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Biomedicines
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Pathological Mechanisms in Diabetes
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Pathological Mechanisms in Diabetes

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 50230

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Maria Grau

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Guest Editor
Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
Interests: eHealth; preventive medicine; public health; noncommunicable diseases; empowerment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes constitutes a worldwide public health problem that affected 463 million people (9.3% of the world’s population) in 2019. Recent projections suggest that this prevalence is likely to increase in the next 20 years, affecting 592 million people (10.1%) in 2035. The average life expectancy of a 50-year-old individual with diabetes is 6 years shorter than it would be without the disease. Indeed, diabetes has been associated with premature death from cardiovascular diseases (coronary heart disease, stroke, and heart failure), several cancers (liver, colorectal, and lung), infections (COVID-19), and other diseases (chronic obstructive pulmonary disease and liver and kidney disease). The scope of this Special Issue is to unravel the molecular mechanisms involved in the association between diabetes and comorbidities and to describe the clinical and therapeutic implications of such associations.

Dr. Maria Grau
Guest Editor

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Keywords

  • cardiovascular diseases/complications
  • cardiovascular diseases/mortality
  • chronic kidney disease/complications
  • chronic kidney disease/mortality
  • COPD/complications
  • COPD/mortality
  • COVID-19
  • diabetes mellitus, type 1/complications
  • diabetes mellitus, type 1/mortality
  • diabetes mellitus, type 2/complications
  • diabetes mellitus, type 2/mortality
  • liver disease/complications
  • liver disease/mortality
  • neoplasms/complications
  • neoplasms/mortality
  • SARS-CoV-2

Published Papers (16 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 209 KiB  
Editorial
Diabetes: A Multifaceted Disorder
by María Grau and Carles Pericas
Biomedicines 2022, 10(7), 1698; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071698 - 14 Jul 2022
Cited by 1 | Viewed by 1372
Abstract
Diabetes is a chronic disease associated with increased morbidity and mortality from cardiovascular diseases cancer, chronic obstructive pulmonary disease, and kidney or liver disease [...] Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)

Research

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13 pages, 2232 KiB  
Article
Genetic Ablation of the Nutrient Sensor Ogt in Endocrine Progenitors Is Dispensable for β-Cell Development but Essential for Maintenance of β-Cell Mass
by Alicia Wong, Brian Akhaphong, Daniel Baumann and Emilyn U. Alejandro
Biomedicines 2023, 11(1), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11010105 - 30 Dec 2022
Viewed by 1493
Abstract
Previously we utilized a murine model to demonstrate that Ogt deletion in pancreatic progenitors (OgtKOPanc) causes pancreatic hypoplasia, partly mediated by a reduction in the Pdx1-expressing pancreatic progenitor pool. Here, we continue to explore the role of Ogt in pancreas development [...] Read more.
Previously we utilized a murine model to demonstrate that Ogt deletion in pancreatic progenitors (OgtKOPanc) causes pancreatic hypoplasia, partly mediated by a reduction in the Pdx1-expressing pancreatic progenitor pool. Here, we continue to explore the role of Ogt in pancreas development by deletion of Ogt in the endocrine progenitors (OgtKOEndo). At birth OgtKOEndo, were normoglycemic and had comparable pancreas weight and α-cell, and β-cell mass to littermate controls. At postnatal day 23, OgtKOEndo displayed wide ranging but generally elevated blood glucose levels, with histological analyses showing aberrant islet architecture with α-cells invading the islet core. By postnatal day 60, these mice were overtly diabetic and showed significant loss of both α-cell and β-cell mass. Together, these results highlight the indispensable role of Ogt in maintenance of β-cell mass and glucose homeostasis. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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21 pages, 4002 KiB  
Article
Fecal Bacterial Community and Metagenome Function in Asians with Type 2 Diabetes, According to Enterotypes
by Xuangao Wu and Sunmin Park
Biomedicines 2022, 10(11), 2998; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10112998 - 21 Nov 2022
Cited by 6 | Viewed by 2445
Abstract
The role of gut microbes has been suggested in type 2 diabetes (T2DM) risk. However, their results remain controversial. We hypothesized that Asians with T2DM had different fecal bacterial compositions, co-abundance networks, and metagenome functions compared to healthy individuals, according to enterotypes. This [...] Read more.
