Romanian Journal of Diabetes Nutrition and Metabolic Diseases

Sex-differences in dietary macronutrient intake and its association with metabolic syndrome components in adults with type 2 diabetes: a cross-sectional study

Wed, 30 Sep 2026 00:00:00 +0300

Metabolic syndrome (MetS) is highly prevalent in patients with type 2 diabetes (T2D) and increases cardiovascular risk. Sex-specific associations between macronutrient intake and MetS remain insufficiently explored. This study aimed to assess MetS prevalence and examine sex differences in associations between dietary macronutrient intake and MetS components. A cross-sectional study was conducted among 425 Moroccan adults with T2D. MetS was defined using harmonized IDF, AHA, and NHLBI criteria. Dietary intake was assessed using a 24-hour recall, and isoenergetic macronutrient substitution models were applied. The prevalence of MetS was 72.9%, higher in women than men (81.2% vs. 58.4%). Women showed higher BMI, waist circumference, and poorer metabolic profiles. In men, MetS was associated with central obesity, inadequate sleep, and family history of cardiometabolic disease. Replacing protein with fat was associated with lower odds of MetS (OR=0.58; 95% CI: 0.35–0.98), abdominal obesity (OR=0.60; 95% CI: 0.37–0.97), and hypertriglyceridemia (OR=0.57; 95% CI: 0.33–0.95). No significant associations were observed in women. MetS is highly prevalent among Moroccan adults with T2D, with clear sex differences. Macronutrient substitution was associated with favorable metabolic outcomes only in men, highlighting the importance of sex-specific nutritional strategies.

Determinants of hyperhomocysteinemia in sports pratice among individuals with type 2 diabetes in Cote d’Ivoire

Wed, 30 Sep 2026 00:00:00 +0300

Several studies have established a link between nutrition, physical activity, and hyperhomocysteinemia. High-intensity physical activity has been implicated as a risk factor for hyperhomocysteinemia. The objective of this study was to investigate the causes of increased homocysteine levels through physical activity in type 2 diabetics in Côte d’Ivoire. This was a descriptive cross-sectional study conducted on 181 volunteers type 2 diabetics, aged from 23 to 86 years, regularly monitored at the Abidjan Antidiabetic Center. They were submitted to the WHO Global Physical Activity Questionnaire. Homocysteine levels were measured using the enzymatic cycling method. The study revealed that the factors increasing homocysteine levels through physical activity in Ivorian type 2 diabetics were: high-intensity exercise (2.2%), particularly in males; moderate exercise equivalent to intense exercise in those over 70 years, due to the physiological decline in renal function associated with aging; the sedentary lifestyle (46.96%), particularly in those over 50 years of age; and age itself in relation to a sedentary lifestyle. Conversely, moderate exercise (50.83%) did not increase hyperhomocysteinemia, either across the 20–69 age group or according to normo- or hyperhomocysteinemic status. Moderate physical activity is protective against hyperhomocysteinemia. It can be recommended and prescribed for hyperhomocysteinemia prevention and treatment.

Limited predictive value of HbA1c, fructosamine, hemoglobin glycation index and glycation gap for early kidney injury in newly diagnosed type 2 diabetes mellitus

Diep Thao Pham, Tram Thuy Nguyen, Minh Thi Hoang, Thuan Quang Huynh — Wed, 30 Sep 2026 00:00:00 +0300

