Risk Factors for Atonic Postpartum Hemorrhage: A Systematic Review and Meta-analysis.

Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.

https://drc.bmj.com/content/bmjdrc/9/1/e002032.full.pdf

Glycemic variability and cardiovascular disease in patients with type 2 diabetes.

Cardiovascular disease remains a major contributor to morbidity and mortality in the US and elsewhere, and stroke is a leading cause of disability worldwide. Despite recent success in diminishing stroke incidence in the general US population, in parallel there is now a concerning propensity for strokes to happen at younger ages. Specifically, the incidence of stroke for US adults 20-44 years of age increased from 17 per 100,000 US adults in 1993 to 28 per 100,000 in 2015. Occurrence of strokes in young adults is particularly problematic as these patients are often affected by physical disability, depression, cognitive impairment and loss of productivity, all of which have vast personal, social and economic implications. These concerning trends among young adults are likely due to increasing trends in the prevalence of modifiable risk factors amongst this population including hypertension, hyperlipidemia, obesity and diabetes, highlighting the importance of early detection and aggressive prevention strategies in the general population at early ages. In parallel and compounding to the issue, troublesome trends are evident regarding increasing rates of substance abuse among young adults. Higher rates of strokes have been noted particularly among young African Americans, indicating the need for tailored prevention and social efforts targeting this and other vulnerable groups, including the primordial prevention of risk factors in the first place, reducing stroke rates in the presence of prevalent risk factors such as hypertension, and improving outcomes through enhanced healthcare access. In this narrative review we aim to emphasize the importance of stroke in young adults as a growing public health issue and increase awareness among clinicians and the public health sector. For this purpose, we summarize the available data on stroke in young adults and discuss the underlying epidemiology, etiology, risk factors, prognosis and opportunities for timely prevention of stroke specifically at young ages. Furthermore, this review highlights the gaps in knowledge and proposes future directions moving forward.

Stroke in young adults: Current trends, opportunities for prevention and pathways forward.

Diabetes and its complications have become a global challenge of public health. Herein, we aimed to develop a long-acting delivery system of lixisenatide (Lixi), a glucose-dependent antidiabetic peptide, based on an injectable hydrogel for the synchronous treatment of type 2 diabetes mellitus (T2DM) and associated complications. Two triblock copolymers, poly(e-caprolactone-co-glycolic acid)-poly(ethylene glycol)-poly(e-caprolactone-co-glycolic acid) and poly(d,l-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(d,l-lactic acid-co-glycolic acid) possessing temperature-induced sol-gel transitions, were synthesized by us. Compared to the two single-component hydrogels, their 1/1 mixture hydrogel not only maintained the temperature-induced gelation but also exhibited a steadier degradation profile in vivo. Both in vitro and in vivo release studies demonstrated that the mixture hydrogel provided the sustained release of Lixi for up to 9 days, which was attributed to balanced electrostatic interactions between the positive charges in the peptide and the negative charges in the polymer carrier. The hypoglycemic efficacy of Lixi delivered from the mixture hydrogel after a single subcutaneous injection into diabetic db/db mice was comparable to that of twice-daily administrations of Lixi solution for up to 9 days. Furthermore, three successive administrations of the abovementioned gel system within a month significantly increased the plasma insulin level, lowered glycosylated hemoglobin, and improved the pancreatic function of the animals. These results were superior or equivalent to those of twice-daily injections of Lixi solution for 30 days, but the number of injections was markedly reduced from 60 to 3. Finally, an improvement in hyperlipidemia, augmentation of nerve fiber density, and enhancement of motor nerve conduction velocity in the gel formulation-treated db/db mice indicated that the sustained delivery of Lixi arrested and even ameliorated diabetic complications. These findings suggested that the Lixi-loaded mixture hydrogel has great potential for the treatment of T2DM with significant improvements in the health and quality of life of patients.