The role of gut microbes has been suggested in type 2 diabetes (T2DM) risk. However, their results remain controversial. We hypothesized that Asians with T2DM had different fecal bacterial compositions, co-abundance networks, and metagenome functions compared to healthy individuals, according to enterotypes. This hypothesis was examined using the combined gut microbiota data from human fecal samples from previous studies. The human fecal bacterial FASTA/Q files from 36 different T2DM studies in Asians were combined (healthy, n = 3378; T2DM, n = 551), and operational taxonomic units (OTUs) and their counts were obtained using qiime2 tools. In the machine learning approaches, fecal bacteria rich in T2DM were found. They were separated into two enterotypes, Lachnospiraceae (ET-L) and Prevotellaceae (ET-P). The Shannon and Chao1 indices, representing α-diversity, were significantly lower in the T2DM group compared to the healthy group in ET-L (p < 0.05) but not in ET-P. In the Shapley additive explanations analysis of ET-L, Escherichia fergusonii, Collinsella aerofaciens, Streptococcus vestibularis, and Bifidobacterium longum were higher (p < 0.001), while Phocaeicola vulgatus, Bacteroides uniformis, and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group (p < 0.00005). In ET-P, Escherichia fergusonii, Megasphaera elsdenii, and Oscillibacter valericigenes were higher, and Bacteroides koreensis and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group. In ET-L and ET-P, bacteria in the healthy and T2DM groups positively interacted with each other within each group (p < 0.0001) but negatively interacted between the T2DM and healthy groups in the network analysis (p < 0.0001). In the metagenome functions of the fecal bacteria, the gluconeogenesis, glycolysis, and amino acid metabolism pathways were higher, whereas insulin signaling and adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling pathways were lower in the T2DM group than in the healthy group for both enterotypes (p < 0.00005). In conclusion, Asians with T2DM exhibited gut dysbiosis, potentially linked to intestinal permeability and the enteric vagus nervous system. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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16 pages, 2518 KiB  
Article
Lipotoxicity in a Vicious Cycle of Pancreatic Beta Cell Exhaustion
by Vladimir Grubelnik, Jan Zmazek, Matej Završnik and Marko Marhl
Biomedicines 2022, 10(7), 1627; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10071627 - 7 Jul 2022
Cited by 2 | Viewed by 1518
Abstract
Hyperlipidemia is a common metabolic disorder in modern society and may precede hyperglycemia and diabetes by several years. Exactly how disorders of lipid and glucose metabolism are related is still a mystery in many respects. We analyze the effects of hyperlipidemia, particularly free [...] Read more.
Hyperlipidemia is a common metabolic disorder in modern society and may precede hyperglycemia and diabetes by several years. Exactly how disorders of lipid and glucose metabolism are related is still a mystery in many respects. We analyze the effects of hyperlipidemia, particularly free fatty acids, on pancreatic beta cells and insulin secretion. We have developed a computational model to quantitatively estimate the effects of specific metabolic pathways on insulin secretion and to assess the effects of short- and long-term exposure of beta cells to elevated concentrations of free fatty acids. We show that the major trigger for insulin secretion is the anaplerotic pathway via the phosphoenolpyruvate cycle, which is affected by free fatty acids via uncoupling protein 2 and proton leak and is particularly destructive in long-term chronic exposure to free fatty acids, leading to increased insulin secretion at low blood glucose and inadequate insulin secretion at high blood glucose. This results in beta cells remaining highly active in the “resting” state at low glucose and being unable to respond to anaplerotic signals at high pyruvate levels, as is the case with high blood glucose. The observed fatty-acid-induced disruption of anaplerotic pathways makes sense in the context of the physiological role of insulin as one of the major anabolic hormones. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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24 pages, 6185 KiB  
Article
Incorporation of Oxidized Phenylalanine Derivatives into Insulin Signaling Relevant Proteins May Link Oxidative Stress to Signaling Conditions Underlying Chronic Insulin Resistance
by Judit Mohás-Cseh, Gergő Attila Molnár, Marianna Pap, Boglárka Laczy, Tibor Vas, Melinda Kertész, Krisztina Németh, Csaba Hetényi, Orsolya Csikós, Gábor K. Tóth, Attila Reményi and István Wittmann
Biomedicines 2022, 10(5), 975; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10050975 - 22 Apr 2022
Cited by 5 | Viewed by 2147
Abstract
A link between oxidative stress and insulin resistance has been suggested. Hydroxyl free radicals are known to be able to convert phenylalanine (Phe) into the non-physiological tyrosine isoforms ortho- and meta-tyrosine (o-Tyr, m-Tyr). The aim of our study was to examine the role [...] Read more.
