Category Archives: Genetics

Accessibility, Acclimation, Altitude Science, Athletic Training, Genetics, Health, High Altitude

Peak Performance: Coach wants a Blood Test

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Iron Deficiency without Anemia in Individuals Living at Altitude 

Madeline Larson, PA-S2

People living at high altitude typically have higher hemoglobin levels compared to those at sea level. This physiological adaptation occurs due to the lower oxygen availability at high elevations which stimulates the production of erythropoietin, a hormone that prompts the bone marrow to produce more red blood cells made famous by the Lance Armstrong blood-doping scandal. Hemoglobin, the protein in red blood cells that carries oxygen, thus increases to enhance the blood’s oxygen-carrying capacity. This adaptation helps individuals efficiently transport oxygen to tissues despite the reduced atmospheric pressure. Over time, this increased hemoglobin level helps maintain adequate oxygen delivery to vital organs, supporting overall health and physical performance in the challenging high-altitude environment.

Despite this natural adaptation of increased hemoglobin levels, people living at high altitude are still susceptible to anemia. Chronic exposure to lower oxygen levels can sometimes lead to a condition where the body’s capacity to produce red blood cells is insufficient to meet increased demands. This can be due to various factors, including inadequate dietary iron, vitamin deficiencies, or underlying health conditions that impair red blood cell production or lifespan. Additionally, individuals who move to high altitudes without sufficient acclimatization may experience a temporary drop in hemoglobin levels until their bodies adjust. Addressing anemia in such environments often involves a combination of dietary adjustments, supplementation, and medical interventions to ensure that the red blood cell count remains adequate to maintain optimal oxygen transport and overall health.

In people living at high altitudes, the threshold for diagnosing anemia is often adjusted to account for the lower oxygen levels in the environment. At high altitudes, the normal range for hemoglobin and hematocrit levels can be higher due to the body’s adaptation to reduced oxygen levels.

For example:

  • Hemoglobin Threshold: At sea level, anemia is commonly defined as a hemoglobin level below 13.0 grams per deciliter (g/dL) in men and 12.0 g/dL in women. In high-altitude areas, these thresholds might be higher. For instance, at elevations above 2,500 meters (8,200 feet), a hemoglobin level of around 14.0 g/dL in men and 13.0 g/dL in women might be considered the lower limit of normal.
  • Hematocrit Threshold: Similarly, normal hematocrit levels are adjusted. At sea level, anemia is typically diagnosed with hematocrit levels below 39% in men and 36% in women. At high altitudes, these values might be adjusted to about 42% for men and 40% for women.

These adjustments are necessary because high-altitude residents tend to have higher hemoglobin and hematocrit levels as a physiological response to lower oxygen availability. If someone at high altitude presents with symptoms of anemia but has hemoglobin or hematocrit levels within the high-altitude normal range, further evaluation might be needed to assess their overall health and adapt to the specific altitude.

Understanding Iron Deficiency Without Anemia: What You Need to Know

Iron is an essential mineral that plays a crucial role in various bodily functions, most notably in the production of hemoglobin, which is vital for oxygen transport in the blood. While many people are familiar with iron deficiency anemia, where low iron levels lead to a reduced number of red blood cells, there is another, often overlooked, condition: iron deficiency without anemia. Understanding this condition is important for addressing health issues that can arise even in the absence of anemia. 

What is Iron Deficiency Without Anemia?

Iron deficiency without anemia occurs when the body’s iron levels are insufficient, but the quantity of red blood cells and their capacity to carry oxygen remain within normal ranges. Essentially, it’s a state where iron stores are low, but the body has not yet progressed to a point where anemia develops. This can make it a bit tricky to diagnose since standard blood tests for anemia might not immediately show abnormalities.

Symptoms and Effects

The symptoms of iron deficiency without anemia can be subtle and may vary from person to person. Common signs include:

  • Fatigue and Weakness: Even without anemia, low iron can lead to feelings of tiredness and decreased energy levels. Coaches notice that some competitive athletes benefit from addressing iron deficiency without anemia.
  • Frequent Headaches: Iron is involved in various enzymatic processes in the body, and a deficiency might contribute to headaches or migraines.
  • Cold Hands and Feet: Poor circulation or lower iron levels can result in feeling unusually cold.
  • Brittle Nails and Hair: Iron deficiency can affect the health and strength of nails and hair.
  • Restless Legs Syndrome: Some people with low iron levels experience uncomfortable sensations in their legs, particularly at night.

Causes of Iron Deficiency Without Anemia

Several factors can contribute to iron deficiency without leading to anemia:

  • Dietary Intake: Inadequate consumption of iron-rich foods, such as red meat, legumes, and fortified cereals, can lead to low iron levels.
  • Increased Iron Requirements: Certain life stages and conditions, such as pregnancy, heavy menstrual periods, or intense physical activity, can increase iron needs.
  • Absorption Issues: Conditions like celiac disease or inflammatory bowel disease can impair iron absorption.
  • Chronic Inflammation: Chronic illnesses or inflammatory conditions can affect iron metabolism and utilization, even if anemia does not develop.

Diagnosis and Testing

Diagnosing iron deficiency without anemia typically involves a combination of tests and assessments:

  • Serum Ferritin Levels: Ferritin is a protein that stores iron in the body. Low levels can indicate depleted iron stores, even if anemia is not present.
  • Serum Iron and Transferrin Saturation: These tests measure the amount of circulating iron and how well it is being transported in the blood.
  • Complete Blood Count (CBC): While a normal CBC might not show anemia, it can help rule out other conditions.

Treatment and Management

Addressing iron deficiency without anemia often involves dietary and lifestyle changes:

  • Iron-Rich Diet: Incorporate foods high in iron, such as lean meats, leafy green vegetables, nuts, and seeds. Iron from animal sources (heme iron) is generally more easily absorbed than plant-based iron (non-heme iron).
  • Vitamin C Intake: Consuming vitamin C-rich foods like oranges, strawberries, and bell peppers can enhance the absorption of non-heme iron.
  • Iron Supplements: In some cases, a healthcare provider may recommend iron supplements. It’s important to follow dosing instructions carefully, as excessive iron intake can have adverse effects.
  • Address Underlying Causes: If an underlying condition is contributing to iron deficiency, treating that condition is crucial for resolving the deficiency.

Conclusion

While long-term adaptation to high altitude allows individuals to increase their iron available for erythropoiesis due to higher demand, those who have not adapted or are vulnerable due to exercise or pregnancy, are at risk of depleting their iron stores. Iron deficiency without anemia is a condition that requires attention to prevent potential health issues and improve overall well-being. 

Resources & References:

Alkhaldy HY, Hadi RA, Alghamdi KA, Alqahtani SM, Al Jabbar ISH, Al Ghamdi IS, Bakheet OSE, Saleh RAM, Shehata SF, Aziz S. The pattern of iron deficiency with and without anemia among medical college girl students in high altitude southern Saudi Arabia. J Family Med Prim Care. 2020 Sep 30;9(9):5018-5025. doi: 10.4103/jfmpc.jfmpc_730_20. PMID: 33209838; PMCID: PMC7652112.