This study aims to evaluate the predictive value of protein glycation markers, including glycated hemoglobin (HbA1c), fructosamine, glycation gap (GG), and hemoglobin glycation index (HGI), for early kidney injury in patients with newly diagnosed type 2 diabetes mellitus (T2DM). A cross-sectional analytical study was conducted in 103 patients with newly diagnosed T2DM. Early kidney injury was assessed using the urinary albumin-to-creatinine ratio (uACR). The predictive performance of HbA1c, fructosamine, GG, and HGI for albuminuria was evaluated using univariate and multivariable logistic regression analyses adjusted for age, sex, and body mass index (BMI), along with receiver operating characteristic (ROC) curve analysis. The study showed that in logistic regression analyses, none of the glycation markers independently predicted albuminuria after adjustment for age, sex, and BMI (all p>0.05). ROC analysis demonstrated poor discriminatory performance for HbA1c (AUC=0.597), fructosamine (AUC=0.602), and the combined model (AUC=0.599), and none of the AUC values reached statistical significance (all p>0.05). In patients with newly diagnosed T2DM, HbA1c, fructosamine, HGI, and GG did not independently predict albuminuria. These findings suggest that protein glycation markers have limited value as biomarkers for identifying early kidney injury at the time of T2DM diagnosis.

Medication safety in diabetes care and addressing medication errors and drug interactions

Wed, 30 Sep 2026 00:00:00 +0300

Didactic lectures are the major mode of traditional teaching (TT) in medical education, but they might not adequately equip students with skills for clinical practice. Early Clinical Exposure (ECE) combines hospital-based learning and clinical case discussion in the initial stages of medical education, perhaps enhancing knowledge retention, clinical problem-solving, and confidence. This study compares the relative effectiveness of ECE and TT for teaching physiology to first-year MBBS students. A prospective, cross-sectional study was done on 250 SRM University first-year MBBS students. Students first received TT in gastrointestinal physiology, then ECE. Pre-test, post-test, and retention test at one and three months evaluated learning and retention of knowledge. Case-based problem-solving exercises and student confidence surveys were employed to compare clinical application skills. Data analysis was performed using paired t-tests and ANOVA, with p-values<0.05 as statistically significant. ECE better enhanced learning achievements than TT, with mean scores rising from 42.3% (pre-test) to 78.4% (post-ECE). Retention of knowledge at three months was better in the ECE group (74–80%) than in the TT group (38–50%). Diagnostic ability and clinical use were significantly enhanced, with problem-solving times being shortened by 43% in ECE. Confidence in making a diagnosis was boosted from 48% (TT) to 89% (ECE) (p<0.001). ECE is more effective than TT in improving knowledge recall, clinical problem-solving, and student confidence. These conclusions recommend the incorporation of ECE into medical school curricula to enhance the transition between theory and practice.

Excess weight and its association with dietary habits, sleep quality, and physical activity among adolescents from a public school in Peru

María Ramos, Rafael Durán — Wed, 30 Sep 2026 00:00:00 +0300

Excess weight among adolescents in Latin America has reached alarming levels, with Peru above global averages. Yet what drives this trend in vulnerable school settings remains poorly studied. This study evaluated the association between dietary habits, sleep quality, and physical activity with excess weight among adolescents from a public school in Peru. A cross-sectional study was conducted with 193 adolescents aged 12 to 17 years enrolled in secondary education. Three validated instruments assessed the study variables. Excess weight was determined by BMI-for-age; Chi-square and Cramer’s V were applied. Overall, 67.36% of adolescents had excess weight, with higher prevalence in females (74.74%) than males (60.20%; p=0.031). Dietary habits were significantly associated with excess weight (p=0.034), but in an unexpected direction: those without excess weight showed more unhealthy habits (76.19%) than those with excess weight (60.77%). No significant associations were found with sleep quality (p=0.666) or physical activity (p=0.897). The prevalence of excess weight (67.36%) far exceeded national figures, pointing to a serious vulnerability in this school setting. The unexpected direction of the dietary habits association raises important questions about what drives excess weight in vulnerable settings, reinforcing the need for comprehensive preventive programs.

