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18 pages, 2262 KiB

Open AccessArticle

Telomere Length as Both Cause and Consequence in Type 1 Diabetes: Evidence from Bidirectional Mendelian Randomization

by Guanping Wei, Ruiping Chen, Shupeng Liu, Shenhua Cai and Zhijun Feng

Biomedicines 2025, 13(4), 774; https://doi.org/10.3390/biomedicines13040774 - 22 Mar 2025

Viewed by 405

Abstract

Background/Objectives: Diabetes is the most prevalent metabolic disease globally, characterized by dysregulated glucose control and accompanied by multiple refractory complications. As a critical marker of cellular homeostasis, telomere length (TL) may be associated with the progression of diabetes. However, the causal relationship between [...] Read more.

Background/Objectives: Diabetes is the most prevalent metabolic disease globally, characterized by dysregulated glucose control and accompanied by multiple refractory complications. As a critical marker of cellular homeostasis, telomere length (TL) may be associated with the progression of diabetes. However, the causal relationship between diabetes and TL remains unclear, particularly whether cellular homeostasis imbalance acts as a consequence of diabetic complications or a precipitating factor in disease development. Methods: We performed a bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. Following the three core assumptions of MR analysis, we conducted quality control on all instrumental variables to ensure methodological rigor. The inverse variance weighted (IVW) method served as the primary analytical method, supplemented by additional MR methods to evaluate the significance of the results. Furthermore, we performed sensitivity analyses to ensure the reliability and robustness of the findings. Results: Forward analysis revealed that shortened TL significantly increases the risk of broadly defined Type 1 diabetes (T1D) and unspecified types of diabetes (p < 0.05). Additionally, we identified a positive causal relationship between TL and several diabetes-related complications, including co-morbidities, diabetic nephropathy, and diabetic ketoacidosis (p < 0.05). Interestingly, the reverse analysis demonstrated a positive causal effect of T1D and its complications on TL (p < 0.05); however, this effect disappeared after adjusting for insulin use (p > 0.05). Conclusions: Bidirectional MR analyses revealed a complex relationship between TL and T1D, where shortened telomeres increase T1D risk while T1D itself may trigger compensatory mechanisms affecting telomere maintenance, with insulin playing a crucial regulatory role in this relationship. These findings suggest telomere biology may be fundamentally involved in T1D pathogenesis and could inform future therapeutic approaches. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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16 pages, 1017 KiB

Open AccessArticle

Alpha-Lipoic Acid Treatment Reduces the Levels of Advanced End Glycation Products in Type 2 Diabetes Patients with Neuropathy

by Sára Csiha, Marcell Hernyák, Ágnes Molnár, Hajnalka Lőrincz, Mónika Katkó, György Paragh, Miklós Bodor, Mariann Harangi, Ferenc Sztanek and Eszter Berta

Biomedicines 2025, 13(2), 438; https://doi.org/10.3390/biomedicines13020438 - 11 Feb 2025

Cited by 1 | Viewed by 2651

Abstract

Background/Objectives: Type 2 diabetes mellitus (T2DM) and its macro- and microvascular complications are major health concerns with multiple factors, like advanced end glycation products (AGEs), in the background. AGEs induce long-lasting functional modification of the proteins and collagen in the vascular wall and [...] Read more.

Background/Objectives: Type 2 diabetes mellitus (T2DM) and its macro- and microvascular complications are major health concerns with multiple factors, like advanced end glycation products (AGEs), in the background. AGEs induce long-lasting functional modification of the proteins and collagen in the vascular wall and nerve tissue. We investigated the effect of alpha-lipoic acid (ALA) treatment on AGEs, soluble AGE receptor (sRAGE), the AGE/sRAGE ratio, and the parameters of endothelial dysfunction and their correlations. Methods: In our 6-month intervention study, 54 T2DM patients with neuropathy treated according to the actual therapeutic guidelines with unchanged oral antidiabetic drugs were included and treated by daily oral administration of 600 mg ALA. A total of 24 gender and age-matched T2DM patients without neuropathy served as controls. Results: In our work, we first demonstrated the attenuating effect of alpha lipoic acid therapy on AGEs in humans (11.89 (9.44–12.88) to 10.95 (9.81–12.82) AU/μg (p = 0.017)). sRAGE levels or the AGEs/sRAGE ratio were not affected by ALA treatment or by the presence of neuropathy. We found a correlation between the changes of AGEs and the improvement of current perception threshold and progranulin levels, and an inverse correlation with the change of asymmetric dimethylarginine. Conclusions: According to our results, ALA decreases AGEs, which may contribute to the clinically well-known beneficial effect in diabetic neuropathy and improvement of endothelial function. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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13 pages, 1651 KiB

