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16 pages, 575 KiB  
Article
Polycystic Ovary Syndrome Attenuates TSH-Lowering Effect of Metformin in Young Women with Subclinical Hypothyroidism
by Robert Krysiak, Karolina Kowalcze, Johannes Ott, Sofia Burgio, Simona Zaami and Bogusław Okopień
Pharmaceuticals 2025, 18(8), 1149; https://doi.org/10.3390/ph18081149 - 1 Aug 2025
Viewed by 238
Abstract
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: [...] Read more.
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article
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22 pages, 994 KiB  
Article
Correlations Between Coffee Intake, Glycemic Control, Cardiovascular Risk, and Sleep in Type 2 Diabetes and Hypertension: A 12-Month Observational Study
by Tatiana Palotta Minari, José Fernando Vilela-Martin, Juan Carlos Yugar-Toledo and Luciana Pellegrini Pisani
Biomedicines 2025, 13(8), 1875; https://doi.org/10.3390/biomedicines13081875 - 1 Aug 2025
Viewed by 173
Abstract
Background: The consumption of coffee has been widely debated regarding its effects on health. This study aims to analyze the correlations between daily coffee intake and sleep, blood pressure, anthropometric measurements, and biochemical markers in individuals with type 2 diabetes (T2D) and hypertension [...] Read more.
Background: The consumption of coffee has been widely debated regarding its effects on health. This study aims to analyze the correlations between daily coffee intake and sleep, blood pressure, anthropometric measurements, and biochemical markers in individuals with type 2 diabetes (T2D) and hypertension over a 12-month period. Methods: An observational study was conducted with 40 participants with T2D and hypertension, comprising 20 females and 20 males. Participants were monitored for their daily coffee consumption over a 12-month period, being assessed every 3 months. Linear regression was utilized to assess interactions and relationships between variables, providing insights into potential predictive associations. Additionally, correlation analysis was performed using Pearson’s and Spearman’s tests to evaluate the strength and direction of linear and non-linear relationships. Statistical significance was set at p < 0.05. Results: Significant changes were observed in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), body weight, body mass index, sleep duration, nocturnal awakenings, and waist-to-hip ratio (p < 0.05) over the 12-month study in both sexes. No significant differences were noted in the remaining parameters (p > 0.05). The coffee consumed by the participants was of the “traditional type” and contained sugar (2 g per cup) for 100% of the participants. An intake of 4.17 ± 0.360 cups per day was found at baseline and 5.41 ± 0.316 cups at 12 months (p > 0.05). Regarding correlation analysis, a higher coffee intake was significantly associated with shorter sleep duration in women (r = −0.731; p = 0.037). Conversely, greater coffee consumption correlated with lower LDL cholesterol (LDL-C) levels in women (r = −0.820; p = 0.044). Additionally, a longer sleep duration was linked to lower FBG (r = −0.841; p = 0.031), HbA1c (r = −0.831; p = 0.037), and LDL-C levels in women (r = −0.713; p = 0.050). No significant correlations were observed for the other parameters in both sexes (p > 0.05). Conclusions: In women, coffee consumption may negatively affect sleep duration while potentially offering beneficial effects on LDL-C levels, even when sweetened with sugar. Additionally, a longer sleep duration in women appears to be associated with improvements in FBG, HbA1c, and LDL-C. These correlations emphasize the importance of a balanced approach to coffee consumption, weighing both its potential health benefits and drawbacks in postmenopausal women. However, since this study does not establish causality, further randomized clinical trials are warranted to investigate the underlying mechanisms and long-term implications—particularly in the context of T2D and hypertension. Full article
(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (3rd Edition))
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12 pages, 269 KiB  
Article
Exploring the Interplay Between Glycated Albumin, AGEs, and Inflammation in Old Patients with CKD
by Simone Vettoretti, Lara Caldiroli, Paolo Molinari, Amanda Villa, Massimiliano M. Corsi Romanelli, Elena Vianello, Elena Dozio and Simonetta Genovesi
Metabolites 2025, 15(8), 515; https://doi.org/10.3390/metabo15080515 - 1 Aug 2025
Viewed by 183
Abstract
Introduction: Chronic kidney disease (CKD) increases cardiovascular risk through mechanisms such as oxidative stress and the accumulation of advanced glycation end products (AGEs). Glycated albumin (GA) is associated with cardiovascular risk in CKD patients, but its relationship with AGEs and systemic inflammation remains [...] Read more.
