Diabetic retinopathy (DR) is a major microvascular complication of diabetes and is the leading cause of blindness and visual impairment among working-age populations worldwide. The loss of vision caused by diabetes significantly reduces the quality of life and has a major impact on the overall burden of visual impairment. This study assessed the global burden of blindness and visual impairment caused by diabetes among the working population from 1990 to 2021, and predicted the future trends in 2050. Based on data from the Global Burden of Disease Study 2021, we analyzed trends from 1990 to 2021 in the burden of diabetes-related blindness and visual impairment. Key metrics included case numbers and rates of prevalence and years lived with disability (YLDs). Decomposition analysis identified drivers of burden changes, and health inequality analysis assessed disparities by socioeconomic status. We used ARIMA and exponential smoothing models to forecast prevalence and YLDs from 2022 to 2050. From 1990 to 2021, the global burden of blindness and visual impairment caused by diabetes among the working population significantly increased.From 1990 to 2021, the global burden of blindness and visual impairment caused by diabetes among the working population significantly increased. Comparative analysis shows that the number of cases of type 2 diabetes and the number of YLDs are much higher than those of type 1 diabetes. Moreover, the burden on women has always been higher than that on men. Among the working population, blindness and visual impairments caused by diabetes pose a serious and increasingly severe public health threat worldwide, with the impact on women being particularly significant.Among the working population, blindness and visual impairments caused by diabetes pose a serious and increasingly severe public health threat worldwide, with the impact on women being particularly significant. Therefore, urgent action is needed to raise awareness of diabetic retinopathy among both clinicians and the general public, improve the level of early detection and treatment, reduce preventable vision loss, and alleviate the impact on family life and social economic burden caused by this decline in quality of life. Therefore, urgent action is needed to raise awareness of diabetic retinopathy among both clinicians and the general public, improve the level of early detection and treatment, reduce preventable vision loss, and alleviate the impact on family life and social economic burden resulting from this decline in quality of life.
Despite the efforts of experts and healthcare providers, poor adherence to treatment in people with type 2 diabetes is still one of the major challenges associated with this disease. However, the rate and associated factors among these patients in Iran are unknown. Therefore, the present study aimed to estimate the level of adherence to treatment and identify its determinant factors among patients with type 2 diabetes in Iran. In the present study, we conducted a mixed method systematic review of studies related to the adherence to treatment and its causes among patients with type 2 diabetes in Iran, published between 2011 and 2024. Studies were collected from Iranian and international databases and were evaluated using the Oxford University's critical appraisal tools. A quantitative meta-analysis of the data was performed to determine the prevalence, and attributable risk of each of the identified factors. Of the 57 initial screened studies, 41 eligible studies were identified that provided evidence on the rates and barriers to treatment adherence in different regions of Iran. The level of adherence to treatment was reported in 28 studies, with 14.29% of studies reporting favorable treatment adherence and 85.71% of them reporting poor treatment adherence. Barriers to treatment adherence also included patient-related factors, including patient demographic characteristics, disease awareness and perception, patient self-efficacy, patient concerns about medication side effects, disease-related beliefs, patient social support, and patient psychological characteristics and factors related to the treatment team, which included the performance of the treatment team and the patient's relationship with the treatment team. The present study showed that the adherence to treatment status in patients with type 2 diabetes in Iran is a lower than recommended standards. Poor adherence to treatment can lead to irreversible side effects in these patients and also impose an additional burden on the patient and healthcare systems. Therefore, further research is needed to clarify the extent of the prevalence rate as well as to determine the factors that influence adherence and can be effective in targeted interventions to promote adherence, optimize diabetes control, and limit diabetes progression.
