UIAA Medical Commission Recommendations for Mountaineers, Hillwalkers, Trekkers, and Rock and Ice Climbers with Diabetes.

Hillebrandt, David, Anil Gurtoo, Thomas Kupper, Paul Richards, Volker Schöffl, Pankaj Shah, Rianne van der Spek, Nikki Wallis, and Jim Milledge. UIAA Medical Commission recommendations for mountaineers, hillwalkers, trekkers, and rock and ice climbers with diabetes. High Alt Med Biol. 24: 110-126.-The object of this advice article is not only to give the diabetic mountaineer general guidance but also to inform his or her medical team of practical aspects of care that may not be standard for nonmountaineers. The guidelines are produced in seven sections. The first is an introduction to the guidelines, and the second is an introduction to this medical problem and is designed to be read and understood by diabetic patients and their companions. The third section is for use in an emergency in mountains. The fourth is for rock, ice, and competition climbers operating in a less remote environment. These initial sections are deliberately written in simple language. The fifth and sixth sections are written for clinicians and those with skills to read more technical information, and the seventh looks at modern technology and its pros and cons in diabetes management in a remote area. Sections One and Two could be laminated and carried when in the mountains, giving practical advice.

Thermal lesions of the SCN do not abolish all gene expression rhythms in rat white adipose tissue, NAMPT remains rhythmic.

Obesity and type 2 diabetes mellitus are major health concerns worldwide. In obese-type 2 diabetic patients, the function of the central brain clock in the hypothalamus, as well as rhythmicity in white adipose tissue (WAT), are reduced. To better understand how peripheral clocks in white adipose tissue (WAT) are synchronized, we assessed the importance of the central brain clock for daily WAT rhythms. We compared gene expression rhythms of core clock genes (Bmal1, Per2, Cry1, Cry2, RevErbα, and DBP) and metabolic genes (SREBP1c, PPARα, PPARγ, FAS, LPL, HSL, CPT1b, Glut4, leptin, adiponectin, visfatin/NAMPT, and resistin) in epididymal and subcutaneous white adipose tissue (eWAT and sWAT) of SCN-lesioned and sham-lesioned rats housed in regular L/D conditions. Despite complete behavioral and hormonal arrhythmicity, SCN lesioning only abolished Cry2 and DBP rhythmicity in WAT, whereas the other clock gene rhythms were significantly reduced, but not completely abolished. We observed no major differences in the effect of SCN lesions between the two WAT depots. In contrast to clock genes, all metabolic genes lost their daily rhythmicity in WAT, with the exception of NAMPT. Interestingly, NAMPT rhythmicity was even less affected by SCN lesioning than the core clock genes, suggesting that it is either strongly coupled to the remaining rhythmicity in clock gene expression, or very sensitive to other external rhythmic factors. The L/D cycle could be such a rhythmic external factor that generates modulating signals by photic masking via the intrinsic photosensitive retinal ganglion cells in combination with the autonomic nervous system. Our findings indicate that in normal weight rats, gene expression rhythms in WAT can be maintained independent of the central brain clock.

Daily Gene Expression Rhythms in Rat White Adipose Tissue Do Not Differ Between Subcutaneous and Intra-Abdominal Depots.

White adipose tissue (WAT) is present in different depots throughout the body. Although all depots are exposed to systemic humoral signals, they are not functionally identical. Studies in clock gene knockout animals and in shift workers suggest that daily rhythmicity may play an important role in lipid metabolism. Differences in rhythmicity between fat depots might explain differences in depot function; therefore, we measured mRNA expression of clock genes and metabolic genes on a 3-h interval over a 24-h period in the subcutaneous inguinal depot and in the intra-abdominal perirenal, epididymal, and mesenteric depots of male Wistar rats. We analyzed rhythmicity using CircWave software. Additionally, we measured plasma concentrations of glucose, insulin, corticosterone, and leptin. The clock genes (Bmal1/Per2/Cry1/Cry2/RevErbα/DBP) showed robust daily gene expression rhythms, which did not vary between WAT depots. Metabolic gene expression rhythms (SREBP1c/PPARα/PPARγ/FAS/LPL/Glut4/HSL/CPT1b/leptin/visfatin/resistin) were more variable between depots. However, no distinct differences between intra-abdominal and subcutaneous rhythms were found. Concluding, specific fat depots are not associated with differences in clock gene expression rhythms and, therefore, do not provide a likely explanation for the differences in metabolic function between different fat depots.