A link between oxidative stress and insulin resistance has been suggested. Hydroxyl free radicals are known to be able to convert phenylalanine (Phe) into the non-physiological tyrosine isoforms ortho- and meta-tyrosine (o-Tyr, m-Tyr). The aim of our study was to examine the role of o-Tyr and m-Tyr in the development of insulin resistance. We found that insulin-induced uptake of glucose was blunted in cultures of 3T3-L1 grown on media containing o- or m-Tyr. We show that these modified amino acids are incorporated into cellular proteins. We focused on insulin receptor substrate 1 (IRS-1), which plays a role in insulin signaling. The activating phosphorylation of IRS-1 was increased by insulin, the effect of which was abolished in cells grown in m-Tyr or o-Tyr media. We found that phosphorylation of m- or o-Tyr containing IRS-1 segments by insulin receptor (IR) kinase was greatly reduced, PTP-1B phosphatase was incapable of dephosphorylating phosphorylated m- or o-Tyr IRS-1 peptides, and the SH2 domains of phosphoinositide 3-kinase (PI3K) bound the o-Tyr IRS-1 peptides with greatly reduced affinity. According to our data, m- or o-Tyr incorporation into IRS-1 modifies its protein–protein interactions with regulating enzymes and effectors, thus IRS-1 eventually loses its capacity to play its role in insulin signaling, leading to insulin resistance. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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37 pages, 8745 KiB  
Article
Clinical Interest of Serum Alpha-2 Macroglobulin, Apolipoprotein A1, and Haptoglobin in Patients with Non-Alcoholic Fatty Liver Disease, with and without Type 2 Diabetes, before or during COVID-19
by Olivier Deckmyn, Thierry Poynard, Pierre Bedossa, Valérie Paradis, Valentina Peta, Raluca Pais, Vlad Ratziu, Dominique Thabut, Angelique Brzustowski, Jean-François Gautier, Patrice Cacoub and Dominique Valla
Biomedicines 2022, 10(3), 699; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030699 - 17 Mar 2022
Cited by 7 | Viewed by 3386
Abstract
In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened [...] Read more.