Kaylee Sarna, Gary M Brittenham, Cynthia M Beall, Detecting anaemia at high altitude, Evolution, Medicine, and Public Health, Volume 2020, Issue 1, 2020, Pages 68–69, https://doi.org/10.1093/emph/eoaa011

Martina U. Muckenthaler, Heimo Mairbäurl, and Max Gassmann. Iron metabolism in high-altitude residents. 2020 Jan 9: https://journals.physiology.org/doi/pdf/10.1152/japplphysiol.00019.2020

Acclimation, Altitude Science, Diabetes, Exposure, Genetics, Health, High Altitude

Living High and Testing Higher: Can Living at High Altitudes Skew Diagnostic Diabetes Tests? 

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by Hailey Garin PA-S

Diabetes is very prevalent in our society, with around 11% of the population in the United States diagnosed with this disease2. A key diagnostic test used in healthcare is the hemoglobin A1c (HbA1c) blood test. This blood test measures an individual’s average blood sugar over a 3-month period. A value of less than 5.7% is normal, 5.7%-6.4% is pre-diabetic range, and 6.5% and greater is a diagnosis of diabetes1. There are other blood tests that are used in the diagnoses of diabetes including fasting plasma glucose (FPG) and 2-hour postprandial glucose (2-h PG) testing. FPG testing measures blood sugar levels after 8 or more hours of fasting. A FPG value of 126 mg/dl or greater is diagnostic of diabetes. The 2-h PG test is a blood sugar reading 2 hours after eating a meal. A 2-h PG value of 200 mg/dl or higher is diagnostic of diabetes3. Currently the HbA1c blood test is the most used to diagnose diabetes, and many individuals around the world are diagnosed and placed on medications based off HbA1c results alone.

But is this appropriate for individuals living at altitude? 

A groundbreaking study completed in mainland China has begun to answer this question for us. Altitudes and Hemoglobin A1c Values: An Analysis Based on Two Nationwide Cross-sectional Studies by Zheng et al was published in 2024. In this study, 95,000 adults were examined by comparing HbA1c, fasting blood glucose, and 2-hour postprandial (after a meal) glucose levels between individuals living above and below 2,500 meters (8,200 feet)4. 

A key finding of this study was that individuals living above 2,500 meters had higher HbA1c levels but the same FPG and 2-h PG results as individuals below 2,500 meters4. The individuals at altitude may have HbA1c levels that are falsely elevated. This inaccuracy can lead to an inappropriate diagnosis of diabetes in individuals living at altitude. The researchers explained that oxygen levels at higher elevations are lower, and the body reacts to these low levels by increasing levels of red blood cells and the lifespan of red blood cells. When lifespan is increased, the hemoglobin is exposed to glucose in our blood stream for longer, eliciting a higher HbA1c result despite normal blood sugar levels4. 

Another study by Bazo-Alvarez et. al in 2017 sought to evaluate the relationship between HbA1c and FPG among individuals at sea level compared to those at high altitude.

The study analyzed data from 3613 Peruvian adults without diagnosed diabetes from both sea level and high altitude (>3000m). The mean values for hemoglobin, HbA1c, and FPG differed significantly between these populations. The correlation between HbA1c and FPG was quadratic at sea level but linear at high altitude, suggesting different glucose metabolism patterns. Additionally, for an HbA1c value of 48 mmol/mol (6.5%), corresponding mean FPG values were significantly different: 6.6 mmol/l at sea level versus 14.8 mmol/l at high altitude.

These studies show that one-size-fits all screening for diabetes may not work for everyone, especially those living at altitude. Ebert Family Clinic, at 2743m (9000 ft) in the Colorado Rocky Mountains, has been researching the effects of altitude on many aspects of health including examining HbA1c levels in our residents and thus far we have seen elevated HbA1c levels in our otherwise healthy, “thin”, and active patients despite implementing appropriate lifestyle interventions to lower blood sugar. This can lead to unnecessary health anxiety that we hope to avoid by determining if HbA1c will continue to be an appropriate diagnostic tool with our residents living well above 2,500 meters.

References

1. Centers for Disease Control and Prevention. (n.d.-a). A1C test for diabetes and Prediabetes. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/diabetes-testing/prediabetes-a1c-test.html 

2. Centers for Disease Control and Prevention. (n.d.-b). National Diabetes Statistics Report. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/php/data-research/index.html 

3. U.S. Department of Health and Human Services. (n.d.). Diabetes tests & diagnosis – NIDDK. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/tests-diagnosis 

4. Zheng, R., Xu, Y., Li, M., Wang, L., Lu, J., Wang, T., Xu, M., Zhao, Z., Zheng, J., Dai, M., Zhang, D., Chen, Y., Wang, S., Lin, H., Wang, W., Ning, G., & Bi, Y. (2024). Altitudes and hemoglobin A1C values: An analysis based on two nationwide cross-sectional studies. Diabetes Care, 47(2). https://doi.org/10.2337/dc23-1549 

Accessibility, Acclimation, Altitude Science, Athletic Training, Child Growth & Development, Exposure, Genetics, Health, High Altitude, Medicine, Postural Orthostatic Tachycardia Syndrome (POTS)

Thin Air Making You Lightheaded?

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by Joy Plutowski, PA-S2

Feeling lightheaded after going to a high altitude is a key symptom of acute mountain sickness (AMS)—a condition caused by the reduced oxygen available in thin mountain air. AMS often comes with other symptoms like headache, nausea, and fatigue, usually starting after a recent climb to higher elevations.

But what if it’s not just AMS? For people with conditions like postural orthostatic tachycardia syndrome (POTS), which affects blood flow and heart rate, lightheadedness at altitude could be a clue to an underlying issue. While AMS happens because of low oxygen, POTS is tied to a problem with how the nervous system regulates the body. In some cases, going to altitude might even uncover undiagnosed POTS, as symptoms can become more noticeable in these conditions.

Living With POTS

Living with POTS has been a journey of adaptation, requiring constant vigilance and adjustment to manage a complex array of symptoms. Each new environment brings its own challenges, demanding a personalized approach to maintaining stability. My recent clinical rotation in Frisco, Colorado, situated at 9,000 feet above sea level, provided an invaluable opportunity to observe firsthand how altitude influences the physiology of POTS. An overnight stay in Denver for partial acclimatization helped mitigate some initial altitude-related exacerbations, but the first few days at higher elevation were marked by pronounced symptoms, including lightheadedness, tachycardia, and insomnia. Physically demanding activities, such as snowboarding, pushed my body to its limits, resulting in extreme fatigue and heightened tachycardia. Despite these challenges, I observed gradual improvement; by the second week, I had returned to my baseline—if not better than during my time in the heat of Phoenix, Arizona. Interestingly, the colder temperatures of the region seemed to offer symptomatic relief, likely through vasoconstriction that may enhance circulation. These experiences have deepened my understanding of POTS as a highly individualized condition, emphasizing the critical importance of lifestyle modifications, environmental considerations, and a patient-specific approach to management. My journey underscores how adaptability and tailored interventions can significantly improve functionality and quality of life for those navigating the complexities of this syndrome.

What is POTS?

Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic condition characterized by an abnormal increase in heart rate upon standing. It is a form of dysautonomia, involving dysregulation of the autonomic nervous system, which balances the sympathetic (“fight or flight”) and parasympathetic (“rest and digest”) systems. The autonomic nervous system regulates involuntary bodily functions such as heart rate, blood pressure, and digestion. POTS primarily affects women, with symptoms often appearing in their teens or twenties. It is estimated to affect between 1 to 3 million people in the United States, though it is likely underdiagnosed due to lack of awareness. Under normal conditions, standing triggers the body to constrict blood vessels and slightly increase heart rate to counteract gravity’s effects. In POTS, this response is impaired, leading to blood pooling in the lower extremities and reduced blood flow to the brain. The exact cause of POTS is not fully understood, but it is commonly linked to viral infections, autoimmune conditions, genetic predispositions, small fiber neuropathy, impaired norepinephrine regulation, or hypovolemia (low blood volume). Notably, long-COVID, a range of long-term symptoms and conditions resulting from an acute COVID infection, is linked to POTS. Approximately 1% of patients with an acute COVID-19 infection go on to develop orthostatic intolerance (Cheshire, 2024). Studies also show that keeping up with COVID-19 vaccinations can prevent long-COVID.