Open AccessArticle

TrkB Receptor Antagonism Enhances Insulin Secretion and Increases Pancreatic Islet Size in Rats Fed a Cafeteria-Style Diet

by Jorge Agustín Velasco-Gutierrez, Elena Roces de Alvarez-Buylla, Sergio Montero, Alejandrina Rodríguez-Hernández, Saraí Limón Miranda, Karmina Martínez-Santillan, María del Rosario Álvarez-Valadez, Mónica Lemus, Alejandra Flores-Silva and Adolfo Virgen-Ortiz

Biomedicines 2025, 13(1), 126; https://doi.org/10.3390/biomedicines13010126 - 8 Jan 2025

Viewed by 963

Abstract

Background: In recent years, the role of neurotrophins and their receptors in peripheral tissues has been of great interest. At a metabolic level, the brain-derived neurotrophic factor (BDNF) and its receptor trkB have been reported to participate in insulin secretion from the pancreas [...] Read more.

Background: In recent years, the role of neurotrophins and their receptors in peripheral tissues has been of great interest. At a metabolic level, the brain-derived neurotrophic factor (BDNF) and its receptor trkB have been reported to participate in insulin secretion from the pancreas in response to increases in circulating blood glucose. Objetive: To determines the role of the BDNF-trkB pathway in insulin secretion and pancreatic morphology in rats fed a cafeteria-style diet for 16 weeks. Methods: For the study, male rats of the Wistar strain were divided into three groups as follows: (1) control group (standard diet), (2) CAF group (cafeteria-style diet) and (3) CAF group treated with ANA-12 (TrkB receptor antagonist). After 4 months of intervention, the glucose and insulin tolerance curves, serum insulin levels, body fat and hematoxylin-eosin staining pancreas were evaluated. Results: The results showed that the cafeteria-style diet induced an increase in the amount of body fat, alterations in the glucose tolerance curve, increased insulin circulation levels, increased HOMA indices and increased pancreatic islet size. The antagonism of the trkB receptor in the rats fed a cafeteria-style diet enhanced some effects such as the accumulation of body fat and insulin secretion and induced a greater increase in the pancreas islet size. Conclusions: Under conditions of cafeteria-style diet-induced obesity, the antagonism of the BDNF-trkB pathway had no enhanced effect on the increase in insulin secretion or pancreatic islet size. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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15 pages, 1910 KiB

Open AccessArticle

Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice

by Balzhima Shagdarova, Viktoria Melnikova, Valentina Kostenko, Mariya Konovalova, Vsevolod Zhuikov, Valery Varlamov and Elena Svirshchevskaya

Biomedicines 2024, 12(10), 2358; https://doi.org/10.3390/biomedicines12102358 - 16 Oct 2024

Cited by 1 | Viewed by 1430

Abstract

Background: The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for [...] Read more.

Background: The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Methods: Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. Results: For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Conclusions: Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi’s protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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13 pages, 1882 KiB

Open AccessArticle

Association of Circulating Markers of Microbial Translocation and Hepatic Inflammation with Liver Injury in Patients with Type 2 Diabetes

by Leila Gobejishvili, Vatsalya Vatsalya, Diana V. Avila, Yana B. Feygin, Craig J. McClain, Sriprakash Mokshagundam and Shirish Barve

Biomedicines 2024, 12(6), 1227; https://doi.org/10.3390/biomedicines12061227 - 31 May 2024

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Abstract

Background: Virtually the entire spectrum of liver disease is observed in association with type 2 diabetes mellitus (T2DM); indeed, T2DM is now the most common cause of liver disease in the U.S. We conducted a pilot study to investigate the relevance of increased [...] Read more.

