Background: Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Methods: Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. Results: The geometric mean serum TSH (2.5th–97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74–7.04 mIU/L) and 2.34 mIU/L (0.61–8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, p -value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27–4.2 mIU/L) and NACB standard interval in the TIDE study (0.74–7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%, p < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27–4.2 and 4.2–7.04 mIU/L TSH groups. Conclusions: Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.

Background: Iodine intake is associated with thyroid autoimmunity. In this study, we evaluated the changes in thyroid autoimmunity after 20 years of universal salt iodization (USI) in China. Methods: A total of 78,470 subjects (18 years or older) from 31 provincial regions of mainland China participated in the study. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), TSH receptor antibody, thyrotropin (TSH), and urinary iodine concentration (UIC) were measured. Results: Positive TPOAb and TgAb were detected in 10.19% [CI 9.80–10.59] and 9.70% [CI 9.28–10.13] of the subjects, respectively. The prevalence of positive isolated TPOAb (i-TPOAb), positive isolated TgAb (i-TgAb), and double positive TPOAb and TgAb (d-Ab) was 4.52%, 4.16%, and 5.94%, respectively. The prevalence of thyroid antibody positivity was the highest in the iodine-deficient (UIC <100 μg/L) groups. The prevalence of i-TPOAb was inversely associated with more than adequate iodine intake (MAI) and excessive iodine intake (EI); the odds ratio (OR) was 0.89 [CI 0.81–0.98] for MAI and 0.90 [CI 0.81–0.99] for EI. We observed that i-TgAb, like i-TPOAb, was a high-risk factor for subnormal TSH levels (OR = 3.64 [CI 2.62–5.05]) and elevated TSH levels (OR = 1.62 [CI 1.49–1.77]). The prevalence of thyroid antibody positivity varied among five ethnic groups. Conclusions: After two decades of USI, the prevalence of thyroid antibody positivity has remained low. MAI and EI had an inverse relationship with TPOAb positivity, which reveals that UIC between 100 and 299 μg/L is optimal and safe for thyroid autoimmunity. These conclusions need to be confirmed in a follow-up study because this study was a cross-sectional study.

Objective: The purpose of this study was to determine whether vitamin D levels correlate with procalcitonin (PCT) levels and mortality in septic patients. Methods: The following data were collected from 236 patients upon admission to intensive care units (ICUs): demographics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; Sequential Organ Failure Assessment (SOFA) score; 25-hydroxyvitamin D (25OHD), PCT, intact PTH, albumin, creatinine, and ionized calcium (iCa) levels; 25OHD sampling seasonality; fluid load (colloid and crystalloid before 25OHD sampling); mechanical ventilation duration; and length of stay (LOS) in the ICU. The primary endpoint was all-cause mortality 28 days after ICU admission. Results: Patients with 25OHD deficiency had significantly higher APACHE II and SOFA scores, positive blood culture rates, PCT levels, intact PTH levels, and 28-day mortality rates. These patients also had lower iCa levels, longer LOS in the ICU, and longer ventilator durations than patients with 25OHD insufficiency or sufficiency. Age, sex, 25OHD sampling seasonality, serum albumin and creatinine levels, and fluid load did not vary among the 3 groups. Serum 25OHD levels at admission were significantly negatively correlated with PCT levels. PTH responders had significantly higher 28-day mortality rates than did PTH nonresponders. Cox regression showed that a 25OHD level of <20 ng/mL was an independent risk factor for 28-day mortality. Conclusions: Lower serum 25OHD levels at ICU admission were associated with 28-day mortality in septic patients. Serum 25OHD levels were inversely correlated with PCT levels. Hypovitaminosis D was associated with higher mortality rates in PTH responders than in nonresponders.

