Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

Júnior, Wellington Santana da Silva; Godoy-Matos, Amélio F.; Kraemer‐Aguiar, Luiz Guilherme

doi:10.1155/2015/816164

Cited by 44 publications

(21 citation statements)

References 82 publications

(117 reference statements)

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“…Sitagliptin was the first agent of this class to be approved by the FDA in 2006 [7] . The DPP-4 enzyme has many functions including biological roles in pro-inflammatory pathways [8] . DPP-4 is also known as CD26 and is widely expressed in various cell types throughout the body including the skin, but the role of the DPP-4 enzyme in autoimmune pathogenesis has not yet been clearly elucidated [9,10] .…”

Section: Discussionmentioning

confidence: 99%

Linagliptin-Associated Alopecia and Bullous Pemphigoid

Someili

Azzam

Hilal

2019

European Journal of Case Reports in Internal Medicine

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Bullous pemphigoid is a chronic autoimmune blistering disease. Recently, several reports suggested dipeptidyl peptidase 4 (DPP-4) inhibitors, also known as gliptins, were a potential cause of drug-induced bullous pemphigoid but not of both bullous pemphigoid and alopecia areata together. Here we describe the case of a 68-year-old man with type 2 diabetes mellitus who developed new onset diffuse alopecia on the scalp with diffuse tense bullae over his body a few months after linagliptin was introduced for better control of his diabetes. DPP-4 inhibitors are not known to increase the risk of alopecia. To the best of our knowledge, this is the first report of linagliptin-associated alopecia areata and bullous pemphigoid, which may help demonstrate if there are any links between DPP-4 inhibitors and alopecia. LEARNING POINTS • This is the first report of linagliptin-associated alopecia areata and bullous pemphigoid (BP), which may help demonstrate a link between DPP-4 inhibitors and alopecia. • Since the time of onset of BP after initiation of a DPP-4 inhibitor varies, a high index of suspicion is needed for diagnosis. • Early diagnosis is essential as DPP-4 inhibitor withdrawal has a significant effect on disease remission.

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Section: Discussionmentioning

confidence: 99%

Linagliptin-Associated Alopecia and Bullous Pemphigoid

Someili

Azzam

Hilal

2019

European Journal of Case Reports in Internal Medicine

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“…DPP-4 is a ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of Type 2 Diabetes Mellitus. DPP4 is mainly secreted by adipocytes and endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function [ 103 ].…”

Section: Role Of Adipose Tissues In Obesity-induced Inflammation Amentioning

confidence: 99%

Differential Role of Adipose Tissues in Obesity and Related Metabolic and Vascular Complications

Gómez-Hernández

Beneit

Díaz-Castroverde

et al. 2016

International Journal of Endocrinology

157

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This review focuses on the contribution of white, brown, and perivascular adipose tissues to the pathophysiology of obesity and its associated metabolic and vascular complications. Weight gain in obesity generates excess of fat, usually visceral fat, and activates the inflammatory response in the adipocytes and then in other tissues such as liver. Therefore, low systemic inflammation responsible for insulin resistance contributes to atherosclerotic process. Furthermore, an inverse relationship between body mass index and brown adipose tissue activity has been described. For these reasons, in recent years, in order to combat obesity and its related complications, as a complement to conventional treatments, a new insight is focusing on the role of the thermogenic function of brown and perivascular adipose tissues as a promising therapy in humans. These lines of knowledge are focused on the design of new drugs, or other approaches, in order to increase the mass and/or activity of brown adipose tissue or the browning process of beige cells from white adipose tissue. These new treatments may contribute not only to reduce obesity but also to prevent highly prevalent complications such as type 2 diabetes and other vascular alterations, such as hypertension or atherosclerosis.

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“…It is a protease that cleaves off amino-terminal dipeptides that have L-proline, L-alanine or serine in the penultimate position2. As a cell surface protein, DPP4 is involved in regulation of the immune system, signal transduction and apoptosis3. A soluble form of DPP4 circulates in the plasma.…”

mentioning

confidence: 99%

Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients

Li¹,

Chen²,

Chen³

et al. 2016

Sci Rep

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Dipeptidyl peptidase-4 (DPP4) is an important regulator of incretins and inflammation, and it is involved in the pathophysiological process of myocardial infarction (MI). This study investigated the role of plasma DPP4 activity (DPP4a) in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone percutaneous coronary intervention (PCI). We recruited 747 consecutive PCI-treated STEMI patients from a tertiary referral center from January 2014 to October 2015. The outcomes of interest were the rates of no-reflow, in-hospital major adverse cardiac or cerebrovascular events (iMACCE), in-hospital complications (IHC) and in-hospital major bleeding. The DPP4a was lower in STEMI patients compared with the controls (p < 0.0001). Multivariate logistic-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase in DPP4a was associated with an increased rate of no-reflow events (odds ratio [OR]: 1.07; 95% CI: 1.02–1.11; p < 0.01) and a decreased rate of major bleeding events (OR: 0.90; 95% CI: 0.82–0.98; p = 0.02). There were no associations between DPP4a and either iMACCE or IHC. In conclusions, high levels of DPP4a are independently associated with an increased rate of no-reflow events and a decreased rate of major bleeding events in PCT-treated STEMI patients.

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Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

Cited by 44 publications

References 82 publications

Linagliptin-Associated Alopecia and Bullous Pemphigoid

Linagliptin-Associated Alopecia and Bullous Pemphigoid

Differential Role of Adipose Tissues in Obesity and Related Metabolic and Vascular Complications

Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients

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