The hallmark symptom of POTS is an excessive increase in heart rate of over 30 bpm quickly after standing (WP, 2024). Common symptoms include tachycardia, palpitations, dizziness, and fainting (syncope or near-syncope), brain fog, headaches, lightheadedness, and severe fatigue. Less common symptoms include nausea, bloating, abdominal discomfort, shakiness, and exercise intolerance. POTS symptoms are often worsened by factors such as dehydration, heat, prolonged standing, illness, or physical stress. Diagnosing POTS involves a tilt-table test which monitors heart rate and blood pressure during positional changes. Treatment for POTS focuses on improving symptoms and quality of life through lifestyle adjustments. Key components include hydration, increased salt intake, compression garments, graded exercise therapy, and psychological support. Medications such as Fludrocortisone or Midodrine, that both increase blood pressure, may be added if the provider deems it fit. The course of POTS varies widely; some individuals experience significant improvement with treatment, others may have persistent symptoms. Early diagnosis and a multidisciplinary approach can lead to better outcomes.

The Effect of Altitude on the Autonomic Nervous System

Altitude significantly influences the autonomic nervous system due to reduced oxygen levels and atmospheric pressure, which challenge the body’s ability to maintain homeostasis. At higher elevations, the sympathetic nervous system becomes more active, increasing heart rate and blood pressure to compensate for lower oxygen availability. This is because hypoxia alters chemoreceptor and baroreceptor function, leading to increased sympathetic excitation and decreased parasympathetic tone.

During a study at 4300 m, urine norepinephrine levels—a marker of sympathetic activity—peaked 4–6 days after altitude exposure (Mazzeo, 1998). The study compared women in different hormonal phases when exposed to high altitude. The urinary norepinephrine levels heart rates both increased over time in both follicular and luteal phases. The differences between the two were not statistically significant, showing that women experience sympathetic increase at altitude regardless of what phase of their cycle. This was done in comparison to a previous study showing the same findings in men (Mazzeo, 1998). 

A line graph indicating the rise follicular and luteal heart rates in beats per minute as days at altitude increase.
A line graph indicating increasing amounts per 24 hours of urinary norepinephrine.

Other physiological responses include increased ventilation, cardiac output, and heart rate. However, with acclimatization, heart rate and cardiac output typically return to sea-level values within 9–12 days (Hainsworth et al., 2007). Over time, improved oxygen-carrying capacity enhances tolerance to orthostatic stress. All in all, orthostatic tolerance during hypobaric hypoxia involves three mechanisms: cardiovascular control of heart rate and cardiac output, cerebrovascular responses to hypocapnic hypoxia (due to hyperventilation), and elevated sympathetic activity (Blaber et al., 2003). 

For individuals with POTS, altitude-related stresses may exacerbate symptoms. Hypoxia and reduced barometric pressure can worsen fatigue, brain fog, and dizziness by increasing the body’s effort to oxygenate tissues. Reduced oxygen delivery to the brain and tissues may intensify lightheadedness and syncope— which is already common in POTS.

Although acclimatization typically occurs within 1–2 weeks at altitude in healthy individuals, research on acclimatization in POTS patients is limited. Further studies are needed to determine whether individuals with autonomic dysfunction can adapt as effectively as those without.

Living With POTS at Altitude 

Living with POTS at altitude presents unique challenges that require careful management, as patients may find it harder to adapt to the altitude-induced changes in blood oxygenation and pressure regulation. These challenges are compounded by the existing difficulties they face in maintaining autonomic stability. The reduced oxygen levels and increased demands on the cardiovascular system can amplify POTS symptoms, making daily activities more difficult. Patients with POTS generally understand their triggers and have a protocol that was formulated with their provider. Such strategies include staying well-hydrated, using compression garments, increasing salt intake, decreasing alcohol and caffeine consumption, and avoiding sudden changes in posture. Also, gradual exposure to altitude helps the body adapt to the reduced oxygen and barometric pressure, minimizing symptom flares. For individuals with POTS visiting high-altitude environments, strict adherence to their treatment regimen, including lifestyle modifications and potentially pharmacologic interventions, is paramount for managing their condition effectively.

References

Blaber AP, Hartley T, Pretorius PJ (2003) Effect of acute exposure to 3,660 m altitude on orthostatic responses and tolerance. J Appl Physiol 95:591–601

Cheshire WP. (2024) Postural tachycardia syndrome. UpToDate. 

Hainsworth, R., Drinkhill, M. J., & Rivera-Chira, M. (2007). The autonomic nervous system at high altitude. Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 17(1), 13–19

Mazzeo RS, Child A, Butterfield GE, et al. (1998) Catecholamine response during 12  days of high-altitude exposure (4,300 m) in women. J Appl Physiol 84:1151–1157

Joy Plutowski is a second-year PA student born and raised in Arizona. She completed her undergraduate degree in biology at Arizona State University and is now pursuing her master’s at Midwestern University in Glendale, AZ. Before PA school, she worked as a medical scribe for an interventional cardiologist, a field she is interested in pursuing. Currently, she has the wonderful opportunity of completing her pediatrics rotation in Frisco, CO. In her free time, Joy enjoys exploring national parks, playing video games, dancing, and most recently, snowboarding. 

Acclimation, Altitude Science, Exposure, Genetics, Health, High Altitude

Boy Scouts and Skiers: Reducing the Risk of Developing Acute Mountain Sickness

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Thousands of boy scouts travel to Philmont Scout Ranch (PSR) in Cimarron, New Mexico each year in hopes of improving their wilderness survival skills by ascending its rugged, mountainous terrain. Elevations at PSR range from 2011 to 3792 m, in sharp contrast to the lower elevations the boy scouts are used to. Those with a history of daily headaches, gastrointestinal illnesses, and prior acute mountain sickness were found to be most at risk of developing altitude related illnesses while ascending PSR. The incidence of acute mountain sickness was 13.7% at PSR when participants ascended from base camp (2011 m) to 3000m+ as compared to up to 67% in other staged ascent studies [3]. Similarly to PSR, millions of people ascend the Colorado Rocky Mountains during ski season and face the same potential complications. This risk makes it abundantly important to investigate potential ways to prevent the development of altitude related illnesses.

Oxygen from inspired air (air breathed in) flows down its concentration gradient from the alveolar space into the blood, where it is carried primarily bound to hemoglobin and delivered to tissue. At high altitudes, oxygen availability and barometric pressure decrease remarkably, hindering the concentration gradient and increasing the risk of tissue hypoxia [2]. Progressive tissue hypoxia eventually leads to high altitude illnesses (HAI), which are cerebral and pulmonary syndromes resulting from rapid ascent. The likelihood of developing these disease processes can be greatly reduced if the body is given time to acclimate to the increased altitude. This is especially relevant during the holidays, when many are traveling from lower altitudes to higher altitudes abruptly for vacation or to visit with family.

