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Article ; Online: The effects of sodium-glucose cotransporter 2 inhibitors beyond the cardio-renal-metabolic spectrum: will gliflozins have a different fate than statins?

Koufakis, Theocharis / Tsimihodimos, Vasilis / Metallidis, Symeon / Kotsa, Kalliopi / Doumas, Michael

2023 Volume 24, Issue 16, Page(s) 1753–1756

MeSH term(s)	Humans ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Kidney ; Hypoglycemic Agents/pharmacology ; Glucose ; Sodium/pharmacology ; Diabetes Mellitus, Type 2/drug therapy
Chemical Substances	Sodium-Glucose Transporter 2 Inhibitors ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypoglycemic Agents ; Glucose (IY9XDZ35W2) ; Sodium (9NEZ333N27)
Language	English
Publishing date	2023-08-21
Publishing country	England
Document type	Editorial
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2023.2250255
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Zs.A 5130: Show issues

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Article ; Online: COVID-19 and sulfonylureas: A reminder of the pleiotropic actions of an old class of drugs just before their swansong.

Koufakis, Theocharis / Popovic, Djordje S / Metallidis, Symeon / Kotsa, Kalliopi

Metabolism: clinical and experimental

2022 Volume 133, Page(s) 155221

MeSH term(s)	Diabetes Mellitus, Type 2 ; Humans ; Hypoglycemic Agents/pharmacology ; Hypoglycemic Agents/therapeutic use ; Sulfonylurea Compounds/pharmacology ; Sulfonylurea Compounds/therapeutic use ; COVID-19 Drug Treatment
Chemical Substances	Hypoglycemic Agents ; Sulfonylurea Compounds
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Letter
ZDB-ID	80230-x
ISSN	1532-8600 ; 0026-0495
ISSN (online)	1532-8600
ISSN	0026-0495
DOI	10.1016/j.metabol.2022.155221
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Article ; Online: Intestinal SGLT1 as a therapeutic target in COVID-19-related diabetes: A "two-edged sword" hypothesis.

Koufakis, Theocharis / Metallidis, Symeon / Zebekakis, Pantelis / Kotsa, Kalliopi

British journal of clinical pharmacology

2021 Volume 87, Issue 10, Page(s) 3643–3646

Abstract: Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, ... ...

Abstract	Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.
MeSH term(s)	Blood Glucose ; COVID-19 ; Diabetes Mellitus ; Glucose ; Humans ; SARS-CoV-2 ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
Chemical Substances	Blood Glucose ; Sodium-Glucose Transporter 2 Inhibitors ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.14800
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Zs.A 1118: Show issues

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Article ; Online: Sodium-glucose co-transporter 2 inhibitors in COVID-19: meeting at the crossroads between heart, diabetes and infectious diseases.

Koufakis, Theocharis / Pavlidis, Antonis N / Metallidis, Symeon / Kotsa, Kalliopi

International journal of clinical pharmacy

2021 Volume 43, Issue 3, Page(s) 764–767

Abstract: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering agents which have changed the landscape of diabetes therapy, due to their remarkable cardiorenal protective properties. The attack of severe acute respiratory ... ...

Abstract	Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering agents which have changed the landscape of diabetes therapy, due to their remarkable cardiorenal protective properties. The attack of severe acute respiratory syndrome coronavirus 2 on the heart and kidneys shares similarities with diabetes; therefore, the notion that SGLT2i might have a role in the future management of Coronavirus Disease 2019 (COVID-19) is based on a solid pathophysiological hypothesis. SGLT2i have been proved to decrease the expression of proinflammatory cytokines, ameliorate oxidative stress and reduce sympathetic activity, thus resulting in downregulation of both systemic and adipose tissue inflammation. On the other hand, they have been linked to an increased risk of euglycemic diabetic ketoacidosis. Therefore, the efficacy and safety of SGLT2i in COVID-19 are still debatable and remain to be clarified by ongoing randomized trials, to assess whether the benefits of treatment with these drugs outweigh the potential risks.
MeSH term(s)	COVID-19/complications ; COVID-19/drug therapy ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/virology ; Humans ; Risk Assessment ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
Chemical Substances	Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2021-03-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2601204-2
ISSN	2210-7711 ; 2210-7703 ; 0928-1231
ISSN (online)	2210-7711
ISSN	2210-7703 ; 0928-1231
DOI	10.1007/s11096-021-01256-9
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Article ; Online: The role of sexual dimorphism in susceptibility to SARS-CoV-2 infection, disease severity, and mortality: facts, controversies and future perspectives.

Pegiou, Stavroula / Rentzeperi, Elpiniki / Koufakis, Theocharis / Metallidis, Symeon / Kotsa, Kalliopi

Microbes and infection

2021 Volume 23, Issue 9-10, Page(s) 104850

Abstract: Former studies have revealed intersex variability in immune response to infectious diseases, including Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological surveillance of the ... ...