Glutamate and glutamine, two closely related amino acids, play vital roles in cellular metabolism, neurotransmission, immune regulation, and, in maintaining pancreatic β‑cell structure and function. The former serves as the primary excitatory neurotransmitter and is essential for energy metabolism, protein synthesis, and insulin secretion. Its counterpart, glutamine, the amide derivative of glutamate, supports mitochondrial activity, nucleotide biosynthesis, and serves as an alternative metabolic fuel during physiological stress. Dysregulation of glutamate and glutamine pathways has been increasingly associated with the pathogenesis of both type 1 and 2 diabetes. In type 1 diabetes, disruptions in the glutamate‑glutamine cycle contribute to pancreatic β‑cell dysfunction and autoimmune‑mediated destruction. In type 2 diabetes, altered glutamate metabolism promotes insulin resistance and pancreatic β‑cell apoptosis, largely through mechanisms involving oxidative stress and inflammation. The glutamate‑glutamine cycle within pancreatic β‑cells is essential for insulin production and cellular homeostasis. Impairment of this cycle may play a key role in the development of diabetic complications, including neuropathy, nephropathy, and retinopathy. Emerging evidence suggests that targeting glutamate and glutamine metabolism offers promising therapeutic strategies for diabetes and its associated complications. Potential interventions include modulation of specific receptors, regulation of key metabolic enzymes, and amino acid supplementation, each aimed at restoring the metabolic balance of these amino acids, enhancing insulin sensitivity, and reducing tissue damage. This review underscores the critical importance of understanding glutamate and glutamine dynamics in the pancreas, with the goal of identifying innovative approaches for the treatment and prevention of diabetes and its complications.
The co-occurring epidemics of diabetes and obesity have increased the prevalence of Cardio-Kidney-Metabolic (CKM) syndrome. Comparative studies on long-term trends of its three core components [ischemic heart disease (IHD), diabetic kidney disease (DKD), non-alcoholic fatty liver disease (NAFLD)] across major countries are still limited. We analyzed age-standardized disability-adjusted life year (DALY) rates of IHD, DKD, and NAFLD attributable to high fasting plasma glucose (HFPG) from 1990 to 2021 among seven representative middle-and high-income countries using Global Burden of Disease 2021 data. We assessed temporal trends, conducted hierarchical clustering, and projected burdens to 2050. We found substantial cross-country heterogeneity. From 1990 to 2021, IHD burden decreased significantly in the United States and Japan, while trends in China and India showed high uncertainty (coefficients of variation >100%) and should be interpreted with caution. DKD burden increased in Saudi Arabia and the United States but decreased in China. NAFLD burden increased in Saudi Arabia, the United States, India, and South Africa, while declining in China and Japan. Cluster analysis identified three patterns: "High IHD Burden" (India), "High Metabolic Burden" (Saudi Arabia), and "Low-Moderate Burden" (other countries). HFPG was associated with the largest share of DKD burden (Population Attributable Fraction [PAF] >80%) and a substantially smaller share of NAFLD burden (PAF <11%).Projections to 2050 show a sharp rise in DKD in the United States and India, together with increasing NAFLD burden, indicating a shift toward metabolic organ damage. The burden of CKM syndrome is substantial and dynamic, with marked cross-country differences. These findings support the need for integrated, multi-organ risk management strategies for metabolic disorders.
Cardiometabolic conditions-including cardiovascular disease, type 2 diabetes, and obesity-are highly prevalent among individuals with psychotic disorders. These conditions contribute substantially to reduced life expectancy, diminished quality of life, and increased societal and economic burdens. Thus, effective, individualized interventions are urgently needed. Outpatient psychiatric clinics offer an ideal setting for such efforts owing to regular patient contact and access to multidisciplinary care. We have developed a comprehensive, clinically integrated trial aimed at improving cardiometabolic health, promoting healthier lifestyles, and enhancing quality of life for individuals with psychotic disorders receiving care in the Greater Gothenburg region. LAGOM is a multicenter, naturalistic, quasi-experimental case‒control trial conducted across six geographically separate outpatient psychosis clinics within the Department of Psychotic Disorders at Sahlgrenska University Hospital, a multi-site university hospital in the Greater Gothenburg region. A total of 650 adults with psychotic disorders will be recruited from these clinics. Two clinics will implement the LAGOM intervention, whereas four will serve as control sites delivering usual care. The intervention is embedded within routine psychiatric care and grounded in behavioral science. It includes comprehensive cardiometabolic risk assessments, two visual motivational tools (QRISK3 and a body composition analyzer), personalized follow-up plans, risk-oriented referrals to primary care, and structured education for patients, relatives, and staff. The intervention is designed to be scalable, sustainable, and tailored to individual patient needs. If proven superior to usual care, this pragmatic, multicomponent intervention-delivered within routine psychiatric care-could improve cardiometabolic health and quality of life for individuals with psychotic disorders. Embedding the intervention within existing clinical structures enhances its scalability and feasibility and, if effective, could serve as a model for wider implementation. ClinicalTrials.gov (NCT06781801; date registered: 16 January 2025). Recruitment started on 27 February 2025 and will be completed on 31 December 2026. The current clinical investigation plan version is 3.1, dated 21 October 2025.