This raises the question: should travelers spend the night in Denver before ascending into the mountains to allow for acclimatization and reduce the risk of HAI?

The rate of acclimatization, or the body’s ability to adjust to and accommodate increased oxygen requirement, is difficult to generalize given rate of ascension is not the only factor that influences the development of HAI. This process can take anywhere from days to potentially months depending on a number of factors including cardiopulmonary comorbidities, a history of HAI, genetics, certain medications, substance usage, and degree of physical exertion amongst others [5].

Despite the multifactorial nature of developing HAI, rate of ascent remains one of the primary risk factors. Studies have shown that spending time at moderate altitude before ascending to higher altitudes in a process called “staged ascent” decreases the likelihood of developing HAI in unacclimatized individuals [4]. A recent study conducted at the U.S. Army Research Institute of Environmental Medicine assessed incidence of acute mountain sickness (AMS, a subcategory of HAI), in unacclimatized individuals who were staged for 2 days at altitudes of 2500 m, 3000 m, and 3500 m respectively before ascending to 4300 m. Another group ascended directly to 4300 m without staging. Ultimately, the incidence of AMS was significantly lower in the staged groups than in the direct ascent group; AMS incidence in the staged groups was up to 67%, while AMS incidence in the direct ascent group was up to 83% [1].

Two graphs, A and B, illustrate the incidence of acute mountain sickness by percent at elevations of 2500m, 3000m, 3500m and a control group, as well as peak acute mountain sickness severity ranked from 0 to 2 for the same elevations and a control group.

Graphs A and B show that the incidence of AMS at 4300 m is reduced when unacclimatized individuals are staged at 2500 m, 3000 m, and 3500 m as compared to those who directly ascended to 4300 m [1].

Given the above information, unacclimatized individuals, skiers and boy scouts alike, may benefit from spending the night in Denver before coming to the mountains, as this mimics staged ascent and thus decreases the incidence of HAI.

Tall, snowy pines rise up out of powdery snow on a ski slope overlooking forests stretching out toward a range of white peaks in the distance under a sunny blue sky.
View from the top of Keystone Resort taken while snowboarding (elevation 3782 m)

References

[1] Beth A. Beidleman et al. “Acute Mountain Sickness is Reduced Following 2 Days of Staging During Subsequent Ascent to 4300m”. In: High Altitude Medicine & Biology 19.4 (2018). Published Online: 21 December 2018, pp. xxx–xxx. doi: 10.1089/ham.2018.0048. 

[2] Chris Imray et al. “Acute Mountain Sickness: Pathophysiology, Prevention, and Treatment”. In: Progress in Cardiovascular Diseases 52.6 (May 2010), pp. 467–484. doi: 10.1016/j.pcad.2009.11.003.

[3] Courtney LL Sharp et al. “Incidence of Acute Mountain Sickness in Adolescents Backpacking at Philmont Scout Ranch”. In: Wilderness and Environmental Medicine 35.4 (2024), pp. 403-408

[4] Andrew M. Luks, Erik R. Swenson, and Peter B¨artsch. “Acute high-altitude sickness”. In: European Respiratory Review 26.143 (Jan. 2017), p. 160096. doi: 10.1183/16000617.0096-2016.

[5] Michael Schneider et al. “Acute mountain sickness: influence of susceptibility, preexposure, and ascent rate”. In: Medicine & Science in Sports & Exercise 34.12 (Dec. 2002), pp. 1886–1891

Matison Miratsky is a physician assistant student who attends Midwestern University in Arizona with plans to go into OB/GYN. Before PA school, she grew up in Denver, Colorado and attended the University of Colorado at Boulder. She worked in an emergency department in Denver, then at a family medicine clinic in Arizona. Her personal interests include snowboarding, watching movies, spending time with family, and cooking.

Acclimation, Altitude Science, Child Growth & Development, Genetics, Health, High Altitude, Huts, Medicine, Summit Huts

Unveiling the Hidden Risks of Living at High Altitude on our Kidney Health, and What it Might Mean for Your Child

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The hallmark concern for the body living at high altitude is low oxygen. We breathe in less, and thus less is sent throughout our blood stream to our tissues. We are quick to think about how this affects our heart and lungs, but what about our kidneys? What are our kidneys even responsible for?

Kidneys filter, reabsorb, and excrete our blood in the form of urine. They connect our cardiovascular system with our genitourinary system. The flow through the kidneys also helps monitor and adjust our blood pressure. Their importance is truly undervalued. When they receive less oxygen than preferred (hypoxia), they will become injured. Specifically, the glomerulus (term for the filter) will become affected. When this happens, it is not efficient at filtration, and protein will spill out into our urine (proteinuria), a key feature of High Altitude Renal Syndrome (HARS).

Zooming further in below

And even further…

Another issue involves uric acid, the chemical at fault for causing gout. Due to the filter injury sustained from low oxygen, uric acid excretion is affected. It can thus build up in our musculoskeletal system and other tissues. It is famous for causing red, swollen, and painful joints. The enzyme that helps create uric acid (xanthine oxidase) is also turned on by reactive oxygen species during hypoxia. This then causes further uric acid crystal deposition in our body. This can present in patients from adolescent years through adulthood, ranging from fleeting pain to amputations from severe bone infections. We have found that for younger patients, diet plays a lesser part than genetic predisposition and hypoxia.

So how is this treated? We are still researching the best course of action. We can treat with drugs that work by inhibiting the previously specified enzyme: xanthine oxidase. These include oral allopurinol, febuxostat, and even IV pegloticase infusions. But we are primarily focused on prevention and holistic care here, so we would prefer to use supplemental oxygen therapy for those that struggle to maintain oxygen saturations in the healthy ranges. Acetazolamide is also helpful in cases. This medication works to increase our respiratory drive, helping us breathe off CO2 and breathe in more oxygen. Contact us to see what method might be right for you.

This research was brought to us by a stroke of luck. A stranger on an airplane, and a son’s coworker. This stranger happened to be a nephrologist (kidney doctor) who is studying how altitude affects the kidneys. In working with him and his team at University of Colorado Anschutz, the team at Ebert Family Clinic in Frisco, Colorado (9000′) have been ordering broader lab panels (including uric acid) for their patients and seeking those with questionable renal labs. Another patient seen by the Ebert Family Clinic team has been severely impacted by gout. With multiple amputations before the patient’s 30th birthday, this case has motivated the health care team to prevent this from happening to others in their high altitude community.

Screenshot

Carter Odean is a third-year medical student at Rocky Vista University. He was born and raised outside of Denver, Colorado before heading to Gonzaga University in Spokane, Washington where he studied biology and completed research on an invasive bee species there while playing club lacrosse. After graduating in 2019, he then came back to Denver to complete his Master’s in Biomedical Sciences at Regis University. After Regis, he started as a Clinical Research Coordinator at Anschutz Medical campus, working on multiple Diabetes Mellitus Type 2 research trials. He is in the Rural & Wilderness Track which is his favorite part about school. He plans to work as a rural Pediatrician or Family Medicine Physician. In his free time, you can find him dirt biking, fly fishing, skiing, and relaxing with friends and family. 

