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Countries and companies in the developing world are rushing to sell bonds at the fastest clip in at least a decade, taking advantage of high appetite for emerging-market assets to issue debt amid what investors say could be sharper swings ahead in global debt markets.

Last week’s more than $27 billion bond deluge included deals from Saudi Arabia, Turkey’s sovereign wealth fund and Brazilian oil giant Petrobras. The demand is such that JPMorgan strategists raised their forecasts for EM sovereign debt issuance, now expecting a record year for the asset class.

Introduction

Diabetes mellitus is primarily classified into type 1 diabetes (T1D) and type 2 diabetes (T2D). However, some patients exhibit clinical features intermediate between T1D and T2D, a condition termed latent autoimmune diabetes in adults (LADA), also known as type 1.5 diabetes. LADA is a slowly progressive autoimmune diabetes characterized by the presence of autoantibodies, with glutamic acid decarboxylase 65 antibodies (GAD65-Ab) being the most significant immunological marker. GAD65-Ab may coexist with other pancreatic autoantibodies, such as insulin autoantibodies (IAA), which serve as early indicators of pancreatic β-cell dysfunction and play a crucial role in the pathogenesis of LADA.¹

Patients with one autoimmune disorder are at an increased risk of developing another. LADA has been associated with other autoimmune diseases, including Hashimoto’s thyroiditis, Sjögren’s syndrome, and dermatomyositis, which share common autoimmune components and genetic susceptibility loci, such as human leukocyte antigen DR (HLA-DR), cytotoxic T-lymphocyte-associated protein 4(CTLA-4), CD25, protein tyrosine phosphatase non-receptor 22(PTPN22), and forkhead box P3 (FOXP3) genes.^2–6 Recent studies suggest that specific variants in these genes, such as those in PTPN22, may determine the onset of distinct diseases with different phenotypic and clinical characteristics.^7–9 These findings, both clinically and mechanistically, support the association between autoimmune thyroid diseases and LADA. However, the clinical characteristics of thyroid dysfunction in LADA patients from the Xuzhou region of Jiangsu, China, remain unclear. Therefore, the objective of this study is to investigate the clinical features and risk factors associated with thyroid dysfunction in LADA patients in Xuzhou, Jiangsu, to facilitate early intervention and treatment.

Materials and Methods

We conducted a single-center, cross-sectional study involving 95 hospitalized LADA patients from the Affiliated Hospital of Xuzhou Medical University between January 2024 and April 2025. The patients were divided into two groups based on the presence or absence of thyroid dysfunction: 39 LADA patients without thyroid dysfunction and 56 LADA patients with thyroid dysfunction.

Inclusion Criteria

1. Diagnosis of LADA (based on WHO criteria and the latest guidelines).
2. No recent use of medications affecting thyroid function.

Exclusion Criteria

1. Known history of thyroid disease.
2. Pregnancy or severe hepatic/renal dysfunction.
3. Other types of diabetes.

Data collection included clinical parameters and thyroid function assessment. The following variables were recorded: age, disease duration (Duration), systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), uric acid (UA), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), GAD65-Ab (GADA), urinary albumin-to-creatinine ratio (UACR), triglyceride-glucose index (TyG), TyG-body mass index (TyG-BMI), estimated glomerular filtration rate (eGFR), fasting C-peptide (FCP), postprandial 2-hour C-peptide (P2hCP), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), thyrotropin receptor antibodies (TRAb), IAA, 25-hydroxyvitamin D [25(OH)D], proinsulin (PI), and calcitonin (CT). Blood samples were stored at −80°C. Thyroid function was evaluated by measuring FT3, FT4, TSH, TPOAb, TGAb, and TRAb levels using chemiluminescence assays.

