Protocol ID/number Kilimanjaro challenge

RESEARCH PROTOCOLS Kilimanjaro Challenge, 10-26 October 2008

Protocol ID/number Kilimanjaro challenge

Protocol ID/number Kilimanjaro challenge

Compilations of various studies involving blood sample collections Study 1: glucose measurements under controlled hypobaric conditions Introduction As physical exercise improves metabolic control and decreases the risk on developing longterm complications many type 1 diabetes mellitus (T1DM) patients now participate in al forms of physical activity. (1?) Extreme sports such as high altitude mountaineering emphasize the need for frequent and reliable monitoring of blood glucose levels. However, previous expeditions with T1DM patients have proven accurate monitoring of blood glucose levels to be compromised at high altitude. (2) Blood glucose monitoring using glucose oxidation based methods underestimate true blood glucose levels. Glucose dehydrogenase based blood glucose measurement proved to be more accurate at high altitude. However, next to hypobaric oxygen conditions, low temperature and alternating air humidity at high altitude independently compromise accurate blood glucose monitoring. (3,4). Available blood glucose meters are multiple and previous research has led to an wide range of inaccurate readings by different blood glucose meters. As accurate monitoring of blood glucose in T1DM patients is of major importance to safely recreate at high altitude adequate knowledge of which blood glucose monitoring method to use is needed. Aims To determine the accuracy of different blood glucose meters at various temperatures and simulated altitudes. Hypotheses We hypothesize that glucose dehydrogenase based blood glucose meters will be more accurate as compared to oxidase based blood glucose meters at high altitude (>2000m). However, at low temperatures both meters will give faulty readings Methods Using a hypobaric chamber different blood glucose meters using either the glucose oxidaseor glucose dehydrogenase – based methods will be tested at simulated altitudes of 0m, and from the virtual 1500 m every 500 m till 5000 m. Preferably, blood glucose meters will also be tested under different temperatures; 20 C, 10 C, and 0 C. Testing will take place using standard specifically prepared blood samples (5, 10, 15, en 20 mmol/l). Glucose meters to be used To be determined by Marion Fokkert, Pieter de Mol, and Bert Dikkeschei / Robbert Slingerland; see suggestions in Dutch text. References 1. Steppel JH ea: Exercise in the management of type 1 diabetes mellitus; Rev Endocr Metab Disord 2003 2. Brubaker PL; Adventure travel and type 1 diabetes; Diabetes care 2005 3. Oberg et al. Performance of glucose dehydrogenase – and glucose oxidase- based blood glucose meters at high altitude and low temperature; Diabetes Care; 28(5), 2005,

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4. Finks et al. Effect of high altitude on blood glucose meter performance; Diabet. Technol Ther.; 4(5), 2002

Study 2 Function and dysfunction of various methods for glucose measurement at altitude Introduction As physical exercise improves metabolic control and decreases the risk on developing longterm complications many type 1 diabetes mellitus (T1DM) patients now participate in al forms of physical activity. Extreme sports such as high altitude mountaineering emphasize the need for frequent and reliable monitoring of blood glucose levels. However, previous expeditions with T1DM patients have proven accurate monitoring of blood glucose levels to be compromised at high altitude. (1) Blood glucose monitoring using glucose oxidation based methods underestimate true blood glucose levels: possibly because essential oxygen for an adequate chemical reaction and accurate blood glucose determination is simply reduced under hypobaric conditions. Glucose dehydrogenase based blood glucose measurement proved to be more accurate at high altitude. However, next to hypobaric oxygen conditions, low temperature and alternating air humidity at high altitude independently compromise accurate blood glucose monitoring. (2,3). Most previous research has taken place under simulated conditions, though field research at high altitude and low temperatures is scarce. As accurate monitoring of blood glucose in T1DM patients is of major importance to safely recreate at high altitude adequate knowledge of which blood glucose monitoring method to use is needed. Aims To determine the accuracy of different blood glucose meters: glucose oxidation based and glucose dehydrogenase based methods at different altitudes and temperatures during the ascend of Mt Kilimanjaro (5895m).

Hypotheses Glucose oxidation based blood glucose meters will progressively underestimate true blood glucose levels at altitudes > 2500m. Both glucose oxidation- and glucose dehydrogenase – based blood glucose meters will be affected by low temperature and possibly air humidity.