The war in Sudan, which began in April 2023, has displaced millions and severely disrupted the healthcare system. This study assessed the association between armed conflict, displacement, and glycemic control in people living with diabetes (PWD), as well as the prevalence of diabetes-related complications in this context. This is a cross-sectional study. Using systematic random sampling, 385 displaced adults living with diabetes, aged 19 years or older, were recruited. The study was conducted at the diabetes center in Port Sudan from October 2024 to May 2025. Data on sociodemographic characteristics, clinical history, and barriers to care were collected through structured questionnaires. Bivariate analyses and binary logistic regression were used to identify factors associated with uncontrolled diabetes. Participants had a mean age of 53 ± 12 years; 51.4% were female. All were displaced because of the armed conflict. The mean HbA1c was 9.38% (± 2.42); only 16.6% of participants achieved glycemic control (HbA1c < 7.0%). Poor adherence to diabetes management was reported by 15.8% of patients, with an average HbA1c of 12.09% in this group. A high prevalence of complications was observed, with 26.5% and 20.8% of patients having diabetic foot and diabetic retinopathy, respectively. In regression analysis, poor adherence was the sole factor significantly associated with uncontrolled diabetes (OR 41.96, 95% CI [11.04, 159.52], p < 0.001). Female gender and higher education were associated with higher mean HbA1c in bivariate analysis (9.63% vs. 9.11%, p = 0.015; p = 0.007, respectively) but were not independent predictors in the multivariate model. Stress exposure was nearly universal (99.2%) but not significantly associated with glycemic control in this sample. In this cross-sectional study of displaced PWD, the context of armed conflict in Sudan was associated with a high prevalence of poor glycemic control; diabetic foot syndrome was present in 26.5% and retinopathy in 20.8% of participants; as these were self-reported and patient overlap was not assessed, these figures represent individual prevalences rather than cumulative burden. Adherence to management was the key modifiable factor correlated with glycemic outcomes. These findings highlight an urgent need for conflict-sensitive diabetes management strategies. Humanitarian responses should consider ensuring reliable, affordable access to care and support programs as a potential means to address the cascade of diabetes-related complications in conflict settings. The online version contains supplementary material available at 10.1007/s40200-026-02009-z.
Understanding patterns of active and passive smoking among individuals with diabetes is essential for targeted prevention, improved glycemic control, and reduction of cardiometabolic complications. The Middle East and North Africa (MENA) region, which includes Iran, has the highest age-standardized diabetes prevalence worldwide, yet evidence on smoking patterns among Iranian adults with diabetes remains limited. We used data from the 2021 WHO STEPS survey, a nationally representative population-based study conducted across all 31 provinces of Iran. Adults aged ≥ 25 years were included. Diabetes was defined by self-reported physician diagnosis, glucose-lowering medication use, fasting plasma glucose (FPG) ≥ 126 mg/dL, or hemoglobin A1c (HbA1c) ≥ 6.5%. Among 18,119 eligible participants, 3,078 adults with complete data met diabetes criteria and were included in weighted analyses. We estimated the prevalence of current smoking and passive smoke exposure and compared cardiometabolic indicators across smoking categories. Survey-weighted logistic regression identified determinants of smoking behavior. Among 3,078 adults with diabetes, mean age was 58.4 years (95% CI: 57.8, 59.0) and 53.1% (95% CI: 50.3, 55.9) were female. Overall, 12.2% (95% CI: 10.6, 14.0) were current smokers and 26.0% (95% CI: 23.8, 28.3) reported passive exposure. Smoking patterns varied substantially by sex, age, body mass index (BMI), residence, and employment status. Compared with never smokers, current smokers had lower high-density lipoprotein cholesterol (HDL-C), higher triglycerides, and lower systolic blood pressure (SBP). Male sex strongly predicted current smoking (aOR: 4.69, 95% CI: 3.65, 6.01), whereas age ≥ 60 years was associated with lower odds of both active smoking (aOR: 0.61, 95% CI: 0.48, 0.77) and passive exposure (aOR: 0.67, 95% CI: 0.53, 0.86). Active and passive smoking are common among Iranian adults with diabetes and show substantial gender differences. Their associations with unfavorable lipid profiles underscore the need for integrating gender-responsive tobacco control approaches into diabetes care and prevention programs. The online version contains supplementary material available at 10.1007/s40200-026-01990-9.