In patients with non-alcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM), alpha-2 macroglobulin (A2M), apolipoprotein A1 (ApoA1), and haptoglobin are associated with the risk of liver fibrosis, inflammation (NASH), and COVID-19. We assessed if these associations were worsened by T2DM after adjustment by age, sex, obesity, and COVID-19. Three datasets were used: the “Control Population”, which enabled standardization of protein serum levels according to age and sex (N = 27,382); the “NAFLD-Biopsy” cohort for associations with liver features (N = 926); and the USA “NAFLD-Serum” cohort for protein kinetics before and during COVID-19 (N = 421,021). The impact of T2DM was assessed by comparing regression curves adjusted by age, sex, and obesity for the liver features in “NAFLD-Biopsy”, and before and during COVID-19 pandemic peaks in “NAFLD-Serum”. Patients with NAFLD without T2DM, compared with the values of controls, had increased A2M, decreased ApoA1, and increased haptoglobin serum levels. In patients with both NAFLD and T2DM, these significant mean differences were magnified, and even more during the COVID-19 pandemic in comparison with the year 2019 (all p < 0.001), with a maximum ApoA1 decrease of 0.21 g/L in women, and a maximum haptoglobin increase of 0.17 g/L in men. In conclusion, T2DM is associated with abnormal levels of A2M, ApoA1, and haptoglobin independently of NAFLD, age, sex, obesity, and COVID-19. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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13 pages, 883 KiB  
Article
Effects of a 13-Week Personalized Lifestyle Intervention Based on the Diabetes Subtype for People with Newly Diagnosed Type 2 Diabetes
by Iris M. de Hoogh, Wilrike J. Pasman, André Boorsma, Ben van Ommen and Suzan Wopereis
Biomedicines 2022, 10(3), 643; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030643 - 10 Mar 2022
Cited by 3 | Viewed by 2679
Abstract
A type 2 diabetes mellitus (T2DM) subtyping method that determines the T2DM phenotype based on an extended oral glucose tolerance test is proposed. It assigns participants to one of seven subtypes according to their β-cell function and the presence of hepatic and/or muscle [...] Read more.
A type 2 diabetes mellitus (T2DM) subtyping method that determines the T2DM phenotype based on an extended oral glucose tolerance test is proposed. It assigns participants to one of seven subtypes according to their β-cell function and the presence of hepatic and/or muscle insulin resistance. The effectiveness of this subtyping approach and subsequent personalized lifestyle treatment in ameliorating T2DM was assessed in a primary care setting. Sixty participants, newly diagnosed with (pre)diabetes type 2 and not taking diabetes medication, completed the intervention. Retrospectively collected data of 60 people with T2DM from usual care were used as controls. Bodyweight (p < 0.01) and HbA1c (p < 0.01) were significantly reduced after 13 weeks in the intervention group, but not in the usual care group. The intervention group achieved 75.0% diabetes remission after 13 weeks (fasting glucose ≤ 6.9 mmol/L and HbA1c < 6.5% (48 mmol/mol)); for the usual care group, this was 22.0%. Lasting (two years) remission was especially achieved in subgroups with isolated hepatic insulin resistance. Our study shows that a personalized diagnosis and lifestyle intervention for T2DM in a primary care setting may be more effective in improving T2DM-related parameters than usual care, with long-term effects seen especially in subgroups with hepatic insulin resistance. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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14 pages, 1924 KiB  
Article
Placental Insulin Receptor Transiently Regulates Glucose Homeostasis in the Adult Mouse Offspring of Multiparous Dams
by Grace Chung, Ramkumar Mohan, Megan Beetch, Seokwon Jo and Emilyn Uy Alejandro
Biomedicines 2022, 10(3), 575; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030575 - 1 Mar 2022
Cited by 2 | Viewed by 2470
Abstract
In pregnancies complicated by maternal obesity and gestational diabetes mellitus, there is strong evidence to suggest that the insulin signaling pathway in the placenta may be impaired. This may have potential effects on the programming of the metabolic health in the offspring; however, [...] Read more.
