Publications by authors named "Nikolaos Papanas"

260 Publications

Still Science in the Summer.

Int J Low Extrem Wounds 2021 Jun;20(2):81-82

Environmental-Occupational Health Sciences and Non Communicable Diseases Centre of Excellence, Research Institute of Health Sciences, Chiang Mai University, Chiang Mai, Thailand.

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http://dx.doi.org/10.1177/15347346211017006DOI Listing
June 2021

Antidiabetic and Other Therapies Used in Subjects with Diabetes and Chronic Kidney Disease in a Hospital-Based Clinic Population in Greece.

J Clin Med 2021 May 13;10(10). Epub 2021 May 13.

Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.

(1) Background: Type 2 diabetes mellitus (T2DM) is the main cause of chronic kidney disease (CKD). In Greece, in a population from hospital-based diabetes clinics ( = 1759), the overall prevalence of diabetic chronic kidney disease (DCKD) was 45% including mild, moderate, and severe CKD. The aim of this study was to describe and analyze how T2DM patients with mild-to-severe CKD are managed by diabetologists in Greece and assess the achievement rates in glycemic, blood pressure and low-density lipoprotein-cholesterol (LDL-C) control. (2) Methods: This cross-sectional multicenter study took place from June 2015 to March 2016 and collected data from diabetes centers in public hospitals all over Greece. (3) Results: With regard to the anti-diabetes treatment, most participants were on metformin, DPP-4 (Dipeptidyl Peptidase-4 inhibitors) inhibitors and insulin. Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers were the most prescribed medications for hypertension. For the management of dyslipidemia, most participants were on statins. For patients with DCKD, the levels of HbA1c, blood pressure and LDL-C were 7.2%, 137.7/76.9 mmHg and 95.9 mg/dL, respectively (mean values). (4) Conclusions: The outcomes of this study suggest that management of DCKD can be further improved and should be enhanced. These results may contribute to the whole health care system in Greece. In addition, the better understanding of therapeutic strategies used by diabetologists treating these patients offers educational benefits to primary care physicians, which can result in an overall more successful and efficient management of subjects with T2DM and DCKD.
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http://dx.doi.org/10.3390/jcm10102104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153603PMC
May 2021

Diabetic neuropathy: A narrative review of risk factors, classification, screening and current pathogenic treatment options (Review).

Exp Ther Med 2021 Jul 29;22(1):690. Epub 2021 Apr 29.

Department of Diabetes, Nutrition and Metabolic Diseases, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Diabetic neuropathy (DN) is a frequent complication of diabetes mellitus (DM) with severe consequences as it progresses and influences all human body systems. This review discusses the risk factors for DN, the main characteristics of the clinical forms of DN, the screening methods and the current therapeutic options. Distal symmetric DN is the primary clinical form, and DM patients should be screened for this complication. The most important treatment of DN remains good glucose control, generally defined as HbA1c ≤7%. Symptomatic treatment improves life quality in diabetic patients. Pharmacological agents such as alpha (α)-lipoic acid and benfotiamine have been validated in several studies since they act on specific pathways such as increased oxidative stress (α-lipoic acid exerts antioxidant effects) and the excessive production of advanced glycosylation products (benfotiamine may inhibit their production via the normalization of glucose). Timely diagnosis of DN is significant to avoid several complications, including lower limb amputations and cardiac arrhythmias.
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http://dx.doi.org/10.3892/etm.2021.10122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111877PMC
July 2021

Blood Vessel Density Measured Using Dynamic Optical Coherence Tomography is a Tool for Wound Healers.

Int J Low Extrem Wounds 2021 May 7:15347346211017334. Epub 2021 May 7.

Democritus University of Thrace, Alexandroupolis, Greece.

