Establishment of a reference interval for total carbon dioxide using indirect methods in Chinese populations living in high-altitude areas: A retrospective real-world analysis.

BACKGROUND: Hypoxia leads to different concentrations of the bicarbonate buffer system in Tibetan people. Indirect methods were used to establish the reference interval (RI) for total carbon dioxide (tCO2) based on big data from the adult population of Tibet, a high-altitude area in Western China. METHODS: Anonymous tCO2 test data (n = 442,714) were collected from the People's Hospital of the Tibet Autonomous Region from January 2018, to December 2021. Multiple linear regression and variance component analyses were performed to assess the effects of sex, age, and race on tCO2 levels. Indirect methods, including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR, were used to calculate the total RI and ethnicity-partitioned RI. RESULTS: A total of 230,821 real-world tCO2 test results were eligible. Sex, age, and race were significantly associated with the tCO2 levels. The total and ethnically-partitioned RIs estimated using the five indirect methods were comparable. The total RI of tCO2 was 14-24 mmol/L (calculated using Hoffmann and refineR) and 15-24 mmol/L (Bhattacharya, EM and kosmic). For Han nationality, the RIs were 14-25 mmol/L (calculated using Hoffmann and Bhattacharya), 16-23 mmol/L (EM), 15-24 mmol/L (kosmic), and 14.2-24.5 mmol/L (refineR). For the Tibetan population, the RIs were 14-24 mmol/L (calculated using Hoffmann and refineR), 15-24 mmol/L (Bhattacharya and kosmic), and 15-23 mmol/L (EM). The established RIs were significantly lower than those living at lower altitudes area (22-29 mmol/L) that was provided by the manufacturer. CONCLUSION: The tCO2 RI of the populations living on the Tibetan Plateau was significantly lower than those at the lower altitudes. The RIs established using indirect methods are suitable for clinical applications in Tibet.

Establishment of Reference Intervals for Thyroid-Associated Hormones Using refineR Algorithm in Chinese Population at High-Altitude Areas.

Objectives: Diagnosis of thyroid disease among individuals dwelling at high altitude remains a challenge. Reference intervals (RIs) for thyroid-associated hormones among Tibetans living at various high altitudes were established to improve diagnosis. Methods: One thousand two hundred eighty-one subjects were randomly recruited from Nyingchi, Shigatse/Lhasa, and Ali of Tibet. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured by the Cobas e601 electrochemiluminescence analyzer. We used multiple linear regression and variance component analysis to assess the effect of sex, age, and altitude on hormones. RIs were established by refineR algorithm and compared with those provided by the manufacturer. Results: Serum TSH was significantly lower in males than in females, while FT3 and FT4 were higher in males. Both FT3 and FT4 decreased with increasing age. FT3 increased with altitude, while TSH and FT4 were less influenced by altitude. The RI for TSH was 0.764-5.784 µIU/ml, while for FT4, the RIs were 12.36-19.38 pmol/L in females and 14.84-20.18 pmol/L in males. The RIs for FT3 at Nyingchi, Shigatse/Lhasa, and Ali in females were 4.09-4.98, 4.31-5.45, and 4.82-5.58 pmol/L, while in males, the values were 4.82-5.41, 4.88-5.95, and 5.26-6.06 pmol/L, respectively. The obtained RIs for TSH and FT4 were generally higher, while that for FT3 was narrower than the RIs provided by Cobas. Conclusions: Specific RIs were established for thyroid-associated hormones among Tibetans, which were significantly different from those provided by the manufacturer.

Evaluation of bone metabolism-associated biomarkers in Tibet, China.

AIM: To measure and evaluate the distribution and possible contributing factors of seven bone metabolism-associated biomarkers in Tibet, a plateau province of China. METHODS: A total of 1615 individuals were recruited from Tibet at three different altitudes. The levels and possible contributing factors of serum calcium, serum phosphorus, ALP, 25OHD, PINP, CTX, and PTH were evaluated. RESULTS: In total, 1246 Tibetan adults (males: n = 543) were eventually enrolled in this study. Multiple linear regression recognized age, sex, altitude, and BMI as the major effect factors. The levels of ALP, PINP, and CTX in males continuously decreased with age; however, those in females increased after approximately 39 years of age. Males had higher 25OHD levels (23.9 vs. 15.4 ng/ml) but lower levels of serum phosphorus (1.12 vs. 1.19 mmol/L) and PTH (41.3 vs. 47.4 pg/ml) than females. Before the age of 50, males had higher levels of calcium, ALP, PINP, and CTX than females, and the opposite trend was observed after the age of 50. The highest levels of serum calcium and phosphorus and the lowest levels of PINP and CTX were found in the Shigatse/Lhasa region, suggesting a better bone metabolism status. Compared with reports from plain areas of China, significantly higher levels of PINP (65.3 vs. 49.36 ng/ml) and CTX (0.46 vs. 0.37 ng/ml) were recorded in Tibetan adults. CONCLUSION: A more active bone turnover status was found in Tibetan adults than in individuals from the plain areas of China.

An evaluation of urine and serum iodine status in the population of Tibet, China: No longer an iodine-deficient region.

OBJECTIVES: Iodine is a critical trace element for the synthesis of thyroid-related hormones, and either low or high iodine status can lead to thyroid dysfunction. This study aimed to evaluate the iodine status of the Tibetan population. METHODS: From September 2016 to August 2018, we enrolled 1499 healthy adults from three areas of varying altitudes in Tibet. Urine iodine concentrations (UICs), adjusted UICs, and serum iodine concentrations (SICs) were measured using inductively coupled plasma mass spectrometry. RESULTS: The median UIC, adjusted UIC, and SIC was 137.9 µg/L, 118.4 µg/gCr, and 58.3 µg/L, respectively. Of the participants, 30.4% had UICs <100 µg/L, 63.0% had UICs ranging from 100 to 300 µg/L, and 9.6% had UICs >300 µg/L. The correlation between UIC, adjusted UIC, and SIC was good (r > 0.65, P < 0.01). The SICs were more stable than the UICs, and were not associated with age or sex. The prevalence of clinical hyperthyroidism, clinical hypothyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, positive thyroid peroxide antibody, positive thyroglobulin antibody, either positive and both positive was 0.5%, 1.3%, 1.7% and 17.9%, 9.3%, 6.5%, 12.5%, and 2.5%, respectively. The prevalence of almost all thyroid disorders was higher in women than in men. CONCLUSION: This multicenter cross-sectional study found that the human iodine status of adults in Tibet was considered adequate, based on the World Health Organization's criteria.