Introduction: Chronic kidney disease (CKD) increases cardiovascular risk through mechanisms such as oxidative stress and the accumulation of advanced glycation end products (AGEs). Glycated albumin (GA) is associated with cardiovascular risk in CKD patients, but its relationship with AGEs and systemic inflammation remains unclear. This study investigated these associations in old patients with severe CKD, with and without diabetes. Methods: We conducted a cross-sectional analysis in 122 patients aged ≥ 65 years with CKD stages G3a–G5, including 67 diabetics and 55 non-diabetics. Patients with confounding comorbidities were excluded. We measured GA, AGEs, various AGEs receptors (RAGE) isoforms, and inflammatory cytokines (CRP, IL-6, TNFα, and MCP-1) using standardized assays. Statistical analyses included group comparisons, correlation coefficients, and multivariate regression. Results: Of 122 patients (mean age 77.7 ± 11.3 years), diabetics had higher GA percentages than non-diabetics (22.0 ± 7.1% vs. 17.5 ± 5.4%, p = 0.0001), while AGEs (2931 ± 763 vs. 3156 ± 809 AU; p = 0.118) and inflammatory markers (CRP 0.240[0.380] vs. 0.200[0.280] mg/dL; p = 0.142; IL-6 3.4[4.0] vs. 3.0[3.8] pg/mL; p = 0.238) were similar between groups. Overall, GA was inversely correlated with estimated glomerular filtration rate (eGFR) (ρ = −0.189, p = 0.037) and positively with glycated hemoglobin (HbA1c) (ρ = 0.525, p < 0.0001), but showed no significant correlation with AGEs, RAGE isoforms, or inflammatory cytokines. In multivariate analysis, only HbA1c remained independently associated with GA (β = 0.222, p = 0.005). Conclusions: In old patients with severe CKD, GA appears to be a more useful marker of glycemic control than glycation stress, the latter of which is the result of multiple factors, including impaired kidney function and systemic inflammation. Full article
16 pages, 661 KiB  
Article
Comparative Evaluation of ARB Monotherapy and SGLT2/ACE Inhibitor Combination Therapy in the Renal Function of Diabetes Mellitus Patients: A Retrospective, Longitudinal Cohort Study
by Andrew W. Ngai, Aqsa Baig, Muhammad Zia, Karen Arca-Contreras, Nadeem Ul Haque, Veronica Livetsky, Marcelina Rokicki and Shiryn D. Sukhram
Int. J. Mol. Sci. 2025, 26(15), 7412; https://doi.org/10.3390/ijms26157412 - 1 Aug 2025
Viewed by 341
Abstract
Diabetic nephropathy affects approximately 30–40% of individuals with diabetes mellitus (DM) and is a major contributor to end-stage renal disease (ESRD). While angiotensin II receptor blockers (ARBs) have long served as a standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently gained attention for [...] Read more.
Diabetic nephropathy affects approximately 30–40% of individuals with diabetes mellitus (DM) and is a major contributor to end-stage renal disease (ESRD). While angiotensin II receptor blockers (ARBs) have long served as a standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently gained attention for their renal and cardiovascular benefits. However, comparative real-world data on their long-term renal effectiveness remain limited. We conducted a retrospective, longitudinal study over a 2-year period to compare the impact of ARB monotherapy versus SGLT2i and angiotensin-converting enzyme inhibitor (ACEi) combination therapy on the progression of chronic kidney disease (CKD) in patients with DM. A total of 126 patients were included and grouped based on treatment regimen. Renal biomarkers were analyzed using t-tests and ANOVA (p < 0.01). Albuminuria was qualitatively classified via urinalysis as negative, level 1 (+1), level 2 (+2), or level 3 (+3). The ARB group demonstrated higher estimated glomerular filtration rate (eGFR) and lower serum creatinine (sCr) levels than the combination therapy group, with glycated hemoglobin (HbA1c), potassium (K+), and blood pressure remaining within normal limits in both cohorts. Albuminuria remained stable over time, with 60.8% of ARB users and 73.1% of combination therapy users exhibiting persistently or on-average negative results. Despite the expected additive benefits of SGLT2i/ACEi therapy, ARB monotherapy was associated with slightly more favorable renal function markers and a lower incidence of severe albuminuria. These findings suggest a need for further controlled studies to clarify the comparative long-term renal effects of these treatment regimens. Full article
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13 pages, 259 KiB  
Article
Excessive Daytime Sleepiness and Associated Cardiometabolic Factors in Latino Individuals of Mexican Ancestry at High Risk of Type 2 Diabetes: An El Banco Biobank Cross-Sectional Study
by Ludovica Verde, Dawn K. Coletta, Yann C. Klimentidis, Linsday N. Kohler, Lisa Soltani, Oscar D. Parra, Sairam Parthasarathy, Lawrence J. Mandarino and Giovanna Muscogiuri
Nutrients 2025, 17(15), 2476; https://doi.org/10.3390/nu17152476 - 29 Jul 2025
Viewed by 187
Abstract
Background/Objectives: Latinos, particularly those of Mexican ancestry, experience high rates of type 2 diabetes and sleep disturbances, exacerbating adverse health outcomes. This study aimed to examine the prevalence of excessive daytime sleepiness and its associations with diet, cardiometabolic risk factors, and glycemic [...] Read more.