Stress prevalence and associated risk factors among patients with metabolic syndrome defined by NCEP ATP III criteria

Wed, 30 Sep 2026 00:00:00 +0300

Metabolic syndrome (MetS) is a major cardiometabolic disorder characterized by the clustering of abdominal obesity, hypertension, impaired glucose regulation, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol. Psychosocial stress may further increase the disease burden by adversely affecting lifestyle behaviors, treatment adherence, and control of cardiometabolic risk factors. However, evidence regarding the prevalence and determinants of stress among individuals with MetS in routine clinical settings remains limited. To determine the prevalence of stress and identify its associated factors among adults with metabolic syndrome. A hospital-based analytical cross-sectional study was conducted among 486 adult participants. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Stress was assessed using the stress subscale of the Depression, Anxiety and Stress Scale-21 (DASS-21). Sociodemographic, behavioral, clinical, and metabolic characteristics were collected using a structured proforma. Associations between stress and potential predictors were assessed using bivariate analysis, followed by multivariable logistic regression to identify independent correlates. Metabolic syndrome was present in 59.5% of participants. Overall, 61.3% experienced stress. Stress was significantly more prevalent among participants with MetS than among those without MetS (72.7% vs. 44.7%). Among individuals with MetS, stress prevalence increased progressively with a greater number of abnormal NCEP ATP III components. Poor sleep quality showed the strongest independent association with stress (AOR=3.81), while lower educational status, low physical activity, female sex, abdominal obesity, and greater metabolic clustering were also independently associated with stress. Stress was highly prevalent among individuals with MetS and was strongly associated with adverse behavioral, socioeconomic, and metabolic characteristics. Routine screening and management of psychosocial stress should be integrated into comprehensive MetS care.

Serum interleukin-6 as an inflammatory biomarker in type 2 diabetes mellitus: correlation with diabetic peripheral neuropathy and diagnostic performance

Ahmed Yaseen Abed, Alaa Ahmed Fezea — Wed, 30 Sep 2026 00:00:00 +0300

Diabetic peripheral neuropathy (DPN) is a common, debilitating complication of type 2 diabetes mellitus (T2DM); interleukin-6 (IL-6) has been increasingly implicated in its pathogenesis, yet Iraqi data remain scarce. We compared serum IL-6 between T2DM patients with and without DPN, assessed its correlation with neuropathy severity, and evaluated its diagnostic performance. A cross-sectional study was conducted on 90 patients with T2DM, equally divided into two groups based on DPN status assessed using the Michigan Neuropathy Screening Instrument (MNSI). Serum IL-6 was measured by ELISA and analysed using the Mann-Whitney U test, Spearman correlation, ROC curve analysis, and multivariable logistic regression. Median serum IL-6 was higher in DPN patients (194.38 pg/mL; IQR: 144.16–338.89) than in those without DPN (97.01 pg/mL; IQR: 71.39–148.26; p<0.001) and correlated strongly with MNSI score (rho=0.693, p<0.001), with no correlation to HbA1c or fasting glucose. IL-6 independently predicted DPN (OR=1.020; 95% CI: 1.010–1.031; p<0.001), with good diagnostic accuracy (AUC=0.843; 95% CI: 0.763–0.922; cut-off 110.34 pg/mL; sensitivity 91.1%; specificity 64.4%). Serum IL-6 is significantly elevated in DPN and correlates with its severity independent of glycaemic control, showing good diagnostic accuracy as a potential adjunctive screening biomarker in resource-limited settings.

Prevalence, clinical profile and risk factors of metabolic dysfunction–associated steatotic liver disease (MASLD) in newly diagnosed type 2 diabetes mellitus

