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Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus

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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 December 2022) | Viewed by 18124

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Dr. Chrysi Koliaki

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First Propaedeutic Department of Internal Medicine and Diabetes Center, National Kapodistrian University of Athens, Laiko University Hospital, 11527 Athens, Greece
Interests: diabetes mellitus; obesity; non-alcoholic fatty liver disease (NAFLD); bariatric surgery; body composition; cardiovascular disease; insulin resistance; metabolically healthy obese; mitochondrial function
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Prof. Dr. Nicholas Katsilambros

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1. First Department of Propaedeutic Medicine, National Kapodistrian University of Athens, Laiko University Hospital, 11527 Athens, Greece
2. Research Laboratory Christeas Hall, Medical School, National Kapodistrian University of Athens, 11527 Athens, Greece
Interests: appetite-related hormones; diabetes mellitus; nutrition and atherosclerosis; obesity; postprandial metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Diabetes mellitus, the contemporary metabolic pandemic, represents a complex multifactorial syndrome characterized by abnormalities in every single aspect of cellular energy metabolism. Type 1 diabetes mellitus (T1DM) is associated with reduced endogenous insulin secretion due to progressive autoimmune destruction of insulin-producing pancreatic β-cells. Type 2 diabetes mellitus (T2DM) is associated with both insulin resistance and defective insulin secretion. Beyond T1DM and T2DM, distinct phenotypes of diabetes with varying degrees of insulin resistance and pancreatic β-cell defects have been characterized in the literature. The major pathophysiological mechanisms underlying the pathogenesis of diabetes and its related complications involve insulin resistance; immunological defects; an impaired incretin effect; gluco- and lipotoxicity; inflammation; oxidative stress; endoplasmic reticulum stress; defective autophagy mechanisms; proapoptotic pathways; alterations in the gut microbiome; and abnormal mitochondrial function in insulin-responsive tissues such as liver, skeletal muscle, adipose tissue, vessels, nervous system and myocardium. In recent years, evidence-based treatment algorithms for diabetic patients, focusing on patients’ comorbidities as a critical determinant of the selection of the most appropriate glucose-lowering treatment, have been proposed. The most relevant comorbidities are atherosclerotic cardiovascular disease, heart failure, chronic kidney disease and obesity. Sodium-glucose co-transporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 (GLP-1) receptor agonists are prominent in current therapeutic practice due to their pleiotropic, mainly cardio- and renoprotective, effects.

The aim of this Special Issue is to provide a platform for sharing all the novel insights into the pathophysiology and treatment of diabetes mellitus. Both original research and comprehensive review articles on this topic are invited for submission. Papers on potential novel biomarkers for the prediction of diabetes and its complications (including the omics technology); pathophysiological concepts related to the mechanisms described above; and treatment strategies (medical nutrition, metabolic surgery, drugs, innovative approaches based on nanotechnology or artificial intelligence) in the context of precision diabetology are particularly welcome.

Dr. Chrysi Koliaki
Prof. Dr. Nicholas Katsilambros
Guest Editors

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Keywords

type 1 diabetes mellitus
type 2 diabetes mellitus
insulin resistance
pathophysiology
treatment
precision medicine

Published Papers (8 papers)

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10 pages, 1005 KiB

Open AccessArticle

Telomere Shortening in Three Diabetes Mellitus Types in a Mexican Sample

by Pavel Cuevas Diaz, Humberto Nicolini, German Alberto Nolasco-Rosales, Isela Juarez Rojop, Carlos Alfonso Tovilla-Zarate, Ester Rodriguez Sanchez and Alma Delia Genis-Mendoza

Biomedicines 2023, 11(3), 730; https://doi.org/10.3390/biomedicines11030730 - 28 Feb 2023

Cited by 4 | Viewed by 1556

Abstract

This study aimed to explore the role of telomere length in three different diabetes types: latent autoimmune diabetes of adulthood (LADA), latent autoimmune diabetes in the young (LADY), and type 2 diabetes mellitus (T2DM). A total of 115 patients were included, 72 (62.61%) had LADA, 30 (26.09%) had T2DM, and 13 (11.30%) had LADY. Telomere length was measured using real-time Polymerase Chain Reaction. For statistical analysis, we used the ANOVA test, X2 test, and the Mann–Whitney U test. Patients with T2DM had higher BMI compared to LADA and LADY groups, with a BMI average of 31.32 kg/m² (p = 0.0235). While the LADA group had more patients with comorbidities, there was not a statistically significant difference (p = 0.3164, p = 0.3315, p = 0.3742 for each of the previously mentioned conditions). There was a difference between those patients with T2DM who took metformin plus any other oral antidiabetic agent and those who took metformin plus insulin, the ones who had longer telomeres. LADA patients had shorter telomeres compared to T2DM patients but not LADY patients. Furthermore, T2DM may have longer telomeres thanks to the protective effects of both metformin and insulin, despite the higher BMI in this group. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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13 pages, 4204 KiB

