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Circadian rhythms are intrinsic 24-hour cycles that coordinate key metabolic processes, including glucose homeostasis, lipid metabolism, and energy expenditure. Disruption of these rhythms, due to sleep disturbances, shift work, or irregular feeding schedules, contributes to the development of obesity, insulin resistance, and dyslipidemia. Core clock genes, including circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT-like 1 (BMAL1), period gene (PER), and cryptochrome (CRY), play a central role in orchestrating these metabolic pathways. Chronotherapy, aligning lifestyle, behavioral, and pharmacologic interventions with circadian timing, represents a promising, yet underexplored, strategy for metabolic disease management. Evidence suggests that interventions such as time-restricted feeding, light therapy, pharmacologic modulators of clock gene expression, and wearable technology can improve glucose control, lipid profiles, and body weight. This review synthesizes current knowledge on the molecular regulation of metabolism by circadian clocks, elucidates mechanistic links between rhythm disruption and metabolic dysfunction, and explores translational strategies to restore circadian homeostasis. By targeting circadian rhythms, personalized and cost-effective interventions can be developed to mitigate the global burden of metabolic disorders. Future research should focus on large-scale clinical trials, precision chronotherapy, and integration of wearable devices to optimize the timing of interventions, ultimately enhancing treatment efficacy and long-term metabolic health.
Circadian rhythms are intrinsic 24-hour cycles that coordinate key metabolic processes, including glucose homeostasis, lipid metabolism, and energy expenditure. Disruption of these rhythms, due to sleep disturbances, shift work, or irregular feeding schedules, contributes to the development of obesity, insulin resistance, and dyslipidemia. Core clock genes, including circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT-like 1 (BMAL1), period gene (PER), and cryptochrome (CRY), play a central role in orchestrating these metabolic pathways. Chronotherapy, aligning lifestyle, behavioral, and pharmacologic interventions with circadian timing, represents a promising, yet underexplored, strategy for metabolic disease management. Evidence suggests that interventions such as time-restricted feeding, light therapy, pharmacologic modulators of clock gene expression, and wearable technology can improve glucose control, lipid profiles, and body weight. This review synthesizes current knowledge on the molecular regulation of metabolism by circadian clocks, elucidates mechanistic links between rhythm disruption and metabolic dysfunction, and explores translational strategies to restore circadian homeostasis. By targeting circadian rhythms, personalized and cost-effective interventions can be developed to mitigate the global burden of metabolic disorders. Future research should focus on large-scale clinical trials, precision chronotherapy, and integration of wearable devices to optimize the timing of interventions, ultimately enhancing treatment efficacy and long-term metabolic health.
DOI: https://doi.org/10.37349/eemd.2026.101467
Osteoarthritis (OA) is the most prevalent form of arthritis and a leading cause of disability worldwide. Epidemiological studies indicate that its global prevalence is rising, particularly among women, who often experience more severe disease than men. This sex disparity is most pronounced around menopause and is influenced by female-specific biological and hormonal factors, joint morphology, reproductive history, and sex-specific comorbidities that contribute to disease onset and progression. A mechanistic understanding of these factors is essential to identify individuals at risk, implement preventive strategies, enable early diagnosis, and mitigate complications, ultimately preserving function and quality of life. This review focuses on the determinants underlying the higher incidence and severity of OA in women, highlighting the interplay between hormonal changes, anatomy, and systemic factors.
Osteoarthritis (OA) is the most prevalent form of arthritis and a leading cause of disability worldwide. Epidemiological studies indicate that its global prevalence is rising, particularly among women, who often experience more severe disease than men. This sex disparity is most pronounced around menopause and is influenced by female-specific biological and hormonal factors, joint morphology, reproductive history, and sex-specific comorbidities that contribute to disease onset and progression. A mechanistic understanding of these factors is essential to identify individuals at risk, implement preventive strategies, enable early diagnosis, and mitigate complications, ultimately preserving function and quality of life. This review focuses on the determinants underlying the higher incidence and severity of OA in women, highlighting the interplay between hormonal changes, anatomy, and systemic factors.
DOI: https://doi.org/10.37349/eemd.2026.101466
Epiploic appendagitis is a rare, self-limiting inflammatory condition of the colonic epiploic appendages. It commonly presents with acute focal lower quadrant abdominal pain and may mimic appendicitis, colitis, or diverticulitis. Rapid weight loss has been proposed as a potential predisposing factor, although clinical evidence remains limited. This report describes a case of epiploic appendagitis occurring in temporal association with substantial and relatively rapid weight reduction during treatment with tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. A 45-year-old individual with a history of obesity, prediabetes, hypertension, hypothyroidism, and inflammatory bowel syndrome presented to primary care with right lower quadrant abdominal pain. Initial evaluation attributed symptoms to constipation; however, pain progressed despite management. Computed tomography (CT) of the abdomen and pelvis with contrast was obtained due to concern for appendicitis and demonstrated imaging findings consistent with epiploic appendagitis localized to the cecum. The patient had experienced clinically significant and relatively rapid weight loss during tirzepatide dose escalation prior to presentation. Management was conservative with nonsteroidal anti-inflammatory drugs and supportive care, without surgical intervention. Symptoms resolved completely within two weeks, and tirzepatide therapy was continued without recurrence. Although epiploic appendagitis has not been identified as a safety signal in randomized trials, systematic reviews, or pharmacovigilance analyses of GLP-1/GIP receptor agonists, this case highlights epiploic appendagitis as an important diagnostic consideration in patients presenting with focal abdominal pain during periods of substantial weight loss. Awareness of this uncommon condition may help prevent misdiagnosis and unnecessary interventions as pharmacologic weight loss therapies become more widely used.
Epiploic appendagitis is a rare, self-limiting inflammatory condition of the colonic epiploic appendages. It commonly presents with acute focal lower quadrant abdominal pain and may mimic appendicitis, colitis, or diverticulitis. Rapid weight loss has been proposed as a potential predisposing factor, although clinical evidence remains limited. This report describes a case of epiploic appendagitis occurring in temporal association with substantial and relatively rapid weight reduction during treatment with tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. A 45-year-old individual with a history of obesity, prediabetes, hypertension, hypothyroidism, and inflammatory bowel syndrome presented to primary care with right lower quadrant abdominal pain. Initial evaluation attributed symptoms to constipation; however, pain progressed despite management. Computed tomography (CT) of the abdomen and pelvis with contrast was obtained due to concern for appendicitis and demonstrated imaging findings consistent with epiploic appendagitis localized to the cecum. The patient had experienced clinically significant and relatively rapid weight loss during tirzepatide dose escalation prior to presentation. Management was conservative with nonsteroidal anti-inflammatory drugs and supportive care, without surgical intervention. Symptoms resolved completely within two weeks, and tirzepatide therapy was continued without recurrence. Although epiploic appendagitis has not been identified as a safety signal in randomized trials, systematic reviews, or pharmacovigilance analyses of GLP-1/GIP receptor agonists, this case highlights epiploic appendagitis as an important diagnostic consideration in patients presenting with focal abdominal pain during periods of substantial weight loss. Awareness of this uncommon condition may help prevent misdiagnosis and unnecessary interventions as pharmacologic weight loss therapies become more widely used.
