Global burden of type 1 diabetes in adults aged 65 years and older, 1990-2019: population based study.

OBJECTIVES: To estimate the burden, trends, and inequalities of type 1 diabetes mellitus (T1DM) among older adults at global, regional, and national level from 1990 to 2019. DESIGN: Population based study. POPULATION: Adults aged ≥65 years from 21 regions and 204 countries and territories (Global Burden of Disease and Risk Factors Study 2019)from 1990 to 2019. MAIN OUTCOME MEASURES: Primary outcomes were T1DM related age standardised prevalence, mortality, disability adjusted life years (DALYs), and average annual percentage change. RESULTS: The global age standardised prevalence of T1DM among adults aged ≥65 years increased from 400 (95% uncertainty interval (UI) 332 to 476) per 100 000 population in 1990 to 514 (417 to 624) per 100 000 population in 2019, with an average annual trend of 0.86% (95% confidence interval (CI) 0.79% to 0.93%); while mortality decreased from 4.74 (95% UI 3.44 to 5.9) per 100 000 population to 3.54 (2.91 to 4.59) per 100 000 population, with an average annual trend of -1.00% (95% CI -1.09% to -0.91%), and age standardised DALYs decreased from 113 (95% UI 89 to 137) per 100 000 population to 103 (85 to 127) per 100 000 population, with an average annual trend of -0.33% (95% CI -0.41% to -0.25%). The most significant decrease in DALYs was observed among those aged <79 years: 65-69 (-0.44% per year (95% CI -0.53% to -0.34%)), 70-74 (-0.34% per year (-0.41% to -0.27%)), and 75-79 years (-0.42% per year (-0.58% to -0.26%)). Mortality fell 13 times faster in countries with a high sociodemographic index versus countries with a low-middle sociodemographic index (-2.17% per year (95% CI -2.31% to -2.02%) v -0.16% per year (-0.45% to 0.12%)). While the highest prevalence remained in high income North America, Australasia, and western Europe, the highest DALY rates were found in southern sub-Saharan Africa, Oceania, and the Caribbean. A high fasting plasma glucose level remained the highest risk factor for DALYs among older adults during 1990-2019. CONCLUSIONS: The life expectancy of older people with T1DM has increased since the 1990s along with a considerable decrease in associated mortality and DALYs. T1DM related mortality and DALYs were lower in women aged ≥65 years, those living in regions with a high sociodemographic index, and those aged <79 years. Management of high fasting plasma glucose remains a major challenge for older people with T1DM, and targeted clinical guidelines are needed.

Changing Iodine Status and the Incidence of Thyroid Disease in Mainland China: A Prospective 20-Year Follow-Up Study.

Background: We aimed to assess the long-term effects of the transition in iodine status on the incidence of thyroid disorders over 20 years of follow-up. Methods: The original prospective cohort study, started in 1999 (n = 3761), classified three regions in north China based on iodine status (insufficient iodine, more than adequate iodine, and excessive iodine, respectively) for 5 years. Subsequently, participants were followed for up to another 15 years to assess the long-term effects of shifts to adequate iodine on the incidence of thyroid disorders. Panshan transitioned from insufficient to adequate iodine, and Huanghua transitioned from excessive to more than adequate iodine. Both regions were compared with Zhangwu, in which iodine status changed from more than adequate to adequate iodine (from 214 to 167.2 µg/L). A cluster sampling method was used to select participants in the three regions. Participants completed questionnaires and underwent thyroid ultrasonography. Urinary iodine concentrations (UICs), serum thyroid hormone concentration, and thyroid antibodies were measured. Results: When the iodine status changed from insufficient to adequate (with the median UIC increasing from 88 to 141.9 µg/L), the incidence density of subclinical hyperthyroidism, positive thyroperoxidase antibody, positive thyroglobulin antibody (TgAb), and goiter decreased significantly (p < 0.05 for all). Additionally, the cumulative incidence of subclinical hypothyroidism was significantly lower compared with the region where the iodine status changed from being more than adequate to adequate (1.9% vs. 6.0%, p < 0.001). When the iodine status changed from excessive to more than adequate (median UIC from 634 to 266.7 µg/L), a significant decrease in the incidence density of subclinical hyperthyroidism, positive thyroid antibodies, positive TgAb, and goiter (p < 0.05 for all) were also found. However, an increase in thyroid nodule incidence density (17.26 vs. 28.25 per 1000 person-years, p < 0.001) was seen. Conclusions: The incidence of thyroid disorders (except for thyroid nodules) stabilized or decreased among adults in the three communities from year 5 to year 15 of follow-up. Appropriate iodine fortification is safe and effective over the long term. Restoring urinary iodine to appropriate levels reduces population risk for thyroid disorders.