Maternal nutrition can influence offspring metabolism through metabolic programming, potentially leading to long-term disorders such as obesity and type 2 diabetes. However, the cellular- and tissue-level mechanisms involved in the metabolic programming, particularly regarding the endocrine pancreas, remain unclear. This study investigated the effects of maternal high-fat (HF) diet exposure on the biometric/metabolic profiles, β-cell morphometry, insulin secretion, and islet levels of the SNARE protein VAMP-2 and cytoskeletal F-actin, both critical to insulin granule exocytosis, in mouse offspring. Female C57BL6 mice were fed either a control (CON, 4.5% lipids) or a HF diet (35% lipids) during pregnancy and lactation. The offspring from both groups were evaluated at 3, 12, and 90 days of age. The offspring from HF diet-fed mothers exhibited significantly lower body weight from day 3 and increased visceral adiposity, hyperinsulinemia, glucose intolerance, and insulin resistance, associated with no significant changes in postprandial glycemia by adulthood. These alterations were accompanied by significant morphometric changes in the endocrine pancreas, including a reduction in total islet area, β-cell area, and β-cell number per islet, detectable from day 3 until adulthood. Additionally, adult islets from HF offspring showed elevated cellular F-actin labeling and reduced VAMP-2 protein levels, correlating with impaired glucose-stimulated insulin secretion in vitro. In conclusion, maternal HF diet exposure leads to metabolic disturbances and impaired β-cell function in offspring. These include reduced β-cell mass and secretory capacity, potentially due to an impaired cytoskeletal organization and insulin granule exocytosis, highlighting the long-term impact of maternal nutrition on offspring health.
Tobacco exposure is a well-established risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD); however, its global burden remains poorly quantified. This study estimated the global, regional, and national burden of MASLD attributable to tobacco from 1990 to 2023 and projected trends to 2038. Using Global Burden of Disease Study 2023 data, deaths, disability-adjusted life-years (DALYs), age-standardized mortality rates (ASMRs), and age-standardized DALY rates (ASDRs) were estimated across 204 countries and territories. We assessed temporal trends using average annual percentage change, performed decomposition analysis, evaluated cross-national health inequalities with slope and concentration indices, and projected rates to 2038 using Bayesian age-period-cohort models. Globally, deaths increased 2.3-fold (from 1,479 to 3,473) and DALYs 2.2-fold (from 41,636 to 90,682) from 1990 to 2023, whereas the ASMR (0.04 per 100,000) and ASDR (1.00 per 100,000) remained stable. The burden was 6- to 7-fold higher in males than in females, with substantial geographic heterogeneity: declines were observed in the high-income Asia Pacific region, whereas sharp increases occurred in Australasia, Southern Latin America, and North Africa and the Middle East. Population growth and ageing drove the absolute burden increase. Health inequalities widened. Projections indicate declining ASMRs and ASDRs through 2038, with more rapid declines in females. Although age-standardized rates remained stable, the absolute burden more than doubled over three decades, with significant disparities by sex, region, and socioeconomic status. Targeted tobacco control and MASLD prevention strategies are urgently needed, particularly in high-burden regions and among males. Abbreviations: MASLD, metabolic dysfunction-associated steatotic liver disease; DALYs, disability-adjusted life-years; ASDR, age-standardized DALYs rate; ASMR, age-standardized mortality rate; SDI, socio-demographic index. The online version contains supplementary material available at 10.1007/s40200-026-01997-2.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated substantial weight loss and metabolic benefits in overweight and obese populations. However, their cardio-metabolic efficacy and safety profile in Chinese adults remain incompletely characterized. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing GLP-1RAs or dual GLP-1/GIP receptor agonists with placebo in overweight or obese Chinese adults. Searches were performed in PubMed, Cochrane CENTRAL, and Scopus from inception to October 12, 2025. Outcomes included changes in body weight, waist circumference, HbA1c, fasting glucose, cholesterol, systolic and diastolic blood pressure, and adverse events. Effect sizes were pooled using random-effects models and reported as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). Five RCTs comprising 2,204 participants were included, of whom 1,522 received GLP-1RA therapy and 682 received placebo. GLP-1RAs significantly reduced body weight (MD: -10.06 kg; 95% CI: -15.56 to - 4.56), waist circumference (MD: -7.06 cm; 95% CI: -9.85 to - 4.26), HbA1c (MD: -0.41%; 95% CI: -0.56 to - 0.27), fasting glucose (MD: -0.48 mmol/L; 95% CI: -0.69 to - 0.27), cholesterol (MD: -7.95 mg/dL; 95% CI: -9.57 to - 6.33), systolic blood pressure (MD: -4.26 mmHg; 95% CI: -6.28 to - 2.23), and diastolic blood pressure (MD: -2.44 mmHg; 95% CI: -3.70 to - 1.18). GLP-1RAs were associated with increased risks of gastrointestinal adverse events, including nausea, diarrhea, and vomiting, but not serious adverse events. Among overweight or obese Chinese adults, GLP-1RAs produce clinically significant improvements in body weight and multiple cardiometabolic risk factors while maintaining an acceptable safety profile. These findings support the role of GLP-1RAs as effective long-term therapeutic options for metabolic risk reduction in this population. Not applicable. The online version contains supplementary material available at 10.1007/s40200-026-02000-8.