Background: Virtually the entire spectrum of liver disease is observed in association with type 2 diabetes mellitus (T2DM); indeed, T2DM is now the most common cause of liver disease in the U.S. We conducted a pilot study to investigate the relevance of increased microbial translocation and systemic inflammation in the development of liver injury in patients with T2DM. Methods: Patients with T2DM (n = 17) and non-diabetic controls (NDC; n = 11) aged 25–80 yrs. participated in this study. Serum levels of endotoxin, calprotectin, soluble CD14 and CD163, and several inflammatory cytokines were measured. In addition to standard liver injury markers, ALT and AST, novel serum markers of liver injury, keratin 18 (K-18) M30 (apoptosis-associated caspase-cleaved keratin 18), and M65 (soluble keratin 18) were evaluated. Statistical analyses were performed using the Mann–Whitney test to assess differences between study groups. Pearson’s correlation analysis was performed to determine the strength of association between two variables using GraphPad Prism 9.5.0 software. Results: Patients with T2DM had significantly higher levels of sCD14 in comparison to NDC, suggesting an increase in gut permeability, microbial translocation, and monocyte/macrophage activation. Importantly, relevant to the ensuing inflammatory responses, the increase in sCD14 in patients with T2DM was accompanied by a significant increase in sCD163, a marker of hepatic Kupffer cell activation and inflammation. Further, a positive correlation was observed between sCD163 and endotoxin and sCD14 in T2DM patients but not in NDC. In association with these changes, keratin 18 (K-18)-based serum markers (M65 and M30) that reflect hepatocyte death were significantly higher in the T2DM group indicating ongoing liver injury. Notably, both M65 and M30 levels correlated with sCD14 and sCD163, suggesting that immune cell activation and hepatic inflammation may be linked to the development of liver injury in T2DM. Conclusions: These findings suggest that the pathogenic changes in the gut–liver axis, marked by increased microbial translocation, may be a major component in the etiology of hepatocyte inflammation and injury in patients with T2DM. However, larger longitudinal studies, including histological evidence, are needed to confirm these observations. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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14 pages, 5077 KiB

Open AccessArticle

The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes

by Johanna Barth, Ivonne Loeffler, Tzvetanka Bondeva, Marita Liebisch and Gunter Wolf

Biomedicines 2023, 11(9), 2475; https://doi.org/10.3390/biomedicines11092475 - 7 Sep 2023

Cited by 1 | Viewed by 1586

Abstract

Epigenetic alterations contribute to the pathogenesis of chronic diseases such as diabetes mellitus. Previous studies of our group showed that diabetic conditions reduce the trimethylation of H3K27 in podocytes in a NIPP1- (nuclear inhibitor of protein phosphatase 1) and EZH2- (enhancer of zeste [...] Read more.

Epigenetic alterations contribute to the pathogenesis of chronic diseases such as diabetes mellitus. Previous studies of our group showed that diabetic conditions reduce the trimethylation of H3K27 in podocytes in a NIPP1- (nuclear inhibitor of protein phosphatase 1) and EZH2- (enhancer of zeste homolog 2) dependent manner. It has been previously reported that in differentiated podocytes, hypoxia decreases the expression of slit diaphragm proteins and promotes foot process effacement, thereby contributing to the progression of renal disease. The exact mechanisms are, however, not completely understood. The aim of this study was to analyze the role of hypoxia and HIFs (hypoxia-inducible factor) on epigenetic changes in podocytes affecting NIPP1, EZH2 and H3K27me3, in vitro and in vivo. In vivo studies were performed with mice exposed to 10% systemic hypoxia for 3 days or injected with 3,4-DHB (dihydroxybenzoate), a PHD (prolyl hydroxylase) inhibitor, 24 h prior analyses. Immunodetection of H3K27me3, NIPP1 and EZH2 in glomerular podocytes revealed, to the best of our knowledge for the first time, that hypoxic conditions and pharmacological HIFs activation significantly reduce the expression of NIPP1 and EZH2 and diminish H3K27 trimethylation. These findings are also supported by in vitro studies using murine-differentiated podocytes. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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16 pages, 3474 KiB

Open AccessArticle

New Synthesized Activating Transcription Factor 3 Inducer SW20.1 Suppresses Resistin-Induced Metabolic Syndrome

by Tu T. Tran, Wei-Jan Huang, Heng Lin and Hsi-Hsien Chen

Biomedicines 2023, 11(6), 1509; https://doi.org/10.3390/biomedicines11061509 - 23 May 2023

Cited by 1 | Viewed by 2834

Abstract

Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) [...] Read more.