Wed, 30 Sep 2026 00:00:00 +0300

There is a high incidence of association metabolic dysfunction–associated steatotic liver disease (MASLD) among patients with type 2 diabetes mellitus (T2DM) which if not detected and treated at the earliest can result into serious complications. We aim to study the prevalence, clinical profile and risk factors of MASLD in newly diagnosed type 2 diabetes patients. This was a cross-sectional study involving 272 individuals with new onset T2DM diagnosed in previous 6 months who met the inclusion criteria. Patients were stratified according to the presence/absence of MASLD. MASLD presence and severity were defined by ultrasonographic detection of steatosis in the absence of other liver diseases. The anthropometric, clinical and laboratory data were collected retrospectively. Parameters as predictors of MASLD were identified using linear regression models. The prevalence of MASLD by Ultrasound examination was 64%, with higher prevalence in females (71.4%) than males (57.5%). The patients with MASLD demonstrated significantly higher mean BMI, waist-hip ratio, AST, ALT, GGT, SUA, FPG, FINS and triglycerides but lower HDL. Pearson correlation showed significantly positive associations of MASLD severity with BMI (p<0.001), WHR (p<0.001), TG (p=0.013), AST (0.009), ALT (p=0.004) and TG (p=0.012). Linear regression analysis confirmed independent positive associations of MASLD with BMI (p=0.032), WHR (p=0.025), ALT (p=0.032), HDL (P=019) and TG (p=0.012). The significant prevalence of MASLD in newly diagnosed T2DM patients in this study underscores the importance of incorporating routine screening in diabetic care for early detection and management of hepatic impairment, aiming to reduce the burden of liver-related complications in diabetic populations.

Psychometric properties of the multidimensional fatigue inventory in people with type 2 diabetes mellitus

Wed, 30 Sep 2026 00:00:00 +0300

The purpose of this study was to examine the test-retest reliability and discriminant validity of the Multidimensional Fatigue Inventory (MFI) in people with type 2 diabetes mellitus (T2DM). The study recruited 30 people with T2DM. Test-retest reliability of the MFI was examined by re-administration of the MFI after an interval of one day. Cronbach’s α, intraclass correlation (ICC), standard error of measurement (SEM), and smallest detectable change (SDC) were calculated. Bland-Altman limits of agreement (LoA) were determined. Discriminant validity was assessed using Spearman’s test. Internal consistency values were adequate for the MFI-total score and five MFI subscales, with Cronbach’s α ranging from 0.97 to 0.99. ICCs ranged from 0.97 to 0.99. The Bland-Altman analysis revealed high stability and low variation of MFI. High discriminant validity was observed for MFI (r=0.33, p=0.08). In order to measure the different aspects of fatigue in people with T2DM, MFI can be considered a comprehensive instrument.

The effect of quercetin on systemic inflammatory response and metabolism in rats under surgical and prolonged psychogenic stress

Roman Ryabushko, Heorhii Kostenko, Oleksandr Shkidchenko, Vitalii Kostenko — Wed, 30 Sep 2026 00:00:00 +0300

Prolonged psychogenic stress resembling post-traumatic stress disorder (PTSD), combined with surgical trauma, induces systemic inflammatory and metabolic disturbances. Quercetin, a natural polyphenol with antioxidant and anti-inflammatory properties, may attenuate these effects. This study evaluated the effects of water-soluble quercetin on systemic inflammatory response (SIR), carbohydrate metabolism, and lipid metabolism in rats subjected to surgical trauma following Single Prolonged Stress (SPS). Twenty-one adult male Wistar rats were allocated to three groups (n=7): control animals receiving polyvinylpyrrolidone (PVP), SPS plus surgical trauma animals receiving PVP, and SPS plus surgical trauma animals receiving a water-soluble quercetin–PVP complex equivalent to 20 mg/kg quercetin. Treatments were administered intragastrically for 7 days. Serum cortisol, ceruloplasmin, tumor necrosis factor-alpha (TNF-α), interleukins (IL-6 and IL-10), glucose, insulin, and lipid profile parameters were assessed using spectrophotometric and ELISA methods. Combined SPS and surgical trauma induced marked hypothalamic–pituitary–adrenal axis activation, systemic inflammation, insulin resistance, and dyslipidemia. Quercetin reduced serum cortisol and ceruloplasmin levels and markedly decreased TNF-α and IL-6 concentrations, while restoring the IL-10/IL-6 ratio toward control values. Quercetin also reduced blood glucose and HOMA-IR, although insulin levels remained elevated compared with controls. Lipid abnormalities were partially corrected, as evidenced by increased HDL cholesterol and decreased triglyceride and VLDL cholesterol levels, without significant changes in total or LDL cholesterol. Water-soluble quercetin attenuated stress- and surgery-induced inflammatory and metabolic disturbances, suggesting potential as an adjunctive strategy for reducing systemic inflammation and cardiometabolic alterations associated with combined psychological and surgical stress.