Statistical analysis was performed using SPSS 24.0. Normally distributed data were expressed as mean ± standard deviation and compared using independent samples t-tests. Non-normally distributed data were expressed as median (interquartile range) and analyzed using the Mann–Whitney U-test. To explore correlations between variables, Pearson’s correlation analysis was performed for features with P < 0.05, and a heatmap of correlation coefficients was generated. Univariate logistic regression analysis was also conducted. A P-value < 0.05 was considered statistically significant.

All participants provided written informed consent, and the study was approved by the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University. The study complies with the Declaration of Helsinki.

Results

Baseline characteristics (Table 1) revealed significant differences between the two groups in UACR, FCP, P2hCP, FT3, FT4, TPOAb, TGAb, TRAb, and IAA (all P < 0.05). Compared to LADA patients without thyroid dysfunction, those with thyroid dysfunction exhibited higher UACR, lower FCP and P2hCP levels, reduced FT3 and FT4, significantly elevated TPOAb and TGAb, and increased TRAb and IAA levels.

Table 1 Comparison of Baseline Characteristics Between LADA Patients without Thyroid Dysfunction and LADA Patients with Thyroid Dysfunction

Subsequently, to explore inter-feature correlations, we performed Pearson correlation tests on variables with P < 0.05, calculating correlation coefficients between variables and generating Pearson correlation heatmaps. We investigated associations among UACR, FCP, P2hCP, FT3, FT4, TPOAb, TGAb, TRAb, and IAA in LADA patients. The correlation analysis revealed that FCP showed positive correlations with P2hCP and FT3, while demonstrating a negative correlation with IAA. FT3 was positively correlated with P2hCP and FT4. Additionally, TPOAb exhibited positive correlations with both TGAb and TRAb (see Table 2 and Figure 1).

Table 2 Correlations Among UACR, FCP, P2hCP, FT3, FT4, TPOAb, TGAb, TRAb, and IAA in LADA Patients

Figure 1 Heatmap of Pearson Correlation Coefficients Among UACR, FCP, P2hCP, FT3, FT4, TPOAb, TGAb, TRAb, and IAA in LADA Patients.

Finally, univariate binary logistic regression analysis (Table 3) revealed that lower FCP, P2hCP, and FT3 levels, as well as higher TPOAb and TGAb levels, were associated with the occurrence of thyroid dysfunction in LADA patients.

Table 3 Univariate Binary Logistic Regression Analysis of Thyroid Dysfunction in LADA Patients

Discussion

Our findings demonstrate that LADA patients with thyroid dysfunction exhibit significantly higher UACR, lower FCP and P2hCP levels, decreased FT3 and FT4, along with markedly elevated TPOAb and TGAb, and increased TRAb and IAA levels. These results suggest that compared to LADA patients without thyroid dysfunction, those with concomitant thyroid abnormalities are more prone to diabetic nephropathy, exhibit more severe islet dysfunction, and have higher susceptibility to autoimmune thyroid diseases—particularly Hashimoto’s thyroiditis—while also indicating greater disease severity and progression risk in LADA.

The observed association between thyroid dysfunction and LADA corroborates previous cross-sectional observations.^10–14 A 2025 Diabetologia study further elucidated this relationship mechanistically, revealing that MHC-driven immune responses—encompassing both innate and adaptive pathways—represent the primary shared biological pathway connecting LADA with Crohn’s disease, ulcerative colitis, hypothyroidism, hyperthyroidism, and vitiligo. These pathways involve diverse immune cells (B cells, T cells, and natural killer cells) and molecules (cytokines, immunoglobulins, and interferons).¹⁵

