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Metabolites
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Metabolism in Diabetes Progression and Diabetic Complications
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Metabolism in Diabetes Progression and Diabetic Complications

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 11185

Special Issue Editor

Prof. Dr. Jan W. Eriksson

E-Mail Website
Guest Editor
Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, 751 85 Uppsala, Sweden
Interests: diabetology; metabolism; insulin resistance; adipose tissue in diabetes; diabetic complications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

About 500 million people worldwide have diabetes. It is a major burden both to those affected and to society as a whole. In recent years, the options for prevention, treatment and care have markedly improved. Nonetheless, diabetes and its comorbidities, in particular chronic organ complications, still are linked to a decreased quality of life, disabilities, premature death and major health-economic challenges to society. It is paramount to further improve our tools to counter the progression of hormonal and metabolic derangements of diabetes as well as of macro- and microvascular damage that eventually leads to debilitating conditions, such as cerebrovascular, heart, kidney, nerve and eye disease.

In this Special Issue on ‘Metabolism in Diabetes Progression and Diabetic Complications’, we aim to collect several important papers on diabetes and its complications, focusing on markers, mechanisms and therapeutic principles that will improve understanding and management of diabetes progression. The scope includes the early development of diabetes, continuing alterations in the regulation and action of insulin and other hormones as well as the development of chronic diabetes complications and other comorbidities. The contributions may be in the format of original papers as well as reviews. We welcome your submissions during the period of March–December 2023.

Prof. Dr. Jan W. Eriksson
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • diabetes
  • diabetology
  • insulin resistance
  • hormone secretion
  • adipose tissue in diabetes
  • metabolic derangements
  • diabetic complications
  • chronic organ complications

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Published Papers (5 papers)

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Research

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17 pages, 7899 KiB  
Article
Metabolomic Profiling of Adipose Tissue in Type 2 Diabetes: Associations with Obesity and Insulin Resistance
by Argyri Mathioudaki, Giovanni Fanni, Jan W. Eriksson and Maria J. Pereira
Metabolites 2024, 14(8), 411; https://doi.org/10.3390/metabo14080411 - 26 Jul 2024
Viewed by 1058
Abstract
The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) [...] Read more.
The global prevalence of Type 2 Diabetes (T2D) poses significant public health challenges due to its associated severe complications. Insulin resistance is central to T2D pathophysiology, particularly affecting adipose tissue function. This cross-sectional observational study investigates metabolic alterations in subcutaneous adipose tissue (SAT) associated with T2D to identify potential therapeutic targets. We conducted a comprehensive metabolomic analysis of SAT from 40 participants (20 T2D, 20 ND-T2D), matched for sex, age, and BMI (Body Mass Index). Metabolite quantification was performed using GC/MS and LC/MS/MS platforms. Correlation analyses were conducted to explore associations between metabolites and clinical parameters. We identified 378 metabolites, including significant elevations in TCA cycle (tricarboxylic acid cycle) intermediates, branched-chain amino acids (BCAAs), and carbohydrates, and a significant reduction in the nucleotide-related metabolites in T2D subjects compared to those without T2D. Obesity exacerbated these alterations, particularly in amino acid metabolism. Adipocyte size negatively correlated with BCAAs, while adipocyte glucose uptake positively correlated with unsaturated fatty acids and glycerophospholipids. Our findings reveal distinct metabolic dysregulation in adipose tissue in T2D, particularly in energy metabolism, suggesting potential therapeutic targets for improving insulin sensitivity and metabolic health. Future studies should validate these findings in larger cohorts and explore underlying mechanisms to develop targeted interventions. Full article
(This article belongs to the Special Issue Metabolism in Diabetes Progression and Diabetic Complications)
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14 pages, 1314 KiB  
Article
Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study
by Rui Shen, Chengliang Pan, Guiwen Yi, Zhiyang Li, Chen Dong, Jian Yu, Jiangmei Zhang, Qian Dong, Kunwu Yu and Qiutang Zeng
Metabolites 2024, 14(7), 385; https://doi.org/10.3390/metabo14070385 - 13 Jul 2024
Viewed by 1090
Abstract
Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of [...] Read more.
Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096–1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07–11.99%), the fatty acid group (4.78–12.82%), and the cholesterol group (3.64–11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D. Full article
(This article belongs to the Special Issue Metabolism in Diabetes Progression and Diabetic Complications)
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14 pages, 926 KiB  
Article
Metabolites Potentially Derived from Gut Microbiota Associated with Podocyte, Proximal Tubule, and Renal and Cerebrovascular Endothelial Damage in Early Diabetic Kidney Disease in T2DM Patients
by Lavinia Balint, Carmen Socaciu, Andreea Iulia Socaciu, Adrian Vlad, Florica Gadalean, Flaviu Bob, Oana Milas, Octavian Marius Cretu, Anca Suteanu-Simulescu, Mihaela Glavan, Silvia Ienciu, Maria Mogos, Dragos Catalin Jianu, Sorin Ursoniu, Victor Dumitrascu, Daliborca Vlad, Roxana Popescu and Ligia Petrica
Metabolites 2023, 13(8), 893; https://doi.org/10.3390/metabo13080893 - 28 Jul 2023
Cited by 3 | Viewed by 1916
Abstract
Complications due to type 2 diabetes mellitus (T2DM) such as diabetic kidney disease (DKD) and cerebral small vessel disease (CSVD) have a powerful impact on mortality and morbidity. Our current diagnostic markers have become outdated as T2DM-related complications continue to develop. The aim [...] Read more.
Complications due to type 2 diabetes mellitus (T2DM) such as diabetic kidney disease (DKD) and cerebral small vessel disease (CSVD) have a powerful impact on mortality and morbidity. Our current diagnostic markers have become outdated as T2DM-related complications continue to develop. The aim of the investigation was to point out the relationship between previously selected metabolites which are potentially derived from gut microbiota and indicators of endothelial, proximal tubule (PT), and podocyte dysfunction, and neurosonological indices. The study participants were 20 healthy controls and 90 T2DM patients divided into three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Serum and urine metabolites were determined by untargeted and targeted metabolomic techniques. The markers of endothelial, PT and podocyte dysfunction were assessed by ELISA technique, and the neurosonological indices were provided by an ultrasound device with high resolution (MYLAB 8-ESAOTE Italy). The descriptive statistical analysis was followed by univariable and multivariable linear regression analyses. In conclusion, in serum, arginine (sArg), butenoylcarnitine (sBCA), and indoxyl sulfate (sIS) expressed a biomarker potential in terms of renal endothelial dysfunction and carotid atherosclerosis, whereas sorbitol (sSorb) may be a potential biomarker of blood–brain barrier (BBB) dysfunction. In urine, BCA and IS were associated with markers of podocyte damage, whereas PCS correlated with markers of PT dysfunction. Full article
(This article belongs to the Special Issue Metabolism in Diabetes Progression and Diabetic Complications)