Heart rate variability as a predictor of autonomic dysfunction and cardiovascular risk in periodontitis

Wed, 30 Sep 2026 00:00:00 +0300

Periodontitis is a chronic inflammatory disease damaging the supportive structure of teeth. It has many systemic impacts including cardiac autonomic dysfunction. Heart Rate Variability (HRV) measures an objective analysis of the extent of autonomic regulation and where decreased parasympathetic activity coupled with increased sympathetic predominance was determined to correlate well with risk in cardiovascular function. This research ascertains periodontitis and its correlation to autonomic dysfunction by HRV analysis. In total, 54 periodontitis patients were involved in the study, categorized under four groups, namely Gingivitis (n=14), Mild Periodontitis (n=13), Moderate Periodontitis (n=13), and Severe Periodontitis (n=14). Kubios HRV software version 3.5 was used for the analysis of time-domain and frequency-domain parameters of lead II ECG for HRV analysis. The indices of SNS and PNS were calculated for the assessment of autonomic balance. The correlation between the HRV parameters with the severity of periodontal disease was performed statistically. The SNS index was increased with periodontitis severity (Gingivitis: 1.09±0.60, Mild Periodontitis: 4.25±2.4, Moderate Periodontitis: 3.82±2.2, Severe Periodontitis: 4.45±1.5; p<0.001), which reflected enhanced sympathetic activation. On the other hand, the PNS index was significantly reduced (0.55±0.91 in Gingivitis to -0.98±0.59 in Severe Periodontitis; p<0.001), indicating parasympathetic withdrawal. SDNN, a marker of overall autonomic tone, decreased significantly (p=0.025), while high-frequency (HF) power, indicative of vagal activity, showed a strong negative correlation with periodontitis severity (Rho=-0.58, p<0.001). These findings suggest progressive autonomic dysfunction with increasing periodontal inflammation. Significant autonomic dysfunction, including elevated sympathetic hyperactivity and diminished parasympathetic regulation, is associated with periodontitis and lowers heart rate variability. Higher cardiovascular risk is correlated with the advancement of periodontal disease, underscoring the necessity of HRV evaluation as a possible biomarker. Future studies should examine if treating periodontal disease can enhance systemic health and restore autonomic balance.

Interleukin-33 and interleukin-10 expression in proliferative diabetic retinopathy

Wed, 30 Sep 2026 00:00:00 +0300

Diabetic retinopathy is associated with immune dysregulation driven by chronic hyperglycemia. The role of cytokine balance in its progression remains incompletely understood. To evaluate IL-33 and IL-10 levels and their ratios in patients with diabetic retinopathy depending on disease stage and metabolic control. Patients with proliferative and non-proliferative diabetic retinopathy were stratified by compensated and decompensated diabetes. IL-33 and IL-10 concentrations were measured by ELISA, and IL-33/IL-10 and IL-10/IL-33 ratios were calculated. IL-33 levels did not differ significantly between groups (p>0.05), although a decreasing trend was observed in non-proliferative diabetic retinopathy with compensated diabetes. IL-10 levels were significantly higher in non-proliferative diabetic retinopathy compared with proliferative (p<0.05). The IL-33/IL-10 ratio was increased in proliferative, indicating higher pro-inflammatory potential, while it was reduced in non-proliferative diabetic retinopathy with decompensated diabetes. Conversely, the IL-10/IL-33 ratio was elevated in decompensated diabetes regardless of retinopathy stage (p<0.05). Cytokine balance between IL-33 and IL-10 depends on both disease stage and metabolic control. IL-10 may exhibit context-dependent pro-inflammatory effects in decompensated diabetes. Cytokine ratios may serve as potential biomarkers of immune dysregulation in diabetic retinopathy.