References

  1. Schoene, R.B. “High altitude renal syndrome: polycythemia, hyperuricemia, microalbuminuria, and hypertension.” High Alt Med Biol. 2002 Spring;3(1):65-73. doi: 10.1089/152702902753639371. PMID: 11949751.
  2. Bigham, A.W., Lee, F.S. “Tibetan and Andean patterns of adaptation to high-altitude hypoxia.” Hum Biol. 2014 Oct;86(4):321-37. doi: 10.3378/027.086.0401. PMID: 25700353; PMCID: PMC4438718.
  3. Beall, C.M., Cavalleri, G.L., Deng, L., et al. “Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders.” Proc Natl Acad Sci U S A. 2010 Mar 9;107(25):11459-64. doi: 10.1073/pnas.1002443107. Epub 2010 Feb 22. PMID: 20176925; PMCID: PMC2895106.
  4. Simonson, T.S., Yang, Y., Huff, C.D., et al. “Genetic evidence for high-altitude adaptation in Tibet.” Science. 2010 Sep 10;329(5987):72-5. doi: 10.1126/science.1189406. PMID: 20616233; PMCID: PMC3490534.
  5. Schoene, R.B., Swenson, E.R. “Cobalt-Induced Chronic Mountain Sickness: Pathophysiological Mechanisms and Genetic Susceptibility.” High Alt Med Biol. 2017 Mar;18(1):1-5. doi: 10.1089/ham.2016.0106. PMID: 28145824.Baillie, J.K., Bates, M.G., Thompson, A.A., et al. “Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude.” Chest. 2007 Dec;132(6):S275. doi: 10.1378/chest.132.6.275. PMID: 18079246.
  6. Yu, K.H., Wu, Y.J., Tseng, W.C., et al. “Risk of end-stage renal disease associated with gout: a nationwide population study.” Arthritis Res Ther. 2012 Jun 27;14(3):R83. doi: 10.1186/ar3818. PMID: 22738152; PMCID: PMC3446515.
  7. Bhat, A., Deshmukh, A., Anand, S., et al. “Acute Myocardial Infarction due to Coronary Artery Embolism in a Patient with Severe Hyperuricemia.” J Assoc Physicians India. 2019 Nov;67(11):90-91. PMID: 31801335.
  8. Khanna, D., Khanna, P.P., Fitzgerald, J.D., et al. “2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia.” Arthritis Care Res (Hoboken). 2012 Oct;64(10):1431-46. doi: 10.1002/acr.21772. PMID: 23024028.
  9. Schoene, R.B., Swenson, E.R. “Treatment of Cobalt-Induced Chronic Mountain Sickness.” High Alt Med Biol. 2017 Mar;18(1):74-77. doi: 10.1089/ham.2016.0135. PMID: 28145823.
  10. Schoene, R.B., Hackett, P.H., Henderson, W.R., et al. “High Altitude Medicine and Physiology, Fourth Edition.” CRC Press, 2007.
  11. Burtscher, M., Mairer, K., Wille, M., et al. “Risk of acute mountain sickness in tourists ascending to 4360 meters by cable car.” High Alt Med Biol. 2004 Summer;5(2):141-6. doi: 10.1089/1527029041352154. PMID: 15265307.
  12. Baumgartner, R.W., Bärtsch, P. “Chronic mountain sickness and the heart.” Prog Cardiovasc Dis. 2010 May-Jun;52(6):540-9. doi: 10.1016/j.pcad.2010.02.009. PMID: 20417390.
Acclimation, Altitude Science, Child Growth & Development, Doc Talk, Genetics, Health, High Altitude

The Frisco Score: A New Tool for Diagnosing HAPE

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by Madison Palmiero, PA-S

While HAPE may be a run-of-the-mill diagnosis for providers with years of experience practicing at altitude, it can be less straightforward for those who are unfamiliar with the condition. There are currently three recognized categories of HAPE. Classic HAPE (C-HAPE)  occurs when someone who resides at low altitude travels to high altitude and develops pulmonary edema. Re-entry HAPE (R-HAPE) occurs when high altitude residents travel to low altitude, then return to high altitude. High-altitude resident pulmonary edema (HARPE) occurs in high altitude residents without a change in altitude. HARPE is often brought on by an upper respiratory tract infection. 

HAPE and pneumonia can have similar presentations including shortness of breath, cough, fatigue, and malaise. Patients with either condition may have decreased oxygen saturation levels and abnormal findings on chest radiography. In response to this phenomena, Dr. Chris Ebert-Santos of Ebert Family Clinic in Frisco, Colorado (9000′) and Sean Finnegan, PA-C set out to develop a scoring system to differentiate the two diagnoses. If providers could easily differentiate between pneumonia and HAPE, this would shorten the time from presentation to diagnosis and would avoid unnecessary antibiotic use.

Dr. Chris and Sean Finnegan, PA-C summarized their research findings into a scoring system named the “Frisco Score”. They analyzed data from St. Anthony Summit Medical Center and associated clinics at or above ~2,760 meters above sea level from January 1, 2018 to May 30, 2023. The study looked at patients under the age of 19 who presented with hypoxemia or other respiratory concerns and had a chest x-ray performed and oxygen saturation measured. The final case review consisted of 138 total patients with 77 diagnosed with HAPE, 38 diagnosed with pneumonia, and 23 diagnosed with concomitant HAPE and pneumonia. Variables found to have no significance included gender, age, heart rate, and temperature. Variables with significance included respiratory rate, number of days ill, oxygen saturation, and chest x-ray findings. These significant variables were used to develop the Frisco Score. They do include a disclaimer that these findings are preliminary results on a small data set. Thus, as of yet, the Frisco Score should not be used on its own to make a diagnosis, but rather should be used as a clinical tool in differentiating conditions with similar presentations. 

Oxygen saturation varied greatly between patients with HAPE and those with pneumonia. Patients diagnosed with HAPE had an average oxygen saturation of 74% and those with pneumonia had an average of 92%. 

Patients who were diagnosed with HAPE had a higher average respiratory rate compared to those diagnosed with pneumonia.

 In patients diagnosed with HAPE, the duration of illness, or number of days ill, was shorter than those diagnosed with pneumonia. 

In comparison of chest x-rays, patients with HAPE were more likely to have diffuse findings and patients with pneumonia were more likely to have focal findings. 

Overall, there were no variables associated with a concomitant diagnosis of pneumonia and HAPE.

The asphalt road in the foreground leads past a sign for Common Spirit St. Anthony Summit Hospital just before the shelter over the entrance to a building labeled "ambulance" with deep green conifer forests stretching halfway up tall grey rocky mountains in the backgroundl.

In summary, patients diagnosed with HAPE had decreased oxygen saturation, increased respiratory rate, and diffuse findings on chest x-ray; while patients diagnosed with pneumonia had a longer duration of illness and focal findings on chest x-ray. The Frisco Score takes these variables into account to help differentiate a diagnosis of HAPE in children. Dr. Chris and Sean Finnegan, PA-C are currently presenting their findings at the 8th World Congress on Mountain and Wilderness Medicine in Snowbird, Utah. They hope that in the near future, the Frisco Score will be used to facilitate the diagnosis of HAPE by providers in high altitude communities state-wide.

References

1. Ebert-Santos, C. (2017). High-Altitude Pulmonary Edema in Mountain Community Residents. High Altitude Medicine & Biology, 18 (3), 278-284. https://doi.org/10.1089/ham.2016.0100

2. Ebert-Santos, C., Finnegan, S. (2024). Differentiating Pneumonia & HAPE in Children.

Acclimation, Altitude Science, Asthma, Child Growth & Development, COVID-19, Doc Talk, Exposure, Genetics, Health, High Altitude, Medicine, Mountaineering, Pandemic, Sleep at Altitude, Technology

Can I Ever Go Back Up To High Altitude Again? – Recurrence Risk of HAPE & HARPE

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by Taylor Kligerman, PA-S

Can I ever return to high altitude? Do I need to move down to a lower elevation?