Dynamic optical coherence tomography (D-OCT) is a relatively new technique that may be used to study the substructures in the retina, in the skin and its microcirculation. Furthermore, D-OCT is a validated method of imaging blood flow in skin microcirculation. The skin around venous and mixed arterio-venous ulcers was imaged and found to have tortuous vessels assumed to be angiogenic sprouts, and classified as dots, blobs, coils, clumps, lines, and curves. When these images were analyzed and measurements of vessel density were made, it was observed that the prevalence of coils and clumps in wound borders was significantly greater compared with those at wound centers. This reinforced the belief of inward growth of vessels from wound edge toward wound center which, in turn, reposed confidence in following the wound edge to study healing. D-OCT imaging permits the structure and the function of the microcirculation to be imaged, and vessel density measured. This offers a new vista of skin microcirculation and using it, to better understand angiogenesis in chronic wounds.
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http://dx.doi.org/10.1177/15347346211017334DOI Listing
May 2021

New Sub-Phenotyping of Subjects at High Risk of Type 2 Diabetes: What Are the Potential Clinical Implications?

Diabetes Ther 2021 Jun 4;12(6):1605-1611. Epub 2021 May 4.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.

Prediabetes is defined as a condition of abnormal glucose metabolism, characterised by plasma glucose above normal range but not as high as required for the diagnosis of diabetes mellitus (DM). It represents a heterogeneous entity of intermediate glucose metabolism, including impaired fasting glucose, impaired glucose tolerance, and borderline glycated haemoglobin. Prediabetes is being increasingly recognised as an important metabolic state not only predisposing to a higher probability of future progression to DM, but also to an increased risk of different micro- and macrovascular complications. The recently proposed sub-phenotyping of individuals at increased risk of type 2 DM, which distinguishes six different clusters, offers the opportunity for the improvement in screening, prevention, and treatment algorithms. Such progress should also enable more efficient and cost-effective strategies aimed at decreasing the disease burden associated with prediabetes.
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http://dx.doi.org/10.1007/s13300-021-01065-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093908PMC
June 2021

Review Failure Index as the Opposite Reflection of the Retraction Rate. A Proposal for a New Journal Metric Index.

Ann Vasc Surg 2021 Apr 24. Epub 2021 Apr 24.

Department of Vascular Surgery, "Democritus" University of Thrace, University General Hospital of Alexandroupolis, Thrace, Greece; University of Cyprus, Nicosia, Cyprus.

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http://dx.doi.org/10.1016/j.avsg.2021.04.006DOI Listing
April 2021

Novel molecular markers of cardiovascular disease risk in type 2 diabetes mellitus.

Biochim Biophys Acta Mol Basis Dis 2021 Aug 20;1867(8):166148. Epub 2021 Apr 20.

Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy; Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine Columbia, South Carolina, USA.

Diabetes represents the leading risk factor for the development of cardiovascular disease (CVD). Chronic hyperglycemia and/or acute post-prandial changes in blood glucose determine an increase in reactive oxygen species (ROS), which play a fundamental role in endothelial dysfunction and in the nuclear transport of pro-atherogenic transcription factors that activate the "inflammasome". In addition, the glycemic alteration favors the formation and stabilization of atherosclerotic plaque through the mechanism of non-enzymatic glycation of different molecules, with the establishment of the so-called "advanced glycosylation end products" (AGE). Laboratory information provided by the level of biomarkers could make a quantitative and qualitative contribution to the clinical process of screening, prediction, prevention, diagnosis, prognosis and monitoring of cardiovascular (CV) risk linked to diabetes. This review describes the importance of specific biomarkers, with particular focus on novel ones, for stratifying and management of diabetes CV risk.
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http://dx.doi.org/10.1016/j.bbadis.2021.166148DOI Listing
August 2021

COVID-19 Toes and Other Skin Lesions During the Pandemic: Emerging Entities?

Int J Low Extrem Wounds 2021 Apr 23:15347346211011843. Epub 2021 Apr 23.

Diabetes Centre-Diabetic Foot Clinic, Democritus University of Thrace, Alexandroupolis, Greece.

There is accumulating evidence to indicate an association between coronavirus infectious disease 2019 (COVID-19) and clusters of incident cutaneous eruptions. Of these, chilblains-like perniosis have received widespread medical and media attention. These typically affect the toes, and have been called "COVID-toes." Other acral lesions such as large bullae have also been reported. However, a definitive causal relationship with the severe acute respiratory syndrome coronavirus 2 has not yet been definitively proven, nor has a pathogenic mechanism been established. These episodes are self-limiting, but we need to know whether long-term sequelae exist.
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http://dx.doi.org/10.1177/15347346211011843DOI Listing
April 2021

Web-based Medical Education During COVID-19 Lockdown: A Step Back or a Leap to the Future?