Glycogen storage disease type Ib without immunodeficiency: 60 years from the first symptoms to the final diagnosis

Wed, 30 Sep 2026 00:00:00 +0300

Glycogen storage disease type Ib (GSD Ib) is a rare, genetically determined disorder belonging to the group of inherited metabolic diseases that disrupt glycogen metabolism. It usually manifests in early childhood with recurrent episodes of severe hypoglycemia, hyperlipidemia, hyperuricemia, hepatomegaly, and profound immunodeficiency due to neutropenia. The presented case concerns a 61-year-old patient diagnosed with GSD Ib in adulthood, based on genetic testing that revealed two pathogenic variants in the SLC37A4 gene. The disease followed an atypical course—without neutropenia or increased susceptibility to infections, while the predominant manifestations were dyslipidemia and hepatomegaly. After the implementation of dietary therapy, including regular administration of uncooked cornstarch, good metabolic control was achieved with normalization of liver size. This case illustrates the considerable clinical heterogeneity of GSD Ib and highlights the importance of considering inborn metabolic disorders in adult patients with chronic, unexplained biochemical abnormalities.

Semaglutide across cardiovascular and kidney outcome trials: a systematic review and stratified synthesis

Antonio Maria Labate, Provvidenza Villari — Wed, 30 Sep 2026 00:00:00 +0300

Semaglutide outcome trials span distinct cardiometabolic populations and endpoint hierarchies, complicating a single pooled interpretation. We synthesized cardiovascular and kidney evidence using prespecified clinical strata. Following PRISMA 2020 and SWiM (PROSPERO CRD420261441534), we included phase 3 randomized, double-blind, placebo-controlled cardiovascular or kidney outcome trials of oral or subcutaneous semaglutide. PubMed/MEDLINE, CENTRAL, ClinicalTrials.gov and WHO ICTRP were searched through 15 July 2026. Risk of bias was assessed with RoB 2 and certainty with GRADE. Within the type 2 diabetes cardiovascular stratum, MACE hazard ratios were combined by inverse-variance common-effect meta-analysis; no estimates were pooled across strata. Five trials (37,267 participants) were included: SUSTAIN-6, PIONEER-6, SOUL, SELECT and FLOW. The type 2 diabetes MACE summary was 0.83 (95% CI 0.76–0.92; I2=0%). SELECT showed a MACE hazard ratio of 0.80 (0.72–0.90), while FLOW showed a primary kidney composite hazard ratio of 0.76 (0.66–0.88). Semaglutide reduced cardiovascular events in type 2 diabetes and obesity without diabetes and kidney events in type 2 diabetes with chronic kidney disease. Stratified interpretation preserves clinically important differences across trial populations and endpoint hierarchies.

Gender-related features of liver mitochondrial dysfunction in the development of metabolic syndrome and its pharmacological correction

