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Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland.

ABSTRACT: To clarify the association between glucose intolerance and high altitudes (2900-4800 m) in a hypoxic environment in Tibetan highlanders and to verify the hypothesis that high altitude dwelling increases vulnerability to diabetes mellitus (DM) accelerated by lifestyle change or ageing.Cross-sectional epidemiological study on Tibetan highlanders.We enrolled 1258 participants aged 40-87 years. The rural population comprised farmers in Domkhar (altitude 2900-3800 m) and nomads in Haiyan (3000-3100 m), Ryuho (4400 m) and Changthang (4300-4800 m). Urban area participants were from Leh (3300 m) and Jiegu (3700 m).Participants were classified into six glucose tolerance-based groups: DM, intermediate hyperglycaemia (IHG), normoglycaemia (NG), fasting DM, fasting IHG and fasting NG. Prevalence of glucose intolerance was compared in farmers, nomads and urban dwellers. Effects of dwelling at high altitude or hypoxia on glucose intolerance were analysed with the confounding factors of age, sex, obesity, lipids, haemoglobin, hypertension and lifestyle, using multiple logistic regression.The prevalence of DM (fasting DM)/IHG (fasting IHG) was 8.9% (6.5%)/25.1% (12.7%), respectively, in all participants. This prevalence was higher in urban dwellers (9.5% (7.1%)/28.5% (11.7%)) and in farmers (8.5% (6.1%)/28.5% (18.3%)) compared with nomads (8.2% (5.7%)/15.7% (9.7%)) (p=0.0140/0.0001). Dwelling at high altitude was significantly associated with fasting IHG+fasting DM/fasting DM (ORs for >4500 and 3500-4499 m were 3.59/4.36 and 2.07/1.76 vs <3500 m, respectively). After adjusting for lifestyle change, hypoxaemia and polycythaemia were closely associated with glucose intolerance.Socioeconomic factors, hypoxaemia and the effects of altitudes >3500 m play a major role in the high prevalence of glucose intolerance in highlanders. Tibetan highlanders may be vulnerable to glucose intolerance, with polycythaemia as a sign of poor hypoxic adaptation, accelerated by lifestyle change and ageing.

SUBMITTER: Okumiya K

PROVIDER: S-EPMC4769430 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Project description:Genome-wide studies on highland adaptation mechanism in terrestrial animal have been widely reported with few available for aquatic animals. Tibetan Schizothoracinae species are ideal model systems to study speciation and adaptation of fish. The Schizothoracine fish, Gymnocypris przewalskii ganzihonensis had underwent the ecological niche shift from salt water to freshwater, and also experienced a recent split from Gymnocypris przewalskii przewalskii. In addition, G. p. ganzihonensis inhabited harsh aquatic environment including low temperature and hypoxia as well as other Schizothoracinae species, its genetic mechanism of highland adaptation have yet to be determined.Our study used comparative genomic analysis based on the transcriptomic data of G. p. ganzihonensis and other four fish genome datasets to investigate the genetic basis of highland adaptation in Schizothoracine fish. We found that Schizothoracine fish lineage on the terminal branch had an elevated dN/dS ratio than its ancestral branch. A total of 202 gene ontology (GO) categories involved into transport, energy metabolism and immune response had accelerated evolutionary rates than zebrafish. Interestingly, we also identified 162 genes showing signature of positive selection (PSG) involved into energy metabolism, transport and immune response in G. p. ganzihonesis. While, we failed to find any PSG related to hypoxia response as previous studies.Comparative genomic analysis based on G. p. ganzihonensis transcriptome data revealed significant genomic signature of accelerated evolution ongoing within Tibetan Schizothoracinae species lineage. Molecular evolution analysis suggested that genes involved in energy metabolism, transport and immune response functions in Schizothoracine fish underwent positive selection, especially in innate immunity including toll-like receptor signaling pathway genes. Taken together, our result as a case study in Schizothoracinae species provides novel insights in understanding the aquatic animal adaptation to extreme environment on the Tibetan Plateau, and also provides valuable genomic resource for further functional verification studies.

