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Current Therapeutic Trends and Challenges in the Management of Patients with Type 2 Diabetes Mellitus

A special issue of International Journal of Environmental Research and Public Health (ISSN 1660-4601).

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 48621

Special Issue Editors


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Guest Editor
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

E-Mail Website
Guest Editor
First Department of Propaedeutic Medicine, 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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The optimal management of patients with type 2 diabetes mellitus (T2DM) is multifactorial. The major goals of treatment are the prevention or delay of complications and the maintenance of quality of life in a relatively cost-effective manner. This requires an efficient control of hyperglycemia to reduce glucotoxicity, an improvement of coexistent cardiovascular risk factors to optimise cardiovascular outcomes, regular monitoring and re-assessment of treatment goals to ensure patients’ adherence to therapy, and importantly, a patient-focused approach to enhance patient engagement in self-care activities. Individual patient factors and preferences should be carefully considered in order to inform the process of therapeutic decision-making. In this context, the updated position statements of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) place particular emphasis on individualizing glycemic control targets based upon patient preferences, risk of treatment-related adverse effects (especially hypoglycemia and weight gain), and clinical characteristics such as age, frailty and comorbid conditions. Those comorbidities which are particularly relevant for individualizing T2DM treatment are atherosclerotic cardiovascular disease, heart failure and chronic kidney disease. The key factors to guide the selection of appropriate glucose-lowering medication after lifestyle modification and metformin, which are considered as first-line treatment in all patients, are efficacy, safety, tolerability, individual patient preferences and comorbidities, side effects and costs.

The present Special Issue aims to cover a broad range of pharmacological and non-pharmacological therapeutic options for T2DM with proven efficacy to reduce complications and optimise quality of life. Both conventional treatment modalities, as recommended in consensus reports and evidence-based treatment algorithms of international scientific societies, and novel experimental therapies based on solid underlying pathophysiological concepts, can be presented. In this Special Issue, we invite the submission of manuscripts (original research or review articles) addressing fundamental aspects of T2DM management including, but not limited to, medical nutrition therapy, physical activity, bariatric (metabolic) surgery, stress management techniques, oral and injectable formulations, diabetes self-management, education and support, and the integration of evolving technologies such as continuous glucose monitoring. Papers addressing T2DM management in specific patient subgroups such as older patients, pregnant women, adolescents and patients with specific comorbidities such as obesity, non-alcoholic fatty liver disease, established cardiovascular disease and chronic kidney disease, are particularly welcome. We encourage authors to focus on recent therapeutic advances in the field of T2DM management, present novel data and emerging therapeutic concepts, and discuss with a critical perspective both advantages and possible caveats or limitations of specific treatment strategies. All therapeutic approaches discussed should be targeted at reducing complications and optimising health outcomes in patients with T2DM, in the context of comprehensive cardiovascular risk management and individualized (patient-centered) care.

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

Manuscript Submission Information

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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. International Journal of Environmental Research and Public Health 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 2500 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

  • Bariatric surgery
  • Cardiovascular disease
  • Comorbidities
  • Hyperglycemia
  • Individualized treatment
  • Lifestyle modification
  • Medical nutrition
  • Obesity
  • Type 2 diabetes mellitus

Published Papers (6 papers)

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Editorial

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8 pages, 280 KiB  
Editorial
Important Considerations for the Treatment of Patients with Diabetes Mellitus and Heart Failure from a Diabetologist’s Perspective: Lessons Learned from Cardiovascular Outcome Trials
by Chrysi Koliaki and Nicholas Katsilambros
Int. J. Environ. Res. Public Health 2020, 17(1), 155; https://doi.org/10.3390/ijerph17010155 - 24 Dec 2019
Cited by 4 | Viewed by 2281
Abstract
Heart failure (HF) represents an important cardiovascular complication of type 2 diabetes mellitus (T2DM) associated with substantial morbidity and mortality, and is emphasized in recent cardiovascular outcome trials (CVOTs) as a critical outcome for patients with T2DM. Treatment of T2DM in patients with [...] Read more.
Heart failure (HF) represents an important cardiovascular complication of type 2 diabetes mellitus (T2DM) associated with substantial morbidity and mortality, and is emphasized in recent cardiovascular outcome trials (CVOTs) as a critical outcome for patients with T2DM. Treatment of T2DM in patients with HF can be challenging, considering that these patients are usually elderly, frail and have extensive comorbidities, most importantly chronic kidney disease. The complexity of medical regimens, the high risk clinical characteristics of patients and the potential of HF therapies to interfere with glucose metabolism, and conversely the emerging potential of some antidiabetic agents to modulate HF outcomes, are only some of the challenges that need to be addressed in the framework of a team-based personalized approach. The presence of established HF or the high risk of developing HF in the future has influenced recent guideline recommendations and can guide therapeutic decision making. Metformin remains first-line treatment for overweight T2DM patients at moderate cardiovascular risk. Although not contraindicated, metformin is no longer considered as first-line therapy for patients with established HF or at risk for HF, since there is robust scientific evidence that treatment with other glucose-lowering agents such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) should be prioritized in this population due to their strong and remarkably consistent beneficial effects on HF outcomes. Full article