Non-communicable diseases (NCDs) account for around four-fifths of deaths in Iran, yet their burden varies across provinces alongside differences in socio-demographic development. We assessed national and subnational trends in NCD burden in Iran and quantified associations between Socio-demographic Index (SDI) and burden metrics. Age-standardized rates (ASRs) of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) for NCDs and responsible risk factors were retrieved from Global Burden of Diseases 2021 study. Provinces were ranked into SDI quintiles. Generalized estimating equations (GEE) with clustering by province were used to estimate the link between SDI and burden indicators. From 1990 to 2021, total NCD deaths in Iran increased by 83.4%, while ASRs of mortality, DALYs, and YLLs declined across all SDI strata and gaps narrowed. Per 0.1-unit higher SDI, ASRs of DALYs and mortality were lower, but ASRs of incidence and prevalence were significantly higher. ASR of mortality and DALY of cardiovascular diseases, chronic respiratory diseases, and neoplasms improved with SDI, whereas those for diabetes and kidney diseases worsened. In 2021, the top five risk factors for death and DALYs were high systolic blood pressure, high body mass index, elevated fasting plasma glucose, dietary risks, and air pollution, with only minor differences across SDI strata. Despite reduced interprovincial SDI disparities, age-standardized NCD mortality and DALY rates remained lower at higher SDI levels; however, this pattern varied by cause. Stronger prevention and equitable NCD management in Iran remain critical. The online version contains supplementary material available at 10.1007/s40200-026-01999-0.
To compare the predictive performance of five insulin resistance (IR) indices for the risk of metabolic syndrome (MS) incidence. This is a cohort study including 1129 Algerian adults free of MS at baseline, followed for up to 49 months (median follow-up: 45 months; IQR, 22-49 months). Incident MS was defined according to the NCEP-ATPIII criteria. Five IR indices: triglyceride-glucose index (TYG), TYG-body mass index (TYG-BMI), TYG-waist circumference (TYG-WC), and estimated glucose disposal rate (eGDR), using BMI or WC, were evaluated using Cox models, adjusted for cardio-metabolic confounding factors. Their performance was evaluated using time-dependent ROC curves, Harrell's C-index, Kaplan-Meier curves, and incremental predictive improvement (net reclassification improvement (NRI) and integrated discrimination improvement (IDI)). Sensitivity analyses were performed using stratification based on gender, age, and baseline metabolic phenotypes. During follow-up, 291 participants developed MS (25.8%). TYG-WC demonstrated the highest predictive performance among the evaluated indices within the NCEP-ATPIII framework: aHR = 1.44 per standard deviation (95% CI [1.24-1.66]). Values above 775.9 were associated with a 2.65-fold increased risk at the 49-month horizon, with a C-index of 0.83, mAUC of model curves of 0.828, and quasi-perfect calibration (slope = 0.984). It also provided the best incremental improvement (NRI = 0.076, IDI = 0.041). Indices incorporating waist circumference consistently demonstrated modestly better predictive performance than their BMI-based counterparts and showed significant improvement in risk reclassification (NRI), whereas BMI-based indices did not. The associations remained robust across gender, age, and obesity status. Within the NCEP-ATPIII framework, TYG-WC demonstrated the highest predictive performance among the evaluated indices and may represent a simple and clinically useful tool for metabolic risk stratification and early identification of individuals at increased risk of MS. The online version contains supplementary material available at 10.1007/s40200-026-02021-3.