Background: Type 2 diabetes (T2DM) combined with fatty liver is a subtype of metabolic fatty liver disease (MAFLD), and the relationship between T2DM and MAFLD is close and mutually influential. However, the connection and mechanisms between the two are still unclear. Therefore, we aimed to identify potential biomarkers for diagnosing both conditions.Methods: We performed differential expression analysis and weighted gene correlation network analysis (WGCNA) on publicly available data on the two diseases in the Gene Expression Omnibus database to find genes related to both conditions. We utilised protein–protein interactions (PPIs), Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes to identify T2DM-associated MAFLD genes and potential mechanisms. Candidate biomarkers were screened using machine learning algorithms combined with 12 cytoHubba algorithms, and a diagnostic model for T2DM-related MAFLD was constructed and evaluated.The CIBERSORT method was used to investigate immune cell infiltration in MAFLD and the immunological significance of central genes. Finally, we collected whole blood from patients with T2DM-related MAFLD, MAFLD patients and healthy individuals, and used high-fat, high-glucose combined with high-fat cell models to verify the expression of hub genes.Results: Differential expression analysis and WGCNA identified 354 genes in the MAFLD dataset. The differential expression analysis of the T2DM-peripheral blood mononuclear cells/liver dataset screened 91 T2DM-associated secreted proteins. PPI analysis revealed two important modules of T2DM-related pathogenic genes in MAFLD, which contained 49 nodes, suggesting their involvement in cell interaction, inflammation, and other processes. TNFSF10, SERPINB2, and TNFRSF1A were the only coexisting genes shared between MAFLD key genes and T2DM-related secreted proteins, enabling the construction of highly accurate diagnostic models for both disorders. Additionally, high-fat, high-glucose combined with high-fat cell models were successfully produced. The expression patterns of TNFRSF1A and SERPINB2 were verified in patient blood and our cellular model. Immune dysregulation was observed in MAFLD, with TNFRSF1A and SERPINB2 strongly linked to immune regulation.Conclusion: The sensitivity and accuracy in diagnosing and predicting T2DM-associated MAFLD can be greatly improved using SERPINB2 and TNFRSF1A. These genes may significantly influence the development of T2DM-associated MAFLD, offering new diagnostic options for patients with T2DM combined with MAFLD.

The current study was performed to investigate the effects and potential effects of irbesartan pretreatment on pancreatic β‐cell apoptosis in a streptozotocin‐ (STZ‐) induced acute mouse model of prediabetes. Twenty‐four male BALB/C mice (18–22 g) were randomly divided into three groups: normal control group (NC, n = 6), STZ group (STZ, n = 8), and irbesartan + STZ group (IRB + STZ, n = 10). In the IRB + STZ group, mice were administered irbesartan (300 mg/kg per day) by gavage for one week. The STZ group and IRB + STZ group received STZ (80 mg/kg by intraperitoneal (IP) injection once). The NC group received normal saline (80 mg/kg by IP injection once). Fasting blood glucose prior to STZ injection and presacrifice was analysed using samples withdrawn from the caudal vein to confirm the induction of prediabetes. Haematoxylin and eosin staining, immunohistochemical detection of insulin, and apoptosis analysis were performed. Reverse transcription‐quantitative polymerase chain reaction was used to detect angiotensin II type 1 receptor (AT1R), caspase‐3, and p38 mitogen‐activated protein kinase (MAPK) mRNA expression. Blood glucose was significantly higher in the STZ group (9.01 ± 1.1089 vs 4.78 ± 0.7026) and IRB + STZ group (7.86 ± 1.1811 vs 4.78 ± 0.7026) compared with the NC group (P < 0.05). In comparison to the STZ group, the islet cell damage was marginally improved in the IRB + STZ group, and the IRB + STZ group had a significantly lower apoptotic rate than the STZ group (22.42 ± 8.3675 vs 50.86 ± 5.3395, P < 0.001). AT1R expression in the IRB + STZ group was lower than that in the STZ group (1.56 ± 1.2207 vs 3.92 ± 2.4392, P < 0.05). The mRNA expression of caspase‐3 in pancreatic tissue was significantly lower in the IRB + STZ group than in the STZ group (0.90 ± 0.7272 vs 1.88 ± 1.0572, P < 0.05). Similarly, the IRB + STZ group also had lower p38MAPK levels than the STZ group (1.16 ± 1.0642 vs 2.55 ± 1.7925, P > 0.05). In conclusion, irbesartan pretreatment improved glucose levels and insulin secretion and decreased islet β‐cell apoptosis to protect islet β cells in an STZ‐induced acute prediabetic mouse model.