Methods

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Eight type 1 diabetes mellitus (T1DM) patients free of complications and eight healty volunteers will be tested regarding their capillary blood glucose, using different blood glucose meters at different altitudes and temperatures during the Mt Kilimanjaro Expedition. The selection of blood glucose meters to be used will be made based on the tests in Chapter 1. A standard solution will be used as reference value in this exercise. References 1. Brubaker PL; Adventure travel and type 1 diabetes; Diabetes care 2005 2. Oberg et al. Performance of glucose dehydrogenase – and glucose oxidasebased blood glucose meters at high altitude and low temperature; Diabetes Care; 28(5), 2005, 3. Finks et al. Effect of high altitude on blood glucose meter performance; Diabet. Technol Ther.; 4(5), 2002

Study 3 Use and function of continuous transcutaneous glucose registration at altitude Introduction An increasing number of T1DM patients participate in extreme physical activity such as long distance running and (extreme) high altitude trekking. The latter, defined as altitudes > 5000m, poses some specific demands on T1DM patients as physiology, glucose metabolism and measurement of glucose levels differ at altitude compared to sea level. Previous expeditions with T1DM patients have proven accurate monitoring of blood glucose levels to be compromised at high altitude. (1) Moreover, previous research on the accuracy of handheld blood glucose meters showed glucose oxidation based meters to underestimate true blood glucose levels. Glucose dehydrogenase based blood glucose measurement proved to be more accurate at high altitude. However, next to hypobaric oxygen conditions, low temperature and alternating air humidity at high altitude independently compromise accurate blood glucose monitoring. (2,3). Available blood glucose meters are multiple and previous research has led to an wide range of inaccurate readings by different blood glucose meters. Furthermore, high altitude trekking is known to cause worsening of glycemic control as determined by HbA1C levels not only in T1DM patients but also in healthy controls. (4) As accurate monitoring of blood glucose in T1DM patients is of major importance to safely recreate at high altitude continuous blood glucose monitoring systems (CGMS) might be the answer in anticipating changes in glycemic control in T1DM patients at high altitude. Previous research shows CGMS to be more informative than conventional blood glucose meters when analyzing glucose profiles up to 72 hrs.(5) Also, CGMS have proven acceptably

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accurate when compared to handheld blood glucose meters although rapidly changing glucose profiles show a greater difference. (6) So far, correlation coefficients were found of approx. r=0.84-0.92 with sensitivity and specificity for detecting hypoglycaemia of 39-67% and 90-94% respectively. (5,6) Lastly, they have been safely used during exercise and augmenting patients to recognize late onset nocturnal hypoglycaemia. (7) Aims 1. To test the efficacy of a continuous glucose monitoring system during prolonged submaximal exercise at altitude (the ascend of Mt Kilimanjaro (5895m) ) using the Medtronic Sensor (CGMS) compared to intermittent capillary blood glucose measurements. 2. To compare accuracy of CGMS with capillary handheld blood glucose meters. 3. To detect nocturnal late onset hypoglycaemia using a CGMS. Hypotheses 1. Using CGMS during different intensity of exercise, differences of glucose metabolism and hormonal influences at high altitude, timely anticipating on fluctuating glucose levels will be achieved. 2. Handheld capillary blood glucose meters will be more accurate at moderate altitudes compared to CGMS. However, as accuracy of capillary blood glucose meters will be influenced by low temperature and air humidity, subcutaneous glucose monitoring will become more accurate at altitudes >2500m compared to capillary blood glucose meters. Methods Eight type 1 diabetes mellitus (T1DM) patients free of complications will use the Medtronic sensor (CGMS) at different altitudes and temperatures during the Mt Kilimanjaro Expedition in October 2008. Trends and accuracy of glucose levels will be compared with handheld capillary blood glucose meters during multiple measurements daily. Furthermore, functioning and efficacy of the Medtronic sensor (CGMS) will be evaluated during the ascend at high altitudes and low temperatures. Lastly, the occurrence rate of late onset nocturnal hypoglycaemia will be determined. References 1. Brubaker PL; Adventure travel and type 1 diabetes; Diabetes care 2005 2. Oberg et al. Performance of glucose dehydrogenase – and glucose oxidase- based blood glucose meters at high altitude and low temperature; Diabetes Care; 28(5), 2005, 3. Finks et al. Effect of high altitude on blood glucose meter performance; Diabet. Technol Ther.; 4(5), 2002 4. Pavan, P et al. Metabolic and cardiovascular parameters in type 1 diabetes at extreme altitude. Diabetes Care; 26(11), 2003

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5. Guerci B et al. Clinical performance of CGMS in type 1 diabetic patients treated by continuous subcutaneous insulin infusion using insulin analogs Diabetes Care. 2003 Mar;26(3):582-9. 6. Bode et al. Alarms based on real time sensor glucose values alert patients to hypo and hyperglycemia: The guardian continuous glucose monitoring system. Diab Technol. Ther. 6(2) 2004. 7. Iscoe KE et al. Efficacy of continuous glucose monitoring during and after prolonged high –intensity cycling exercise: spinning with a continuous glucose monitoring system. Diabetes Technol Ther. 2006 dec;8(6) 627-35