Obesity is an emerging concern globally with increasing prevalence. Obesity is associated with many diseases, such as cardiovascular disease, dyslipidemia, and cancer. Thus, effective new antiobesity drugs should be urgently developed. We synthesized SW20.1, a compound that induces activating transcription factor 3 (ATF3) expression. The results of Oil Red O staining and quantitative real-time polymerase chain reaction revealed that SW20.1 was more effective in reducing lipid accumulation in 3T3-L1 preadipocytes than the previously synthesized ST32db, and that it inhibited the expression of the genes involved in adipogenesis and lipogenesis. A chromatin immunoprecipitation assay indicated that SW20.1 inhibited adipogenesis and lipogenesis by binding to the upstream promoter region of resistin at two sites (−2861/−2854 and −241/−234). In mice, the intraperitoneal administration of SW20.1 reduced body weight, white adipocyte weight in different regions, serum cholesterol levels, adipogenesis-related gene expression, hepatic steatosis, and serum resistin levels. Overall, SW20.1 exerts antiobesity effects by inhibiting resistin through the ATF3 pathway. Our study results indicate that SW20.1 is a promising therapeutic drug for diet-induced obesity. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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13 pages, 2871 KiB

Open AccessArticle

The Relationship between Elevated Homocysteine and Metabolic Syndrome in a Community-Dwelling Middle-Aged and Elderly Population in Taiwan

by Yu-Lin Shih, Chin-Chuan Shih, Tzu-Cheng Huang and Jau-Yuan Chen

Biomedicines 2023, 11(2), 378; https://doi.org/10.3390/biomedicines11020378 - 27 Jan 2023

Cited by 6 | Viewed by 2607

Abstract

(1) Background: Metabolic syndrome has become a serious health problem in society. Homocysteine is a biomarker for cardiovascular disease. We investigated the relationship between homocysteine levels and metabolic syndrome. (2) Methods: A total of 398 middle-aged and elderly individuals were included in our [...] Read more.

(1) Background: Metabolic syndrome has become a serious health problem in society. Homocysteine is a biomarker for cardiovascular disease. We investigated the relationship between homocysteine levels and metabolic syndrome. (2) Methods: A total of 398 middle-aged and elderly individuals were included in our study. First, we divided the participants into two groups: the metabolic syndrome group and the nonmetabolic syndrome group. Second, according to tertiles of homocysteine levels from low to high, the participants were divided into first, second, and third groups. Pearson’s correlation was then calculated for homocysteine levels and metabolic factors. Scatterplots are presented. Finally, the risk of metabolic syndrome in the second and third groups compared with the first group was assessed by multivariate logistic regression. (3) Results: In our study, the metabolic syndrome group had higher homocysteine levels, and the participants in the third group were more likely to have metabolic syndrome. Multivariate logistic regression revealed that the third group, which had the highest homocysteine level, was associated with metabolic syndrome with an odds ratio of 2.32 compared with the first group after adjusting for risk factors. (4) Conclusions: We concluded that high plasma homocysteine levels were independently associated with MetS in our study population. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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Review

Jump to: Research

17 pages, 1193 KiB

Open AccessReview

Metabolic Syndrome, Kidney-Related Adiposity, and Kidney Microcirculation: Unraveling the Damage

by Kyu Won Jang, Jin Hur, Dong Won Lee and Seo Rin Kim

Biomedicines 2024, 12(12), 2706; https://doi.org/10.3390/biomedicines12122706 - 27 Nov 2024

Cited by 1 | Viewed by 1495

Abstract

Metabolic syndrome (MetS) is a cluster of interrelated risk factors, including insulin resistance, hypertension, dyslipidemia, and visceral adiposity, all of which contribute to kidney microvascular injury and the progression of chronic kidney disease (CKD). However, the specific impact of each component of MetS [...] Read more.