Background/Objectives: Latinos, particularly those of Mexican ancestry, experience high rates of type 2 diabetes and sleep disturbances, exacerbating adverse health outcomes. This study aimed to examine the prevalence of excessive daytime sleepiness and its associations with diet, cardiometabolic risk factors, and glycemic control in this population. Methods: This cross-sectional study utilized data from the El Banco por Salud biobank, including 1685 participants (aged 52.6 ± 14.5 years, BMI: 32.4 ± 7.0 kg/m2) recruited from Federally Qualified Community Health Centers. Excessive daytime sleepiness was assessed using the Epworth Sleepiness Scale, while dietary information was obtained via the Brief Dietary Assessment Tool for Hispanics. Primary outcomes included cardiometabolic risk factors and glycated hemoglobin (HbA1c) levels. Results: Excessive daytime sleepiness (Epworth Sleepiness Scale > 10) was present in 22.0% of participants and was associated with higher BMI (p < 0.001), larger waist circumference (p = 0.002), poorer diet quality, increased dyslipidemia (p = 0.036), and elevated HbA1c (p = 0.007). Linear regression analyses confirmed that excessive daytime sleepiness was significantly associated with higher HbA1c levels, both in unadjusted (R2 = 0.011; p < 0.001) and adjusted for demographic, anthropometric, and socioeconomic factors (R2 = 0.107; p = 0.004) models. Conclusions: Excessive daytime sleepiness among Latinos of Mexican ancestry is associated with unhealthy dietary patterns and poor glycemic control, highlighting the need for targeted interventions addressing sleep and dietary habits in this vulnerable population. Full article
(This article belongs to the Special Issue The Diabetes Diet: Making a Healthy Eating Plan)
16 pages, 1920 KiB  
Review
Time-Restricted Eating Improves Glycemic Control in Patients with Type 2 Diabetes: A Meta-Analysis and Systematic Review
by Taegwang Nam, Hyeongbin Oh, Anna Kim and Yongtaek Oh
Int. J. Mol. Sci. 2025, 26(15), 7310; https://doi.org/10.3390/ijms26157310 - 29 Jul 2025
Viewed by 634
Abstract
Time-restricted eating (TRE), a dietary strategy that aligns food intake with circadian rhythms, has emerged as a promising non-pharmacological approach for improving glycemic control in patients with type 2 diabetes. This systematic review and meta-analysis evaluated the effects of TRE on glycemic outcomes [...] Read more.