Int J Low Extrem Wounds 2021 Apr 23:15347346211011848. Epub 2021 Apr 23.

37791Department of Vascular Surgery, Democritus University of Thrace, Alexandroupolis, Greece.

The impact of coronavirus infectious disease (COVID-19) on medical education has been substantial. Medical students require considerable clinical exposure. However, due to the risk of COVID-19, the majority of medical schools globally have discontinued their normal activities. The strengths of virtual teaching now include a variety of web-based resources. New interactive forms of virtual teaching are being developed to enable students to interact with patients from their homes. Conversely, students have received decreased clinical training in certain medical and surgical specialities, which may, in turn, reduce their performance, confidence, and abilities as future physicians. We sought to analyze the effect of telemedicine on the quality of medical education in this new emerging era and highlight the benefits and drawbacks of web-based medical training in building up future physicians. The COVID-19 pandemic has posed an unparalleled challenge to medical schools, which are aiming to deliver quality education to students virtually, balancing between evidence-based and experience-based medicine.
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http://dx.doi.org/10.1177/15347346211011848DOI Listing
April 2021

The contribution of dietary glycemic index and glycemic load to the development of microvascular complications of diabetes.

Nutrition 2021 Mar 6;89:111234. Epub 2021 Mar 6.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address:

Lifestyle modification, including a healthy diet, is of paramount importance in the management of diabetes mellitus. To this end, diets have been proposed with low glycemic index (an index of carbohydrate food expressing how quickly this nutrient can increase blood glucose) and glycemic load (an index obtained by multiplying the glycemic index by the grams of carbohydrate, then dividing by 100). The aim of this review was to discuss the potential contribution of diets with low glycemic index and glycemic load in diabetic microvascular complications. Currently, their role to the prevention and delay of microvascular complications in diabetes mellitus remains unclear, and further knowledge is desirable.
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http://dx.doi.org/10.1016/j.nut.2021.111234DOI Listing
March 2021

Considerations for single- versus multiple-drug pharmacotherapy in the management of painful diabetic neuropathy.

Expert Opin Pharmacother 2021 Apr 5:1-14. Epub 2021 Apr 5.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

Introduction: The efficacy of monotherapy to reduce pain from diabetic peripheral neuropathy (DPN) is frequently not satisfactory and guidelines do not provide unanimous treatment options. In this context, multiple drug pharmacotherapy may provide benefit.

Areas Covered: The aim of the present review is to describe the clinical trials addressing the pharmacotherapy of painful DPN. Studies discussing efficacy and tolerability of pharmacological agents that were assessed in monotherapy and in combination treatment are reported and discussed.

Expert Opinion: Several clinical trials have reported benefit of multiple-drug pharmacotherapy. Nevertheless, untoward effects of combination treatment are of concern. Importantly, some trials were restricted to comparison with placebo and other compared only with active comparator(s). Only limited clinical trials assessed selected cohorts of individuals experiencing different stages of painful DPN. Despite current limitations, some evidence of studies implicating a comparison to all active comparators points to safety and effectiveness of the combination of oxycodone with pregabalin and that of pregabalin with the 5% lidocaine plaster but future, clear-cut studies are required to drive evidence-based decisions in the clinical setting.
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http://dx.doi.org/10.1080/14656566.2021.1909570DOI Listing
April 2021

Review Article: The Flagship of Evidence-Based Medicine.

Int J Low Extrem Wounds 2021 Jun 22;20(2):83-87. Epub 2021 Mar 22.

Democritus University, Alexandroupolis, Greece.

Global literature is ever-growing and physicians rely on it for evidence-based decision making. Review articles summarize available literature and provide the current state of knowledge on a given topic. Various review types exist, the main ones being narrative and systematic reviews. The former are based on studies selected in an undefined manner. They express the authors' opinions of a given topic, lack a systematic search, and are prone to bias. By contrast, the latter represent an unbiased synthesis of knowledge on a particular topic and attempt to offer all relevant evidence. A systematic review may include a meta-analysis, which combines the results of quantitative studies using statistical techniques to provide a more precise summary of the evidence. With a dramatic increase in literature complexity, new "next-generation" types of reviews emerged to improve the quality of evidence synthesis: network meta-analysis, umbrella review, and meta-analysis of individual patient data, among others. Finally, scoping reviews are a special type, conducted as precursors to systematic reviews aiming to reveal specific knowledge gaps in a given subject.
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http://dx.doi.org/10.1177/1534734621995636DOI Listing
June 2021

Sweet Readers Love the Spring.