DOI: https://doi.org/10.37349/eemd.2026.101465
The hypothesis that early-life antibiotic exposure predisposes to obesity has, over the past decade, gained substantial traction across both biomedical literature and public discourse. Its appeal lies in a seemingly coherent mechanistic framework: disruption of the developing intestinal microbiota is presumed to induce long-lasting alterations in metabolic homeostasis, thereby promoting increased adiposity. However, reported effect sizes are consistently modest, with odds ratios typically ranging from 1.1 to 1.3, values that approach the limits of residual confounding and statistical imprecision. Studies incorporating rigorous adjustment for familial environment, socioeconomic status, and dietary patterns observe a complete loss of the association, underscoring the dominant influence of these confounders. This review revisits the conceptual emergence and sustained prominence of the antibiotic-obesity paradigm, positioning it as a case study in the amplification of weak epidemiological signals through mechanistic plausibility. Notwithstanding its methodological limitations, the hypothesis has exerted a constructive influence by fostering more judicious antibiotic use and stimulating renewed investigation into host-microbiota interactions within the context of metabolic disease.
The hypothesis that early-life antibiotic exposure predisposes to obesity has, over the past decade, gained substantial traction across both biomedical literature and public discourse. Its appeal lies in a seemingly coherent mechanistic framework: disruption of the developing intestinal microbiota is presumed to induce long-lasting alterations in metabolic homeostasis, thereby promoting increased adiposity. However, reported effect sizes are consistently modest, with odds ratios typically ranging from 1.1 to 1.3, values that approach the limits of residual confounding and statistical imprecision. Studies incorporating rigorous adjustment for familial environment, socioeconomic status, and dietary patterns observe a complete loss of the association, underscoring the dominant influence of these confounders. This review revisits the conceptual emergence and sustained prominence of the antibiotic-obesity paradigm, positioning it as a case study in the amplification of weak epidemiological signals through mechanistic plausibility. Notwithstanding its methodological limitations, the hypothesis has exerted a constructive influence by fostering more judicious antibiotic use and stimulating renewed investigation into host-microbiota interactions within the context of metabolic disease.
DOI: https://doi.org/10.37349/eemd.2026.101464
Aim:
Necrotizing fasciitis (NF) is a severe and early challenging-to-identify complication of diabetic foot (DF). This study aimed to develop and validate a novel risk assessment model for NF with DF patients utilizing conventional clinical indicators.
Methods:
A retrospective analysis was conducted on 815 DF patients admitted to the First Affiliated Hospital of Chongqing Medical University between October 2018 and April 2022. Based on the presence of NF, patients were stratified into a DF group (n = 703) and a DF complicated with NF (DNF) group (n = 112). Clinically and statistically significant variables were converted into categorical form. A new risk assessment for DNF (NRADNF) nomogram was developed via multivariable stepwise logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) for discriminative ability, the Hosmer-Lemeshow goodness-of-fit test for calibration, decision curve analysis (DCA) for clinical utility, and bootstrap resampling for stability.
Results:
The final NRADNF model incorporated six indicators: age < 60 years, body temperature ≥ 38°C, foot skin necrosis, neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5, hypersensitive C-reactive protein > 20 mg/L, and hemoglobin ≤ 100 g/L. The model demonstrated favorable predictive performance with an AUC of 0.815 (95% CI: 0.773, 0.857), and it was significantly superior to the RADNF model by our team (P = 0.027). Calibration curves and the Hosmer-Lemeshow test indicated good accuracy. DCA confirmed the model’s clinical net benefit, and internal validation via bootstrap resampling supported its stability.
Conclusions:
Based on its favorable predictive performance and accessible indicators, the NRADNF model is suitable for preliminary screening of DNF in clinical practice.
Aim:
Necrotizing fasciitis (NF) is a severe and early challenging-to-identify complication of diabetic foot (DF). This study aimed to develop and validate a novel risk assessment model for NF with DF patients utilizing conventional clinical indicators.
Methods:
A retrospective analysis was conducted on 815 DF patients admitted to the First Affiliated Hospital of Chongqing Medical University between October 2018 and April 2022. Based on the presence of NF, patients were stratified into a DF group (n = 703) and a DF complicated with NF (DNF) group (n = 112). Clinically and statistically significant variables were converted into categorical form. A new risk assessment for DNF (NRADNF) nomogram was developed via multivariable stepwise logistic regression. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) for discriminative ability, the Hosmer-Lemeshow goodness-of-fit test for calibration, decision curve analysis (DCA) for clinical utility, and bootstrap resampling for stability.
Results:
The final NRADNF model incorporated six indicators: age < 60 years, body temperature ≥ 38°C, foot skin necrosis, neutrophil-to-lymphocyte ratio (NLR) ≥ 8.5, hypersensitive C-reactive protein > 20 mg/L, and hemoglobin ≤ 100 g/L. The model demonstrated favorable predictive performance with an AUC of 0.815 (95% CI: 0.773, 0.857), and it was significantly superior to the RADNF model by our team (P = 0.027). Calibration curves and the Hosmer-Lemeshow test indicated good accuracy. DCA confirmed the model’s clinical net benefit, and internal validation via bootstrap resampling supported its stability.
Conclusions:
Based on its favorable predictive performance and accessible indicators, the NRADNF model is suitable for preliminary screening of DNF in clinical practice.
DOI: https://doi.org/10.37349/eemd.2026.101463
Aim:
In Mexico, 18.3% of patients over 20 years of age suffer from type 2 diabetes mellitus (T2DM). Visceral fat has been identified as a risk factor for developing T2DM, considering that its effect depends mainly on the amount, it has been proposed that its location also participates in the genesis of T2DM. This paper aims to analyze whether the location of fatty depots participates in the appearance of T2DM in patients with metabolic syndrome.
Methods:
A total of 101 patients with metabolic syndrome according to the criteria of the International Diabetes Federation were included. In all of them, epicardial fat (EF) was measured by echocardiography, according to the Iacobelis criteria. Preperitoneal fat (PreF), mesenteric fat (MF), and perirenal fat (PF) were also measured by ultrasound. The statistical methods used were the odds ratio (OR) and Fisher’s exact test.
Results:
We found a significant association between EF thickness (OR 8.28, 95% CI 2.16–31.70, p = 0.001) and MF (OR 4.27, 95% CI 1.63–11.13, p = 0.0037) with T2DM, 60% of patients with increased PF presented T2DM. Interestingly, no patient with a PF less than 10 mm presented with T2DM. We found no association between PreF and T2DM (OR 0.88, 95% CI 0.32–2.40).