Abstract	Former studies have revealed intersex variability in immune response to infectious diseases, including Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological surveillance of the ongoing pandemic has demonstrated a male vulnerability to morbidity and mortality, despite similar infection rates between the two sexes. Divergence in the frequency of comorbidities between males and females, differences in hormonal profile, chromosomal composition and gender behavior have all been proposed as potential causative factors. Data deriving from the immunization process indirectly support the existence of a sex-specific response to SARS-CoV-2, since females apparently produce higher numbers of antibodies while simultaneously exhibiting higher rates of side effects, indicating a stronger immune reactivity to the vaccine's elements. Interpreting intersex differences in immune response to SARS-CoV-2 could lead to a deeper understanding of the COVID-19 pathophysiology and enable healthcare professionals to conduct a more accurate patient risk assessment and better predict the clinical outcome of the disease. This narrative review aims to discuss the pathophysiological and behavioral basis of the disproportionate male morbidity and mortality observed in COVID-19, in the context of most research findings in the field.
MeSH term(s)	COVID-19/physiopathology ; Chromosomes, Human, X ; Female ; Gonadal Steroid Hormones ; Humans ; Male ; SARS-CoV-2 ; Severity of Illness Index ; Sex Characteristics ; Sexism ; Vaccination
Chemical Substances	Gonadal Steroid Hormones
Language	English
Publishing date	2021-06-12
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	1465093-9
ISSN	1769-714X ; 1286-4579
ISSN (online)	1769-714X
ISSN	1286-4579
DOI	10.1016/j.micinf.2021.104850
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Zs.A 5014: Show issues

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Article ; Online: Looking deeper into the findings of DARE-19: Failure or an open door to future success?

Koufakis, Theocharis / Maltese, Giuseppe / Metallidis, Symeon / Zebekakis, Pantelis / Kotsa, Kalliopi

Pharmacological research

2021 Volume 173, Page(s) 105872

MeSH term(s)	Glucosides ; Sodium-Glucose Transporter 2 Inhibitors
Chemical Substances	Glucosides ; Sodium-Glucose Transporter 2 Inhibitors
Language	English
Publishing date	2021-09-04
Publishing country	Netherlands
Document type	Letter ; Comment
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2021.105872
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Zs.A 721: Show issues

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Article ; Online: The role of autoimmunity in the pathophysiology of type 2 diabetes: Looking at the other side of the moon.

Koufakis, Theocharis / Dimitriadis, George / Metallidis, Symeon / Zebekakis, Pantelis / Kotsa, Kalliopi

Obesity reviews : an official journal of the International Association for the Study of Obesity

2021 Volume 22, Issue 8, Page(s) e13231

Abstract: Efforts to unravel the pathophysiological mechanisms of type 2 diabetes (T2D) have been traditionally trapped into a metabolic perspective. However, T2D is a phenotypically and pathophysiologically heterogenous disorder, and the need for a tailored ... ...

Abstract	Efforts to unravel the pathophysiological mechanisms of type 2 diabetes (T2D) have been traditionally trapped into a metabolic perspective. However, T2D is a phenotypically and pathophysiologically heterogenous disorder, and the need for a tailored approach in its management is becoming increasingly evident. There is emerging evidence that irregular immune responses contribute to the development of hyperglycemia in T2D and, inversely, that insulin resistance is a component of the pathogenesis of autoimmune diabetes. Nevertheless, it has not yet been fully elucidated to what extent the presence of conventional autoimmune markers, such as autoantibodies, in subjects with T2D might affect the natural history of the disease and particularly each response to various treatments. The challenge for future research in the field is the discovery of novel genetic, molecular, or phenotypical indicators that would enable the characterization of specific subpopulations of people with T2D who would benefit most from the addition of immunomodulatory therapies to standard glucose-lowering treatment. This narrative review aims to discuss the plausible mechanisms through which the immune system might be implicated in the development of metabolic disturbances in T2D and obesity and explore a potential role of immunotherapy in the future management of the disorder and its complications.
MeSH term(s)	Autoantibodies ; Autoimmunity ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Humans ; Insulin Resistance
Chemical Substances	Autoantibodies
Language	English
Publishing date	2021-03-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2147980-X
ISSN	1467-789X ; 1467-7881
ISSN (online)	1467-789X
ISSN	1467-7881
DOI	10.1111/obr.13231
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Article: Predominance of Clostridioides difficile PCR ribotype 181 in northern Greece, 2016–2019

Kachrimanidou, Melina / Metallidis, Symeon / Tsachouridou, Olga / Harmanus, Celine / Lola, Vassiliki / Protonotariou, Efthymia / Skoura, Lemonia / Kuijper, Ed

Anaerobe. 2022 Aug., v. 76

2022

Abstract: The epidemiology of Clostridioides difficile infection (CDI) has undergone many changes since the beginning of this century and continues to evolve based on recent studies. Here, we performed a molecular analysis of C. difficile isolates in northern ... ...