Int J Low Extrem Wounds 2021 Mar;20(1)

NCD Centre of Excellence, Research Institute of Health Sciences, Chiang Mai University, Chiang Mai, Thailand.

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http://dx.doi.org/10.1177/15347346211000035DOI Listing
March 2021

Expert Opinion: A Call for Basal Insulin Titration in Patients with Type 2 Diabetes in Daily Practice: Southeast European Perspective.

Diabetes Ther 2021 May 15;12(5):1575-1589. Epub 2021 Mar 15.

Department of Endocrinology, Faculty of Medicine, Medical University of Sofia, Sofia, Bulgaria.

Therapeutic inertia related to insulin treatment, i.e. delays in initiation, especially titration of basal insulin, is a significant problem in daily practice in Southeast European countries. This phenomenon can be traced back to several patient-, physician- and health system-related factors. In recognition of the issue of inadequate insulin titration, 11 leading experts from countries in this region held a consensus-seeking meeting to review the current status of insulin initiation after non-insulin treatment and the potential barriers to insulin titration to provide an algorithm and tools for outpatient physicians and for patients aimed at optimizing basal insulin titration. The experts reached a consensus on the majority of the topics and proposed recommendations on how clinical inertia can be overcome. The outcomes of the meeting have been summarized in this paper.
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http://dx.doi.org/10.1007/s13300-021-01037-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957039PMC
May 2021

Reduction of Depression in Diabetes: A New Pleiotropic Action of Metformin?

Diabetes Ther 2021 Apr 14;12(4):965-968. Epub 2021 Mar 14.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

Metformin remains the cornerstone of management for type 2 diabetes mellitus (T2DM). It is also known that it has beneficial pleiotropic actions. In addition, there is emerging evidence that this agent may prove beneficial in ameliorating depression in T2DM. The underlying mechanisms of this new action remain elusive, but experimental studies point to improved synaptic function and increased serotonin activity, along with the known inflammatory and antioxidant properties of metformin. Obviously, we need to further explore the potential utility of such antidepressant effects among T2DM subjects in everyday reality.
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http://dx.doi.org/10.1007/s13300-021-01044-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955898PMC
April 2021

Double Diabetes: A Growing Problem Requiring Solutions.

Exp Clin Endocrinol Diabetes 2021 Feb 26. Epub 2021 Feb 26.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, GREECE.

The growing proportion of type 1 diabetes mellitus (T1DM) patients with clinical features of insulin resistance (IR) has led to the description of a distinctive T1DM subgroup, still unrecognised by current guidelines, called double diabetes, assumingly associated with poorer metabolic phenotype and increased risk of micro- and macrovascular complications. The main goal of identifying double diabetes, estimated to be present in up to half of T1DM patients, is timely implementation of appropriate therapeutic interventions to reduce the increased risk of chronic complications and other adverse metabolic traits associated with this condition. Proposed diagnostic criteria are largely divided into three different groups: family history of type 2 diabetes mellitus (T2DM), obesity/metabolic syndrome, and IR. Estimated glucose disposal rate may prove the most reliable marker of double diabetes. In addition to general measures (diet, physical activity, antihypertensive, and lipid-lowering medications, etc.) and development of new insulin preparations with more hepatic action, double diabetes patients may derive more benefit from agents developed for T2DM. Indeed, such potentially promising agents include glucagon-like peptide-1 receptor agonists, sodium-glucose contrasporter-2 inhibitors, and their combination. We are now awaiting long-term trials assessing metabolic and vascular benefits of these medications in double diabetes.
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http://dx.doi.org/10.1055/a-1392-0590DOI Listing
February 2021

Skin AGEs and diabetic neuropathy.

BMC Endocr Disord 2021 Feb 23;21(1):28. Epub 2021 Feb 23.

Diabetes Centre-Diabetic Foot Clinic, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, G. Kondyli 22c, 68100, Alexandroupolis, Greece.

Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for measurement of tissue-bound AGEs is tissue biopsy. However, their assessment with the newer, fast and simple method of skin autofluorescence (sAF) has recently gained special interest by virtue of its non-invasive, highly reproducible nature and its acceptable correlation with the reference method of skin biopsy. Accumulation of tissue AGEs evaluated by sAF has been shown to independently correlate with DN. Importantly, increasing evidence underscores their potential value as early biomarkers of the latter. Further important associations include diabetic nephropathy, diabetic retinopathy and cardiovascular autonomic neuropathy. However, the value of the implementation of screening with skin AGEs for DN remains unclear. The aim of the present review is to critically summarise current evidence on the association between skin AGEs and diabetic microvascular complications, with a particular emphasis on diabetic neuropathy, and to note the most important limitations of existing knowledge. Longer follow-up studies are also highly anticipated to clarify its role and provide data on patient selection and cost-effectiveness.
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http://dx.doi.org/10.1186/s12902-021-00697-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903740PMC
February 2021

New-Onset Diabetes in COVID-19: Time to Frame Its Fearful Symmetry.

Diabetes Ther 2021 Feb 26;12(2):461-464. Epub 2020 Dec 26.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

There is increasing evidence that coronavirus disease 2019 (COVID-19) may lead to new-onset diabetes mellitus (DM). This may occur even in patients without predisposing factors for impaired glucose metabolism. Both impaired pancreatic insulin secretion and insulin resistance have been implicated as underlying mechanisms. Importantly, new-onset hyperglycaemia is associated with worse prognosis in patients with COVID-19. Indeed, its prognosis may be even more sinister than in patients with pre-existing DM. More research data and knowledge are currently being collected to improve our insights into this constellation and to guide therapies in clinical reality.
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http://dx.doi.org/10.1007/s13300-020-00988-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765692PMC
February 2021

Diabetic Retinopathy in Patients With Diabetic Foot Ulcer: A Systematic Review.

Int J Low Extrem Wounds 2021 Jun 22;20(2):98-103. Epub 2020 Dec 22.

University of Medicine and Pharmacy "Carol Davila" Bucharest, Bucharest, Romania.

This review discusses the evidence on diabetic retinopathy (DR) in patients with diabetic foot ulceration (DFU). A systematic literature review was performed on PubMed, Medline, Springer Nature, and Scopus, following the PRISMA guidelines, using the following terms, individually or in combination: "diabetic foot ulcer" OR "diabetic foot syndrome" OR "DFU" and "diabetic retinopathy." The initial search yielded 648 articles published between 1975 and 2020. After applying exclusion and inclusion criteria, a total of 9 articles were analyzed, assessing the correlations between DR and DFU. In all cases, DR and especially proliferative diabetic retinopathy were significantly higher in the presence of DFU, though the frequency of DR showed large variability (22.5% to 95.6%). There was a significant correlation between advanced stages of DFU and increased frequency of DR and proliferative diabetic retinopathy. On the other hand, there is a risk of accelerated progression of DR in nonhealing DFUs, possibly related to chronic inflammation and associated infection. Hence, patients with DFUs should be monitored by an ophthalmologist, and those with DR should be promptly referred to a specialized diabetic foot clinic.
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http://dx.doi.org/10.1177/1534734620982237DOI Listing
June 2021

Efficacy and Safety of Adjunctive Cilostazol to Clopidogrel-Treated Diabetic Patients With Symptomatic Lower Extremity Artery Disease in the Prevention of Ischemic Vascular Events.

J Am Heart Assoc 2021 Jan 17;10(1):e018184. Epub 2020 Dec 17.

Internal Medicine Clinic General Hospital of Sitia Crete Greece.

Background Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti-inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2-arm, multicenter, open-label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow-up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex-adjusted hazard ratio [HR], 0.468; 95% CI, 0.252-0.870; =0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; =0.046) and improved the ankle-brachial index and pain-free walking distance values (=0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex-adjusted HR, 1.080; 95% CI, 0.579-2.015; =0.809). Conclusions Adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.
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http://dx.doi.org/10.1161/JAHA.120.018184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955466PMC
January 2021

Ultrasound: The Magic Wand for Wound Healers.