Conclusions:
The results suggest that the location of adipose tissue plays an important role in the development of T2DM. This may be due to the type of adipocytokines secreted by the various fat deposits and their metabolic effects.
Aim:
In Mexico, 18.3% of patients over 20 years of age suffer from type 2 diabetes mellitus (T2DM). Visceral fat has been identified as a risk factor for developing T2DM, considering that its effect depends mainly on the amount, it has been proposed that its location also participates in the genesis of T2DM. This paper aims to analyze whether the location of fatty depots participates in the appearance of T2DM in patients with metabolic syndrome.
Methods:
A total of 101 patients with metabolic syndrome according to the criteria of the International Diabetes Federation were included. In all of them, epicardial fat (EF) was measured by echocardiography, according to the Iacobelis criteria. Preperitoneal fat (PreF), mesenteric fat (MF), and perirenal fat (PF) were also measured by ultrasound. The statistical methods used were the odds ratio (OR) and Fisher’s exact test.
Results:
We found a significant association between EF thickness (OR 8.28, 95% CI 2.16–31.70, p = 0.001) and MF (OR 4.27, 95% CI 1.63–11.13, p = 0.0037) with T2DM, 60% of patients with increased PF presented T2DM. Interestingly, no patient with a PF less than 10 mm presented with T2DM. We found no association between PreF and T2DM (OR 0.88, 95% CI 0.32–2.40).
Conclusions:
The results suggest that the location of adipose tissue plays an important role in the development of T2DM. This may be due to the type of adipocytokines secreted by the various fat deposits and their metabolic effects.
DOI: https://doi.org/10.37349/eemd.2026.101462
This article belongs to the special issue Current Views on Pathogenesis, Diagnosis and Management of Type 2 Diabetes Mellitus and Its Complications and Related Conditions
Diabetes and metabolic dysfunction represent growing global health challenges, and current therapies mitigate hyperglycemia without sufficiently altering the underlying disease processes. Rapid advances in regenerative medicine, gene editing, and nano-enabled drug delivery are reshaping therapeutic possibilities, offering the potential to restore β-cell function, enhance insulin sensitivity, and personalize care at an unprecedented scale. This review synthesizes emerging therapeutic strategies with the greatest translational promise, including stem cell-derived islet replacement, immune-evasive encapsulation devices, CRISPR-based gene correction, and targeted or glucose-responsive nanocarriers engineered for noninvasive insulin delivery. Complementary advances in multi-omics profiling, proteogenomics, microbiome science, and artificial intelligence are enabling stratification of patients based on molecular signatures, optimizing therapeutic selection, and predicting clinical outcomes. Despite remarkable breakthroughs—such as the early-phase clinical success of stem cell-derived β-cell replacement and organ-targeted lipid nanoparticles (LNPs)—significant barriers remain, including immunogenicity, off-target editing, scalability, ethical concerns, and long-term safety. By integrating mechanistic insights with translational developments, this review outlines a forward-looking perspective on next-generation treatments poised to shift diabetes care from glycemic management toward disease modification and personalized metabolic restoration.
Diabetes and metabolic dysfunction represent growing global health challenges, and current therapies mitigate hyperglycemia without sufficiently altering the underlying disease processes. Rapid advances in regenerative medicine, gene editing, and nano-enabled drug delivery are reshaping therapeutic possibilities, offering the potential to restore β-cell function, enhance insulin sensitivity, and personalize care at an unprecedented scale. This review synthesizes emerging therapeutic strategies with the greatest translational promise, including stem cell-derived islet replacement, immune-evasive encapsulation devices, CRISPR-based gene correction, and targeted or glucose-responsive nanocarriers engineered for noninvasive insulin delivery. Complementary advances in multi-omics profiling, proteogenomics, microbiome science, and artificial intelligence are enabling stratification of patients based on molecular signatures, optimizing therapeutic selection, and predicting clinical outcomes. Despite remarkable breakthroughs—such as the early-phase clinical success of stem cell-derived β-cell replacement and organ-targeted lipid nanoparticles (LNPs)—significant barriers remain, including immunogenicity, off-target editing, scalability, ethical concerns, and long-term safety. By integrating mechanistic insights with translational developments, this review outlines a forward-looking perspective on next-generation treatments poised to shift diabetes care from glycemic management toward disease modification and personalized metabolic restoration.
DOI: https://doi.org/10.37349/eemd.2026.101461
This article belongs to the special issue Innovative Strategies for Diabetes and Metabolic Disorders: Current and Future Directions
The dominant paradigm for healthy ageing in women+ (all genders) focuses on estrogen and sees the menopause, per se, as a major health problem (with low estrogen and progesterone levels). In reality, the risks for diseases that increase at older ages originate during the menstruating years. Rarely discussed evidence supports the central role of progesterone and normally ovulatory menstrual cycles in preventing early cardiovascular disease, fragility fractures, dementia, and cancers. Menstrual cycles with normal and predictable lengths but disturbed ovulation, including short luteal phases with lower progesterone production as well as anovulation without progesterone, likely occur in over 25% of all such cycles. These Subclinical Ovulatory Disturbances are usually an adaptive and protective response to physiological, sociocultural, or emotional stressors. Ovulatory disturbances and risks for health issues during ageing are intrinsically related to the social determinants of health—wholesome food, plentiful physical activity, strong communities, and access to timely and appropriate medical care. This review discusses the empirical evidence that normal ovulation and progesterone production during the premenopausal years lead to the prevention of early heart attacks and fragility fractures. Few studies document the effects of prevalent Subclinical Ovulatory Disturbances on brain issues (sleep, night sweats, ischemic strokes, pain, and addictions) and cancer risks. Serious gaps in women+’s fundamental reproductive physiology must be addressed with unbiased (population-based), rigorously collected longitudinal physiological, hormonal, and sociocultural data. Progesterone therapy during perimenopause and menopause also indirectly leads to healthy ageing through effective treatment of night sweats, hot flushes, and disturbed sleep, which are associated with cardiovascular problems and osteoporosis. Not only is progesterone effective for vasomotor symptoms in menopause, but also effective in perimenopause, a time of high and chaotic estrogen levels. In sum, strong summarized evidence suggests that progesterone and ovulation need further exploration for their important roles in promoting healthy ageing for women+.