Research

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11 pages, 998 KiB  
Article
Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study
by Chien-Hsieh Chiang, Chia-Sheng Kuo, Wan-Wan Lin, Jun-Han Su, Jin-De Chen and Kuo-Chin Huang
Int. J. Environ. Res. Public Health 2019, 16(12), 2097; https://doi.org/10.3390/ijerph16122097 - 13 Jun 2019
Cited by 3 | Viewed by 3089
Abstract
This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed [...] Read more.
This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed type 2 diabetes patients on any antidiabetic agents in Taiwan before and after exclusion of chronic viral hepatitis, respectively. A total of 5832 and 1237 HCC cases were identified before and after exclusion of chronic viral hepatitis, respectively. Incident HCC risks were positively associated with any use of premixed insulin analogues (adjusted odds ratio (OR), 1.27; 95% CI 1.04 to 1.55) among total participants, especially among current users (adjusted OR, 1.45; 95% CI 1.12 to 1.89). However, the association between HCC occurrence and premixed insulin analogues diminished among participants without chronic viral hepatitis (adjusted OR, 1.35; 95% CI 0.92 to 1.98). We also observed a significant multiplicative interaction between chronic viral hepatitis and premixed insulin analogues on HCC risks (P = 0.010). Conclusions: Chronic viral hepatitis signifies the role of premixed insulin analogues in HCC oncogenesis. We recommend a closer liver surveillance among patients prescribed premixed insulin analogues with concomitant chronic viral hepatitis. Full article
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Review