Time-restricted eating (TRE), a dietary strategy that aligns food intake with circadian rhythms, has emerged as a promising non-pharmacological approach for improving glycemic control in patients with type 2 diabetes. This systematic review and meta-analysis evaluated the effects of TRE on glycemic outcomes by analyzing eight randomized controlled trials involving 312 participants with type 2 diabetes or impaired fasting glucose. Meta-analyses of six eligible studies demonstrated that TRE significantly reduced fasting glucose (mean difference [MD]: −0.74 mmol/L; 95% CI: −1.13 to −0.36) and glycated hemoglobin (ΔHbA1c) (MD: −0.11%; 95% CI: −0.15 to −0.07) and increased time in range (TIR) for blood glucose (MD: +10.51%; 95% CI: 6.81 to 14.21). Improvements in fasting glucose and HbA1c were modest but consistent, while the increase in TIR showed no between-study heterogeneity, suggesting a robust and reproducible benefit of TRE on glycemic stability. These findings support the clinical feasibility and effectiveness of TRE as a dietary intervention in diabetes management. However, further high-quality trials with standardized protocols and longer follow-up are needed to confirm long-term efficacy and inform guidelines. Full article
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19 pages, 316 KiB  
Article
Comparison of the Usefulness of Optical Coherence Tomography Angiography and Fluorescein Angiography in the Diagnosis of Diabetic Macular Edema
by Alfred Niewiem, Krzysztof Broniarek and Katarzyna Michalska-Małecka
Diagnostics 2025, 15(15), 1873; https://doi.org/10.3390/diagnostics15151873 - 25 Jul 2025
Viewed by 239
Abstract
Background/Objectives: Diabetic macular edema (DME) is the primary cause of vision loss in people with diabetes, and if untreated, it can result in irreversible macular damage. Both fluorescein angiography (FA), the gold standard, and optical coherence tomography angiography (OCTA) are used for evaluation [...] Read more.
Background/Objectives: Diabetic macular edema (DME) is the primary cause of vision loss in people with diabetes, and if untreated, it can result in irreversible macular damage. Both fluorescein angiography (FA), the gold standard, and optical coherence tomography angiography (OCTA) are used for evaluation of this disease. The objective of this study was to compare the diagnostic value of both. Methods: We conducted a comparative analysis of 98 patients aged 18–80 years with significant DME and best-corrected visual acuity ≥0.1 according to the Snellen chart. Participants underwent glycated hemoglobin blood test (HbA1c) and ophthalmological examinations, including OCTA and FA. OCTA 3 × 3 mm scans of superficial (SCP) and deep capillary plexus (DCP) along with FA scans were exported to the Gimp computer program. Size of the foveal avascular zone (FAZ), the number of visible microaneurysms (MAs), and ETDRS report number 11 classification of the images were assessed. Results: FAZ size differed significantly in superficial plexus (0.41 mm2), deep plexus (0.43 mm2) OCTA, and FA (0.38 mm2) (p < 0.001). FAZ size in DCP OCTA closely correlated with that of FA (τ = 0.79, p < 0.001). The total number of MAs visualized in the OCTA was significantly lower than in FA (p < 0.001). ETDRS classification of scans revealed that the level of consistency between the examinations was moderate to very strong. Conclusions: OCTA may be useful in evaluating macular ischemia. It is less sensitive in detecting MAs in DME eyes. FAZ has sharper boundaries and is larger when measured in OCTA. Poor glycemic control results in higher incidence of MAs in macula. Full article
(This article belongs to the Section Biomedical Optics)
39 pages, 2934 KiB  
Review
Phytocannabinoids as Novel SGLT2 Modulators for Renal Glucose Reabsorption in Type 2 Diabetes Management
by Raymond Rubianto Tjandrawinata, Dante Saksono Harbuwono, Sidartawan Soegondo, Nurpudji Astuti Taslim and Fahrul Nurkolis
Pharmaceuticals 2025, 18(8), 1101; https://doi.org/10.3390/ph18081101 - 24 Jul 2025
Viewed by 485
Abstract
Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target [...] Read more.
Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ9-Tetrahydrocannabinol or Δ9-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC50 values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article
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18 pages, 3248 KiB  
Article
Electrochemical Nanostructured Aptasensor for Direct Detection of Glycated Hemoglobin
by Luminita Fritea, Cosmin-Mihai Cotrut, Iulian Antoniac, Simona Daniela Cavalu, Luciana Dobjanschi, Angela Antonescu, Liviu Moldovan, Maria Domuta and Florin Banica
Int. J. Mol. Sci. 2025, 26(15), 7140; https://doi.org/10.3390/ijms26157140 - 24 Jul 2025
Viewed by 265
Abstract
Glycated hemoglobin (HbA1c) is an important biomarker applied for the diagnosis, evaluation, and management of diabetes; therefore, its accurate determination is crucial. In this study, an innovative nanoplatform was developed, integrating carbon nanotubes (CNTs) with enhanced hydrophilicity achieved through cyclodextrin (CD) functionalization, and [...] Read more.
