Extreme altitude mountaineering and Type 1 diabetes; the Diabetes Federation of Ireland Kilimanjaro Expedition

Moore, Kent J.; Vizzard, N.; Coleman, Christina; mcmahon, jeannette; Hayes, RP; Thompson, Chris

doi:10.1046/j.0742-3071.2001.00568.x

Cited by 66 publications

(96 citation statements)

References 9 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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“…Furthermore, whether insulin requirements increase or decrease in response to very high altitude in type 1 diabetes remains subject to debate (8)(9)(10).…”

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confidence: 99%

Increased insulin requirements during exercise at very high altitude in type 1 diabetes

Mol

Vries²,

Koning³

et al. 2012

NED. TIJDSCHR. DIABET.

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OBJECTIVE-Safe, very high altitude trekking in subjects with type 1 diabetes requires understanding of glucose regulation at high altitude. We investigated insulin requirements, energy expenditure, and glucose levels at very high altitude in relation to acute mountain sickness (AMS) symptoms in individuals with type 1 diabetes.RESEARCH DESIGN AND METHODS-Eight individuals with complication-free type 1 diabetes took part in a 14-day expedition to Mount Meru (4,562 m) and Mount Kilimanjaro (5,895 m) in Tanzania. Daily insulin doses, glucose levels, energy expenditure, and AMS symptoms were determined. Also, energy expenditure and AMS symptoms were compared with a healthy control group.RESULTS-We found a positive relation between AMS symptoms and insulin requirements (r = 0.78; P = 0.041) and AMS symptoms and glucose levels (r = 0.86; P = 0.014) for Mount Kilimanjaro. Compared with sea level, insulin doses tended to decrease by 14.2% (19.7) (median [interquartile range]) (P = 0.41), whereas glucose levels remained stable up to 5,000 m altitude. However, at altitudes .5,000 m, insulin dose was unchanged (36.8 6 17 vs. 37.6 6 19.1 international units [mean 6 SD] P = 0.75), but glucose levels (7.5 6 0.6 vs. 9.5 6 0.8 mmol/L [mean 6 SD] P = 0.067) and AMS scores (1.3 6 1.6 vs. 4.4 6 4 points [mean 6 SD] P = 0.091) tended to increase. Energy expenditure and AMS symptoms were comparable in both groups (P = 0.84).CONCLUSIONS-Our data indicate that in complication-free individuals with type 1 diabetes, insulin requirements tend to increase during altitudes above 5,000 m despite high energy expenditure. This change may be explained, at least partly, by AMS.

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“…54 Blurring of vision can occur during hypoglycaemic situations. HAR related to hypoxia can occur at altitudes higher than 5000 meters.…”

Section: Diabetic Retinopathy and High Altitudesmentioning

confidence: 99%

Ocular Problems in High-Altitude Traveling: A Review With Focus on Management

Izadi

Pourazizi

Alemzadeh-Ansari

2017

Int J Travel Med Glob Health

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Extreme altitude mountaineering and Type 1 diabetes; the Diabetes Federation of Ireland Kilimanjaro Expedition

Cited by 66 publications

References 9 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

Increased insulin requirements during exercise at very high altitude in type 1 diabetes

Ocular Problems in High-Altitude Traveling: A Review With Focus on Management

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