Global, regional, and national burdens of HIV and other sexually transmitted infections in adolescents and young adults aged 10-24 years from 1990 to 2019: a trend analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: Sexually transmitted infections (STIs), including HIV, are major sexual health issues among adolescents and young adults globally, but data on the burden and trends of these diseases are sparse. We aimed to assess the trends in the burden of HIV and other STIs among adolescents and young adults aged 10-24 years from 1990 to 2019 on the global, regional, and national level. METHODS: In this trend analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we reported on the number, rates per 100 000 population, and average annual percentage changes (AAPCs) of incidence and disability-adjusted life-years (DALYs) of HIV and other STIs (syphilis, chlamydia, gonorrhoea, trichomonas, and genital herpes) at the global, regional, and national level among individuals aged 10-24 years. We further analysed these global trends by age, sex, and social development index (SDI). We also used joinpoint regression analysis to identify the year with the most substantial changes in global trends. FINDINGS: Globally, the incidence of HIV among adolescents and young adults decreased from 34·5 per 100 000 population (95% uncertainty interval [UI] 29·3 to 39·7) in 1990 to 22·7 per 100 000 population (20·3 to 25·8) in 2019, AAPC -2·6 [95% CI -3·1 to -2·0]); specific years in which HIV incidence decreased significantly were 1998, 2005, and 2014. Incidence of other STIs increased from 6986·3 per 100 000 population (95% UI 5504·8-8645·0) in 1990 to 7088·7 100 000 population (5620·1-8697) in 2019 (AAPC 0·2 [95% CI 0·1-0·3]); we found a substantial decrease in the incidence of other STIs in 2011 only. The rate of decrease in the incidence of other global STIs between 2009 and 2019 was approximately one-fifth the rate of the decrease in the global incidence of HIV for the same time period (AAPC -0·7 [95% CI -0·8 to -0·7] vs AAPC -3·4 [-3·8 to -3·1]). Regionally, sub-Saharan Africa had the highest incidence and highest DALYs from HIV and other STIs, and Oceania and Eastern Europe had the largest increase in the incidence and DALYs from HIV and other STIs between 1990 and 2019. By SDI quintile, the middle-SDI countries had the largest increase in HIV incidence between 1990 and 2019 and the DALYs from other STIs in the same period decreased in all SDI quintiles. Globally, females accounted for 278 076 (65·8%) of the 0·42 million incident HIV cases in 2019 and 68 115 077 (51·6%) of the 132·0 million incident cases of other STIs. Of all age groups, adolescents aged 10-14 years had the largest increase in the incidence of other STIs between 1990 and 2019 (from 1158·9 per 100 000 population [95% UI 857·8-1556·5] in 1990 to 1215·4 per 100 000 population [893·5-1616·1] in 2019; AAPC 0·1 [95% CI 0·1-0·2]). The individual STIs with the highest incident rates varied between age groups and sex. INTERPRETATION: Global HIV incidence among adolescents and young adults decreased between 1990 and 2019, with significant decreases coinciding with the implementation of antiretroviral therapy and pre-exposure prophylaxis. The incidence of other STIs in this population increased over the same period and only started decreasing in 2011, at a rate of only one-fifth of the rate of decrease of HIV. Earlier sexual health education and targeted STI screening are urgently required for adolescents and young adults. FUNDING: National Natural Science Foundation of China and the China Postdoctoral Science Foundation.