Open AccessArticle

Doxycycline Prevents Preclinical Atherosclerosis, Pancreatic Islet Loss and Improves Insulin Secretion after Glycemic Stimulation: Preclinical Study in Individuals with a High-Fat Diet

by Alejandrina Rodriguez-Hernandez, Marina Delgado-Machuca, Rodolfo Guardado-Mendoza, Martha A. Mendoza-Hernandez, Valery Melnikov, Osiris G. Delgado-Enciso, Daniel Tiburcio-Jimenez, Gabriel Ceja-Espiritu, Gustavo A. Hernandez-Fuentes, Armando Gamboa-Dominguez, Jose Guzman-Esquivel, Margarita L. Martinez-Fierro, Iram P. Rodriguez-Sanchez and Ivan Delgado-Enciso

Biomedicines 2023, 11(3), 717; https://doi.org/10.3390/biomedicines11030717 - 27 Feb 2023

Viewed by 3245

Abstract

Doxycycline (Doxy) is an antibiotic, which has exhibited anti-inflammatory activity and glucose metabolism improvement. The present study was proposed to evaluate its effects on glucose metabolism and other associated processes, such as lipemia and adipogenesis, as well as, to evaluate its effects on the liver, pancreas, and aorta in subjects fed with an occidental high-fat diet (HFD). The trial followed three groups of BALB/c mice for 6 months: (1) Standard diet (SD); (2) HFD-placebo (saline solution); and (3) HFD-Doxy (10 mg/kg/day). Intrahepatic fat accumulation (steatohepatosis) and the epididymal fat pad, as well as the hepatic inflammatory infiltrate and ALT serum levels were higher in both groups with the HFD (with/without doxycycline) in comparison with the SD group. The thickness of the aorta (preclinic atherosclerosis) was significantly elevated in the HFD group with respect to the HFD + Doxy and SD group, these two being similar groups to each other. The HFD-Doxy group had pancreatic morphological parameters very similar to those of the SD group; on the contrary, the HFD group reduced the number of pancreatic islets and the number of β cells per mm², in addition to losing large islets. The index of β cell function (∆Insulin0–30/∆Glucose0–30 ratio) was significantly higher in the HFD + Doxy group, compared to the rest of the groups. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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14 pages, 635 KiB

Open AccessArticle

Hand Grip Strength Relative to Waist Circumference as a Means to Identify Men and Women Possessing Intact Mobility in a Cohort of Older Adults with Type 2 Diabetes

by Ofer S. Kis, Assaf Buch, Roy Eldor and Daniel S. Moran

Biomedicines 2023, 11(2), 352; https://doi.org/10.3390/biomedicines11020352 - 26 Jan 2023

Cited by 1 | Viewed by 1530

Abstract

Possessing intact mobility in older adults assures their continued independence. The early identification of reduced mobility in older adults with type 2 diabetes (T2DM) is paramount for preventing their future physical deterioration. Hand grip strength (HGS), relative to body size, is associated with mobility in older T2DM patients. This study aims to identify an HGS index that best identifies mobilityintact older T2DM patients, along with its optimal cut-off point. The baseline data are from a cohort of 122 older T2DM patients (59% women) (mean age of 70.2 ± 4.4 years). Three mobility tests encompassing three main mobility domains were measured, including usual gait speed (UGS), timed up and go (TUG), and a two-minute walk test (2MWT). Passing scores were defined as those either above the established cut-off points or above the 25th percentile of population norms. Passing all three tests was considered as possessing intact mobility. Receiver operating characteristic (ROC) curves of the most relevant HGS indices were constructed to determine the area under the curve (AUC) that best identifies patients with intact mobility. In a sample of 122 older adults with T2DM, 63.9% of women and 60% of men were found to possess intact mobility. HGS relative to waist circumference (WC) was found to have the strongest association with intact mobility, presenting the highest AUC in both men (0.78) and women (0.72) for discriminating mobility status, with an optimal cut-off of 0.355 (kg/cm) and 0.245 (kg/cm) in men and women, respectively. HGS relative to WC best differentiated between mobility-intact older adults with T2DM and those with mobility limitations, especially in men. Using HGS/WC as a simple and safe screening mode for mobility in a clinical setting could potentially identify older patients with T2DM that require therapeutic interventions. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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13 pages, 2265 KiB