The dominant paradigm for healthy ageing in women+ (all genders) focuses on estrogen and sees the menopause, per se, as a major health problem (with low estrogen and progesterone levels). In reality, the risks for diseases that increase at older ages originate during the menstruating years. Rarely discussed evidence supports the central role of progesterone and normally ovulatory menstrual cycles in preventing early cardiovascular disease, fragility fractures, dementia, and cancers. Menstrual cycles with normal and predictable lengths but disturbed ovulation, including short luteal phases with lower progesterone production as well as anovulation without progesterone, likely occur in over 25% of all such cycles. These Subclinical Ovulatory Disturbances are usually an adaptive and protective response to physiological, sociocultural, or emotional stressors. Ovulatory disturbances and risks for health issues during ageing are intrinsically related to the social determinants of health—wholesome food, plentiful physical activity, strong communities, and access to timely and appropriate medical care. This review discusses the empirical evidence that normal ovulation and progesterone production during the premenopausal years lead to the prevention of early heart attacks and fragility fractures. Few studies document the effects of prevalent Subclinical Ovulatory Disturbances on brain issues (sleep, night sweats, ischemic strokes, pain, and addictions) and cancer risks. Serious gaps in women+’s fundamental reproductive physiology must be addressed with unbiased (population-based), rigorously collected longitudinal physiological, hormonal, and sociocultural data. Progesterone therapy during perimenopause and menopause also indirectly leads to healthy ageing through effective treatment of night sweats, hot flushes, and disturbed sleep, which are associated with cardiovascular problems and osteoporosis. Not only is progesterone effective for vasomotor symptoms in menopause, but also effective in perimenopause, a time of high and chaotic estrogen levels. In sum, strong summarized evidence suggests that progesterone and ovulation need further exploration for their important roles in promoting healthy ageing for women+.
DOI: https://doi.org/10.37349/eemd.2026.101460
This article belongs to the special issue The Fountain of Youth: Decoding the Hormonal Regulation of Aging
Aim:
Hypertriglyceridemia is linked to increased risk of diabetes diagnosis, incidence, and mortality. However, whether individuals with normal triglyceride levels (i.e., < 1.7 mmol/L) uniformly exhibit low diabetes risk remains underexplored. Specifically, it is unclear whether triglyceride levels within the normal range are associated with plasma glucose levels and the prevalence of type 2 diabetes (T2DM). This study aimed to address these gaps by examining the associations between triglyceride levels and fasting plasma glucose, as well as between triglyceride levels and T2DM, in individuals with triglycerides in the normal range.
Methods:
This cross-sectional study included 16,706 Chinese adults with triglyceride levels below 1.7 mmol/L. Among them, 1,067 had T2DM. Associations between triglyceride levels and fasting plasma glucose were assessed using linear regression, while associations with T2DM were evaluated using binary logistic regression. The optimal triglyceride cut-off for T2DM diagnosis was determined via receiver operating characteristic (ROC) curve analysis.
Results:
Triglyceride levels were positively associated with fasting plasma glucose after multivariate adjustment (β = 0.034, P < 0.001). A one-unit increase in the natural log of triglyceride levels was associated with a 61% higher adjusted odds of T2DM [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.19–2.17; P = 0.002]. The optimal triglyceride cut-off for T2DM diagnosis was 1.09 mmol/L. Participants with triglyceride levels ≥ 1.09 mmol/L had a 28% higher odds of T2DM (OR, 1.28; 95% CI, 1.07–1.53; P = 0.006) compared to those with levels below the cut-off.
Conclusions:
Among individuals with normal triglyceride levels, higher triglyceride concentrations were associated with higher odds of T2DM diagnosis, with an optimal diagnostic cut-off of 1.09 mmol/L. These findings suggest that adults with triglyceride levels more than 1.09 mmol/L may benefit from closer monitoring for T2DM development.
Aim:
Hypertriglyceridemia is linked to increased risk of diabetes diagnosis, incidence, and mortality. However, whether individuals with normal triglyceride levels (i.e., < 1.7 mmol/L) uniformly exhibit low diabetes risk remains underexplored. Specifically, it is unclear whether triglyceride levels within the normal range are associated with plasma glucose levels and the prevalence of type 2 diabetes (T2DM). This study aimed to address these gaps by examining the associations between triglyceride levels and fasting plasma glucose, as well as between triglyceride levels and T2DM, in individuals with triglycerides in the normal range.
Methods:
This cross-sectional study included 16,706 Chinese adults with triglyceride levels below 1.7 mmol/L. Among them, 1,067 had T2DM. Associations between triglyceride levels and fasting plasma glucose were assessed using linear regression, while associations with T2DM were evaluated using binary logistic regression. The optimal triglyceride cut-off for T2DM diagnosis was determined via receiver operating characteristic (ROC) curve analysis.
Results:
Triglyceride levels were positively associated with fasting plasma glucose after multivariate adjustment (β = 0.034, P < 0.001). A one-unit increase in the natural log of triglyceride levels was associated with a 61% higher adjusted odds of T2DM [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.19–2.17; P = 0.002]. The optimal triglyceride cut-off for T2DM diagnosis was 1.09 mmol/L. Participants with triglyceride levels ≥ 1.09 mmol/L had a 28% higher odds of T2DM (OR, 1.28; 95% CI, 1.07–1.53; P = 0.006) compared to those with levels below the cut-off.
Conclusions:
Among individuals with normal triglyceride levels, higher triglyceride concentrations were associated with higher odds of T2DM diagnosis, with an optimal diagnostic cut-off of 1.09 mmol/L. These findings suggest that adults with triglyceride levels more than 1.09 mmol/L may benefit from closer monitoring for T2DM development.
DOI: https://doi.org/10.37349/eemd.2026.101459
This article belongs to the special issue Current Views on Pathogenesis, Diagnosis and Management of Type 2 Diabetes Mellitus and Its Complications and Related Conditions
This commentary discusses a recent article (J Diabetes 2025;17(3):e70063), focusing on interpreting the study’s sex-stratified results in a broader clinical and mechanistic context. The authors of this systematic review and meta-analysis of 14 randomized trials demonstrate that women achieve greater weight loss induced by glucagon-like peptide-1 (GLP-1) receptor agonists compared to men (mean difference of 1.04 kg or 1.69%). Analyses specific to different drugs consistently show that women benefit more from dulaglutide, liraglutide, semaglutide, and retatrutide, with trials focused on obesity further emphasizing this gap. Sensitivity analyses confirm the reliability of these findings and indicate the absence of publication bias. We discuss the clinical implications of these results, suggesting that healthcare providers should consider sex differences when counseling, monitoring, and dosing patients. We also advocate for future trials that are adequately powered and stratified by sex to evaluate factors such as adherence, adverse events, and body composition. Mechanistic hypotheses, such as sex-related pharmacokinetics, estrogen-GLP-1 synergy, and varying inflammatory responses, should be investigated further to inform precision dosing. Lastly, we recommend that regulatory agencies revisit current labeling, which claims no sex differences, as more sex-stratified evidence becomes available. It is important to acknowledge the existing heterogeneity and remaining uncertainties in this area of research.
