Austrian Moderate Altitude Study 2000 (AMAS 2000). The effects of moderate altitude (1,700 m) on cardiovascular and metabolic variables in patients with metabolic syndrome

Schobersberger, Wolfgang; Schmid, Peter; Lechleitner, Monika; Duvillard, Serge P. von; Hörtnagl, Helmut; Gunga, Hanns‐Christian; Klingler, Antón; Fries, Dietmar; Kirsch, K.; Spiesberger, Reinhard; Pokan, Rochus; Hofmann, Peter; Hoppichler, Fritz; Riedmann, Gebhard; Baumgartner, Holger; Humpeler, Egon

doi:10.1007/s00421-002-0736-8

Cited by 105 publications

(96 citation statements)

References 24 publications

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“…Furthermore, 5-10 days of adaptation to hypoxia returns hyperglycemia to basal levels in healthy people (5). Moreover chronic hypoxic exposure reduces fasting insulin and improves insulin resistance in type 2 diabetic patients (44)(45)(46) and decreases the insulin dosage in type 1 diabetic patients (47,48). Of note, lower insulin levels or reduced insulin signaling is beneficial for health and longevity (49,50).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Corticotropin-Releasing Hormone–Induced Insulinotropic Role by High-Altitude Hypoxia

et al. 2014

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We have shown that hypoxia reduces plasma insulin, which correlates with corticotropin-releasing hormone (CRH) receptor 1 (CRHR1) in rats, but the mechanism remains unclear. Here, we report that hypobaric hypoxia at an altitude of 5,000 m for 8 h enhances rat plasma CRH, corticosterone, and glucose levels, whereas the plasma insulin and pancreatic ATP/ADP ratio is reduced. In islets cultured under normoxia, CRH stimulated insulin release in a glucose-and CRH-level-dependent manner by activating CRHR1 and thus the cAMP-dependent protein kinase pathway and calcium influx through L-type channels. In islets cultured under hypoxia, however, the insulinotropic effect of CRH was inactivated due to reduced ATP and cAMP and coincident loss of intracellular calcium oscillations. Serum and glucocorticoid-inducible kinase 1 (SGK1) also played an inhibitory role. In human volunteers rapidly ascended to 3,860 m, plasma CRH and glucose levels increased without a detectable change in plasma insulin. By contrast, volunteers with acute mountain sickness (AMS) exhibited a marked decrease in HOMA insulin sensitivity (HOMA-IS) and enhanced plasma CRH. In conclusion, hypoxia may attenuate the CRH-insulinotropic effect by reducing cellular ATP/ADP ratio, cAMP and calcium influx, and upregulated SGK1. Hypoxia may not affect HOMA-IS in healthy volunteers but reduces it in AMS volunteers.To enjoy social activities, millions of people travel to high altitudes every year. High-altitude hypoxia often induces dysfunction and illness, particularly acute mountain sickness (AMS) (1). During the construction of the QinghaiTibet railway (at altitudes of 3,000-5,000 m) in China, .100,000 construction workers were involved, and 51% of them developed AMS (2). Moreover, since the railway began service, .10 million travelers have visited the Tibet region in 2012, of whom 31% developed AMS despite traveling with an oxygen supply on the train (3). Increasing evidence in both humans and animals suggests that exposure to either high-altitude or hypobaric hypoxia influences plasma insulin levels and glucose homeostasis, depending on the oxygen level and duration of exposure (4-9). We previously showed that subacute hypoxia at an altitude of 5,000 m for 5 days reduces plasma insulin in rats, and this effect is blocked by a corticotropin-releasing hormone (CRH) receptor 1 (CRHR1) antagonist in vivo (10). However, the underlying mechanisms have not been clearly addressed.Insulin, the unique hypoglycemic hormone, plays a crucial role in maintaining glucose sensing in pancreatic b-cells and regulating glucose uptake in a variety of tissues and cells during health and disease (11,12). Apart from glucose, many neural and endocrine hormones regulate pancreatic insulin release (13). In particular, CRH is the key regulator of the hypothalamic-pituitary-adrenal (HPA) axis; is activated by a variety of stressors, including hypoxia; and mediates a variety of neural and endocrine

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Section: Discussionmentioning

confidence: 99%

Inactivation of Corticotropin-Releasing Hormone–Induced Insulinotropic Role by High-Altitude Hypoxia

et al. 2014

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“…There were no differences in glycemia between subjects using insulin, metformin, sulfonylurea derivatives, dipeptidyl peptidase-4 inhibitors, or thiazolidinedione, although the number of subjects using these drugs was small (30). Schobersberger et al (31) found reductions in glucose concentrations and HOMA-IR after oral glucose loading, following 3 weeks of exercise at an altitude of 1,700 m in subjects with metabolic syndrome, four of whom had type 2 diabetes. These findings indicate increased insulin sensitivity at high to very high altitude and a possible additive effect of hypoxia and exercise in subjects with type 2 diabetes.…”

