Commercial Pilots on Insulin - ESAM€¦ · Ries Simons FEB 2014 Restoration of self-awareness of...

Commercial Pilots on Insulin ?

Ries Simons, consultant Aerospace Medicine

Chairman Advisory Board - European Society of Aerospace Medicine

Ries Simons FEB 2014

I have no financial relationships to disclose.

Ries Simons, M.D.

I will not discuss off-label use and/or investigational use

in my presentation

Ries Simons FEB 2014

March 2012

www.esam.aero

Ries Simons FEB 2014

Ries Simons FEB 2014

There is consensus on the need for insulin in T1 and T2DM treatment to prevent microvascular and macrovascular complications.

Hypoglycaemia represents a significant and unacceptable threat to flight safety.

Discussion Statements

Ries Simons FEB 2014

Hypoglycaemia should always be prevented (not only in pilots)

Hypoglycaemia → syndromes of defective glucose regulation

→ impaired awareness of hypoglycemia

→ reduction neuroendocrine/symptomatic responsesto hypoglycaemia

[Cryer, 1992 ; Heller & Cryer, 1991]

Vicious Circle of Hypoglycaemia

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Risk Factors for Hypoglycaemia

Use of insulin or sulfonylureas

Have a lower HbA1c

Prior hypoglycaemia

C-peptide negativity

Long duration of DM

Hypoglycaemia unawareness

Alcohol / β-blockers / ACE-inhibitors

Irregular eating habits / fasting / fear of hyperglycaemia

Exercise

Older people

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Type 2 diabetics on insulin can also become hypoglycaemic !

Risk of severe hypoglycaemia ≈ similar in T2 and T1 DM

when matched for disease duration

Risk of car crashes:

no clear relationship with type of diabetes[2nd EU Working Group on Diabetes and Driving, 2005]

[Leese et al., 2003; Swinnen et al., 2009]

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Factors preventing Hypoglycaemia in Pilots

Consider only stable cases

Frequent monitoring of blood glucose (SMBG/CGM)

Use of long-acting + rapid-acting insulin analogues

Training in absolute avoidance of hypoglycaemia

Identify hypoglycaemic unawareness by

hyperinsulinaemic-hypoglycaemic clamp tests ?

Being a professional pilot

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CGM may reduce overall hypoglycemic exposure in well-controlled type 1 diabetes [Juvenile Diabetes Research Foundation CGM Study Group, 2009]

Real-time CGM reduced severe hypoglycemia in hypo-unaware T1DM patients [Choudhary et al., Diabetes Care 2013]

Continuous Glucose Monitoring

Frequent monitoring of blood glucose (SMBG or CGM)

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[Jensen et al., 2013]

CGM may be inaccurate in the hypoglycemic range, with hypoglycemic events confirmed by SMBG but not CGM[Rebrin et al., 2010; Kovatchev et al., 2008; Bode et al., 2004]

CGM + model: optimises prediction [Jensen et al., 2013]

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Heller et al., Lancet 2012; 379:1489-97

Type 1 DM

Long acting analogues: Less Hypos ?

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Long acting analogues: Less Hypos ?

Type 2 DM

Garber et al., Lancet 2012; 379:1498-507

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Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial (Leelarathna et al., 2013)

After HypoCOMPaSS education, mean BG at which subjects first felt hypoglycemic increased: from 2.6 to 3.1 mmol/L and symptom and plasma metanephrine responses to hypoglycemia were higher.

18 subjects with T1D and IAH: mean age 50, T1D duration 35 yrs, HbA1c 8.1% [65 mmol/mol]

Training aimed at absolute avoidance of hypoglycaemia

Other training programmes: BGAT, HyPOS, DAFNE

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“Healthy” reaction: hyperinsulinaemic hypoglycaemia characterized by a significant increase in the plasma adrenaline concentration and by decreases in peripheral resistance and diastolic blood pressure.

Hyperinsulinaemic-hypoglycaemic clamp test when in doubt?

[Laitinen et al, 2003 – n=18]

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Identify hypoglycaemic unawareness:hyperinsulinaemic-hypoglycaemic clamp tests ?

