New Therapeutic Targets in Tissue-Specific Manifestations of Type 2 Diabetes

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Endocrinology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 14679

Special Issue Editors


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Guest Editor
Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, Aristotle University of Thessaloniki, General Hospital “Hippokration”, 57001 Thessaloniki, Greece
Interests: type 2 diabetes mellitus; diabetic complications; cardiovascular disease; heart failure; chronic kidney disease
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Guest Editor
Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: internal medicine; hypertension; cardiovascular disease; clinical research
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Third Department of Cardiology, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: cardiovascular disease; chronic kidney disease; diabetes mellitus; hypertension; complications; heart failure

Special Issue Information

Dear Colleagues,

Type 2 diabetes mellitus is a growing global pandemic, and projections concerning its prevalence are pessimistic. It is closely related to micro- and macrovascular complications, which augment overall morbidity and mortality, while also affecting patients’ quality of life. In addition to classic diabetic complications, type 2 diabetes mellitus is also interconnected with several other diseases, such as non-alcoholic fatty liver disease, dyslipidemia, and metabolic syndrome. There is increasing evidence regarding the tissue-specific manifestations of type 2 diabetes mellitus.

The aim of the present Special Issue is to highlight new research on tissue-specific manifestations of type 2 diabetes mellitus, from pathogenesis to treatment, along with narrative and systematic reviews summarizing relevant evidence published so far. We welcome original articles, narrative reviews, systematic reviews, and meta-analyses.

Dr. Dimitrios Patoulias
Dr. Michael Doumas
Dr. Christodoulos Papadopoulos
Guest Editors

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Keywords

  • type 2 diabetes mellitus
  • cardiovascular disease
  • chronic kidney disease
  • metabolic syndrome
  • SGLT-2 inhibitors
  • GLP-1 receptor agonists
  • newer antidiabetics

Published Papers (4 papers)

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Research

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12 pages, 321 KiB  
Article
The Associations between Kidney Function and Sexual Dysfunction among Males and Females with Type 2 Diabetes Mellitus
by Alexandra Katsimardou, Dimitrios Patoulias, Ioanna Zografou, Zoi Tegou, Konstantinos Imprialos, Konstantinos Stavropoulos, Maria Toumpourleka, Asterios Karagiannis, Konstantinos Petidis and Michael Doumas
Medicina 2023, 59(5), 969; https://doi.org/10.3390/medicina59050969 - 17 May 2023
Cited by 1 | Viewed by 1347
Abstract
Background and Objectives: Diabetic kidney disease (DKD), expressed either as albuminuria, low estimated glomerular filtration rate (eGFR) or both, and sexual dysfunction (SD), are common complications among type 2 diabetes mellitus (T2DM) patients. This study aims to assess whether an association exists [...] Read more.
Background and Objectives: Diabetic kidney disease (DKD), expressed either as albuminuria, low estimated glomerular filtration rate (eGFR) or both, and sexual dysfunction (SD), are common complications among type 2 diabetes mellitus (T2DM) patients. This study aims to assess whether an association exists between DKD and SD, erectile dysfunction (ED) or female sexual dysfunction (FSD) in a T2DM population. Materials and Methods: A cross-sectional study was designed and conducted among T2DM patients. The presence of SD was assessed using the International Index of Erectile Function and the Female Sexual Function Index questionnaires for males and females, respectively, and patients were evaluated for DKD. Results: Overall, 80 patients, 50 males and 30 females, agreed to participate. Sexual dysfunction was present in 80% of the study population. Among the participants, 45% had DKD, 38.5% had albuminuria and/or proteinuria and 24.1% had an eGFR below 60 mL/min/1.73 m2. The eGFR was associated with SD, ED and FSD. Moreover, SD and ED were proven as significant determinants for lower eGFR values in multiple linear regression analyses. DKD was associated with lower lubrication scores and eGFR was associated with lower desire, arousal, lubrication and total scores; however, the multivariate linear regression analyses showed no significant associations between them. Older age resulted in significantly lower arousal, lubrication, orgasm and total FSFI scores. Conclusions: SD is commonly encountered in older T2DM patients and DKD affects almost half of them. The eGFR has been significantly associated with SD, ED and FSD, while SD and ED were proven to be significant determinants for the eGFR levels. Full article
10 pages, 634 KiB  
Article
Effect of Empagliflozin and Dapagliflozin on Ambulatory Arterial Stiffness in Patients with Type 2 Diabetes Mellitus and Cardiovascular Co-Morbidities: A Prospective, Observational Study
by Dimitrios Patoulias, Christodoulos Papadopoulos, Ioanna Zografou, Alexandra Katsimardou, Asterios Karagiannis and Michael Doumas
Medicina 2022, 58(9), 1167; https://doi.org/10.3390/medicina58091167 - 27 Aug 2022
Cited by 4 | Viewed by 2147
Abstract
Background and Objectives: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease. Arterial stiffness is an independent prognostic marker for cardiovascular disease development. We aimed at determining the effect of two different sodium-glucose co-transporter-2 (SGLT-2) inhibitors on [...] Read more.
Background and Objectives: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease. Arterial stiffness is an independent prognostic marker for cardiovascular disease development. We aimed at determining the effect of two different sodium-glucose co-transporter-2 (SGLT-2) inhibitors on ambulatory arterial stiffness in individuals with T2DM. Materials and Methods: In this single-center, single-arm, prospective study performed from January 2020 to August 2021, we planned to enroll adult subjects with T2DM and stable antidiabetic and antihypertensive treatment, assigned either to empagliflozin or dapagliflozin for 6 months. All eligible subjects underwent ambulatory blood pressure monitoring. We set as the primary efficacy outcome the change in ambulatory pulse wave velocity (PWV) from baseline to week 24. Results: We finally enrolled 46 diabetic subjects, with a mean age of 62.89 (8.53) years and mean T2DM duration of 9.72 (6.37) years. Thirty patients received dapagliflozin, while sixteen patients received empagliflozin. Due to COVID-19 pandemic restrictive measures during the study, the mean follow-up period extended from 6 months to 9.98 (3.27) months. Regarding the prespecified primary efficacy outcome, we found that the SGLT-2 inhibitor treatment did not have a significant effect on PWV (p = 0.65). Prior history of cardiovascular disease did not significantly affect the observed effects. Other indices of arterial stiffness, such as augmentation index and central pulse pressure, were not significantly affected, neither by empagliflozin nor by dapagliflozin. Conclusions: SGLT-2 inhibitor treatment with empagliflozin or dapagliflozin in subjects with T2DM failed to improve ambulatory PWV over a mean follow-up of 10 months. Registration number: ISRCTN88851713. Full article
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Review