Disease processes often differ at high altitudes. Some conditions have only been known to occur at high elevations. Most of the resources cited in this blog refer to ‘high altitude’ being at or above 2,500 meters or 8,200 feet.

Ebert Family Clinic in Frisco, Colorado is at 9,075 ft. Many areas in the immediate vicinity are over 10,000′, with some patients living above 11,000′. Two of the more common conditions seen in patients at Ebert Family Clinic are high altitude pulmonary edema (HAPE) and high altitude resident pulmonary edema (HARPE), similar conditions that affect slightly different populations in this region of the Colorado Rocky Mountains.

In “classic” HAPE, a visitor may come from a low-altitude area to Frisco on a trip to ski with friends. On the first or second day, the person notices a nagging cough. They might wonder if they caught a virus on the plane ride to Denver. The cough is usually followed by shortness of breath that begins to make daily tasks overwhelmingly difficult. One of the dangerous aspects of HAPE is a gradual onset leading patients to believe their symptoms are caused by something else. A similar phenomenon is seen in re-entry HAPE, where a resident of a high altitude location travels to low altitude for a trip and upon return experiences these same symptoms [1].

In HARPE, a person living and working here in Frisco may be getting ill or slowly recovering from a viral illness and notices a worsening cough and fatigue. These cases are even more insidious, going unrecognized, and so treatment is sought very late. Dr. Christine Ebert-Santos and her team at Ebert Family Clinic hypothesize that while residents have adequately acclimated to the high-altitude environment, the additional lowering of blood oxygen due to a respiratory illness with inflammation may be the inciting event in these cases.

In both cases, symptoms are difficult to confidently identify as a serious illness versus an upper respiratory infection, or simply difficulty adjusting to altitude. For this reason, Dr. Chris recommends that everyone staying overnight at high altitude obtain a pulse oximeter. Many people became familiar with the use of these instruments during the COVID-19 pandemic. The pulse oximeter measures what percent of your blood is carrying oxygen. At high altitude, a healthy level of oxygenation is typically ≥90%. This is an easy way to both identify potential HAPE/HARPE, as well as reassure patients they are safely coping with the high-altitude environment [2].

HAPE and HARPE are both a direct result of hypobaric hypoxia, a lack of oxygen availability at altitude due to decreased atmospheric pressures. At certain levels of hypoxia, we observe a breakdown in the walls between blood vessels and the structures in lungs responsible for oxygenating blood. The process is still not totally understood, but some causes of this breakdown include an inadequate increase in breathing rates, reduced blood delivered to the lungs, reduced fluid being cleared from the lungs, and excessive constriction of blood vessels throughout the body. These processes cause fluid accumulation throughout the lungs in the areas responsible for gas exchange making it harder to oxygenate the blood [3].

We do know that genetics play a significant role in a person’s risk of developing HAPE/HARPE. Studies have proposed many different genes that may contribute, but research has not, so far, given healthcare providers a clear picture of which patients are most at-risk. Studies have shown that those at higher risk of pulmonary hypertension (high blood pressure in the blood vessels of your lungs), are more likely to develop HAPE [4]. This includes some types of congenital heart defects [5,6]. High blood pressures in the lungs reach a tipping point and appear to be the first event in this process. However, while elevated blood pressures in the lungs are essential for HAPE/HARPE, this by itself, does not cause the condition. The other ingredient necessary for HAPE/HARPE to develop is uneven tightening of the blood vessels in the lungs. When blood vessels are constricted locally, the blood flow is shifted mainly to the more open vessels, and this is where we primarily see fluid leakage. As the blood-oxygen barrier is broken down in these areas, we may also see hemorrhage in the air sacs of the lungs [3].

One observation healthcare providers and scientists have observed is that HAPE/HARPE can be rapidly reversed by either descending from altitude or using supplemental oxygen. Both strategies increase the availability of oxygen in the lungs, reducing the pressure on the lungs’ blood vessels by vasodilation, quickly improving the integrity of the blood-oxygen barrier.

In a preliminary review of over 100 cases of emergency room patients in Frisco diagnosed with hypoxemia (low blood oxygen content) Dr. Chris and her team have begun to see trends that suggest the availability of at-home oxygen markedly reduces the risk of a trip to the hospital. This demonstrates that patients with both at-home pulse oximeters and supplemental oxygen have the capability to notice possible symptoms of HAPE, assess their blood oxygen content, and apply supplemental oxygen if needed. This stops the development of HAPE/HARPE before damage is done in the lungs. In the case of many of our patients, these at-home supplies prevent emergencies and allow patients time to schedule an appointment with their primary care provider to better evaluate symptoms.

Additionally, Dr. Chris and her team have observed that patients with histories of asthma, cancer, pneumonia, and previous HAPE/HARPE are often better educated and alert to these early signs of hypoxia and begin treatment earlier on in the course of HAPE/HARPE, reducing the relative incidence identified by medical facilities. There are many reasons to seek emergent care such as low oxygen with a fever. Patients with other existing diseases causing chronically low oxygen such as chronic lung disease may not be appropriately treated with  supplemental oxygen, although this is a very small portion of the population. Discussions with healthcare providers on the appropriate prevention plan for each patient will help educate and prevent emergency care visits in both residents and visitors.

A young child with short brown hair and glasses with dark, round frames wears a nasal canula for oxygen.

Studies of larger populations have yet to be published. A review of the case reports in smaller populations suggests that the previously estimated recurrence rate of 60-80% is exaggerated. This is a significant finding as healthcare providers have relied on this recurrence rate to make recommendations to their patients who have been diagnosed with HAPE. A review of 21 cases of children in Colorado diagnosed with HAPE reported that 42% experienced at least one recurrence [7]. This study was conducted by voluntary completion of a survey by the patients (or their families) which could lead to significant participation bias affecting the results. Patients more impacted by HAPE are more likely to complete these surveys. Another study looking at three cases of gradual re-ascent following an uncomplicated HAPE diagnosis showed no evidence of recurrence. The paper also suggested there may be some remodeling of the lung anatomy after an episode of HAPE that helps protect a patient from reoccurrence [8]. Similar suggestions of remodeling have been proposed through evidence of altitude being a protective factor in preventing death as demonstrated by fatality reports from COVID-19[9].

A review article from 2022 by Ucros et al showed a recurrence rate of 21%, high among mountain residents who travel to lower altitudes and develop reentry HAPE. An ongoing analysis of 248 hypoxic children seen in the emergency department in Frisco, Colorado at 9,000 feet found a recurrence of around 40%, again mostly reentry HAPE and HARPE, since residents have a much higher exposure to the hypoxic environment adding to their risk. Rick for visitors with classic HAPE is difficult to determine, as they are unlike to be seen in the same medical facility, but the medical history taken during the encounters in this study do not reflect any recurrence.

Without larger studies and selection of participants to eliminate other variables like preexisting diseases, we are left to speculate on the true rate of reoccurrence based on the limited information we have. Strategies to reduce the risk of HAPE/HARPE such as access to supplemental oxygen, pulse oximeters, and prescription medications [10] are the best way to prevent HAPE/HARPE. Research should also continue to seek evidence of individuals most at risk for developing HAPE/HARPE [11].