Cardiometabolic multimorbidity (CMM) represents an increasing public health concern among aging populations. We aimed to construct and evaluate a multidimensional index integrating inflammation, metabolism, and physiological function-the CTI-FI (C-reactive protein-triglyceride-glucose and frailty index), and examine its association with incident CMM among middle-aged and older Chinese adults. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), a nationally representative prospective cohort. Baseline CTI-FI and cumulative CTI-FI exposure (cuCTI-FI) were calculated, and CTI-FI change patterns were identified using K-means clustering based on repeated measurements. Cox proportional hazards models and restricted cubic spline analyses were performed to evaluate the associations between CTI-FI measures and incident CMM. The incremental value of cuCTI-FI beyond the China-PAR model was assessed using discrimination, calibration-related metrics, and decision curve analysis. Among 4,438 participants, higher baseline CTI-FI and cuCTI-FI levels were consistently associated with increased risk of incident CMM in a dose-response manner (both P_trend < 0.001). In fully adjusted models, participants in the highest tertiles of baseline CTI-FI and cuCTI-FI had higher risks of incident CMM (HR: 3.47, 95% CI: 2.62-4.59; and HR: 5.27, 95% CI: 3.92-7.09, respectively). CTI-FI change pattern analysis suggested that participants with persistently higher or increasing CTI-FI levels had greater CMM risk compared with those with stable-low levels (HR: 4.89, 95% CI: 3.78-6.32). Incorporating cuCTI-FI into the China-PAR model improved model discrimination, with AUC increasing from 0.704 to 0.759. The associations remained generally consistent across most subgroup analyses. Higher baseline and cumulative CTI-FI levels were associated with increased risk of incident CMM among middle-aged and older Chinese adults. The addition of cuCTI-FI to conventional risk factors provided additional information for CMM risk assessment. Further validation in independent populations is needed to determine its potential application in broader risk assessment settings.Clinical trial number.Not applicable. The online version contains supplementary material available at 10.1007/s40200-026-02026-y.
Effective diabetes management requires a patient-centered approach. Research has shown mixed results regarding the impact of patient satisfaction on outcomes. This study examines the associations between different aspects of patient satisfaction, glycemic control, and diabetes complications. This cross-sectional study used data from the National Program for Prevention and Control of Diabetes in Iran from 2018 to 2021. Satisfaction was assessed across: (1) treatment and follow-up interventions, (2) physical health and management of complications, (3) personal and social relationships, and (4) participation and education on health improvement. Statistical analyses were performed using SPSS version 26. Satisfaction with treatment showed associations with increased prevalence of obesity (AOR: 1.146), lipid disorders (AOR: 1.100), ischemic heart disease (AOR: 1.129), and microvascular complications. Conversely, higher satisfaction with physical health was associated with lower rates of complications. Satisfaction with social relationships was associated with lower odds of several complications but higher diabetic foot risk. Participation and education satisfaction were associated with improved glycemic control but had mixed associations with complications. While patient satisfaction is generally associated with better glycemic control, it does not always lead to better long-term health outcomes. Future interventions should consider the alignment of treatment satisfaction and clinical effectiveness in diabetes control. Not Applicable. The online version contains supplementary material available at 10.1007/s40200-026-01998-1.
Comprehensive analyses of non-communicable diseases (NCDs) in children and adolescents that disentangle age, period, and cohort effects, assess health system efficiency, and project future trends remain limited. This study aims to address these gaps using data from the Global Burden of Disease Study 2021. Utilizing data from GBD 2021, we analyzed age-standardized rates (ASRs) of prevalence, incidence, mortality, and disability-adjusted life years (DALYs) for NCDs. Analyses included joinpoint regression to assess trends, age-period-cohort (APC) modeling to distinguish age, period, and birth cohort effects, frontier analysis to evaluate health system efficiency relative to socio-demographic index (SDI), and Bayesian APC modeling to project future burden to 2035. Inequalities were measured using the Slope Index of Inequality and Concentration Index. From 1990 to 2021, while global age-standardized mortality rate (ASMR) and DALY rate (ASDR) decreased substantially (AAPC:-2.20% and-1.30%, respectively), the age-standardized incidence rate (ASIR) increased (AAPC: +0.05%). The age-standardized prevalence rate (ASPR) remained largely stable (AAPC:-0.02%). Notably, the burden of mental disorders and diabetes and kidney diseases rose significantly. Adolescents (15-19 years) experienced increasing ASPR, contrasting with declines in younger children. Marked disparities were observed: lower SDI regions carried the highest burden, yet higher SDI regions showed rising ASIR. APC analysis confirmed strong age effects and modest cohort improvements. Frontier analysis identified significant efficiency gaps, even among high-SDI countries. Projections suggest a rising incidence in the 5-14 year age groups by 2035, alongside continued declines in mortality and DALYs. The shifting NCD burden toward non-fatal morbidity, especially mental and metabolic conditions in adolescents, requires developmentally tailored interventions. Addressing health system inefficiencies and socioeconomic disparities is crucial to reduce the future NCD burden and achieve Sustainable Development Goals.