Int J Low Extrem Wounds 2020 Dec;19(4):291-292

NCD Centre of Excellence, Research Institute of Health Sciences, Chiang Mai University, Chiang Mai, Thailand.

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http://dx.doi.org/10.1177/1534734620977227DOI Listing
December 2020

Diabetes Mellitus and Hypertension as Major Risk Factors of Mortality From Covid-19 Pneumonia.

Exp Clin Endocrinol Diabetes 2020 Dec 9. Epub 2020 Dec 9.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece.

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http://dx.doi.org/10.1055/a-1325-0381DOI Listing
December 2020

Local Antibiotic Delivery Systems in the Surgical Treatment of Diabetic Foot Osteomyelitis: Again, No Benefit?

Int J Low Extrem Wounds 2020 Dec 9:1534734620973961. Epub 2020 Dec 9.

Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece.

This retrospective study aimed to compare the outcomes and healing parameters of 3 groups of surgical treatment combined with and without local antibiotic administration in diabetic foot osteomyelitis (DFO). Overall, 25 patients with DFO who met the criteria were included in the study. Surgical debridement was used with systemic antibiotic administration alone (group A; n = 8) or combined with local application of antibiotic-loaded polymethylmethacrylate beads (group B; n = 9) or antibiotic-loaded hydroxyapatite and calcium sulfate beads (group C; n = 8). In total, 87.5% patients in group A, 100% in group B, and 87.5% in group C healed ( = .543). Median time to healing was 17 weeks in group A, 18 weeks in group B, and 19 weeks in group C ( = .094). One patient (12.5%) in group A was amputated. DFO recurrence rate was 12.5% in group A and 12.5% in group C ( = .543). Median hospitalization was 9 days in group A, 8 days in group B, and 9 days in group C ( = .081). In conclusion, adjunctive local antibiotic therapy was not shown to improve outcomes in surgically treated DFO.
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http://dx.doi.org/10.1177/1534734620973961DOI Listing
December 2020

1 h post-load plasma glucose: Should it be re-examined as a diagnostic criterion of diabetes?

Prim Care Diabetes 2021 Jun 26;15(3):622. Epub 2020 Nov 26.

Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, 681 00 Alexandroupolis, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.pcd.2020.11.006DOI Listing
June 2021

Metabolic Syndrome and Abnormal Peri-Organ or Intra-Organ Fat (APIFat) Deposition in Chronic Obstructive Pulmonary Disease: An Overview.

Metabolites 2020 Nov 15;10(11). Epub 2020 Nov 15.

Department of Clinical Biochemistry, Royal Free Hospital campus, University College London Medical School, University College London (UCL), London NW3 2QG, UK.

Chronic obstructive pulmonary disease (COPD) is a common disorder with an increasing prevalence, characterised by persistent respiratory symptoms and airflow limitation. Systemic inflammation is involved in the pathogenesis of COPD and can also predispose to metabolic disorders (e.g., metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD)). Such comorbidities can negatively affect COPD outcomes, cardiovascular risk, and quality of life. Apart from NAFLD, abnormal peri-organ or intra-organ fat (APIFat) could be considered as markers for cardiometabolic diseases and even for COPD. The present narrative review considers the associations of COPD with MetS, NAFLD, and other APIFat, including epicardial, perirenal, peripancreatic, and intramuscular adipose tissue. Further research is needed to define these relationships and identify any potential clinical implications.
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http://dx.doi.org/10.3390/metabo10110465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696438PMC
November 2020

Genetic variation in , a gene coding for an NLRP3 inflammasome-associated protein, alters the genetic risk for diabetic nephropathy in the context of type 2 diabetes mellitus.

Diab Vasc Dis Res 2020 Nov-Dec;17(6):1479164120970892

1st Laboratory of Medical Biology-Genetics, Department of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Background: Approximately one third of type 2 diabetes mellitus (T2DM) cases present with diabetic nephropathy (DN), the leading cause of end-stage renal disease. Inflammation plays an important role in T2DM disease and DN pathogenesis. NLRP3 inflammasomes are complexes that regulate interleukin-1B (IL-1B) and IL-18 secretion, both involved in inflammatory responses. Activation of NLRP3 is associated with DN onset and progression. Here, we explore whether DN is associated with variants in genes encoding key members of the NLRP3 inflammasome pathway.