A woman with reddish-brown, straight hair just below her shoulders, wears a white coat over a mustard-colored shirt, smiling.

Taylor Kligerman is a third-year medical student at Rocky Vista University with plans to complete a residency in emergency medicine. She was born and raised in Flossmoor, IL, and became interested in medicine following her first medical mission trip to Gonaïves, Haiti in 2010. Taylor has extensive experience in wilderness and remote emergency medicine. Before starting medical school, she was certified as a wilderness EMT and gained experience in remote areas of Canada and Western North Carolina on whitewater expeditions and as a volunteer with local search and rescue. Her personal interests include camping, skiing, and all paddle sports.

References

  1. Ucrós S, Aparicio C, Castro-Rodriguez JA, Ivy D. High altitude pulmonary edema in children: A systematic review. Pediatr Pulmonol. 2023;58(4):1059-1067. doi:10.1002/ppul.26294
  2. Deweber K, Scorza K. Return to activity at altitude after high-altitude illness. Sports Health. 2010;2(4):291-300. doi:10.1177/1941738110373065
  3. Bärtsch P. High altitude pulmonary edema. Med Sci Sports Exerc. 1999;31(1 Suppl):S23-S27. doi:10.1097/00005768-199901001-00004
  4. Eichstaedt C, Benjamin N, Grünig E. Genetics of pulmonary hypertension and high-altitude pulmonary edema. J Appl Physiol. 2020;128:1432
  5. Das BB, Wolfe RR, Chan K, Larsen GL, Reeves JT, Ivy D. High-Altitude Pulmonary Edema in Children with Underlying Cardiopulmonary Disorders and Pulmonary Hypertension Living at Altitude. Arch Pediatr Adolesc Med. 2004;158(12):1170–1176. doi:10.1001/archpedi.158.12.1170
  6. Liptzin DR, Abman SH, Giesenhagen A, Ivy DD. An Approach to Children with Pulmonary Edema at High Altitude. High Alt Med Biol. 2018;19(1):91-98. doi:10.1089/ham.2017.0096
  7. Kelly TD, Meier M, Weinman JP, Ivy D, Brinton JT, Liptzin DR. High-Altitude Pulmonary Edema in Colorado Children: A Cross-Sectional Survey and Retrospective Review. High Alt Med Biol. 2022;23(2):119-124. doi:10.1089/ham.2021.0121
  8. Litch JA, Bishop RA. Reascent following resolution of high altitude pulmonary edema (HAPE). High Alt Med Biol. 2001;2(1):53-55. doi:10.1089/152702901750067927
  9. Gerken J, Zapata D, Kuivinen D, Zapata I. Comorbidities, sociodemographic factors, and determinants of health on COVID-19 fatalities in the United States. Front Public Health. 2022;10:993662. Published 2022 Nov 3. doi:10.3389/fpubh.2022.993662
  10. Luks A, Swenson E, Bärtsch P. Acute high-altitude sickness. European Respiratory Review. 2017;26: 160096; DOI: 10.1183/16000617.0096-2016
  11. Dehnert C, Grünig E, Mereles D, von Lennep N, Bärtsch P. Identification of individuals susceptible to high-altitude pulmonary oedema at low altitude. European Respiratory Journal 2005;25(3):545-551; DOI: 10.1183/09031936.05.00070404
Accessibility, Acclimation, Altitude Science, Asthma, Child Growth & Development, Doc Talk, Exposure, Genetics, Health, High Altitude, Medicine

Hypoxia in the Emergency Department: Preliminary Analysis of Data from the Highest Atitude Population in North America & Children with Hypoxia

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Hypoxia is a common presentation at the emergency department for the St Anthony Summit Medical Center, located at 2800 meters above sea level (msl) in Colorado. Children under 18 are brought in with respiratory symptoms, trauma, congenital heart and lung abnormalities, and high altitude pulmonary edema (HAPE). Many complain of shortness of breath and/or cough and are found to be hypoxic, defined as an oxygen saturation below 89% on room air for this elevation. Patients who live at altitude may perform home pulse oximetry and arrive for treatment and diagnosis of known hypoxia. Extensive and ongoing analysis of the data from children found to be hypoxic in the emergency department raises many questions, including how residents vs nonresidents present, how often  these cases are preceded by febrile illness and what chief complaint is most frequently cited. 

Understanding the presentation of hypoxia in children at altitude can help ensure that healthcare providers are following a comprehensive approach with awareness of the overlapping symptoms of HAPE, pneumonia and asthma. Below is a graphic summary of 36 cases illustrating the clinical, social and geographic factors contributing to hypoxia at altitude in residents and visitors. A further analysis of over 200 children with hypoxia presenting to the emergency room at 9000 feet is underway including x-ray findings.

The graphs below were created by the author, using data extracted directly from a review of patient charts (specifically, those of children presenting to the local hospital in Summit County, Colorado (9000 feet) with hypoxia).

Graphs 1-4 show chief complaints of cough (CC) and shortness of breath (SOB) compared by age and by residence (res: includes altitudes above 2100 meters above sea level), the front range (a high altitude region of the Rocky Mountains running north-south between Casper, Wyoming and Pueblo, Colorado) averaging 1500 msl, and out of the state of Colorado (OOS).

Graphs 9 and 10 show lowest oxygen by age at admission and lowest O2 organized by days spent in the county (residents are excluded from this data). 

Erin Snyder is a new graduate physician assistant who graduated this fall after spending her final rotation in Frisco with the Ebert clinic. She is now working in pediatric hematology at Children’s Hospital Colorado. And her free time she enjoys skiing, hiking and spending time with her cat Charlie.

Accessibility, Acclimation, Altitude Science, Child Growth & Development, Diabetes, Exposure, Genetics, Health, High Altitude, Medicine, Mountaineering

The Impact of High Altitude on Diabetes Diagnosis: The Relationship between Hemoglobin A1c and Fasting Plasma Glucose

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Type 2 Diabetes (T2D) has emerged as a global concern, with its prevalence steadily increasing. The test of choice to diagnose and monitor T2D is hemoglobin A1c (HbA1c), which tracks average blood sugar levels over the last three months. Normal HbA1c levels are below 5.7%, 5.7% to 6.4% indicates prediabetes, and 6.5% or higher indicates diabetes. Within the prediabetes range, high HbA1c levels increase the risk of developing T2D. Additionally, levels above 6.5% correlate with greater risk for diabetes complications.1 Fasting Plasma Glucose (FPG) is an additional test that indicates an immediate blood sugar level following a period of fasting. Normal FPG levels are below 100 mg/dL (5.5 mmol/L), 100 to 125 mg/dL (5.6 to 6.9 mmol/L) suggests prediabetes, whereas 126 mg/dL (7 mmol/L) or higher generally indicates diabetes.2 Because HbA1c provides an overview of blood sugar levels spanning the past 2-3 months, it offers a more comprehensive insight into blood sugar management and is the preferred diagnostic test for T2D.3 Recent studies are unveiling discrepancies between HbA1c and glucose testing, prompting discussions on specific diagnostic criteria for different populations.

People living at high altitude experience unique physiological adaptations, such as higher hemoglobin levels and specific glucose metabolism patterns. Acknowledging these adaptations, a 2017 study by Bazo-Alvarez et. al sought to evaluate the relationship between HbA1c and FPG among individuals at sea level compared to those at high altitude.