Glycated hemoglobin (HbA1c) is an important biomarker applied for the diagnosis, evaluation, and management of diabetes; therefore, its accurate determination is crucial. In this study, an innovative nanoplatform was developed, integrating carbon nanotubes (CNTs) with enhanced hydrophilicity achieved through cyclodextrin (CD) functionalization, and combined with gold nanoparticles (AuNPs) electrochemically deposited onto a screen-printed carbon electrode. The nanomaterials significantly improved the analytical performance of the sensor due to their increased surface area and high electrical conductivity. This nanoplatform was employed as a substrate for the covalent attachment of thiolated ferrocene-labeled HbA1c specific aptamer through Au-S binding. The electrochemical signal of ferrocene was covered by a stronger oxidation peak of Fe2+ from the HbA1c structure, leading to the elaboration of a nanostructured aptasensor capable of the direct detection of HbA1c. The electrochemical aptasensor presented a very wide linear range (0.688–11.5%), an acceptable limit of detection (0.098%), and good selectivity and stability, being successfully applied on real samples. This miniaturized, simple, easy-to-use, and fast-responding aptasensor, requiring only a small sample volume, can be considered as a promising candidate for the efficient on-site determination of HbA1c. Full article
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14 pages, 1004 KiB  
Article
Beyond Weight Loss: Comparative Effects of Tirzepatide Plus Low-Energy Ketogenic Versus Low-Calorie Diet on Hepatic Steatosis and Stiffness in MASLD
by Luigi Schiavo, Biagio Santella, Monica Mingo, Gianluca Rossetti, Marcello Orio and Vincenzo Pilone
Nutrients 2025, 17(15), 2409; https://doi.org/10.3390/nu17152409 - 24 Jul 2025
Viewed by 453
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver condition globally, strongly linked to obesity, insulin resistance, and type 2 diabetes (T2D). Tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improves glycemic control and reduces body weight and the liver fat content in patients with obesity and T2D. However, its effect on liver-specific outcomes such as steatosis and fibrosis remains incompletely characterized. Low-energy ketogenic therapy (LEKT), a nutritional strategy characterized by carbohydrate restriction and nutritional ketosis, may enhance hepatic β-oxidation and reduce hepatic lipogenesis. To date, however, the combination of TZP and LEKT has not been studied in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the hepatic and metabolic effects of TZP combined with either LEKT or a conventional low-calorie diet (LCD) over a 12-week period. Methods: Sixty adult patients with MASLD undergoing TZP therapy were prospectively assigned to either an LEKT or a conventional LCD, with 30 participants per group. As primary endpoints, the controlled attenuation parameter (CAP, an index of hepatic steatosis) and liver stiffness measurement (LSM, an index of liver fibrosis) were assessed at the baseline and after 12 weeks using FibroScan®. Secondary outcomes included changes in body mass index (BMI), glycated hemoglobin (HbA1c), and liver enzymes. Adherence to both diet and pharmacological treatment, as well as tolerability, were systematically monitored throughout the intervention period. Results: Both groups showed significant reductions in body weight (TZP + LEKT, p = 0.0289; TZP + LCD, p = 0.0278), with no significant intergroup difference (p = 0.665). CAP and LSM improved significantly in both groups, but reductions were greater in the TZP + LEKT group (CAP −12.5%, p < 0.001; LSM −22.7%, p < 0.001) versus LCD (CAP −6.7%, p = 0.014; LSM −9.2%, p = 0.022). Between-group differences were statistically significant for both CAP (p = 0.01) and LSM (p = 0.03). Conclusions: Based on these preliminary findings, we support the hypothesis that the combination of TZP and LEKT may be superior to TZP with an LCD in reducing hepatic steatosis and stiffness in individuals with obesity. Full article
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16 pages, 614 KiB  
Article
Diet Therapy Improves Body Composition, Blood Pressure and Glycemic Status in Individuals Living with Type 2 Diabetes: A Prospective Cohort Study
by Collins Afriyie Appiah, Harriet Wugah, Janet Adede Carboo, Mary Amoako, Michael Akenteng Wiafe and Frank Ekow Atta Hayford
Obesities 2025, 5(3), 56; https://doi.org/10.3390/obesities5030056 - 17 Jul 2025
Viewed by 351
Abstract
Westernization of traditional diets has been implicated in the rising burden of overweight/obesity and type 2 diabetes, especially in developing countries. In recent times, diet therapy is increasingly being recognized as an essential component of diabetes care. This study assessed the effect of [...] Read more.