Diabetes mellitus (DM) substantially increases chronic complication risks. Diabetic kidney disease (DKD), one of the most prevalent microvascular complications affecting up to 25% of DM patients, constitutes a leading cause of chronic kidney disease and end-stage renal disease,^16,17 imposing significant economic burdens and severely compromising quality of life. Thyroid hormones critically influence glucose metabolism, where both overt and subclinical thyroid dysfunction adversely affect disease control in DM patients, particularly in LADA. DKD diagnosis primarily relies on elevated urinary albumin-to-creatinine ratio (UACR) and reduced estimated glomerular filtration rate (eGFR). The 2025 Diabetologia study reported higher retinopathy incidence in LADA versus T2DM, corroborating prior findings.^15,18 Clinically, elevated UACR shows positive association with subclinical hypothyroidism (OR 3.51, 95% CI: 1.10–10.0),^19,20 aligning with our results. Mechanistically, thyroid hormones and DKD interact bidirectionally: hyperglycemia-induced inflammation suppresses 5’-deiodinase activity, impairing peripheral T4-to-T3 conversion²¹ and reducing FT3, thereby disrupting the hypothalamic-pituitary-thyroid axis.²² Concurrently, glomerular structural damage in DKD promotes protein loss, further depressing FT3 and exacerbating hypothyroidism.^23,24 Thus, worsening DKD severity progressively lowers FT3, intensifying thyroid dysfunction, which in turn accelerates DKD progression—creating a vicious cycle.

Correlation analyses revealed positive associations between FT3 and FCP/P2hCP/FT4. Clinically, severe LADA often manifests low T3 syndrome which is a thyroid hormone metabolism disorder caused by systemic non-thyroidal illnesses, where pronounced glucotoxicity exacerbates islet dysfunction—consistent with the proposed mechanism of hyperglycemia-induced 5’-deiodinase suppression impairing T3 conversion.^21,22 We also observed positive correlations among TPOAb, TGAb, and TRAb, explaining the frequent coexistence of autoimmune disorders (eg, Hashimoto’s thyroiditis and Graves’ disease) through shared immunopathogenic mechanisms.¹⁵ Notably, the inverse FCP-IAA correlation aligns with 2024 Endocrine findings: elevated plasmablasts and Breg (B10) phenotypes in LADA positively correlate with islet cell antibodies and IAA but negatively with FCP, suggesting PB-mediated β-cell destruction²⁵—mechanistically supporting our observations.

Univariate binary logistic regression confirmed that low FCP, P2hCP, and FT3, alongside high TPOAb and TGAb, predict thyroid dysfunction in LADA. Prior studies validate thyroid antibodies as key predictors.²⁶ Thus, we recommend: (1) annual/biennial thyroid antibody and FT3 screening from LADA onset to minimize undiagnosed thyroid dysfunction;²⁷ and (2) triannual/semiannual islet function assessments to optimize insulin initiation timing and tailor thyroid therapy, enabling early intervention to mitigate progression risks.

Limitations: First, single-center design and limited sample size may introduce bias, necessitating multicenter cohorts with refined subgroup analyses. Second, GADA assay specificity (98%) permits potential misclassification of T2DM as LADA, potentially attenuating observed thyroid dysfunction associations. Finally, the study selected a hospitalized population, which may introduce some selection bias and lacks a healthy control group. Therefore, further improvements are needed in future research.

Conclusion

In conclusion, our study identifies low FCP/P2hCP/FT3 and high TPOAb/TGAb as predictors of thyroid dysfunction in LADA, warranting regular thyroid and islet function monitoring for timely intervention.

Ethical Statement

Ethics approval and consent to participate Written informed consent for all data was obtained from patients during their hospitalization, and the Ethics Committee of the Affiliated Hospital of Xuzhou Medical University approved the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest in this work.

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NEW YORK (AP) — Armen Kirakosian remembers the frustrations of his first job as a call center agent nearly 10 years ago: the aggravated customers, the constant searching through menus for information and the notes he had to physically write for each call he handled.

Thanks to artificial intelligence, the 29-year-old from Athens, Greece, is no longer writing notes or clicking on countless menus. He often has full customer profiles in front of him when a person calls in and may already know what problem the customer has before even saying “hello.” He can spend more time actually serving the customer.

“A.I. has taken (the) robot out of us,” Kirakosian said.