This commentary discusses a recent article (J Diabetes 2025;17(3):e70063), focusing on interpreting the study’s sex-stratified results in a broader clinical and mechanistic context. The authors of this systematic review and meta-analysis of 14 randomized trials demonstrate that women achieve greater weight loss induced by glucagon-like peptide-1 (GLP-1) receptor agonists compared to men (mean difference of 1.04 kg or 1.69%). Analyses specific to different drugs consistently show that women benefit more from dulaglutide, liraglutide, semaglutide, and retatrutide, with trials focused on obesity further emphasizing this gap. Sensitivity analyses confirm the reliability of these findings and indicate the absence of publication bias. We discuss the clinical implications of these results, suggesting that healthcare providers should consider sex differences when counseling, monitoring, and dosing patients. We also advocate for future trials that are adequately powered and stratified by sex to evaluate factors such as adherence, adverse events, and body composition. Mechanistic hypotheses, such as sex-related pharmacokinetics, estrogen-GLP-1 synergy, and varying inflammatory responses, should be investigated further to inform precision dosing. Lastly, we recommend that regulatory agencies revisit current labeling, which claims no sex differences, as more sex-stratified evidence becomes available. It is important to acknowledge the existing heterogeneity and remaining uncertainties in this area of research.
DOI: https://doi.org/10.37349/eemd.2026.101458
A pro-inflammatory state with elevated cytokines influenced by both environmental and genetic factors is a key characteristic of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Cytokines promote immune cell infiltration and degradation of the pancreatic islets, which play a direct role in the development of insulin resistance in T1DM. Cytokines also interfere with insulin signaling pathways and lead to metabolic dysfunction, contributing to the development of insulin resistance in patients with T2DM. In this narrative review, we have discussed the mechanisms of action and specific effects on insulin resistance of different cytokines, the influence of single-nucleotide polymorphisms and genetic factors that alter cytokine levels, and the development of insulin resistance. Further, we have discussed the complication of diabetes with a focus on diabetic foot ulcers, wounds, impaired wound healing, and reduced angiogenesis in association with the role of cytokines. Finally, the discussion addresses interventions for managing cytokines, such as Treg-based therapies, along with the various challenges presented by therapies targeting cytokine dysregulation and their effects on insulin resistance.
A pro-inflammatory state with elevated cytokines influenced by both environmental and genetic factors is a key characteristic of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Cytokines promote immune cell infiltration and degradation of the pancreatic islets, which play a direct role in the development of insulin resistance in T1DM. Cytokines also interfere with insulin signaling pathways and lead to metabolic dysfunction, contributing to the development of insulin resistance in patients with T2DM. In this narrative review, we have discussed the mechanisms of action and specific effects on insulin resistance of different cytokines, the influence of single-nucleotide polymorphisms and genetic factors that alter cytokine levels, and the development of insulin resistance. Further, we have discussed the complication of diabetes with a focus on diabetic foot ulcers, wounds, impaired wound healing, and reduced angiogenesis in association with the role of cytokines. Finally, the discussion addresses interventions for managing cytokines, such as Treg-based therapies, along with the various challenges presented by therapies targeting cytokine dysregulation and their effects on insulin resistance.
DOI: https://doi.org/10.37349/eemd.2026.101457
This article belongs to the special issue Role of Dysregulated Cytokine Signaling Pathways in Metabolic Disease
Osteoporosis is a disabling disease with a significant impact on the global population, particularly among older men and postmenopausal women. Several factors contribute to the increasing prevalence of osteoporosis, including greater life expectancy and the absence of symptoms in its early stages. The morbidity, mortality, and substantial economic burden associated with osteoporosis, especially due to hip fractures and related complications, constitute a major public health concern. Diagnosis should involve a comprehensive biochemical profile, along with additional tests to rule out secondary causes, which are often underdiagnosed and can influence the progression of the disease. Preventive measures and early diagnosis are essential to maintaining bone health and preventing fractures and disability. This review will focus on the definition, diagnostic approach, and key considerations prior to initiating treatment in patients with osteoporosis. Fracture risk prediction tools, including Fracture Risk Assessment Tool (FRAX), and treatment strategies are not addressed, as this review focuses on the appropriate diagnostic evaluation of osteoporosis and the systematic exclusion of secondary causes.
Osteoporosis is a disabling disease with a significant impact on the global population, particularly among older men and postmenopausal women. Several factors contribute to the increasing prevalence of osteoporosis, including greater life expectancy and the absence of symptoms in its early stages. The morbidity, mortality, and substantial economic burden associated with osteoporosis, especially due to hip fractures and related complications, constitute a major public health concern. Diagnosis should involve a comprehensive biochemical profile, along with additional tests to rule out secondary causes, which are often underdiagnosed and can influence the progression of the disease. Preventive measures and early diagnosis are essential to maintaining bone health and preventing fractures and disability. This review will focus on the definition, diagnostic approach, and key considerations prior to initiating treatment in patients with osteoporosis. Fracture risk prediction tools, including Fracture Risk Assessment Tool (FRAX), and treatment strategies are not addressed, as this review focuses on the appropriate diagnostic evaluation of osteoporosis and the systematic exclusion of secondary causes.
DOI: https://doi.org/10.37349/eemd.2026.101456
Background:
Metabolic syndrome and dyslipidaemia increase the risk of death by two or three times. In this context, the role of apolipoprotein A-I (Apo A-I), the main structural protein of high-density lipoprotein (HDL), stands out, since its anti-inflammatory potential reduces cardiovascular risk. Further, genetic modifications, such as the rs670 single-nucleotide polymorphism (SNP), in the promoter region of the APOA1 gene are associated with the development of cardiovascular events, dyslipidemia, and diabetes, as well as metabolic syndrome. Thus, this study aims to investigate the relation between the occurrence of dyslipidemia and the rs670 SNP genotypes.
Methods:
An integrative and systematic review was performed with the LitVar2 database according to the PRISMA protocol standards. Studies were researched up to August 2025. Then, a meta-analysis was performed using the fixed-effects model, since the study was considered homogeneous based on the I2 value (< 50%).
Results:
Of the 99 found articles in the database, 5 referred to metabolic disorders (n = 7,705—4 Chinese studies and 1 Iranian study) and were published between 2015 and 2018. Three (n = 2,784 patients or 36.13%) of the articles indicated an association between the polymorphic allele and a higher risk of developing dyslipidemia with a relative risk of 1.16 (IC 95% 1.09–1.23, p < 0.01, I2 = 0%). Relative risk (IC 95%) was presented, and p < 0.05 was defined as the significance criterion.
Discussion:
This study reinforces a possible association between the influence of SNP rs670 and dyslipidemia. This emphasizes the importance of conducting further research incorporating a larger and more diverse study group, as well as investigating the genetic and environmental influence on the phenotypic expression of the rs670 SNP.
Background:
Metabolic syndrome and dyslipidaemia increase the risk of death by two or three times. In this context, the role of apolipoprotein A-I (Apo A-I), the main structural protein of high-density lipoprotein (HDL), stands out, since its anti-inflammatory potential reduces cardiovascular risk. Further, genetic modifications, such as the rs670 single-nucleotide polymorphism (SNP), in the promoter region of the APOA1 gene are associated with the development of cardiovascular events, dyslipidemia, and diabetes, as well as metabolic syndrome. Thus, this study aims to investigate the relation between the occurrence of dyslipidemia and the rs670 SNP genotypes.