Project description:BackgroundThe Tibetan highland fish, Gymnocypris przewalskii, migrates from Lake Qinghai to its spawning grounds every summer. This seasonal reproduction is critically regulated by intrinsic and extrinsic signals. However, the molecular mechanisms that process environmental oscillations to initiate the seasonal mating are largely unknown.ResultsA transcriptomic analysis was conducted on the brain and gonad of male and female G. przewalskii in reproductive and nonreproductive seasons. We obtained 2034, 760, 1158 and 17,856 differentially expressed genes between the reproductively active and dormant female brain, male brain, ovary and testis. Among these genes, DIO2 was upregulated in the reproductively active brain and gonad of both males and females. Neuroactive ligand-receptor genes were activated in male and female brain. Functional enrichment analysis suggested that retinol metabolism was uniquely stimulated in reproductively active males. Genes involved in GnRH signaling and sex hormone synthesis exhibited higher expression levels in brain and gonad during the reproductive season. A co-expression network classified all the genes into 9 modules. The network pinpointed CDC42 as the hub gene that connected the pathways in responsible for modulating reproduction in G. przewalskii. Meanwhile, the sex pheromone receptor gene prostaglandin receptor was identified to link to multiple endocrine receptors, such as GnRHR2 in the network.ConclusionsThe current study profiled transcriptomic variations between reproductively active and dormant fish, highlighting the potential regulatory mechanisms of seasonal reproduction in G. przewalskii. Our data suggested that the seasonal regulation of reproduction in G. przewalskii was controlled by the external stimulation of photoperiodic variations. The activated transcription of neuroendocrine and sex hormone synthesis genes contributed to seasonal reproduction regulation in G. przewalskii, which was presumably influenced by the increased day-length during the breeding season.

Project description:BackgroundNutritional risk is associated with adverse clinical outcomes and is more prevalent among pulmonology patients than among patients in other departments. High-altitude environments can affect patients with chronic respiratory diseases, but evidence of the prevalence of nutritional risk among hospitalized patients with respiratory diseases in high-altitude areas is limited. This study aimed to investigate the nutritional risk and status of inpatients with different major respiratory diagnoses permanently living on the Tibetan Plateau (≥3,000 m above sea level).MethodsIn this cross-sectional study, we consecutively recruited inpatients admitted to the Department of Respiratory and Critical Care Medicine at the Tibet Autonomous Region People's Hospital of Lhasa between November 2020 and May 2021. We used the Nutrition Risk Screening (NRS) 2002 tool to assess nutritional risk among these patients. An NRS 2002 score ≥3 points indicates nutritional risk; a score ≥5 indicates high nutritional risk. According to NRS-2002 scores, patients were divided into three groups (NRS-2002 0-2, 3-4, and ≥5). The differences in age, sex, major respiratory diagnoses, comorbidities, body mass index, and laboratory findings among the groups were analyzed.ResultsA total of 289 eligible Tibetan patients were enrolled in the study, and 46.1% (133/246) of them were at nutritional risk (NRS-2002 score ≥3). Twenty-one (7.3%) patients were at high nutritional risk (NRS-2002 score ≥5). The proportions of patients at nutritional risk were relatively high among patients with lung cancer (58.8%), interstitial lung disease (58.3%), pulmonary embolism (52.9%), and tuberculosis (50.0%). Laboratory findings showed that patients with NRS-2002 scores of 3-4 and ≥5 had lower red blood cell counts, serum albumin and hemoglobin levels, and higher C-reactive protein (CRP) levels than those with NRS-2002 scores < 3.ConclusionThe prevalence of nutritional risk was high among pulmonology department inpatients permanently living on the Tibetan Plateau. Patients with lung cancer, interstitial lung disease, pulmonary embolism or tuberculosis were more likely to have nutritional risk than patients with other diagnoses. The nutritional risk of inpatients in the respiratory department in the plateau area should not be ignored, and patients at high nutritional risk should receive timely intervention.

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Glucose intolerance associated with hypoxia in people living at high altitudes in the Tibetan highland.

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