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22 pages, 662 KiB  
Review
Remission of Type 2 Diabetes Mellitus after Bariatric Surgery: Fact or Fiction?
by Dimitrios Tsilingiris, Chrysi Koliaki and Alexander Kokkinos
Int. J. Environ. Res. Public Health 2019, 16(17), 3171; https://doi.org/10.3390/ijerph16173171 - 30 Aug 2019
Cited by 42 | Viewed by 6330
Abstract
Although type 2 diabetes mellitus (T2DM) has been traditionally viewed as an intractable chronic medical condition, accumulating evidence points towards the notion that a complete remission of T2DM is feasible following a choice of medical and/or surgical interventions. This has been paralleled by [...] Read more.
Although type 2 diabetes mellitus (T2DM) has been traditionally viewed as an intractable chronic medical condition, accumulating evidence points towards the notion that a complete remission of T2DM is feasible following a choice of medical and/or surgical interventions. This has been paralleled by increasing interest in the establishment of a universal definition for T2DM remission which, under given circumstances, could be considered equivalent to a “cure”. The efficacy of bariatric surgery in particular for achieving glycemic control has highlighted surgery as a candidate curative intervention for T2DM. Herein, available evidence regarding available surgical modalities and the mechanisms that drive metabolic amelioration after bariatric surgery are reviewed. Furthermore, reports from observational and randomized studies with regard to T2DM remission are reviewed, along with concepts relevant to the variety of definitions used for T2DM remission and other potential sources of discrepancy in success rates among different studies. Full article
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27 pages, 378 KiB  
Review
SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects
by Anastasios Tentolouris, Panayotis Vlachakis, Evangelia Tzeravini, Ioanna Eleftheriadou and Nikolaos Tentolouris
Int. J. Environ. Res. Public Health 2019, 16(16), 2965; https://doi.org/10.3390/ijerph16162965 - 17 Aug 2019
Cited by 151 | Viewed by 15113
Abstract
Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the latest class of antidiabetic medication that inhibit the absorption of glucose from the proximal tubule of the kidney and hence cause [...] Read more.
Type 2 diabetes mellitus is a chronic metabolic disease associated with high cardiovascular (CV) risk. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the latest class of antidiabetic medication that inhibit the absorption of glucose from the proximal tubule of the kidney and hence cause glycosuria. Four SGLT2i are currently commercially available in many countries: canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT2i reduce glycated hemoglobin by 0.5%–1.0% and have shown favorable effects on body weight, blood pressure, lipid profile, arterial stiffness and endothelial function. More importantly, SGLT2i have demonstrated impressive cardioprotective and renoprotective effects. The main mechanisms underlying their cardioprotective effects have been attributed to improvement in cardiac cell metabolism, improvement in ventricular loading conditions, inhibition of the Na+/H+ exchange in the myocardial cells, alteration in adipokines and cytokines production, as well as reduction of cardiac cells necrosis and cardiac fibrosis. The main adverse events of SGLT2i include urinary tract and genital infections, as well as euglycemic diabetic ketoacidosis. Concerns have also been raised about the association of SGLT2i with lower limb amputations, Fournier gangrene, risk of bone fractures, female breast cancer, male bladder cancer, orthostatic hypotension, and acute kidney injury. Full article
20 pages, 623 KiB  
Review
The Role of DPP-4 Inhibitors in the Treatment Algorithm of Type 2 Diabetes Mellitus: When to Select, What to Expect
by Konstantinos Makrilakis
Int. J. Environ. Res. Public Health 2019, 16(15), 2720; https://doi.org/10.3390/ijerph16152720 - 30 Jul 2019
Cited by 87 | Viewed by 15521
Abstract
Type 2 diabetes mellitus is a growing global public health problem, the prevalence of which is projected to increase in the succeeding decades. It is potentially associated with many complications, affecting multiple organs and causing a huge burden to the society. Due to [...] Read more.
Type 2 diabetes mellitus is a growing global public health problem, the prevalence of which is projected to increase in the succeeding decades. It is potentially associated with many complications, affecting multiple organs and causing a huge burden to the society. Due to its multi-factorial pathophysiology, its treatment is varied and based upon a multitude of pharmacologic agents aiming to tackle the many aspects of the disease pathophysiology (increasing insulin availability [either through direct insulin administration or through agents that promote insulin secretion], improving sensitivity to insulin, delaying the delivery and absorption of carbohydrates from the gastrointestinal tract, or increasing urinary glucose excretion). DPP-4 (dipeptidyl peptidase-4) inhibitors (or “gliptins”) represent a class of oral anti-hyperglycemic agents that inhibit the enzyme DPP-4, thus augmenting the biological activity of the “incretin” hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) and restoring many of the pathophysiological problems of diabetes. They have already been used over more than a decade in the treatment of the disease. The current manuscript will review the mechanism of action, therapeutic utility, and the role of DPP-4 inhibitors for the treatment of type 2 diabetes mellitus. Full article
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13 pages, 2841 KiB  
Review
Epidermal Growth Factor is Effective in the Treatment of Diabetic Foot Ulcers: Meta-Analysis and Systematic Review
by Thien Quoc Bui, Quoc Van Phu Bui, Dávid Németh, Péter Hegyi, Zsolt Szakács, Zoltán Rumbus, Barbara Tóth, Gabriella Emri, Andrea Párniczky, Patricia Sarlós and Orsolya Varga
Int. J. Environ. Res. Public Health 2019, 16(14), 2584; https://doi.org/10.3390/ijerph16142584 - 19 Jul 2019
Cited by 21 | Viewed by 5441
Abstract
Diabetic foot ulcers (DFUs) are one the common complications of diabetes mellitus. Many trials were performed to evaluate the effect of recombinant human epidermal growth factor (rhEGF) in healing DFUs. This meta-analysis was performed to synthesize the evidence of rhEGF treatment in DFUs [...] Read more.
Diabetic foot ulcers (DFUs) are one the common complications of diabetes mellitus. Many trials were performed to evaluate the effect of recombinant human epidermal growth factor (rhEGF) in healing DFUs. This meta-analysis was performed to synthesize the evidence of rhEGF treatment in DFUs in comparison to placebo. Databases included for the search were PubMed, EMBASE, the Cochrane Library, Web of Science, EBSCOhost, ScienceDirect, and Scopus (up to January 2019). The outcome of interest was the complete healing rate of DFUs. We performed random effects meta-analysis stratified by the types of administration route (intralesional injection and topical apply) by calculating the odds ratios (OR) and 95% confidence interval (95% CI). A total of six studies involving 530 patients were eligible for analysis. The combined OR (intralesional injection and topical apply) was 4.005 (95% CI: (2.248; 7.135), p < 0.001). The ORs for intralesional injection and topical application were 3.599 (95% CI: (1.213; 10.677), p = 0.021) and 4.176 (95% CI: (2.112; 8.256), p < 0.001), respectively. Statistical heterogeneity might not be important in overall treatment (I2 = 15.17, p = 0.317) and both of the subgroups (I2: 24.56, p = 0.25 and I2: 33.26, p = 0.213, respectively). Our results support the use of rhEGF in the treatment of DFUs. Full article
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