Abstract	The epidemiology of Clostridioides difficile infection (CDI) has undergone many changes since the beginning of this century and continues to evolve based on recent studies. Here, we performed a molecular analysis of C. difficile isolates in northern Greece across 10 health-care facilities, spanning from 2016 to 2019. 221 C. difficile isolates were cultured from stool samples of hospitalized patients with diarrhea and screened by PCR for the presence of the toxin A (tcdA), toxin B (tcdB), the binary toxin (cdtA and cdtB) genes and the regulating gene of tcdC. PCR ribotyping of the cultured isolates was performed by a standardized protocol for capillary gel-based PCR ribotyping and an international database with well-documented reference strains. Thirty-five different PCR ribotypes were identified. The most common RTs identified were: 181 (36%, 80/221), 017 (10%, 21/221), 126 (9%, 19/221), 078 (4%, 9/221) and 012 (4%, 8/221). Notably, the predominant RT181, with toxin profile tcdA⁺tcdB⁺cdtA⁺cdtB⁺, was identified in seven out of ten participating hospitals. Multiple C. difficile ribotypes have been circulating in the northern Greece region with RTs 181 (closely related to 027), 017, 126 and 078 being predominant.
Keywords	Clostridium difficile ; databases ; diarrhea ; epidemiology ; genes ; health services ; ribotypes ; toxins ; Greece
Language	English
Dates of publication	2022-08
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1237621-8
ISSN	1075-9964
ISSN	1075-9964
DOI	10.1016/j.anaerobe.2022.102601
Database	NAL-Catalogue (AGRICOLA)

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Article: The role of autoimmunity in the pathophysiology of type 2 diabetes: Looking at the other side of the moon

Koufakis, Theocharis / Dimitriadis, George / Metallidis, Symeon / Zebekakis, Pantelis / Kotsa, Kalliopi

Obesity reviews. 2021 Aug., v. 22, no. 8

2021

Abstract	Efforts to unravel the pathophysiological mechanisms of type 2 diabetes (T2D) have been traditionally trapped into a metabolic perspective. However, T2D is a phenotypically and pathophysiologically heterogenous disorder, and the need for a tailored approach in its management is becoming increasingly evident. There is emerging evidence that irregular immune responses contribute to the development of hyperglycemia in T2D and, inversely, that insulin resistance is a component of the pathogenesis of autoimmune diabetes. Nevertheless, it has not yet been fully elucidated to what extent the presence of conventional autoimmune markers, such as autoantibodies, in subjects with T2D might affect the natural history of the disease and particularly each response to various treatments. The challenge for future research in the field is the discovery of novel genetic, molecular, or phenotypical indicators that would enable the characterization of specific subpopulations of people with T2D who would benefit most from the addition of immunomodulatory therapies to standard glucose‐lowering treatment. This narrative review aims to discuss the plausible mechanisms through which the immune system might be implicated in the development of metabolic disturbances in T2D and obesity and explore a potential role of immunotherapy in the future management of the disorder and its complications.
Keywords	autoantibodies ; autoimmunity ; hyperglycemia ; immune system ; immunotherapy ; insulin resistance ; insulin-dependent diabetes mellitus ; natural history ; noninsulin-dependent diabetes mellitus ; obesity ; pathogenesis ; pathophysiology ; people
Language	English
Dates of publication	2021-08
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2147980-X
ISSN	1467-789X ; 1467-7881
ISSN (online)	1467-789X
ISSN	1467-7881
DOI	10.1111/obr.13231
Database	NAL-Catalogue (AGRICOLA)

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Zs.A 5908: Show issues

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Article: Herpes Zoster and Diabetes Mellitus: A Review.

Papagianni, Marianthi / Metallidis, Symeon / Tziomalos, Konstantinos

Diabetes therapy : research, treatment and education of diabetes and related disorders

2018 Volume 9, Issue 2, Page(s) 545–550

Abstract: Accumulating evidence suggests that diabetes mellitus (DM) represents an important risk factor for both herpes zoster and post-herpetic neuralgia. Moreover, post-herpetic neuralgia appears to be more severe and persistent in diabetic patients. On the ... ...

Abstract	Accumulating evidence suggests that diabetes mellitus (DM) represents an important risk factor for both herpes zoster and post-herpetic neuralgia. Moreover, post-herpetic neuralgia appears to be more severe and persistent in diabetic patients. On the other hand, a novel vaccine against varicella-zoster virus (VZV) was recently introduced in clinical practice. Given the increased risk and severity of herpes zoster infection in patients with DM, this vaccine might be useful in this population. However, there are limited data regarding the efficacy and safety of vaccination against herpes zoster in the diabetic population. The aim of the present review is to discuss the incidence and consequences of herpes zoster infection in DM and to comment on the role of vaccination against VZV in these patients.
Language	English
Publishing date	2018-03-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2566702-6
ISSN	1869-6961 ; 1869-6953
ISSN (online)	1869-6961
ISSN	1869-6953
DOI	10.1007/s13300-018-0394-4
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