Burden of carbon monoxide poisoning in China, 1990-2019: A systematic analysis of data from the global burden of disease study 2019.

Background: Carbon monoxide (CO) poisoning is one of the most common toxic occupational diseases, but related data in China are scarce. A better understanding of the burden of CO poisoning is essential for improving its management. Methods: A systematic analysis of data from the Global Burden of Disease (GBD) Study 2019 was conducted. Following the general analytical strategy used in the GBD Study 2019, the sex- and age-specific incidence and mortality rates of CO poisoning and disability-adjusted life years (DALYs) due to CO poisoning in China were analyzed. Estimated average annual percentage changes (AAPCs) in age-standardized rates were calculated by joinpoint regression analysis. The effects of age, period and cohort on the incidence of CO poisoning and DALYs due to CO poisoning were estimated by an age-period-cohort model. Results: The age-standardized incidence and mortality rates as well as DALYs of CO poisoning per 100,000 population were estimated to be 21.82 [95% uncertainty interval (UI): 15.05-29.98], 0.93 (95% UI: 0.63-1.11), and 40.92 (95% UI: 28.43-47.85), respectively, in 2019. From 1990 to 2019, the AAPCs in the age-standardized incidence significantly increased in both males and females, while the age-standardized mortality rates and DALYs significantly decreased in both males and females. The incidence of CO poisoning peaked in individuals aged 15-19 years. Males had a higher burden of CO poisoning than females. The age effect showed that the relative risks (RRs) of incident CO poisoning decreased with age among males and females and that individuals aged 15-24 years had the highest RRs. The RRs of incident CO poisoning increased with time. The cohort effect showed that the incidence increased in successive birth cohorts. Conclusions: The incidence of CO poisoning in China increased from 1990 to 2019. More attention should be given to improving the burden of CO poisoning in Chinese adolescents. The results of this study can be used by health authorities to inform preventative measures to reduce the burden of CO poisoning.

Global, regional, and national burdens of common micronutrient deficiencies from 1990 to 2019: A secondary trend analysis based on the Global Burden of Disease 2019 study.

BACKGROUND: Understanding micronutrient deficiency burdens and trends can help guide effective intervention strategies. This study aims to elucidate trends in common micronutrient deficiencies, in particular, dietary iron, iodine and vitamin A deficiencies, from 1990 to 2019 using Global Burden of Disease (GBD) 2019 study data. METHODS: We analyzed data from the GBD 2019 study to calculate the prevalence, incidence, and disability-adjusted life year (DALY) rates of micronutrient deficiencies in geographic populations worldwide from 1990 to 2019. The estimated annual percentage changes (EAPCs) and age-standardized rates were calculated to evaluate the temporal trends. FINDINGS: Globally, the age-standardized prevalence rates of iodine deficiency, vitamin A deficiency, and dietary iron deficiency decreased, with EAPCs of -0.690 (95% CI, -0.842 to -0.538), -3.15 (95% CI, -3.20 to -3.02), and -0.546 (95% CI, -0.585 to -0.507) between 1999 and 2019, respectively. Regarding the sociodemographic index (SDI), the highest age-standardized prevalence, incidence, and DALY rates of micronutrient deficiency were found in low-SDI countries in 2019. There were linear associations between the SDI and the healthcare access and quality (HAQ) index and age-standardized prevalence, incidence, and DALY rates. INTERPRETATION: Global micronutrient deficiency burdens have decreased since 1990. The potential burden of iodine deficiency in some developed countries is worthy of attention. The results of this study could guide policy makers in implementing cost-effective interventions to reduce micronutrient deficiency burdens, particularly in low-SDI and low-HAQ index countries. FUNDING: This work was supported by the National Natural Science Foundation of China (Grant No. 82000753) and the China Postdoctoral Science Foundation (Grant No. 2021MD703910).

Concentration-dependent Differences in Urinary Iodine Measurements Between Inductively Coupled Plasma Mass Spectrometry and the Sandell-Kolthoff Method.