Review

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20 pages, 395 KiB  
Review
Therapeutic Potentials of Reducing Liver Fat in Non-Alcoholic Fatty Liver Disease: Close Association with Type 2 Diabetes
by Georgios Tsamos, Dimitra Vasdeki, Theocharis Koufakis, Vassiliki Michou, Kali Makedou and Georgios Tzimagiorgis
Metabolites 2023, 13(4), 517; https://doi.org/10.3390/metabo13040517 - 4 Apr 2023
Cited by 10 | Viewed by 3697
Abstract
Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular [...] Read more.
Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular carcinoma. It affects almost 30% of adults in the general population and up to 70% of people with type 2 diabetes (T2DM), sharing common pathogenetic pathways with the latter. In addition, NAFLD is closely related to obesity, which acts in synergy with other predisposing conditions, including alcohol consumption, provoking progressive and insidious liver damage. Among the most potent risk factors for accelerating the progression of NAFLD to fibrosis or cirrhosis, diabetes stands out. Despite the rapid rise in NAFLD rates, identifying the optimal treatment remains a challenge. Interestingly, NAFLD amelioration or remission appears to be associated with a lower risk of T2DM, indicating that liver-centric therapies could reduce the risk of developing T2DM and vice versa. Consequently, assessing NAFLD requires a multidisciplinary approach to identify and manage this multisystemic clinical entity early. With the continuously emerging new evidence, innovative therapeutic strategies are being developed for the treatment of NAFLD, prioritizing a combination of lifestyle changes and glucose-lowering medications. Based on recent evidence, this review scrutinizes all practical and sustainable interventions to achieve a resolution of NAFLD through a multimodal approach. Full article
(This article belongs to the Special Issue Metabolism in Diabetes Progression and Diabetic Complications)

Other

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7 pages, 642 KiB  
Case Report
Balancing Risks and Benefits: Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Diabetic Ketoacidosis
by Jan P. Kleinjan, Justin Blom, André P. van Beek, Hjalmar R. Bouma and Peter R. van Dijk
Metabolites 2024, 14(3), 162; https://doi.org/10.3390/metabo14030162 - 13 Mar 2024
Viewed by 2278
Abstract
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a new class of drugs that have been proven beneficial in the management of diabetes, chronic kidney disease, and heart failure and in the mitigation of cardiovascular risk. The benefits of SGLT2i therapy have led to the rapid [...] Read more.
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a new class of drugs that have been proven beneficial in the management of diabetes, chronic kidney disease, and heart failure and in the mitigation of cardiovascular risk. The benefits of SGLT2i therapy have led to the rapid adoption of these drugs in clinical guidelines. Since the introduction of these drugs, concerns have arisen, as diabetic ketoacidosis (DKA) unexpectedly occurred in patients treated with SGLT2i. DKA is an infrequent but serious complication of SGLT2i therapy, and is potentially preventable. The risk factors for the development of SGLT2i-associated DKA are inappropriate dose reductions of insulin, the dietary restriction of carbohydrates, and factors that may increase insulin demand such as excessive alcohol intake and major surgery. Moreover, the risk of SGLT2i-associated DKA is higher in persons with type 1 diabetes. It is crucial that both patients and healthcare providers are aware of the risks of SGLT2i-associated DKA. In an effort to encourage safe prescribing of this effective class of drugs, we present two cases that illustrate the risks of SGLT2i therapy with regard to the development of DKA. Full article
(This article belongs to the Special Issue Metabolism in Diabetes Progression and Diabetic Complications)
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