Roughly 3 million Americans work in call center jobs, and millions more work in call centers around the world, answering billions of inquiries a year about everything from broken iPhones to orders for shoes. Kirakosian works for TTEC, a company that provides third party customer service lines in 22 countries to companies in industries such as autos and banking that need extra capacity or have outsourced their call center operations.

Answering these calls can be thankless work. Roughly half of all customer service agents leave the job after a year, according to McKinsey, with stress and monotonous work being among the reasons employees quit.

Much of what these agents deal with is referred to in the industry as “break/fix,” which means something is broken — or wrong or confusing — and the customer expects the person on the phone to fix the problem. Now, it’s a question of who will be tasked with the fix: a human, a computer, or a human augmented by a computer.

Already, AI agents have taken over more routine call center tasks. Some jobs have been lost and there have been dire forecasts about the future job market for these individuals, ranging from modest single-percentage point losses, to as many as half of all call center jobs going away in the next decade. The drop likely won’t match the more dire predictions, however, because it’s become evident that the industry will still need humans, perhaps with even higher levels of learning and training, as some customer service issues become increasingly harder to solve.

Some finance companies have already experimented with going all in on AI for their customer service issues only to run into AI’s limitations. Klarna, the Swedish buy now, pay later company, replaced its 700-person customer service department with chatbots and AI in 2023. The results were mixed. While the company did save money, overall customer satisfaction rates dropped as well. Earlier this year, Klarna hired a handful of customer service employees back to the firm, acknowledging there were certain issues that AI couldn’t handle as well as a real person, like identity theft.

“Our vision of an AI-first contact center, where AI agents handle the majority of conversations and fewer, better trained and better paid human agents support only the most complex tasks, is quickly becoming a reality,” said Gadi Shamia of Replicant, an AI-software company that trains chatbots to sound more human, in an interview with consultants at McKinsey.

The call center customer’s experience, while improved, is still far from perfect.

The initial customer service call has long been handled through interactive voice response systems, known in the industry as IVR. Customers interact with IVR when they’re told “press one for sales, press two for support, press five for billing.” These crude systems got an update in the 2010s, when customers could prompt the system by saying “sales” or “support” or simple phrases like “I’d like to pay a bill” instead of navigating through a labyrinthian set of menu options.

But customers have little patience for these menus, leading them to “zero out,” which is call center slang for when a customer hits the zero button on their their keypad in hopes of reaching a human. It’s also not uncommon that after a customer “zeros out” they will be put on hold and transferred because they did not end up in the right place for their request.

Aware of Americans’ collective impatience with IVR, Democratic Sen. Ruben Gallego of Arizona and Republican Jim Justice of West Virginia have introduced the “Keep Call Centers in America Act,” which would require clear ways to reach a human agent, and provide incentives to companies that keep call center jobs in the U.S.

Companies are trying to roll out telephone systems that broadly understand customer service requests and predict where to send a customer without navigating a menu. OpenAI, the maker of ChatGPT, is coming out with its “ChatGPT Agent” service for users that’s able to understand phrases like “I need to find a hotel for a wedding next year, please give me options for clothing and gifts.”

Bank of America says it has had increasing success in integrating such features into “Erica,” its chatbot that debuted in 2018. When Erica cannot handle a request, the agent transfers the customer directly to the right department. Erica is now also predictive and analytical, and knows for instance that a customer may repeatedly have a low balance and may need better help budgeting or may have multiple subscriptions to the same service.

Bank of America said this month that Erica has been used 3 billion times since its creation and is increasingly taking on a higher case load of customer service requests. The chatbot’s moniker comes from the last five letters of the company’s name.

James Bednar, vice president of product and innovation at TTEC, has spent much of his career trying to make customer service calls less painful for the caller as well as the company. He said these tools could eventually kill off IVR for good, ending the need for anyone to “zero out.”

“We’re getting to the point where AI will get you to the right person for your problem without you having to route through those menus,” Bednar said.