Oxygen saturation increases over the course of the night in mountaineers at high altitude (3050-6354 m).

BACKGROUND: Blood oxygen saturation (SpO 2 ) is frequently measured to determine acclimatization status in high-altitude travellers. However, little is known about nocturnal time course of SpO 2 (SpO 2N ), but alterations in SpO 2N might be practically relevant as well. To this end, we describe the time-course of SpO 2N in mountaineers at high altitude. METHODS: SpO 2N was continuously measured in ten male mountaineers during a three-week expedition in Peru (3,050-6,354m). Average SpO 2N of the first (SpO 2N1 ) and second half (SpO 2N2 ) of an individual's sleep duration was calculated from 2h intervals of uninterrupted sleep. Heart rate oscillations and sleep dairies were used to exclude periods of wakefulness. SpO 2 was also measured at rest in the morning. RESULTS: SpO 2N significantly increased from SpO 2N1 to SpO 2N2 . The magnitude of this increase (ΔSpO 2 ) was reduced with time spent at altitude. On night 1 (3,050m) SpO 2 increased from 83.4% (N1) to 86.3% (N2). At the same location on night 21, SpO 2 increased from 88.3% to 90.1%, which is a relative change of 4.7% and 2.0%, respectively. This pattern of increase in SpO 2N was perturbed when individual acclimatization was poor or altitude was extreme (5630m). SpO 2N was significantly lower than SpO 2 at rest in the morning. CONCLUSIONS: This study is the first to demonstrate an increase of SpO 2 during the night in mountaineers at high altitude (3,050-6,354m) with high consistency between and within subjects. The magnitude of ΔSpO 2N decreased as acclimatization improved, suggesting that these changes in ΔSpO 2 between nights might be a valuable indicator of individual acclimatization. In addition, the failure of any increase in SpO 2N during the night might indicate insufficient acclimatization. Even though underlying mechanisms for the nocturnal increase remain unclear, the timing of SpO 2N measurement is obviously of utmost importance for its interpretation. Finally our study illustrates the detailed effects of ventilatory acclimatization over several weeks.

Drug Use and Misuse in the Mountains: A UIAA MedCom Consensus Guide for Medical Professionals.

Donegani, Enrico, Peter Paal, Thomas Küpper, Urs Hefti, Buddha Basnyat, Anna Carceller, Pierre Bouzat, Rianne van der Spek, and David Hillebrandt. Drug use and misuse in the mountains: a UIAA MedCom consensus guide for medical professionals. High Alt Med Biol. 17:157-184, 2016.-Aims: The aim of this review is to inform mountaineers about drugs commonly used in mountains. For many years, drugs have been used to enhance performance in mountaineering. It is the UIAA (International Climbing and Mountaineering Federation-Union International des Associations d'Alpinisme) Medcom's duty to protect mountaineers from possible harm caused by uninformed drug use. The UIAA Medcom assessed relevant articles in scientific literature and peer-reviewed studies, trials, observational studies, and case series to provide information for physicians on drugs commonly used in the mountain environment. Recommendations were graded according to criteria set by the American College of Chest Physicians. RESULTS: Prophylactic, therapeutic, and recreational uses of drugs relevant to mountaineering are presented with an assessment of their risks and benefits. CONCLUSIONS: If using drugs not regulated by the World Anti-Doping Agency (WADA), individuals have to determine their own personal standards for enjoyment, challenge, acceptable risk, and ethics. No system of drug testing could ever, or should ever, be policed for recreational climbers. Sponsored climbers or those who climb for status need to carefully consider both the medical and ethical implications if using drugs to aid performance. In some countries (e.g., Switzerland and Germany), administrative systems for mountaineering or medication control dictate a specific stance, but for most recreational mountaineers, any rules would be unenforceable and have to be a personal decision, but should take into account the current best evidence for risk, benefit, and sporting ethics.

Effects of adrenalectomy on daily gene expression rhythms in the rat suprachiasmatic and paraventricular hypothalamic nuclei and in white adipose tissue.