Olha Pryzhbylo, Olga Kmet, Yana Kropatnytska — Wed, 30 Sep 2026 00:00:00 +0300

The liver as a central organ of metabolism regulates homeostasis of carbohydrates, proteins and lipids. At the same time, key organelles of any cell are mitochondria including liver cells as well. Mitochondria play a crucial role in the cellular energy metabolism. Their main function is generation of adenosine triphosphate mainly by means of oxidative phosphorylation providing a continuous supply of energy to various vital cellular processes. Therefore, the objective of our research was the study of gender differences in liver mitochondrial dysfunction with metabolic syndrome development and possibility of its pharmacological correction by means of carbacetam. The experiments were carried out on laboratory nonlinear white male and female rats with the body weight of 0.220–0.250 kg. Metabolic syndrome was simulated by keeping the rats on high fat diet and free access to fructose solution (100 g/L). Carbacetam was administered intraperitoneally in a dose of 5 mg/kg during 14 days. Therefore, the results of our research are indicative of the development of mitochondrial dysfunction in the liver cells of rats of different genders under conditions of simulating metabolic syndrome. Male rats appeared to be more susceptible to damage. At the same time, administration of carbacetam as a modulator of GABA-receptors demonstrated positive changes from the point of view of mitochondrial functioning. These changes include a decreased relative rate of mitochondrial swelling and decreased peroxide oxidation of lipids and proteins with increasing activity of antioxidant defense enzymes.

Hyperuricemia and cardiometabolic disease: current evidence linking uric acid to obesity, insulin resistance and type 2 diabetes mellitus

Liliya Pashova-Stoyanova — Wed, 30 Sep 2026 00:00:00 +0300

Hyperuricemia has long been regarded as the biochemical hallmark of gout; however, accumulating evidence indicates that its clinical relevance extends considerably beyond crystal-induced arthropathy. Elevated serum uric acid levels are increasingly encountered in individuals with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), hypertension, and cardiovascular disease, positioning hyperuricemia as a potentially integral component of the cardiometabolic continuum. This narrative review synthesizes current evidence linking serum uric acid to obesity, insulin resistance, T2DM, and cardiovascular risk. Epidemiological data consistently demonstrate robust associations between uric acid levels and adverse cardiometabolic profiles. Complementary experimental findings support plausible pathogenic mechanisms, including oxidative stress, mitochondrial dysfunction, endothelial injury, chronic low-grade inflammation, and activation of the renin-angiotensin-aldosterone system. Special emphasis is placed on the bidirectional relationship between obesity and hyperuricemia, the metabolic consequences of fructose overconsumption, and the emerging utility of uric acid as a predictor of incident metabolic disease. The question of whether hyperuricemia acts primarily as a marker or an active mediator of cardiometabolic dysfunction remains unresolved; current evidence, however, supports a contributory pathophysiological role. A deeper understanding of uric acid metabolism may enhance cardiometabolic risk stratification and inform the development of targeted preventive and therapeutic strategies.

Cognitive impairment in endocrine and metabolic disorders: the role of sigma-1 receptors and the potential of pyrrole derivatives

Taras Kmet, Yevhen Pruhlo, Iryna Yaremii, Olha Kmet, Ksenia Slobodian — Wed, 30 Sep 2026 00:00:00 +0300

In today’s global population aging environment cognitive impairment appears to be increasingly prevalent and become one of the leading causes of disability and mortality in the world. Increasing life expectancy is accompanied by more frequent occurrence of neurodegenerative and metabolically provoked lesions of the central nervous system. In addition to age-related changes, endocrine pathology plays a significant role in the development of cognitive deficiency. This pathology includes diabetes mellitus, thyroid diseases, metabolic syndrome and adrenal pathology. Key pathogenic mechanisms are oxidative stress, neurological inflammation, calcium homeostasis disturbances, endothelial dysfunction and mitochondrial disorders. Sigma-1 receptors (S1R) are of special attention in current studies. They perform the function of intracellular chaperones and regulate a wide range of neural processes including neuroplasticity, synaptic transmission and cellular homeostasis. S1R activation is associated with neuroprotective effects, decrease of neurological inflammation and improvement of cognitive functions. Pyrrole derivatives as potential S1R ligands are considered among the promising areas of pharmacotherapy. They combine antioxidant, anti-inflammatory and neuroprotective properties. Modern S1R agonists including Pridopidine, Blarcamesine and Dimethyltryptamine in particular, are of special interest. They demonstrate positive results in preclinical and clinical studies. Therefore, targeting of Sigma-1 receptors is a promising approach to the development of new effective means for the correction of cognitive impairment, especially in patients with metabolic and endocrine disorders.