Section: Glucoregulatory Effects In Subjects With Diabetesmentioning

confidence: 99%

Physical Activity at Altitude: Challenges for People With Diabetes

Mol

Vries²,

Koning

et al. 2014

Diabetes Care

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A growing number of subjects with diabetes take part in physical activities at altitude such as skiing, climbing, and trekking. Exercise under conditions of hypobaric hypoxia poses some unique challenges on subjects with diabetes, and the presence of diabetes can complicate safe and successful participation in mountain activities. Among others, altitude can alter glucoregulation. Furthermore, cold temperatures and altitude can complicate accurate reading of glucose monitoring equipment and storage of insulin. These factors potentially lead to dangerous hyperglycemia or hypoglycemia. Over the last years, more information has become available on this subject. PURPOSETo provide an up-to-date overview of the pathophysiological changes during physical activity at altitude and the potential problems related to diabetes, including the use of (continuous) blood glucose monitors and insulin pumps. To propose practical recommendations for preparations and travel to altitude for subjects with diabetes. DATA SOURCES AND SYNTHESISWe researched PubMed, medical textbooks, and related Internet sites, and extracted human studies and data based on relevance for diabetes, exercise, and altitude. LIMITATIONSGiven the paucity of controlled trials regarding diabetes and altitude, we composed a narrative review and filled in areas lacking diabetes-specific studies with data obtained from nondiabetic subjects. CONCLUSIONSSubjects with diabetes can take part in activities at high, and even extreme, altitude. However, careful assessment of diabetes-related complications, optimal preparation, and adequate knowledge of glycemic regulation at altitude and altitude-related complications is needed.An increasing number of subjects with diabetes reside at high altitude for short periods of time, partly for work, but mainly for recreational purposes such as skiing, trekking, and climbing. Exercise under conditions of hypobaric hypoxia poses some unique challenges for subjects with diabetes and could potentially lead to dangerous situations such as unexpected hypoglycemia and hyperglycemia, inaccurate

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“…Augmented blood levels of immunological markers are a common finding during and after long-term strenuous exercise, where, due to skeletal muscle injury, infiammatory processes are induced. Although different changes of specific parameters like TNF-a, TNFRl, IL-Iß or IL-6 have been reportcd in the literature, high post-exercise values of one or more of the.se proinflammatory agonists have constantly been reported (4,12,20,21). Another limitation of the present study is that measurement of systemic parameters does not afways retlect significant changes in a local microenvironment.…”

Section: Discussionmentioning

confidence: 69%

“…Previous publications of data derived from the AMAS study reported favorable effects to a 3-week exposure to 1700 m on body mass, blood pressure, heart rate, Insulin resistance and glucose tolerance (11,12). Among the mediators chosen for the present study to represent an activated immune system in patients with metabolic Syndrome, only neopterin and sTNF-R75 showed a slight but transient increase on days 4 and/or 9 at moderate altitude as compared to baseline levels.…”

Section: Discussionmentioning

confidence: 79%

AMAS (Austrian Moderate Altitude Study)-2000: Effects of Hiking Holidays at Moderate Altitude on Immune System Markers in Persons with Metabolic Syndrome.

Schobersberger¹,

Hoffmann²,

Fries³

et al. 2004

Pteridines

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Recent studies have shown a strong association between indices of inflammation and metabolic Syndrome. Proinflammatory mediators like tumor necrosis factor-a may act as a trigger for insulin insensitivity. Therefore. patients with tnetabolic Syndrome might be at higher risk of insulin resistance when confronted with additional Stimuli of the immune system. These Stimuli are not restricted to thc presence of pathogens but include environmental factors like physical exercise and hypoxemia as well. With respect to these interdependencies, one may assume higher risk for patients with metabolic Syndrome who perform physical exercise in alpine regions. We investigated the effects of a 3-weeks holiday with moderate sporting activities at moderate altitude (1700 m) on the conceiitrations of neopterin, tumor necrosis factor-a, serum soluble 75kD type TNF receptor (sTNF-R75), and interleukin-6 in vacationers with metabolic Syndrome. Only serum neopterin and sTNF-R75 concentrations transiently increased during the stay at moderate altitude compared to pre-altitude levels (P<0.05). Interestingly, after return to 500 m sea-level neopterin concentrations dropped beyond baseline concentrations (p<0.05). However, the variations in neopterin concentrations might not be of clinical relevance since they did not exceed the threshold indicating significant activation of the cellular immune system. We conclude that a 3-week sojourn at moderate altitude including individually adapted physical exercise does not represent accumulated risk factors in subjects with metabolic Syndrome.

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Austrian Moderate Altitude Study 2000 (AMAS 2000). The effects of moderate altitude (1,700 m) on cardiovascular and metabolic variables in patients with metabolic syndrome

Cited by 105 publications

References 24 publications

Inactivation of Corticotropin-Releasing Hormone–Induced Insulinotropic Role by High-Altitude Hypoxia

Inactivation of Corticotropin-Releasing Hormone–Induced Insulinotropic Role by High-Altitude Hypoxia

Physical Activity at Altitude: Challenges for People With Diabetes

AMAS (Austrian Moderate Altitude Study)-2000: Effects of Hiking Holidays at Moderate Altitude on Immune System Markers in Persons with Metabolic Syndrome.

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