Hyperinsulinemic hypoglycemic clamp: insulin is infused at a constant rate but blood glucose is allowed to fall and is fixed at a hypoglycemic level.

The hypoglycemic clamp can be used to test hypoglycemic counterregulation.

Antecedent hypoglycemia blunted the counterregulatory responses (epinephrine and sympathetic nerve activity) in type 2 and type 1 diabetics (compared with healthy controls) [Davis et al., 2009]

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The only method to exclude impaired performance due to

in-flight hypoglycaemia will be to ensure that BG levels are

≥5 mmol/l (≥91 mg/dl) during the entire flight operation [Warren & Frier, 2005]

Discussion Statement

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ESAM Recommendation

ITDM applicants may be considered for aeromedical certification:

on a case by case basis

using a protocol based on the principles developed by

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Important entry criteria to the protocol:

Evidence of stable glycaemic control

HbA1c between 6.5 and 8.0% (42–64 mmol/mol) blood glucose analysis over 3 months before application:

≤5% of readings <4.0 mmol/L80% of readings 5 - 15 mmol/L)

no recurrent (≤ 2) severe hypoglycaemia in past 5 years no severe hypoglycaemia in the preceding 1 year

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Pre- and In-Flight Requirements

5-15 mmol/l (91 - 273 mg/dl)

>6 mmol/l (110 mg/dl)

5.5-16.5 mmol/l (100-300 mg/dl)

5-15 mmol/l (91 - 273 mg/dl)

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ADA/EASD recommendations

HbA1c concentration of between 6 and 7% (42–53 mmol/mol)

This enables pilots to have safe in-flight blood glucose, because in stable patients these HbA1c values are associated with average estimated glucose concentrations of between

7.0 mmol/L and 8.6 mmol/L (126 -154 mg/dL)

(eAG [mg/dl] = 28.7 x HbA1c – 46.7)[American Diabetes Association, 2011; Nathan et al., 2008]

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Commercial pilots: more complicated?

Pro: Multi-pilot OPS: in-flight BG management easy to do

Con: Circadian problems

Con: Irregular rosters

Con: Delays

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Commercial pilots: more complicated?

Con: Circadian problems

Con: Irregular rosters

Con: Delays

Problems may be overcome by:

tailor-made training

self-management BG

long acting insulin analogue + ‘on demand’ short acting analogues

long-haul simulator ‘try-outs’ at circadian difficult times of day + delays

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Avoid to come near upper limit of 15 mmol/L (273 mg/dL):

seems safe for cognitive-motor function* [Cox et al. 2005]

may allow too high BG during big part of professional life high BG during long-haul flight may cause dehydration (?)

Considerations regarding Commercial Pilots:

Flying is their job: 8-11 hrs / 4-5 days a week

* Would this also apply to slightly hypoxic pilots?

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King et al. (2011). Changes in Altitude Cause Unintended Insulin Delivery From Insulin Pumps: Mechanisms and implications.

Diabetes Care 34:1932–1933, 2011

In-flight: + 1.37 U of 5 Animas Pumps (0.685% of cartridge volume)

+ 1.01 U of 5 Medtronic Pumps (0.561% of cartridge volume)

Rapid Decompression: + >8 Units All Pumps

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We will confidently fly with an insulin-treated pilot who has astable glycaemic control, has no substantial disease complications, and is compliant with self measurement and management of pre-flight and in-flight blood glucose.

Civil aviation authorities should continue to aim for consistency in guidelines between international authorities and consider individual cases of insulin-treated pilots for certification.

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Data of all pilots flying with insulin should be systematically collected to assess the usefulness and safety of the

recommendations

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Insulin treated ATCOs

Should be considered on a case by case basis

Same principles as for pilots, but easier to replace in case of symptoms

When started on insulin treatment, ATCO must be reassigned to non-safety related duties for 3 months or until criteria for acceptableblood glucose regulations are met.

ITDM ATCOs should identify themselves to supervisors/colleagues,who should be informed about symptoms of hypoglycemia.

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A huge challenge both for the applicant

and the examiner . . . . . .

The art of medicine is to give the best individual guidance,

based on science and individual clinical considerations . . .

But it is satisfying, because