In pregnancies complicated by maternal obesity and gestational diabetes mellitus, there is strong evidence to suggest that the insulin signaling pathway in the placenta may be impaired. This may have potential effects on the programming of the metabolic health in the offspring; however, a direct link between the placental insulin signaling pathway and the offspring health remains unknown. Here, we aimed to understand whether specific placental loss of the insulin receptor (InsR) has a lasting effect on the offspring health in mice. Obesity and glucose homeostasis were assessed in the adult mouse offspring on a normal chow diet (NCD) followed by a high-fat diet (HFD) challenge. Compared to their littermate controls, InsR KOplacenta offspring were born with normal body weight and pancreatic β-cell mass. Adult InsR KOplacenta mice exhibited normal glucose homeostasis on an NCD. Interestingly, under a HFD challenge, adult male InsR KOplacenta offspring demonstrated lower body weight and a mildly improved glucose homeostasis associated with parity. Together, our data show that placenta-specific insulin receptor deletion does not adversely affect offspring glucose homeostasis during adulthood. Rather, there may potentially be a mild and transient protective effect in the mouse offspring of multiparous dams under the condition of a diet-induced obesogenic challenge. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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17 pages, 3560 KiB  
Article
MORG1—A Negative Modulator of Renal Lipid Metabolism in Murine Diabetes
by Eric Jankowski, Sophie Wulf, Nadja Ziller, Gunter Wolf and Ivonne Loeffler
Biomedicines 2022, 10(1), 30; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10010030 - 23 Dec 2021
Cited by 4 | Viewed by 3052
Abstract
Renal fatty acid (FA) metabolism is severely altered in type 1 and 2 diabetes mellitus (T1DM and T2DM). Increasing evidence suggests that altered lipid metabolism is linked to tubulointerstitial fibrosis (TIF). Our previous work has demonstrated that mice with reduced MORG1 expression, a [...] Read more.
Renal fatty acid (FA) metabolism is severely altered in type 1 and 2 diabetes mellitus (T1DM and T2DM). Increasing evidence suggests that altered lipid metabolism is linked to tubulointerstitial fibrosis (TIF). Our previous work has demonstrated that mice with reduced MORG1 expression, a scaffold protein in HIF and ERK signaling, are protected against TIF in the db/db mouse model. Renal TGF-ß1 expression and EMT-like changes were reduced in mice with single-allele deficiency of MORG1. Given the well-known role of HIF and ERK signaling in metabolic regulation, here we examined whether protection was also associated with a restoration of lipid metabolism. Despite similar features of TIF in T1DM and T2DM, diabetes-associated changes in renal lipid metabolism differ between both diseases. We found that de novo synthesis of FA/cholesterol and β-oxidation were more strongly disrupted in T1DM, whereas pathological fat uptake into tubular cells mediates lipotoxicity in T2DM. Thus, diminished MORG1 expression exerts renoprotection in the diabetic nephropathy by modulating important factors of TIF and lipid dysregulation to a variable extent in T1DM and T2DM. Prospectively, targeting MORG1 appears to be a promising strategy to reduce lipid metabolic alterations in diabetic nephropathy. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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15 pages, 1116 KiB  
Article
New Insights on the Relationship between Leptin, Ghrelin, and Leptin/Ghrelin Ratio Enforced by Body Mass Index in Obesity and Diabetes
by Adela-Viviana Sitar-Tǎut, Angela Cozma, Adriana Fodor, Sorina-Cezara Coste, Olga Hilda Orasan, Vasile Negrean, Dana Pop and Dan-Andrei Sitar-Tǎut
Biomedicines 2021, 9(11), 1657; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9111657 - 10 Nov 2021
Cited by 18 | Viewed by 8625
Abstract
Currently, adipose tissue is considered an endocrine organ, however, there are still many questions regarding the roles of adipokines—leptin and ghrelin being two adipokines. The purpose of the study was to assess the relationship between the adipokines and their ratio with obesity and [...] Read more.