Westernization of traditional diets has been implicated in the rising burden of overweight/obesity and type 2 diabetes, especially in developing countries. In recent times, diet therapy is increasingly being recognized as an essential component of diabetes care. This study assessed the effect of diet therapy on body composition, antioxidant nutrient intake, and glycemic status in individuals living with type 2 diabetes (ILWT2D). In this prospective observational cohort study, 45 ILWT2D who were receiving diet therapy (personalized dietary counseling) in addition to standard medical treatment (intervention group) were compared with 45 ILWT2D receiving only standard medical treatment (comparator group). Antioxidant micronutrient intake was assessed using a 24-h dietary recall. Body composition indices, including body mass index (BMI), percentage body fat (%BF), and visceral fat (VF), were assessed. Participants’ fasting blood glucose (FBG), glycated hemoglobin (HbA1C) levels, and blood pressure (BP) were measured. All measurements were performed before and after a three-month period. There were significant improvements in BMI (27.8 ± 6.0 kg/m2 vs. 26.9 ± 5.5 kg/m2, p = 0.003), %BF (37.8 ± 11.9% vs. 35.5 ± 10.5%, p < 0.001), visceral fat (9.8 ± 3.4 vs. 9.1 ± 3.2, p < 0.001), systolic BP (136.9 ± 19.9 mmHg vs. 124.6 ± 13.0 mmHg, p < 0.001), FBG (8.8 ± 2.8 mmol/L vs. 6.7 ± 1.5 mmol/L, p < 0.001), and HbA1c (7.3 ± 1.0% vs. 6.4 ± 0.8%, p < 0.001) in the intervention group from baseline to endline, but not in the comparator group. In contrast, %BF increased within the comparator group (39.9 ± 7.8 vs. 40.7 ± 7.4; p = 0.029). Vitamin A intake increased significantly (227.5 ± 184.3 µg vs. 318.8 ± 274.7 µg, p = 0.038) within the intervention group but not in the comparator group (174.9 ± 154.3 µg, 193.7 ± 101.4 µg, p = 0.54). There were no significant changes in zinc, copper, selenium, and vitamin C intakes (p > 0.05) in the intervention group from the baseline to endline, unlike those in the comparator group who showed a significant increase in the intake of these nutrients. There was a significant increase in vitamin A intake among the ILWT2D who received dietary counseling as an intervention compared to those who did not. Additionally, the ILWT2D who received dietary counseling had significant improvements in their body composition (BMI, body fat, and visceral fat) and systolic blood pressure, compared to those who did not. The ILWT2D who received the intervention had significantly better glycemic control (FBG and HbA1c) than their counterparts who did not. Thus, this study suggests the potential of diet therapy as a viable non-pharmacological treatment approach for individuals living with type 2 diabetes. Full article
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13 pages, 1054 KiB  
Article
The Stress Hyperglycemia Ratio as a Predictor of Clinical Outcomes in Acute Pancreatitis: A Retrospective Cohort Study
by Ping Zhu, Xinwei Wang, Cheng Hu, Xiaoxin Zhang, Ziqi Lin, Tao Jin, Lan Li, Na Shi, Xinmin Yang, Wei Huang, Qing Xia and Lihui Deng
J. Clin. Med. 2025, 14(14), 4970; https://doi.org/10.3390/jcm14144970 - 14 Jul 2025
Viewed by 367
Abstract
Background: The stress hyperglycemia ratio (SHR) has emerged as a promising biomarker for assessing stress-induced hyperglycemia (SH) but has not been evaluated in patients with acute pancreatitis (AP). This study investigates the role of the SHR in predicting adverse clinical outcomes in [...] Read more.
