Antiplatelet and Antithrombotic Therapy in Type I Diabetes Mellitus: Update on Current Data.

Diabetes mellitus type 1 (T1DM) is an autoimmune disease characterized by a markedly elevated cardiovascular (CV) risk due to premature atherosclerosis. Previous studies have shown that intense glycemic control reduces the incidence of CV disease. Antiplatelet therapy is considered to be a very important therapy for secondary prevention of recurrent atherothrombotic events in patients with DM, while it may be considered for primary prevention in individuals with T1DM with additional CV risk factors. The aim of the present review is to summarize existing literature data regarding the thrombotic risk in T1DM patients and discuss current treatment strategies.

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

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; P=0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; P=0.046) and improved the ankle-brachial index and pain-free walking distance values (P=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; P=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.

The Oral Dipeptidyl-Peptidase-4 Inhibitor Sitagliptin Increases Circulating Levels Of Stromal-Derived Factor-1 Alpha.

Recent studies have demonstrated that stromal derived factor-1α (SDF-1α) is a substrate of dipeptidyl-peptidase-4 (DPP-4) inhibitors. It has also been shown that SDF-1α shares anti-apoptotic as well as nephroprotective properties and exerts a beneficial effect in the cardiovascular system. Therefore, the aim of this study was to estimate the effect of treatment with the DDP-4 inhibitor sitagliptin on SDF-1α levels in subjects with type 2 diabetes mellitus (T2D). Overall, 32 patients (16 males) with T2D, mean age (±SD) 67.2±8.3 years, HbA1c 6.4±0.5%, body-mass index (BMI) 29.1±4.9 Kg/m2, T2D duration 8.5±4.0 years receiving metformin monotherapy (17 participants) or metformin plus sitagliptin (15 participants) without known cardiovascular disease were enrolled. Patients on metformin plus sitagliptin exhibited higher plasma levels of SDF-1α compared with those on metformin monotherapy (19.6±4.1 versus 6.9±1.3 pg/ml, respectively, p=0.01). Multivariate regression analysis after controlling for age, sex, body-mass index, smoking, arterial hypertension, dyslipidaemia and other confounders showed that SDF-1α levels were positively correlated with DPP-4 inhibitor treatment (beta=0.91, p=0.001), and negatively with T2D duration (beta=- 0.42, p=0.05), ΗDL-cholesterol levels (beta=- 0.46, p=0.02) and HbA1c (beta=- 0.41, p=0.05). In conclusion, these results suggest that sitagliptin treatment may exert a favourable effect on SDF-1α levels.

Type 2 diabetes and quality of life.

It is true that a primary goal of diabetes early diagnosis and treatment is quality of life (QoL). The term QoL is still confusing but it is agreed that it composes of four components: The physical component, mental, cogitative component, psychological and social component. Many articles have been written addressing those four components. During the last five years 15500 articles and reviews have been written addressing diabetes and coronary arterial disease, 16100 addressing diabetes and renal function, 28900 addressing diabetes and retinopathy, 16800 addressing diabetic foot ulcers and other 26300 addressing diabetic neuropathy. Moreover 17200 articles are dealing with diabetic sexual dysfunction, 24500 with the correlation of diabetes and depression 17500 about diabetes and dementia, only 1 about diabetes and family functioning and 1950000 about diabetes and QoL, indicating the worldwide interest. In order to confront this metabolic anomaly and its consequences, researchers developed numerous generic and disease specific psychometric tools. With the aid of those psychometric tools the scientific community has started to realize the gruesome effect of diabetes on patients' lives. Diabetic's QoL becomes worse when complications start to develop or comorbidities coexist. Dominant amongst complications, in health-related quality of life (HRQoL) lowering, but not related to risk factors (genetic, the weight of birth, or others) is coronary arterial disease followed by renal failure, blindness, and the combination of micro- and macro-vascular complications and in some studies by sexual dysfunction. Moreover many are the comorbidities which deteriorate further the effect of diabetes in a patient life. Among them obesity, hypertension, dyslipidemia, depression, arthritis are the most common. Most intriguing field for research is the interaction of diabetes and depression and in some cases the progression to dementia. Many aspects and combinations of actions are under researchers' microscope regarding the improvement of HRQoL scores. Until now, the studies performed, have demonstrated little to moderate benefit. More of them are needed to draw safe conclusions on the topic of the best combination of actions to optimize the HRQoL scores.