Metabolic syndrome (MetS) is a cluster of interrelated risk factors, including insulin resistance, hypertension, dyslipidemia, and visceral adiposity, all of which contribute to kidney microvascular injury and the progression of chronic kidney disease (CKD). However, the specific impact of each component of MetS on kidney microcirculation remains unclear. Given the increasing prevalence of obesity, understanding how visceral fat—particularly fat surrounding the kidneys—affects kidney microcirculation is critical. This review examines the consequences of visceral obesity and other components of MetS on renal microcirculation. These kidney-related fat deposits can contribute to the mechanical compression of renal vasculature, promote inflammation and oxidative stress, and induce endothelial dysfunction, all of which accelerate kidney damage. Each factor of MetS initiates a series of hemodynamic and metabolic disturbances that impair kidney microcirculation, leading to vascular remodeling and microvascular rarefaction. The review concludes by discussing therapeutic strategies targeting the individual components of MetS, which have shown promise in alleviating inflammation and oxidative stress. Integrated approaches that address both of the components of MetS and kidney-related adiposity may improve renal outcomes and slow the progression of CKD. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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28 pages, 8191 KiB

Open AccessReview

Metabolic Side Effects from Antipsychotic Treatment with Clozapine Linked to Aryl Hydrocarbon Receptor (AhR) Activation

by Karin Fehsel

Biomedicines 2024, 12(10), 2294; https://doi.org/10.3390/biomedicines12102294 - 10 Oct 2024

Viewed by 2176

Abstract

Metabolic syndrome (MetS) is the most common adverse drug reaction from psychiatric pharmacotherapy. Neuroreceptor blockade by the antipsychotic drug clozapine induces MetS in about 30% of patients. Similar to insulin resistance, clozapine impedes Akt kinase activation, leading to intracellular glucose and glutathione depletion. [...] Read more.

Metabolic syndrome (MetS) is the most common adverse drug reaction from psychiatric pharmacotherapy. Neuroreceptor blockade by the antipsychotic drug clozapine induces MetS in about 30% of patients. Similar to insulin resistance, clozapine impedes Akt kinase activation, leading to intracellular glucose and glutathione depletion. Additional cystine shortage triggers tryptophan degradation to kynurenine, which is a well-known AhR ligand. Ligand-bound AhR downregulates the intracellular iron pool, thereby increasing the risk of mitochondrial dysfunction. Scavenging iron stabilizes the transcription factor HIF-1, which shifts the metabolism toward transient glycolysis. Furthermore, the AhR inhibits AMPK activation, leading to obesity and liver steatosis. Increasing glucose uptake by AMPK activation prevents dyslipidemia and liver damage and, therefore, reduces the risk of MetS. In line with the in vitro results, feeding experiments with rats revealed a disturbed glucose-/lipid-/iron-metabolism from clozapine treatment with hyperglycemia and hepatic iron deposits in female rats and steatosis and anemia in male animals. Decreased energy expenditure from clozapine treatment seems to be the cause of the fast weight gain in the first weeks of treatment. In patients, this weight gain due to neuroleptic treatment correlates with an improvement in psychotic syndromes and can even be used to anticipate the therapeutic effect of the treatment. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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16 pages, 1041 KiB

Open AccessReview

Genetic Insights into Age-Related Macular Degeneration

by Bhumika, Nalini S. Bora and Puran S. Bora

Biomedicines 2024, 12(7), 1479; https://doi.org/10.3390/biomedicines12071479 - 4 Jul 2024

Cited by 9 | Viewed by 3435

Abstract

One of the major causes of vision impairment among elderly people in developed nations is age-related macular degeneration (AMD). The distinctive features of AMD are the accumulation of extracellular deposits called drusen and the gradual deterioration of photoreceptors and nearby tissues in the [...] Read more.

One of the major causes of vision impairment among elderly people in developed nations is age-related macular degeneration (AMD). The distinctive features of AMD are the accumulation of extracellular deposits called drusen and the gradual deterioration of photoreceptors and nearby tissues in the macula. AMD is a complex and multifaceted disease influenced by several factors such as aging, environmental risk factors, and a person’s genetic susceptibility to the condition. The interaction among these factors leads to the initiation and advancement of AMD, where genetic predisposition plays a crucial role. With the advent of high-throughput genotyping technologies, many novel genetic loci associated with AMD have been identified, enhancing our knowledge of its genetic architecture. The common genetic variants linked to AMD are found on chromosome 1q32 (in the complement factor H gene) and 10q26 (age-related maculopathy susceptibility 2 and high-temperature requirement A serine peptidase 1 genes) loci, along with several other risk variants. This review summarizes the common genetic variants of complement pathways, lipid metabolism, and extracellular matrix proteins associated with AMD risk, highlighting the intricate pathways contributing to AMD pathogenesis. Knowledge of the genetic underpinnings of AMD will allow for the future development of personalized diagnostics and targeted therapeutic interventions, paving the way for more effective management of AMD and improved outcomes for affected individuals. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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13 pages, 767 KiB