Study 4 Hematocrit changes at high altitude Background Adaptation takes place when going to high altitude. It is defined as having three stages: 1. acute: first 72 hours 2. subacute: from 72 hours until the slope of the hematocrit increases 3. chronic: hematocrit level is constant (optimal level) Recent research showed a necessary 40 days to achieve a complete and optimal hematocrit adaptation. (Zubieta-Calleja GR ea; J. Physiol Pharmacol. 2007) Others studied 50 healthy army men working 4 days at an altitude of 3550 m with a 3 days rest at sea-level. Hematocrit was elevated at altitude, but lower than in permanent residents. (Brito J ea; High Alt. Med. Biol. 2007) Objective To evaluate the increase of hematocrit at high altitude. Methods Hematocrit will be measured at different altitudes during the Kilimanjaro Challenge 2008. Eight type I diabetics and 8 healthy controls will ascend Mount Meru, descend to a lower altitude and ascend Mount Kilimanjaro thereafter. Research questions Will hematocrit elevate during this relative short stay at high altitude? If hematocrit increases, how fast will it increase and how fast will decrease to the level of sea-level? Is there an association with Acute Mountain Sickness? Are there consistent differences between non-diabetic and diabetic subjects?

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Study 5: Evaluation of energy expenditure in type I diabetics and healthy controls during the Kilimanjaro Challenge 2008 Introduction Maintaining a healthy weight and an active lifestyle are seen as the key to fighting serious medical conditions like obesity, cardiovascular disease and diabetes. The SenseWear® Armband has been designed to deliver objective parameters such as total energy expenditure and the duration of physical activity in order to provide a good guidance in lifestyle management. (SenseWear®: behavior therapy that makes sense) The SenseWear® also proved to be of aid in clinical use. Nutrional problems are common in cancer patients and are frequently due to metabolic derangements. Thus, accurately assessing energy expenditure is important for the planning of adequate nutrition support. Indirect calorimetry is the golden standard, but not always available. The SenseWear® seemed to provide an accurate estimation of the energy expenditure. (Cereda E ea; JPEN 2007) The SenseWear® Armband was succesfully tested in healthy subjects and turned out to be an acceptable device for measuring resting energy expenditure. (Malavolti M ea; Nutr.Metab.Cardiov.Dis. 2007) It was also the best estimate of total energy expenditure in a treadmill-test of healthy subjects. (King GA ea; Med.Sci.Sports.Exerc. 2004) Other research showed a slight underestimation of the inclined walking energy expenditure. (Fruin ML ea; Med.Sci.Sports.Exerc. 2004) Research made clear it seems necessary to apply exercisespecific algorithms to the SenseWear® Armband to enhance its accuracy (Jakiicic JM ea; Med.Sci.Sports.Exerc. 2004) This also appeared to be necessary in obese subjects (Papazoglou D ea; Obesity 2006), cardiac rehabilitation patients (Cole PJ ea; J.Sports.Med.Phys.Fitness 2004) and children (Dorminy CA; Med.Sci.Sports.Exerc. 2008; Arvidsson D ea; Med.Sci.Sports.Exerc. 2007) Objective Measurement of energy expenditure during an high altitude expedition in type I diabetics compared to healthy controls. Methods A group of 8 selected patients with type I diabetes and a group of 8 selected healthy subjects will ascend Mount Kilimanjaro during the Kilimanjaro Challenge 2008. During the expedition the SenseWear® Armband will be used for estimation of the energy expenditure. Research questions What is the energy expenditure during the Kilimanjaro Challenge 2008? What is the energy expenditure in both groups over the time? Is there a difference between type I diabetics compared to healthy controls? What is the relation between energy expenditure and insuline-use?

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Study 6: 6a: Insulin use in Type I diabetics while ascending Mount Kilimanjaro Background More than 30.000 climbers try to reach the summit of Mount Kilimanjaro every year and among them climbers with type I diabetes.(T1DM) Summit success rates in diabetics do not differ from paired fit individuals without T1DM in extreme high altitude mountaineering (>5000m) Also, cardiovascular performance in T1DM patients free of complications is similar to healthy subjects up to 5800m altitude. (1,2,3) Both in healthy subjects as in T1DM patients, high altitude trekking is known to cause worsening of glycemic control as determined by HbA1C levels. (3) Furthermore, insulin requirements change during physical exercise at altitude. However, reports are controversial as increments in insulin dosage are reported by some where decrements are reported by others. (3,4) Physiologic response to short term (