It is assumed that in mammals the circadian rhythms of peripheral clocks are synchronized to the environment via neural, humoral and/or behavioral outputs of the central pacemaker in the suprachiasmatic nucleus of the hypothalamus (SCN). With regard to the humoral outputs, the daily rhythm of the adrenal hormone corticosterone is considered as an important candidate. To examine whether adrenal hormones are necessary for the maintenance of daily rhythms in gene expression in white adipose tissue (WAT), we used RT-PCR to check rhythmic as well as 24 h mean gene expression in WAT from adrenalectomized (ADX) and sham-operated rats. In addition, we investigated the effect of adrenalectomy on gene expression in the hypothalamic SCN and paraventricular nucleus (PVN). Adrenalectomy hardly affected daily rhythms of clock gene expression in WAT. On the other hand, >80% of the rhythmic metabolic/adipokine genes in WAT lost their daily rhythmicity in ADX rats. Likewise, in the hypothalamus adrenalectomy had no major effects on daily rhythms in gene expression, but it did change the expression level of some of the neuropeptide genes. Together, these data indicate that adrenal hormones are important for the maintenance of daily rhythms in metabolic/adipokine gene expression in WAT, without playing a major role in clock gene expression in either WAT or hypothalamus.

Timing of fat and liquid sugar intake alters substrate oxidation and food efficiency in male Wistar rats.

In addition to the amount of ingested calories, both timing of food intake and meal composition are determinants of body weight gain. However, at present, it is unknown if the inappropriate timing of diet components is responsible for body weight gain. In the present study, we therefore studied a time-dependent effect of the diet composition on energy homeostasis. Male Wistar rats were subjected to chow ad libitum (chow group) or a choice diet with saturated fat, a 30% sugar solution, chow and tap water. The choice diet was provided either with all components ad libitum (AL), with ad libitum access to chow, tap water and a 30% sugar solution, but with access to saturated fat only during the light period (LF), or with ad libitum access to chow, tap water and saturated fat, but access to a 30% sugar solution only during the light period (LS). Caloric intake and body weight gain were monitored during 31 days. Energy expenditure was measured in the third week in calorimetric cages. All rats on a choice diet showed hyperphagia and gained more body weight compared to the chow group. Within the choice diet groups, rats on the LS diet were most food efficient (i.e. gained most body weight per ingested calorie) and showed a lower respiratory exchange ratio (RER) with an anti-phasic pattern, whereas no differences in locomotor activity or heat production were found. Collectively these data indicate that the timing of the diet composition affects food efficiency, most likely due to a shifted oxidation pattern, which can predispose for obesity. Further studies are underway to assess putative mechanisms involved in this dysregulation.

The suprachiasmatic nucleus controls circadian energy metabolism and hepatic insulin sensitivity.

Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus. Here, we studied the direct contribution of the suprachiasmatic nucleus (SCN), the central pacemaker in the circadian system, in the development of insulin resistance. Exclusive bilateral SCN lesions in male C57Bl/6J mice, as verified by immunochemistry, showed a small but significant increase in body weight (+17%), which was accounted for by an increase in fat mass. In contrast, mice with collateral damage to the ventromedial hypothalamus and paraventricular nucleus showed severe obesity and insulin resistance. Mice with exclusive SCN ablation revealed a loss of circadian rhythm in activity, oxygen consumption, and food intake. Hyperinsulinemic-euglycemic clamp analysis 8 weeks after lesioning showed that the glucose infusion rate was significantly lower in SCN lesioned mice compared with sham-operated mice (-63%). Although insulin potently inhibited endogenous glucose production (-84%), this was greatly reduced in SCN lesioned mice (-7%), indicating severe hepatic insulin resistance. Our data show that SCN malfunctioning plays an important role in the disturbance of energy balance and suggest that an absence of central clock activity, in a genetically intact animal, may lead to the development of insulin resistance.

Circadian rhythms in white adipose tissue.

Adipose tissue is an important endocrine organ. It is involved in the regulation of energy metabolism by secreting factors (adipokines) that regulate appetite, food intake, glucose disposal, and energy expenditure. Many of these adipokines display profound day/night rhythms, and accumulating evidence links disruption of these rhythms to metabolic diseases such as obesity and type 2 diabetes. Here, we briefly present the circadian system, describe the development of white adipose tissue (WAT) and its depot-specific characteristics and innervation, we discuss energy storage in WAT and, lastly, review recent findings that link circadian rhythmicity to adipose tissue biology and obesity.