Open AccessReview

Prediabetes and Cardiometabolic Risk: The Need for Improved Diagnostic Strategies and Treatment to Prevent Diabetes and Cardiovascular Disease

by Juan Carlos Lizarzaburu-Robles, William H. Herman, Alonso Garro-Mendiola, Alba Galdón Sanz-Pastor and Oscar Lorenzo

Biomedicines 2024, 12(2), 363; https://doi.org/10.3390/biomedicines12020363 - 4 Feb 2024

Cited by 5 | Viewed by 3774

Abstract

The progression from prediabetes to type-2 diabetes depends on multiple pathophysiological, clinical, and epidemiological factors that generally overlap. Both insulin resistance and decreased insulin secretion are considered to be the main causes. The diagnosis and approach to the prediabetic patient are heterogeneous. There [...] Read more.

The progression from prediabetes to type-2 diabetes depends on multiple pathophysiological, clinical, and epidemiological factors that generally overlap. Both insulin resistance and decreased insulin secretion are considered to be the main causes. The diagnosis and approach to the prediabetic patient are heterogeneous. There is no agreement on the diagnostic criteria to identify prediabetic subjects or the approach to those with insufficient responses to treatment, with respect to regression to normal glycemic values or the prevention of complications. The stratification of prediabetic patients, considering the indicators of impaired fasting glucose, impaired glucose tolerance, or HbA1c, can help to identify the sub-phenotypes of subjects at risk for T2DM. However, considering other associated risk factors, such as impaired lipid profiles, or risk scores, such as the Finnish Diabetes Risk Score, may improve classification. Nevertheless, we still do not have enough information regarding cardiovascular risk reduction. The sub-phenotyping of subjects with prediabetes may provide an opportunity to improve the screening and management of cardiometabolic risk in subjects with prediabetes. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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45 pages, 2553 KiB

Open AccessReview

Targeting the Metabolic Paradigms in Cancer and Diabetes

by Mira Bosso, Dania Haddad, Ashraf Al Madhoun and Fahd Al-Mulla

Biomedicines 2024, 12(1), 211; https://doi.org/10.3390/biomedicines12010211 - 17 Jan 2024

Cited by 12 | Viewed by 3814

Abstract

Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the [...] Read more.

Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the contrasting roles of oxidative phosphorylation (OXPHOS) and glycolysis as primary energy-generating pathways within cells. Building on earlier research, we explore how a shift towards one pathway over the other serves as a foundational aspect in the development of cancer and T2D. Unlike previous reviews, we posit that this shift may occur in seemingly opposing yet complementary directions, akin to the Yin and Yang concept. These metabolic fluctuations reveal an intricate network of underlying defective signaling pathways, orchestrating the pathogenesis and progression of each disease. The Warburg phenomenon, characterized by the prevalence of aerobic glycolysis over minimal to no OXPHOS, emerges as the predominant metabolic phenotype in cancer. Conversely, in T2D, the prevailing metabolic paradigm has traditionally been perceived in terms of discrete irregularities rather than an OXPHOS-to-glycolysis shift. Throughout T2D pathogenesis, OXPHOS remains consistently heightened due to chronic hyperglycemia or hyperinsulinemia. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, featuring differential tissue-specific alterations that affect OXPHOS. Recent findings suggest that addressing the metabolic imbalance in both cancer and diabetes could offer an effective treatment strategy. Numerous pharmaceutical and nutritional modalities exhibiting therapeutic effects in both conditions ultimately modulate the OXPHOS–glycolysis axis. Noteworthy nutritional adjuncts, such as alpha-lipoic acid, flavonoids, and glutamine, demonstrate the ability to reprogram metabolism, exerting anti-tumor and anti-diabetic effects. Similarly, pharmacological agents like metformin exhibit therapeutic efficacy in both T2D and cancer. This review discusses the molecular mechanisms underlying these metabolic shifts and explores promising therapeutic strategies aimed at reversing the metabolic imbalance in both disease scenarios. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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35 pages, 3280 KiB