A large amount of historical data regarding urinary iodine concentration (UIC) were measured with the Sandell-Kolthoff (S-K) method for iodine nutrition surveillance. The congruence in urinary iodine measurements between inductively coupled plasma mass spectrometry (ICP-MS) and the S-K method has been debated. A total of 2064 adult urine samples were included in the present study. The UIC measurement results obtained simultaneously by standardized ICP-MS and the S-K method were analyzed. The UIC obtained with ICP-MS was significantly higher than that obtained with the S-K method (158 µg/L vs. 148 µg/L, p < 0.001). The Bland-Altman difference plot showed a small but significant mean difference of 6.12 µg/L between the two methods. The stratified analysis showed that the correlation coefficient was higher in the UIC < 300 µg/L group than the UIC ≥ 300 µg/L group (0.93 vs. 0.88, p = 0.0001). The mean difference between the S-K and ICP-MS methods was positively correlated with the UIC. The ICP-MS and S-K methods were comparable when the UIC was less than 300 µg/L; however, UIC values between 300 and 600 µg/L should be compared with caution after considering the research objective. We do not suggest comparing UICs obtained from the ICP-MS and S-K methods in iodine monitoring studies if the UIC is greater than 600 µg/L.

Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy.

Alpha-enolase (ENO1) is a ubiquitous protein. Patients with autoimmune thyroiditis-associated encephalopathy have high serum ENO1Ab titers. We aimed to explore whether ENO1Ab was the pathogenic antibody in the thyroid and brain. The serum ENO1Ab titers were significantly increased in the mice immunized with Thyroglobulin (Tg). And in the mice immunized with ENO1, serum levels of both TgAb and thyroid-stimulating hormone (TSH) were significantly increased. Obvious CD16+ cell infiltration, IgG deposit and cleaved caspase-3 were observed in the thyroid of ENO1-immunized mice. Spatial learning and memory abilities and synaptic functions were impaired in ENO1-immunized mice. Furthermore, the expression levels of Iba-1, GFAP, interlukin-6, CDK5, and phosphorylated tau were increased, and endothelial tight junction proteins were decreased in the brain of ENO1-immunized mice. These results suggest that ENO1Ab can cause thyrocyte damage via ADCC effect and impair cerebral function by disrupting the blood-brain barrier.

Different Thyroidal Responses to Human Chorionic Gonadotropin Under Different Thyroid Peroxidase Antibody and/or Thyroglobulin Antibody Positivity Conditions During the First Half of Pregnancy.

BACKGROUND: Thyroid peroxidase antibody (TPOAb) positivity can attenuate gestational thyroid responses to human chorionic gonadotropin (hCG) during pregnancy, whereas the effects of thyroglobulin antibodies (TgAb) remain unknown. The aim of our study was to explore the thyroid response to hCG in women with thyrotropin (TSH) levels within the method-specific reference range under different conditions of thyroid autoimmunity. METHODS: The study screened 822 women at 7-20 weeks of gestation using the pregnancy-specific reference range for TSH. Serum TSH, free thyroxine (fT4), TPOAb, TgAb, and ß-hCG levels were measured using electrochemiluminescence immunoassays. RESULTS: The enrolled pregnant women were subdivided into four subgroups based on TPOAb/TgAb positivity: co-positive for TPOAb and TgAb (group 1), isolated TPOAb positive (group 2), isolated TgAb positive (group 3), and co-negative for TPOAb and TgAb (group 4). TSH was negatively associated with hCG in all four groups (p < 0.05). fT4 was positively associated with hCG in groups 3 and 4 (p < 0.01) but not in groups 1 (p = 0.096) and 2 (p = 0.758). Group 2 was further stratified into tertiles according to TPOAb concentrations. No negative TSH/hCG association was observed in the middle- and upper-tertile groups when TPOAb were ≥53 IU/mL (p > 0.05). There was no positive fT4/hCG association in any of the three subgroups (p > 0.05). Similarly, group 3 was further stratified into tertiles according to TgAb levels. TSH was negatively associated with hCG in the lower and middle tertiles (p < 0.01), but the association was not found in the upper tertile when TgAb was ≥356 IU/mL (p = 0.191). fT4 was positively associated with hCG in the lower tertile (p = 0.027) but not in subgroups when TgAb was ≥219 IU/mL (p > 0.05). CONCLUSIONS: When TSH was within the pregnancy-specific reference range, high concentrations of TPOAb and TgAb attenuated the fT4 stimulation and suppression of TSH by hCG. The results imply that TgAb, in addition to TPOAb, could also interfere with thyroidal responses to hCG during the first half of pregnancy.

Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via Integrin/EGFR-ERK/MAPK signaling pathway.

Our previous study showed that Calreticulin (CRT) promoted the development of pancreatic cancer (PC) through ERK/MAPK pathway. We next investigate whether CRT promotes EGF-induced epithelial-mesenchymal transition (EMT) in PC via Integrin/EGFR-ERK/MAPK signaling, which has not been reported yet to our knowledge. EGF simultaneously induced EMT and activated Integrin/EGFR-ERK/MAPK signaling pathway in 3 PC cells. However, CRT silencing significantly inhibited EGF function, including inhibiting EGF-induced EMT-like cell morphology, EGF-enhanced cell invasion and migration, and EGF induced the decrease of E-cadherin, ZO-1, and ß-catenin and the increase of the key proteins in Integrin/EGFR-ERK/MAPK signaling (pEGFR-tyr1173, Fibronectin, Integrinß1, c-Myc and pERK). Conversely, CRT overexpression rescued the change of EMT-related proteins induced by EGF in CRT silencing PC cells. Additionally, CRT was co-stained with pEGFR1173 (with EGF), Fibronectin and Integrinß1 by IF under confocal microscopy and was co-immunoprecipitated with Fibronectin, Integrinß1 and c-Myc in both PC cells, all of which indicating a close interaction of CRT with Integrin/EGFR-ERK/MAPK signaling pathway in PC. In vivo, CRT silencing inhibited subcutaneous tumor growth and liver metastasis of pancreatic tumor. A positive relationship of CRT with Fibronectin, Integrinß1, c-Myc and pERK and a negative association of CRT with E-cad was also observed in vivo and clinical samples. Meanwhile, overexpression of the above proteins was closely associated with multiple aggressive clinicopathological characteristics and the poor prognosis of PC patients. CRT promotes EGF-induced EMT in PC cells via Integrin/EGFR-ERK/MAPK signaling pathway, which would be a promising therapy target for PC.

Serum fibroblast growth factor 19 is decreased in patients with overt hypothyroidism and subclinical hypothyroidism.

As a newly emerging metabolic regulator, accumulating evidence suggests that the circulating fibroblast growth factor 19 (FGF19) level correlated with lipid and glucose metabolism. Several independent groups have found that FGF19 was highly likely associated with multiple metabolic disorders. Thyroid dysfunction is believed to be associated with metabolism diseases. However, to date, few studies have investigated the role of FGF19 in patients with thyroid dysfunctions. For this purpose, a cross-sectional study was done to estimate the role of FGF19 in patients with different thyroid functions. Compared with the healthy control, the present study revealed that serum FGF19 levels were significantly decreased in overt hypothyroidism patients (78.7 [52.7-121.2] vs 292.4 [210.2-426.5] pg/mL, P <0.001). FGF19 concentration was also lower in the subclinical hypothyroidism group than it was in the healthy control group (95.8 [71.7-126.3] vs 292.4 [210.2-426.5] pg/mL, P <0.001). However, there was no significant difference in FGF19 level between the isolated thyroid autoantibody positive group and the healthy control group (252.0 [205.9-353.5] vs 292.4 [210.2-426.5] pg/mL, P >0.05). Also, serum thyroid stimulating hormone (TSH) was an independent predictor of FGF19. In conclusion, thyroid insufficiency but not thyroid autoimmunity may have impacted serum FGF19 concentrations. As the role of FGF19 is becoming more and more important in the pathogenesis of many metabolic diseases, we proposed that the thyroid hormone level should be taken into account when the serum concentration is explained. Further studies are needed to elucidate the role of FGF19 in the development of hypothyroidism.

The Effects of Serum ANGPTL8/betatrophin on the Risk of Developing the Metabolic Syndrome - A Prospective Study.