Open AccessArticle

Pancreatic Pathological Changes in Murine Toxoplasmosis and Possible Association with Diabetes Mellitus

by Asmaa M. El-kady, Amal M. Alzahrani, Hayam Elshazly, Eman Abdullah Alshehri, Majed H. Wakid, Hattan S. Gattan, Wafa Abdullah I. Al-Megrin, Mashael S. Alfaifi, Khalil Mohamed, Waheeb Alharbi, Hatem A. Elshabrawy and Salwa S. Younis

Biomedicines 2023, 11(1), 18; https://doi.org/10.3390/biomedicines11010018 - 22 Dec 2022

Viewed by 1969

Abstract

Background: Previous studies have reported involvement of Toxoplasma gondii (T. gondii) infections in the pathogenesis of some autoimmune diseases, such as polymyositis, rheumatoid arthritis, autoimmune thyroiditis, and Crohn’s disease. However, data on the association between T. gondii infections and Type 1 diabetes mellitus (T1DM) are still controversial. Therefore, in the present study, we aimed to investigate the pancreatic pathological changes in mouse models with acute and chronic toxoplasmosis and their association with T1DM. Materials and Methods: Three groups (10 mice each) of male Swiss Albino mice were used. One group of mice was left uninfected, whereas the second and third groups were infected with the acute virulent T. gondii RH strain and the chronic less virulent Me49 T. gondii strain, respectively. T. gondii-induced pancreatic pathological changes were evaluated by histopathological examination of pancreatic tissues. Moreover, the expression of insulin, levels of caspase-3, and the pancreatic infiltration of CD8⁺ T cells were evaluated using immunohistochemical staining. Results: Pancreatic tissues of T. gondii-infected animals showed significant pathological alterations and variable degrees of insulitis. Mice with acute toxoplasmosis exhibited marked enlargement and reduced numbers of islets of Langerhans. However, mice with chronic toxoplasmosis showed considerable reduction in size and number of islets of Langerhans. Moreover, insulin staining revealed significant reduction in β cell numbers, whereas caspase-3 staining showed induced apoptosis in islets of Langerhans of acute toxoplasmosis and chronic toxoplasmosis mice compared to uninfected mice. We detected infiltration of CD8⁺ T cells only in islets of Langerhans of mice with chronic toxoplasmosis. Conclusions: Acute and chronic toxoplasmosis mice displayed marked pancreatic pathological changes with reduced numbers of islets of Langerhans and insulin-producing-β cells. Since damage of β cells of islets of Langerhans is associated with the development of T1DM, our findings may support a link between T. gondii infections and the development of T1DM. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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14 pages, 3278 KiB

Open AccessArticle

Intensive Periodontal Treatment Does Not Affect the Lipid Profile and Endothelial Function of Patients with Type 2 Diabetes: A Randomized Clinical Trial

by Biagio Rapone, Elisabetta Ferrara, Erda Qorri, Mir Faeq Ali Quadri, Gianna Dipalma, Antonio Mancini, Massimo Del Fabbro, Antonio Scarano, Gianluca Tartaglia and Francesco Inchingolo

Biomedicines 2022, 10(10), 2524; https://doi.org/10.3390/biomedicines10102524 - 09 Oct 2022

Cited by 3 | Viewed by 1375

Abstract

Background: Local eradication of periodontal infection could potentially have a much broader impact on the diabetic condition by also contributing to the modification of the lipid profile, which is directly compromised in the alteration of endothelium-dependent vasodilation. The aim of this trial was to assess the benefits of intensive periodontal treatment (IPT) on the lipid profile and endothelial function of diabetic patients. Methods: This was a 6-month, randomized controlled trial involving diabetic patients with generalized periodontitis. The study group comprised 290 individuals who were randomly assigned to receive Intensive Periodontal Treatment (IPT, Intervention Group) or conventional adult prophylaxis (Control Periodontal Treatment, CPT, Control Group). Outcomes encompassed lipid profile involving serum total cholesterol, serum triglyceride, low-density lipoprotein cholesterol, high-density lipo-protein cholesterol, and flow-mediated vasodilation (FMD) as an index of endothelium-dependent vasodilation (primary outcomes); periodontal indices and high-sensitive C-reactive protein were evaluated at baseline, 3 and 6 months after periodontal treatment. Results: An increase in endothelium-dependent flow-mediated dilatation (FMD) was observed in the Intensive Periodontal Treatment group in comparison with Control (p < 0.001), but results are not statistically different. There were no differences in lipid profile in individuals of both groups. Conclusions: An intensive periodontal treatment might improve endothelial function, suggesting a direct beneficial effect on the vasculature, possibly mediated by systemic inflammatory reduction. However, no statistically significant differences between groups were observed, and no benefits were proved on lipid profile. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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12 pages, 1025 KiB