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15 pages, 1132 KiB  
Review
The Effects of Sodium-Glucose Cotransporter 2-Inhibitors on Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease or Steatohepatitis and Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials
by Ioana-Cristina Bica, Roxana Adriana Stoica, Teodor Salmen, Andrej Janež, Špela Volčanšek, Djordje Popovic, Emir Muzurovic, Manfredi Rizzo and Anca Pantea Stoian
Medicina 2023, 59(6), 1136; https://doi.org/10.3390/medicina59061136 - 12 Jun 2023
Cited by 10 | Viewed by 3043
Abstract
Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome and share multiple causal associations. Both conditions have an alarmingly increasing incidence and lead to multiple complications, which have an impact on a variety of organs and [...] Read more.
Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome and share multiple causal associations. Both conditions have an alarmingly increasing incidence and lead to multiple complications, which have an impact on a variety of organs and systems, such as the kidneys, eyes, and nervous and cardiovascular systems, or may cause metabolic disruptions. Sodium-glucose cotransporter 2-inhibitors (SGLT2-i), as an antidiabetic class with well-established cardiovascular benefits, and its class members have also been studied for their presumed effects on steatosis and fibrosis improvement in patients with NAFLD or non-alcoholic steatohepatitis (NASH). The MEDLINE and Cochrane databases were searched for randomized controlled trials examining the efficacy of SGLT2-i on the treatment of NAFLD/NASH in patients with T2DM. Of the originally identified 179 articles, 21 articles were included for final data analysis. Dapagliflozin, empagliflozin, and canagliflozin are some of the most used and studied SGLT2-i agents which have proven efficacy in treating patients with NAFLD/NASH by addressing/targeting different pathophysiological targets/mechanisms: insulin sensitivity improvement, weight loss, especially visceral fat loss, glucotoxicity, and lipotoxicity improvement or even improvement of chronic inflammation. Despite the considerable variability in study duration, sample size, and diagnostic method, the SGLT2-i agents used resulted in improvements in non-invasive markers of steatosis or even fibrosis in patients with T2DM. This systematic review offers encouraging results that place the SGLT2-i class at the top of the therapeutic arsenal for patients diagnosed with T2DM and NAFLD/NASH. Full article
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Other

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14 pages, 3771 KiB  
Systematic Review
Effect of Fenugreek on Hyperglycemia: A Systematic Review and Meta-Analysis
by Muhammed Shabil, Ganesh Bushi, Pavan Kalyan Bodige, Pavan Sagar Maradi, Bibhu Prasad Patra, Bijaya K. Padhi and Jagdish Khubchandani
Medicina 2023, 59(2), 248; https://doi.org/10.3390/medicina59020248 - 27 Jan 2023
Cited by 4 | Viewed by 7504
Abstract
Fenugreek is used for medicinal purposes in various traditions. Some studies have demonstrated that the seeds of this plant may have an anti-diabetic effect by lowering fasting blood sugar levels and improving glucose tolerance. We conducted a systematic review of the hypoglycemic effects [...] Read more.
Fenugreek is used for medicinal purposes in various traditions. Some studies have demonstrated that the seeds of this plant may have an anti-diabetic effect by lowering fasting blood sugar levels and improving glucose tolerance. We conducted a systematic review of the hypoglycemic effects of fenugreek. An electronic literature search was carried out in the PubMed, Google Scholar, Scopus, and Cochrane Library databases through 18 November 2022 to find trials that assessed fasting blood glucose, postprandial blood glucose, and HbA1c changes in participants treated with fenugreek and in the control group. The mean difference with 95% confidence intervals (CI) was calculated to represent the analysis. Fourteen trials, consisting of 894 participants, were included in the meta-analysis. The results showed a reduction in fasting blood glucose levels (MD: 3.70, 95% CI of −27.02, 19.62; p = 0.76), postprandial blood glucose (MD: −10.61, 95% CI of −68.48, 47.26; p = 0.72), and HbA1c (MD: −0.88, 95% CI −1.49, −0.27; p = 0.00) with fenugreek consumption. While this review and included trials that found beneficial effects of fenugreek consumption on glycemic control, the quality and heterogeneity of studies remain a concern. Given the wider availability and lower cost of fenugreek, rigorous double-blinded randomized controlled trials should be conducted with fenugreek to understand its true potential as a diabetes control herbal agent. Full article
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