ANGPTL8/betatrophin is a recently discovered hormone, which mainly synthesized and secreted by liver and adipose tissue, playing a critical role in pancreatic beta cell proliferation. Previous studies have suggested that serum ANGPTL8/betatrophin levels are associated with obesity and diabetes mellitus. Here, we evaluated the prospective association between ANGPTL8/betatrophin and the metabolic syndrome from a community-based cohort of 153 adults without metabolic syndrome. After 3.5-year follow-up, we observed an inverse correlation between the baseline ANGPTL8/betatrophin levels and the incidence of metabolic syndrome, even after multivariate adjustments. In receiver operating characteristic analysis, the area underneath the curve for ANGPTL8/betatrophin was 0.70 in males and 0.86 in females, and the optimal cut-off values were 23.9 ng/mL and 31.1 ng/mL, respectively. This article suggests that ANGPTL8/betatrophin might be useful in predicting newly-onset metabolic syndrome and its progression in clinical setting.

Effect of Prolonged Iodine Overdose on Type 2 Iodothyronine Deiodinase Ubiquitination-Related Enzymes in the Rat Pituitary.

The purpose of this study is to determine the effect of prolonged iodine overdose on type 2 iodothyronine deiodinase (D2) ubiquitination-related enzymes. Male Wistar rats were fed different doses of iodine and were then euthanized at the 4, 8, 12, or 24 weeks (4w, 8w, 12w, or 24w) after iodine administration. Urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), total thyroxine (TT4), and total triiodothyronine (TT3) were determined. Real-time quantitative RT-PCR and Western blot were used to measure mRNA and protein expression levels of pituitary D2 as well as two D2-specific ubiquitin ligases [WD repeat and SOCS box-containing protein 1 (WSB-1), membrane-associated ring finger (C3HC4) 6 (MARCH6 or TEB4)] and two D2-specific deubiquitinating enzymes [ubiquitin-specific peptidase 20 (USP20) and ubiquitin-specific peptidase 33 (USP33)]. The mRNA and protein expression levels of USP19, a TEB4-specific deubiquitinating enzyme, were also measured. Prolonged high iodine intake significantly increased TSH expression. At 12w, TSH was 1.57-, 1.44-, and 2.11-fold of NI group in 6HI, 10HI, and 50HI groups, respectively. At 24w, TSH had increased to 2.11-fold in the 50HI group. The pituitary D2 protein level decreased at 12w and 24w; though the mRNA level did not change. Prolonged iodine intake increased mRNA and protein expression levels of pituitary WSB-1 and TEB4. High iodine intake had no discernible effects on USP20. Temporary increases in USP33 and USP19 mRNA levels were observed. The enzymes related to D2 ubiquitination change with prolonged high iodine intake. Increased D2 ubiquitination suppresses the activity of D2, causing a decrease in negative feedback of the hypothalamic-pituitary-thyroid axis.

Inflammatory mediators, tumor necrosis factor-α and interferon-γ, induce EMT in human PTC cell lines.

Inflammatory mediators, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, promote adverse outcomes in numerous types of cancer; however, their role in papillary thyroid cancer (PTC) remains unclear. The aim of the present study was to investigate the influence of TNF-α and IFN-γ on the migration, invasion and epithelial-mesenchymal transition (EMT) of the three PTC cell lines, TPC-1, BCPAP and K1. The effect of TNF-α and IFN-γ on cell migration and invasion was assessed by wound-healing and Transwell assays. In addition, the mRNA and protein expression levels of the EMT makers, E-cadherin, N-cadherin and vimentin, were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunoblot analysis. The wound-healing and Transwell experiments revealed that TNF-α and IFN-γ increased the migratory and invasive behavior of PTC cells (P<0.05). RT-qPCR revealed that TNF-α and IFN-γ downregulated E-cadherin mRNA, while they upregulated N-cadherin and vimentin mRNA expression levels. These results were further confirmed by the immunoblot analysis. The results of the present study suggest that TNF-α and IFN-γ induce EMT and malignant progression in human PTC cells.