Currently, adipose tissue is considered an endocrine organ, however, there are still many questions regarding the roles of adipokines—leptin and ghrelin being two adipokines. The purpose of the study was to assess the relationship between the adipokines and their ratio with obesity and diabetes. Methods: Sixty patients (mean age 61.88 ± 10.08) were evaluated. Cardiovascular risk factors, leptin, ghrelin, and insulin resistance score values were assessed. The patients were classified according to their body mass index (BMI) as normal weight, overweight, and obese. Results: 20% normal weight, 51.7% overweight, 28.3% obese, and 23.3% diabetic. Obese patients had higher leptin values (in obese 34,360 pg/mL vs. overweight 18,000 pg/mL vs. normal weight 14,350 pg/mL, p = 0.0049) and leptin/ghrelin ratio (1055 ± 641 vs. 771.36 ± 921 vs. 370.7 ± 257, p = 0.0228). Stratifying the analyses according to the presence of obesity and patients’ gender, differences were found for leptin (p = 0.0020 in women, p = 0.0055 in men) and leptin/ghrelin ratio (p = 0.048 in women, p = 0.004 in men). Mean leptin/BMI and leptin/ghrelin/BMI ratios were significantly higher, and the ghrelin/BMI ratio was significantly lower in obese and diabetic patients. In conclusion, obesity and diabetes are associated with changes not only in the total amount but also in the level of adipokines/kg/m2. Changes appear even in overweight subjects, offering a basis for early intervention in diabetic and obese patients. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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21 pages, 7739 KiB  
Article
Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes
by Midori Fujishiro, Hisamitsu Ishihara, Katsuhiko Ogawa, Takayo Murase, Takashi Nakamura, Kentaro Watanabe, Hideyuki Sakoda, Hiraku Ono, Takeshi Yamamotoya, Yusuke Nakatsu, Tomoichiro Asano and Akifumi Kushiyama
Biomedicines 2021, 9(8), 1052; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9081052 - 19 Aug 2021
Cited by 2 | Viewed by 2308
Abstract
To unravel associations between plasma xanthine oxidoreductase (XOR) and diabetic vascular complications, especially distal symmetric polyneuropathy (DSP), we investigated plasma XOR activities using a novel assay. Patients with type 2 diabetes mellitus (T2DM) with available nerve conduction study (NCS) data were analyzed. None [...] Read more.
To unravel associations between plasma xanthine oxidoreductase (XOR) and diabetic vascular complications, especially distal symmetric polyneuropathy (DSP), we investigated plasma XOR activities using a novel assay. Patients with type 2 diabetes mellitus (T2DM) with available nerve conduction study (NCS) data were analyzed. None were currently taking XOR inhibitors. XOR activity of fasting blood samples was assayed using a stable isotope-labeled substrate and LC-TQMS. JMP Clinical version 5.0. was used for analysis. We analyzed 54 patients. Mean age was 64.7 years, mean body mass index was 26.0 kg/m2, and mean glycated hemoglobin was 9.4%. The logarithmically transformed plasma XOR activity (ln-XOR) correlated positively with hypoxanthine, xanthine, visceral fatty area, and liver dysfunction but negatively with HDL cholesterol. ln-XOR correlated negatively with diabetes duration and maximum intima-media thickness. Stepwise multiple regression analysis revealed ln-XOR to be among selected explanatory factors for various NCS parameters. Receiver operating characteristic curves showed the discriminatory power of ln-XOR. Principal component analysis revealed a negative relationship of ln-XOR with F-waves as well as positive relationships of ln-XOR with hepatic steatosis and obesity-related disorders. Taken together, our results show plasma XOR activity to be among potential disease status predictors in T2DM patients. Plasma XOR activity measurements might reliably detect pre-symptomatic DSP. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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Review

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12 pages, 875 KiB  
Review
Type 2 Diabetes Mellitus and COVID-19: A Narrative Review
by Cristina Rey-Reñones, Sara Martinez-Torres, Francisco M. Martín-Luján, Carles Pericas, Ana Redondo, Carles Vilaplana-Carnerero, Angela Dominguez and María Grau
Biomedicines 2022, 10(9), 2089; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10092089 - 26 Aug 2022
Cited by 14 | Viewed by 3643
Abstract
Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder. The incidence and prevalence of patients with T2DM are increasing worldwide, even reaching epidemic values in most high- and middle-income countries. T2DM could be a risk factor of developing complications in other diseases. Indeed, [...] Read more.