Methods: Using genome-wide association data, we performed a pilot case-control association study, between 101 DN-T2DM and 185 non-DN-T2DM cases from the Hellenic population across six NLRP3 inflammasome pathway genes.

Results: Three common variants confer decreased risk for DN, namely rs11665831 (OR = 0.62,  = 0.016), rs11083925 (OR = 0.65,  = 0.021), and rs2043211 (OR = 0.66,  = 0.026), independent of sex or co-inheritance with an variant.

Conclusion: CARD8 acts as an NLRP3, NF-κB and caspase-1 inhibitor; perhaps, alterations in the cross-talk between CARD8, NF-κB, and NLRP3, which could affect the pro-inflammatory environment in T2DM, render diabetic carriers of certain common variants potentially less likely to develop T2DM-related pro-inflammatory responses followed by DN. These preliminary, yet novel, observations will require validation in larger cohorts from several ethnic groups.
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http://dx.doi.org/10.1177/1479164120970892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919199PMC
January 2021

Nonpharmacological Management of Diabetic Foot Ulcers: An Update.

Int J Low Extrem Wounds 2020 Oct 19:1534734620963561. Epub 2020 Oct 19.

First Department of Propaedeutic Internal Medicine and Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital.

Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes mellitus that is associated with increased morbidity and mortality, as well as substantial economic burden for the health care system. The standard of care for DFUs includes pressure off-loading, sharp debridement, and wound moisture balance, along with infection control and management of peripheral arterial disease. A variety of advanced modalities that target distinct pathophysiological aspects of impaired wound healing in diabetes are being studied as possible adjunct therapies for difficult to heal ulcers. These modalities include growth factors, stem cells, cultured fibroblasts and keratinocytes, bioengineered skin substitutes, acellular bioproducts, human amniotic membranes, oxygen therapy, negative pressure wound therapy, and energy therapies. Additionally, the use of advanced biomaterials and gene delivery systems is being investigated as a method of effective delivery of substances to the wound bed. In the present narrative review, we outline the latest advances in the nonpharmacological management of DFUs and summarize the efficacy of various standard and advanced treatment modalities.
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http://dx.doi.org/10.1177/1534734620963561DOI Listing
October 2020

Endothelial Dysfunction and Platelet Hyperaggregation in type 2 Diabetes Mellitus: The era of novel anti-diabetic agents.

Curr Med Chem 2020 Oct 9. Epub 2020 Oct 9.

First Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA University Hospital of Thessaloniki. Greece.

Background: Diabetes mellitus (DM) incidence is ever-increasing and along with its microvascular and macrovascular complications is associated with a high morbidity and mortality burden globally. Major components of diabetes pathophysiology include glucotoxicity, lipotoxicity and insulin resistance, disturbing the vascular wall integrity and leading to endothelial dysfunction and platelet hyperaggregation.

Objective: This review aims to identify and summarize the effect of novel anti-diabetic agents (glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter -2 inhibitors) on endothelial (EF) and platelet function (PF) and evaluate the consistency with the results of cardiovascular outcomes studies.

Methods: We performed a structured search of the PubMed database for peer-reviewed research of the literature between 1981 and 2020 regarding the effect of DM and novel anti-diabetic agents on EF and PF.

Results: We analyzed data regarding the effect of novel anti-diabetic agents on EF and PF as well as the pathophysiological interplay between DM, PF, and EF. The available studies use different methods to evaluate these outcomes and the results of different studies are rather conflicting as a result of different study designs, combinations of drugs tested, small study samples and patient population heterogeneity.

Conclusion: The currently available data do not unequivocally support a consistent effect of novel antidiabetic agents on EF and PF. Further study is required ideally with validation of the results with clinical outcomes.
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http://dx.doi.org/10.2174/0929867327666201009143816DOI Listing
October 2020

Dryness of Foot Skin Assessed by the Visual Indicator Test and Risk of Diabetic Foot Ulceration: A Prospective Observational Study.

Front Endocrinol (Lausanne) 2020 8;11:625. Epub 2020 Sep 8.

First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.