Open AccessArticle

Evaluation of Morphological Changes in Retinal Vessels in Type 1 Diabetes Mellitus Patients with the Use of Adaptive Optics

by Wojciech Matuszewski, Katarzyna Gontarz-Nowak, Joanna M. Harazny and Elżbieta Bandurska-Stankiewicz

Biomedicines 2022, 10(8), 1926; https://doi.org/10.3390/biomedicines10081926 - 09 Aug 2022

Cited by 3 | Viewed by 1572

Abstract

Introduction. Diabetes mellitus contributes to the development of microvascular complications in the eye. Moreover, it affects multiple end organs, including brain damage, leading to premature death. The use of adaptive optics technique allows to perform non-invasive in vivo assessment of retinal vessels and to identify changes in arterioles about 100 μm in diameter. The retinal vasculature may be a model of the cerebral vessels both morphologically and functionally. Aim. To evaluate morphological parameters of retinal arterioles in patients with type 1 diabetes mellitus (DM1). Material and methods. The study included 22 DM1 patients (13 females) aged 43.00 ± 9.45 years with a mean diabetes duration of 22.55 ± 10.05 years, and 23 healthy volunteers (10 females) aged 41.09 ± 10.99 years. Blood pressure, BMI, waist circumference, and metabolic control markers of diabetes were measured in both groups. Vascular examinations were performed using an rtx1 adaptive optics retinal camera (Imagine Eyes, Orsay, France); the vessel wall thickness (WT), lumen diameter (LD), wall-to-lumen ratio (WLR), and vascular wall cross-sectional area (WCSA) were assessed. Statistical analysis was performed with the application of IMB SPSS version 23 software. Results. The DM1 group did not differ significantly in age, BMI, waist circumference, blood pressure, or axial length of the eye compared to the control group. Intraocular pressure (IOP) in both groups was normal, but in the DM1 group it was significantly higher. The DM1 group had significantly higher WT, WLR, and WCSA. These parameters correlated significantly with the duration of diabetes, but not with IOP. Conclusions. The presented study demonstrates the presence of significant morphological changes in retinal vessels in DM1 patients without previously diagnosed diabetic retinopathy. Similar changes may occur in the brain and may be early indicators of cardiovascular risk, but further investigation is required to confirm that. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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13 pages, 6128 KiB

Open AccessArticle

A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight

by Daichi Katayama, Nobuhiko Nagano, Shoichi Shimizu, Kimitaka Nakazaki, Kengo Matsuda, Wataru Tokunaga, Kazumasa Fuwa, Ryoji Aoki and Ichiro Morioka

Biomedicines 2022, 10(7), 1642; https://doi.org/10.3390/biomedicines10071642 - 08 Jul 2022

Cited by 1 | Viewed by 1828

Abstract

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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18 pages, 2844 KiB

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The Cause and Effect Relationship of Diabetes after Acute Pancreatitis

by Mariola Śliwińska-Mossoń, Iwona Bil-Lula and Grzegorz Marek

Biomedicines 2023, 11(3), 667; https://doi.org/10.3390/biomedicines11030667 - 22 Feb 2023

Cited by 7 | Viewed by 4197

Abstract

Acute pancreatitis (AP) is an acute inflammation of the pancreas associated with high morbidity and mortality. Endocrine pancreatic insufficiency secondary to AP has drawn increasing attention in recent years. The aim of this paper is to analyze the available clinical and experimental literature to determine the cause and effect relationship of diabetes type 3c (T3cDM; pancreatogenic diabetes) after acute pancreatitis. The clinico-pathological features and management challenges of pancreatogenic diabetes overlap with other secondary causes of diabetes. A complex pathogenesis involving pancreatic exocrine insufficiency, dysfunction of insulin secretion, and insulin resistance is likely the cause of T3cDM after AP. To obtain an improved understanding of the pathophysiology of diabetes after AP, more research is now needed to understand the risk of complications related to the pancreas and diabetes in these patients. Full article

(This article belongs to the Special Issue Novel Aspects in the Pathophysiology and Treatment of Diabetes Mellitus)

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