Type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder. The incidence and prevalence of patients with T2DM are increasing worldwide, even reaching epidemic values in most high- and middle-income countries. T2DM could be a risk factor of developing complications in other diseases. Indeed, some studies suggest a bidirectional interaction between T2DM and COVID-19. A growing body of evidence shows that COVID-19 prognosis in individuals with T2DM is worse compared with those without. Moreover, various studies have reported the emergence of newly diagnosed patients with T2DM after SARS-CoV-2 infection. The most common treatments for T2DM may influence SARS-CoV-2 and their implication in infection is briefly discussed in this review. A better understanding of the link between TD2M and COVID-19 could proactively identify risk factors and, as a result, develop strategies to improve the prognosis for these patients. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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14 pages, 674 KiB  
Review
Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus
by Hideaki Kaneto, Tomohiko Kimura, Masashi Shimoda, Atsushi Obata, Junpei Sanada, Yoshiro Fushimi, Taka-aki Matsuoka and Kohei Kaku
Biomedicines 2022, 10(4), 818; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10040818 - 31 Mar 2022
Cited by 7 | Viewed by 3203
Abstract
Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic β-cells and the preservation of mature β-cell function. However, when β-cells are continuously exposed to a high glucose [...] Read more.
Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic β-cells and the preservation of mature β-cell function. However, when β-cells are continuously exposed to a high glucose concentration for a long period of time, the expression levels of several insulin gene transcription factors are substantially suppressed, which finally leads to pancreatic β-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for β-cell failure. It is likely that reduced expression levels of MafA and PDX-1 and/or incretin receptor in β-cells are closely associated with β-cell failure in type 2 diabetes mellitus. Additionally, since incretin receptor expression is reduced in the advanced stage of diabetes mellitus, incretin-based medicines show more favorable effects against β-cell failure, especially in the early stage of diabetes mellitus compared to the advanced stage. On the other hand, many subjects have recently suffered from life-threatening coronavirus infection, and coronavirus infection has brought about a new and persistent pandemic. Additionally, the spread of coronavirus infection has led to various limitations on the activities of daily life and has restricted economic development worldwide. It has been reported recently that SARS-CoV-2 directly infects β-cells through neuropilin-1, leading to apoptotic β-cell death and a reduction in insulin secretion. In this review article, we feature a possible molecular mechanism for pancreatic β-cell failure, which is often observed in type 2 diabetes mellitus. Finally, we are hopeful that coronavirus infection will decline and normal daily life will soon resume all over the world. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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13 pages, 1693 KiB  
Review
Novel Biomarkers of Inflammation for the Management of Diabetes: Immunoglobulin-Free Light Chains
by Akira Matsumori
Biomedicines 2022, 10(3), 666; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10030666 - 13 Mar 2022
Cited by 8 | Viewed by 2662
Abstract
Virus infection, inflammation and genetic factors are important factors in the pathogenesis of diabetes mellitus. The nuclear factor-kappa B (NF-κB) is a family of transcription factors that bind the enhancer of the κ light chain gene of B cell immunoglobulin. NF-κB plays an [...] Read more.
Virus infection, inflammation and genetic factors are important factors in the pathogenesis of diabetes mellitus. The nuclear factor-kappa B (NF-κB) is a family of transcription factors that bind the enhancer of the κ light chain gene of B cell immunoglobulin. NF-κB plays an essential role in the activation and development of B cells, and the activation of NF-κB is critical in the inflammation and development of diabetes mellitus. Recently, immunoglobulin-free light chain (FLC) λ was found to be increased in the sera of patients with diabetes mellitus, and the FLC λ and κ/λ ratios are more specific and sensitive markers for the diagnosis of diabetes relative to glycated hemoglobin A1c. Thus, FLCs may be promising biomarkers of inflammation that could relate to the activation of NF-κB. We suggest that NF-κB could be a target for an anti-inflammatory strategy in preventing and treating diabetes when FLCs are modified. FLCs could be a surrogate endpoint in the management of diabetes. In this review, the role of inflammation in the pathogenesis of diabetes, as well as the novel inflammatory biomarkers of FLCs for the management of diabetes, are discussed. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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17 pages, 3740 KiB  
Review
Dysregulation of β-Cell Proliferation in Diabetes: Possibilities of Combination Therapy in the Development of a Comprehensive Treatment
by Natsuki Eguchi, Arvin John Toribio, Michael Alexander, Ivana Xu, David Lee Whaley, Luis F. Hernandez, Donald Dafoe and Hirohito Ichii
Biomedicines 2022, 10(2), 472; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020472 - 17 Feb 2022
Cited by 6 | Viewed by 2877
Abstract
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia as a result of insufficient insulin levels and/or impaired function as a result of autoimmune destruction or insulin resistance. While Type 1 DM (T1DM) and Type 2 DM (T2DM) occur through different [...] Read more.