The study analyzed data from 3613 Peruvian adults without diagnosed diabetes from both sea level and high altitude (>3000m). The mean values for hemoglobin, HbA1c, and FPG differed significantly between these populations. The correlation between HbA1c and FPG was quadratic at sea level but linear at high altitude, suggesting different glucose metabolism patterns. Additionally, for an HbA1c value of 48 mmol/mol (6.5%), corresponding mean FPG values were significantly different: 6.6 mmol/l at sea level versus 14.8 mmol/l at high altitude.

Tall, snowy mountain peaks rise in the distance over rows of deep green pine trees growing out of the hills around a bike. path in the foreground.

This significant difference in predictive values suggests potential controversy in utilizing HbA1c as a diagnostic tool for diabetes in high altitude settings. Using HbA1c at altitude potentially underdiagnoses and under treats patients. To ensure a more accurate diagnosis of T2D at high altitude, reevaluating diagnostic criteria, possibly leaning towards FPG or oral glucose tolerance testing (OGTT) might be necessary.

In conclusion, this study emphasizes the need for careful consideration when diagnosing diabetes in high-altitude regions. Future research is warranted, including studies replicating the findings of the cross-sectional study by Bazo-Alvarez and longitudinal studies exposing the long-term effects of the diagnostic discrepancy of HbA1c in high altitude patients. This additional data will ensure accurate diagnosis and appropriate management of diabetic patients at high altitude.

References

  1. Centers for Disease Control and Prevention. A1C Test. Accessed 12/26/23. Available from: https://www.cdc.gov/diabetes/managing/managing-blood-sugar/a1c.html
  2. World Health Organization. Fasting Blood Glucose. Accessed 12/26/23. Available from: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/2380#:~:text=When%20fasting%20blood%20glucose%20is,separate%20tests%2C%20diabetes%20is%20diagnosed   
  3. Sherwani, S.I., et al. 2016. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients. Biomark. Insights. 2016 Jul; 11: 95-104. DOI: 10.4137/BMI.S38440.
  4. Bazo-Alvarez, J. C., et al. Glycated haemoglobin (HbA1c) and fasting plasma glucose relationships in sea-level and high-altitude settings. Diabet. Med. 2017 Jun; 34(6): 804-812. DOI: 10.1111/dme.13335.

Ambra Saurini is a second-year physician assistant student at Red Rocks Community College in Arvada, CO. She was born and raised in Denver, but Italian is her first language and she spent summers visiting her grandparents in Italy. She received her undergraduate degree in integrative physiology from the University of Colorado at Boulder. Before PA school, she worked as a research assistant in the Sleep and Development Lab at CU and as a medical assistant at Panorama Orthopedics and Spine Center. In her free time, she enjoys trying new restaurants and coffee shops, hiking, and spending time outside with her two-year old daughter, Chiara.

Acclimation, Altitude Science, Doc Talk, Genetics, Health, High Altitude

RED FLAGS AT ALTITUDE: When Your Doctor Tells You Your Labs AreNormal But the Results in the Patient Portal Are Flagged

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It comes as no surprise that living at altitude can take some adjustment. Travelers visiting just for a quick ski trip recognize  immediately, sometimes even at Denver International Airport when first arriving at Colorado’s Mile High City at 5280 feet, that the air is “thinner” than where they might have journeyed from. That thinner air we all feel is due to our altitude living at 9,075 feet (2) here in Frisco, CO. Our bodies can feel the atmospheric changes even if we do not recognize them ourselves. As a point of reference, on the rather extreme side, the “death zone” that comes to mind when thinking of the behemoth Mount Everest, is any elevation of 26,247 feet and above (3), a  zone we might not be as familiar with is the deterioration zone which begins at a mere 15,000 feet (3). In this zone, the symptoms are variable, but  common manifestations are lethargy, weight loss, poor appetite, and irritability (4). Altitude experts identify 8,000 feet as the elevation where  symptoms such as headaches and pulmonary edema are more likely to manifest. The good and bad effects of altitude are proportional to the elevation and variable between individuals. For all of you ‘fourteener’ fanatics out there, including myself, this comes as a reminder that we are closer than we think to detrimental elevation in our atmosphere. With this  frame of reference fresh in our minds, let us take a closer look at how living in at the elevation of Frisco, Colorado at 9000 feet or the neighboring towns can affect our health. 

Mountain residents who have blood tests done commonly see “red flags” next to some lab values. In particular, the complete blood count, commonly referred to as CBC. To most of us, those red flags are an alarming indicator that something must be terribly awry but au contraire,  there is an explanation why we need not worry. For those of us living at altitude, there is a reduced atmospheric pressure, so although the fraction of oxygen in the air is still 21%, the molecules are further apart. Fewer oxygen molecules enter our lungs and bloodstream  delivering less oxygen to our tissues(5). Remember now, we are not living on top of Mount Everest, so we are not in any danger, because our bodies are doing behind-the-scenes work for us! Our bodies are adapting by increasing the amount of red blood cells, which carry oxygen in our blood, throughout our bodies so that every organ is being supplied with the good stuff! This is exactly why athletes come here to train, to get their bodies to produce more red blood cells so they can perform at their absolute best. After three months of life in the mountains, nearly everyone has elevated red blood cells, hemoglobin, hematocrit, and red cell indices such as the MCV, (mean corpuscular volume), MCHC (mean corpuscular hemoglobin content) and MCH (mean corpuscular hemoglobin). A “normal” hemoglobin in a man who lived for years in the mountains was a signal to his doctor that the patient was anemic and in fact turned out to have colon cancer.

A more immediate response to the low oxygen environment at altitude is an increase in respiratory rate. In an interview with physician experts on altitude Dr. Elizabeth Winfield and Dr. Erik Swenson on May 30, 2023, both think this is the reason there is often a red flag for the carbon dioxide (CO2) as low, usually 17 to 19 with 20 being normal.  Because this affects the acid base balance, the serum chloride ( Cl) may be slightly elevated, 107 to 108 instead of 106. Dr. Winfield also explains to her patients that fasting for labs may cause mild dehydration leading to a slightly higher BUN, blood urea nitrogen, a marker of kidney function.  Another physiological response to altitude is a lower plasma volume, which may cause slight elevation in the serum protein and albumin.

So when you doctor calls you and tells you your labs are normal, ask them to drill down and explain the red flags.  If you find out something new, please put a comment on our blog and share with the world! Few health care providers really understand all the changes in the human body living in hypobaric hypoxic (low pressure, low oxygen) environments.

References 

1. Image. https://ichef.bbci.co.uk/news/624/cpsprodpb/960F/production/_83851483_c0249925-red_blood_cells,_illustration-spl.jpg. 

2. Town of Frisco Colorado. (2023). Maps. https://www.friscogov.com/your-government/maps/. 

3. Lankford, H. V. (2021). The death zone: Lessons from history. Wilderness & Environmental Medicine, 32(1), pp. 114-120. https://doi.org/10.1016/j.wem.2020.09.002. 

4. West, J. C. (2013). Case law update. Legal liability in emergency medicine and risk management considerations. Journal of healthcare risk management: the journal of the American Society for Healthcare Risk Management, 33(1), pp. 53-60. 

5. Cabrales, P., Govender, K. and Williams, A.T. (2020), What determines blood viscosity at the highest city in the world?. J Physiol, 598: 3817-3818. https://doi.org/10.1113/JP280206

6. Image. https://cdn.allsummitcounty.com/images/content/5717_13913_Frisco_Colorado_Main_Street_lg.jpg