Diabetes-related stigma adversely affects psychological wellbeing, self-care behaviors, and glycemic control in individuals with Type 1 diabetes (T1D). Despite the high prevalence of T1D in the Middle East and North Africa region, validated Arabic instruments to assess stigma remain limited. This study aimed to translate, culturally adapt, and evaluate the psychometric properties of the Arabic version of the Type 1 Diabetes Stigma Assessment Scale (DSAS-1-Ar) from the original English instrument. A cross-sectional study was conducted among 299 adults with T1D attending the Endocrinology and Diabetes Centre in Jazan, Saudi Arabia, recruited using consecutive sampling (response rate 99.3%). Translation followed established cross-cultural adaptation guidelines. Construct validity was examined using confirmatory factor analysis, with three competing structural models tested. In addition, Known-groups comparisons were executed between DSAS-1-Ar scores and self-reported clinical variables. All 19 items loaded significantly onto their hypothesized latent factors (Treated Differently (TD), Blame and Judgment (BJ), and Identity Concerns (IC); standardised loadings 0.642-0.947). Internal consistency was good (total α = 0.985, ω = 0.986). None of the three compared structural models met conventional fit thresholds (CFI range 0.812-0.888; RMSEA range 0.167-0.202). SRMR for the three-factor model was acceptable (0.065), while CFI (0.816) and RMSEA (0.202) indicated suboptimal global fit. Known-groups validation analyses yielded plausibly different scores across distinct populations; e.g. higher stigma scores among females, older participants and those with diabetes-related complications. The DSAS-1-Ar represents an important initial step toward assessing T1D-related stigma in Arabic-speaking populations. Items loaded strongly onto theoretically assigned subscales and internal consistency was good. However, global CFA fit indices were suboptimal, indicating that the factor structure requires further evaluation in this cultural context. Future studies can include assessing convergent validity, test-retest stability, and model fit in more diverse Arabic-speaking samples. Clinical trial number: not applicable. The online version contains supplementary material available at 10.1007/s40200-026-02022-2.
This study examines the relationship between hematologic-inflammatory indices and all-cause mortality in individuals with type 2 diabetes and hypertension. Using data from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study, 1,170 diabetic and 2,022 hypertensive participants were analyzed. The systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte-platelet ratio (NLPR) were calculated from complete blood counts and assessed using Cox regression models and Kaplan-Meier curves. Over 10 years, mortality rates were 11.3% in diabetic and 6.9% in hypertensive participants. In diabetic individuals, SII/100 was associated with mortality in both unadjusted and adjusted models (HR: 1.10, P = 0.006; adjusted HR: 1.15, P = 0.001), while NLR was also significantly associated (HR: 1.38, P < 0.001; adjusted HR: 1.48, P = 0.002). PLR/100 was not significant in the unadjusted model (HR: 1.37, P = 0.174) but became significant after adjustment (HR: 1.86, P = 0.013). In hypertensive patients, NLR was significant only in the unadjusted model (HR: 1.26, P = 0.019) and lost significance after adjustment (adjusted HR: 1.21, P = 0.080). SII/100 was not significantly associated with mortality in either unadjusted or adjusted models (HR: 1.02, P = 0.603; adjusted HR: 1.05, P = 0.297). Among individuals with both diabetes and hypertension, NLR, PLR/100, and SII/100 remained significantly associated with mortality in adjusted models. Kaplan-Meier analysis showed consistent associations for NLR, whereas PLR, SII, and NLPR curves were mostly non-significant. Hematologic-inflammatory indices, particularly NLR, were associated with all-cause mortality mainly among individuals with diabetes and those with both diabetes and hypertension; however, the associations varied by index and disease subgroup. Not applicable.