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia as a result of insufficient insulin levels and/or impaired function as a result of autoimmune destruction or insulin resistance. While Type 1 DM (T1DM) and Type 2 DM (T2DM) occur through different pathological processes, both result in β-cell destruction and/or dysfunction, which ultimately lead to insufficient β-cell mass to maintain normoglycemia. Therefore, therapeutic agents capable of inducing β-cell proliferation is crucial in treating and reversing diabetes; unfortunately, adult human β-cell proliferation has been shown to be very limited (~0.2% of β-cells/24 h) and poorly responsive to many mitogens. Furthermore, diabetogenic insults result in damage to β cells, making it ever more difficult to induce proliferation. In this review, we discuss β-cell mass/proliferation pathways dysregulated in diabetes and current therapeutic agents studied to induce β-cell proliferation. Furthermore, we discuss possible combination therapies of proliferation agents with immunosuppressants and antioxidative therapy to improve overall long-term outcomes of diabetes. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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Other

25 pages, 3832 KiB  
Systematic Review
Optical Coherence Tomography Angiography in Diabetic Patients: A Systematic Review
by Ana Boned-Murillo, Henar Albertos-Arranz, María Dolores Diaz-Barreda, Elvira Orduna-Hospital, Ana Sánchez-Cano, Antonio Ferreras, Nicolás Cuenca and Isabel Pinilla
Biomedicines 2022, 10(1), 88; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10010088 - 31 Dec 2021
Cited by 23 | Viewed by 3106
Abstract
Background: Diabetic retinopathy (DR) is the leading cause of legal blindness in the working population in developed countries. Optical coherence tomography (OCT) angiography (OCTA) has risen as an essential tool in the diagnosis and control of diabetic patients, with and without DR, allowing [...] Read more.
Background: Diabetic retinopathy (DR) is the leading cause of legal blindness in the working population in developed countries. Optical coherence tomography (OCT) angiography (OCTA) has risen as an essential tool in the diagnosis and control of diabetic patients, with and without DR, allowing visualisation of the retinal and choroidal microvasculature, their qualitative and quantitative changes, the progression of vascular disease, quantification of ischaemic areas, and the detection of preclinical changes. The aim of this article is to analyse the current applications of OCTA and provide an updated overview of them in the evaluation of DR. Methods: A systematic literature search was performed in PubMed and Embase, including the keywords “OCTA” OR “OCT angiography” OR “optical coherence tomography angiography” AND “diabetes” OR “diabetes mellitus” OR “diabetic retinopathy” OR “diabetic maculopathy” OR “diabetic macular oedema” OR “diabetic macular ischaemia”. Of the 1456 studies initially identified, 107 studies were screened after duplication, and those articles that did not meet the selection criteria were removed. Finally, after looking for missing data, we included 135 studies in this review. Results: We present the common and distinctive findings in the analysed papers after the literature search including the diagnostic use of OCTA in diabetes mellitus (DM) patients. We describe previous findings in retinal vascularization, including microaneurysms, foveal avascular zone (FAZ) changes in both size and morphology, changes in vascular perfusion, the appearance of retinal microvascular abnormalities or new vessels, and diabetic macular oedema (DME) and the use of deep learning technology applied to this disease. Conclusion: OCTA findings enable the diagnosis and follow-up of DM patients, including those with no detectable lesions with other devices. The evaluation of retinal and choroidal plexuses using OCTA is a fundamental tool for the diagnosis and prognosis of DR. Full article
(This article belongs to the Special Issue Pathological Mechanisms in Diabetes)
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