfactory HbA1C ~ 7 – 8 per cent;
• Adequate self-monitoring with a memory chip glucose meter;
• No evidence of hypoglycaemic unawareness;
• Good diabetes education and understanding;
• Positive attitude to monitoring and self-care.
An annual assessment may include:
• Review of adequate self-monitoring with a glucose meter;
• Review of blood glucose control with satisfactory, stable HbA1C;
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Manual of Civil Aviation Medicine 1(142)
