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ACUTE HYPOBARIC HIPOXIA DOES NOT AFFECT THE INSULIN REQUIREMENT IN WELL-CONTROLLED DIABETICS.
Conxita Leal, Jordi Admetlla,Teresa Pagés, Ginés Viscor, Antoni Ricart 

Introduction
The effects of acute hypoxia on the metabolism of glycemia in patients with type 1 diabetes mellitus are little known. The data we have at present are based on the study of diabetic alpinists at high altitude. Exposure to altitude implies an increase of the activity of counterinsulin hormones, which has led to the supposition that at high altitudes higher doses of insulin would be required. However, previous field studies (Admetlla 2002) are not conclusive. 

Materials and methods
To clarify the role of acute hypoxia in the metabolism of glucose and in the sensitivity to insulin, 6 diabetic subjects, 5 of whom had wide previous experience at high altitude, were submitted to 2 sessions of 3 hours’ duration each in a hypobaric chamber, during which the subjects’ glycemia was monitored by continuous recording sensors. The work protocol was approved (20 April 2005) by the Bioethics Committee of the Universidad de Barcelona (Institutional Review Board IRB00003099). All the subjects were given a complete medical check-up at the beginning of the study and agreed to follow the general guidelines in their diet and physical activity for the whole duration of the study.

The study lasted for four days, during which the physical activity and the diet of the participants was monitored. Each subject self-managed and self-reported both the physical activity and the diet, which were similar each day.  On the first day, the glucose sensors were implanted and the subjects were allowed to familiarize themselves with the operation of these devices. On the two complete recording days that followed, a morning schedule (9:00-13:00h) was developed of sessions in the hypobaric chamber, although only on the second occasion was the vacuum system used, attaining a simulated altitude condition equivalent to 5000m. In this way, it was possible to compare the values and tendencies in all the parameters between both days (controls in normoxia and in hypoxia). On the fourth day, only the collection of morning urine samples were carried out and the data of the monitoring teams were recovered.

On the morning of the first day of the study, the subjects were implanted with a subcutaneous glucose sensor (CGMSgold Medtronic Mini-Med, Sylmar, CA, USA). This device continued to function until the morning of the fourth day. Following the manufacturer’s instructions, each subject calibrated their own instrument at least 4 times each day with the glycemia values obtained in a capillary sample from the middle finger of the hand. On the second and third days, two blood extractions were drawn from an antecubital vein for all the subjects participating in the study: one prior to beginning and the other on ending the morning session in the hypobaric chamber. The parameters analyzed were: the red series, glucose, glucagon, cortisol, growth hormone, insulin, C-peptide, and vanillylmandelic acid (VMA). Cortisol was determined via a urine sample collected from the first morning urine. All the analyses were carried out by a homologated laboratory by standard means. Physical activity was monitored by a podometer, along with the diet and insulin dosage via various questionnaires, in each one of the subjects on the days of data collection. 

Results and conclusions
The diet, the exercise, and the glycemia variations throughout the day were similar on both days, the one for normoxia and the one for hypoxia. No significant differences were found in any of the parameters measured between normoxia and hypoxia. These findings appear to indicate that hypoxia itself does not have a determining effect on glycemia in well-controlled diabetics, which is not surprising if we consider that for obvious reasons of ethics and security the administration of insulin in the patients was not restricted. However, there was no variation in the insulin requirements between the two days, either, which shows that neither sensitivity to insulin nor the net rate of glucose use is affected by an acute hypobaric hypoxia.

It must be noted that the study has an important limitation imposed by the design itself: the exposure to hypoxia was acute—intense and short. For this reason, the results cannot be extrapolated to other real situations on the mountain, where diet and exercise are not controlled, or where other factors can influence, such as the degree of individual acclimatation, the cold, or fatigue. Studies will be needed with more prolonged or intermittent exposures to define the response of diabetics to altitude.
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