Chronic hyperglycemia is the primary risk factor for the development of complications in diabetes mellitus (DM); however, it is believed that frequent or large glucose fluctuations may independently contribute to diabetes-related complications. Postprandial spikes in blood glucose, as well as hypoglycemic events, are blamed for increased cardiovascular events in DM. Glycemic variability (GV) includes both of these events; hence, minimizing GV can prevent future cardiovascular events. Correcting GV emerges as a target to be pursued in clinical practice to safely reduce the mean blood glucose and to determine its direct effects on vascular complications in diabetes. Modern diabetes management modalities, including glucagon-related peptide-1-based therapy, newer insulins, modern insulin pumps and bariatric surgery, significantly reduce GV. However, defining GV remains a challenge primarily due to the difficulty of measuring it and the lack of consensus regarding the optimal approach for its management. The purpose of this manuscript was not only to review the most recent evidence on GV but also to help readers better understand the available measurement options and how the various definitions relate differently to the development of diabetic complications.

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Peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM) exhibits broad clinical characteristics and various consequences and is known as one of the major macrovascular complications of T2DM. Atherosclerosis is recognized as the most direct and important cause of PAD, but acute or chronic limb ischemia may be the result of various risk factors. In light of the increasing number of patients who undergo peripheral vascular procedures, the number of subjects who are exposed to the risks for PAD and related complications is increasing. In this review, we will discuss the clinical and epidemiological characteristics of PAD, as well as the clinical significance of PAD in T2DM subjects.

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Over the past decade, growing evidence has established the gut microbiota as one of the most important determinants of metabolic disorders such as obesity and type 2 diabetes. Indeed, obesogenic diet can drastically alter bacterial populations (i.e., dysbiosis) leading to activation of pro-inflammatory mechanisms and metabolic endotoxemia, therefore promoting insulin resistance and cardiometabolic disorders. To counteract these deleterious effects, probiotic strains have been developed with the aim of reshaping the microbiome to improve gut health. In this review, we focus on benefits of widely used probiotics describing their potential mechanisms of action, especially their ability to decrease metabolic endotoxemia by restoring the disrupted intestinal mucosal barrier. We also discuss the perspective of using new bacterial strains such as butyrate-producing bacteria and the mucolytic Akkermansia muciniphila, as well as the use of prebiotics to enhance the functionality of probiotics. Finally, this review introduces the notion of genetically engineered bacterial strains specifically developed to deliver anti-inflammatory molecules to the gut.

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