Methods:
An integrative and systematic review was performed with the LitVar2 database according to the PRISMA protocol standards. Studies were researched up to August 2025. Then, a meta-analysis was performed using the fixed-effects model, since the study was considered homogeneous based on the I2 value (< 50%).
Results:
Of the 99 found articles in the database, 5 referred to metabolic disorders (n = 7,705—4 Chinese studies and 1 Iranian study) and were published between 2015 and 2018. Three (n = 2,784 patients or 36.13%) of the articles indicated an association between the polymorphic allele and a higher risk of developing dyslipidemia with a relative risk of 1.16 (IC 95% 1.09–1.23, p < 0.01, I2 = 0%). Relative risk (IC 95%) was presented, and p < 0.05 was defined as the significance criterion.
Discussion:
This study reinforces a possible association between the influence of SNP rs670 and dyslipidemia. This emphasizes the importance of conducting further research incorporating a larger and more diverse study group, as well as investigating the genetic and environmental influence on the phenotypic expression of the rs670 SNP.
DOI: https://doi.org/10.37349/eemd.2026.101455
Endocrine hypertension (HT) includes a group of secondary hypertensive disorders caused by hormonal excess, primarily primary aldosteronism (PA), pheochromocytoma and paraganglioma (PPGL), and Cushing syndrome (CS). Although relatively uncommon, these conditions confer a disproportionately high cardiovascular risk that extends beyond blood pressure elevation. Aldosterone, catecholamines, and cortisol each induce myocardial fibrosis, oxidative stress, and endothelial dysfunction, leading to left ventricular hypertrophy (LVH), arrhythmias, and heart failure. In PA, chronic aldosterone excess activates mineralocorticoid receptors in cardiac and vascular tissues, promoting collagen deposition, diastolic dysfunction, and atrial fibrillation (AF) that may regress after adrenalectomy or pharmacologic blockade. PPGL causes episodic catecholamine surges resulting in β-adrenergic overstimulation, calcium overload, and microvascular ischemia, producing reversible or sometimes persistent catecholamine-induced cardiotoxicity. CS induces concentric hypertrophy, metabolic derangements, and vascular injury through prolonged glucocorticoid exposure, with cardiovascular recovery often incomplete after biochemical remission. Despite distinct hormonal origins, these disorders share convergent mechanisms, including fibroblast activation, mitochondrial injury, and maladaptive remodeling, that define endocrine cardiomyopathy. Early detection and targeted hormonal treatment can reverse much of the cardiac and vascular damage, whereas delayed recognition leads to irreversible fibrosis and persistent diastolic dysfunction. Recognition of these hormone-specific mechanisms is crucial for clinicians to anticipate, manage, and prevent these deleterious cardiovascular effects. Advances in molecular genetics, cardiac imaging, and biomarker research are improving our understanding of genotype-phenotype relationships and long-term reversibility of injury. Endocrine HT should therefore be recognized as a systemic cardiovascular disorder in which hormonal excess functions as a primary pathogenic driver; timely diagnosis and multidisciplinary care remain key to reducing morbidity and mortality.
Endocrine hypertension (HT) includes a group of secondary hypertensive disorders caused by hormonal excess, primarily primary aldosteronism (PA), pheochromocytoma and paraganglioma (PPGL), and Cushing syndrome (CS). Although relatively uncommon, these conditions confer a disproportionately high cardiovascular risk that extends beyond blood pressure elevation. Aldosterone, catecholamines, and cortisol each induce myocardial fibrosis, oxidative stress, and endothelial dysfunction, leading to left ventricular hypertrophy (LVH), arrhythmias, and heart failure. In PA, chronic aldosterone excess activates mineralocorticoid receptors in cardiac and vascular tissues, promoting collagen deposition, diastolic dysfunction, and atrial fibrillation (AF) that may regress after adrenalectomy or pharmacologic blockade. PPGL causes episodic catecholamine surges resulting in β-adrenergic overstimulation, calcium overload, and microvascular ischemia, producing reversible or sometimes persistent catecholamine-induced cardiotoxicity. CS induces concentric hypertrophy, metabolic derangements, and vascular injury through prolonged glucocorticoid exposure, with cardiovascular recovery often incomplete after biochemical remission. Despite distinct hormonal origins, these disorders share convergent mechanisms, including fibroblast activation, mitochondrial injury, and maladaptive remodeling, that define endocrine cardiomyopathy. Early detection and targeted hormonal treatment can reverse much of the cardiac and vascular damage, whereas delayed recognition leads to irreversible fibrosis and persistent diastolic dysfunction. Recognition of these hormone-specific mechanisms is crucial for clinicians to anticipate, manage, and prevent these deleterious cardiovascular effects. Advances in molecular genetics, cardiac imaging, and biomarker research are improving our understanding of genotype-phenotype relationships and long-term reversibility of injury. Endocrine HT should therefore be recognized as a systemic cardiovascular disorder in which hormonal excess functions as a primary pathogenic driver; timely diagnosis and multidisciplinary care remain key to reducing morbidity and mortality.
DOI: https://doi.org/10.37349/eemd.2026.101454
The global prevalence of obesity and type 2 diabetes mellitus (T2DM)—the most common metabolic disorders—has reached epidemic proportions over the past half-century, with obesity being a key driver of insulin resistance and T2DM development. These disorders are characterized by metaflammation (chronic low-grade inflammation across multiple metabolic organs like adipose tissue, liver, muscle, and the gut), which disrupts metabolic homeostasis, exacerbates insulin resistance, impairs insulin secretion, and links to other comorbidities such as cardiovascular diseases. A major advance in understanding inflammation resolution is the identification of specialized pro-resolving mediators (SPMs), a family of lipid mediators including resolvins, lipoxins, protectins, and maresins. Derived from polyunsaturated fatty acids (e.g., EPA, DHA), SPMs actively regulate inflammation resolution by constraining pro-inflammatory cell infiltration (e.g., neutrophils), promoting anti-inflammatory macrophage polarization (M2), enhancing efferocytosis (clearance of apoptotic cells), and preserving tissue barrier integrity—without inducing immunosuppression. This review summarizes evidence from human and animal studies on obesity-related metaflammation in metabolic tissues and the role of SPMs in resolving this inflammation. It details SPM mechanisms (e.g., maintaining adipose tissue homeostasis, improving insulin sensitivity, alleviating hepatic steatosis) and highlights their dysregulation in obesity (e.g., impaired biosynthesis, reduced receptor expression) as a critical driver of metabolic dysfunction. Finally, the review discusses the therapeutic potential of SPM-targeted strategies (e.g., ω-3 PUFA supplementation, SPM receptor activation) for alleviating obesity, T2DM, metabolic dysfunction-associated steatotic liver disease (MAFLD), and other metabolic disorders, along with future research directions in this field.