Sustained Release Strategy Designed for Lixisenatide Delivery to Synchronously Treat Diabetes and Associated Complications

Diet is a critical element determining human health and diseases, and unbalanced food habits are major risk factors for the development of obesity and related metabolic disorders. Despite technological and pharmacological advances, as well as intensification of awareness campaigns, the prevalence of metabolic disorders worldwide is still increasing. Thus, novel therapeutic approaches with increased efficacy are urgently required, which often depends on cellular and molecular investigations using robust animal models. In the absence of perfect rodent models, those induced by excessive consumption of fat and sugars better replicate the key aspects that are the root causes of human metabolic diseases. However, the results obtained using these models cannot be directly compared, particularly because of the use of different dietary protocols, and animal species and strains, among other confounding factors. This review article revisits diet-induced models of obesity and related metabolic disorders, namely, metabolic syndrome, prediabetes, diabetes and nonalcoholic fatty liver disease. A critical analysis focused on the main pathophysiological features of rodent models, as opposed to the criteria defined for humans, is provided as a practical guide with a translational perspective for the establishment of animal models of obesity-related metabolic diseases.

Diet-induced rodent models of obesity-related metabolic disorders-A guide to a translational perspective.

Diabetes is a significant health problem worldwide, and its association with cardiovascular disease (CVD) was reported in several studies. Hyperglycemia and insulin resistance seen in diabetes and prediabetes lead to an increase in reactive oxygen species, which triggers intracellular molecular signaling. The resulting prothrombotic state and increase in inflammatory mediators expedite atherosclerotic changes and the development of macrovascular complications. Individuals with diabetes or prediabetes have a higher risk of developing myocardial infarction, stroke, and peripheral artery disease. However, no significant difference in cardiovascular morbidity has been observed with tight glycemic control despite a reduction in some CVD outcomes, and the risk of adverse outcomes such as hypoglycemia was increased. Recently, some GLP-1 receptor agonists and SGLT-2 inhibitors have been shown to reduce cardiovascular events and mortality. In this review we give an overview of the risk and pathogenesis of cardiovascular disease among diabetic and prediabetic patients, as well as the implication of recent changes in diabetes management.

/pdf/macrovascular-complications-in-patients-with-diabetes-and-3c9ogjco6w.pdf

Macrovascular Complications in Patients with Diabetes and Prediabetes.

Pulmonary ischemia and reperfusion (I/R) injury occurs in many clinical conditions and causes severe damage to the lungs. Diabetes mellitus (DM) predisposes to pulmonary I/R injury. We previously found that remote liver ischemia preconditioning protected lungs against pulmonary I/R injury. The aim of the present study was to investigate whether remote liver ischemic postconditioning (RLIPost) attenuates pulmonary damage induced by I/R injury in non-diabetic or diabetic rats. Male Sprague-Dawley rats were assigned into non-diabetic and diabetic groups. All rats except for the sham were exposed to 45 min of left hilum occlusion followed by 2 h of reperfusion. RLIPost was conducted at the onset of pulmonary reperfusion by four cycles of 5 min of liver ischemia and reperfusion. Lung injury was assessed by the wet/dry weight ratio, pulmonary oxygenation, histopathological changes, apoptosis and the expression of inflammatory cytokines. Reperfusion-associated protein phosphorylation states were determined. RLIPost offered strong pulmonary-protection in both non-diabetic and diabetic rats, as reflected in reduced water content and pulmonary structural damage, recovery of lung function, inhibition of apoptosis and inflammation after ischemia-reperfusion. RLIPost induced the activation of pulmonary STAT-3, a key component in the SAFE pathway, but not activation of the proteins in the RISK pathway, in non-diabetic rats. In contrast, RLIPost-induced pulmonary protection in diabetic lungs was independent of SAFE or RISK pathway activation. These results demonstrate that RLIPost exerts pulmonary protection against I/R-induced lung injury in non-diabetic and diabetic rats. The underlying mechanism for protection may be different in non-diabetic (STAT-3 dependent) versus diabetic (STAT-3 independent) rats.

/pdf/protective-effect-of-remote-liver-ischemic-postconditioning-2atcy8kf.pdf

Protective effect of remote liver ischemic postconditioning on pulmonary ischemia and reperfusion injury in diabetic and non-diabetic rats

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Macrovascular Complications in Patients with Diabetes and Prediabetes.

Protective effect of remote liver ischemic postconditioning on pulmonary ischemia and reperfusion injury in diabetic and non-diabetic rats