Previous cross-sectional studies have shown an association between sudomotor dysfunction and diabetic foot ulceration (DFU). The aim of this prospective multicenter study was to determine the role of dryness of foot skin and of established neurological modalities in the prediction of risk for foot ulceration in a cohort of individuals with diabetes mellitus (DM). The study was conducted from 2012 to 2017. A total of 308 subjects with DM without history of DFU or critical limb ischemia completed the study. Diabetic neuropathy was assessed using the neuropathy symptom score (NSS) and neuropathy disability score (NDS). In a subset of participants, vibration perception threshold (VPT) was evaluated. Dryness of foot skin was assessed by the visual indicator plaster method (IPM). The diagnostic performance of the above neurological modalities for prediction of DFU was tested by receiver operating characteristic curve (ROC) analysis. During the 6-year follow-up, 55 patients (annual ulceration incidence 2.97%) developed DFU. Multivariate Cox-regression analysis after controlling for the effect of age, gender, and DM duration demonstrated that the risk (hazard ratio, 95% confidence intervals) of DFU increased significantly with either abnormal IPM (3.319, 1.460-7.545, = 0.004) or high (≥6) NDS (2.782, 1.546-5.007, = 0.001) or high (≥25 volts) VPT (2.587, 1.277-5.242, = 0.008). ROC analysis showed that all neurological modalities could discriminate participants who developed DFU ( < 0.001). IPM testing showed high sensitivity (0.86) and low specificity (0.49), while high vs. low NDS and VPT showed low sensitivity (0.40 and 0.39, respectively) and high specificity (0.87 and 0.89, respectively) for identification of patients at risk for DFU. Dryness of foot skin assessed by the IPM predicts the development of DFU. IPM testing has high sensitivity, whereas high NDS and VPT have high specificity in identifying subjects at risk for DFU. The IPM can be included in the screening methods for identification of the foot at risk.
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http://dx.doi.org/10.3389/fendo.2020.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506164PMC
May 2021

Adherence to the National Guidelines for Follow-Up Protocol in Subjects with Type 2 Diabetes Mellitus in Greece: The GLANCE Study.

Diabetes Ther 2020 Dec 3;11(12):2887-2908. Epub 2020 Oct 3.

First Department of Propaedeutic Internal Medicine, Laiko General Hospital, National Kapodistrian University of Athens Medical School, Athens, Greece.

Introduction: Physician adherence, or lack therefore, to diabetes care and follow-up guidelines may be linked to the rates of achieving suboptimal glycaemic, blood pressure and lipid targets in people with type 2 diabetes mellitus (T2DM). In this cross-sectional study we evaluated physician adherence to the patient follow-up protocol (PFP) of the 2017 Hellenic Diabetes Association (HDA) guidelines and also assessed glycated haemoglobin (HbA), blood pressure and lipid control achievement rates in the routine care setting in Greece.

Methods: Eligible subjects were adults with T2DM receiving oral hypoglycaemic agents (OHAs) for ≥ 1 year who had ≥ 2 HbA measurements in the previous year and an HbA target < 7%. Overall adherence at the subject level was defined as the percentage of the 62 HDA PFP items that had been met during the past year.

Results: Between June and December 2018, 601 eligible subjects (54.6% men; mean age 65.2 years; median T2DM duration 5.9 years, of whom 96.5% had ≥ 1 medical condition/comorbidity), were enrolled into the study by 53 hospital- and office-based endocrinologists, internists and general practitioners. The main OHAs prescribed at enrolment were metformin (91.0%), dipeptidyl peptidase-4 inhibitors (60.7%), sodium-glucose co-transporter-2 inhibitors (23.5%) and sulphonylureas (16.3%). Mean overall physician adherence to the PFP was 43.6%. Predictors of greater higher physicans' adherence were female sex (p = 0.026), > 3 medical conditions/comorbidities (p = 0.043) and diabetic complications (p < 0.001). HbA, low-density lipoprotein-cholesterol, systolic/diastolic blood pressure and composite metabolic targets were achieved by 82.1, 57.0, 42.6 and 21.6% of subjects, respectively.

Conclusions: In Greek routine care, physician adherence to the PFP of the 2017 HDA guidelines is suboptimal. Future efforts should focus on identifying the barriers to an adequate adherence by physicians to the full PFP, with the aim to provide optimal patient care.
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http://dx.doi.org/10.1007/s13300-020-00935-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644661PMC
December 2020