The global prevalence of obesity and type 2 diabetes mellitus (T2DM)—the most common metabolic disorders—has reached epidemic proportions over the past half-century, with obesity being a key driver of insulin resistance and T2DM development. These disorders are characterized by metaflammation (chronic low-grade inflammation across multiple metabolic organs like adipose tissue, liver, muscle, and the gut), which disrupts metabolic homeostasis, exacerbates insulin resistance, impairs insulin secretion, and links to other comorbidities such as cardiovascular diseases. A major advance in understanding inflammation resolution is the identification of specialized pro-resolving mediators (SPMs), a family of lipid mediators including resolvins, lipoxins, protectins, and maresins. Derived from polyunsaturated fatty acids (e.g., EPA, DHA), SPMs actively regulate inflammation resolution by constraining pro-inflammatory cell infiltration (e.g., neutrophils), promoting anti-inflammatory macrophage polarization (M2), enhancing efferocytosis (clearance of apoptotic cells), and preserving tissue barrier integrity—without inducing immunosuppression. This review summarizes evidence from human and animal studies on obesity-related metaflammation in metabolic tissues and the role of SPMs in resolving this inflammation. It details SPM mechanisms (e.g., maintaining adipose tissue homeostasis, improving insulin sensitivity, alleviating hepatic steatosis) and highlights their dysregulation in obesity (e.g., impaired biosynthesis, reduced receptor expression) as a critical driver of metabolic dysfunction. Finally, the review discusses the therapeutic potential of SPM-targeted strategies (e.g., ω-3 PUFA supplementation, SPM receptor activation) for alleviating obesity, T2DM, metabolic dysfunction-associated steatotic liver disease (MAFLD), and other metabolic disorders, along with future research directions in this field.
DOI: https://doi.org/10.37349/eemd.2026.101453
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and dual incretin agonists have demonstrated significant potential in improving adipose tissue function beyond their established effects on appetite suppression and weight loss. These agents not only reduce overall fat mass but also induce favorable changes in fat distribution and adipose tissue quality. Notably, they enhance brown adipose tissue (BAT) activity and promote the browning of white adipose tissue (WAT), thereby increasing energy expenditure. They are associated with reductions in adipocyte size, particularly within visceral fat depots, alongside improvements in metabolic health markers. The aim of this publication is to provide a literature review on the effects of GLP-1RAs and dual incretin agonists on adipocyte type and size, adipose tissue functional remodeling, and their implications for obesity management. These findings highlight the capacity of incretin-based therapies to modulate adipose tissue biology, offering metabolic benefits that extend beyond weight reduction.
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and dual incretin agonists have demonstrated significant potential in improving adipose tissue function beyond their established effects on appetite suppression and weight loss. These agents not only reduce overall fat mass but also induce favorable changes in fat distribution and adipose tissue quality. Notably, they enhance brown adipose tissue (BAT) activity and promote the browning of white adipose tissue (WAT), thereby increasing energy expenditure. They are associated with reductions in adipocyte size, particularly within visceral fat depots, alongside improvements in metabolic health markers. The aim of this publication is to provide a literature review on the effects of GLP-1RAs and dual incretin agonists on adipocyte type and size, adipose tissue functional remodeling, and their implications for obesity management. These findings highlight the capacity of incretin-based therapies to modulate adipose tissue biology, offering metabolic benefits that extend beyond weight reduction.
DOI: https://doi.org/10.37349/eemd.2025.101452
The glucocorticoid receptor alpha (GRα) is traditionally viewed as a stress-response element with anti-inflammatory properties. Mechanistically, convergent evidence from global and tissue-specific knockout models, translational clinical studies, and evolutionary analyses indicates that GRα’s vital role in maintaining systemic homeostasis challenges its peripheral classification in clinical medicine. To reconceptualize GRα as a master regulator of organismal survival by analyzing its non-redundant, multisystemic functions and evaluating its relevance in health, development, and critical illness. This narrative synthesis combines structured searches performed using the Consensus AI research platform with evidence from genetic knockout models, tissue-specific deletion studies, and translational clinical research. Key findings are framed within comparative receptor analyses and integrated into broader physiological models of homeostasis and allostasis. Evolutionarily, global loss of GRα is perinatally lethal, characterized by failure of lung maturation and respiratory adaptation, accompanied by metabolic and neuroendocrine dysregulation. Tissue-specific deletions reveal essential roles in immune regulation, mitochondrial bioenergetics, cardiovascular function, and neuroendocrine stability. While several other receptors (including MR) are also essential for survival, GRα is distinctive for the breadth of cross-system coordination it provides. GRα exhibits both genomic and non-genomic actions that support rapid stress adaptation and promote restoration of systemic stability. Clinically, despite this broad integrative role, GRα’s survival-critical functions remain underrecognized in therapeutic strategies. Overall, the evidence supports GRα as a central integrator of postnatal survival, metabolic resilience, and immunological competence. GRα is a vital receptor whose systemic regulatory functions exceed its historical classification as a stress hormone mediator. Its role is not ancillary but foundational, anchoring survival across immune, metabolic, cardiovascular, and neuroendocrine systems. The collapse of this receptor’s function is not simply a component of disease—it is the tipping point that drives the organism from adaptation toward systemic breakdown. Recognizing GRα as a master survival receptor redefines therapeutic priorities, guiding biomarker-driven restoration of homeostasis in critical illness.
The glucocorticoid receptor alpha (GRα) is traditionally viewed as a stress-response element with anti-inflammatory properties. Mechanistically, convergent evidence from global and tissue-specific knockout models, translational clinical studies, and evolutionary analyses indicates that GRα’s vital role in maintaining systemic homeostasis challenges its peripheral classification in clinical medicine. To reconceptualize GRα as a master regulator of organismal survival by analyzing its non-redundant, multisystemic functions and evaluating its relevance in health, development, and critical illness. This narrative synthesis combines structured searches performed using the Consensus AI research platform with evidence from genetic knockout models, tissue-specific deletion studies, and translational clinical research. Key findings are framed within comparative receptor analyses and integrated into broader physiological models of homeostasis and allostasis. Evolutionarily, global loss of GRα is perinatally lethal, characterized by failure of lung maturation and respiratory adaptation, accompanied by metabolic and neuroendocrine dysregulation. Tissue-specific deletions reveal essential roles in immune regulation, mitochondrial bioenergetics, cardiovascular function, and neuroendocrine stability. While several other receptors (including MR) are also essential for survival, GRα is distinctive for the breadth of cross-system coordination it provides. GRα exhibits both genomic and non-genomic actions that support rapid stress adaptation and promote restoration of systemic stability. Clinically, despite this broad integrative role, GRα’s survival-critical functions remain underrecognized in therapeutic strategies. Overall, the evidence supports GRα as a central integrator of postnatal survival, metabolic resilience, and immunological competence. GRα is a vital receptor whose systemic regulatory functions exceed its historical classification as a stress hormone mediator. Its role is not ancillary but foundational, anchoring survival across immune, metabolic, cardiovascular, and neuroendocrine systems. The collapse of this receptor’s function is not simply a component of disease—it is the tipping point that drives the organism from adaptation toward systemic breakdown. Recognizing GRα as a master survival receptor redefines therapeutic priorities, guiding biomarker-driven restoration of homeostasis in critical illness.