Open AccessReview

Valproate-Induced Metabolic Syndrome

by Natalia A. Shnayder, Violetta V. Grechkina, Vera V. Trefilova, Ilya S. Efremov, Evgenia A. Dontceva, Ekaterina A. Narodova, Marina M. Petrova, Irina A. Soloveva, Liia E. Tepnadze, Polina A. Reznichenko, Mustafa Al-Zamil, Gulnara I. Altynbekova, Anna I. Strelnik and Regina F. Nasyrova

Biomedicines 2023, 11(5), 1499; https://doi.org/10.3390/biomedicines11051499 - 22 May 2023

Cited by 9 | Viewed by 4426

Abstract

Valproic acid (VPA) and its salts (sodium calcium magnesium and orotic) are psychotropic drugs that are widely used in neurology and psychiatry. The long-term use of VPA increases the risk of developing adverse drug reactions (ADRs), among which metabolic syndrome (MetS) plays a [...] Read more.

Valproic acid (VPA) and its salts (sodium calcium magnesium and orotic) are psychotropic drugs that are widely used in neurology and psychiatry. The long-term use of VPA increases the risk of developing adverse drug reactions (ADRs), among which metabolic syndrome (MetS) plays a special role. MetS belongs to a cluster of metabolic conditions such as abdominal obesity, high blood pressure, high blood glucose, high serum triglycerides, and low serum high-density lipoprotein. Valproate-induced MetS (VPA-MetS) is a common ADR that needs an updated multidisciplinary approach to its prevention and diagnosis. In this review, we consider the results of studies of blood (serum and plasma) and the urinary biomarkers of VPA-MetS. These metabolic biomarkers may provide the key to the development of a new multidisciplinary personalized strategy for the prevention and diagnosis of VPA-MetS in patients with neurological diseases, psychiatric disorders, and addiction diseases. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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23 pages, 755 KiB

Open AccessEditor’s ChoiceReview

Non-Alcoholic Fatty Liver Disease or Type 2 Diabetes Mellitus—The Chicken or the Egg Dilemma

by Marcin Kosmalski, Agnieszka Śliwińska and Józef Drzewoski

Biomedicines 2023, 11(4), 1097; https://doi.org/10.3390/biomedicines11041097 - 4 Apr 2023

Cited by 23 | Viewed by 7394

Abstract

In clinical practice, we often deal with patients who suffer from non-alcoholic fatty liver disease (NAFLD) concurrent with type 2 diabetes mellitus (T2DM). The etiopathogenesis of NAFLD is mainly connected with insulin resistance (IR) and obesity. Similarly, the latter patients are in the [...] Read more.

In clinical practice, we often deal with patients who suffer from non-alcoholic fatty liver disease (NAFLD) concurrent with type 2 diabetes mellitus (T2DM). The etiopathogenesis of NAFLD is mainly connected with insulin resistance (IR) and obesity. Similarly, the latter patients are in the process of developing T2DM. However, the mechanisms of NAFLD and T2DM coexistence have not been fully elucidated. Considering that both diseases and their complications are of epidemic proportions and significantly affect the length and quality of life, we aimed to answer which of these diseases appears first and thereby highlight the need for their diagnosis and treatment. To address this question, we present and discuss the epidemiological data, diagnoses, complications and pathomechanisms of these two coexisting metabolic diseases. This question is difficult to answer due to the lack of a uniform procedure for NAFLD diagnosis and the asymptomatic nature of both diseases, especially at their beginning stages. To conclude, most researchers suggest that NAFLD appears as the first disease and starts the sequence of circumstances leading ultimately to the development of T2DM. However, there are also data suggesting that T2DM develops before NAFLD. Despite the fact that we cannot definitively answer this question, it is very important to bring the attention of clinicians and researchers to the coexistence of NAFLD and T2DM in order to prevent their consequences. Full article

(This article belongs to the Special Issue Advanced Research in Metabolic Syndrome)

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