Background: The stress hyperglycemia ratio (SHR) has emerged as a promising biomarker for assessing stress-induced hyperglycemia (SH) but has not been evaluated in patients with acute pancreatitis (AP). This study investigates the role of the SHR in predicting adverse clinical outcomes in patients with AP. Methods: Adult patients with AP who were admitted within 72 h of the onset of abdominal pain were screened in the database. Eligible patients with glycated hemoglobin (HbA1c) and blood glucose were analyzed. The SHR was calculated using admission blood glucose and HbA1c levels. Patients were categorized into four groups: SHR1 (≤1.03), SHR2 (1.04–1.25), SHR3 (1.26–1.46), and SHR4 (≥1.47). The primary outcome was persistent organ failure (POF). The secondary outcomes included acute peripancreatic fluid collection (APFC) and high-dependency unit/intensive care unit (HDU/ICU) admission. Restricted cubic spline (RCS) analysis was used to assess nonlinear associations and identify SHR threshold values. Univariable and multivariable logistic regression models were used to adjust for potential confounders and evaluate the relationship between the SHR and clinical outcomes. Results: A total of 486 patients with AP were included in this study, comprising 85 with POF and 401 without POF. SHR levels and severity were significantly correlated, with the highest quartile in the greatest proportion of severe acute pancreatitis (SAP). Higher SHR levels were significantly associated with an increased risk of POF, APFC, and HDU/ICU admission. RCS analysis revealed a nonlinear relationship between the SHR and APFC (p = 0.009). Based on the RCS and quartile analysis, SHR > 1.25 was identified as the threshold for increased risk. After adjusting for confounders, SHR > 1.25 remained independently associated with higher risks of POF (OR: 2.49, 95% CI: 1.39–4.46, p = 0.002), APFC (OR: 2.85, 95% CI: 1.92–4.24, p < 0.001), and ICU admission (OR: 1.74, 95% CI: 1.12–2.69, p = 0.013). Conclusions: The SHR is independently associated with adverse clinical outcomes in AP, including POF, APFC, and HDU/ICU admission. These findings suggest that the SHR may serve as a valuable biomarker for risk stratification and early intervention in AP management. Full article
(This article belongs to the Special Issue Acute Pancreatitis: Clinical Management and Treatment)
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17 pages, 1830 KiB  
Article
From Inflammation to Dysfunction: The Impact of a First Acute Pancreatitis Episode on Pancreatic Function
by Marina Balaban, Daniel Vasile Balaban, Iulia Enache, Ioan Cristian Nedelcu, Mariana Jinga and Cristian Gheorghe
J. Clin. Med. 2025, 14(14), 4932; https://doi.org/10.3390/jcm14144932 - 11 Jul 2025
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Abstract
Background/Objectives: The complexity of acute pancreatitis (AP) extends beyond its immediate complications. This study aimed to evaluate both exocrine and endocrine pancreatic dysfunctions following a first episode of AP, assessed at diagnosis and during a 6-month follow-up period. Methods: A prospective [...] Read more.
Background/Objectives: The complexity of acute pancreatitis (AP) extends beyond its immediate complications. This study aimed to evaluate both exocrine and endocrine pancreatic dysfunctions following a first episode of AP, assessed at diagnosis and during a 6-month follow-up period. Methods: A prospective analysis was conducted on patients with a first episode of AP. Pancreatic endocrine function was evaluated using fasting glucose and glycated hemoglobin (HbA1c) levels, while pancreatic exocrine function was assessed through fecal elastase-1 (FE-1) testing and the novel Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q). Results: Altogether, data from 112 time-point observations were analyzed with respect to endocrine and exocrine insufficiency after a first episode of AP, with 60 patients enrolled at baseline, 33 (55%) completing the first follow-up, and 19 (31.67%) completing the second follow-up. Based on PEI-Q scores, 75% of patients showed pancreatic exocrine insufficiency (PEI) at baseline. This rate decreased significantly to 33.3% at 2 months, with a further slight decline to 26.3% at 6 months. In contrast, FE-1 testing identified PEI in only 23% of patients at baseline, with a similar progressive improvement in time. Regarding the endocrine function, hyperglycemia was noted at baseline (mean serum glucose 120.75 ± 49.89 mg/dL), with a decreasing trend and normalization observed at follow-up. Conclusions: The pancreas has a remarkable recovery potential, with both exocrine and endocrine dysfunctions seen during the hospitalization for AP being transient. However, follow-up after AP is essential, as pancreatic insufficiency can significantly impact patients’ quality of life. Full article
(This article belongs to the Special Issue Acute Pancreatitis: Clinical Management and Treatment)
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10 pages, 462 KiB  
Article
Is the Presence of a Depressive Disorder a Risk Factor for Worse Metabolic Outcomes Among Patients with Type 2 Diabetes Treated with GLP-1 Analogs?
by Joana Nicolau, Pilar Sanchís, María Isabel Tamayo, Guadalupe Pérez-Bec, Guido Sfondrini, Mireia Grimalt and Lluís Masmiquel
Diabetology 2025, 6(7), 68; https://doi.org/10.3390/diabetology6070068 - 7 Jul 2025
Viewed by 394
Abstract
Background/Objectives: Type 2 diabetes mellitus (T2DM) is frequently associated with depressive disorder (DD), which negatively impacts glycemic control and overall metabolic outcomes. Recent evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert neuroprotective effects and modulate mood. Likewise, it is unknown [...] Read more.