DOI: https://doi.org/10.37349/eemd.2025.101451
Psychiatric medication is vital in the treatment of a wide range of mental and behavioral health conditions, but has moderate metabolic consequences. The common side effects are weight gain, dyslipidemia, increased adiposity, elevated body mass index, increased insulin resistance, and metabolic alterations. Metabolic risk is lower with antidepressants than with antipsychotics. The side effects are linked to the metabolic syndrome, increasing the risk of heart disease, stroke, and type 2 diabetes. Cardiovascular diseases, dysglycemia and diabetes, atherogenic dyslipidemia, and metabolic syndrome are common complications associated with the use of antipsychotics. Therefore, it is essential to comprehend the metabolic alterations and develop strategies for early detection and intervention to mitigate these effects. This review discusses the metabolic alterations associated with common antipsychotic medications, followed by strategies to attenuate the effects.
Psychiatric medication is vital in the treatment of a wide range of mental and behavioral health conditions, but has moderate metabolic consequences. The common side effects are weight gain, dyslipidemia, increased adiposity, elevated body mass index, increased insulin resistance, and metabolic alterations. Metabolic risk is lower with antidepressants than with antipsychotics. The side effects are linked to the metabolic syndrome, increasing the risk of heart disease, stroke, and type 2 diabetes. Cardiovascular diseases, dysglycemia and diabetes, atherogenic dyslipidemia, and metabolic syndrome are common complications associated with the use of antipsychotics. Therefore, it is essential to comprehend the metabolic alterations and develop strategies for early detection and intervention to mitigate these effects. This review discusses the metabolic alterations associated with common antipsychotic medications, followed by strategies to attenuate the effects.
DOI: https://doi.org/10.37349/eemd.2025.101450
This article belongs to the special issue Regulators of Glucose Homeostasis, Lipid Metabolism and Energy Balance
In this Commentary, we highlight the following issues concerning the development of increasingly more powerful incretin-based therapeutics (IBT) that to date have not been addressed with the attention they may deserve: 1. The appropriateness of BMI-based inclusion criteria for a drug capable of producing weight loss approaching that seen after bariatric surgery; 2. significant limitations inherent in communicating the results of an obesity trial involving a potent IBT; 3. the one-size-fits-all dosing strategies in trials may introduce new challenges for sponsors in the race to develop increasingly powerful IBT; 4. the currently imposed limitations on what can be communicated in the approved IBT product label create an advantageously unlevel playing field for opportunists such as compounding pharmacies. Proposals on how to address these issues are made in the text. While it is realized that the presented topics and solutions are not without controversy, they are intended to provoke further discussion.
In this Commentary, we highlight the following issues concerning the development of increasingly more powerful incretin-based therapeutics (IBT) that to date have not been addressed with the attention they may deserve: 1. The appropriateness of BMI-based inclusion criteria for a drug capable of producing weight loss approaching that seen after bariatric surgery; 2. significant limitations inherent in communicating the results of an obesity trial involving a potent IBT; 3. the one-size-fits-all dosing strategies in trials may introduce new challenges for sponsors in the race to develop increasingly powerful IBT; 4. the currently imposed limitations on what can be communicated in the approved IBT product label create an advantageously unlevel playing field for opportunists such as compounding pharmacies. Proposals on how to address these issues are made in the text. While it is realized that the presented topics and solutions are not without controversy, they are intended to provoke further discussion.
DOI: https://doi.org/10.37349/eemd.2025.101449
This article belongs to the special issue Regulators of Glucose Homeostasis, Lipid Metabolism and Energy Balance
Aim:
To investigate the natural history and progression of non-alcoholic fatty liver disease (NAFLD) in Chinese adults using a community-based longitudinal cohort.
Methods:
We analyzed data from 24,893 adults in the Beijing Health Management Cohort (2016–2021) with annual follow-up, including questionnaires, physical examinations, and laboratory tests. Participants were categorized into three states: healthy (S1, n = 17,906), NAFLD with body mass index (BMI) < 24 kg/m2 (S2, n = 1,139), and NAFLD with BMI ≥ 24 kg/m2 (S3, n = 5,848). Transition probabilities, mean sojourn times, and determinants of progression were estimated using a multi-state Markov model, with analyses stratified by sex.
Results:
Most individuals remained in their baseline state. Females in S1 were more likely to stay healthy than males (93.76% vs. 83.52%), while males had a higher risk of progression to S3 (12.59% vs. 4.23%). Females in S3 had a greater chance of reverting to S1 (21.33% vs. 18.18%). Mean sojourn time in S1 was longer for females (18.58 vs. 6.97 years), whereas males spent more time in S3 (5.37 vs. 4.18 years). Age, hyperuricemia, abdominal obesity, high triglycerides, and low high-density lipoprotein cholesterol (HDL-C) significantly increased the risk of progression.
Conclusions:
Sex differences strongly affect NAFLD progression in Chinese adults. Males are more likely to deteriorate, while females show higher recovery. Metabolic factors and obesity are key targets for early prevention and intervention.
Aim:
To investigate the natural history and progression of non-alcoholic fatty liver disease (NAFLD) in Chinese adults using a community-based longitudinal cohort.
Methods:
We analyzed data from 24,893 adults in the Beijing Health Management Cohort (2016–2021) with annual follow-up, including questionnaires, physical examinations, and laboratory tests. Participants were categorized into three states: healthy (S1, n = 17,906), NAFLD with body mass index (BMI) < 24 kg/m2 (S2, n = 1,139), and NAFLD with BMI ≥ 24 kg/m2 (S3, n = 5,848). Transition probabilities, mean sojourn times, and determinants of progression were estimated using a multi-state Markov model, with analyses stratified by sex.
Results:
Most individuals remained in their baseline state. Females in S1 were more likely to stay healthy than males (93.76% vs. 83.52%), while males had a higher risk of progression to S3 (12.59% vs. 4.23%). Females in S3 had a greater chance of reverting to S1 (21.33% vs. 18.18%). Mean sojourn time in S1 was longer for females (18.58 vs. 6.97 years), whereas males spent more time in S3 (5.37 vs. 4.18 years). Age, hyperuricemia, abdominal obesity, high triglycerides, and low high-density lipoprotein cholesterol (HDL-C) significantly increased the risk of progression.
Conclusions:
Sex differences strongly affect NAFLD progression in Chinese adults. Males are more likely to deteriorate, while females show higher recovery. Metabolic factors and obesity are key targets for early prevention and intervention.
DOI: https://doi.org/10.37349/eemd.2025.101448