Obesity and type 2 diabetes (T2D) increase the risk of sarcopenia and mobility decline, yet the underlying muscle contractile alterations remain poorly understood. This study investigated how severe obesity and T2D affect muscle power, force-velocity relationships, and muscle quality. In this cross-sectional study, 45 middle-aged individuals were categorized as non-obesity (Non-O; BMI 18.5-30 kg/m2), obesity (O; BMI ≥ 35 kg/m2), and obesity with T2D (O + T2D; BMI ≥ 35 kg/m2). Isokinetic torque and power of knee extensors (KE) and dorsiflexors (DF) were measured (DF: 0-120°/s; KE: 0-270°/s). Muscle volume and fat infiltration (FF, %) were quantified using MRI. Outcomes included absolute, specific (relative to muscle volume), and normalized (relative to body weight) power. Functional capacity was assessed with five-times sit-to-stand (5xSTS) and 10-m walk (10MWT) tests. KE power was 51W lower in O + T2D than O (P = 0.008) with larger deficits at higher velocities (interaction, P = 0.027). O and O + T2D exhibited lower normalized KE power (-0.8 and -1.1 W/kg vs. Non-O; both P < 0.001). KE FF was higher in O (5%) than Non-O (3%, P = 0.003), and highest in O + T2D (7%, P = 0.023). DF torque declined faster with velocity in O and O + T2D (P ≤ 0.012). Specific power did not differ. KE normalized power was the strongest predictor of performance (5xSTS: R2 = 0.57,P = 0.003; 10MWT: R2 = 0.71,P < 0.001). Severe obesity impairs normalized muscle power, with T2D exacerbating KE power deficits and fatty infiltration. These muscle contractile impairments may contribute to functional decline already in middle-aged individuals.
Placenta-derived extracellular vesicles (EVs), particularly exosomes, serve as key mediators that influence metabolic programming in offspring under adverse early nutritional conditions, such as maternal obesity or gestational diabetes. They respond to maternal nutritional disturbances-such as obesity or gestational diabetes-by altering the composition of the miRNAs and proteins they carry. Evidence from in vivo and in vitro studies suggests that these modified EVs influence offspring metabolic programming through multiple putative pathways: regulating fetal pancreatic β-cell development and function, modulating lipogenesis via PPARγ signaling, affecting placental angiogenesis, and promoting inflammation and epigenetic alterations. By transmitting maternal environmental signals to the fetus, placental EVs are hypothesized to contribute to long-term metabolic phenotypes and disease susceptibility. This review critically examines the current evidence positioning placental EVs as key messengers in maternal-fetal communication, evaluates the strength of evidence supporting their role in shaping offspring metabolic health, identifies major knowledge gaps (e.g., limited direct evidence in human offspring, lack of standardized isolation methods), and suggests their potential as early intervention biomarkers or therapeutic targets for preventing metabolic disorders in offspring. We also highlight the need for prospective cohort studies and mechanistic validation in appropriate animal models to establish causality.
Quality of life (QoL) in type 2 diabetes mellitus (T2DM) is frequently impaired by disease-related complications and symptoms. Aromatherapy has been proposed as a non-pharmacological means of improving QoL. This review evaluates randomized controlled trials (RCTs) of aromatherapy and QoL in adults with T2DM experiencing diabetes-related complications. The review was prospectively registered in PROSPERO (CRD42024625423) and reported according to PRISMA. Web of Science, PubMed, Scopus, CINAHL, Google Scholar and the Cochrane Library were searched between December 2024 and January 2025. Eligibility criteria followed the PICOS framework, and full database-specific search strings are reported. Two reviewers independently performed study selection, data extraction and quality appraisal using the Joanna Briggs Institute (JBI) checklist for RCTs. Owing to heterogeneity, the data were synthesized narratively. Four RCTs comprising 293 randomized participants were included; three enrolled patients with diabetic peripheral neuropathic pain and one patients with insomnia. Aromatherapy was delivered by massage in three trials and by inhalation in one. JBI scores ranged from 9 to 12 of 13 (three high, one moderate quality). Randomization, baseline comparability and analysis were adequate throughout, whereas allocation concealment was unclear in three trials and blinding was incomplete in the massage trials. All four trials reported significant QoL improvement. Aromatherapy may improve QoL in complicated T2DM, but the evidence is limited by few small trials and by susceptibility to performance and detection bias. Adequately powered, registered, placebo-controlled RCTs with concealed allocation and blinded outcome assessment are needed. The online version contains supplementary material available at 10.1007/s40200-026-02033-z.