Background/Objectives: Type 2 diabetes mellitus (T2DM) is frequently associated with depressive disorder (DD), which negatively impacts glycemic control and overall metabolic outcomes. Recent evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may exert neuroprotective effects and modulate mood. Likewise, it is unknown whether the presence of a DD, due to increased brain inflammation, could lead to a poorer response to GLP-1 RAs in terms of weight loss. This study evaluates the impact of DD on metabolic outcomes in individuals treated with GLP-1 RAs. Methods: We conducted a retrospective longitudinal study including 115 patients with T2DM treated with GLP-1 RAs for at least six months. DD was identified based on a documented clinical diagnosis, chronic antidepressant use, or a Beck Depression Inventory (BDI) score ≥16. Metabolic parameters, including glycated hemoglobin (HbA1c), fasting glucose, the body mass index (BMI), the waist circumference, and triglycerides, were compared between patients with and without DD. Results: Patients with DD had significantly higher baseline HbA1c (7.5% vs. 6.9%, p = 0.01), fasting glucose, and triglyceride levels. The waist circumference was also higher in the DD group (p = 0.001). However, no significant differences were observed in weight loss or BMI reductions following the GLP-1 RA treatment. Final HbA1c levels remained higher in the DD group (7.2% vs. 7.0%, p = 0.01). Conclusions: While DD is associated with a poorer baseline metabolic control in T2DM, it does not appear to impair the weight loss efficacy with GLP-1 RAs. However, patients with DD maintain higher post-treatment HbA1c levels, underscoring the need for integrated metabolic and psychiatric care in diabetes management. Full article
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14 pages, 613 KiB  
Systematic Review
Efficacy and Safety of GLP-1 Receptor Agonists and SGLT-2 Inhibitors in the Treatment of Diabetes Mellitus and Obesity in Liver Transplant Recipients: A Systematic Review
by Elena Garlatti Costa, Davide Bitetto, Ezio Fornasiere, Elisa Fumolo, Alberto Ferrarese and Pierluigi Toniutto
J. Clin. Med. 2025, 14(13), 4619; https://doi.org/10.3390/jcm14134619 - 30 Jun 2025
Viewed by 715
Abstract
Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) have significantly improved the management of diabetes mellitus (DM). In the general population, these drugs have additional benefits, such as weight loss, improvement of liver steatosis, and a cardiorenal protective effect. [...] Read more.
Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) have significantly improved the management of diabetes mellitus (DM). In the general population, these drugs have additional benefits, such as weight loss, improvement of liver steatosis, and a cardiorenal protective effect. However, data regarding the effects of GLP-1RAs or SGLT-2Is in the treatment of posttransplant diabetes mellitus (PTDM), obesity, and their potential cardiorenal protective effects in liver transplant (LT) recipients remain limited. PTDM increases the risk of developing graft steatosis, experiencing major cardiovascular events (MACEs), and developing chronic kidney disease and reduces long-term survival in LT recipients. The aim of this systematic review was to evaluate the efficacy and safety of GLP-1RAs and SGLT-2Is in the treatment of PTDM in LT recipients. Methods: Twelve retrospective studies (five specifically conducted in LT recipients and seven in mixed solid organ transplant cohorts, including LT recipients) that collectively enrolled 402 LT recipients treated with GLP-1RAs and/or SGLT-2Is for PTDM were selected. Results: GLP-1Ras and SGLT-2Is reduced serum glycated hemoglobin levels, body weight, and insulin requirements in LT recipients. Some studies reported benefits in reducing graft steatosis, improving renal function, and in reducing the occurrence of MACEs. Common adverse events included gastrointestinal symptoms, which rarely required treatment discontinuation. Conclusions: GLP-1RAs and SGLT-2Is represent promising treatment options for PTDM in LT recipients, offering metabolic benefits with manageable side effects. However, further prospective studies are needed to establish the long-term safety and efficacy, as well as the favorable impact on patient survival, of these drugs in LT recipients. Full article
(This article belongs to the Special Issue Up-to-Date Research in Liver Transplantation)
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